An Introduction to Brain and

Behavior
Bryan Kolb Ian Q. G. Campbell
University of Whishaw Teskey
Lethbridge University of Lethbridge University of Calgary

Fifth Edition
This book is dedicated to Cornelius H. “Case” Vanderwolf
(1935–2015), with whom each of us studied. Case did his Ph.D.
with Donald O. Hebb and postdoctoral research with Konrad
Ackert and Roger Sperry, figures whose research is featured
prominently in this book. He was an advocate of the theory that
the study of behavior provided the window to the organization of
the brain, and he was especially encouraging of our first attempt
at book writing.
Publisher, Psychology and Sociology: Rachel Losh
Senior Acquisitions Editor: Daniel DeBonis
Development Editor: Barbara Brooks
Assistant Editor: Katie Pachnos
Senior Marketing Manager: Lindsay Johnson
Marketing Assistant: Morgan Ratner
Executive Media Editor: Rachel Comerford
Associate Media Editor: Jessica Lauffer
Director, Content Management Enhancement: Tracey Kuehn
Managing Editor, Sciences and Social Sciences: Lisa Kinne
Project Editor: Edgar Doolan
Media Producer: Elizabeth Dougherty
Copy Editor: Kate Daly
Senior Photo Editor: Cecilia Varas
Photo Researcher: Richard Fox
Senior Production Manager: Paul Rohloff
Director of Design, Content Management Enhancement: Diana Blume
Design Manager: Blake Logan
Interior Design: Charles Yuen
Art Manager: Matthew McAdams
Illustration Coordinator: Janice Donnola
New Illustrations: Evelyn Pence, Matthew McAdams
Composition: codeMantra
Printing and Binding: RR Donelley
Cover Art: ALFRED PASIEKA/SCIENCE PHOTO LIBRARY/Getty
Images
Chapter Opener Illustrations: Katherine Streeter
Library of Congress Control Number: 2015957301
ISBN-13: 978-1-4641-0601-9
ISBN-10: 1-4641-0601-0
Copyright © 2016, 2014, 2011, 2006 by Worth Publishers
All rights reserved.
Printed in the United States of America
First printing
Worth Publishers
One New York Plaza
Suite 4500
New York, New York 10004-1562
www.macmillanhighered.com
 ABOUT THE AUTHORS
Bryan Kolb received his Ph.D.
from The Pennsylvania State
University in 1973. He conducted
postdoctoral work at the University
of Western Ontario and the
Montreal Neurological Institute.
He moved to the University of
Lethbridge in 1976, where he is
Professor of Neuroscience and
holds a Board of Governors Chair
in Neuroscience. His current
research examines how neurons of
the cerebral cortex change in
response to various factors,
including hormones, experience, Deborah Muirhead
psychoactive drugs, neurotrophins,
and injury, and how these changes are related to behavior in the normal
and diseased brain. Kolb has received the distinguished teaching medal
from the University of Lethbridge. He is a Fellow of the Royal Society
of Canada and of the Canadian Psychological Association (CPA), the
American Psychological Association, and the Association of
Psychological Science. He is a recipient of the Hebb Prize from CPA and
from the Canadian Society for Brain, Behaviour, and Cognitive Science
and has received four honorary doctorates. He is a Senior Fellow of the
Experience-Based Brain and Behavioral Development program of the
Canadian Institute for Advanced Research. He and his wife train and
show horses in Western riding performance events.
Ian Q. Whishaw received his Ph.D. from Western University and is a
Professor of Neuroscience at the University of Lethbridge. He has held
visiting appointments at the University of Texas, University of Michigan,
Cambridge University, and the University of Strasbourg. He is a fellow
of Clair Hall, Cambridge, and of the Canadian Psychological
Association, the American Psychological Association, and the Royal
Society of Canada. He is a recipient of the Canadian Humane Society
Bronze Medal for bravery, the Ingrid Speaker Gold Medal for research,
and the distinguished teaching medal from the University of Lethbridge.
He has received the Key to the City of Lethbridge and has honorary
doctorates from Thompson Rivers
University and the University of
Lethbridge. His research addresses
the neural basis of skilled
movement and the neural basis of
brain disease, and the Institute for
Scientific Information includes
him in its list of most cited
neuroscientists. His hobby is
training horses for Western
performance events.
G. Campbell Teskey received
his Ph.D. from Western University
in 1990 and then conducted David Benard
postdoctoral work at McMaster
University. In 1992 he relocated to
the University of Calgary, where
he is a professor in the Department
of Cell Biology and Anatomy and
the Hotchkiss Brain Institute. His
current research program examines
the development, organization, and
plasticity of the motor cortex, as
well as how seizures alter brain
function. Teskey has won
numerous teaching awards, has
developed new courses, and is a
founder of the Bachelor’s of
Science in Neuroscience program
at his home university. He serves Tannis Teskey
as Education Director for the
Hotchkiss Brain Institute and chairs the Education Committee of
Campus Alberta Neuroscience. His hobbies include hiking, biking,
kayaking, and skiing.
 CONTENTS IN BRIEF
Preface
Media and Supplements

CHAPTER 1 What Are the Origins of Brain and

Behavior?
CHAPTER 2 What Is the Nervous System’s
Functional Anatomy?
CHAPTER 3 What Are the Nervous System’s
Functional Units?
CHAPTER 4 How Do Neurons Use Electrical
Signals to Transmit Information?
CHAPTER 5 How Do Neurons Communicate and
Adapt?
CHAPTER 6 How Do Drugs and Hormones
Influence the Brain and Behavior?
CHAPTER 7 How Do We Study the Brain’s
Structures and Functions?
CHAPTER 8 How Does the Nervous System
Develop and Adapt?
CHAPTER 9 How Do We Sense, Perceive, and See
the World?
CHAPTER 10 How Do We Hear, Speak, and Make
Music?
CHAPTER 11 How Does the Nervous System
Respond to Stimulation and Produce
Movement?
CHAPTER 12 What Causes Emotional and Motivated
Behavior?
 CHAPTER 13 Why Do We Sleep and Dream?
CHAPTER 14 How Do We Learn and Remember?
CHAPTER 15 How Does the Brain Think?
CHAPTER 16 What Happens When the Brain
Misbehaves?
Answers to Section Review Self-Tests
Glossary
References
Name Index
Subject Index
 CONTENTS
PREFACE
MEDIA AND SUPPLEMENTS

CHAPTER 1 What Are the Origins of Brain

and Behavior?
CLINICAL FOCUS 1-1 Living with Traumatic Brain Injury
1-1 Neuroscience in the Twenty-First Century
Why Study Brain and Behavior?
What Is the Brain?
What Is Behavior?
1-2 Perspectives on Brain and Behavior
Aristotle and Mentalism
Descartes and Dualism
Darwin and Materialism
COMPARATIVE FOCUS 1-2 The Speaking Brain
EXPERIMENT 1-1 Question: How do parents transmit heritable factors
to offspring?
Contemporary Perspectives on Brain and Behavior
1-3 Evolution of Brains and of Behavior
Origin of Brain Cells and Brains
THE BASICS: Classification of Life
Evolution of Nervous Systems in Animals
Chordate Nervous System
1-4 Evolution of the Human Brain and Behavior
Humans: Members of the Primate Order
Australopithecus : Our Distant Ancestor
The First Humans
Relating Brain Size and Behavior
COMPARATIVE FOCUS 1-3 The Elephant’s Brain
Why the Hominid Brain Enlarged
1-5 Modern Human Brain Size and Intelligence
Meaning of Human Brain Size Comparisons
Acquisition of Culture
SUMMARY
KEY TERMS

CHAPTER 2 What Is the Nervous System’s

Functional Anatomy?
RESEARCH FOCUS 2-1 Agenesis of the Cerebellum
2-1 Overview of Brain Function and Structure
Plastic Patterns of Neural Organization
Functional Organization of the Nervous System
The Brain’s Surface Features
THE BASICS: Finding Your Way Around the Brain
CLINICAL FOCUS 2-2 Meningitis and Encephalitis
The Brain’s Internal Features
CLINICAL FOCUS 2-3 Stroke

2-2 The Nervous System’s Evolutionary Development

Stages in Brain Evolution
The Nervous System and Intelligent Behavior
EXPERIMENT 2-1 Question: Does intelligent behavior require a
vertebrate nervous system organization?
2-3 The Central Nervous System: Mediating Behavior
Spinal Cord
Brainstem
Forebrain
Cerebral Cortex
Basal Ganglia
Limbic System
Olfactory System
2-4 Somatic Nervous System: Transmitting Information
Cranial Nerves
Spinal Nerves
Somatic Nervous System Connections
Integrating Spinal Functions
CLINICAL FOCUS 2-4 Magendie, Bell, and Bell Palsy
2-5 Autonomic and Enteric Nervous Systems: Visceral
Relations
ANS: Balancing Internal Functions
ENS: Controlling the Gut
2-6 Ten Principles of Nervous System Function
Principle 1: The Nervous System Produces Movement in a
Perceptual World the Brain Constructs
Principle 2: Neuroplasticity Is the Hallmark of Nervous System
Functioning
Principle 3: Many Brain Circuits Are Crossed
Principle 4: The CNS Functions on Multiple Levels
Principle 5: The Brain Is Symmetrical and Asymmetrical
Principle 6: Brain Systems Are Organized Hierarchically and in
Parallel
Principle 7: Sensory and Motor Divisions Permeate the Nervous
System
Principle 8: The Brain Divides Sensory Input for Object
Recognition and Motor Control
Principle 9: Brain Functions Are Localized and Distributed
Principle 10: The Nervous System Works by Juxtaposing
Excitation and Inhibition
SUMMARY
KEY TERMS

CHAPTER 3 What Are the Nervous System’s

Functional Units?
RESEARCH FOCUS 3-1 A Genetic Diagnosis
3-1 Cells of the Nervous System
RESEARCH FOCUS 3-2 Brainbow: Rainbow Neurons
Neurons: The Basis of Information Processing
Five Types of Glial Cells
EXPERIMENT 3-1 Question: Can the principles of neural excitation
and inhibition control the activity of a simple robot?
CLINICAL FOCUS 3-3 Brain Tumors
3-2 Internal Structure of a Cell
The Cell as a Factory
THE BASICS: Chemistry Review
Cell Membrane: Barrier and Gatekeeper
The Nucleus and Protein Synthesis
The Endoplasmic Reticulum and Protein Manufacture
Proteins: The Cell’s Product
Golgi Bodies and Microtubules: Protein Packaging and Shipment
Crossing the Cell Membrane: Channels, Gates, and Pumps
3-3 Genes, Cells, and Behavior
Mendelian Genetics and the Genetic Code
Applying Mendel’s Principles
CLINICAL FOCUS 3-4 Huntington Disease
Genetic Engineering
Phenotypic Plasticity and the Epigenetic Code
SUMMARY
KEY TERMS

CHAPTER 4 How Do Neurons Use Electrical

Signals to Transmit Information?
CLINICAL FOCUS 4-1 Epilepsy

4-1 Searching for Electrical Activity in the Nervous

System
Early Clues That Linked Electricity and Neuronal Activity
THE BASICS Electricity and Electrical Stimulation
Tools for Measuring a Neuron’s Electrical Activity
How Ion Movement Produces Electrical Charges
4-2 Electrical Activity of a Membrane
Resting Potential
Maintaining the Resting Potential
Graded Potentials
Action Potential
Nerve Impulse
Refractory Periods and Nerve Action
Saltatory Conduction and the Myelin Sheath
CLINICAL FOCUS 4-2 Multiple Sclerosis
4-3 How Neurons Integrate Information
Excitatory and Inhibitory Postsynaptic Potentials
EXPERIMENT 4-1 Question: How does stimulating a neuron
influence its excitability?
Summation of Inputs
Voltage-Sensitive Channels and the Action Potential
The Versatile Neuron
RESEARCH FOCUS 4-3 Optogenetics and Light-Sensitive Ion
Channels
4-4 Into the Nervous System and Back Out
How Sensory Stimuli Produce Action Potentials
How Nerve Impulses Produce Movement
CLINICAL FOCUS 4-4 ALS: Lou Gehrig’s Disease
SUMMARY
KEY TERMS

CHAPTER 5 How Do Neurons Communicate

and Adapt?
RESEARCH FOCUS 5-1 The Basis of Neural Communication in a
Heartbeat
5-1 A Chemical Message
EXPERIMENT 5-1 Question: How does a neuron pass on a message?
CLINICAL FOCUS 5-2 Parkinson Disease
Structure of Synapses
Neurotransmission in Four Steps
Varieties of Synapses
Excitatory and Inhibitory Messages
Evolution of Complex Neurotransmission Systems
5-2 Varieties of Neurotransmitters and Receptors
Four Criteria for Identifying Neurotransmitters
Four Classes of Neurotransmitters
CLINICAL FOCUS 5-3 Awakening with L -Dopa
Varieties of Receptors
5-3 Neurotransmitter Systems and Behavior
Neurotransmission in the Somatic Nervous System
Dual Activating Systems of the Autonomic Nervous System
Enteric Nervous System Autonomy
Four Activating Systems in the Central Nervous System
CLINICAL FOCUS 5-4 The Case of the Frozen Addict
5-4 Adaptive Role of Synapses in Learning and Memory
Habituation Response
EXPERIMENT 5-2 Question: What happens to the gill response after
repeated stimulation?
Sensitization Response
EXPERIMENT 5-3 Question: What happens to the gill response in
sensitization?
Learning as a Change in Synapse Number
RESEARCH FOCUS 5-5 Dendritic Spines: Small but Mighty
SUMMARY
KEY TERMS

CHAPTER 6 How Do Drugs and Hormones

Influence the Brain and Behavior?
CLINICAL FOCUS 6-1 Cognitive Enhancement
6-1 Principles of Psychopharmacology
Drug Routes into the Nervous System
Drug Action at Synapses: Agonists and Antagonists
An Acetylcholine Synapse: Examples of Drug Action
Tolerance
EXPERIMENT 6-1 Question: Will the consumption of alcohol
produce tolerance?
Sensitization
EXPERIMENT 6-2Question: Does the injection of a drug always
produce the same behavior?
6-2 Grouping Psychoactive Drugs
Group I: Antianxiety Agents and Sedative-Hypnotics
CLINICAL FOCUS 6-2 Fetal Alcohol Spectrum Disorder
Group II: Antipsychotic Agents
Group III: Antidepressants and Mood Stabilizers
CLINICAL FOCUS 6-3 Major Depression
Group IV: Opioid Analgesics
Group V: Psychotropics
6-3 Factors Influencing Individual Responses to Drugs
Behavior on Drugs
Addiction and Dependence
Sex Differences in Addiction
6-4 Explaining and Treating Drug Abuse
Wanting-and-Liking Theory
Why Doesn’t Everyone Abuse Drugs?
Treating Drug Abuse
Can Drugs Cause Brain Damage?
CLINICAL FOCUS 6-4 Drug-Induced Psychosis
6-5 Hormones
Hierarchical Control of Hormones
Classes and Functions of Hormones
Homeostatic Hormones
Gonadal Hormones
Anabolic–Androgenic Steroids
Glucocorticoids and Stress
SUMMARY
KEY TERMS

CHAPTER 7 How Do We Study the Brain’s

Structures and Functions?
RESEARCH FOCUS 7-1 Tuning In to Language
7-1 Measuring and Manipulating Brain and Behavior
Linking Neuroanatomy and Behavior
Question: Do hippocampal neurons contribute to
EXPERIMENT 7-1
memory formation?
Methods of Behavioral Neuroscience
Manipulating Brain–Behavior Interactions
7-2 Measuring the Brain’s Electrical Activity
Recording Action Potentials from Single Cells
EEG: Recording Graded Potentials from Thousands of Cells
Mapping Brain Function with Event-Related Potentials
CLINICAL FOCUS 7-2 Mild Head Injury and Depression
Magnetoencephalography
7-3 Anatomical Imaging Techniques: CT and MRI
7-4 Functional Brain Imaging
Functional Magnetic Resonance Imaging
Optical Tomography
Positron Emission Tomography
7-5 Chemical and Genetic Measures of Brain and
Behavior
Measuring Brain Chemistry
Measuring Genes in Brain and Behavior
CLINICAL FOCUS 7-3 Cannabis Use, Psychosis, and Genetics
Epigenetics: Measuring Gene Expression
7-6 Comparing Neuroscience Research Methods
7-7 Using Animals in Brain–Behavior Research
Benefits of Animal Models of Disease
Animal Welfare and Scientific Experimentation
RESEARCH FOCUS 7-4 Attention-Deficit/Hyperactivity Disorder
SUMMARY
KEY TERMS

CHAPTER 8 How Does the Nervous System

Develop and Adapt?
RESEARCH FOCUS 8-1 Linking Socioeconomic Status to Cortical
Development
8-1 Three Perspectives on Brain Development
Correlating Emerging Brain Structures with Emerging
Behaviors
Correlating Emerging Behaviors with Neural Maturation
Identifying Influences on Brain and Behavior
8-2 Neurobiology of Development
Gross Development of the Human Nervous System
Origins of Neurons and Glia
Neuronal Growth and Development
CLINICAL FOCUS 8-2 Autism Spectrum Disorder
Unique Aspects of Frontal Lobe Development
Glial Development
8-3 Using Emerging Behaviors to Infer Neural Maturation
Motor Behaviors
Language Development
Development of Problem-Solving Ability
EXPERIMENT 8-1 Question: In what sequence do the forebrain
structures required for learning and memory mature?
A Caution about Linking Correlation to Causation
8-4 Brain Development and the Environment
Experience and Cortical Organization
RESEARCH FOCUS 8-3 Increased Cortical Activation for Second
Languages
Experience and Neural Connectivity
Critical Periods for Experience and Brain Development
Abnormal Experience and Brain Development
Hormones and Brain Development
CLINICAL FOCUS 8-4 Romanian Orphans
Gut Bacteria and Brain Development
Injury and Brain Development
Drugs and Brain Development
Other Sources of Abnormal Brain Development
CLINICAL FOCUS 8-5 Schizophrenia

Developmental Disability
8-5 How Do Any of Us Develop a Normal Brain?
SUMMARY
KEY TERMS

CHAPTER 9 How Do We Sense, Perceive, and

See the World?
CLINICAL FOCUS 9-1 Migraines and a Case of Blindsight
9-1 Nature of Sensation and Perception
Sensory Receptors
Neural Relays
Sensory Coding and Representation
Perception
9-2 The Visual System’s Functional Anatomy
Structure of the Retina
THE BASICS Visible Light and the Structure of the Eye
Photoreceptors
CLINICAL FOCUS 9-2 Visual Illuminance
Types of Retinal Neurons
Visual Pathways
Dorsal and Ventral Visual Streams
9-3 Location in the Visual World
Coding Location in the Retina
Location in the Lateral Geniculate Nucleus and Region V1
Visual Corpus Callosum
9-4 Neuronal Activity
Seeing Shape
Seeing Color
RESEARCH FOCUS 9-3 Color-Deficient Vision
Neuronal Activity in the Dorsal Stream
9-5 The Visual Brain in Action
Injury to the Visual Pathway Leading to the Cortex
Injury to the What Pathway
CLINICAL FOCUS 9-4 Carbon Monoxide Poisoning
Injury to the How Pathway
SUMMARY
KEY TERMS

CHAPTER 10 How Do We Hear, Speak, and

Make Music?
RESEARCH FOCUS 10-1 Evolution of Language and Music
10-1 Sound Waves: Stimulus for Audition
Physical Properties of Sound Waves
Perception of Sound
Properties of Language and Music as Sounds
10-2 Functional Anatomy of the Auditory System
Structure of the Ear
Auditory Receptors
RESEARCH FOCUS 10-2 Otoacoustic Emissions
Pathways to the Auditory Cortex
Auditory Cortex
RESEARCH FOCUS 10-3 Seeing with Sound
10-3 Neural Activity and Hearing
Hearing Pitch
Detecting Loudness
Detecting Location
Detecting Patterns in Sound
10-4 Anatomy of Language and Music
Processing Language
CLINICAL FOCUS 10-4 Left-Hemisphere Dysfunction
Processing Music
CLINICAL FOCUS 10-5 Cerebral Aneurysms
RESEARCH FOCUS 10-6 The Brain’s Music System
10-5 Auditory Communication in Nonhuman Species
Birdsong
Echolocation in Bats
SUMMARY
KEY TERMS

CHAPTER 11 How Does the Nervous System

Respond to Stimulation and Produce
Movement?
RESEARCH FOCUS 11-1 Neuroprosthetics

11-1 A Hierarchy of Movement Control

THE BASICS Relating the Somatosensory and Motor Systems
Forebrain: Initiating Movement
Experimental Evidence for a Movement Hierarchy
Brainstem: Species-Typical Movement
EXPERIMENT 11-1Question: What are the effects of brainstem
stimulation under different conditions?
CLINICAL FOCUS 11-2 Cerebral Palsy
Spinal Cord: Executing Movement
CLINICAL FOCUS 11-3 Spinal Cord Injury
11-2 Motor System Organization
Motor Cortex
Question: How does the motor cortex take part in
Experiment 11-2
the control of movement?
Motor Cortex and Skilled Movement
Plasticity in the Motor Cortex
Question: What is the effect of rehabilitation on the
Experiment 11-3
cortical representation of the forelimb after brain damage?
Corticospinal Tracts
Motor Neurons
Control of Muscles
11-3 Basal Ganglia, Cerebellum, and Movement
Basal Ganglia and the Force of Movement
CLINICAL FOCUS 11-4 Tourette Syndrome
Cerebellum and Movement Skill
Question: Does the cerebellum help to make
Experiment 11-4
adjustments required to keep movements accurate?
11-4 Somatosensory System Receptors and Pathways
Somatosensory Receptors and Perception
Posterior Root Ganglion Neurons
Somatosensory Pathways to the Brain
Spinal Reflexes
Feeling and Treating Pain
RESEARCH FOCUS 11-5 Phantom Limb Pain
Vestibular System and Balance
11-5 Exploring the Somatosensory Cortex
Somatosensory Homunculus
RESEARCH FOCUS 11-6 Tickling

Effects of Somatosensory Cortex Damage

Somatosensory Cortex and Complex Movement
SUMMARY
KEY TERMS

CHAPTER 12 What Causes Emotional and

Motivated Behavior?
RESEARCH FOCUS 12-1 The Pain of Rejection
12-1 Identifying the Causes of Behavior
Behavior for Brain Maintenance
Neural Circuits and Behavior
12-2 The Chemical Senses
Olfaction
Gustation
12-3 Evolution, Environment, and Behavior
Evolutionary Influences on Behavior
Environmental Influences on Behavior
Inferring Purpose in Behavior: To Know a Fly
12-4 Neuroanatomy of Motivated and Emotional Behavior
Regulatory and Nonregulatory Behavior
Regulatory Function of the Hypothalamic Circuit
Organizing Function of the Limbic Circuit
Executive Function of the Frontal Lobes
CLINICAL FOCUS 12-2 Agenesis of the Frontal Lobes
Stimulating and Expressing Emotion
Amygdala and Emotional Behavior
Prefrontal Cortex and Emotional Behavior
Emotional Disorders
CLINICAL FOCUS 12-3 Anxiety Disorders
12-5 Control of Regulatory and Nonregulatory Behavior
Controlling Eating
CLINICAL FOCUS 12-4 Weight Loss Strategies
Experiment 12-1 Question: Does the hypothalamus play a role in
eating?
Controlling Drinking
Controlling Sexual Behavior
CLINICAL FOCUS 12-5 Androgen Insensitivity Syndrome and the
Androgenital Syndrome
Sexual Orientation, Sexual Identity, and Brain Organization
Cognitive Influences on Sexual Behavior
12-6 Reward
SUMMARY
KEY TERMS

CHAPTER 13 Why Do We Sleep and Dream?

CLINICAL FOCUS 13-1 Doing the Right Thing at the Right Time
13-1 A Clock for All Seasons
Origins of Biological Rhythms
Biological Clocks
Experiment 13-1 Question: Is plant movement exogenous or
endogenous?
Measuring Biological Rhythms
Free-Running Rhythms
Zeitgebers
CLINICAL FOCUS 13-2 Seasonal Affective Disorder
13-2 Neural Basis of the Biological Clock
Suprachiasmatic Rhythms
Keeping Time
Pacemaking Circadian Rhythms
RESEARCH FOCUS 13-3 Synchronizing Biorhythms at the Molecular
Level
Pacemaking Circannual Rhythms
Cognitive and Emotional Rhythms
13-3 Sleep Stages and Dreaming
Measuring How Long We Sleep
Measuring Sleep in the Laboratory
Stages of Waking and Sleeping
A Typical Night’s Sleep
Contrasting NREM Sleep and REM Sleep
CLINICAL FOCUS 13-4 Restless Legs Syndrome
Dreaming
What We Dream About
13-4 What Does Sleep Accomplish?
Sleep As a Biological Adaptation
Sleep As a Restorative Process
Sleep and Memory Storage
13-5 Neural Bases of Sleep
Reticular Activating System and Sleep
Neural Basis of EEG Changes Associated with Waking
Neural Basis of REM Sleep
13-6 Sleep Disorders
Disorders of NREM Sleep
CLINICAL FOCUS 13-5 Sleep Apnea
Disorders of REM Sleep
13-7 What Does Sleep Tell Us about Consciousness?
SUMMARY
KEY TERMS

CHAPTER 14 How Do We Learn and

Remember?
CLINICAL FOCUS 14-1 Remediating Dyslexia
14-1 Connecting Learning and Memory
Studying Learning and Memory in the Laboratory
Question: Does an animal learn the association
Experiment 14-1
between emotional experience and environmental stimuli?
Two Categories of Memory
What Makes Explicit and Implicit Memory Different?
What Is Special about Personal Memories?
14-2 Dissociating Memory Circuits
Disconnecting Explicit Memory
Disconnecting Implicit Memory
CLINICAL FOCUS 14-2 Patient Boswell’s Amnesia
14-3 Neural Systems Underlying Explicit and Implicit
Memories
Neural Circuit for Explicit Memories
CLINICAL FOCUS 14-3 Alzheimer Disease
CLINICAL FOCUS 14-4 Korsakoff Syndrome
Consolidation of Explicit Memories
Neural Circuit for Implicit Memories
Neural Circuit for Emotional Memories
14-4 Structural Basis of Brain Plasticity
Long-Term Potentiation
Measuring Synaptic Change
Enriched Experience and Plasticity
Sensory or Motor Training and Plasticity
Question: Does the learning of a fine motor skill
Experiment 14-2
alter the cortical motor map?
RESEARCH FOCUS 14-5 Movement, Learning, and Neuroplasticity
Experience-Dependent Change in the Human Brain
Epigenetics of Memory
Plasticity, Hormones, Trophic Factors, and Drugs
Question: What effect do repeated doses of
Experiment 14-3
amphetamine, a psychomotor stimulant, have on neurons?
Some Guiding Principles of Brain Plasticity
14-5 Recovery from Brain Injury
Donna’s Experience with Traumatic Brain Injury
Three-Legged Cat Solution
New-Circuit Solution
Question: Does nerve growth factor stimulate
Experiment 14-4
recovery from stroke, influence neural structure, or both?
Lost Neuron Replacement Solution
SUMMARY
KEY TERMS

CHAPTER 15 How Does the Brain Think?

RESEARCH FOCUS 15-1 Split Brain
15-1 The Nature of Thought
Characteristics of Human Thought
Neural Unit of Thought
COMPARATIVE FOCUS 15-2 Animal Intelligence
Question: How do individual neurons mediate
Experiment 15-1
cognitive activity?
15-2 Cognition and the Association Cortex
Knowledge about Objects
Multisensory Integration
Spatial Cognition
Attention
Experiment 15-2 Question: Can neurons learn to respond selectively
to stimuli?
Planning
Imitation and Understanding
RESEARCH FOCUS 15-3 The Rise and Fall of Mirror Neurons
15-3 Expanding Frontiers of Cognitive Neuroscience
CLINICAL FOCUS 15-4 Neuropsychological Assessment
Mapping the Brain
Cognition and the Cerebellum
Social Neuroscience
Neuroeconomics
15-4 Cerebral Asymmetry in Thinking
Anatomical Asymmetry
Functional Asymmetry in Neurological Patients
Functional Asymmetry in the Healthy Brain
Functional Asymmetry in the Split Brain
Explaining Cerebral Asymmetry
Question: Will severing the corpus callosum affect
Experiment 15-3
the way in which the brain responds?
(A) Question: How can the right hemisphere of a
Experiment 15-4
split-brain subject show that it knows information? (B) Question:
What happens if both hemispheres are asked to respond to
competing information?
Left Hemisphere, Language, and Thought
15-5 Variations in Cognitive Organization
Sex Differences in Cognitive Organization
Handedness and Cognitive Organization
CLINICAL FOCUS 15-5 Sodium Amobarbital Test
Synesthesia
CLINICAL FOCUS 15-6 A Case of Synesthesia
15-6 Intelligence
Concept of General Intelligence
Multiple Intelligences
Divergent and Convergent Intelligence
Intelligence, Heredity, Epigenetics, and the Synapse
15-7 Consciousness
Why Are We Conscious?
What Is the Neural Basis of Consciousness?
Question: Can people alter their movements without
Experiment 15-5
conscious awareness?
SUMMARY
KEY TERMS

CHAPTER 16 What Happens When the Brain

Misbehaves?
RESEARCH FOCUS 16-1 Posttraumatic Stress Disorder
16-1 Multidisciplinary Research on Brain and Behavioral
Disorders
Causes of Disordered Behavior
Investigating the Neurobiology of Behavioral Disorders
16-2 Classifying and Treating Brain and Behavioral
Disorders
Identifying and Classifying Behavioral Disorders
Treatments for Disorders
RESEARCH FOCUS 16-2 Treating
Behavioral Disorders with
Transcranial Magnetic Stimulation
16-3 Understanding and Treating Neurological Disorders
Traumatic Brain Injury
CLINICAL FOCUS 16-3 Concussion

Stroke
Epilepsy
Multiple Sclerosis
Neurodegenerative Disorders
Are All Degenerative Dementias Aspects of a Single Disease?
Age-Related Cognitive Loss
16-4 Understanding and Treating Psychiatric Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Mood Disorders
RESEARCH FOCUS 16-4 Antidepressant Action and Brain Repair
Anxiety Disorders
16-5 Is Misbehavior Always Bad?
SUMMARY
KEY TERMS
ANSWERS TO SECTION REVIEW SELF-TESTS
GLOSSARY
REFERENCES
NAME INDEX
SUBJECT INDEX
 PREFACE
The Fifth Edition of An Introduction to Brain and Behavior continues
to reflect the evolution of behavioral neuroscience. In keeping with this
evolution, we welcome G. Campbell Teskey, whose fresh perspective—
especially on topics related to neurophysiology and nervous system
disorders—enhances our author team.
Other major changes in this edition include a deeper emphasis on
genetics and epigenetics throughout. Epigenetics is especially important
for understanding brain and behavior because environmentally induced
modifications in gene expression alter the brain and ultimately
behavioral development. Thus, experience—especially early experience
—modifies how brain development unfolds. These modifications—of at
least some behavioral traits—can be transferred across generations, a
process known as epigenetic inheritance. We introduce it in the case
study at the end of Section 3-3 .
This edition fully addresses advances in imaging technology,
including techniques that are fueling the burgeoning field of
connectomics and progress toward a comprehensive map of neural
connections—a brain connectome. These exciting advances are
especially relevant in the second half of the book, where we review
higher-level functions.
Imaging advances and epigenetics concepts and research continue as a
prime focus in this revision but are not our sole focus. In Chapter 2 we
introduce the enteric nervous system, which controls the gut, and later
chapters elaborate on ENS functioning. Section 7-1 introduces the
emerging field of synthetic neurobiology, elaborated in Section 16-2 .
Section 5-2 adds new research on lipid neurotransmitters and detail on
receptor subtypes.
The range of updates and new coverage in the Fifth Edition text and
Focus features is listed, chapter by chapter, in the margins of these
Preface pages. See for yourself the breadth and scope of the revision;
then read on to learn more about the big-picture improvements in the
Fifth Edition.
With encouraging feedback from readers, the book’s learning
apparatus continues to feature sets of self-test questions at the end of the
major sections in each chapter. These Section Reviews help students
track their understanding as they progress. Answers appear at the back of
the book.
We continue to expand the popular margin notes. Beyond offering
useful asides to the text narrative, these marginalia increase the reader’s
ease in finding information, especially when related concepts are
introduced early in the text then elaborated on in later chapters. Readers
can return quickly to an earlier discussion to refresh their knowledge or
jump ahead to learn more. The margin notes also help instructors move
through the book to preview later discussions.
The illustrated Experiments, one of the book’s most popular features,
show readers how researchers design experiments, that is, how they
approach the study of brain–behavior relationships. The Basics features
let students brush up or get up to speed on their science foundation—
knowledge that helps them comprehend behavioral neuroscience.
We have made some big changes, yet much of the book remains
familiar. In shaping content throughout, we continue to examine the
nervous system with a focus on function, on how our behavior and our
brain interact, by asking key questions that students and neuroscientists
ask:
• Why do we have a brain?
• How is the nervous system organized, functionally as well as
anatomically?
• How do drugs and hormones affect our behavior?
• How does the brain learn?
• How does the brain think?
FIFTH EDITION UPDATES

CHAPTER 1: ORIGINS
NEW: locked-in syndrome in §1-1 features the case of Martin Pistorius.
NEW: Figure 1-12 , Neanderthal Woman, and NEW text describes H.
sapiens sapiens–H. neanderthalis intermingling.
NEW discussion in §1-4 and Comparative Focus 1-3 explain brain cell
packing density.
UPDATED coverage, Altered Maturation, in §1-4, simplifies the
concept neoteny.
NEW section, Acquisition of Culture, in §1-5, introduces the concept
memes.

CHAPTER 2: NEUROANATOMY
NEW: Research Focus 2-1 , Agenesis of the Cerebellum.
UPDATED Figure 2-2 charts ENS in anatomic and functional nervous
system organization.
NEW: §2-5 introduces the enteric nervous system, diagrammed in
NEW Figure 2-31 .

CHAPTER 3: NEURONAL ANATOMY

UPDATED Focus 3-3 describes chlorotoxin-based methods for
identifying and treating brain tumors.
NEW photos: social roboticist Heather Knight with Marilyn Monrobot,
Figure 3-6 ; Woody Guthrie, Focus 3-4; Chris Burke, Figure 3-22 .

CHAPTER 4: NERVOUS SYSTEM ELECTRICAL ACTIVITY

UPDATED Focus 4-1, Epilepsy, details electrographic seizure and
alternatives to drug treatments.
UPDATED: Multiple Sclerosis now Focus 4-2; Focus 4-4, ALS: Lou
Gehrig’s Disease, profiles Stephen Hawking’s 50-year-plus battle with
ALS.
CONDENSED: Myasthenia gravis coverage and photos conclude §4-4.
Every chapter’s central question highlights the brain–behavior
relationship. When we first describe how neurons communicate in
Section 5-4 , for example, we also describe how synaptic plasticity
serves as the basis of learning. Later, in Section 14-4 , we expand on
plasticity as we explore learning and memory.
As it was when we wrote the First Edition, our goal in this new
edition is to bring coherence to a vast subject by helping students
understand the big picture. Asking fundamental questions about the brain
has another benefit: it piques students’ interest and challenges them to
join us on the journey of discovery that is brain science.
Scientific understanding of the human brain and human behavior
continues to grow at an exponential pace. We want to communicate the
excitement of recent breakthroughs in brain science and to relate some of
our own experiences from a combined 120+ years of studying brain and
behavior, both to make the field’s developing core concepts and latest
revelations understandable and to transport uninitiated students to the
frontiers of physiological psychology.
Areas of Emphasis
To convey the excitement of neuroscience as researchers understand it,
we interweave evolution, genetics, and epigenetics;
psychopharmacology; and neural plasticity and connectivity, including
CNS and ENS interactions, throughout the book.
EVOLUTION Our perspective—neuroscience in an evolutionary
context—recurs in almost every chapter. By focusing on comparative
behavior and anatomy, we address nervous system evolution in depth in
Chapters 1 and 2 , evolution of the synapse in Section 5-1 , and evolution
of visual pathways in Section 9-2 . We add ideas about how natural
selection might promote overeating in Section 12-5 and evolutionary
theories of sleeping and dreaming in Section 13-3 . We describe the
evolution of sex differences in spatial cognition and language in Section
15-5 and links between our evolved reactions to stress and anxiety
disorders in Section 16-4 .
GENETICS AND EPIGENETICS We introduce the foundations of
genetic and epigenetic research in Sections 1-3 and 2-1 and begin to
elaborate on them in Section 3-3 . Chapter 5 includes discussions of
metabotropic receptors and DNA and of learning and genes. The
interplay of genes and drug action is integral to Chapter 6 , as are the
developmental roles of genes and gene methylation to Chapter 8 .
Section 9-4 explains the genetics of color vision, and the genetics of
sleep disorders anchors Section 13-6 . Section 14-4 now includes the role
of epigenetics in memory. Sections 16-1 and 16-3 consider the roles of
genetics and of prions in understanding the causes of behavioral
disorders.
PSYCHOPHARMACOLOGY Chapter 6 investigates how drugs and
hormones affect behavior, topics we revisit often through the book. You
will find coverage of drugs and information transfer in Section 4-3 ,
drugs and cellular communication in Section 5-3 , and synthetic
neurobiology in Section 7-1 . Section 12-6 covers drugs and motivation;
Section 13-6 , drugs and sleep disorders; and Section 14-4 , neuronal
changes with drug use. Section 16-2 discusses the promise of the
liposome as a delivery vehicle in pharmacological treatments, and
Section 16-4 , drugs used as treatments for a range of behavioral
disorders.
CONNECTIVITY Neural plasticity is a hallmark of this book. We
introduce the concept in Section 1-5 , define it in Section 2-1 , develop it
in Section 2-6 , and expand on it throughout. At the conclusion of
Section 14-4 , we elaborate seven Guiding Principles of Brain Plasticity.
We describe the expanding boundaries of connectomics in Section 15-3 .
The new field of psychotropics, which identifies the connection between
the gut microbiome and its effects on the enteric nervous system—as
well as on the central nervous system—appears in Sections 2-5 and 12-5
.

CHAPTER 5: NEUROTRANSMISSION
NEW in §5-2: Lipid Transmitters focuses on endocannabinoids ;
Varieties of Receptors introduces subunits plus NEW Table 5-3 , Small-
Molecule Transmitter Receptors.
NEW in §5-3: enteric nervous system–CNS autonomy.
REVAMPED: neural bases of habituation and sensitization responses in
Aplysia, in §5-4.

CHAPTER 6: DRUGS AND HORMONES

STREAMLINED Table 6-1 , Grouping Psychoactive Drugs.
UPDATED coverage: endogenous opioid peptides and anandamide
psychedelics in §6-2.
UPDATED statistics in Figure 6-16 , Drug Use in the United States.
REVAMPED: Glucocorticoids and Stress in §6-5 features discrete
sections on Activating a Stress Response and on Ending one.

CHAPTER 7: RESEARCH METHODS

REFOCUSED: Figure 7-5 , Pathology in Parkinson Disease,
accompanies discussion of Brain Lesions in §7-1.
NEW coverage: synthetic biology and chemogenetics, including
DREADD, and temporary and reversible lesion techniques in §7-1.
REVAMPED: Single-Cell Recording begins §7-2, including NEW
Figure 7-8 , Spatially Related Cells.
NEW: Tables 7-1 and 7-2 summarize neuroscience research methods
that Measure and Manipulate Brain–Behavior Relations, in §7-6.
UPDATED in §7-7: Animal Models of Disease and Animal Welfare and
Scientific Experimentation.

CHAPTER 8: DEVELOPMENT
NEW Clinical Focus 8-1, Linking SES to Cortical Development, sets a
chapterwide theme.
NEW in §8-4: infant sexual differentiation now introduces Hormones
and Brain Development; Gut Bacteria and Brain Development reveals
the microbiome’s influence.
UPDATED in §8-4: fetal exposure statistics in Drugs and Brain
Development; coverage of SIDS.
Scientific Background Provided
We describe the journey of discovery that is neuroscience in a way that
students just beginning to study the brain and behavior can understand;
then they can use our clinical examples to tie its relevance to the real
world. Our approach provides the background students need to
understand introductory brain science. Multiple illustrated Experiments
in 13 chapters help them visualize the scientific method and how
scientists think. The Basics features in 6 chapters address the fact that
understanding brain function requires understanding information from all
the basic sciences.
These encounters can prove both a surprise and a shock to students
who come to the course without the necessary background. The Basics
features in Chapters 1 and 2 address the relevant evolutionary and
anatomical background. In Chapter 3 , The Basics provides a short
introduction to chemistry before the text describes the brain’s chemical
activities. In Chapter 4 The Basics addresses electricity before exploring
the brain’s electrical activity.
Readers already comfortable with the material can easily skip it; less
experienced readers can learn it and use it as a context for neuroscience.
Students with this background can tackle brain science with greater
confidence. Similarly, for students with limited knowledge of basic
psychology, we review such facts as stages of behavioral development in
Chapter 8 and forms of learning and memory in Chapter 14 .
Students in social science disciplines often remark on the amount of
biology and chemistry in the book, whereas an equal number of students
in biological sciences remark on the amount of psychology. More than
half the students enrolled in the Bachelor’s of Science in Neuroscience
program at the University of Lethbridge have switched from a
biochemistry or psychology major after taking this course. We must be
doing something right!
Chapter 7 showcases the range of methods behavioral neuroscientists
use to measure and manipulate brain and behavior—traditional methods
and such cutting-edge techniques as optical tomography, resting-state
fMRI, chemogenetics, and DREADD. Expanded discussions of
techniques appear where appropriate, especially in Research Focus
features, including Focus 3-2, Brainbow: Rainbow Neurons; Focus 4-3,
Optogenetics and Light-Sensitive Channels; and Focus 16-1,
Posttraumatic Stress Disorder, which includes treatments based on
virtual reality exposure therapies.
Finally, because critical thinking is vital to progress in science, select
discussions throughout the book center on relevant aspects. Section 1-2
concludes with The Separate Realms of Science and Belief. Focus 15-3,
The Rise and Fall of Mirror Neurons, demonstrates how the media—and
even scientists—can fail to question the validity of research results.
Section 12-5 introduces the idea that gender identity comprises a broad
spectrum rather than a female–male dichotomy. Section 7-7 considers
issues of animal welfare in scientific research and the use of laboratory
animal models to mimic human neurologic and psychiatric disorders.
Clinical Focus Maintained
Neuroscience is a human science. Everything in this book is relevant to
our lives, and everything in our lives is relevant to neuroscience.
Understanding neuroscience helps us understand how we learn, how we
develop, and how we can help people with brain and behavioral
disorders. Knowledge of how we learn, how we develop, and the
symptoms of brain and behavioral disorders offer insights into
neuroscience.
Clinical material also helps to make neurobiology particularly
relevant to students who are going on to a career in psychology, social
work, or another profession related to mental health, as well as to
students of the biological sciences. We integrate clinical information
throughout the text and Clinical Focus features, and we expand on it in
Chapter 16 , the book’s capstone, as well.

CHAPTER 9: SENSATION, PERCEPTION, AND VISION

NEW Focus 9-1 photo echoed chapterwide, illustrating receptive fields,
§9-1; visual stream functions, §9-2; neural spatial coding (§9-3),
luminance contrast, §9-4; visual pathway injury, §9-5.
UPDATED: §9-2 introduces Müller cells’ role in retinal function;
discussion of photoreceptor luminance expanded.
NEW photos in Focus 9-3, Color-Deficient Vision, contrast trichromatic
vision to protanopia and deuteranopia.
NEW photo: the dress that sparked a controversy illustrates color
constancy in §9-4.

CHAPTER 10: AUDITION

NEW: Clinical Focus 10-2, Otoacoustic Emissions.
NEW Figure 10-15 illustrates EXPANDED text coverage of cochlear
implants.
NEW photo in Figure 10-17 : an owl skull illustrates interaural intensity
difference (IID).
UPDATED coverage, Music as Therapy, concludes §10-4.
UPDATED: Echolocation in Bats in §10-5.

CHAPTER 11: MOVEMENT AND SOMATOSENSATION

NEW photo: a robotic arm controlled by a brain–computer–brain
interface in UPDATED Research Focus 11-1 , Neuroprosthetics.
NEW: Focus 11-2, Cerebral Palsy, introduces the connectome as an
investigative tool.
NEW photo: wheelchair basketball team scrimmage in Focus 11-3,
Spinal Cord Injury.
NEW Figure 11-8 illustrates EXPANDED coverage of Graziano’s
movement categories.
In An Introduction to Brain and Behavior, the placement of some
topics is novel relative to traditional treatments. We include brief
descriptions of brain diseases close to discussions of basic associated
processes, as exemplified in the integrated coverage of Parkinson disease
through Chapter 5 , How Do Neurons Communicate and Adapt? This
strategy helps first-time students repeatedly forge close links between
what they are learning and real-life issues.
To provide a consistent disease nomenclature, the Fifth Edition
follows the system advocated by the World Health Organization for
diseases named after their putative discoverers. Down syndrome, for
example, has largely replaced Down’s syndrome in the popular and
scientific literature. We extend that convention to Parkinson disease and
Alzheimer disease, among other eponymous diseases and disorders.
The nearly 150 disorders we cover are cross-referenced in the Index
of Disorders inside the book’s front cover. Chapter 16 expands on the
nature of neuroscience research and the multidisciplinary treatment
methods for neurological and psychiatric disorders described in
preceding chapters. Its discussion of causes and classifications of
abnormal behavior includes updated Table 16-3 , now thoroughly revised
to conform to the DSM-5 classification.
We emphasize questions that relate to the biological bases of
behavior. For us, the excitement of neuroscience lies in understanding
how the brain explains what we do, whether it is talking, sleeping,
seeing, or learning. Readers will therefore find nearly as many
illustrations about behavior as illustrations about the brain. This
emphasis on explaining the biological foundation of behavior is another
reason that we include a mix of Clinical, Research, and Comparative
Focus features throughout the text.
Abundant Chapter Pedagogy
Building on the innovative teaching devices described so far, numerous
in-text pedagogical aids adorn every chapter, beginning with an outline
and an opening Focus feature that draws students into the chapter’s topic.
Focus features dot each chapter to connect brain and behavior to relevant
clinical or research experience. Within chapters, definitions of boldface
key terms introduced in the text appear in the margins as reinforcement,
margin notes link topics together, and end-of-section Review self-tests
help students check their grasp of major points.
Each chapter ends with a Summary—several include summarizing
tables or illustrations to help students visualize or review big-picture
concepts—and a list of Key Terms, each referenced to the page number
on which the term is defined. Following this Preface, the Media and
Supplements section describes the wide array of supplemental materials
designed exclusively for students and teachers using the Fifth Edition.
Superb Visual Reinforcement
Our most important learning aid appears on nearly every page in the
book: an expansive and, we believe, exceptional set of illustrations.
Overwhelmingly, readers agree that, hand in hand with our words, the
diagrams describe and illuminate the nervous system. Important
anatomical illustrations are large-format to ease perusal. We have
retained applications photos that range from a dance class for Parkinson
patients in Section 5-3 to a seniors’ bridge game in Section 16-3 . New
photos include, to illustrate color constancy in Section 9-4 , the dress that
inspired a social media controversy.
Illustrations are consistent from chapter to chapter so as to reinforce
one another. We consistently color-code diagrams that illustrate each
aspect of the neuron, depict each structural region in the brain, and
demark nervous system divisions. We include many varieties of
micrographic images to show what a particular neural structure actually
looks like. These illustrations and images are included on our
PowerPoint presentations and integrated as labeling exercises in our
Study Guide and Testing materials.

CHAPTER 12: EMOTION, MOTIVATION, CHEMICAL SENSES

UPDATED estimates of the number of smells humans can discriminate
in §12-2.
UPDATED: Stimulating and Expressing Emotion in §12-4 explains how
the ENS interacts with other neural systems.
NEW: mindfulness training as a treatment strategy for anxiety disorders
in Clinical Focus 12-3 .
UPDATED: Clinical Focus 12-4 includes a high-fiber food component
in any weight loss strategy; Figure 12-24 charts the ENS, hormones, and
cognition as major factors in controlling eating.
UPDATED in §12-5: the spectrum of gender identity, including
transgender identity, illustrated by Bruce Jenner’s transition to Caitlyn
Jenner.
NEW Figure 12-30 : mapped by rs-fMRI, areas affected by nicotine
illustrate the breadth of the brain’s reward system.
 CHAPTER 13: SLEEP
NEW photo: schoolchildren using light treatment to combat SAD in
Focus 13-2.
NEW table: Recommended Sleep Duration times, by age group, in §13-
3.
UPDATED: REM Sleep Disorders in §13-6 includes NEW subsections:
Sleep Paralysis, Cataplexy, and REM Sleep Behavioral Disorder.

CHAPTER 14: LEARNING AND MEMORY

NEW discussion: highly superior autobiographical memory (HSAM) in
§14-1.
NEW: Figure 14-12 illustrates EXPANDED discussion of spatially
related cells that constitute our neural GPS.
NEW neuroimages: Figure 14-6 , impaired autobiographical memory;
Focus 14-3, neurofibrillary tangle formed by misfolded tau proteins;
Figure 14-26 , brain sections show cortical stroke and repair via induced
neurogenesis.
Teaching Through Metaphors, Examples,
and Principles
If a textbook is not enjoyable, it has little chance of teaching well. We
heighten students’ interest through abundant use of metaphors and
examples. Students read about patients whose brain injuries offer
insights into brain function, and we examine car engines, robots, and
prehistoric flutes for the same purpose. Frequent illustrated Experiments,
comparative biology examples, and representative Comparative Focus
features help students understand how much we humans have in
common with creatures as far distant from us as sea slugs and as close to
us as chimpanzees.
We also facilitate learning by reemphasizing main points and by
distilling sets of principles about brain function that offer a framework to
guide students’ thinking. Thus, Section 2-6 introduces ten key principles
that explain how the parts of the nervous system work together. Section
14-4 summarizes seven guiding principles of neuroplasticity. These sets
of principles form the basis of many discussions throughout the book.
Frequently, marginal notes remind readers when they encounter these
principles again—and where to review them in depth.
Big-Picture Emphasis
One challenge in writing an introductory book on any topic is deciding
what to include and what to exclude. We organize discussions to focus
on the bigger picture—a focus exemplified by the ten principles of
nervous system function introduced in Section 2-6 and echoed
throughout the book. Any set of principles may be arbitrary yet
nevertheless afford students a useful framework for understanding the
brain’s activities.
In Chapters 8 through 16 we tackle behavioral topics in a more
general way than most contemporary books do. In Chapter 12 , for
instance, we revisit experiments and ideas from the 1960s to understand
why animals behave as they do, then we consider emotional and
motivated behaviors as diverse as eating and anxiety attacks in humans.
In Chapter 14 , the larger picture of learning and memory is presented
alongside a discussion of recovery from traumatic brain injury.
This broad focus helps students grasp the big picture that behavioral
neuroscience paints. While broadening our focus requires us to leave out
some details, our experience with students and teachers through four
earlier editions confirms that discussing the larger problems and issues in
brain and behavior is of greater interest to students, especially those new
to this field, and is more often remembered than are myriad details
without context.
As in preceding editions, we are selective in our citation of the truly
massive literature on the brain and behavior because we believe that too
many citations can disrupt the text’s flow and distract students from the
task of mastering concepts. We provide citations to classic works by
including the names of the researchers and by mentioning where the
research was performed. In areas where controversy or new
breakthroughs predominate, we also include detailed citations—177 in
all—to papers (especially reviews) from the years 2013 to 2016. An end-
of-book References section lists, by chapter, all the literature used in
developing the book, reflecting the addition of about 200 new citations
total in this edition and elimination of other, now superseded, research.

CHAPTER 15: COGNITION

NEW: Hebb’s cell assembly diagram concludes §15-1.
NEW: Research Focus 15-3 , The Rise and Fall of Mirror Neurons.
UPDATED discussions: connectomics and the Human Connectome
Project in §15-3.
NEW research: Cognition and the Cerebellum in §15-3.
NEW: Figure 15-20 maps sex differences in female–male hemispheric
connectivity.
UPDATED: research in §15-5 on brain networks and gender identity.
NEW research on bilingual brain connectivity concludes §15-6.

CHAPTER 16: DISORDERS AND DYSFUNCTION

UPDATED Focus 16-1, PTSD, illustrates increasingly effective VR
exposure therapies.
UPDATED Table 16-3 thoroughly revised to conform to DSM-5.
NEW coverage, §16-2, diagrams a liposome for drug delivery.
NEW chart: in §16-3 F.A.S.T. test for spotting stroke.
NEW discussion in §16-3: Are All Degenerative Dementias Aspects of a
Single Disease? outlines prion theory and its implications, and Figure
16-13 diagrams healthy and misfolded proteins.
Acknowledgements
As in past editions of this text and Fundamentals of Human
Neuropsychology, we have a special debt to Barbara Brooks, our long-
time development editor, who has left a strong imprint on both books.
We sincerely thank as well the many people who also contributed to
the development of this edition. The staff at Worth Publishers is
remarkable and makes revisions a joy to do. We thank our sponsoring
editor, Daniel DeBonis, more than ably assisted by Katie Pachnos; our
project editor, Edgar Doolan; and production manager Paul Rohloff.
We thank design manager Blake Logan for a striking cover and
Charles Yuen for a fresh, inviting, accessible new interior design. Thanks
also to Cecilia Varas for coordinating photo research and to Richard Fox,
who found photographs and other illustrative materials that we would not
have found on our own. We are indebted to Macmillan art manager Matt
McAdams, illustration coordinator Janice Donnola, and medical
illustrator Evelyn Pence for their excellent work in creating new
illustrations.
Our colleagues, too, have helped in the development of every edition.
For their contributions in shaping the Fifth Edition, we are especially
indebted to the reviewers who provided extensive comments on selected
chapters and illustrations: Nancy Blum, California State University,
Northridge ; Kelly Bordner, Southern Connecticut State University ;
Benjamin Clark, University of New Mexico ; Roslyn Fitch, University of
Connecticut ; Trevor Gilbert, University of Calgary ; Nicholas Grahame,
Indiana University–Purdue University Indianapolis ; Kenneth Troy
Harker, University of New Brunswick ; Jason Ivanoff, St. Mary’s
University ; Dwight Kravitz, The George Washington University ; Ralph
Lydic, University of Tennessee, Knoxville ; Paul Meyer, The State
University of New York at Buffalo ; Jaime Olavarria, University of
Washington ; Christopher Robison, Florida State University ; Claire
Scavuzzo, University of Alberta ; Sarah Schock, University of Ottawa ;
Robert Stackman, Florida Atlantic University ; Sandra Trafalis, San Jose
State University ; Douglas Wallace, Northern Illinois University ;
Matthew Will, University of Missouri, Columbia ; and Harris Philip
Zeigler, Hunter College.
Likewise, we continue to be indebted to the colleagues who provided
extensive comments on selected chapters and illustrations during the
development of the Fourth Edition: Mark Basham, Regis University ;
Pam Costa, Tacoma Community College ; Russ Costa, Westminster
College ; Renee Countryman, Austin College ; Kristen D’Anci, Salem
State University ; Trevor James Hamilton, Grant MacGewn University ;
Christian Hart, Texas Woman’s University ; Matthew Holahan, Carleton
University ; Chris Jones, College of the Desert ; Joy Kannarkat, Norfolk
State University ; Jennifer Koontz, Orange Coast College ; Kate
Makerec, William Paterson University of New Jersey ; Daniel Montoya,
Fayetteville State University ; Barbara Oswald, Miami University of
Ohio ; Gabriel Radvansky, University of Notre Dame ; Jackie Rose,
Western Washington University ; Steven Schandler, Chapman University
; Maharaj Singh, Marquette University ; Manda Williamson, University
of Nebraska—Lincoln.
We’d also like to thank the reviewers who contributed their thoughts
to the Third Edition: Chana Akins, University of Kentucky ; Michael
Anch, Saint Louis University ; Maura Mitrushina, California State
University, Northridge ; Paul Wellman, Texas A&M University ; and
Ilsun White, Morehead State University. The methods chapter was new
to the Third Edition and posed the additional challenge of taking what
easily could read like a seed catalog and making it engaging to readers.
We therefore are indebted to Margaret G. Ruddy, The College of New
Jersey, and Ann Voorhies, University of Washington, for providing
extensive advice on the initial version of Chapter 7 .
In addition, we thank the reviewers who provided their thoughts on
the Second Edition: Barry Anton, University of Puget Sound ; R. Bruce
Bolster, University of Winnipeg ; James Canfield, University of
Washington ; Edward Castañeda, University of New Mexico ; Darragh P.
Devine, University of Florida ; Kenneth Green, California State
University, Long Beach ; Eric Jackson, University of New Mexico ;
Michael Nelson, University of Missouri, Rolla ; Joshua S. Rodefer,
University of Iowa ; Charlene Wages, Francis Marion University ; Doug
Wallace, Northern Illinois University ; Patricia Wallace, Northern
Illinois University ; and Edie Woods, Madonna University. Sheri
Mizumori, University of Washington, deserves special thanks for reading
the entire manuscript for accuracy and providing fresh ideas that proved
invaluable.
Finally, we must thank our tolerant wives for putting up with sudden
changes in plans as chapters returned, in manuscript or in proof, with
hopes for quick turnarounds. We also thank our colleague Robbin Gibb,
who uses the book and has provided much feedback, in addition to our
undergraduate and graduate students, technicians, and postdoctoral
fellows who kept our research programs moving forward when we were
engaged in revising the book.
Bryan Kolb, Ian Q. Whishaw, G. Campbell Teskey
 MEDIA AND SUPPLEMENTS
An Introduction to Brain and Behavior, Fifth Edition, features a wide
array of supplemental materials designed exclusively for students and
teachers of the text. For more information about any of the items, please
visit Worth Publishers’ catalog at www.macmillanhighered.com .

to Accompany An Introduction to Brain and

Behavior, Fifth Edition, can be previewed and purchased at
http://www.macmillanhighered.com/launchpad/kolbintro5e .
For Students
LaunchPad with LearningCurve Quizzing
A comprehensive Web resource for teaching and learning psychology
LaunchPad combines Worth Publishers’ award-winning media with
an innovative platform for easy navigation. For students, it is the
ultimate online study guide, with rich interactive tutorials, videos,
interactive e-Book, and the LearningCurve adaptive quizzing system. For
instructors, LaunchPad is a full-course space where class documents can
be posted, quizzes are easily assigned and graded, and students’ progress
can be assessed and recorded. Whether you are looking for the most
effective study tools or a robust platform for an online course,
LaunchPad is a powerful way to enhance your class.
LaunchPad for An Introduction to Brain and Behavior, Fifth Edition,
includes the following resources:
• THE LEARNINGCURVE quizzing system, written by Carolyn
Ensley of Wilfrid Laurier University, is a new media component for
this edition. LearningCurve combines adaptive question selection,
immediate and valuable feedback, and a gamelike interface to engage
students in a learning experience that is unique to them. Each
LearningCurve quiz is fully integrated with other resources in
LaunchPad through the Personalized Study Plan, so that students will
be able to review with Worth’s extensive library of videos and
activities. And state-of-the-art question analysis reports allow
instructors to track the progress of individual students as well as their
class as a whole.
 An Introduction to Brain and Behavior, Fifth Edition, and
can be ordered together with
ISBN 10: 1-319-06192-3
ISBN-13: 978-1-319-06192-0
• SUMMATIVE QUIZZES, another new media component to this
edition, were written by Linda Lockwood of the Metropolitan State
University. Each quiz is written on the topics discussed throughout
each chapter and features a variety of multiple-choice questions
presented to students randomly from question pools. Valuable to both
student and instructor, the summative quizzes are a useful learning tool
to propel students’ understanding of the information introduced in the
book.
• AN INTERACTIVE E-BOOK allows students to highlight,
bookmark, and make notes, just as they would with a printed textbook.
The search function and in-text glossary definitions make the text
ready for the digital age.
• STUDENT VIDEO ACTIVITIES include engaging modules that
instructors can easily assign for student assessment. Videos cover a
variety of topics and are sure to spark discussion and encourage
critical thinking.
• THE SCIENTIFIC AMERICAN NEWSFEED delivers weekly
articles, podcasts, and news briefs on the very latest developments in
 psychology from the first name in popular science journalism.
• THE NEUROSCIENCE TOOL KIT is a powerful Web-based tool
for learning the core concepts of behavioral neuroscience—by
witnessing them firsthand. These 30 interactive tutorials allow students
to see the nervous system in action via dynamic illustrations,
animations, and models that demystify the neural mechanisms behind
behavior. Carefully crafted multiple-choice assessments make it easy
to assign and assess each activity. Based on Worth Publishers’
groundbreaking CD-ROM, Foundations of Behavioral Neuroscience,
the Neuroscience Tool Kit is a valuable accompaniment to any
biopsychology course.

• PSYCHOLOGY AND THE REAL WORLD: ESSAYS

ILLUSTRATING FUNDAMENTAL CONTRIBUTIONS TO
SOCIETY, SECOND EDITION is a superb collection of essays by
major researchers describing their landmark studies. Published in
association with the not-for-profit FABBS Foundation, this engaging
reader includes Bruce McEwen’s work on the neurobiology of stress
and adaptation, Jeremy Wolfe’s look at the importance of visual
search, Elizabeth Loftus’s reflections on her study of false memories,
and Daniel Wegner’s study of thought suppression. A portion of the
proceeds is donated to FABBS to support societies of cognitive,
psychological, behavioral, and brain sciences.
For Instructors
REVISED! INSTRUCTOR’S RESOURCES This invaluable tool, for new and
experienced instructors alike, was revised by Catherine Smith of
Carleton University. It includes chapter-by-chapter learning objectives
and chapter overviews, detailed lecture outlines, thorough chapter
summaries, chapter key terms, in-class demonstrations and activities,
springboard topics for discussion and debate, ideas for research and term
paper projects, homework assignments and exercises, and suggested
readings from journals and periodicals. Course-planning suggestions and
a guide to videos and Internet resources also are included. The
Instructor’s Resources can be downloaded from Worth’s online catalog at
www.macmillanhighered.com .

Assessment Tools
Downloadable Diploma Computerized Test Bank Prepared and
revised by Christopher Striemer of Grant MacEwan University, the Test
Bank includes a battery of more than 1300 multiple-choice and short-
answer test questions, as well as diagram exercises. Each item is keyed
to the page in the textbook on which the answer can be found. All the
questions have been thoroughly reviewed and edited for accuracy and
clarity. The Diploma software allows users to add, edit, scramble, or
reorder items. The Test Bank also allows you to export into a variety of
formats that are compatible with many Internet-based testing products.
For more information on Diploma, please visit
https://blackboard.secure.force.com . The Test Bank files can be
downloaded from Worth’s online catalog at
www.macmillanhighered.com .

Presentation
Illustration Slides and Lecture Slides Available for download from
www.macmillanhighered.com , these slides can either be used as they are
or customized to fit the needs of your course. There are two sets of slides
for each chapter. The Illustration slides feature all the figures, photos,
and tables. The Lecture slides, prepared and revised by Matthew
Holahan of Carleton University, feature main points of the chapter with
selected figures and illustrations.
CHAPTER

What Are the Origins of

Brain and Behavior?
 Katherine Streeter

CLINICAL FOCUS 1-1 LIVING WITH TRAUMATIC BRAIN

INJURY
1-1 NEUROSCIENCE IN THE TWENTY-FIRST CENTURY
WHY STUDY BRAIN AND BEHAVIOR?
WHAT IS THE BRAIN?
WHAT IS BEHAVIOR?
1-2 PERSPECTIVES ON BRAIN AND BEHAVIOR
ARISTOTLE AND MENTALISM
DESCARTES AND DUALISM
DARWIN AND MATERIALISM
COMPARATIVE FOCUS 1-2 THE SPEAKING BRAIN
EXPERIMENT 1-1 QUESTION: HOW DO PARENTS TRANSMIT
HERITABLE FACTORS TO OFFSPRING?
CONTEMPORARY PERSPECTIVES ON BRAIN AND BEHAVIOR
1-3 EVOLUTION OF BRAINS AND OF BEHAVIOR
ORIGIN OF BRAIN CELLS AND BRAINS
THE BASICS CLASSIFICATION OF LIFE
EVOLUTION OF NERVOUS SYSTEMS IN ANIMALS
CHORDATE NERVOUS SYSTEM
1-4 EVOLUTION OF THE HUMAN BRAIN AND BEHAVIOR
HUMANS: MEMBERS OF THE PRIMATE ORDER
AUSTRALOPITHECUS : OUR DISTANT ANCESTOR
THE FIRST HUMANS
RELATING BRAIN SIZE AND BEHAVIOR
COMPARATIVE FOCUS 1-3 THE ELEPHANT’S BRAIN
WHY THE HOMINID BRAIN ENLARGED
1-5 MODERN HUMAN BRAIN SIZE AND INTELLIGENCE
MEANING OF HUMAN BRAIN SIZE COMPARISONS
ACQUISITION OF CULTURE
CLINICAL FOCUS 1-1

Living with Traumatic Brain Injury

Fred Linge, a clinical psychologist with a degree in brain research,
wrote this description 12 years after his head injury occurred:
In the second it took for my car to crash head-on, my life was permanently changed, and
I became another statistic in what has been called “the silent epidemic.”
During the next months, my family and I began to understand something of the
reality of the experience of head injury. I had begun the painful task of recognizing and
accepting my physical, mental, and emotional deficits. I couldn’t taste or smell. I
couldn’t read even the simplest sentence without forgetting the beginning before I got to
the end. I had a hair-trigger temper that could ignite instantly into rage over the most
trivial incident.…
Two years after my injury, I wrote a short article: “What Does It Feel Like to Be
Brain Damaged?” At that time, I was still intensely focusing on myself and my own
struggle. (Every head-injured survivor I have met seems to go through this stage of
narcissistic preoccupation, which creates a necessary shield to protect them from the
painful realities of the situation until they have a chance to heal.) I had very little sense
of anything beyond the material world and could only write about things that could be
described in factual terms. I wrote, for example, about my various impairments and how
I learned to compensate for them by a variety of methods.
At this point in my life, I began to involve myself with other brain-damaged people.
This came about in part after the publication of my article. To my surprise, it was
reprinted in many different publications, copied, and handed out to thousands of
survivors and families. It brought me an enormous outpouring of letters, phone calls,
and personal visits that continue to this day. Many were struggling as I had struggled,
with no diagnosis, no planning, no rehabilitation, and most of all, no hope…. The
catastrophic effect of my injury was such that I was shattered and then remolded by the
experience, and I emerged from it a profoundly different person with a different set of
convictions, values, and priorities. (Linge, 1990)
 Susan Walsh/AP/Wide World Photos
U.S. Representative Gabrielle Giffords (D-AZ) reenacts her
swearing-in with House Speaker John Boehner in January 2011,
days before a gunshot through the left side of her brain left her
near death.

Valerie Macon/Getty Images

Giffords and husband, astronaut Mark Kelly, 16 months later:
she had regained limited speech, but mobility on her right side
remained limited.
 In the years after his traumatic brain injury (TBI)—a wound to
the brain that results from a blow to the head—Fred Linge made a
journey. Before the car crash, he gave little thought to the relation
between his brain and his behavior. After the crash, adapting to his
injured brain and behavior dominated his life. On his journey, Linge
learned how his injured brain affected his behavior, he relearned
many skills, and he learned to compensate for the impairments his
changed brain imposed on him.
 Neuroscience in the Twenty-First
1-1

Century
Fred Linge emerged profoundly changed from his journey of learning to
live with traumatic brain injury (TBI). The purpose of this book is to
take you on a journey toward understanding the link between brain and
behavior: how the brain is organized to produce behavior. Evidence
comes from studying three sources: (1) the evolution of brain and
behavior in diverse animal species, (2) how the brain is related to
behavior in typical people, and (3) how the brain changes in people with
brain damage or other brain dysfunction. The knowledge emerging from
these three lines of study is changing how we think about ourselves, how
we structure education and our social interactions, and how we aid those
with brain injury, disease, and disorder.
traumatic brain injury (TBI) Wound to the brain that results from
a blow to the head.
Illustrated Experiments through the book reveal how neuroscientists
conduct research, beginning with Experiment 1-1 in Section 1-2 .
We will marvel at the potential for future discoveries. We will begin
to understand how genes influence the brain’s structure and activity. We
will learn how our experience in turn changes our genes. We will review
developments in brain imaging techniques that allow us to watch our
own brain in action as we think and solve problems or sleep. We will
consider the goals of brain–behavior research in arresting the progress of
brain disease and finding cures for brain disease and injury. We will
marvel at the injured brain interacting with machines that serve as
prosthetics. We will consider the possibility of repairing and even
replacing malfunctioning brains. We will also consider the possibility of
interacting with artificial brains—brains of our making that can, in
principle, match our intelligence or perhaps even surpass it. Our journey
will broaden your understanding of what makes us human.

Why Study Brain and Behavior?

The brain is a physical object, a living tissue, a body organ. Behavior is
action, momentarily observable but fleeting. Brain and behavior differ
greatly but are linked. They have evolved together: one is responsible for
the other, which is responsible for the other, and so on. There are three
reasons for linking the study of the brain to the study of behavior:
1. How the brain produces behavior is a major unanswered scientific
question. Scientists and students study the brain to understand
humanity. Understanding brain function will allow improvements in
many aspects of our world, including educational systems, economic
systems, and social systems. Many chapters in this book touch on the
relation between psychological questions related to brain and behavior
and philosophical questions related to humanity. For example, in
Chapters 14 and 15 , we address how we become conscious, how we
speak, and how we remember.
2. The brain is the most complex living organ on Earth and is found in
many groups of animals. Students of the brain want to understand its
place in the biological order of our planet. This chapter describes the
basic structure and evolution of brains, especially the human brain.
Chapter 2 surveys its functional anatomy, and Chapters 3 through 5
describe the functioning of brain cells—the building blocks of every
animal’s brain.
3. A growing list of behavioral disorders can be explained and treated as
we increase our understanding of the brain. More than 2000 disorders
may in some way be related to brain abnormalities. As indexed inside
the front cover of this book, we detail relations between brain
disorders and behavioral disorders in every chapter, especially in the
Focus features.
None of us can predict how the knowledge we gain about the brain
and behavior may prove useful. A former psychology major wrote to tell
us that she took our course because she was unable to register in a
preferred course. She felt that, although our course was interesting, it
was “biology, not psychology.” After graduating and getting a job in a
social service agency, she has found to her delight that understanding the
links between brain and behavior is in fact a source of insight into many
of her clients’ disorders and the treatment options available for them.

What Is the Brain?

Brain, the Anglo-Saxon word for the tissue found within the skull, is but
a part of the human nervous system ( Figure 1-1 ). Most connections
between the brain and the rest of the body are made through the spinal
cord, which descends from the brainstem through a canal in the
backbone.
spinal cord Part of the central nervous system encased within the
vertebrae (spinal column); provides most of the connections
between the brain and the rest of the body.

Major Divisions of the Human Nervous

FIGURE 1-1

System The brain and spinal cord together make up the central
nervous system. All of the nerve processes radiating out beyond the brain
and spinal cord and all of the neurons outside the CNS connect to sensory
receptors, muscles, and internal body organs to form the peripheral
nervous system.

Together, the brain and spinal cord make up the central nervous
system (CNS). The CNS is encased in bone, the brain by the skull and
the spinal cord by the backbone, or vertebrae. The CNS is called central
both because it is physically the nervous system’s core and is as well the
core structure mediating behavior. All of the processes radiating out
beyond the brain and spinal cord constitute the peripheral nervous
system (PNS).
central nervous system (CNS) The brain and spinal cord, which
together mediate behavior.
peripheral nervous system (PNS) All of the neurons in the body
outside the brain and spinal cord; provides sensory and motor
connections to and from the central nervous system.
The human nervous system is composed of cells, as is the rest of the
body, and these nerve cells, or neurons, control behavior most directly.
Neurons in the brain communicate with one another, with sensory
receptors in the skin, with muscles, and with internal body organs. As
shown in Figure 1-2 , the human brain comprises two major sets of
structures. The cerebrum (forebrain), shown in Figure 1-2A , has two
nearly symmetrical halves, called hemispheres, one on the left and one
on the right. The cerebrum is responsible for most of our conscious
behaviors. It enfolds the brainstem (Figure 1-2B ), a set of structures
responsible for most of our unconscious behaviors. The second major
brainstem structure, the cerebellum, is specialized for learning and
coordinating our movements. Its conjoint evolution with the cerebrum
suggests that it assists the cerebrum in generating many behaviors.
neuron Specialized nerve cell engaged in information processing.
cerebrum (forebrain) Major structure of the forebrain that consists
of two mirror-image hemispheres (left and right) and is responsible
for most conscious behavior.
hemisphere Literally, half a sphere, referring to one side of the
cerebrum.
brainstem Central structure of the brain; responsible for most
unconscious behavior.
cerebellum Major brainstem structure specialized for learning and
coordinating movements; assists the cerebrum in generating many
behaviors.
(A) Cerebrum (forebrain)
(B) Right hemisphere of cerebrum
 FIGURE 1-2 The Human Brain (A) Shown head-on, as oriented
within the human skull, are the nearly symmetrical left and right
hemispheres of the cerebrum. (B) A cut through the middle of the brain
from back to front reveals the right hemispheres of the cerebrum and
cerebellum and the right side of the brainstem. The spinal cord (not
shown) emerges from the base of the brainstem. Chapter 2 describes the
brain’s functional anatomy.

Focus 2-1 elaborates cerebellar function by describing a man born

without one.
For his postgraduate research, our friend Harvey chose to study the
electrical activity given off by the brain. He had decided that he wanted
to live on as a brain in a bottle after his body died. He expected that his
research would allow his bottled brain to communicate with others who
could read its electrical signals. Harvey mastered the techniques used to
study the brain’s electrical activity but failed in his objective, not only
because the goal was technically impossible but also because he lacked a
full understanding of what brain means.
Harvey clearly wanted to preserve not just his brain but his self —his
consciousness, his language, and his memory. This meaning of brain
refers to something other than the organ found inside the skull. It refers
to the brain as the body organ that exerts control over behavior. It is what
we intend when we talk of someone smart being a brain or speak of the
computer that guides a spacecraft as being the vessel’s brain. The term
brain, then, signifies both the organ itself and the fact that this organ
produces behavior.
To return to Harvey’s experiment, the effect of placing even the entire
CNS in a bottle would be to separate it from the PNS and thus from the
sensations and movements the PNS mediates. Could the brain function
without sensory information and without the ability to move? Some
evidence suggests that it could not.
One line of research and philosophical argument, called embodied
behavior, proposes that the movements we make and the movements we
perceive in others are central to our behavior (Prinz, 2008). That is, we
understand one another not only by listening to words but also by
observing gestures and other body language. We think not only with
silent language but also with overt gestures and body language. Thus, the
brain as an intelligent entity cannot be divorced from the body’s
activities.
 embodied behavior Theory that the movements we make and the
movements we perceive in others are central to communication with
others.
In the 1920s, Edmond Jacobson wondered what would happen if our
muscles completely stopped moving, a question relevant to Harvey’s
experiment. Jacobson believed that, even when we think we are entirely
motionless, we still make subliminal movements related to our thoughts.
The muscles of the larynx subliminally move when we think in words,
for instance, and we make subliminal eye movements when we imagine
or visualize some action or a person, place, or thing. In Jacobson’s
experiment, then, people practiced “total” relaxation and were later
asked what the experience was like. They reported a condition of mental
emptiness, as if the brain had gone blank (Jacobson, 1932).
In 1957, Woodburn Heron investigated another question related to
Harvey’s experiment: How would the brain cope without sensory input?
He examined the effects of sensory deprivation, including feedback from
movement, by having participants each lie on a bed in a bare, soundproof
room and remain completely still. Padded tubes covered their arms so
that they had no sense of touch, and translucent goggles cut off their
vision. The participants reported that the experience was extremely
unpleasant, not just because of the social isolation but also because they
lost their focus. Some even hallucinated, as if their brain was somehow
trying to create the sensory experiences that they suddenly lacked. Most
asked to be released from the study before it ended.
Figure 12-1 illustrates Heron’s experimental setting. Note : we refer
to healthy people who take part in research studies as participants
and to those with brain or behavioral impairments as subjects or as
patients.
Findings from these lines of research suggest that (1) the CNS needs
ongoing sensory stimulation from the environment and from its own
body’s movement and (2) the brain communicates by producing
movement and observing others’ movements. Thus, when we use the
term brain to mean an intelligent, functioning organ, we are referring to
an active brain that is connected to the rest of the nervous system and
producing behavior.
Yet other evidence suggests that the brain can produce levels of
consciousness with greatly reduced sensory and motor stimulation.
When Martin Pistorius was 12 years old, his health began to deteriorate.
Eventually, he lapsed into a coma. His parents placed Martin in a nursing
home, where over a number of years he became conscious of his
condition, locked-in syndrome, although he remained completely
paralyzed and unable to communicate.
locked-in syndrome Condition in which a patient is aware and
awake but cannot move or communicate verbally because of
complete paralysis of nearly all voluntary muscles except the eyes.
Martin’s condition persisted until, when he was 25, a nurse noticed
him making some small facial movements. He seemed to be trying to
communicate. With rehabilitation, he made excellent progress toward
recovering movement, including using a voice synthesizer. Pistorius has
since married. His book Ghost Boy describes his frustration and
helplessness during years of enduring locked-in syndrome. We return to
this idea of the nature of consciousness in Section 1-2 .
Patients such as Martin Pistorius reveal that the brain can be
conscious to a great extent in the absence of overt behavior. Whether it
can maintain consciousness in the absence of all movement and sensory
experience, the goal of Harvey’s brain in a bottle experiment, remains
unknown.

What Is Behavior?
Irenäus Eibl-Eibesfeldt began his textbook Ethology: The Biology of
Behavior, published in 1970, with the following definition: “Behavior
consists of patterns in time.” These patterns can be made up of
movements, vocalizations, or changes in appearance, such as the facial
movements associated with smiling. The expression patterns in time
includes thinking. We cannot directly observe someone’s thoughts. The
changes in the brain’s electrical and biochemical activity that are
associated with thought show, however, that thinking, too, is a behavior
that forms patterns in time.
The behavioral patterns of animals vary enormously. Animals produce
behaviors that consist of inherited responses, and they also produce
learned behaviors. Most behaviors consist of a mix of inherited and
learned actions. Figure 1-3 illustrates the contributions of mainly
inherited and mainly learned behavior in the eating behavior of two
animal species, crossbills and roof rats.
 A crossbill’s beak is specifically designed to open pine cones.
This behavior is innate.

A baby roof rat must learn from its mother how to eat pine
cones. This behavior is learned.

FIGURE 1-3 Innate and Learned Behaviors Some animal

behaviors are largely innate and fixed (top). Others are largely learned
(bottom). Learning is a form of cultural transmission. Top: Information from J.
Weiner (1995). The beak of the finch (p. 183). New York: Vintage. Bottom: Information from J.
Terkel (1995). Cultural transmission in the black rat: Pinecone feeding. Advances in the Study of
Behavior, 24, p. 122.

A crossbill beak seems awkwardly crossed at the tip, yet it is

exquisitely evolved to eat pine cones. If its shape is changed even
slightly, the bird is unable to eat the pine cones it prefers until its beak
grows back. For crossbills, eating is largely a fixed behavioral pattern: it
is inherited and does not require much modification through learning.
Roof rats, in contrast, are rodents with sharp incisor teeth that appear to
have evolved to cut into anything. Pine cones are an unusual food for the
rats, although they have been found to eat them. But roof rats can eat
pine cones efficiently only if an experienced mother teaches them to do
so. This eating is not only learned, it is cultural in that parents teach it to
offspring. We expand on the concept of culture in Section 1-5 .
The mixture of inherited and learned constraints on behavior varies
considerably from species to species. Generally, animals with smaller,
simpler nervous systems exhibit a narrow range of behaviors that depend
mainly on heredity. Animals with complex nervous systems have more
behavioral options that depend on learning. We humans believe that we
are the animal species with the most complex nervous system and the
greatest capacity for learning new responses. Most of our most complex
behaviors, including reading, writing, mathematics, and using
smartphones, were learned long after our brain evolved its present form.
But most human behaviors retain some mixture of inheritance and
learning, because we humans have not thrown away our simpler nervous
systems. Like other animals, we retain many inherited ways of
responding. The sucking response of a newborn human infant, for
example, is an inherited eating pattern, but later in life eating is strongly
influenced by learning and by culture.
 1-1 REVIEW
Neuroscience in the Twenty-First Century
Before you continue, check your understanding.
1 . ___________ is a wound to the brain that results from a blow to the
head.
2 . The brain and spinal cord together make up the ___________. All of
the nerve fibers radiating out beyond the brain and spinal cord as well
as all of the neurons outside the brain and spinal cord form the
___________.
3 . One major set of brain structures, the ___________, or ___________,
has nearly symmetrical left and right ___________ enfolding the
___________, which connects to the spinal cord.
4 . A simple definition of behavior is any kind of movement in a living
organism. All behaviors have both a cause and a function, but they
vary in complexity and in the degree to which they are ___________,
or automatic, and the degree to which they depend on ___________.
5 . Explain the concept of embodied behavior in a statement or brief
paragraph.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 1-2 Perspectives on Brain and Behavior
Back to our central topic, how the study of brain and behavior are related.
Many philosophers have reasoned about the causes of behavior. Their
speculations can be classified into three broad approaches: mentalism,
dualism, and materialism. After describing each, we explain why
contemporary brain investigators subscribe to the materialist view. In
reviewing these theories, you will recognize that some familiar
“commonsense” ideas about behavior derive from these long-standing
perspectives.

Aristotle and Mentalism

The hypothesis that the mind (or soul or psyche) controls behavior can be
traced back more than 2000 years to ancient Greece. In classical
mythology, Psyche, a mortal, became the wife of the young god Cupid.
Venus, Cupid’s mother, opposed his marriage, so she harassed Psyche
with almost impossible tasks.
 Erich Lessing/Art Resource NY
François Gérard, Psyche and Cupid (1798)

Psyche performed the tasks with such dedication, intelligence, and

compassion that she was made immortal, thus removing Venus’s
objection to her. The ancient Greek philosopher Aristotle was alluding to
this story when he suggested that all human intellectual functions are
produced by a person’s psyche. The psyche, Aristotle argued, is
responsible for life, and its departure from the body results in death.
psyche Synonym for mind, an entity once proposed to be the source
of human behavior.
Aristotle’s account of behavior marks the beginning of modern
psychology, but the brain played no role in it. Aristotle thought the brain
existed to cool the blood. Even if he had thought that the brain ruled
behavior, as did some other philosophers and physicians of his time, it
would have made little difference in the absence of any idea of how a
body organ could produce behavior (Gross, 1995).
To Aristotle, the psyche was responsible for human consciousness,
perceptions, and emotions and for such processes as imagination, opinion,
desire, pleasure, pain, memory, and reason. The nonmaterial psyche was
an entity independent of the body. In formulating the concept of a soul,
Christianity adopted Aristotle’s view that a nonmaterial entity governs
our behavior and that our essential consciousness survives our death.
Mind is an Anglo-Saxon word for memory, and when psyche was
translated into English, it became mind. The philosophical position that a
person’s mind (psyche) is responsible for behavior is mentalism.
Mentalism has influenced modern behavioral science, because many
terms that originated with Aristotle—consciousness, sensation,
perception, attention, imagination, emotion, motivation, memory, and
volition among them—survive today as descriptions of behavior. Indeed,
we use these terms in this book, and they frequently appear as chapter
titles in contemporary psychology and neuroscience textbooks.
mind Proposed nonmaterial entity responsible for intelligence,
attention, awareness, and consciousness.
mentalism Explanation of behavior as a function of the nonmaterial
mind.

Descartes and Dualism

In the first book on brain and behavior, René Descartes (1664), a French
philosopher, proposed a new explanation of behavior in which he retained
the mind’s prominence but gave the brain an important role. Descartes
placed the seat of the mind in the brain and linked the mind to the body.
He stated in the first sentence of Treatise on Man (1664) that mind and
body “must be joined and united to constitute people.”
Descartes’s innovation was the insight into how body organs produce
their actions. He realized that mechanical and physical principles could
explain most activities of body and brain—motion, digestion, and
breathing, for example. Descartes was influenced by complex machines,
including gears, clocks, and waterwheels, being built in Paris at the time.
He saw mechanical gadgets on public display. In the water gardens in
Paris, one device caused a hidden statue to approach and spray water
when an unsuspecting stroller walked past it. The statue’s actions were
triggered when the person stepped on a pedal hidden in the sidewalk.
Influenced by these clever devices, Descartes developed mechanical
principles to explain bodily functions.
But Descartes could not imagine how consciousness could be reduced
to a mechanistic explanation. He thus retained the idea that a nonmaterial
mind governs rational behavior. Descartes did, however, develop a
mechanical explanation for how the mind interacts with the body to
produce movement, working through a small structure at the brain’s
center, the pineal body (pineal gland ). He concluded that the mind
instructed the pineal body, which lies beside fluid-filled brain cavities
called ventricles, to direct fluid from them through nerves and into
muscles (Figure 1-4 ). When the fluid expanded the muscles, the body
would move.
 FIGURE 1-4 Dualist Hypothesis To explain how the mind controls the
body, Descartes suggested that the mind resides in the pineal gland, where
it directs the flow of fluid through the ventricles and into the muscles to
move the body. The pineal gland actually influences daily and seasonal
biorhythms; see Section 13-2 .

Descartes’s thesis that the mind directed the body was a serious
attempt to give the brain an understandable role in controlling behavior.
This idea that behavior is controlled by two entities, a mind and a body, is
dualism (from Latin, meaning two ). To Descartes, the mind received
information from the body through the brain. The mind also directed the
body through the brain. The rational mind, then, depended on the brain
both for information and to control behavior.
dualism Philosophical position that both a nonmaterial mind and a
material body contribute to behavior.
Problems plague Descartes’s dualistic theory. It quickly became
apparent to scientists that people who have a damaged pineal body or
even no pineal body still display typical intelligent behavior. Today, we
understand that the pineal gland’s role in behavior is relegated to
biological rhythms; it does not govern human behavior. We now know
that fluid is not pumped from the brain into muscles when they contract.
Placing an arm in a bucket of water and contracting its muscles does not
cause the water level in the bucket to rise, as it should if the volume of the
muscle increased because fluid had been pumped into it. We now also
know that there is no obvious way for a nonmaterial entity to influence
the body: doing so requires the spontaneous generation of energy, which
violates the physical law of conservation of matter and energy.
The difficulty in Descartes’s theory of how a nonmaterial mind and a
physical brain might interact has come to be called the mind–body
problem. Nevertheless, Descartes proposed that his theory could be
tested to determine whether an organism possessed a mind, Descartes
proposed the language test and the action test. To pass the language test,
an organism, or even an intelligent machine such as a robot, must use
language to describe and reason about things that are not physically
present. The action test requires behavior based on reasoning, not just an
automatic response to a particular situation. Descartes proposed that
nonhuman animals and machines would be unable to pass the tests
because they lacked a mind.
mind–body problem Difficulty of explaining how a nonmaterial
mind and a material body interact.
The contemporary version of Descartes’ language test, the Turing test,
is named for Alan Turing, an English mathematician. In 1950, Turing
proposed that a machine could be judged conscious if a questioner could
not distinguish its answers from a human’s. Machines are close to passing
the Turing test; some might argue that it’s happened. Experimental
research also casts doubt on Descartes’s view that nonhuman animals
cannot pass the language and action tests. Studies of language in apes and
other animals partly seek to discover whether other species can describe
and reason about things that are not present. Comparative Focus 1-2, The
Speaking Brain, summarizes a contemporary approach to studying
language in animals.
A 2014 film, The Imitation Game, dramatizes Turing’s efforts during
World War II to crack the Nazi’s Enigma code.
Descartes’s theory of mind led to bad results. Based on dualism, some
people argued that young children and the insane must lack minds,
because they often fail to reason appropriately. We still use the expression
he’s lost his mind to describe someone who is mentally ill. Some
proponents of dualism also reasoned that, if someone lacked a mind, that
person was simply a machine, not due respect or kindness. Cruel
treatment of animals, children, and the mentally ill has for centuries been
justified by Descartes’s theory. It is unlikely that Descartes himself
intended these interpretations. Reportedly he was very kind to his own
dog, Monsieur Grat.

Darwin and Materialism

By the mid-nineteenth century, another brain–behavior theory emerged.
Materialism advanced the idea that the workings of the brain and the rest
of the nervous system alone fully explain rational behavior. The mind,
literally, is immaterial. Materialism came to prominence when supported
by the evolutionary theory of Alfred Russel Wallace and Charles Darwin.
materialism Philosophical position that behavior can be explained as
a function of the nervous system without recourse to the mind.
COMPARATIVE FOCUS 1-2

The Speaking Brain

Language is such a striking characteristic of our species that it was
once thought unique to humans. Yet evolutionary theory finds it
unlikely that language appeared full-blown in modern humans.
Language does have antecedents in other animals. Many species
lacking a cerebral cortex, including fishes and frogs, are capable of
elaborate vocalizations, and vocalization is still more elaborate in
species having a cerebral cortex, such as birds, whales, and primates.
But can nonhuman animals speak?
In language studies with chimpanzees, humans’ closest living
relatives, scientists have used two approaches: language training and
analyzing spontaneous vocalizations and gestures (Gillespie-Lynch
et al., 2014). To show that nonverbal forms of language might have
preceded verbal language, Beatrice and Alan Gardner (1969) taught
a version of American Sign Language (ASL) to a chimpanzee named
Washoe. Sue Savage-Rumbaugh and her coworkers (1999) taught a
pygmy chimpanzee named Malatta the symbolic language Yerkish.
(The pygmy chimpanzee, or bonobo, is a species thought to be an
even closer relative of humans than other chimps.)
Malatta’s son Kanzi accompanied his mother to class and became
an excellent Yerkish student. Kanzi also displayed clear evidence of
understanding complex human speech. While recording his
vocalizations when interacting with people and eating, Jared
Taglialatela and coworkers found that Kanzi made many sounds
associated with their meanings, or semantic context. For example,
Kanzi associated various peeps with specific foods. The research
group also found that chimps use a raspberry or extended grunt
sound in a specific context to attract the attention of others, including
people.
Imaging brain blood flow associated with the use of
chimpanzeeish indicates that humans and chimpanzees activate the
same brain regions when they speak (Taglialatela, 2011). Wild
bonobos are found to use one distinct call to attract others to feeding
 locations and another to initiate a trip. The animals also use
numerous gestures to signal intent to others.
Stewart Watson and colleagues (2015) report that in two
chimpanzee colonies, the animals used different referential calls
(names) for apples. When the groups were combined, both modified
their calls and adopted a common call, an example of gestural drift
analogous to people adopting the speech patterns of those around
them. The study demonstrates that chimpanzees can learn and share
referential calls.

Laurentiu Garofeanu/Barcroft USA/Barcoft Media via Getty Images

Kanzi

Evolution by Natural Selection

Wallace and Darwin independently arrived at the same conclusion—the
idea that all living things are related. Both outlined this view in papers
presented at the Linnaean Society of London in July 1858. Darwin
further elaborated the topic in his book On the Origin of Species by
Means of Natural Selection, published in 1859. The Origin of Species
presented a wealth of supporting detail, which is why Darwin is regarded
as the founder of modern evolutionary theory.
Both Darwin and Wallace had looked carefully at the anatomy of
animals and at animal behavior. Both were struck by the myriad
characteristics common to so many species despite their diversity. For
example, the skeleton, muscles, and body parts of humans, monkeys, and
other mammals are remarkably similar. So is their behavior: many
animal species reach for food with their forelimbs.
 Such observations led first to the idea that living organisms must be
related, an idea widely held even before Wallace and Darwin. More
important, these same observations led Darwin to explain how the great
diversity in the biological world could have evolved from common
ancestry. Darwin proposed that animals have traits in common because
these traits are passed from parents to their offspring.
Natural selection is Darwin’s theory for explaining how new species
evolve and how existing species change over time. A species is a group
of organisms that can breed among themselves. Individual organisms of
any species vary extensively in their phenotype, the characteristics we
can see or measure. No two individuals of any species are exactly alike.
Some are big, some are small, some are fat, some are fast, some are
light-colored, and some have large teeth.
natural selection Darwin’s theory for explaining how new species
evolve and how existing species change over time. Differential
success in the reproduction of different characteristics (phenotypes)
results from the interaction of organisms with their environment.
species Group of organisms that can interbreed.
phenotype Set of individual characteristics that can be seen or
measured.
Figure 2-1 illustrates this principle of phenotypic plasticity.
Individual organisms whose characteristics best help them to survive
in their environment are likely to leave more offspring than are less-fit
members. This unequal ability of individual members to survive and
reproduce leads to a gradual change in a species’ population over time,
with characteristics favorable for survival in a particular habitat
becoming more prevalent in succeeding generations. Natural selection is
nature’s blueprint for the methods of artificial selection practiced for
centuries by plant and animal breeders to produce organisms with
desirable traits.
Natural Selection and Heritable Factors
Neither Darwin nor Wallace understood the basis of the great variation in
plant and animal species they observed. Another scientist, the monk
Gregor Mendel, discovered one principle underlying phenotypic
variation and how traits pass from parents to their offspring. Through
experiments he conducted on pea plants in his monastery garden
beginning about 1857, Mendel deduced that heritable factors, which we
now call genes, govern various physical traits displayed by the species.
Section 3-3 explains what constitutes a gene, how genes function,
and how genes can change, or mutate.
Members of a species that have a particular genetic makeup, or
genotype, are likely to express (turn on) similar phenotypic traits, as
posited in the Procedure section of Experiment 1-1 . If the gene or
combination of genes for a trait, say, flower color, is passed on to
offspring, the offspring will express the same trait, as illustrated at the
top of the Results section in Experiment 1-1 . Two white-flowered pea
plants produce white-flowered offspring in the first generation, or F1,
and purple-flowered parents produce purple-flowered offspring.
Observing this result, Mendel reasoned that two alternative heritable
elements govern the trait flower color.
genotype Particular genetic makeup of an individual.
 EXPERIMENT 1-1

Question: How do parents transmit heritable factors to

offspring?
Procedure
Mendel crossbred pea plants, then observed which traits parent plants
passed to their offspring in successive generations.
Results

Conclusion: An individual inherits two factors (genes) for each trait,

but the effects of one gene may hide the other gene in the individual.
The hidden gene can resurface after crossbreeding.

Mendel then experimented with crossbreeding F1 purple and white

pea plant flowers. The illustration at the bottom of the Results section in
Experiment 1-1 shows that second-generation (F2) offspring all express
the purple phenotype. Had the element that expresses white flowers
disappeared? To find out, Mendel crossbred the F2 purple flowers. The
third generation, F3, produced flowers in the ratio of roughly 1 white to
3 purple blooms.
This result suggested to Mendel that the trait for white flowers had
not disappeared but rather was hidden by the trait for purple flowers. He
concluded that individuals inherit two factors, or genes, for each trait, but
one may dominate and hide (suppress) the other in the individual’s
phenotype.
 Thus, the unequal ability of individual organisms to survive and
reproduce is related to the different genes they inherit from their parents
and pass on to their offspring. By the same token, similar characteristics
within or between species are usually due to similar genes. For instance,
genes that produce the nervous system in different animal species tend to
be very similar.
Interplay of Genes, Environment, and Experience
The principles of inheritance that Mendel demonstrated through his
experiments have led to countless discoveries about genetics. We now
know that new traits appear because new gene combinations are
inherited from parents, existing genes change or mutate, suppressed
genes are re-expressed, expressed genes are suppressed, or genes or parts
of genes are deleted or duplicated.
But genes alone cannot explain most inherited traits. Mendel realized
that environment participates in expression of traits: planting tall peas in
poor soil reduces their height, for example. Experience likewise plays a
part. The experience of children who attend a substandard school, for
example, is far different from that of children who attend a model school.
Epigenetics is the study of differences in gene expression related to
environment and experience. Epigenetic factors do not change your
genes, but they do influence how your genes express the traits you’ve
inherited from your parents. Epigenetic changes can persist throughout a
lifetime, and their cumulative effects can make dramatic differences in
how your genes work. Epigenetic factors described throughout this book
are revolutionizing our understanding of gene–brain interactions in
typical brain development and in brain function. They will also help
investigators understand, and develop new treatments for, some
neurological disorders.
epigenetics Differences in gene expression related to environment
and experience.
Consult Section 3-3 for details on genetic and epigenetic principles.
Summarizing Materialism
Darwin’s theory of natural selection, Mendel’s discovery of genetic
inheritance, and the reality of epigenetics have three important
implications for studying the brain and behavior:
1. Because all animal species are related, their brains must be related. A
large body of research confirms first that all animals’ brain cells are so
similar that these cells must be related and second that all animal
brains are so similar that they must be related as well. Brain
researchers study the nervous systems of animals as different as slugs,
fruit flies, rats, and monkeys, knowing that they can extend their
findings to the human nervous system.
Section 3-1 describes the varieties of neurons and other brain cells.
2. Because all animal species are related, their behavior must be related.
In his book The Expression of the Emotions in Man and Animals,
Darwin (1872) argued that emotional expressions are similar in
humans and other animals because we inherited them from a common
ancestor. Figure 1-5 offers evidence. That people the world over
display the same behavior suggests that the trait is inherited rather than
learned.
Jerome Tisne/Getty Images
O. Benn/Stone Images
A. Cassidy/Stone Images
 © Robert Harding Picture Library Ltd/Alamy

FIGURE 1-5An Inherited Behavior People the world over display the same
emotional expressions that they recognize in others—these smiles, for example. This
evidence supports Darwin’s suggestion that emotional expression is an inherited
behavior.

More on emotions and their expression in Sections 12-2 , 12-4 , and

14-3 .
3. Brain and behavior in complex animals such as humans evolved from
simpler animals’ brains and behaviors and also depend on learning.
Coming up in Section 1-3 we trace the evolution of nervous systems
and their increasingly complex repertoires of actions, from a simple
netlike arrangement to a multipart nervous system with a brain that
controls behavior.

Contemporary Perspectives on Brain and

Behavior
Where do modern students of the brain stand on the perspectives of
mentalism, dualism, and materialism? In his influential 1949 book, The
Organization of Behavior, psychologist Donald O. Hebb describes the
scientific acceptance of materialism in a folksy manner:
Modern psychology takes completely for granted that behavior and neural function are
perfectly correlated, that one is completely caused by the other. There is no separate soul or
life force to stick a finger into the brain now and then and make neural cells do what they
would not otherwise. (Hebb, 1949, p. iii)

Hebb’s claim dovetails with his theory of how the brain produces
consciousness. He suggested that learning is enabled by neurons forming
new connections with one another in the brain. He called the resulting
neuronal network a cell assembly. As the neural substrate for the learned
experience, cell assemblies interact: one cell assembly becomes
connected to another. This linking of cell assemblies is thus the linking
of memories, which to Hebb is what consciousness is.
Hebb’s argument is materialistic. The contemporary philosophical
school eliminative materialism takes the position that if behavior can be
described adequately without recourse to the mind, then the mental
explanation should be eliminated. Daniel Dennett (1978) and other
philosophers, who have considered such mental attributes as
consciousness, pain, and attention, argue that an understanding of brain
function can replace mental explanations of these attributes. Mentalism,
by contrast, defines consciousness as an entity, attribute, or thing. Let us
use the concept of consciousness to illustrate the argument for
eliminative materialism.
Recovering Consciousness: A Case Study
Darwin offered no suggestion about how the brain produces
consciousness, although his theory predicted that it must. One patient’s
case study offers insight into how the study of brain and behavior begins
to describe consciousness. The patient, a 38-year-old man, had lingered
in a minimally conscious state (MCS) for more than 6 years after an
assault. He was occasionally able to communicate with single words,
occasionally able to follow simple commands. He was able to make a
few movements but could not feed himself despite 2 years of inpatient
rehabilitation and 4 years in a nursing home.
minimally conscious state (MCS) Condition in which a person can
display some rudimentary behaviors, such as smiling or uttering a
few words, but is otherwise not conscious.
This patient is one of approximately 1.4 million people each year in
the United States who, as described by Fred Linge in Clinical Focus 1-1 ,
contend with TBI. Among them, as many as 100,000 may become
comatose; as few as 20 percent recover consciousness. Among the
remaining TBI patients, some are diagnosed as being in a persistent
vegetative state (PVS), alive but unable to communicate or to function
independently at even the most basic level. Their brain damage is so
extensive that no recovery can be expected. Others, such as the MCS
assault victim described earlier, are so diagnosed because behavioral
observation and brain imaging studies suggest that they do have a great
deal of functional brain tissue remaining.
persistent vegetative state (PVS) Condition in which a person is
alive but unaware, unable to communicate or to function
independently at even the most basic level.
Adrian Owen (2015) and his colleagues have found that by imaging
the brain of comatose patients they can assess the extent to which the
patients are conscious by the patterns of activity in their brain. Using an
imaging system that measures brain function in terms of oxygen use,
Owen’s group discovered that some comatose patients are actually
locked in, as was Martin Pistorius, whom you met in Section 1-1 .
Furthermore, these investigators devised ways to communicate with
conscious patients by teaching them a language that signals changes in
their brains’ activity patterns. For example, while imaging the brain of
control subjects, Owen’s group asks them to imagine hitting a tennis ball
with a racket. The group identifies the active brain region associated with
the imaginary act. They then ask patients to imagine hitting a tennis ball
and so determine from their brain images whether they understand. If the
patient understands the instruction and so demonstrates consciousness,
procedures for further communication and rehabilitation can begin.
 On the rehabilitation front, Nicholas Schiff and his colleagues (Schiff
& Fins, 2007) reasoned that, if they could stimulate their MCS patient’s
brain by administering a small electrical current, they could improve his
behavioral abilities. As part of a clinical trial (a consensual experiment
directed toward developing a treatment), they implanted thin wire
electrodes in his brainstem so they could administer a small electrical
current.
clinical trial Consensual experiment directed toward developing a
treatment.
Through these electrodes, which are visible in the X-ray image shown
in Figure 1-6 , the investigators applied the electrical stimulation for 12
hours each day. The procedure is called deep brain stimulation (DBS).
The researchers found dramatic improvement in the patient’s behavior
and ability to follow commands. For the first time, he was able to feed
himself and swallow food. He could even interact with his caregivers and
watch television, and he showed further improvement in response to
rehabilitation.
deep brain stimulation (DBS) Neurosurgery in which electrodes
implanted in the brain stimulate a targeted area with a low-voltage
electrical current to facilitate behavior.
 Zephyr/Science Source

FIGURE 1-6 Deep Brain Stimulation X-ray image showing

electrodes implanted in the thalamus, a structure deep in the brain near
the tip of the brainstem, for DBS. DBS can treat disorders such as
Parkinson disease and depression (see Section 16-3 ) and aid recovery
from TBI (see Section 14-5 ).

The experimenters’ very practical measures of consciousness are

formalized by the Glasgow Coma Scale (GCS), one indicator of the
degree of unconsciousness and of recovery from unconsciousness. The
GCS rates eye movement, body movement, and speech on a 15-point
scale. A low score indicates coma and a high score indicates
consciousness. Thus, the ability to follow commands, to eat, to speak,
and even to watch TV provide quantifiable measures of consciousness
contrasting sharply with the qualitative description that sees
consciousness as a single entity. Eliminative materialists would argue,
therefore, that the objective, measurably improved GCS score of
behaviors in a brain-injured patient is more useful than a subjective
mentalistic explanation that consciousness has “improved.”
People under the age of 19 can be especially vulnerable to head
trauma and concussion when they participate in recreational activities
and sporting competitions. The Centers for Disease Control and
Prevention has cited bicycling and football injuries as leading causes of
TBI in this population. TBI can also lead to accelerated brain aging, an
area of growing concern for participants in athletic competitions that lead
to repeated concussion or other head trauma, and to military combatants.
More research on and treatments for MCS and TBI in Sections 7-3 ,
14-5 , and 15-7 . Concussion is the topic of Focus 16-3.
The Separate Realms of Science and Belief
Contemporary brain theory is materialistic. Although materialists, your
authors included, continue to use subjective mentalistic words such as
consciousness, pain, and attention to describe more complex behaviors,
at the same time they recognize that these words do not describe mental
entities. Materialism argues for objective, measurable descriptions of
behavior that can be referenced to brain activity.
Some people may question materialism’s tenet that only the brain is
responsible for behavior because they think it denies religion. But
materialism is neutral with respect to religion. Many of the world’s major
religions accept both evolution and the brain’s centrality in behavior as
important scientific theories. Fred Linge, introduced in Clinical Focus 1-
1 , has strong religious beliefs, as do the other members of his family.
They used their religious strength to aid in his recovery. Yet despite their
religious beliefs, they realize that Linge’s brain injury caused his
changed behavior and that learning to compensate for his impairments
caused his brain function to improve.
Indeed, many behavioral scientists hold religious beliefs and see no
contradiction between them and their engagement with science. Science
is not a belief system but rather a set of procedures designed to allow
investigators to confirm answers to a question independently. As outlined
in Experiment 1-1 , this four-step procedure allows anyone to replicate,
or repeat, their original conclusions—or find that they cannot.
The four-step experimental procedure is (1) formulate a question
(hypothesis), (2) design a procedure to test it, (3) evaluate the
results, (4) confirm or modify the hypothesis.
 1-2 REVIEW
Perspectives on Brain and Behavior
Before you continue, check your understanding.
1 . The view that behavior is the product of an intangible entity called the
mind (psyche) is ___________. The notion that the immaterial mind
acts through the material brain to produce language and rational
behavior is ___________. ___________, the view that brain function
fully accounts for all behavior, guides contemporary research on the
brain and behavior.
2 . The implication that the brains and behaviors of complex animals
such as humans evolved from the brains and behaviors of simpler
animals draws on the theory of ___________ advanced by
___________.
3 . The brain demonstrates a remarkable ability to recover, even after
severe brain injury, but an injured person may linger in a
___________, occasionally able to communicate or to follow simple
commands but otherwise not conscious. Those who have such
extensive brain damage that no recovery can be expected remain in a
___________, alive but unable to communicate or to function
independently at even the most basic level.
4 . Darwin and Mendel were nineteenth-century contemporaries. Briefly
contrast the methods they used to reach their scientific conclusions.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 1-3 Evolution of Brains and of Behavior
Neither nervous system nor brain is common to all living organisms;
rather, nervous systems and behavior have built up and changed bit by
bit as animals have evolved. We trace the evolution of the human brain
and behavior by describing (1) animals that first developed a nervous
system and muscles with which to move, (2) how the nervous system
grew more complex as the brain evolved to mediate complex behavior,
and (3) how the human brain evolved its present complexity.
The popular interpretation of human evolution is that we are
descended from apes. Actually, humans are apes. Other living apes are
not our ancestors, although we are related to them through a common
ancestor, a forebear from which two or more lineages or family groups
arise. To demonstrate the difference, consider the following story.
common ancestor Forebear of two or more lineages or family
groups; ancestral to both groups.
Two people named Joan Campbell are introduced at a party, and their
names provide a rich conversation starter. Although both belong to the
Campbell lineage (family line), one Joan is not descended from the other.
The two women live in different parts of North America, one in Texas
and the other in Ontario, and both their families have been there for
many generations.
Nevertheless, after comparing family histories, the two Joans discover
that they have ancestors in common. The Texas Campbells are
descended from Jeeves Campbell, brother of Matthew Campbell, from
whom the Ontario Campbells are descended. Jeeves and Matthew both
boarded the same fur-trading ship when it stopped for water in the
Orkney Islands north of Scotland before sailing to North America in
colonial times.
The Joan Campbells’ common ancestors, then, were the mother and
father of Jeeves and Matthew. Both the Texas and the Ontario Campbell
family lines are descended from this man and woman. If the two Joan
Campbells were to compare their genes, they would find similarities that
correspond to their common lineage.
In much the same way, humans and other apes are descended from
common ancestors. But unlike the Joan Campbells, we do not know
exactly who those distant relatives were. By comparing the brain and
behavioral characteristics of humans and related animals and by
comparing their genes, however, scientists are tracing our lineage back
farther and farther to piece together the origins of our brain and behavior.
Some living animal species display characteristics more similar to
those of a common ancestor than do others. For example, in some ways
chimpanzees are more similar to the common ancestor of humans and
chimpanzees than are modern humans. In the following sections, we
trace some major evolutionary events that led to human brains and
human behavior by looking at the nervous systems of living animal
species and the fossils of extinct animal species.

Origin of Brain Cells and Brains

Earth formed about 4.5 billion years ago, and the first life-forms arose
about a billion years later. About 700 million years ago, animals evolved
the first brain cells, and by 250 million years ago, the first brain had
evolved. A humanlike brain first developed only about 6 million years
ago, and our modern human brain has been around for only the past
200,000 years or so.
Although life arose very early in our planet’s history, then, brain cells
and brains evolved comparatively recently. Large, complex brains, such
as ours, appeared only an eyeblink ago in evolutionary terms. If you are
familiar with the principles of taxonomic classification, which names and
orders living organisms according to their evolutionary relationships,
read on. If you prefer a brief review before you continue, turn first to The
Basics: Classification of Life on pages 16 –17 .
 THE BASICS

Classification of Life
Taxonomy is the branch of biology concerned with naming and
classifying species by grouping representative organisms according to
their common characteristics and their relationships to one another.
As shown in the left column of the figure Taxonomy of Modern
Humans, which illustrates the human lineage, the broadest unit of
classification is a kingdom, with more subordinate groups being
phylum, class, order, family, genus, and species. This taxonomic
hierarchy is useful in helping us trace the evolution of brain cells and
the brain.
We humans belong to the animal kingdom, the chordate phylum, the
mammalian class, the primate order, the great ape family, the genus
Homo, and the species sapiens. Animals are usually identified by their
genus and species names. So we humans are called Homo sapiens
sapiens, meaning wise, wise human.
The branches in the figure Cladogram, which shows the taxonomy
of the animal kingdom, represent the evolutionary sequence
(phylogeny) that connects all living organisms. Cladograms are read
from left to right: the most recently evolved organism (animal) or trait
(muscles and neurons) is farthest to the right.
Of the five kingdoms of living organisms represented in the
cladogram, only the one most recently evolved, Animalia, contains
species with muscles and nervous systems. It is noteworthy that
muscles and nervous systems evolved together to underlie the forms of
movement (behavior) that distinguish members of the animal kingdom.
The figure Evolution of the Nervous System shows the taxonomy of
the 15 groups, or phyla, of Animalia, classified according to increasing
complexity of nervous systems and movement.
Taxonomy of Modern Humans
 In proceeding to the right from the nerve net, we find that nervous
systems in somewhat more recently evolved phyla, such as flatworms,
have more complex structure. These organisms have heads and tails,
and their bodies show both bilateral symmetry (one half of the body is
the mirror image of the other) and segmentation (the body is composed
of similarly organized parts). The structure of the human spinal cord
resembles this segmented nervous system.

Cladogram

Evolution of Nervous Systems in Animals

A nervous system is not essential for life. In fact, most organisms both in the
past and at present have done without one. In animals that do have a nervous
system, comparison of a wide variety of species broadly outlines how the
nervous system has evolved. We summarize this evolution in the following
general steps:
 Evolution of the Nervous System on page 17 offers a visual recap.
1. Neurons and muscles. Brain cells and muscles evolved first, allowing
animals to move.
2. Nerve net. The nervous system representative of evolutionarily older
phyla, such as jellyfishes and sea anemones, is extremely simple. It
consists of a diffuse nerve net, which has no structure that resembles a
brain or spinal cord but consists entirely of neurons that receive sensory
information and connect directly to other neurons that move muscles.
Look again at Figure 1-1 and imagine that the brain and spinal cord have
been removed. The human PNS is reminiscent of the nerve net in
phylogenetically simpler animals.
nerve net Simple nervous system that has no center but consists of
neurons that receive sensory information and connect directly to other
neurons that move muscles.
3. Bilateral symmetry. In more complex animals such as flatworms, the
nervous system is more organized, and it features bilateral symmetry :
the nervous system on one side of the animal mirrors that on the other
side. The human nervous system is also bilaterally symmetrical (see
Figure 1-1 ).
bilateral symmetry Body plan in which organs or parts present on
both sides of the body are mirror images in appearance. For example,
the hands are bilaterally symmetrical, whereas the heart is not.
In the context of the brain’s overall bilateral symmetry, Section 15-4
examines asymmetries between its cerebral hemispheres.
4. Segmentation. The body of animals such as earthworms consists of a
series of similar muscular segments. Their nervous system has similar
repeating segments. The human spinal cord and brain display such
segmentation : the vertebrae contain the similar repeating nervous system
segments of the spinal cord.
segmentation Division into a number of parts that are similar; refers to
the idea that many animals, including vertebrates, are composed of
similarly organized body segments.
Figure 2-28 maps the human spinal cord’s segments.
5. Ganglia. In still more recently evolved invertebrate phyla, including
clams, snails, and octopuses, are clusters of neurons called ganglia that
resemble primitive brains and function somewhat like them in that they
are command centers. In some phyla, encephalization, having the ganglia
 in the head, is distinctive. For example, insects’ ganglia are sufficiently
large to merit the term brain.
ganglia Collection of nerve cells that function somewhat like a brain.
6. Spinal cord. In relatively highly evolved chordates —animals that have
both a brain and a spinal cord—a single nervous system pathway connects
the brain with sensory receptors and muscles. Chordates get their name
from the notochord, a flexible rod that runs the length of the back. In
humans, the notochord is present only in the embryo; by birth, bony
vertebrae encase the spinal cord.
chordate Animal that has both a brain and a spinal cord.
7. Brain. The chordate phylum, of which amphibians, reptiles, birds, and
mammals are class members, displays the greatest degree of
encephalization: a true brain. Of all of the chordates, humans have the
largest brain relative to body size, but many other chordates have large
brains as well. Although built to a common plan, the brain of each
chordate species displays specializations related to the distinctive
behaviors of that species.

Chordate Nervous System

A chart called a cladogram (from the Greek word clados, meaning branch )
displays groups of related organisms as branches on a tree. The cladogram
in Figure 1-7 represents seven of the nine classes to which the
approximately 38,500 chordate species belong. Wide variation exists among
the nervous systems of chordates, but common to all is the basic structural
pattern of bilateral symmetry, segmentation, and a spinal cord and brain
encased in cartilage or bone.
cladogram Phylogenetic tree that branches repeatedly, suggesting a
taxonomy of organisms based on the time sequence in which
evolutionary branches arise.

FIGURE 1-7 Representative Classes of Chordates This

cladogram illustrates evolutionary relationships among animals that have a
 brain and spinal cord. Brain size increased with the evolution of limbs in
Amphibia. Birds and mammals are the most recently evolved chordates, and
both classes have large brains relative to body size.

As chordates evolved limbs and new forms of locomotion, their brain

became larger. For example, all chordates have a brainstem, but only the
birds and mammals have a large fore-brain. The evolution of more complex
behavior in chordates is closely related to the evolution of the cerebrum and
cerebellum. Their increasing size in various classes of chordates is
illustrated in Figure 1-8 . These increases accommodate new behaviors,
including new forms of locomotion on land, complex movements of the
mouth and hands for eating, improved learning ability, and highly organized
social behavior.
Fish

Frog
Bird

Human
 FIGURE 1-8Brain Evolution The brains of representative chordate
species have many structures in common, illustrating a single basic brain
plan.

The cerebrum and the cerebellum are proportionately small and smooth
in the earliest evolved classes (e.g., fish, amphibians, and reptiles). In later-
evolved chordates, especially the birds and mammals, these structures are
much more prominent. In many large-brained mammals, both structures are
extensively folded, which greatly increases their surface area while allowing
them to fit into a small skull, just as folding a large piece of paper enables it
to occupy a small envelope.
Increased size and folding are particularly pronounced in dolphins and
primates, animals with large brains relative to their body size. Because
relatively large brains with a complex cerebrum and cerebellum have
evolved in a number of animal lineages, humans are neither unique nor
special in these respects. We humans are distinguished, however, in
belonging to the large-brained primate lineage and are unique in having the
largest, most complex brain in this lineage.
 1-3 REVIEW
Evolution of Brains and of Behavior
Before you continue, check your understanding.
1 . Because brain cells and muscles evolved only once in the animal
kingdom, a similar basic pattern exists in the ___________ of all
animals.
2 . Evolutionary relationships among the nervous systems of animal
lineages are classified by increasing complexity, progressing from the
simplest ___________ to a ___________ segmented nervous system
to nervous systems controlled by ___________ to nervous systems in
the phylum ___________, which feature a brain and spinal cord.
3 . A branching diagram that represents groups of related animals is
called a ___________.
4 . Given that a relatively large brain with a complex cerebrum and
cerebellum has evolved in a number of animal lineages, what if
anything makes the human brain unique?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Evolution of the Human Brain and
1-4

Behavior
Anyone can see similarities among humans, apes, and monkeys. Those
similarities extend to the brain as well. In this section, we consider the
brain and behaviors of some more prominent ancestors that link ancestral
apes to our brain and our behaviors. Then we consider the relation
between brain complexity and behavior across species. We conclude by
surveying leading hypotheses about how the human brain evolved to
become so large and the behavior that it mediates so complex. The
evolutionary evidence shows that we humans are specialized in having an
upright posture, making and using tools, and developing language but that
we are not special, because our ancestors also shared these traits, at least
to some degree.

FIGURE 1-9 Representatives of the Primate Order This

cladogram illustrates hypothetical relationships among members of the
primate order. Humans are members of the great ape family. In general,
brain size increases across the groupings, with humans having the largest
brain of all primates.

Humans: Members of the Primate Order

Humans are members of the primate order, a subcategory of mammals
that includes apes, Old World monkeys, New World monkeys, tarsiers,
and lemurs as well (Figure 1-9 ). We humans are but one of about 275
primate species. Primates have excellent color vision, with the eyes
positioned at the front of the face to enhance depth perception. They use
their highly developed visual sense to deftly guide their hand movements.
Female primates usually have only one infant per pregnancy, and they
spend a great deal more time caring for their young than most other
animals do. Primate brains are on average larger than those of animals in
other mammalian orders, such as rodents (mice, rats, beavers, squirrels)
and carnivores (wolves, bears, cats, weasels).
Humans are members of the great ape family, which includes
orangutans, gorillas, and chimpanzees. Apes are arboreal animals with
limber shoulders that allow them to brachiate in trees (swing from one
handhold to another), a trait retained by humans, who generally do not
live in trees these days. Nevertheless, freeing the arms at the shoulder is
handy for all sorts of human activities, from traversing monkey bars on
the playground to competing in the Olympic hammer toss to raising a
hand to ask a question in class. Apes are distinguished as well by their
intelligence and large brain, traits that humans exemplify.
Among the apes, we are most closely related to the chimpanzee,
having had a common ancestor between 5 million and 10 million years
ago. Between that common ancestor and us over the past 5 million years,
many hominids —primates that walk upright—in our lineage evolved.
During most of this time, a number of hominid species coexisted. At
present, however, we are the only surviving hominid species.
hominid General term referring to primates that walk upright,
including all forms of humans, living and extinct.

Australopithecus : Our Distant Ancestor

One of our hominid ancestors is probably an Australopithecus species
(from the Latin austral, meaning southern, and the Greek pithekos,
meaning ape. ) Figure 1-10 shows reconstructions of the face and body of
one such animal, Australopithecus africanus. Many species of
Australopithecus lived, some at the same time, so it is uncertain which is
our common ancestor.
(A)
Australopithecus
Homo sapiens “Lucy”
(B)
FIGURE 1-10 Australopithecus africanus (A) The hominid Australopithecus
walked upright with free hands, as do modern humans, but its brain was about one-third
the size of ours. (B) Human and Australopithecus figures compared on the basis of the
most complete Australopithecus skeleton yet found, a young female about 1 meter tall,
popularly known as Lucy, who lived 3 million years ago.

These early hominids were among the first primates to show distinctly
human traits, including walking upright and using tools. Scientists have
deduced their upright posture from the shape of their back, pelvic, knee,
and foot bones and from a set of fossilized footprints that a family of
australopiths left behind, walking through freshly fallen volcanic ash
some 3.8 million years ago. These footprints feature impressions of a
well-developed arch and an unrotated big toe—more like humans’ than
other apes’. (Nevertheless, australopiths retained the ability to skillfully
climb trees.) The bone structure of their hands evinces tool use (Pickering
et al., 2011).
Australian Raymond Dart coined Australopithecus in naming the
skull of a child he found among fossilized remains from a limestone
quarry near Taung, South Africa, in 1924. Choosing so to represent
his native land probably was no accident.

The First Humans

One of the first finds to be designated as genus Homo (human) dates to
about 2 million years ago. The remains were found by Mary and Louis
Leakey in the Olduvai Gorge in Tanzania in 1964. The primates that left
these skeletal remains had a strong resemblance to Australopithecus but
more closely resembled modern humans in one important respect: they
made simple stone tools. The Leakeys named the species Homo habilis
(handy human ) to signify that its members were toolmakers. To date, the
earliest member of the genus Homo, found in Ethiopia, dates to about 2.8
million years ago. The fossils reveal a jaw and teeth much smaller than in
any Australopithecus species but characteristic to humans (Villmoare et
al., 2015).
 Early humans may have followed such proposed routes out of Africa, first
to Asia and Europe, eventually to Australia, and finally to the Americas.

The first humans who spread beyond Africa migrated into Europe and
Asia. This species was Homo erectus (upright human ), so named because
of the mistaken notion that its predecessor, H. habilis, had a stooped
posture. Homo erectus first shows up in the fossil record about 1.6 million
years ago. As shown in Figure 1-11 , its brain was bigger than that of any
preceding hominid, overlapping in size the measurements of present-day
human brains. The tools made by H. erectus were more sophisticated than
those made by H. habilis. An especially small subspecies of H. erectus,
about 3 feet tall, was found on the Indonesian island of Flores. Named
Homo floresiensis, these hominids lived up to about 13,000 years ago
(Gordon et al., 2008).
 FIGURE 1-11 Increases in Hominid Brain Size The brain of
Australopithecus was about the same size as that of living nonhuman apes,
but succeeding members of the human lineage display increased brain
size. Data from Johanson and Edey, 1981

Modern humans, Homo sapiens sapiens, appeared within about the

past 200,000 years. Most anthropologists think that they also migrated
from Africa. Until about 30,000 years ago in Europe and 18,000 years
ago in Asia, H. sapiens sapiens coexisted and interbred with other H.
sapiens species, collectively called archaic humans. In Europe, for
example, H. sapiens sapiens lived alongside another subspecies of
modern humans, H. neanderthalis, named for the Neander Thal (Valley),
Germany, where the first Neanderthal skulls were found. As the first
fossil ancestral humans to be discovered, Neanderthals have maintained a
preeminent place in the study of modern human ancestors.
Neanderthals had brains as large as or larger than those of modern
humans, used similar tools, and wore jewelry and makeup. They lived in
family groups similar to modern human ones, made music, cared for their
elders, and buried their dead. From these archeological findings, we can
infer that Neanderthals probably communicated using language and held
religious beliefs.
We do not know how modern humans completely replaced archaic
human species, but perhaps they had advantages in toolmaking, language
use, or social organization. Contemporary genetic evidence shows that
modern European humans who interbred with Neanderthals acquired
genes that adapted them to the cold, to novel disease, and possibly to light
skin that better absorbs vitamin D (Sankararaman et al., 2014).
Reconstructions such as that in Figure 1-12 show how similar to us
Neanderthals really were.
 Philippe Plailly & Atelier Daynes/Science Source

FIGURE 1-12 Neanderthal Woman A facial reconstruction by Elisabeth Daynes

made from a casting of the skull. The female, whom the discoverers called Pierrette, died
a violent death between the ages of 17 and 20. Her 36,000-year-old remains were
discovered in western France in 1979, lying near tools from the Neanderthal period.
Focus 10-1 reports on the discovery of a flute made by Neanderthals.

One possible human lineage is shown in Figure 1-13 . A common

ancestor gave rise to the Australopithecus lineage, and one member of
this group gave rise to the Homo lineage. The bars in Figure 1-13 are not
connected because many more hominid species have been discovered
than are shown, and exact direct ancestors are uncertain. The bars overlap
because many hominid species coexisted until quite recently. The last of
the australopith species disappeared from the fossil record about 1 million
years ago.

FIGURE 1-13 Human Origins The human lineage and a lineage of

extinct Australopithecus probably arose from a common ancestor about 4
million years ago. The ancestor of the human lineage Homo was probably
an animal similar to A. africanus.
Relating Brain Size and Behavior
Scientists who study brain evolution propose that increased brain size and
complexity evolved in different species to enable more complex behavior.
Having a large brain clearly has been adaptive for humans, but many
animals have large brains. Whales’ and elephants’ brains are much larger
than ours. Of course, whales and elephants are much larger than humans
overall. How is relative brain size measured, and what does brain size
signify? Two ways of estimating relative brain size are to compare brain
size to body size and to count brain cells.
Estimating Relative Brain–Body Size
Harry Jerison (1973) developed an index that compares the ratio of brain
size to body size across species. He calculated that as body size increases,
brain size increases at about two-thirds the increase in body weight.
Jerison’s underlying assumption was that even if one knew very little
about an animal’s behavior, its brain size could provide some clues to its
behavioral complexity. The idea is that species exhibiting more complex
behaviors must possess more brain than species whose behaviors are
fewer and less complex.
Using the ratio of actual brain size to expected size, Jerison developed
a quantitative measure, the encephalization quotient (EQ). He defined
an average animal (a domestic cat is Jerison’s pick) as having an EQ of 1.
The diagonal trend line in Figure 1-14 plots the expected brain–body size
ratio of animals with an EQ of 1. Some animals lie below the line: their
brain size is smaller than would be expected for an animal of that size.
Other animals lie above the line: their brain size is larger than would be
expected for an animal of that size.
encephalization quotient (EQ) Jerison’s quantitative measure of
brain size obtained from the ratio of actual brain size to expected
brain size, according to the principle of proper mass, for an animal of
a particular body size.
The lower an animal’s brain falls below the trend line in Figure 1-14 ,
the smaller its EQ. The higher an animal’s brain lies above the trend line,
the larger its EQ. Notice that the rat’s brain is a little smaller (lower EQ)
and the elephant’s brain a little larger (higher EQ) than the ratio predicts.
A modern human, farther above the line than any other animal, has the
highest EQ.
 Ratios of Brain to Body Size in Common
FIGURE 1-14

Mammals As represented logarithmically on this graph, average brain

size relative to body weight falls along a diagonal trend line, where you find
the cat. Data from Jerison, 1973.

Jerison’s EQ provides a rough estimate of comparative brain size, but

body size and brain size can vary independently (Figure 1-15 , top). To
get around this problem, scientists have devised ways to count the cells in
the brain.
Counting Brain Cells
Consider the roundworm Caenorhabditis elegans. C. elegans has 959
cells. Of these, 302 are neurons. In contrast, the blue whale—the largest
animal that has ever lived, weighing as much as 200 tons—has a brain
weighing 15,000 grams (33 lb). In cell number, 30 percent of C. elegans
is nervous system, whereas in terms of body weight, less than 0.01
percent of the blue whale is nervous system.
FIGURE 1-15 Comparing EQs The EQs of some familiar mammals are ranked at
the top of the chart, and members of the primate lineage are ranked at the bottom.
Clearly, intelligence is widespread among animals.

Based on EQs, we would predict that C. elegans has a more complex

behavioral repertoire than a blue whale. But it makes no sense to suggest
that a worm’s behavior is more complex than a whale’s. Obviously a
whale has a lot more neurons than a worm. Our estimate of brain size and
behavioral complexity line up better if we simply compare cell counts.
Karina Fonseca-Azevedo and her colleagues (2012) have devised such
a method, using a counting machine. Not only can they estimate the
number of cells in a brain or a part of the brain but they also can estimate
the brain cells’ packing density. For example, two similar-sized brains
could consist of either diffusely distributed large cells or closely packed
small cells. It turns out that the packing density of cells differs by a lot
among species and brain regions. Rodents have larger, more loosely
packed cells, for example, and primates smaller and more densely packed
cells.
Packing density is relatively constant in the primate lineage, and so EQ
provides a good comparison of their brain sizes (Figure 1-15 , bottom).
Brain cell counts support the EQs Jerison calculated in the primate
lineage: Australopithecus had about 50 billion to 60 billion neurons,
Homo habilis about 60 billion, Homo erectus about 75 billion to 90
billion, and modern humans have about 86 billion neurons.
In terms of brain size and cell counts, then, what makes us humans
unusual (along with archaic humans such as Neanderthals) are our large
brain and many neurons. Although researchers have not made similar
neuron counts in all other animal species with brains larger than the
humans’, if neurons are not densely packed, resembling the somewhat
less-dense packing of a rodent, then they may well have far fewer
neurons. For example, despite their large brains, dolphins’ 30 billion
neurons is similar to the number in chimpanzees, many fewer than in
humans, because dolphin neurons are not densely packed. As detailed in
Comparative Focus 1-3, The Elephant’s Brain, on page 24 , pachyderms
have an enormous number of brain cells, but most are in the cerebellum,
while the number in the elephant cerebrum is equivalent to that of
dolphins and chimpanzees.
COMPARATIVE FOCUS 1-3

The Elephant’s Brain

The cerebrum and cerebellum have evolved into the human brain’s
most distinct and largest structures, larger than in any other primate
brain. Although the cerebellum appears smaller than the cerebrum
physically, its small, tightly packed neurons are four times the
number found in the cerebrum (about 68 billion vs. 16 billion), a 4:1
ratio that humans share with all other primates. Typically, the
cerebrum is described as mediating cognitive functions, whereas the
cerebellum mediates motor function. In fact, both structures
contribute to both kinds of functions in different ways.
African elephants are enormous animals. It is not surprising that
they have the largest brain of all terrestrial animals—three times the
size of a human’s. With such a large brain, why don’t elephants share
humans’ intellectual abilities?
To investigate this question, Suzana Herculano-Houzel and her
colleagues (2014) made a neuronal count of an African elephant.
They found that its brain contains three times as many neurons as the
human brain (257 billion vs. 86 billion neurons). But remarkably,
251 billion of those neurons (97.5 percent) reside in the elephant’s
cerebellum. In contrast, the elephant’s cerebral cortex, with twice the
mass of the human cortex, contains only 5.6 billion neurons, about
one-third the number found in the human cerebrum. The elephant’s
cerebellum contains nearly 45 times as many neurons as its
cerebrum.
What do these numbers tell us about the elephant’s behavior? An
elephant has almost infinite degrees of freedom in the use of its
trunk: with it, it can bathe, lift a tree trunk, pick up a peanut, caress a
baby, or paint a picture. The vast number of neurons in its
cerebellum is probably requisite to controlling the trunk’s sensory
and motor abilities.
The elephant’s cerebral cortex boasts more neurons than most
animals can boast but somewhat fewer than chimpanzees’
cerebrums. The elephant’s cognitive ability also ranks slightly lower
than a chimp’s.
 The Herculano-Houzel study offers a conclusion related to the
function of the human cerebrum, as well. The remarkable cognitive
abilities of humans, which exceed those of all other animal species,
are best explained by the sheer number of cerebral neurons, which
exceed the number found in all other animal species, even those with
much larger brains, including elephants.

An African Elephant’s Brain In this, the largest brain of all

terrestrial animals, both the cerebrum (left) and the cerebellum
(right) are gigantic compared to those of the human brain. But
the cerebellum contains 97.5 percent of the neurons. Reproduced or
adapted from our websites at http://www.brains.rad.msu.edu and http://brainmuseum.org
, supported by the U. S. National Science Foundation.

Why the Hominid Brain Enlarged

The evolution of modern humans—from when humanlike creatures first
appeared until humans like us emerged—spans more than 4 million
years. As the relative size differences of the hominid skulls pictured in
Figure 1-16 illustrate, much of this evolution was associated with
increases in brain and body size and by changes in behavior. These
changes were probably driven by many influences. Among the wide
array of hypotheses that seek to explain why the modern human brain
enlarged so much and so rapidly, we examine four ideas.
 FIGURE 1-16 The Course of Human Evolution The hominid
brain has increased nearly threefold in relative size, illustrated here by the
skulls of Australopithecus afarensis (left), Homo erectus (center), and
modern Homo sapiens (right). Missing parts of the Australopithecus skull,
shown in blue, have been reconstructed. The Origin of Modern Humans (p. 165), by
R. Lewin, 1998, New York: Scientific American Library. Photo by Kevin O’Farrell/Concepts.

One hypothesis suggests that numerous drastic climate changes drove

adaptation by hominids and led to more complex behavior. Another
hypothesis contends that the primate lifestyle favors an increasingly
complex nervous system that humans capitalize on. A third links brain
growth to brain cooling. And a fourth proposes that a changed rate of
maturation favors larger brains. Likely, a combination of all of these
factors was influential.
Climate and the Evolving Hominid Brain
Climate changes have driven many physical changes in hominids,
ranging from brain changes to the emergence of human culture.
Evidence suggests that each new hominid species appeared after climate
changes devastated old environments and led to new ones.
About 8 million years ago, a massive tectonic event (deformation of
Earth’s crust) produced the Great Rift Valley, which runs through the
eastern part of Africa from south to north. The reshaped landmass left a
wet jungle climate to the west and a much drier savannah climate to the
east. To the west, the apes continued unchanged in their former habitat.
But the fossil record shows that in the drier eastern region, apes evolved
rapidly into upright hominids in response to the selective environmental
pressures that formed their new home.

Africa’s Great Rift Valley cut off ape species living in a wetter climate to the
west from species that evolved into hominids, adapted to a drier climate to
the east.

Thereafter, the climate in East Africa did not remain static. It

underwent a number of alterations (Maslin et al., 2015). The appearance
of Homo habilis 3 million years ago and that of Homo erectus 1 million
years ago were associated with these climatic alterations. Climatic
changes also track the disappearance of other members of the human
family. The warming in Europe that ended the ice age as recently as
30,000 years ago contributed to modern humans migrating to the
continent and to the Neanderthal and other archaic European and Asiatic
human species disappearing.
What makes Homo sapiens the survivor? One suggestion is that we
modern humans evolved to adapt to change itself and that this
adaptability has allowed us to populate every region on Earth (Antón et
al, 2014). The caution is that modern humans have been around only a
short time relative to the millions of years that other hominid species
survived: our adaptability has yet to be severely tested.
The Primate Lifestyle
British anthropologist Robin Dunbar (1998) argues that a primate’s
social group size, a cornerstone of its lifestyle, is correlated with brain
size. His conclusion: the average group size of about 150 favored by
modern humans explains their large brains. He cites as evidence that 150
is the estimated group size of hunter-gatherer groups and the average
group size of many contemporary institutions—a company in the
military, for instance—and coincidentally, the number of people that
each of us can gossip about.
Consider how group size might affect how primates forage for food.
Foraging is important for all animals, but while some foraging activities
are simple, others are complex. Eating grass or vegetation is an
individual pursuit: an animal need only munch and move on. Vegetation
eaters such as gorillas do not have especially large brains relative to their
body size. In contrast, apes that eat fruit, such as chimpanzees and
humans, have relatively large brains.
Katharine Milton (2003) documented the relation between fruit
foraging and larger brains by examining the feeding behavior and brain
size of two South American (New World) monkeys of the same body
size. As illustrated in Figure 1-17 , spider monkeys obtain nearly three-
quarters of their nutrients from fruit and have a brain twice as large as
that of the howler monkey, which obtains less than half its nutrients from
fruit.

Paul A. Souders/Corbis
Spider monkey diet
 DC_Columbia/Getty Images
Howler monkey diet

FIGURE 1-17Picky Eaters Katharine Milton examined the feeding

behavior and brain size of two New World monkeys that have the same
body size but different brain sizes and diets.

What is so special about eating fruit? Good sensory skills such as

color vision to see it, good motor skills to reach and manipulate it, good
spatial skills to find it, good memory to return to it, and having friends to
help find it and ward off competitors are all useful fruit-harvesting skills.
Having a parent who can teach fruit-finding skills and being a good
learner are also useful. The payoff in eating fruit is its nutritional value
for nourishing a large, energy-dependent brain that uses more than 20
percent of the body’s resources. These same skills are useful for
obtaining other temporary and perishable types of food, such as those
obtained by scavenging, hunting, and gathering.
A neuron’s metabolic (energy) cost is estimated as relatively constant
across different species but also high relative to that of other types of
body cells. So any adaptive advantage to having more neurons must
support that energy cost. Fonseca-Azevedo and Herculano-Houzel
(2012) suggest that cooking food is a unique contribution to hominid
brain development. Gorillas must spend up to 8 hours of each day
foraging for vegetation and eating it. Chimps and early hominids, with a
more varied diet, could support more neurons provided that they also
spent most of their waking time foraging.
The use of fire by Homo erectus and later hominids allowed for
cooking, which predigests food and thus maximizes caloric gain to the
point that much less time need be devoted to foraging. A high degree of
male–male, female–female, and female–male cooperation in food
gathering and cooking, characteristic of the hominid lifestyle, further
supported the evolution of a larger brain.
Changes in Hominid Physiology
Cooking might foster genetic mutations associated with marked size
reductions in individual muscle fibers in the face and entire masticatory
muscles in hominids (Stedman et al., 2004). The Stedman team
speculates that smaller masticatory muscles paved the way for smaller,
more delicate bones in the head. Smaller bones in turn allowed for
changes in diet and access to more energy-rich food.
A small jaw distinguishes the earliest Homo fossils yet discovered.
Another physiological adaptation may have given a special boost to
greater brain size in our human ancestors: changes in the morphology
(form) of the skull. Dean Falk (Kunz and Iliadis, 2007) developed the
radiator hypothesis from her car mechanic’s remark that to increase the
size of a car’s engine, you also have to increase the size of the radiator
that cools it. Falk reasoned that if the brain’s radiator, the circulating
blood, adapted into a more effective cooling system, brain size could
increase.
Brain cooling is so important because the brain’s metabolic activity
generates a great deal of heat and is at risk for overheating under
conditions of exercise or heat stress. Falk argued that, unlike australopith
skulls, Homo skulls contain holes through which cranial blood vessels
pass. These holes suggest that, compared to earlier hominids, Homo
species had a much more widely dispersed blood flow from the brain,
which would have greatly enhanced brain cooling.
Altered Maturation
All animal species’ life history can be divided into stages. Heterochrony
(from the Greek meaning different times ) is the study of processes that
regulate the onset and end of life stages and their developmental speed
and duration. Several proposals suggest that altered heterochronicity
accounts for the large human brain and other distinctive human features.
In neoteny, juvenile stages of predecessors become adult features of
descendants. Neoteny is common in the animal world. Flightless birds
are neotenic adult birds, domesticated dogs are neotenic wolves, and
sheep are neotenic goats. Many anatomical features link us with the
juvenile stages of other primates, including a small face, vaulted
cranium, unrotated big toe, upright posture, and primary distribution of
hair on the head, armpits, and pubic areas.
neoteny Process in which juvenile stages of predecessors become
adult features of descendants; idea derived from the observation that
 more recently evolved species resemble the young of their common
ancestors.
Because a human infant’s head is large relative to body size, neoteny
has also led to adults with proportionally larger bodies and larger skulls
to house larger brains. The shape of a baby chimpanzee’s head is more
similar to the shape of an adult human’s head than to an adult
chimpanzee’s head (Figure 1-18 ). Along with this physical morphology,
human adults also retain some behaviors of primate infants, including
play, exploration, and intense interest in novelty and learning. The brain
processes that support learning thus are retained in adulthood (Zollikofer,
2012).

PHOTO24/Getty Images
 FLPA/SuperStock

FIGURE 1-18 Neoteny The shape of an adult human’s head more closely
resembles that of a juvenile chimpanzee’s head (left) than an adult chimp’s
head (right). This observation leads to the hypothesis that we humans may
be neotenic descendants of our more apelike common ancestors.

Critics of neoteny offer an alternative view in which all of the stages

of development still occur, but their onset and duration change
(Workman et al., 2013). Evidence for this idea is that each stage of
human development—gestation, infancy, childhood, adulthood—is
prolonged relative to such ancestral species as macaques and
chimpanzees. Prolonged infancy allows the birth and development of
more neurons, more time for their growth to produce a bigger brain.
Prolonged childhood enhances learning time; and prolonged adolescence
allows for the growth of a bigger body.
 1-4 REVIEW
Evolution of the Human Brain and Behavior
Before you continue, check your understanding.
1 . Modern humans share a ___________ with the ___________, our
closest living relative.
2 . Modern humans evolved from a ___________ lineage that
successively featured ___________, ___________, and ___________,
groups in which more than one species existed concurrently.
3 . The ___________ describes brain size relative to body size, but a
complete comparison of different species’ brains requires
___________.
4 . The large human brain evolved in response to a number of pressures
and opportunities, including ___________, ___________,
___________, and ___________.
5 . One hypothesis proposes that Homo sapiens has evolved to adapt to
change itself. Explain the reasoning behind this hypothesis in a brief
paragraph.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Modern Human Brain Size and
1-5

Intelligence
In The Descent of Man, Charles Darwin detailed the following paradox:
No one, I presume, doubts the large proportion which the size of man’s brain bears to his
body, compared to the same proportion in the gorilla or orang, is closely connected with his
higher mental powers…. On the other hand, no one supposes that the intellect of any two
animals or of any two men can be accurately gauged by the cubic contents of their skulls.
(Darwin, 1871, p. 37)

Ignoring Darwin, many have tried to tie individual intelligence to

gross brain size. If the functional unit of the brain is the brain cell and if
larger human brains have more brain cells, does it not follow that brain
size and intelligence are related? It depends.
The evolutionary approach that we have been using to explain how
the large human brain evolved is based on comparisons between species.
Special care attends the extension of evolutionary principles to physical
comparisons within species, especially biological comparisons within or
among groups of modern humans. We now illustrate the difficulty of
within-species comparisons by considering the complexity of correlating
human brain size with intelligence (Deary, 2000). Then we turn to
another aspect of studying the brain and behavior in modern humans—
the fact that unlike that of other animals, so much modern human
behavior is culturally learned.

Meaning of Human Brain Size Comparisons

Over a century ago some investigators promoted a simple conclusion:
people with the largest brains display the most intelligent behavior. The
late Stephen Jay Gould, in his 1981 book The Mismeasure of Man,
reviews much of this early literature and criticizes the research on three
counts: brain measurement, correlating brain size and intelligence, and
what intelligence is.
First, measuring a person’s brain is difficult. If a tape measure is
simply placed around a person’s head, factoring out skull thickness is
impossible. There is also no agreement about whether volume or weight
is a better measure. And no matter which indicator we use, we must
consider body size. The human brain varies in weight from about 1000
grams to more than 2000 grams, but people also vary in body mass. To
what extent should we factor in body mass in deciding whether a
particular brain is large or small? And how should we measure body
mass, given that a person’s total weight can fluctuate widely over time?
Large differences between the brains of individual people do exist,
but the reasons for these differences are numerous and complex.
Consider some examples. People may have larger or smaller brain cells.
Larger people are likely to have a larger brain than smaller people. Men
have a somewhat larger brain than women, but they are proportionately
physically larger. Nevertheless, girls mature more quickly than boys, so
in adolescence the brain and body size differences may be absent. As
people age, they generally lose brain cells, so their brain shrinks.
Neurological diseases associated with aging accelerate the age-related
decrease in brain size. Brain injury near the time of birth often results in
a dramatic reduction in brain size, even in regions distant from the
damage. Stress associated with physical or behavioral deprivation in
infancy also reduces brain size (Herringa et al, 2013). Neurological
disorders associated with a parent’s abuse of alcohol or other drugs are
associated with conditions such as fetal alcohol spectrum disorder
(FASD), in which the brain can be greatly reduced in size. Autism
spectrum disorder (ASD), a largely genetic condition affecting
development, produces a wide variety of brain abnormalities, including
either increases or decreases in brain size in different individuals.
To find information on specific conditions, consult the Index of
Disorders inside the front cover of this book.
Brain size may also increase in individuals. For example, just as good
nutrition in the early years of life can be associated with larger body size,
good nutrition can also be associated with an increase in brain size. The
brain’s plasticity —its ability to change—in response to an enriched
environment is associated with growth of existing brain cells and thus an
increase in brain size. Furthermore, one way in which the brain stores
new skills and memories is to form new connections among brain cells,
and these connections in turn contribute to increased brain size.
plasticity The nervous system’s potential for physical or chemical
change; enhances its adaptability to environmental change and its
ability to compensate for injury. (Also called neuroplasticity.)
Sections 2-1 and 2-6 elaborate on plasticity, Focus 8-1 and Section
8-4 on environment and brain development, Section 11-3 on skilled
movement, Section 14-1 on memory.
 Finally, we must also consider what is meant by intelligence. When
we compare behavior across species, we are comparing species-typical
behavior —behavior displayed by all members of a species. For
example, lamprey eels do not have limbs and cannot walk, whereas
salamanders do have limbs and can walk: the difference in brain size
between the two species can be correlated with this trait. When we
compare behavior within a species, however, we are usually comparing
how well one individual performs a certain task in relation to others—
how well one salamander walks relative to how well another salamander
walks, for example.
species-typical behavior Behavior that is characteristic of all
members of a species, such as walking in amphibians.

Sea lamprey
 Salamander

We can make intraspecies comparisons for humans, but this likewise

presents problems. For one thing, individual performance on a task is
influenced by many factors unrelated to inherent ability, among them
opportunity, interest level, training, motivation, and health. For another,
people vary enormously in their individual abilities, depending on the
particular task. One person may have superior verbal skills but mediocre
spatial abilities; another person may be adept at solving spatial puzzles
but struggle with written work; still another may excel at mathematical
reasoning and be average in everything else. Which of these people
should we consider the most intelligent? Should certain skills carry
greater weight as measures of intelligence? Clearly, it is difficult to say.
Early in the twentieth century, Charles Spearman carried out the first
formal performance analysis among various tests used to rate
intelligence. He found a positive correlation among tests and suggested
that a single common factor explained them. Spearman named it g for
general intelligence factor, but it turns out that g also varies. Many
factors unrelated to inherent ability—among them opportunity, interest
level, training, motivation, and health—influence individual performance
on a task.
For example, when IQ tests that were given to young adults of one
generation are given to the next generation, scores increase by as much
as 25 points, a phenomenon called the Flynn effect (Flynn, 2012). Taken
at face value—though it shouldn’t be—the increase suggests that human
g has risen to such a degree in two generations that most young adults
fall in the superior category relative to their grandparents. Obviously, the
score change has not been accompanied by a similar increase in brain
size. It is more likely that education and other life experiences explain
the Flynn effect.
Howard Gardner (2006), furthermore, proposes that humans have a
number of intelligences—verbal, musical, mathematical, social, and so
on. Each type of intelligence is dependent on the function of a particular
brain region or regions. Hampshire and colleagues (2012), who
presented participants with a battery of typical intelligence assessment
tests, support Gardner’s idea. As participants took the tests, their brain
activity was imaged and recorded. The study identified three separate
abilities—reasoning, short-term memory, and verbal ability—each
associated with a different brain network. The experimenters argue that
this finding provides little support for Spearman’s g. They further
suggest that a wider array of assessments would reveal additional
intelligence networks.
Figure 15-9 illustrates the profusion of brain networks; Section 15-6
relates network efficiency to intelligence.
Given the difficulty in measuring brain size and in defining
intelligence, it is not surprising that scant research appears in the
contemporary literature on the problem of gross brain size and
intelligence. If you are wondering whether having a larger brain might
mean you could study a little less, consider this. The brains of people
who are widely considered highly intelligent have been found to vary in
size from the low end to the high end of the range for our species. The
brain of the brilliant physicist Albert Einstein was average in size.
Section 15-6 expands on theories of intelligence. Einstein’s brain is
pictured in Figure 15-20 .

Acquisition of Culture
In evolutionary terms, the modern human brain developed rapidly. Many
behavioral changes differentiate us from our primate ancestors, and these
adaptations took place more rapidly still, long after the modern brain had
evolved. The most remarkable thing that our brains have made possible
is ever more complex culture —learned behaviors passed from
generation to generation through teaching and experience.
culture Learned behaviors that are passed on from one generation to
the next through teaching and imitation.
Cultural growth and adaptation render many contemporary human
behaviors distinctly different from those of Homo sapiens living 200,000
years ago. Only 30,000 years ago, modern humans made the first artistic
relics: elaborate paintings on cave walls and carved ivory and stone
figurines. Agriculture appears still more recently, about 15,000 years
ago, and reading and writing were invented only about 7000 years ago.
Saint Ambrose, who lived in the fourth century, is reportedly the
first person who could read silently.
Most forms of mathematics and many of our skills in using
mechanical and digital devices have still more recent origins. Early H.
sapiens brains certainly did not evolve to select smart phone apps or
imagine traveling to distant planets. Apparently, the things that the
human brain did evolve to do contained the elements necessary for
adapting to more sophisticated skills.
Alex Mesoudi and his colleagues (2006) suggest that cultural
elements, ideas, behaviors, or styles that spread from person to person—
called memes (after genes, the elements of physical evolution)—can also
be studied within an evolutionary framework. They propose that
individual differences in brain structure may favor the development of
certain memes. Once developed, memes would in turn exert selective
pressure on further brain development. For example, chance variations in
individuals’ brain structure may have favored tool use in some
individuals. Tool use proved so beneficial that toolmaking itself exerted
selective pressure on a population to favor individuals well skilled in tool
fabrication.
meme An idea, behavior, or style that spreads from person to person
within a culture.
Similar arguments can be made with respect to other memes, from
language to music, from mathematics to art. Mesoudi’s reasoning
supports neuroscience’s ongoing expansion into seemingly disparate
disciplines, including linguistics, the arts, business, and economics.
Studying the human brain, far from examining a body organ’s structure,
means investigating how it acquires culture and fosters adaptation as the
world changes and as the brain changes the world.
Section 15-3 explores some of psychology’s expanding frontiers.
 1-5 REVIEW
Modern Human Brain Size and Intelligence
Before you continue, check your understanding.
1 . Behavior that is displayed by all members of a species is called
___________.
2 . Some modern human behavior is inherent to our nervous system, but
far more is learned—passed generation to generation by ___________.
Ideas, behaviors, or styles called ___________ may spread from
person to person and culture to culture.
3 . Spearman proposed a common intelligence factor he called
___________. Gardner supports the idea of ___________.
4 . Explain the reasoning behind the statement that what is true for
evolutionary comparisons across different species may not be true for
comparisons within a single species.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 SUMMARY
1-1 Neuroscience in the Twenty-First Century
Studying the brain and behavior leads us to better understand our origins,
our human nature, the causes of many behavioral disorders, and the
rationale behind treatment for disorders.
The human nervous system is composed of the CNS, which includes
the brain and the spinal cord, and the PNS, through which the brain and
spinal cord communicate with sensory receptors, with muscles and other
tissues, and with the internal organs. The cerebrum and the cerebellum
have undergone the most growth in large-brained animal species.
We define behavior as any kind of movement, including mental
processes such as thinking and imagining. In animals, behavior is caused
by nervous system activity. Behavioral flexibility and complexity vary
greatly across species, as does the nervous system.
For some species, including humans, the brain is the organ that exerts
control over behavior. The brain seems to need ongoing sensory and
motor stimulation to maintain its intelligent activity.
 1-2 Perspectives on Brain and Behavior
Mentalism views behavior as a product of an intangible entity called the
mind (psyche); the brain has little importance. Dualism is the notion that
the immaterial mind acts through the material brain to produce language
and rational behavior, whereas the brain alone is responsible for the
“lower” actions that we have in common with other animal species.
Materialism, the view that brain function fully accounts for all
behavior, language and reasoning included, guides contemporary
research on the brain and behavior. Support for the materialistic view
comes from the study of natural selection—the evolutionary theory that
behaviors such as human language evolved from the simpler language
abilities of human ancestors—and from discoveries about how genes
function. Experiments follow the process of science: first, formulate a
question (hypothesis), then design a procedure to test it, evaluate the
results, and confirm or modify the hypothesis.
After severe TBI, the brain demonstrates a remarkable ability to
recover, but after either mild or severe injury, a person can be left with a
permanent disability that prevents full recovery to former levels of
function. Brain imaging techniques can confirm severe disabilities such
as the MCS, locked-in syndrome, and PVS.
 1-3 Evolution of Brains and of Behavior
Behavioral neuroscientists subscribe to the evolutionary principle that all
living organisms are descended from a common ancestor. Brain cells and
muscles are quite recent developments in the evolution of life on Earth.
Because they evolved only once, a similar basic pattern exists in the
nervous systems of all animals.
The nervous systems of some animal lineages have become more
complex, with evolution featuring first a nerve net, followed by a
bilaterally symmetrical and segmented nervous system, a nervous system
controlled by ganglia, and eventually, in chordates, a nervous system
featuring a brain and spinal cord.
Mammals are a class of chordates characterized by a large brain
relative to body size. Modern humans belong to the primate order, which
is distinguished by especially large brains, and to the family of great
apes, whose members’ limber shoulders allow them to brachiate (hang
and swing by the arms).
 1-4 Evolution of the Human Brain and Behavior
One of our early hominid ancestors was probably an Australopithecus,
who lived in Africa several million years ago. It is from an australopith
species that Homo evolved through species such as Homo habilis and
Homo erectus. Modern humans, Homo sapiens sapiens, appeared about
200,000 years ago.
Since Australopithecus, the hominid brain has increased in size
almost threefold, as has its number of brain cells. The EQ describes brain
size relative to body size, but a complete comparison of different
species’ brains requires brain cell counts. Among the factors
hypothesized to have stimulated brain evolution in human species are
environmental challenges and opportunities, such as climate changes that
favored the natural selection of adaptability and more complex behavior
patterns. Also proposed are lifestyle changes such as social cooperation
and cooking food, changes in physiology, and changed maturation rate.
 1-5 Modern Human Brain Size and Intelligence
Evolutionary principles learned from studying the brain and behavior
across species do not easily apply to the brain and behavior within a
single species, such as Homo sapiens. As animals evolved, larger brains
were associated with more complex behavior. Yet within our species, the
complexity of different brain regions is related to behavioral abilities.
People vary widely in body size and in brain size as well as in varying
kinds of intelligence, making a simple comparison of brain size and
general intelligence unwise.
Recognizing the great extent to which modern human behavior, rather
than being inherent in our nervous systems, results from cultural learning
and transmission is paramount to understanding how our brains function.
Memes may spread from person to person and culture to culture.
 KEY TERMS
bilateral symmetry, p. 18
brainstem, p. 5
central nervous system (CNS), p. 3
cerebellum, p. 5
cerebrum (forebrain), p. 5
chordate, p. 18
cladogram, p. 18
clinical trial, p. 13
common ancestor, p. 15
culture, p. 28
deep brain stimulation (DBS), p. 13
dualism, p. 8
embodied behavior, p. 5
encephalization quotient (EQ), p. 22
epigenetics, p. 11
ganglia, p. 18
genotype, p. 11
hemisphere, p. 5
hominid, p. 20
locked-in syndrome, p. 5
materialism, p. 8
meme, p. 28
mentalism, p. 7
mind, p. 7
mind–body problem, p. 8
minimally conscious state (MCS), p. 13
natural selection, p. 8
neoteny, p. 27
nerve net, p. 17
neuron, p. 3
peripheral nervous system (PNS), p. 3
persistent vegetative state (PVS), p. 13
phenotype, p. 8
plasticity, p. 28
psyche, p. 7
segmentation, p. 18
species, p. 8
species-typical behavior, p. 28
spinal cord, p. 3
traumatic brain injury (TBI), p. 3

Visit Launch Pad to access the e-Book, videos,

Learning Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

What Is the Nervous

System’s Functional
Anatomy?
 Katherine Streeter

RESEARCH FOCUS 2-1 AGENESIS OF THE CEREBELLUM

2-1 OVERVIEW OF BRAIN FUNCTION AND STRUCTURE
PLASTIC PATTERNS OF NEURAL ORGANIZATION
FUNCTIONAL ORGANIZATION OF THE NERVOUS SYSTEM
THE BRAIN’S SURFACE FEATURES
THE BASICS FINDING YOUR WAY AROUND THE BRAIN
CLINICAL FOCUS 2-2 MENINGITIS AND ENCEPHALITIS
THE BRAIN’S INTERNAL FEATURES
CLINICAL FOCUS 2-3 STROKE
2-2 THE NERVOUS SYSTEM’S EVOLUTIONARY
DEVELOPMENT
STAGES IN BRAIN EVOLUTION
THE NERVOUS SYSTEM AND INTELLIGENT BEHAVIOR
EXPERIMENT 2-1 QUESTION: DOES INTELLIGENT BEHAVIOR
REQUIRE A VERTEBRATE NERVOUS SYSTEM ORGANIZATION?
2-3 THE CENTRAL NERVOUS SYSTEM: MEDIATING
BEHAVIOR
SPINAL CORD
BRAINSTEM
FOREBRAIN
CEREBRAL CORTEX
BASAL GANGLIA
LIMBIC SYSTEM
OLFACTORY SYSTEM
2-4 SOMATIC NERVOUS SYSTEM: TRANSMITTING
INFORMATION
CRANIAL NERVES
SPINAL NERVES
 SOMATIC NERVOUS SYSTEM CONNECTIONS
INTEGRATING SPINAL FUNCTIONS
CLINICAL FOCUS 2-4 MAGENDIE, BELL, AND BELL PALSY
2-5 AUTONOMIC AND ENTERIC NERVOUS SYSTEMS:
VISCERAL RELATIONS
ANS: BALANCING INTERNAL FUNCTIONS
ENS: CONTROLLING THE GUT
2-6 TEN PRINCIPLES OF NERVOUS SYSTEM FUNCTION
PRINCIPLE 1: THE NERVOUS SYSTEM PRODUCES MOVEMENT
IN A PERCEPTUAL WORLD THE BRAIN CONSTRUCTS
PRINCIPLE 2: NEUROPLASTICITY IS THE HALLMARK OF
NERVOUS SYSTEM FUNCTIONING
PRINCIPLE 3: MANY BRAIN CIRCUITS ARE CROSSED
PRINCIPLE 4: THE CNS FUNCTIONS ON MULTIPLE LEVELS
PRINCIPLE 5: THE BRAIN IS SYMMETRICAL AND
ASYMMETRICAL
PRINCIPLE 6: BRAIN SYSTEMS ARE ORGANIZED
HIERARCHICALLY AND IN PARALLEL
PRINCIPLE 7: SENSORY AND MOTOR DIVISIONS PERMEATE
THE NERVOUS SYSTEM
PRINCIPLE 8: THE BRAIN DIVIDES SENSORY INPUT FOR
OBJECT RECOGNITION AND MOTOR CONTROL
PRINCIPLE 9: BRAIN FUNCTIONS ARE LOCALIZED AND
DISTRIBUTED
PRINCIPLE 10: THE NERVOUS SYSTEM WORKS BY
JUXTAPOSING EXCITATION AND INHIBITION
RESEARCH FOCUS 2-1

Agenesis of the Cerebellum

When an adult’s brain is damaged, as for example in traumatic brain
injury, we see a pattern of behavioral changes that offer insight into
brain functions, as described by Fred Linge in Clinical Focus 1-1 ,
Living with Traumatic Brain Injury. Naturally occurring brain
injuries rarely remove a single structure completely, leaving the rest
of the brain intact. However, agenesis, the failure of brain regions to
develop, offers researchers a unique window on the brain’s
organization and function, because in rare cases a complete structure
is absent yet the rest of the brain appears normal.
Historically, the cerebellum was viewed as a motor structure, with
the most obvious sign of damage being ataxia, a failure of muscular
coordination and balance. But the cerebellum’s functions are much
more extensive than movement control (e.g., Schmahmann, 2010).
Adult patients with damage to the cerebellum do have motor
disturbances, but they also have cognitive deficits, for example, in
abstract thinking and language and in emotional control.
The cerebellum contains the most neurons of any brain region,
accounting for 80 percent of the neurons in humans and a whopping
97.5 percent of elephants’ neurons—believed to be related to the
dexterity of the elephant’s trunk. What would happen if the
cerebellum failed to develop but the rest of the brain developed
apparently normally? We humans would be missing 80 percent of
our neurons!
The accompanying images contrast the brain of a young man born
with agenesis of the cerebellum (A and B) to the brain of a person
whose brain developed normally (C and D). Even lacking 80 percent
of his neurons, the young man’s behavioral capacities are
remarkable, but his behavior is not typical. Now in his thirties, he
has an office job and lives alone. He has a distinctive speaking
pattern, an awkward gait, and difficulties with balance, as well as
deficits in planning and abstract thinking. His social skills and long-
term memory are good, though, as is his mastery of routine
activities.
 Studies of other people with cerebellar agenesis reveal a
heterogeneous set of symptoms, but neuropsychological assessments
show behavioral deficits reminiscent of people with damage to
frontal and parietal cortical regions (e.g., Baumann et al., 2015),
even though these cerebral regions are intact. Although people with
cerebellar agenesis develop slowly, they show remarkable
improvement over time and seem able to compensate for many of
their symptoms. The individual whose brain you see in images A and
B had severe visuomotor spatial disabilities as a child and
adolescent, but by age 30 he showed significant improvement
(Chheda et al., 2002; Schmahmann et al., 2007; Jeremy D.
Schmahmann and Janet C. Sherman, personal communication).
Other patients’ language develops slowly.

Massachusetts General Hospital; Credit: Courtesy of Jeremy Schmahmann

MRI brain scans of a person with cerebellar agenesis (A, B)
compared to a control person (C, D) of the same age. A and C
are viewed in the coronal plane, B and D in the mid-sagittal
plane. For more about this condition:
www.npr.org/blogs/health/2015/03/16/393351760
 In people with absence of the cerebellum it is thought that brain
plasticity in response to early perturbations emerge as regions of the
cerebral cortex begin to function more efficiently. In fact, it has been
reported that cerebellar agenesis patients appear to have some of the
symptoms of autism early in life. This observation comports with
evidence that dysfunction (rather than absence) of the cerebellum is
related to autism (detailed in Clinical Focus 8-2 , Autism Spectrum
Disorder).

Throughout this book we examine the nervous system with a focus on

function—on how our behavior and our brain interact. In this chapter, we
consider the human nervous system’s organization and how its basic
components function in the context of plasticity, as illustrated in
Research Focus 2-1 , Agenesis of the Cerebellum. First, we emphasize
the brain’s biology. Then we elaborate on function—how the brain works
in concert with the rest of the nervous system. This focus on nervous
system function and plasticity suggests 10 principles of nervous system
organization. We note each principle through the chapter and in detail at
its end, in Section 2-6 . These big ideas apply equally to the micro and
macro views of the nervous system presented in this chapter and to the
broader picture of behavior that emerges in later chapters.
 Overview of Brain Function and
2-1

Structure
The brain’s primary function is to produce behavior, or movement. To
produce behavior as we search, explore, and manipulate our
environment, the brain must absorb information about the world—about
the objects around us: their size, shape, and location. Without stimuli, the
brain cannot orient the body and direct it to produce an appropriate
response.
The nervous system’s organs are designed to admit information from
the world and to convert this information into biological activity that
produces perception, subjective experiences of reality. The brain thus
produces what we believe is reality so that we can move. This subjective
reality is essential to carrying out any complex task.
Principle 1: The nervous system produces movement in a perceptual
world the brain constructs.
When you answer the telephone, for example, your brain directs your
body to reach for it as the nervous system responds to vibrating air
molecules by producing the subjective experience of a ringtone. We
perceive this stimulus as sound and react to it as if it actually exists,
when in fact the sound is merely a fabrication of the brain. That
fabrication is produced by a chain reaction that takes place when
vibrating air molecules hit the eardrum. Without the nervous system,
especially the brain, sound does not exist—only the movement of air
molecules.
But there is more to hearing a phone’s ringtone than vibrating air
molecules. Our mental construct of reality is based not only on the
sensory information we receive but also on the cognitive processes we
might use to interact with that incoming information. Hearing a ringtone
when we are expecting a call has a meaning vastly different from its
ringing at three o’clock in the morning, when we are not expecting a call.
The subjective reality the brain constructs can be better understood by
comparing the sensory realities of two different kinds of animals. You
are probably aware that dogs perceive sounds that humans do not. This
difference in perception does not mean that a dog’s nervous system is
better than ours or that our hearing is poorer. Rather, the perceptual
world constructed by a dog brain simply differs from that of a human
brain. Neither experience is “correct.” The difference in subjective
experience is due merely to two differently evolved systems for
processing sensory stimuli.
Section 9-1 elaborates on the nature of sensation and perception.
When it comes to visual perception, our world is rich with color,
whereas dogs see very little color. Human brains and dog brains
construct different realities. Subjective differences in brains exist for
good reason: they allow different animals to exploit different features in
their environments. Dogs use their hearing to detect the movements of
prey, such as mice in the grass; early humans probably used color vision
for identifying ripe fruit in trees. Evolution, then, fosters adaptability,
equipping each species with a view of the world that helps it survive.

Plastic Patterns of Neural Organization

The brain is plastic : neural tissue has the capacity to adapt to the world
by changing how its functions are organized. Just as the brain of the
young man profiled in Research Focus 2-1 adapted to cerebellar
agenesis, a person blind from birth has enhanced auditory capacities
because some of the brain’s visual regions have been co-opted for
hearing. The brain is also plastic in the sense that connections among
neurons in a given functional system are constantly changing in response
to experience.
For us to learn anything new, neural circuits must change to represent
and store this knowledge. As we learn to play a musical instrument or
speak a new language, the cortical regions taking part can actually
increase in size to accommodate the learning. An important aspect of
human learning and brain plasticity is related to the development of
language and to the expansion of the brain regions related to language.
We have learned to read, to calculate, to compose and play music, and to
develop the sciences. Clearly, the human nervous system evolved long
before we mastered these achievements.
In turn, culture now plays a dominant role in shaping our behavior.
Because we drive cars and communicate electronically, we—and our
nervous system—must differ from those of our ancestors who did not
engage in these activities. The basis for change in the nervous system is
neuroplasticity, the nervous system’s fundamental potential for physical
or chemical change that enhances its adaptability to environmental
change and its ability to compensate for injury.
 neuroplasticity The nervous system’s potential for physical or
chemical change to adapt to environmental change and to
compensate for injury.
Principle 2: Neuroplasticity is the hallmark of nervous system
functioning.
Although it is tempting to see neuroplasticity as a trait unique to
animals’ nervous systems, it is really part of a larger biological capacity
called phenotypic plasticity, the individual’s capacity to develop into
more than one phenotype —the characteristics we can see or measure.
(See Gilbert & Epel, 2009, for a wonderful discussion of biological
plasticity.) Stated simply, an individual’s genotype (genetic makeup)
interacts with the environment to elicit a specific phenotype. This
phenotype emerges from a large genetic repertoire of possibilities, a
phenomenon that in turn results from epigenetic influences.
phenotypic plasticity An individual’s capacity to develop into more
than one phenotype.
Section 1-2 introduces the genotype, phenotype, and epigenetics in
an evolutionary context.
Epigenetic factors do not change genes but rather influence how
genes inherited from parents express specific traits. The two mice
pictured in Figure 2-1 appear very different: one is fat, one thin; one has
dark fur, the other is light-colored. Yet these mice essentially are clones,
genetically identical. They appear so different because their mothers
were fed different diets while pregnant. The diet supplements added
chemical markers, or epigenetic tags, on specific genes. The tags
determine whether the gene is available to influence cells, including
neurons, leading to differences in body structure and eating behavior.
 Randy L. Jirtle, Adjunct Professor of Epigenetics, Department of Biological
Sciences, NC State University, Raleigh, NC

FIGURE 2-1 Phenotypic Plasticity These two mice are genetically

identical but express very different phenotypes because their mothers
were fed different supplements when pregnant.

Functional Organization of the Nervous

System
From an anatomical standpoint, the brain and spinal cord together make
up the central nervous system. The nerve fibers radiating out beyond the
brain and spinal cord, as well as all the neurons outside the brain and
spinal cord, form the peripheral nervous system. Figure 2-2 A charts this
anatomical organization. PNS nerves carry sensory information into the
CNS and carry motor instructions from the CNS to the body’s muscles
and tissues, including those that perform such functions as blood
circulation and digestion.
Figure 2-A restates Figure 1-1 , the gross anatomy of the human
CNS and PNS.
In a functional organization, little changes, but the focus turns to how
the parts of the system work together. Neurons in the somatic division of
the PNS connect through the cranial and spinal nerves to receptors on the
body’s surface and on its muscles. Somatic neurons gather sensory
information for the CNS and convey information from the CNS to move
muscles of the face, body, and limbs. Similarly, the autonomic division
of the PNS enables the CNS to govern the workings of your body’s
internal organs—your heartbeat, urination, pupillary response, and the
diaphragm movements that inflate and deflate your lungs. The enteric
nervous system, which is sometimes considered part of the ANS,
controls digestion and stomach contractions.
And so, from a functional standpoint (Figure 2-2B ), the major PNS
divisions step up to constitute, along with the CNS, an interacting four-
part system:
• The CNS includes the brain and the spinal cord—the nervous system
core, which mediates behavior.

(A) Anatomic Organization

(B) Functional Organization

FIGURE 2-2 Parsing the Nervous System The nervous system

can be conceptualized (A) anatomically and (B) functionally. The
functional approach employed in this book focuses on how the four parts
of the nervous system interact.

• The somatic nervous system (SNS) includes all the spinal and cranial
nerves carrying sensory information to the CNS from the muscles,
 joints, and skin. It also transmits outgoing motor instructions that
produce movement.
somatic nervous system (SNS) Part of the PNS that includes the
cranial and spinal nerves to and from the muscles, joints, and skin,
which produce movement, transmit incoming sensory input, and
inform the CNS about the position and movement of body parts.
• The autonomic nervous system (ANS) balances the body’s internal
organs by producing the rest-and-digest response through the
parasympathetic (calming) nerves or the fight-or-flight response or
vigorous activity through the sympathetic (arousing) nerves.
autonomic nervous system (ANS) Part of the PNS that regulates
the functioning of internal organs and glands.
• The enteric nervous system (ENS), formed by a mesh of neurons
embedded in the lining of the gut, controls the gut. The ENS
communicates with the CNS via the ANS but mostly operates
autonomously.
enteric nervous system (ENS) Mesh of neurons embedded in the
lining of the gut, running from the esophagus through the colon;
controls the gut.
The directional flow of neural information is important. Afferent
(incoming) information is sensory, coming into the CNS or one of its
parts, whereas efferent (outgoing) information is leaving the CNS or one
of its parts. When you step on a tack, the afferent sensory signals are
transmitted from the body into the brain and felt as pain. Efferent signals
from the brain trigger a motor response: you lift your foot ( Figure 2-3 ).
afferent Conducting toward a CNS structure.
efferent Conducting away from a CNS structure.
 FIGURE 2-3 Neural Information Flow

The Brain’s Surface Features

When buying a new car, people like to look under the hood and examine
the engine, the part of the car responsible for most of its behavior—and
misbehavior. All most of us can do is gaze at the maze of tubes, wires,
boxes, and fluid reservoirs. What we see makes no sense except in the
most general way. We know that the engine somehow generates power to
make the car move and to run the sound system, lights, and wipers. But
knowing this tells us nothing about what all the many engine parts do.
When it comes to our behavior, the brain is the engine. In many ways,
examining a brain for the first time is similar to looking under the car
hood. We have a vague sense of what the brain does, but most of us have
no sense of how its parts accomplish these tasks. We may not even be
able to identify those parts. If you are familiar with the anatomical terms
and orientations used in drawings and images of brains, read on. If you
prefer to review this terminology before you continue, consult The
Basics: Finding Your Way Around the Brain on pages 38 –39 .
Protecting the Nervous System
We start our functional overview by opening the hood and observing the
brain snug in its home in the skull. The first thing you encounter is not
the brain but rather a tough triple-layered protective covering, the
meninges (sing. meninx ) (Figure 2-4 ). The outer dura mater (from
Latin, meaning hard mother ) is a tough double layer of fibrous tissue
that encloses the brain and spinal cord in a kind of loose sac. In the
middle is the arachnoid layer (from Greek, meaning like a spider’s web
), an ultrathin sheet of delicate connective tissue that follows the brain’s
contours. The inner layer, or pia mater (from Latin, meaning soft mother
), is a moderately tough membrane of connective tissue fibers that cling
to the brain’s surface.
meninges Three layers of protective tissue—dura mater, arachnoid,
and pia mater—that encase the brain and spinal cord.

Cerebral Protection A triple-layered covering, the

FIGURE 2-4
meninges, encases the brain and spinal cord, and cerebrospinal fluid
(CSF) cushions them.
 THE BASICS

Finding Your Way Around the

Brain
When the first anatomists began to examine the brain with the
primitive tools of their time, the names they chose for brain regions
often manifested their erroneous assumptions about how the brain
works. They named one brain region the gyrus fornicatus because
they thought that it had a role in sexual function, but most of this
region actually has nothing to do with sexual activity.
A Wonderland of Nomenclature
As time went on, the assumptions and tools of brain research changed,
but naming continued to be haphazard and inconsistent. Many brain
structures have several names, and terms are often used
interchangeably. This peculiar nomenclature arose because research
on the brain and behavior spans several centuries and includes
scientists of many nationalities and languages.
Early investigators named structures after themselves or objects or
ideas. They used various languages, especially Latin, Greek, and
English. More recently, investigators have often used numbers or
letters, but even this system lacks coherence, because the numbers
may be Arabic or Roman and are often used in combination with
Greek or Latin letters.
Describing Locations in the Brain
Many names for nervous system structures reflect their anatomical
locations with respect to other body parts of the animal, with respect
to their relative spatial locations, and with respect to a viewer’s
perspective:
• Brain–Body Orientation illustrates brain structure location from the
frame of reference of the human face.
 Brain–Body Orientation

• Spatial Orientation illustrates brain structure location in relation to

other body parts and body orientation.
• Anatomical Orientation illustrates the direction of a cut, or section,
through the human brain (part A) from the perspective of a viewer
(part B).

Spatial Orientation

These orienting terms are derived from Latin. Consult the

accompanying Glossary of Anatomical Location and Orientation for
easy reference. It is common practice to combine orienting terms. A
structure described as dorsolateral, for example, means that it lies up
and to the side.
Finally, the nervous system, like the body, is bilaterally
symmetrical: it has a left side and a right side. Structures that lie on
the same side are ipsilateral; if they lie on opposite sides, they are
contralateral to each other. Structures that occur in each hemisphere
are bilateral. Structures that are close to one another are proximal;
those far from one another are distal.

Coronal section

Horizontal section
Sagittal section
(A) Plane of section
 Living Art Enterprises/Science Source
Frontal view

A coronal section is cut in a vertical plane, from the crown of the

head down, yielding a frontal view of the brain’s internal structures.

Living Art Enterprises/Science Source

Dorsal view

A horizontal section, so-called because the view or the cut falls

along the horizon, is usually viewed looking down on the brain from
above—a dorsal view.

Medial view

A sagittal section is cut lengthways from front to back and

viewed from the side. (Imagine the brain split by an arrow—in
Latin, sagitta. ) Here, a cut in the midsagittal plane divides
the brain into symmetrical halves, a medial view.

(B) View of brain

 Living Art Enterprises/Science Source
Anatomic Orientation

Glossary of Anatomical Location and Orientation

Term Meaning with respect to the nervous system

Anterior Near or toward the front of the animal or the front of the head (see also frontal
and rostral )

Caudal Near or toward the tail of the animal (see also posterior )

Coronal Cut vertically from the crown of the head down; used to reference the plane
of a brain section that reveals a frontal view

Dorsal On or toward the back of a four-legged animal (equivalent to posterior for

human spinal cord); in reference to human brain nuclei, above, and to brain
sections, viewed from above

Frontal Of the front (see also anterior and rostral ); in reference to brain sections, a
viewing orientation from the front

Horizonta Cut along the horizon; used to reference the plane of a brain section that
l reveals a dorsal view

Inferior Below (see also ventral )

Lateral Toward the side of the body or brain

Medial Toward the middle, specifically the body’s midline; in reference to brain
sections, a side view of the central structures

Posterior Near or toward the animal’s tail (see also caudal ); for human spinal cord, at
 the back

Rostral Toward the beak (front) of the animal (see also anterior and frontal )

Sagittal Cut lengthways from front to back of the skull to reveal a medial view into the
brain from the side; a cut in the midsagittal plane divides the brain into
symmetrical halves.

Superior Above (see also dorsal )

Ventral On or toward the belly of four-legged animals (see also inferior ); in reference
to human brain nuclei, below.

Your right hand, if made into a fist, represents the positions of the
lobes of the left hemisphere of your brain.
 FIGURE 2-5 The Cerebral Cortex Each cerebral hemisphere is
divided into four lobes: frontal, parietal, temporal, and occipital, shown at left
as oriented in the head. The brain surface, or cerebral cortex, shown in the
frontal view, is a thin sheet of nerve tissue, heavily folded to fit inside the
skull. Your right fist can map the orientation of the left hemisphere and its
lobes.

Between the arachnoid layer and the pia mater flows cerebrospinal
fluid (CSF), a colorless solution of sodium chloride and other salts. CSF
cushions the brain so that it can move or expand slightly without pressing
on the skull. The symptoms of meningitis, an infection of the meninges and
CSF, are described in Clinical Focus 2-2 , Meningitis and Encephalitis, on
page 42 .
cerebrospinal fluid (CSF) Clear solution of sodium chloride and
other salts that fills the ventricles inside the brain and circulates around
the brain and spinal cord beneath the arachnoid layer in the
subarachnoid space.
Cerebral Geography
After removing the meninges, we can examine the brain’s surface features,
most prominently its two nearly symmetrical left and right hemispheres.
Figure 2-5 diagrams the left hemisphere of a typical human forebrain
oriented in the upright human skull. The outer forebrain consists of a thin,
folded film of nerve tissue, the cerebral cortex, detailed in the frontal view
in Figure 2-5 . The word cortex, Latin for tree bark, is apt, considering the
cortex’s heavily folded surface and its location, covering most of the rest of
the brain. Unlike the bark on a tree, however, the brain’s folds are not
random but rather demarcate its functional cortical zones.
cerebral cortex Thin, heavily folded film of nerve tissue composed of
neurons that is the outer layer of the forebrain. Also called neocortex.
Make a fist with your right hand and hold it up, as shown on the right in
Figure 2-5 , to represent the positions of the forebrain’s broad divisions, or
lobes, in the skull. Each lobe is named for the skull bone it lies beneath.
• The forward-pointing temporal lobe lies at the side of the brain, in
approximately the same place as the thumb on your upraised fist. The
temporal lobe functions in connection with hearing and with language
and musical abilities.
temporal lobe Part of the cerebral cortex that functions in connection
with hearing, language, and musical abilities; lies below the lateral
fissure, beneath the temporal bone at the side of the skull.
• Immediately above your thumbnail, your fingers correspond to the
location of the frontal lobe, often characterized as performing the brain’s
executive functions, such as decision making.
frontal lobe Part of the cerebral cortex often generally characterized
as performing the brain’s executive functions, such as decision
making; lies anterior to the central sulcus and beneath the frontal bone
of the skull.
• The parietal lobe is at the top of the skull, as represented by your
knuckles, behind the frontal lobe and above the temporal lobe. Parietal
functions include directing our movements toward a goal or to perform a
task, such as grasping an object.
parietal lobe Part of the cerebral cortex that directs movements
toward a goal or to perform a task, such as grasping an object; lies
posterior to the central sulcus and beneath the parietal bone at the top
of the skull.
• The area at the back of each hemisphere, near your wrist, constitutes the
occipital lobe, where visual processing begins.
occipital lobe Part of the cerebral cortex where visual processing
begins; lies at the back of the brain and beneath the occipital bone.
Examining the Brain’s Surface from All Angles
As we look at the dorsal view in Figure 2-6 A , the brain’s wrinkled left
and right hemispheres resemble a walnut meat taken whole from its shell.
These hemispheres constitute the cerebrum, the major forebrain structure
and most recently evolved feature of the CNS. Visible from the opposite
ventral view in Figure 2-6B are the brainstem, including the wrinkly
hemispheres of the smaller cerebellum (Latin for little brain ). Both the
cerebrum and the brainstem are visible in the lateral and medial views in
Figure 2-6C and D .

Courtesy of Yakovlev Collection/National Museum of Health and Medicine.

(A) Dorsal view

Courtesy of Yakovlev Collection/National Museum of Health and Medicine.

(B) Ventral view
 Courtesy of Yakovlev Collection/National Museum of Health and Medicine.
(C) Lateral view

(D) Medial view

Courtesy of Yakovlev Collection/National Museum of Health and Medicine.

FIGURE 2-6 Examining the Human Brain Locations of the lobes

of the cerebral hemispheres, shown in dorsal, ventral, lateral, and medial
(top, bottom, side, and midline) views, as are the cerebellum, longitudinal
and lateral fissures, and the central sulcus.
CLINICAL FOCUS 2-2

Meningitis and Encephalitis

Harmful microorganisms can invade the layers of the meninges,
particularly the pia mater and the arachnoid layer, as well as the CSF
flowing between them, to cause a variety of infections that lead to
meningitis. One symptom of this condition, inflammation, places
pressure on the brain. Because the space between meninges and skull is
slight, unrelieved pressure can lead to delirium and, if the infection
progresses, to drowsiness, stupor, and even coma.
Usually the earliest symptom of meningitis is severe headache and a
stiff neck (cervical rigidity). Head retraction (tilting the head backward)
is an extreme form of cervical rigidity. Convulsions, a common
symptom in children, indicate that the inflammation is affecting the
brain.
Infection of the brain itself is called encephalitis. Some of its many
forms have great historical significance. A century ago, during World
War I, a form of encephalitis called sleeping sickness (encephalitis
lethargica) reached epidemic proportions. Its first symptom is sleep
disturbance. People sleep all day and become wakeful, even excited, at
night. Subsequently they show symptoms of Parkinson disease,
including severe tremors, muscular rigidity, and difficulty in controlling
body movements. Many are completely unable to make voluntary
movements, such as walking or even combing their hair. Survivors of
sleeping sickness were immortalized by the neurologist Oliver Sacks in
the book and movie Awakenings. Sacks died in 2015 at age 82.
Encephalitis symptoms are caused by the death of an area deep in
the brain, the substantia nigra (black substance), which you will learn
about in Section 2-3 . Other forms of encephalitis may have different
effects on the brain. For example, Rasmussen encephalitis attacks one
cerebral hemisphere in children. In most cases, the only effective
treatment is radical: hemispherectomy, surgical removal of the entire
affected hemisphere.
CDC/Dr. Edwin P. Ewing, Jr.
 Pus is visible over the surface of this brain infected with meningitis.

Surprisingly, some young children who lose a hemisphere adapt

rather well. They may even complete college, literally with half a brain.
But intellectual disabilities are a more common outcome of
hemispherectomy as a result of encephalitis.

Much of the crinkled-up cerebral cortex is invisible from the brain’s

surface. All we can see are bumps, or gyri (sing. gyrus ), and cracks, or
sulci (sing. sulcus ). Some sulci are so deep that they are called fissures.
The longitudinal fissure runs between the cerebral hemispheres and the
lateral fissure along the sides of the brain. Both are shown in various views
in Figure 2-6 , along with the central sulcus that runs from the lateral
fissures across the top of the cerebrum.
gyri (sing. gyrus) A small protrusion or bump formed by the folding
of the cerebral cortex.
sulci (sing. sulcus) A groove in brain matter; most are in the neocortex
or cerebellum.
Looking at the bottom of the brain, the ventral view in Figure 2-6B , we
see in the midst of the wrinkled cerebrum and ventral to the cerebellum a
smooth, whitish structure with little tubes attached. This central set of
structures is the brainstem, the area responsible for most unconscious
behavior. The tubes mark out the cranial nerves that run to and from the
brain as part of the SNS.
Cerebral Circulation
The brain’s surface appears to be covered with blood vessels. As with the
rest of the body, the arteries feed blood to the brain and send it back through
veins to the kidneys and lungs for cleaning and oxygenation. The cerebral
arteries emerge from the neck to wrap around the outside of the brainstem,
cerebrum, and cerebellum, finally penetrating the brain’s surface to nourish
its inner regions.
Dorsal view
Lateral view
Anterior cerebral artery

Lateral view
Medial view
Middle cerebral artery

Ventral view
Medial view
Posterior cerebral artery

FIGURE 2-7 Major Cerebral Arteries Each of the three major arteries
that feed blood to the cerebral hemispheres branches extensively to supply
the regions shaded in pink.
 Three major arteries send blood to the cerebrum—the anterior, middle,
and posterior cerebral arteries, shown in Figure 2-7 . Because the brain is
highly sensitive to blood loss, a blockage or break in a cerebral artery is
likely to lead to the death of the affected region. This condition, known as
stroke, is the sudden appearance of neurological symptoms as a result of
severely interrupted blood flow. Because the three cerebral arteries supply
different parts of the brain, strokes disrupt different brain functions,
depending on the artery affected.
stroke Sudden appearance of neurological symptoms as a result of
severely interrupted blood flow.
Section 16-3 elaborates on the effects of stroke and its treatment.
Because the brain’s connections are crossed, stroke in the left
hemisphere affects sensation and movement on the right side of the body.
The opposite is true for those with strokes in the right hemisphere. Clinical
Focus 2-3 , Stroke, on page 45 , describes some disruptions that stroke
causes, both to the person who has it and to those who care for stroke
victims.
Principle 3: Many brain circuits are crossed.

The Brain’s Internal Features

The simplest way to examine the inside of something is to cut it in half. Of
course, the orientation of the cut affects what we see. Consider slicing
through a pear. If we cut from side to side, we cut across the core, providing
a dorsal view; if we cut from top to bottom, we cut parallel to the core,
providing a medial view. Our impression of the inside of a pear is clearly
influenced by how we slice it. The same is true of the brain.
Macro View
We can reveal the brain’s inner features by slicing it parallel to the front of
the body, downward through the middle in a coronal section (Figure 2-8A
). The resulting frontal view, shown in Figure 2-8B , makes immediately
apparent that the brain’s interior is not homogeneous. Both dark and light
regions of tissue are visible, and though these regions may not be as
distinctive as car engine parts, they nevertheless represent different brain
components.
The darker regions are gray matter, largely composed of cell bodies and
capillary blood vessels. Gray matter neurons either collect and modify
information or support this activity. The lighter regions are white matter,
mostly nerve fibers with fatty coverings that produce the white appearance,
much as fat droplets in milk make it appear white. White matter fibers form
connections between and among the brain’s cells.
gray matter Areas of the nervous system composed predominantly of
cell bodies and capillary blood vessels that either collect and modify
information or support this activity.
white matter Areas of the nervous system rich in fat-sheathed neural
axons that form the connections between brain cells.

Glauberman/Science Source
(A) Coronal section
(B) Frontal view
FIGURE 2-8 Coronal Brain Section (A) The brain is cut down the
middle parallel to the front of the body; then a coronal section is viewed at a
slight angle. This frontal view (B) displays white matter, gray matter, and the
lateral ventricles. Visible above the ventricles, a large bundle of fibers, the
corpus callosum, joins the hemispheres.

A second feature, apparent at the center of our frontal view in Figure 2-

8B , are the ventricles —two wing-shaped cavities that contain
cerebrospinal fluid. The brain’s four ventricles, shown in place in Figure 2-
9 , are filled with CSF made by the cells lining the ventricles. All four
ventricles are connected, so CSF flows from the two lateral ventricles to the
third and fourth ventricles, which lie on the brain’s midline, and into the
cerebral aqueduct, a canal that runs down the length of the spinal cord. CSF
is also found in the space between the lower layers of the meninges that
wrap around the brain and spinal cord (see Figure 2-4 ).
ventricle One of four cavities in the brain that contain CSF to cushion
the brain; may play a role in maintaining brain metabolism.
Although the ventricles’ functions are not well understood, researchers
think that they play an important role in maintaining brain metabolism. CSF
may allow certain compounds access to the brain, and it probably helps the
brain excrete metabolic wastes. In the event of trauma to the brain or spinal
cord, CSF cushions the blow.
 (A) Lateral view of brain

(B) Frontal view of brain

FIGURE 2-9 Interconnected Cerebral Ventricles The lateral
ventricles are symmetrical, one in each hemisphere. The third and fourth
ventricles lie in the brain’s midline and drain into the cerebral aqueduct, which
runs the length of the spinal cord.
CLINICAL FOCUS 2-3

Stroke
Approximately every minute in the United States, someone has a
stroke with obvious visible symptoms—more than a half million
every year. Worldwide, stroke is the second leading cause of death.
Acute symptoms include facial droop, motor weakness in limbs,
visual disturbance, speech difficulties, and sudden onset of severe
headache.
In addition to visible strokes, at least twice as many silent strokes
may occur each year. These ministrokes occur primarily in the white
matter and do not produce obvious symptoms. (To view a brief video
on silent stroke, go to https://www.youtube.com/watch?
v=J3fb0CaDpEk ).
Even with the best, fastest medical attention, most stroke patients
have some residual motor, sensory, or cognitive deficit. According to
the Canadian Stroke Network, for every 10 people who have a
stroke, 2 die, 6 are disabled to varying degrees, and 2 recover to a
degree but still have a diminished quality of life. Of those who
survive, 1 in 10 risk further stroke.
The consequences of stroke are significant for those who have
them, their family, and their lifestyle. Consider Mr. Anderson, a 45-
year-old electrical engineer, who took his three children to the
movies one Saturday afternoon in 1998 and collapsed. He had a
massive stroke of the middle cerebral artery in his left hemisphere.
The stroke has impaired Mr. Anderson’s language ever since, and
because the brain’s connections are crossed, his right-side motor
control as well.
Seven years after his stroke, Mr. Anderson remained unable to
speak, but he understood simple conversations. Severe difficulties in
moving his right leg required him to use a walker. He could not
move the fingers of his right hand and so had difficulty feeding
himself, among other tasks. Mr. Anderson will probably never return
to his engineering career or drive or get around on his own.
 Like him, most stroke survivors require help to perform everyday
tasks. Caregivers are often female relatives who give up their own
career and other pursuits. Half of the caregivers develop emotional
illness, primarily depression or anxiety or both, in a year or so. Lost
income and stroke-related medical bills significantly affect the
family’s living standard.
We tend to speak of stroke as a single disorder, but two major
types of strokes have been identified. In the more common and often
less severe ischemic stroke, a blood vessel is blocked, as by a clot.
The more severe hemorrhagic stroke results from a burst vessel
bleeding into the brain.
The hopeful news is that ischemic stroke can be treated acutely
with a drug called tissue plasminogen activator (t-PA), which breaks
up clots and allows normal blood flow to return to an affected
region. Unfortunately, there is no treatment for hemorrhagic stroke,
for which the use of clot-preventing t-PA would be disastrous.

Simon Fraser/Science Source

 Dorsal view of a brain with a stroke, imaged by computed
tomography (CT). The dark area in the right hemisphere has
been damaged by the loss of blood flow.

When patients receive t-PA within 3 hours of an ischemic stroke,

the number who make a nearly complete recovery increases by about
25 percent compared with those who receive a placebo (Hatcher and
Starr, 2011). In addition, impairments are reduced in the remaining
patients who survive the stroke. The risk of hemorrhage is about 6
percent in t-PA–treated patients relative to no risk in placebo-treated
patients.
Many people are unable to reach a hospital soon enough for
treatment with t-PA. Most stroke victims do not visit an emergency
department until about 24 hours after symptoms appear, too late for
the treatment. Apparently, most people fail to realize that stroke is an
emergency.
By taking advantage of developments in neuroimaging, research
has shown that it is possible to remove clots from cerebral vessels
mechanically (Appireddy et al., 2015). Although quick treatment
with t-PA is still preferred, these new procedures have expanded the
window of benefit to as long as 8 hours post stroke. There is also
intense interest in developing treatments that will stimulate the brain
to initiate reparative processes during the postacute period. Such
treatment will facilitate the patient’s functional improvement (see a
review by Langhorne et al., 2011).

Cutting through the brain vertically from front to back produces a

sagittal section (Figure 2-10 A ). If we make our cut down the brain’s
midline, that is, in the midsagittal plane, we divide the cerebrum into its
two hemispheres, revealing several distinctive structures in the resulting
medial view (Figure 2-10B ). One feature is a long band of white matter
that runs much of the length of the cerebral hemispheres. This band, the
corpus callosum, contains about 200 million nerve fibers that join the
two hemispheres and allow them to communicate.
corpus callosum Band of white matter containing about 200 million
nerve fibers that connects the two cerebral hemispheres to provide a
route for direct communication between them.
(A)
(B)
 FIGURE 2-10 Sagittal Brain Section (A) A section in the
midsagittal plane separates the hemispheres, allowing (B) a medial view
of the brain’s midline structures, including the subcortical structures that lie
ventral to the corpus callosum.

Figure 2-10B clearly shows that the cortex covers the cerebral
hemispheres above the corpus callosum; below it are various internal
subcortical regions. The brainstem is a subcortical structure that
generally controls basic physiological functions. But many subcortical
regions are forebrain structures intimately related to the cortical areas
that process motor, sensory, perceptual, and cognitive functions. This
relation between the cortex and the subcortex alerts us to the concept that
redundant functions exist at many levels of nervous system organization.
Principle 4: The CNS functions on multiple levels.
If you were to compare medial views of the left and right
hemispheres, you would be struck by their symmetry. The brain, in fact,
has two of nearly every structure, one on each side. The few one-of-a-
kind structures, such as the third and fourth ventricles, lie along the
brain’s midline (see Figure 2-9B ). Another one-of-a-kind structure is the
pineal gland, which Descartes declared the seat of the mind in his
dualistic theory of how the brain works.
Principle 5: The brain is symmetrical and asymmetrical.
Microscopic Inspection: Cells and Fibers
The brain’s fundamental units—its cells—are so small that they can be
viewed only with the aid of a microscope. A microscope quickly reveals
that the brain has two main types of cells, illustrated in Figure 2-11 .
Neurons carry out the brain’s major functions, whereas glial cells aid and
modulate the neurons’ activities—for example, by insulating them. Both
neurons and glia come in many forms, each marked by the work that
they do.
Human brains contain about 86 billion neurons and 87 billion glia.
Section 3-1 examines their structures and functions in detail.
We can see the brain’s internal structures in even greater detail by
dyeing their cells with special stains (Figure 2-12 ). For example, if we
use a dye that selectively stains cell bodies, we can see that the neurons
in the cortical gray matter lie in layers, revealed by the bands of tissue in
Figure 2-12A and C. Each layer contains cells that stain
characteristically. Figure 2-12A and B shows that stained subcortical
regions are composed of clusters, or nuclei, of similar cells.
nuclei (sing. nucleus) A group of cells forming a cluster that can be
identified with special stains to form a functional grouping.

Kasthuri and Lichtman, Harvard University

Nancy Kedersha/Science Photo Library Science Source

FIGURE 2-11 Brain Cells Branches emanate from the cell bodies of a
prototypical neuron (left) and a glial cell (right). This branching
organization increases the cell’s surface area. This type of neuron is called
a pyramidal cell because the cell body is shaped somewhat like a pyramid;
the glial cell is called an astrocyte because of its star-shaped appearance.

Although layers and nuclei appear very different, both form

functional units in the brain. Whether a particular brain region has layers
or nuclei is largely an accident of evolution. By using a stain that
selectively dyes neuronal fibers, as shown in Figure 2-12B and D, we
can see the borders of the subcortical nuclei more clearly. In addition, we
can see that the stained cell bodies lie in regions adjacent to those with
most of the fibers.
 Photos courtesy of Bryan Kolb

FIGURE 2-12 Cortical Layers and Glia Brain sections from the
left hemisphere of a monkey (midline is to the left in each image), viewed
through a microscope. Cells are stained with (A and c) a selective cell
body stain for neurons (gray matter) and (B and D) a selective fiber stain
for insulating glial cells, or myelin (white matter). The images reveal very
different views of the brain at the macro (A and B) and microscopic (C and
D) levels.

A key feature of neurons is that they are connected to one another by

fibers known as axons. When axons run along together, much like the
wires that run from a car engine to the dashboard, they form a nerve or
tract ( Figure 2-13 ). By convention, a tract is a collection of nerve
fibers in the brain and spinal cord, whereas bundles of fibers outside of
the CNS are typically called nerves. Thus, the pathway from the eye to
the brain is the optic nerve, whereas the pathway from the cerebral
cortex to the spinal cord is the corticospinal tract.
nerve Large collection of axons coursing together outside the CNS.
tract Large collection of axons coursing together in the CNS.
FIGURE 2-13 Neuronal Connections
 2-1 REVIEW
Overview of Brain Function and Structure
Before you continue, check your understanding.
1 . The nervous system’s function is to produce movement, or
___________, in a perceptual world constructed by the ___________.
2 . The left and right cerebral hemispheres are each divided into four
lobes: ___________, ___________, ___________, and ___________.
3 . The human nervous system has evolved the potential to change, for
example, to adapt to changes in the world or to compensate for injury.
This attribute is called ___________.
4 . Neural tissue is of two main types: (1) ___________ forms the
connections among cells, and (2) ___________ collects and processes
incoming (afferent) sensory or outgoing (efferent) information.
5 . The nerve fibers that lie in the brain form ___________. Outside the
brain they are called ___________.
6 . Chart the human nervous system’s functional organization.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 The Nervous System’s Evolutionary
2-2

Development
The developing brain, which is less complex than the mature adult brain,
provides a clear picture of its basic structural plan. The striking
biological similarity of embryos as diverse as amphibians and mammals
is evident in the earliest stages of development. In the evolution of
complex nervous systems in vertebrate species, simpler and
evolutionarily more primitive forms have not been discarded and
replaced but rather added to. As a result, all anatomical and functional
features of simpler nervous systems are present in and form the base for
the most complex nervous systems, including ours.
The bilaterally symmetrical nervous system of simple worms, for
example, is common to complex nervous systems. Indeed, we can
recognize in humans the spinal cord that constitutes most of the simplest
fishes’ nervous system. The same is true of the brainstem of more
complex fishes, amphibians, and reptiles. The neocortex, although
particularly complex in humans, is clearly the same organ found in other
mammals.
Section 1-3 outlines nervous system evolution and Section 8-1 ,
developmental similarities among humans and other species.

Stages in Brain Evolution

In a vertebrate embryo, the nervous system begins as a sheet of cells.
This sheet folds into a hollow tube and develops into three regions,
forebrain, midbrain, and hindbrain, recognizable as a series of three
enlargements at the end of the embryonic spinal cord (Figure 2-14 A ).
The adult brain of a fish, amphibian, or reptile is roughly equivalent to
this three-part brain. The prosencephalon (front brain) is responsible for
olfaction, the sense of smell; the mesencephalon (middle brain) is the
seat of vision and hearing; and the rhombencephalon (hindbrain)
controls movement and balance. The spinal cord is part of the hindbrain.
In mammals (Figure 2-14B ), the prosencephalon develops further to
form the subcortical structures known collectively as the diencephalon
(between brain) and the cerebral hemispheres and cortex, or
telencephalon (endbrain). The mammalian hindbrain develops further
into the metencephalon (across brain), which includes the cerebellum,
and the myelencephalon (spinal brain), including the spinal cord.
The human brain is particularly complex, possessing especially large
cerebral hemispheres but retaining most other mammalian brain features
(Figure 2-14C ). Various human cerebral areas—regions in the frontal,
temporal, and parietal lobes—are larger than those of other primates’
brains—necessary to produce language. Language is thought to have
fostered a novel worldview—in the way we think, reflect on our own
thoughts, and imagine.

The Nervous System and Intelligent

Behavior
Most behaviors are the product not of a single locus in the brain but
rather of many interacting brain areas and levels. These several nervous
system layers do not simply replicate function; rather, each region adds a
different dimension to the behavior. This hierarchical organization
affects virtually every human behavior. Abnormalities associated with
brain injury and brain disease that seem bizarre in isolation are but the
normal manifestation of parts of a hierarchically organized brain. Our
evolutionary history, our developmental history, and our own personal
history are integrated at the various anatomical and functional levels of
the nervous system.

Stages in Brain Evolution and

FIGURE 2-14

Development Over the evolution of the mammalian brain, the

forebrain has grown dramatically.

Principle 6: Brain systems are organized hierarchically and in

parallel.
 Is the vertebrate nervous system the only path to evolving intelligent
behavior? Invertebrate animals, such as the octopus, have traveled on an
evolutionary pathway separate from that of vertebrates for over 700
million years. The octopus nervous system, while strikingly different
from ours, is complex. Might the octopus learn much as vertebrate
animals do?
Italian biologists Graziano Fiorito and Pietro Scotto (1992) placed
individuals of Octopus vulgaris (the common octopus) in separate tanks,
each with an independent water supply, and allowed them to interact
visually for 2 hours. As shown in the Procedure section of Experiment
2-1 , the observer octopus watched the demonstrator octopus from an
adjacent tank through a transparent wall. The demonstrator was being
conditioned to learn that a red ball was associated with a reward,
whereas a white ball was associated with a weak electric shock.
As noted in the Results section, the demonstrator animals quickly
learned to distinguish between the colored balls. The observers then were
placed in isolation. When tested later, they selected the same object the
demonstrators had, responded faster than the demonstrators did during
their conditioning, and performed the task correctly for 5 days without
significant error or further conditioning.
 EXPERIMENT 2-1

Question: Does intelligent behavior require a vertebrate

nervous system organization?
Procedure

Results
1. The demonstrator animal quickly learns to distinguish between the
colored balls.
2. When placed in isolation and tested later, the observer animals
selected the same object as the demonstrators, responded faster, and
performed the task correctly for 5 days without significant error.
Conclusion: Invertebrates display intelligent behavior, such as learning
by observation.
Research from G. Fiorito and P. Scotto (1992). Observational learning in Octopus vulgaris.
Science, 256, 545–547.
 2-2 REVIEW
The Nervous System’s Evolutionary Development
Before you continue, check your understanding.
1 . The brains of vertebrate animals have evolved into three regions:
___________, ___________, and ___________.
2 . The functional levels of the nervous system interact, each region
contributing different aspects, or dimensions, to produce
___________.
3 . In a brief paragraph, explain how the evolution of the forebrain in
mammals reinforces the principle that the CNS functions on multiple
levels.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 The Central Nervous System:
2-3

Mediating Behavior
When we look under the hood, we can make some pretty good guesses
about what each part of a car engine does. The battery must provide
electrical power to run the radio and lights, for example, and because
batteries have to be charged, the engine must contain some mechanism
for charging them. We can take the same approach to deduce how the
parts of the brain function. The part connected to the optic nerve coming
from each eye must have something to do with vision. Structures
connected to the auditory nerve coming from each ear must have
something to do with hearing.
From such simple observations, we can begin to understand how the
brain is organized. The real test comes in analyzing actual brain function:
how this seeming jumble of parts produces behaviors as complex as
human thought. The place to start is the brain’s functional anatomy:
learning the name of a particular CNS structure is pointless without also
learning something about what it does. We focus now on the names and
functions of the three major CNS components: spinal cord, brainstem,
and forebrain.

Spinal Cord
Although producing movement is the brain’s principal function,
ultimately the spinal cord executes most body movements, usually
following instructions from the brain but at times acting independently
via the somatic nervous system. To understand how important the spinal
cord is, think of the old saying “running around like a chicken with its
head cut off.” When a chicken’s head is lopped off for the farmer’s
family dinner, the chicken is still capable of running around the barnyard
until it collapses from loss of blood. The chicken accomplishes this feat
because the spinal cord is acting independently of the brain.
Grasping the spinal cord’s complexity is easier once you realize that it
is not a single structure but rather a set of segmented switching stations.
As detailed in Section 2-4 , each spinal segment receives information
from a discrete part of the body and sends out commands to that area.
Spinal nerves, which are part of the SNS, carry sensory information to
the cord from the skin, muscles, and related structures and in turn send
motor instructions to control each muscle.

You can demonstrate movement controlled by the spinal cord in your

own body by tapping your patellar tendon, just below your kneecap (the
patella). The sensory input causes your lower leg to kick out, and try as
you might, it is very hard to prevent the movement. Your brain, in other
words, has trouble inhibiting this spinal reflex: it is automatic.
We explain reflexes in Section 11-4 .

Brainstem
The brainstem begins where the spinal cord enters the skull and extends
upward into the lower areas of the forebrain. The brainstem receives
afferent nerves coming in from all of the body’s senses, and it sends
efferent nerves out to the spinal cord to control virtually all of the body’s
movements except the most complex movements of the fingers and toes.
The brainstem, then, both directs movements and creates a sensory
world.
 brainstem Central structure of the brain, including the hindbrain,
midbrain, thalamus, and hypothalamus, that is responsible for most
unconscious behavior.
Alphabetically, afferent comes before efferent : sensory signals must
enter the brain before an outgoing signal triggers a motor response.
In some vertebrates, such as frogs, the entire brain is largely
equivalent to the mammalian or avian brainstem. And frogs get along
quite well, demonstrating that the brainstem is a fairly sophisticated
piece of machinery. If we had only a brainstem, we would still be able to
construct a world, but it would be a far simpler sensorimotor world, more
like the world a frog experiences.
The brainstem, which is responsible for most unconscious behavior,
can be divided into three regions: hindbrain, midbrain, and diencephalon,
meaning between brain because it borders the brain’s upper and lower
parts. In fact, the between-brain status of the diencephalon can be seen in
a neuroanatomical inconsistency: some anatomists place it in the
brainstem and others place it in the forebrain. Figure 2-15 A illustrates
the location of these three brainstem regions under the cerebral
hemispheres. Figure 2-15B compares the shape of the brainstem regions
to the lower part of your arm when held upright. The hindbrain is long
and thick like your forearm, the midbrain is short and compact like your
wrist, and the diencephalon at the end is bulbous like a fist.
The hindbrain and midbrain are essentially extensions of the spinal
cord; they developed first as vertebrate animals evolved a brain at the
anterior end of the body. It makes sense, therefore, that these lower
brainstem regions should retain a division between structures having
sensory functions and those having motor functions, with sensory
structures lying dorsal and motor ones ventral, or in upright humans,
posterior and anterior.
Principle 7: Sensory and motor divisions permeate the nervous
system.
Each brainstem region performs more than a single task. Each
contains various groupings of nuclei that serve various purposes. All
three regions, in fact, have both sensory and motor functions. However,
the hindbrain is especially important in motor functions, the midbrain in
sensory functions, and the diencephalon in integrative sensorimotor
tasks. Here we consider the central functions of these three regions; later
chapters contain more detailed information about them.

(A)

(B)
 FIGURE 2-15 Brainstem Structures (A) Medial view shows the
relation of the brainstem to the cerebral hemispheres. (B) The shapes and
relative sizes of the brainstem’s three parts are analogous to your fist,
wrist, and forearm.

(A)
(B)
 FIGURE 2-16 The Cerebellum and Movement (A) Their
relatively large cerebellum enables finely coordinated movements such as
flying and landing in birds and pouncing on prey in cats. Slow-moving
animals such as the sloth have a smaller cerebellum relative to brain size.
(B) Like the cerebrum, the human cerebellum has left and right
hemispheres, an extensively folded cortex with gray and white matter, and
subcortical nuclei.

Hindbrain
The hindbrain controls motor functions ranging from breathing to
balance to fine movements, such as those used in dancing. Its most
distinctive structure, and one of the largest in the human brain, is the
cerebellum. Its relative size increases with the physical speed and
dexterity of a species, as shown in Figure 2-16 A .
hindbrain Evolutionarily the oldest part of the brain; contains the
pons, medulla, reticular formation, and cerebellum, structures that
coordinate and control most voluntary and involuntary movements.
Animals that move relatively slowly (such as a sloth) have a relatively
small cerebellum for their body size. Animals that can perform rapid
acrobatic movements (such as a hawk or a cat) have a very large
cerebellum relative to overall brain size. The human cerebellum, which
resembles a cauliflower in the medial view in Figure 2-16B , likewise is
important in controlling complex movements. But cerebellar size in
humans is also related to cognitive capacity. Relative to other mammals,
apes show an expansion of the cerebellum that correlates with increased
capacity for planning and executing complex behavioral sequences,
including tool use and language (see Barton, 2012).
As we look beyond the cerebellum at the rest of the hindbrain, shown
in Figure 2-17 , we find three subparts: the reticular formation, the pons,
and the medulla. Extending the length of the entire brainstem at its core,
the reticular formation is a netlike mixture of neurons (gray matter) and
nerve fibers (white matter). This nerve net gives the structure the mottled
appearance from which its name derives (from Latin rete, meaning net ).
The reticular formation’s nuclei are localized into small patches along its
length. Each has a special function in stimulating the forebrain, such as
in waking from sleep.
reticular formation Midbrain area in which nuclei and fiber
pathways are mixed, producing a netlike appearance; associated
with sleep–wake behavior and behavioral arousal.
 FIGURE 2-17 Hindbrain The principal hindbrain structures integrate
voluntary and involuntary body movements. The reticular formation is
sometimes called the reticular activating system.

The pons and medulla contain substructures that control many vital
body movements. Nuclei in the pons receive inputs from the cerebellum
and actually form a bridge from it to the rest of the brain (in Latin, pons
means bridge ). At the rostral tip of the spinal cord, the medulla’s nuclei
regulate such vital functions as breathing and the cardiovascular system.
For this reason, a blow to the back of the head can kill you: your
breathing stops if the hindbrain control centers are injured.
Midbrain
In the midbrain, a sensory component, the tectum (roof), is dorsal
(posterior in upright humans), whereas a motor structure, the
tegmentum (floor), is ventral (anterior in humans; Figure 2-18 A ). The
tectum receives a massive amount of sensory information from the eyes
and ears. The optic nerve sends a large bundle of fibers to the superior
colliculus, whereas the inferior colliculus receives much of its input from
auditory pathways. The colliculi function not only to process sensory
information but also to produce orienting movements related to sensory
inputs, such as turning your head to see a sound’s source.
midbrain Central part of the brain; contains neural circuits for
hearing and seeing as well as orienting movements.
tectum Roof (area above the ventricle) of the midbrain; its functions
are sensory processing, particularly visual and auditory, and the
production of orienting movements.
 tegmentum Floor (area below the ventricle) of the midbrain; a
collection of nuclei with movement-related, species-specific, and
pain perception functions.
orienting movement Movement related to sensory inputs, such as
turning the head to see the source of a sound.

FIGURE 2-18 Midbrain (A) Structures in the midbrain are critical for
producing orienting movements, species-specific behaviors, and pain
perception. (B) The tegmentum in cross section, revealing various nuclei.
Colliculus comes from collis, Latin for hill. The colliculi resemble four little
hills on the midbrain’s posterior surface.

This orienting behavior is not as simple as it may seem. To produce it,

the auditory and visual systems must share a map of the external world
so that the ears can tell the eyes where to look. If the auditory and visual
maps differed, it would be impossible to use the two together. In fact, the
colliculi also have a tactile map. After all, if you want to look at what’s
making your leg itch, your visual and tactile systems need a common
representation of where that place is so you can scratch the itch by
moving your arm and hand.
Lying ventral to the tectum, the tegmentum (shown in Figure 2-18B in
cross section) is composed of many nuclei, largely with movement-
related functions. Several tegmental nuclei control eye movements. The
red nucleus controls limb movements, and the substantia nigra connects
to the forebrain, a connection especially important in initiating
movements. (Recall from Clinical Focus 2-2 that the symptoms of
Parkinson disease are related to the destruction of the substantia nigra.)
The periaqueductal gray matter (PAG), made up of cell bodies that
surround the aqueduct joining the third and fourth ventricles, contains
circuits controlling species-typical behaviors (e.g., female sexual
behavior). These nuclei also play an important role in the modulation of
pain by opioid drugs.
Principle 8: The brain divides sensory input for object recognition
and motor control.
Diencephalon
The diencephalon, shown in sagittal section in the center of Figure 2-19
, integrates sensory and motor information on its way to the cerebral
cortex. Its two principal structures are the hypothalamus and the
thalamus. The thalamus—one in each hemisphere—lies just to the left of
the brainstem’s tip, and the hypothalamus lies below the thalamus in
each hemisphere.
diencephalon The between brain, which integrates sensory and
motor information on its way to the cerebral cortex.

FIGURE 2-19 Diencephalon The diencephalon (center) is composed

of the thalamus, shown at right, and the hypothalamus and other
structures, shown at left. Thalamic regions connect to discrete cortical
regions. Below the thalamus, at the base of the brain, the hypothalamus
(hypo-, below) and pituitary lie above the roof of the mouth. The
hypothalamus is composed of many nuclei, each with distinctly different
functions.
 The hypothalamus in each hemisphere lies along the brain’s midline;
it is composed of about 22 small nuclei and the nerve fiber systems that
pass through it. Its critical function is to control the body’s production of
hormones, accomplished via its interactions with the pituitary gland,
shown at left in Figure 2-19 . Although constituting only about 0.3
percent of the brain’s weight, the hypothalamus takes part in nearly all
aspects of behavior, including feeding, sleeping, temperature regulation,
sexual and emotional behavior, hormone function, and movement. The
hypothalamus is organized and functions more or less similarly across
mammals. But sex differences have been found in the structures of some
of its parts, owing probably to differences between males and females in
activities such as sexual behavior and parenting.
hypothalamus Diencephalon structure that contains many nuclei
associated with temperature regulation, eating, drinking, and sexual
behavior.
The other principal structure of the diencephalon, the thalamus, is
much larger than the hypothalamus, as are its 20-odd nuclei. Perhaps the
most distinctive thalamic function, shown at the right in Figure 2-19 , is
its role as a gateway for channeling sensory information traveling to the
cerebral cortex from all sensory systems. The thalamus integrates
information from sensory inputs and relays it to the appropriate cortical
area. The optic tract, for example, sends information through a large
fiber bundle to a thalamic region called the lateral geniculate nucleus
(LGN), shown at the right tip of the thalamus in Figure 2-19 . In turn, the
LGN processes some of this information, then sends it to the visual
region of the cortex in each hemisphere.
thalamus Diencephalon structure through which information from
all sensory systems is integrated and projected into the appropriate
region of the neocortex.
The routes to the thalamus may be indirect. For example, the route for
olfaction traverses several synapses before entering the dorsomedial
thalamic nucleus on its way to the forebrain. Analogous sensory regions
of the thalamus receive auditory and tactile information, which is
subsequently relayed to the respective auditory and tactile cortical
regions in each hemisphere. Some thalamic regions have motor functions
or, like its dorsomedial nucleus, which connects to most of the frontal
lobe, perform integrative tasks.
 We examine how thalamic sensory nuclei process incoming
information in Sections 9-2 , 10-2 , 11-4 , 12-2 , and in Section 14-3
, memory pathways.

Forebrain
The largest and most recently evolved region of the mammalian brain is
the forebrain. Its major internal and external structures are shown in
Figure 2-20 . Each of its three principal structures has multiple
functions. To summarize briefly, the cerebral cortex regulates a host of
mental activities ranging from perception to planning; the basal ganglia
control voluntary movement; and the limbic system regulates emotions
and behaviors that produce and require memory.
forebrain Evolutionarily the newest part of the brain; coordinates
advanced cognitive functions such as thinking, planning, and
language; contains the limbic system, basal ganglia, and neocortex.

FIGURE 2-20 Forebrain Structures The major internal and external

forebrain structures integrate sensation, motivation and emotion, and
 memory to enable such advanced cognitive functions as thinking,
planning, and using language.

Extending our analogy between the brainstem and your forearm,

imagine that the fist—the diencephalon—is thrust inside a watermelon—
the forebrain, with the cortex as the rind and the subcortical limbic
system and basal ganglia as the fruit inside. Just as watermelons come in
sizes, so do brains, which in a sense is what evolution has done: the
forebrain varies considerably in size across species.

Cerebral Cortex
The forebrain contains two types of cortex, three- or four-layered and
six-layered. The six-layered neocortex (new bark ) is the tissue visible
when we view the brain from the outside, as in Figure 2-5 . The more
recently evolved neocortex is unique to mammals; its primary function is
to construct a perceptual world and respond to that world. The older,
more primitive three- or four-layered cortex, sometimes called
allocortex, lies adjacent to the neocortex. Allocortex is found in the
brains of other chordates in addition to mammals, especially in birds and
reptiles.
neocortex (cerebral cortex) Most recently evolved outer layer (new
bark ) of the forebrain, composed of about six layers of gray matter;
constructs our reality.
The allocortex plays a role in controlling motivational and emotional
states as well as in certain forms of memory. Although neocortex and
allocortex have anatomical and functional differences, those distinctions
are not critical for most discussions in this book. Therefore, we usually
refer to both types of tissue simply as cortex.
Measured by volume, the cortex makes up most of the forebrain,
constituting 80 percent of the human brain overall. It is the brain region
that has expanded the most in the course of mammalian evolution. The
human neocortex has a surface area as large as 2500 square centimeters
but a thickness of only 1.5 to 3.0 millimeters, an area equivalent to about
four pages of this book. By contrast, a chimpanzee has a cortical area
equivalent to about one page.
The pattern of sulci and gyri formed by the folding of the cortex
varies across species. Some, such as rats, have no sulci or gyri, whereas
in carnivores, such as cats, the gyri form a longitudinal pattern. In
primates, the sulci and gyri form a more diffuse pattern.
Monkey

Chimpanzee

Human

Reproduced or adapted from our websites at http://www.brains.rad.msu . edu and

http://brainmuseum.org , supported by the U. S. National Science Foundation.
The brains of a monkey, chimpanzee, and human, shown here to scale,
differ dramatically in size and in surface appearance. With an
encephalization quotient of 2.0, the monkey’s brain is just over one-quarter
the size of a human’s (EQ 7.0). The chimp’s brain, EQ 2.5, is a bit more
than one-third as large (see Figure 1-15 ).

Cortical Lobes
To review, the human cortex consists of the nearly symmetrical left and
right hemispheres, which are separated by the longitudinal fissure,
shown at left in Figure 2-21 . As shown at right, each hemisphere is
subdivided into four lobes corresponding to the skull bones overlying
them: frontal, temporal, parietal, and occipital. Unfortunately, bone
location and brain function are unrelated. As a result, the cortical lobes
are rather arbitrarily defined anatomical regions that include many
functional zones.
Nevertheless, we can attach some gross functions to each lobe. The
three posterior lobes have sensory functions: the occipital lobe is visual;
the parietal lobe is tactile; and the temporal lobe is visual, auditory, and
gustatory. In contrast, the frontal lobe is motor and is sometimes called
the brain’s executive because it integrates sensory and motor functions
and formulates plans of action. We can also predict some effects of
injuries to each lobe:
Principle 9: Brain functions are localized and distributed.
• People with an injured occipital lobe have deficits in processing visual
information. Although they may perceive light versus dark, they may
be unable to identify either the shape or the color of objects.
• Injuries to the parietal lobe make it difficult to identify or locate
stimulation on the skin. Deficits in moving the arms and hands to
points in space may occur.
• Temporal lobe injuries result in difficulty recognizing sounds, although
unlike people with occipital injuries, those with temporal injury can
still recognize that they are hearing something. Temporal lobe injuries
can also produce difficulties in processing complex visual information,
such as faces.
• Individuals with frontal lobe injuries may have difficulties organizing
and evaluating their ongoing behavior as well as planning for the
future.
Fissures and sulci often establish the boundaries of cortical lobes
(Figure 2-21 , right). For instance, in humans, the central sulcus and
lateral fissure form the boundaries of each frontal lobe as well as the
boundaries of each parietal lobe lying posterior to the central sulcus. The
lateral fissure demarcates each temporal lobe, forming its dorsal
boundary. The occipital lobes are not so clearly separated from the
parietal and temporal lobes because no large fissure marks their
boundaries.
Anatomical features presented in Section 9-2 define occipital lobe
boundaries.
Dorsal view of brain

Lateral view of brain

FIGURE 2-21 Cortical Boundaries

Cortical Layers
In the neocortex, six layers of gray matter sit atop a layer of white matter.
The allocortex, by contrast, has three or four layers of gray matter. The
six layers of the neocortex have distinct characteristics:
• Different layers have different types of cells.
• The cell density varies from layer to layer, ranging from virtually no
cells in layer I (the top layer) to very dense cell packing in layer IV of
the neocortex ( Figure 2-22 ).
• Other differences in appearance are both regional and functional.
These visible differences led neuroanatomists to map the cortex a
century ago. Korbinian Brodmann developed the map in Figure 2-23
around 1905. Because these maps are based on cell characteristics, the
subject of cytology, they are called cytoarchitectonic maps. For
example, viewed through a microscope, sensory cortex in the parietal
lobe, shown in red in Figure 2-22 , has a distinct layer IV. Motor cortex
in the frontal lobe, shown in blue in Figure 2-22 , has a distinctive layer
V. Layer IV is afferent; layer V is efferent. It makes sense that a sensory
region has a large input layer, whereas a motor region has a large output
layer.
cytoarchitectonic map Map of the neocortex based on the
organization, structure, and distribution of the cells.
Staining cortical tissue can reveal chemical differences between cells
and layers. Some regions are rich in one chemical, others rich in another.
These differences presumably relate to functional specialization of
cortical areas.
The one significant difference between the organization of the cortex
and the organization of other brain parts is its range of connections.
Unlike most structures, which connect only to certain brain regions, the
cortex is connected to virtually all other parts of the brain. The cortex, in
other words, is the ultimate meddler. It takes part in everything. This fact
not only makes it difficult to identify specific cortical functions but also
complicates our study of the rest of the brain, because we must always
consider the cortex’s role in other brain regions.
Consider your perception of clouds. You have no doubt gazed up at
clouds on a summer day and imagined sailing ships, elephants, faces, and
countless other objects. Although a cloud does not really look like an
elephant, you can concoct an image of one if you impose your frontal
cortex—that is, your imagination—on the sensory inputs. This kind of
cortical activity is top-down processing because the top level of the
nervous system, the cortex, is influencing how information is processed
in lower regions of the hierarchy—in this case, the midbrain and
hindbrain.
 The cortex influences many behaviors besides object perception. It
influences our cravings for foods, our lust for things (or people), and
how we interpret the meaning of abstract concepts, words, and images.
The cortex ultimately creates our reality, and one reason it serves this
function is that it is so well-connected.

FIGURE 2-22Neocortical Layering Layer IV is relatively thick in the

sensory cortex and relatively thin in the motor cortex. Afferents from the
thalamus connect to layer IV and to layers II and III. Efferents in layers V
and VI connect to other cortical areas and motor structures. Motor layers V
and VI are thicker and denser than sensory layers V and VI.
 FIGURE 2-23 Early Brain Map In his cytoarchitectonic map of the
cortex, Brodmann (1909) defined areas by the organization and
characteristics of the cells he examined. The regions shown in color are
associated with the simplest sensory perceptions of touch (red), vision
(purple), and hearing (orange). As we shall see, the cortical areas that
process sensory information are far more extensive than Brodmann’s
basic areas.

FIGURE 2-24Basal Ganglia A coronal section through the cerebral

hemispheres reveals a frontal view of the basal ganglia relative to
surrounding forebrain structures. Two associated structures likewise
instrumental in controlling and coordinating movement, the substantia
nigra and subthalamic nucleus, also are shown.

Basal Ganglia
A collection of nuclei that lie in the forebrain just below the white matter
of the cortex, the basal ganglia consist of three principal structures: the
caudate nucleus, the putamen, and the globus pallidus, all shown in
Figure 2-24 . Together with the thalamus and two closely associated
nuclei, the substantia nigra and subthalamic nucleus, the basal ganglia
form a system that functions primarily to control voluntary movement.
basal ganglia Subcortical forebrain nuclei that coordinate voluntary
movements of the limbs and body; connected to the thalamus and to
the midbrain.
We can observe the functions of the basal ganglia by analyzing the
behavior resulting from the many diseases that interfere with their
healthy functioning. Parkinson disease, a motor system disorder
characterized by severe tremors, muscular rigidity, and a reduction in
voluntary movement, is among the most common movement disorders
among the elderly. People with Parkinsonism take short, shuffling steps;
display bent posture; and may need a walker to get around. Many have
almost continuous hand tremors and sometimes head tremors as well.
Another disorder of the basal ganglia is Tourette syndrome,
characterized by various motor tics; involuntary vocalizations (including
curse words and animal sounds); and odd, involuntary body movements,
especially of the face and head.
Parkinson disease Disorder of the motor system correlated with a
loss of dopamine from the substantia nigra and characterized by
tremors, muscular rigidity, and a reduction in voluntary movement.
Tourette syndrome Disorder of the basal ganglia characterized by
tics, involuntary vocalizations (including curse words and animal
sounds), and odd, involuntary movements of the body, especially of
the face and head.
Details on Parkinson disease appear in Focus boxes 5-2, 5-3, and 5-
4, Sections 11-3 and 16-3 . Focus 11-4 details Tourette syndrome.
Neither Parkinsonism nor Tourette syndrome is a disorder of
producing movements, as in paralysis. Rather, they are disorders of
controlling movements. The basal ganglia, therefore, must play a critical
role in controlling and coordinating movement patterns rather than in
activating the muscles to move.

Limbic System
In the 1930s, psychiatry was dominated by the theories of Sigmund
Freud, who emphasized the roles of sexuality and emotion in human
behavior. At the time, the brain regions controlling these behaviors had
not been identified, and coincidentally, a group of brain structures
collectively called the limbic lobe had no known function. It was a
simple step to thinking that perhaps the limbic structures played a central
role in sexuality and emotion.
One sign that this hypothesis might be correct came from James
Papez (1937), who discovered that people with rabies have infection in
the limbic structures, and one symptom of rabies is heightened
emotionality. We now know that such a simple view is inaccurate. In
fact, the limbic system is not a unitary system at all. And although some
limbic structures have roles in emotional and sexual behaviors, limbic
structures serve other functions too, including contributing to memory
and motivation.
limbic system Disparate forebrain structures lying between the
neocortex and the brainstem that form a functional system
controlling affective and motivated behaviors and certain forms of
memory; includes cingulate cortex, amygdala, and hippocampus,
among other structures.
Figure 2-25 diagrams the principal limbic structures Papez proposed.
The hippocampus, cingulate cortex (a type of allocortex), and associated
structures participate in certain memory functions as well as in
controlling navigation in space. Many limbic structures, in particular the
amygdala, are also believed to contribute to the rewarding properties of
psychoactive drugs and other potentially addictive substances and
behaviors. Repeated exposure to drugs such as amphetamine or nicotine
produces both chemical and structural changes in the cingulate cortex
and hippocampus, among other structures.
FIGURE 2-25 Limbic System This medial view of the right hemisphere
illustrates the principal structures proposed by Papez to constitute the
limbic system. This structure participates in emotional and sexual
behaviors, motivation, and memory. For a contemporary view of limbic
anatomy, see Figure 12-18 .

Photo via Newscom

 All sorts of behaviors can prove addictive—eating, shopping, sex, video
gaming, gambling, even Twitter! How else to explain these Canadian
coeds tweeting all bundled up when they could be defrosting on the beach
in the Florida sun? More on the limbic system and addiction in Section 6-3
; motivation and emotion, Sections 12-3 and 12-4 ; memory, Section 14-3 ;
and brain disorders, Focus 16-1 and Section 16-4 .

Removal of the amygdala produces truly startling changes in

emotional behavior. A cat with the amygdala removed will wander
through a colony of monkeys, completely undisturbed by their hooting
and threats. No self-respecting cat would normally be caught anywhere
near such bedlam.

Olfactory System
At the very front of the brain lie the olfactory bulbs, the organs
responsible for our sense of smell. The olfactory system is unique among
human senses, as Figure 2-26 shows, because it is almost entirely a
forebrain structure. The other sensory systems project most of their
inputs from the sensory receptors to the midbrain and thalamus.
Olfactory input takes a less direct route: the olfactory bulb sends most of
its inputs to a specialized region, the pyriform cortex, on the brain’s
ventral surface. From there, sensory input progresses to the amygdala
and the dorsomedial thalamus (see Figure 2-19 , right), which routes it to
the frontal cortex.

FIGURE 2-26 Sense of Smell Our small olfactory bulb lies at the base
of the forebrain, connects to receptor cells that lie in the nasal cavity, and
 sends most of this input to the pyriform cortex en route to the amygdala
and thalamus.

Smell is one of the first senses to have evolved in animals, yet

curiously, the olfactory system lies at the front of the human brain and is
considered part of the forebrain (see the ventral view in Figure 2-6 ).
This is partly an accident of evolution. The olfactory bulbs lie near the
olfactory receptors in the nasal cavity. Although they send their inputs to
the pyriform cortex in mammals, their input to the brainstem is more
direct in simpler brains.
Compared with the olfactory bulbs of animals such as rats, cats, and
dogs, which depend more heavily on smell than we do, the human
olfactory bulb is relatively small. Nonetheless, it is very sensitive,
allowing us to distinguish a surprisingly large number of odors. Smell
plays important roles in various aspects of our feeding and sexual
behavior.
Section 12-2 considers the chemical senses smell and taste in the
context of emotional and motivated behavior.
 2-3 REVIEW
The Central Nervous System: Mediating Behavior
Before you continue, check your understanding.
1 . The three functionally distinct sections of the CNS—spinal cord,
brainstem, and forebrain—represent the evolution of multiple
___________.
2 . The ___________ can perceive sensations from the skin and muscles
and produce movements independent of the brain.
3 . The brainstem includes three functional regions. The ___________ is
an extension of the spinal cord; the ___________ is the first brain
region to receive sensory inputs; and the ___________ integrates
sensory and motor information on its way to the cerebral cortex.
4 . The ___________ coordinates fine motor movements and various
cognitive functions.
5 . The forebrain’s subcortical regions include the ___________, which
control voluntary movement, and the ___________, which controls
mood, motivation, and some forms of memory.
6 . The two types of cerebral cortex are the older ___________ and the
___________, which features layers that vary in density to perform
___________, ___________, and ___________ functions.
7 . Briefly describe the functions performed by the forebrain.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Somatic Nervous System:
2-4

Transmitting Information
The SNS is monitored and controlled by the CNS—the cranial nerves by
the brain and the spinal nerves by the spinal cord segments.

Cranial Nerves
The linkages provided by the cranial nerves between the brain and
various parts of the head and neck as well as various internal organs are
illustrated and tabulated in Figure 2-27 . Cranial nerves can have afferent
functions, such as sensory inputs to the brain from the eyes, ears, mouth,
and nose, or they can have efferent functions, such as motor control of the
facial muscles, tongue, and eyes. Some cranial nerves have both sensory
and motor functions, such as modulation of both sensation and movement
in the face.
cranial nerve One of a set of 12 nerve pairs that control sensory and
motor functions of the head, neck, and internal organs.
The 12 pairs of cranial nerves are known both by their numbers and by
their names, as listed in Figure 2-27 . One set of 12 controls the left side
of the head, whereas the other set controls the right side. This
arrangement makes sense for innervating duplicated parts of the head
(such as the eyes), but why separate nerves should control the right and
left sides of a singular structure (such as the tongue) is not so clear. Yet
that is how the cranial nerves work. If you have ever received lidocaine
(often called Novocaine) for dental work, you know that usually just one
side of your tongue becomes numb because the dentist injects the drug
into only one side of your mouth. The rest of the skin and muscles on
each side of the head are similarly controlled by cranial nerves located on
the same side.
We consider many cranial nerves in detail in later chapters’
discussions on topics such as vision, hearing, olfaction, taste, and stress
responses. For now, you simply need to know that cranial nerves form
part of the SNS, providing inputs to the brain from the head’s sensory
organs and muscles and controlling head and facial movements. Some
cranial nerves also contribute to maintaining autonomic functions by
connecting the brain and internal organs (the vagus, cranial nerve 10) and
by influencing other autonomic responses, such as salivation.
Spinal Nerves
The spinal cord lies inside the bony spinal column, which is made up of a
series of small bones called vertebrae (sing. vertebra ), categorized into
five anatomical regions from top to bottom: cervical, thoracic, lumbar,
sacral, and coccygeal, as diagrammed in Figure 2-28 A . You can think of
each vertebra in these five groups as a short segment of the spinal
column. The corresponding spinal cord segment in each vertebral region
functions as that segment’s minibrain.
vertebrae (sing. vertebra) The bones that form the spinal column.

FIGURE 2-27 Cranial Nerves Each of the 12 pairs of cranial nerves

has a different function. A common mnemonic device for learning the order
of the cranial nerves is “On old Olympus’s towering top, a Finn and German
view some hops.” The first letter of each word is, in order, the first letter of
the name of each nerve.

Cranial Name Function

nerve
 1 Olfactory Smell

2 Optic Vision

3 Oculomotor Eye movement

4 Trochlear Eye movement

5 Trigeminal Masticatory movements and facial sensation

6 Abducens Eye movement

7 Facial Facial movement and sensation

8 Auditory Hearing and balance

vestibular

9 Glossopharyngea Tongue and pharynx movement and sensation

l

10 Vagus Heart, blood vessels, viscera, movement of larynx and

pharynx

11 Spinal accessory Neck movement

12 Hypoglossal Tongue movement

This arrangement may seem a bit odd, but it has a long evolutionary
history. Think of a simpler animal, such as a snake, that evolved long
before humans did. A snake’s body is a segmented tube. In that tube is
another tube, the spinal cord, which also is segmented. Each of the
snake’s nervous system segments receives nerve fibers from sensory
receptors in the part of the body adjacent to it, and that nervous system
segment sends fibers back to the muscles in that body part. Each segment,
therefore, works independently.
A complication arises in animals such as humans, whose limbs may
originate at one spinal segment level but extend past other segments of
the spinal column. Your shoulders, for example, may begin at C5
(cervical segment 5), but your arms hang down well past the sacral
segments. So unlike the snake, which has spinal cord segments that
connect to body segments fairly directly adjacent to them, human body’s
segments fall schematically into more of a patchwork pattern, as shown in
Figure 2-28B . This arrangement makes sense if the arms are extended as
they are when we walk on all fours.
Sections 11-1 and 11-4 review the spinal cord’s contributions to
movement and to somatosensation.
 Regardless of their complex pattern, however, our body segments still
correspond to the spinal cord segments. Each of these body segments is
called a dermatome (meaning skin cut ). A dermatome has both a
sensory nerve to send information from the skin, joints, and muscles to
the spinal cord and a motor nerve to control the muscle movements in
that particular body segment.
dermatome Body segment corresponding to a segment of the spinal
cord.
These sensory and motor nerves, known as spinal (or peripheral )
nerves, are functionally equivalent to the cranial nerves of the head.
Whereas the cranial nerves receive information from sensory receptors in
the eyes, ears, facial skin, and so forth, the spinal nerves receive
information from sensory receptors in the rest of the body—that is, in the
PNS. Similarly, whereas the cranial nerves move the muscles of the eyes,
tongue, and face, the peripheral nerves move the muscles of the limbs and
trunk.
 FIGURE 2-28 Spinal Segments and Dermatomes (A) Medial
view showing the five spinal cord segments: cervical (C), thoracic (T),
lumbar (L), sacral (S), and coccygeal. (B) Each segment corresponds to a
region of body surface (a dermatome) identified by the segment number
(e.g., C5 at the base of the neck and L2 in the lower back).

Somatic Nervous System Connections

Like the CNS, the SNS is bilateral (two-sided). Just as the cranial nerves
control functions on the side of the head where they are found, the spinal
nerves on the left side of the spinal cord control the left side of the body,
and those on the right side of the spinal cord control the body’s right side.
Figure 2-29 A on page 62 shows the spinal column in cross section.
Look first at the nerve fibers entering its posterior side. These posterior
fibers (dorsal in four-legged animals) are afferent: they carry in
information from the body’s sensory receptors. The fibers gather as they
enter a spinal cord segment, and this collection of fibers is called a
posterior root in humans (dorsal root in four-legged animals).
Fibers leaving the spinal cord’s anterior side are efferent, carrying
information out from the spinal cord to the muscles. They, too, bundle
together as they exit the spinal cord and so form an anterior root (ventral
root in four-legged animals). The outer part of the spinal cord, pictured in
Figure 2-29B , consists of white matter, or CNS nerve tracts. These tracts
are arranged so that with some exceptions posterior tracts are sensory and
anterior tracts are motor. The inner part of the cord, which has a butterfly
shape, is gray matter composed largely of cell bodies.
The observation that the dorsal spinal cord is sensory and the ventral
side is motor in four-legged animals is one of the nervous system’s very
few established laws, the law of Bell and Magendie. Combined with an
understanding of the spinal cord’s segmental organization, this law
enables neurologists to make accurate inferences about the location of
spinal cord damage or disease on the basis of changes in sensation or
movement. For instance, if a person has numbness in the fingers of the
left hand but can still move the hand fairly normally, one or more of the
posterior (dorsal) nerves in spinal cord segments C7 and C8 must be
damaged. In contrast, if sensation in the hand is normal but the person
cannot move the fingers, the anterior (ventral) roots of the same segments
must be damaged. Clinical Focus 2-4 , Magendie, Bell, and Bell Palsy, on
page 62 , further explores diagnosing spinal cord injury or disease.
 law of Bell and Magendie The principle that sensory fibers are
dorsal and motor fibers are ventral.
Sections 11-1 and 11-4 explore spinal cord injuries and treatments,
and Section 12-3 , the link between spinal injury and loss of emotion.

Integrating Spinal Functions

So far we have emphasized the spinal cord’s segmental organization, but
the spinal cord must also somehow coordinate inputs and outputs across
different segments. For example, many body movements require
coordinating muscles controlled by different segments, just as many
sensory experiences require coordinating sensory inputs to different parts
of the spinal cord. How is this coordination accomplished? The answer is
that the spinal cord segments are interconnected in such a way that
adjacent segments can operate together to direct rather complex
coordinated movements.
Integrating spinal cord activities does not require the brain’s
participation, which is why the headless chicken can run around. Still, a
close working relation must exist between the brain and the spinal cord.
Otherwise, how could we consciously plan and execute our voluntary
actions?
(A)

(B)
 VideoSurgery/Getty Images

FIGURE 2-29 Spinal Nerve Connections (A) A cross section of

the human spinal cord, viewed from the front. The butterfly-shaped inner
regions consist of neural cell bodies (gray matter), and the outer regions
consist of nerve tracts (white matter) traveling to and from the brain. (B) A
posterior view shows the intact human spinal cord exposed.

Somehow information must be relayed back and forth, and examples

of this information sharing are numerous. For instance, tactile
information from sensory nerves in the skin travels not just to the spinal
cord but also to the cerebral cortex through the thalamus. Similarly, the
cerebral cortex and other brain structures can control movements through
their connections to the spinal cord’s anterior roots. So even though the
brain and spinal cord can function independently, the two are intimately
connected in their CNS functions.
CLINICAL FOCUS 2-4

Magendie, Bell, and Bell Palsy

François Magendie, a volatile and committed French experimental
physiologist, reported in a three-page paper in 1822 that he had
succeeded in cutting the dorsal and ventral roots of puppies, animals
in which the roots are sufficiently segregated to allow such surgery.
Magendie found that cutting the dorsal roots caused loss of
sensation, whereas cutting the ventral roots caused loss of
movement.

Dr. P. Marazzi/Science Photo Library/Science Source

A young man with Bell palsy, a paralysis of the facial nerve
(cranial nerve 7) that causes weakness over one side of the face.
He was photographed during an involuntary tic (a nervous
reaction) that affects the right side of the face, causing his right
eye to close tightly.

In 1811, a Scot named Charles Bell proposed functions for these

nerve roots on the basis of anatomical information and the results of
somewhat inconclusive experiments on rabbits. Although Bell’s
findings were not identical with those of Magendie, they were
similar enough to ignite a controversy. Bell hotly disputed
Magendie’s claim to the discovery of dorsal and ventral root
functions. As a result, the principle of sensory and motor segregation
in the nervous system has been named after both researchers: the law
of Bell and Magendie.
 Magendie’s conclusive experiment on puppies was considered
extremely important because for the first time it enabled neurologists
to localize nervous system damage from the symptoms that a patient
displays. Bell went on to describe an example of such localized
cranial motor nerve dysfunction, and it still bears his name—Bell
palsy, a facial paralysis that develops when the motor part of the
facial nerve on one side of the head becomes inflamed (see the
accompanying photograph).
The onset of Bell palsy is typically sudden. Often the stricken
person wakes up in the morning and is shocked to discover the face
paralyzed on one side. He or she cannot open the mouth or
completely close the eye on that side of the head. Most people fully
recover from Bell palsy, although it may take several months. But in
rare instances, such as that of Jean Chrétien, a former prime minister
of Canada, partial paralysis of the mouth is permanent.
 2-4 REVIEW
Somatic Nervous System: Transmitting Information
Before you continue, check your understanding.
1 . Two sets of SNS nerves, the ___________ and the ___________,
receive sensory information or send motor signals to muscles or both.
2 . Both sets of SNS nerves are symmetrically organized, and each set
controls functions on the ___________ side of the body.
3 . The cranial nerves have both sensory and motor functions, receiving
and sending information to the ___________ and to the ___________.
4 . Define the law of Bell and Magendie and explain why it is important.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Autonomic and Enteric Nervous
2-5

Systems: Visceral Relations

Control of the viscera (internal organs), including the heart, gut, liver,
and lungs, requires complex neural systems. Yet the ANS and ENS are
hidden partners, functioning in the background as the CNS controls our
perceptions and behaviors. If we had to focus consciously on visceral
activities, we would do little else. The ANS and ENS interact with the
CNS, but each has distinctive anatomy and functions.

ANS: Balancing Internal Functions

Without our conscious awareness, the ANS stays on the job to keep the
heart beating, the liver releasing glucose, the pupils of the eyes adjusting
to light, and so forth. Without the ANS, which regulates the internal
organs and glands via connections through the SNS to the CNS, life
would quickly cease. Although learning to exert some conscious control
over some of these vegetative activities is possible, such conscious
interference is normally unnecessary. An important reason is that the
ANS must keep working during sleep, when conscious awareness is off
duty. But gastrointestinal disorders are common, and stress is often a
factor. Psychological therapies are often effective in treating such
disorders.
Section 5-3 explains CNS–ANS communication, Figure 6-22
diagrams the stress response, and Section 16-4 discusses how mood
affects reactivity to stress.
It is tempting to think that the ANS’s organization must be pretty
simple because it functions outside our conscious awareness. Yet, like
the SNS, we can think about the ANS as a collection of minibrains with
a surprisingly complex organization. The two ANS divisions work in
opposition. The sympathetic division arouses the body for action, for
example, by stimulating the heart to beat faster and inhibiting digestion
when we exert ourselves during exercise or times of stress—the familiar
fight-or-flight response. The parasympathetic division calms the body
down, for example, by slowing the heartbeat and stimulating digestion to
allow us to rest and digest after exertion and during quiet times.
sympathetic division Part of the autonomic nervous system;
arouses the body for action, such as mediating the involuntary fight-
 or-flight response to alarm by increasing heart rate and blood
pressure.
parasympathetic division Part of the autonomic nervous system;
acts in opposition to the sympathetic division—for example,
preparing the body to rest and digest by reversing the alarm
response or stimulating digestion.
Principle 10: The nervous system works by juxtaposing excitation
(increased neural activity) and inhibition (decreased neural activity).
Like the SNS, the ANS interacts with the rest of the nervous system,
and like the SNS, ANS connections are ipsilateral. Activation of the
sympathetic division starts in the thoracic and lumbar spinal cord
regions. But the spinal nerves do not directly control the target organs.
Rather, the spinal cord is connected to autonomic control centers—
collections of neural cells called ganglia. The ganglia control the internal
organs, and each acts as a mini-brain for specific organs.
The sympathetic ganglia are near the spinal cord on each side,
forming chains that run parallel to the cord, as illustrated at left in Figure
2-30 for one set of ganglia. The parasympathetic division also is
connected to the spinal cord—specifically, to the sacral region—but the
greater part of it derives from three cranial nerves: the vagus nerve,
which calms most of the internal organs, and the facial and oculomotor
nerves, which control salivation and pupil dilation, respectively (review
Figure 2-27 ). In contrast with the sympathetic division, the
parasympathetic division connects with ganglia that are near the target
organs, as shown at right in Figure 2-30 .

ENS: Controlling the Gut

The ENS is sometimes considered part of the ANS, but it functions
largely independently. Digestion is complicated, and evolution has
provided this dedicated nervous system to control it. Some scientists
have even proposed that the CNS evolved from the gut of very simple
organisms.
In fact, the ENS is sometimes called the second brain because, like
the CNS, it contains a diversity of neuron types, the same chemical
transmitters, a profusion of glial cells, and complex integrated neural
circuits. Its estimated 200 million to 500 million neurons roughly equals
the number in the spinal cord. The gut reacts to a range of hormones and
other chemicals with exquisite neural responses. The ENS functions to
control bowel motility, secretion, and blood flow to permit fluid and
nutrient absorption and to support waste elimination (see Avetisyan et
al., 2015). This is no simple task, given the number and balance of
nutrients needed to support the body.

FIGURE 2-30 Autonomic Nervous System The two ANS

pathways exert opposing effects. All fibers connect at “stops” formed by
ganglia en route from the CNS to target ANS organs. Left: Arousing
sympathetic fibers connect to a chain of ganglia near the spinal cord.
Right: Calming parasympathetic fibers connect to individual ganglia near
target organs.

ENS neurons are located in a sheet of tissue (plexus ) lining the

esophagus, stomach, small intestine, and colon. As shown in Figure 2-31
, ENS neurons and glia form ganglia connected by nerve fibers found in
two layers of gut tissue. The brain and ENS connect extensively through
the ANS, especially via the vagus nerve. Although we are not conscious
of our gut “thinking,” the ENS sends information directly to the brain—
information that affects our mental state—and the brain can modify gut
function. Indeed, a growing body of evidence implicates the ENS in
many behavioral disorders, and stress and anxiety commonly modify gut
function, leading to such symptoms as nausea and diarrhea.
Section 12-4 expands on how emotions and the ENS interact,
Section 12-5 on the ENS and eating.
The ENS interacts with gut bacteria, known collectively as the
microbiome. About 1014 microbiota populate the adult gut, outnumbering
the host cells by a factor of 10 (Farmer et al., 2014). The microbiota
influence nutrient absorption and are a source of neurochemicals that
regulate an array of physiological and psychological processes. This
relationship has inspired the development of a class of compounds
known as psychobiotics, live microorganisms used to treat behavioral
disorders. Thus, the microbiota can influence both the CNS and ENS,
leading to changes in behavior.
FIGURE 2-31 Enteric Nervous System The ENS is formed by a
network of neurons embedded in the lining of the gastrointestinal tract.
Congregations of neurons form ganglia that send projections to the ANS
and CNS, in part through the vagus nerve (cranial nerve 10), to control gut
function.
 2-5 REVIEW
Autonomic and Enteric Nervous Systems: Visceral
Relations
Before you continue, check your understanding.
1 . The ANS interacts with the CNS and SNS via sets of autonomic
control centers called ___________, which act as minibrains to control
the internal organs.
2 . The ___________ division of the ANS arouses the body for action,
and the ___________ division calms the organs. The two divisions
work ___________ to allow for quick defensive responses (fight or
flight) or to induce a calming (rest and digest) state.
3 . Why is the ANS essential to life?
4 . The ENS is often called a second brain because of the ___________ it
contains.
5 . The ENS interacts with bacteria that form the ___________, which
absorbs ___________ and produces ___________ that can regulate
CNS and ENS activity.
6 . What are psychobiotics?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Ten Principles of Nervous System
2-6

Function
The balance of the whole nervous system, of the functioning brain, and
of individual cells works in concert to produce behavior. Knowing the
parts of the nervous system and some general notions about what they do
is only the beginning. Learning how the parts work together allows us to
proceed to a closer look, in the chapters that follow, at how the brain
produces behavior.
Thus far, we have identified 10 principles related to the nervous
system’s functioning. Here we elaborate each one. As you progress
through the book, review these ideas regularly with an eye toward
understanding the concept rather than simply memorizing the principle.
Soon you will find yourself applying the principles of function as you
encounter new information about the brain and behavior.

Principle 1: The Nervous System Produces

Movement in a Perceptual World the Brain
Constructs
The nervous system’s fundamental function is to produce behavior, or
movement. Movements are not made in a vacuum but are related to
objects, places, memories, and myriad other forces and factors. Your
mental representation of the world depends on the information sent to
your brain. People who are color-blind perceive the world very
differently from those who perceive color. The perceptual world of
people who have perfect pitch is different from that of those who do not.
Although we tend to think that the world we perceive is what is
actually there, individual realities, both between and within species,
clearly are just rough approximations of what is actually present. The
brain of each animal species produces a reality that is adaptive for that
species to survive. The behavior that the brain produces, in other words,
is directly related to the world that the brain has constructed.

Principle 2: Neuroplasticity Is the Hallmark

of Nervous System Functioning
Experience alters the brain’s organization, and this neuroplasticity is
requisite to learning and memory as well as to survival. In fact, the
nervous system stores information only if neural connections change.
Forgetting is presumably due to a loss of the connections that
represented the memory.
As Experiment 2-1 on page 49 demonstrates, neuroplasticity is a
characteristic not just of the mammalian brain; it is found in the nervous
system of all animals, even the simplest worms. Nonetheless, larger
brains have more capacity for change, and thus their neural organization
is likely to show more plasticity.
Plasticity can be beneficial in recovering from disorders, such as brain
injuries and diseases, as well as in coping with aging. Plasticity also
allows the brain to compensate for developmental abnormalities, an
extreme example being agenesis of brain structures, as discussed in
Research Focus 2-1 . Although beneficial in such circumstances,
neuroplasticity has drawbacks. Brain analyses of animals given addicting
doses of drugs such as cocaine or morphine reveal broad changes in
neural connectivity suspected of underlying some maladaptive behaviors
related to addiction. Among many other examples of pathological
neuroplasticity are those associated with pain, epilepsy, and dementia.
Detail on plasticity and drug addiction in Section 14-4 , on feeling
and treating pain in Section 11-4 , on epilepsy in Focus 4-1. Section
16-3 details diagnosis and treatment of epilepsy and dementias.

Principle 3: Many Brain Circuits Are

Crossed
Most brain inputs and outputs are crossed, that is, serve the opposite side
of the body. Each hemisphere receives sensory stimulation from the
opposite (contralateral) side of the body and controls muscles on the
contralateral side. Crossed organization explains why people who have a
stroke or other damage to the left cerebral hemisphere may have
difficulty in sensing stimulation to the right side of the body or in
moving body parts on the right side. The opposite is true of people
whose stroke occurs in the right cerebral hemisphere.
A crossed nervous system must somehow join both sides of the
perceptual world together. To do so, innumerable neural connections link
the brain’s left and right sides. The most prominent connecting cable is
the corpus callosum. Its roughly 200 million nerve fibers join the left and
right cerebral hemispheres, allowing them to interact.
Figure 9-10 illustrates how the human visual system represents the
world seen through two eyes as a single perception: both eyes
connect with both hemispheres.
Four important exceptions to the crossed-circuit principle are
olfactory sensation and the somatic, autonomic, and enteric PNS
connections. Olfactory information does not cross but rather projects
directly into the same (ipsilateral) side of the brain. The cranial and
spinal nerves that constitute the SNS are connected ipsilaterally, as are
the sympathetic and para-sympathetic ANS division connections.
Likewise, ipsilateral ENS connections link to the ANS on both sides.

Principle 4: The CNS Functions on Multiple

Levels
In simple animals such as worms the spinal cord essentially constitutes
the nervous system. More complex animals, such as fishes, have a
brainstem as well, and yet more complex animals have also evolved a
forebrain. Each new addition to the CNS has added a new level of
behavioral complexity without discarding previous levels of control. As
animals evolved legs, for example, brain structures evolved to move the
legs. Later, the development of independent digit movements required
even more brainpower. Thus, new brain areas add new levels of nervous
system control. The new levels are not autonomous but rather must be
integrated into existing neural systems as refinements and elaborations of
the control earlier levels provided.
Multiple levels of function can be seen not only in the addition of
forebrain areas to refine brainstem control but also in the forebrain itself.
As mammals evolved, they developed an increased capacity to represent
the world in the cortex, an ability related to the addition of more maps.
The new maps must be related to the older ones, however, and again are
simply an elaboration of the perceived sensory world that existed before.

Principle 5: The Brain Is Symmetrical and

Asymmetrical
The left and the right hemispheres look like mirror images, but they have
some dissimilar features. Cortical asymmetry is essential for integrative
tasks, language and body control among them.
Consider speaking. If a language zone existed in both hemispheres,
each connected to one side of the mouth, we would actually be able to
talk out of both sides of our mouth at once. That would make talking
awkward, to say the least. One solution is to locate language control of
the mouth on one side of the brain. Organizing the brain in this way
allows us to speak with a single voice.
A similar problem arises in controlling body movements in space. We
would not want the left and the right hemispheres each trying to take us
to a different place. Again, if a single brain area controls this sort of
spatial processing, problem solved.
Language control is typically situated on the left side, and spatial
functions are typically on the right. The brains of many species have
such symmetrical and asymmetrical features. In the bird brain, the
control of singing is in one hemisphere, usually on the left side, as is
human language. It is likely that birds and humans evolved the same
solution independently—namely, to assign the control to only one side of
the brain.

Principle 6: Brain Systems Are Organized

Hierarchically and in Parallel
When we consider the multiple levels of CNS function, it becomes
apparent that these levels must be extensively interconnected to integrate
their processing and produce unified perceptions or movements. The
nature of neural connectivity leads to the principle that the brain has both
serial (or hierarchical) and parallel circuitry.
A hierarchical circuit hooks up a linear series of all regions concerned
with a particular function. Consider vision. In a serial system, the
information from the eyes goes to regions that detect the simplest
properties, such as color or brightness. This information is passed along
to another region that determines shape, then to another that measures
movement, and so on until at the most complex level the information is
understood to be, say, your grandmother. Information therefore flows
sequentially from simpler to more complex regions in the hierarchy, as
illustrated in Figure 2-32 A .
(A)

(B)

FIGURE 2-32 Models of Neural Information Processing

(A) Simple hierarchical model of serial cortical processing. (B) In a
 distributed hierarchical processing model each of several processing
streams has multiple levels. Areas at each level interconnect.

However, functionally related brain structures are not always linked

linearly. Although the brain has many serial connections, many expected
connections are missing. In the visual system, not all cortical regions are
connected to one another. The simplest explanation is that the
unconnected regions must have widely differing functions.
Parallel circuits operate on a different principle, also illustrated by the
visual system. Imagine looking at a car. As we look at a car door, one set
of visual pathways processes information about its nature, such as color
and shape, whereas another set of pathways processes information about
movements such as those necessary to open the door.
These two visual systems are independent of each other, yet they must
interact somehow. When you pull the car door open, you do not perceive
two different representations—the door’s size, shape, and color on the
one hand and the opening movements on the other. When you open the
door, you have the impression of unity in your conscious experience.
Figure 2-32B illustrates the information flow in such a distributed
hierarchy. If you trace the flow from the primary area to levels 2, 3, and
4, you follow the parallel pathways. And while these multiple parallel
pathways are also connected to one another, those connections are more
selective than connections in a purely serial circuit.
The brain’s subsystems are organized into multiple parallel pathways,
yet our conscious experiences are always unified. As we explore this
conundrum throughout the book, keep in mind that your commonsense
impressions of how the brain works may not always be correct.

Principle 7: Sensory and Motor Divisions

Permeate the Nervous System
The segregation of SNS sensory and motor functions described by the
Bell and Magendie law exists throughout the nervous system.
Distinctions between motor and sensory functions become subtler in the
forebrain.
Sensory and Motor Divisions in the SNS
Spinal nerves are either sensory or motor. Some cranial nerves are
exclusively sensory; some are exclusively motor; and some have two
parts, one sensory and one motor, much like spinal nerves serving the
skin and muscles.
Review cranial nerve and spinal nerve connections in Figures 2-27
and 2-28 .
Sensory and Motor Divisions in the CNS
The lower brainstem regions—hindbrain and midbrain—are essentially
extensions of the spinal cord. They retain the spinal cord’s division, with
sensory structures posterior and motor structures anterior in humans. An
important midbrain function is orienting the body to stimuli. Orienting
movements require sensory input and motor output. The midbrain’s
colliculi, posterior in the human tectum, are the sensory component,
whereas the tegmentum, which is anterior, is a motor structure that
participates in controlling various movements, including orienting.
Figures 2-15 through 2-19 illustrate brainstem structures.
Distinct sensory nuclei are present in the thalamus, too, although their
positions are not segregated, as they are in lower structures. Because all
sensory information reaches the forebrain through the thalamus, to find
separate nuclei associated with vision, hearing, and touch is not
surprising. Separate thalamic nuclei also control movements. Other
nuclei have neither sensory nor motor functions but rather connect to
cortical areas, such as the frontal lobe, that perform more integrative
tasks.
Finally, sensory and motor functions are divided in the cortex in two
ways:
1. Separate sensory and motor cortical regions process a particular set of
sensory inputs, such as vision, hearing, or touch. Others control fine
movements of discrete body parts, such as the fingers.
2. The entire cortex is organized around the sensory and motor
distinction. As diagrammed in Figure 2-22 , layer IV of the cortex
always receives sensory inputs, layers V and VI always send motor
outputs, and layers I, II, and III integrate sensory and motor
operations.

Principle 8: The Brain Divides Sensory

Input for Object Recognition and Motor
Control
Sensory systems evolved first for controlling motion, not for recognizing
things. Simple organisms can detect stimulation such as light and move
to or from it. It is not necessary to perceive an object to direct
movements toward or away from it. Animals only began to evolve ways
of representing their environment as their behaviors became more
complex. Animals with a complex brain evolved separate systems for
recognizing objects and for moving toward them. The human visual
system exemplifies this separation.
Visual information travels from the eyes to the thalamus to visual
regions of the occipital lobe. From the occipital cortex it follows one of
two routes: the ventral stream leads to the temporal lobe for object
identification, whereas the dorsal stream goes to the parietal lobe to
guide movements relative to objects ( Figure 2-33 ). People with ventral
stream injuries are blind for object recognition. They cannot distinguish
a cup from a spoon. Nevertheless, they shape their hands appropriately
when asked to reach for objects that they cannot identify. In contrast,
people with dorsal stream injuries can recognize objects, but they make
clumsy reaching movements because they do not form appropriate hand
postures until they contact objects. Only then do they shape the hand on
the basis of tactile information.
 FIGURE 2-33 Neural Streams The dorsal and ventral streams
mediate vision for action and recognition, respectively.

Recognizing that perception for movement and perception for object

recognition are independent processes has three important implications
for understanding brain organization:
1. The dorsal and ventral visual systems exemplify parallel information
processing in the brain.
2. Although we may think we are aware of our entire sensory world, the
sensory analysis required for some movements clearly is not
conscious.
3. Unconscious and conscious brain processing underlies an important
difference in our cognitive functions. The unconscious movement
system is always acting in the present and in response to ongoing
sensory input. In contrast, the conscious object recognition system
allows us to escape the present and bring to bear information from the
past, thus forming the neural basis of enduring memory.
Sections 9-2 and 9-3 review evidence that led to understanding the
visual streams’ functions and visual information processing.

Principle 9: Brain Functions Are Localized

and Distributed
A great debate in the history of brain research has concerned what
aspects of different functions are actually localized in specific brain
regions. Perhaps the fundamental problem is defining a function.
Language, for example, includes the comprehension of spoken words,
written words, signed words (as in American Sign Language), and even
touched words (as in Braille). Language also includes production of
words orally, in writing, and by signing, as well as constructing whole
linguistic compositions, such as stories, poems, songs, and essays.
Because the function that we call language has many aspects, it is not
surprising that these aspects reside in widely separated areas of the brain.
We see evidence of this widespread distribution in language-related brain
injuries. People with injuries in different locations may selectively lose
the abilities to produce words, to understand words, to read words, to
write words, and so forth. Specific language-related abilities, therefore,
reside in specific locations, but language as a whole is distributed
throughout a wide brain region.
Memory provides another example of this same distributed pattern.
Memories can be richly detailed and can include sensual feelings, words,
images, and much more. Like language, then, aspects of memory are
located in many brain regions distributed throughout a vast area of the
brain.
Figure 14-5 illustrates the extensive distribution of memory areas
through the brain.
Because many functions are both localized and distributed in the
brain, damage to a small brain region produces only focal (specific)
symptoms. Massive brain damage is required to obliterate some
functions. A small injury could impair some aspect of language
functioning, such as naming objects, but it would take widespread injury
to remove all language abilities. In fact, one characteristic of dementing
diseases is that people can endure widespread deterioration of the cortex
yet maintain remarkably normal language functions until late stages of
the disease. Alzheimer disease is a degenerative brain disorder related to
aging that first appears as progressive memory loss and only much later
develops into generalized dementia.
Alzheimer disease Degenerative brain disorder related to aging that
first appears as progressive memory loss and later develops into
generalized dementia.
For Alzheimer neurochemistry, see Section 5-3 ; for incidence and
possible causes, Section 14-3 ; for treatments, Section 16-4 .

Principle 10: The Nervous System Works

by Juxtaposing Excitation and Inhibition
We have emphasized the brain’s role in making movements, but we must
also recognize that the brain prevents movements. To make a directed
movement, such as picking up a glass of water, we must refrain from
other movements, such as waving the hand back and forth. In producing
movement, then, the brain uses both excitation (increased neural
activity) to produce some action and inhibition (decreased neural
activity) to prevent other actions.
excitation Increase in the activity of a neuron or brain area.
 inhibition Decrease in the activity of a neuron or brain area.
Brain injury or disease can produce either a loss or a release of
behavior by changing the balance between excitation and inhibition. A
brain injury in a region that normally initiates speech may render a
person unable to talk—a loss of behavior. A person with an abnormality
in a region that inhibits inappropriate language (such as swearing) may
be unable to inhibit this form of speech. Such a release of behavior can
be seen in Tourette syndrome.
Tourette syndrome and Parkinsonism are dysfunctions of the basal
ganglia, which coordinates voluntary movement.
Patients with Parkinson disease may have uncontrollable shaking of
the hands because the neural system that inhibits such movements has
failed. Paradoxically, they often have difficulty initiating movements and
appear frozen because they cannot generate the excitation needed to
produce deliberate movements.
The juxtaposition of excitation and inhibition, central to the way the
brain produces behavior, can be seen at the level of individual neurons.
All neurons evince a spontaneous activity rate that can be either
increased (excitation) or decreased (inhibition). Some neurons excite
others; some inhibit. Both effects are produced by neuronal
communication via specific neurochemicals.
Chapter 3 details nervous system cell structure; Chapter 4 , how
neurons transmit and integrate information; and Chapter 5 , neuronal
communication and adaptation.
 2-6 REVIEW
Ten Principles of Nervous System Function
Before you continue, check your understanding.
1 . Many of the brain’s input and output circuits are crossed. In the
nervous system, four exceptions to this principle are the ___________,
the ___________, the ___________, and the ___________.
2 . The vertebrate brain has evolved three regions—hindbrain, midbrain,
and forebrain—leading to ___________ and flexibility in controlling
behavior.
3 . One aspect of neural activity that resembles the on–off language of
digital devices is the juxtaposition of ___________ and ___________.
4 . Explain this statement: Perception is not reality.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 SUMMARY
2-1 Overview of Brain Function and Structure
The brain’s primary function is to produce behavior, or movement, in a
perceptual world the brain constructs. This perceptual world is ever-
changing. To adapt, the brain must also change, a property referred to as
neuroplasticity.
To study how the nervous system functions, we abandon the
anatomical divisions between the central nervous system and the
peripheral nervous system to focus instead on function—on how the
CNS interacts with the divisions of the PNS: the somatic, autonomic, and
enteric nervous systems.
 2-2 The Nervous System’s Evolutionary
Development
The vertebrate nervous system evolved from a relatively simple structure
mediating reflexlike behaviors to the complex human brain mediating
advanced cognitive processes. To allow for more complex behavior in an
increasingly sophisticated perceptual world, primitive forms have not
been replaced but rather have been adapted and modified as new
structures have evolved.
The principles of nervous system organization and function generalize
across the three vertebrate brain regions—hindbrain, midbrain, and
forebrain—leading to multiple levels of functioning. The evolution of
neural levels of control thus adds flexibility to behavioral control.
 2-3 Central Nervous System: Mediating Behavior
The CNS includes the brain and the spinal cord. The spinal cord can
perceive sensations from the skin and muscles and produce movements
independent of the brain. The brain can be divided into the brainstem and
forebrain, each made up of hundreds of parts. The brainstem both directs
movements and constructs a sensory world through its connections with
the sensory systems, spinal cord, and forebrain. The forebrain modifies
and elaborates basic sensory and motor functions; regulates cognitive
activity, including thought and memory; and ultimately controls
movement. The most elaborate parts of the brain, the cerebral cortex and
cerebellum, grow disproportionately large in the human brain.
 2-4 Somatic Nervous System: Transmitting
Information
The SNS consists of two sets of spinal nerves that enter and leave the
spinal column, connecting with muscles, skin, and joints in the body, and
the cranial nerves that link the facial muscles and some internal organs to
the brain. Both sets of SNS nerves are symmetrical: one set controls each
side of the body. Some cranial nerves are sensory, some are motor, and
some combine both functions. The spinal cord acts as a minibrain for the
peripheral (spinal) nerves that enter and leave its five segments. Each
spinal segment works independently, although CNS fibers interconnect
them and coordinate their activities.
 2-5 Autonomic and Enteric Nervous Systems:
Visceral Functions
The ANS controls the body’s glands and internal organs and operates
largely outside conscious awareness. Its sympathetic (arousing) and
parasympathetic (calming) divisions work in opposition. The
parasympathetic division directs the organs to rest and digest, whereas
the sympathetic division prepares for fight or flight.
The ENS controls the gut over its entire length, from the esophagus to
the colon, interacting with the brain via the ANS. ENS activity can affect
our behavior and mental state. In turn, the ENS is affected by the
microbiome, the roughly 100 trillion bacteria that inhabit our gut.
 2-6 Ten Principles of Nervous System Function
Ten principles listed in the right column below form the basis for
discussions throughout this book. Understanding them fully will enhance
your study of brain and behavior.
Ten Principles of Nervous System Function
1 The nervous system produces movement in a perceptual world the brain constructs.

2 Neuroplasticity is the hallmark of nervous system functioning.

3 Many brain circuits are crossed.

4 The CNS functions on multiple levels.

5 The brain is symmetrical and asymmetrical.

6 Brain systems are organized hierarchically and in parallel.

7 Sensory and motor divisions permeate the nervous system.

8 The brain divides sensory input for object recognition and motor control.

9 Brain functions are localized and distributed.

1 The nervous system works by juxtaposing excitation and inhibition.

0
 KEY TERMS
afferent, p. 37
Alzheimer disease, p. 70
autonomic nervous system (ANS), p. 37
basal ganglia, p. 56
brainstem, p. 50
cerebral cortex, p. 41
cerebrospinal fluid (CSF), p. 41
corpus callosum, p. 44
cranial nerve, p. 59
cytoarchitectonic map, p. 56
dermatome, p. 60
diencephalon, p. 52
efferent, p. 37
enteric nervous system (ENS), p. 37
excitation, p. 70
forebrain, p. 54
frontal lobe, p. 41
gray matter, p. 43
gyri (sing. gyrus), p. 43
hindbrain, p. 52
hypothalamus, p. 54
inhibition, p. 70
law of Bell and Magendie, p. 60
limbic system, p. 56
meninges, p. 37
midbrain, p. 52
neocortex (cerebral cortex), p. 54
nerve, p. 47
neuroplasticity, p. 37
nuclei (sing. nucleus), p. 47
occipital lobe, p. 41
orienting movement, p. 52
parasympathetic division, p. 63
parietal lobe, p. 41
Parkinson disease, p. 56
phenotypic plasticity, p. 37
reticular formation, p. 52
somatic nervous system (SNS), p. 37
stroke, p. 43
sulci (sing. sulcus), p. 43
sympathetic division, p. 63
tectum, p. 52
tegmentum, p. 52
temporal lobe, p. 41
thalamus, p. 54
Tourette syndrome, p. 56
tract, p. 47
ventricle, p. 44
vertebrae (sing. vertebra), p. 59
white matter, p. 44

Visit Launch Pad to access the e-Book, videos,

Learning Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

What Are the Nervous

System’s Functional
Units?
 Katherine Streeter

RESEARCH FOCUS 3-1 A GENETIC DIAGNOSIS

3-1 CELLS OF THE NERVOUS SYSTEM
RESEARCH FOCUS 3-2 BRAINBOW: RAINBOW NEURONS
NEURONS: THE BASIS OF INFORMATION PROCESSING
FIVE TYPES OF GLIAL CELLS
EXPERIMENT 3-1 QUESTION: CAN THE PRINCIPLES OF
NEURAL EXCITATION AND INHIBITION CONTROL THE
ACTIVITY OF A SIMPLE ROBOT?
CLINICAL FOCUS 3-3 BRAIN TUMORS
3-2 INTERNAL STRUCTURE OF A CELL
THE CELL AS A FACTORY
THE BASICS CHEMISTRY REVIEW
CELL MEMBRANE: BARRIER AND GATEKEEPER
THE NUCLEUS AND PROTEIN SYNTHESIS
THE ENDOPLASMIC RETICULUM AND PROTEIN
MANUFACTURE
PROTEINS: THE CELL’S PRODUCT
GOLGI BODIES AND MICROTUBULES: PROTEIN PACKAGING
AND SHIPMENT
CROSSING THE CELL MEMBRANE: CHANNELS, GATES, AND
PUMPS
3-3 GENES, CELLS, AND BEHAVIOR
MENDELIAN GENETICS AND THE GENETIC CODE
APPLYING MENDEL’S PRINCIPLES
CLINICAL FOCUS 3-4 HUNTINGTON DISEASE
GENETIC ENGINEERING
PHENOTYPIC PLASTICITY AND THE EPIGENETIC CODE
RESEARCH FOCUS 3-1

A Genetic Diagnosis
Fraternal twins Alexis and Noah Beery seemingly acquired cerebral
palsy perinatally (at or near birth). They had poor muscle tone and
could barely walk or sit. Noah drooled and vomited, and Alexis had
tremors.
Typically, children with cerebral palsy, a condition featuring
perinatal brainstem damage, do not get worse with age, but the
twins’ condition deteriorated. Their mother, Retta Beery, observed as
well that Alexis’s symptoms fluctuated: they improved after she slept
or napped, for example.

Courtesy of Retta Beery

Noah, Retta, Joe, and Alexis Beery at Baylor College with the
Solid Sequencer, which decoded the genomes of twins Noah
and Alexis.

In searching the literature for similar cases, Retta found a

photocopy of a 1991 news report that described a child first
diagnosed with cerebral palsy, then found to have a rare condition,
dopa-responsive dystonia. (Dystonia means abnormal muscle tone.)
It stems from a deficiency of a neurochemical, dopamine, produced
by a relatively small cluster of cells in the midbrain.
 When Alexis and Noah received a daily dose of l-dopa, a
chemical that some brain cells convert to dopamine, they displayed
remarkable improvement. “We knew that we were witnessing a
miracle,” Retta recalled.
A few years later, in 2005, Alexis began to have new symptoms
marked by breathing difficulties. At this time the twins’ father, Joe,
worked for Life Technologies, a biotech company that makes
equipment used for sequencing DNA, the genetic coding molecule
found in the nucleus of every cell. Joe arranged for samples of the
twins’ blood to be sent to the Baylor College of Medicine’s DNA
sequencing center.
The twins’ genome was sequenced and compared with that of
their parents and close relatives. The analysis showed that the twins
had an abnormality in a gene on chromosome 2 for an enzyme that
enhances not only dopamine production but also the production of
serotonin, another neurochemical made by brainstem cells
(Bainbridge et al., 2011).
When the twins’ doctors added tryptophan, the enzyme that is
converted to serotonin, to the l-dopa, both twins showed remarkable
improvement. Alexis competed in junior high school track, and Noah
played volleyball in the Junior Olympics. This is the first diagnosis
established through genome sequencing that led to a treatment
success, a scientific miracle indeed.

The Beery twins’ remarkable story highlights how neuroscientists are

applying advances in genetics to treat brain disorders. Understanding
genes, proteins, and cellular function allows us to understand healthy
brain functioning as well.
We begin this chapter by describing nervous system cell structure and
relating structure to functions. Brain cells not only give the nervous
system its structure but also mediate its moment-to-moment activity, the
activity that underlies our behavior. We conclude the chapter by
elaborating on Mendelian genetics and how the science of epigenetics
completes Mendel’s theory.
 3-1 Cells of the Nervous System
Cells have been likened to factories in that they make a product, proteins,
the building blocks of our bodies. But cells are more than factories. Cells
use the proteins they produce to participate in orchestrating our behavior.
Nervous system cells are small, are packed tightly together, and have
the consistency of jelly. To see a brain cell, the observer must distinguish
it from surrounding cells, magnified under a microscope. The first
anatomists to study brain cells developed methods of highlighting
individual cells in nervous system tissue. To make the tissue firm, they
soaked it in formaldehyde to preserve and fix the tissue by binding
together its constituent protein molecules. The fixed tissue was then
sliced in thin sheets (sectioned), colored (stained) with various dyes, and
placed under a microscope for viewing.
RESEARCH FOCUS 3-2

Brainbow: Rainbow Neurons

Were it not for the discovery of stains that can highlight brain cell
features, their complexity and connections would remain unknown.
Jean Livet (2007) and his colleagues at Harvard University developed
a transgenic technique that labels different neurons by highlighting
them with distinct colors, a technique called Brainbow, a play on the
word rainbow. (Transgenic techniques are a form of genetic
engineering discussed in Section 3-3 .)
In the same way a television monitor produces the full range of
colors that the human eye can see by mixing only red, green, and
blue, the Brainbow scientists introduced genes that produce cyan
(blue), green, and red fluorescent proteins into mice cells. The red
gene is obtained from coral, and the blue and green genes are
obtained from jellyfish. (The 2008 Nobel Prize in chemistry was
awarded to Roger Tsien, Osamu Shimomura, and Martin Chalfie for
their discovery and development of fluorescent proteins in coral and
jellyfish.)
The mice also received a bacterial gene called Cre. Cre activates
the color genes inside each cell, but owing to chance factors, the
extent to which each gene is activated varies. As the mice develop,
the variable expression of the color-coding genes results in cells that
fluoresce in at least a hundred hues. When viewed through a
fluorescent microscope sensitive to these wavelengths, individual
brain cells and their connections can be visualized because they have
slightly different hues, as illustrated in the accompanying
micrographs.
Because individual cells can be visualized, Brainbow offers a way
to describe where each neuron sends its processes and how it
interconnects with other neurons. You have probably seen an
electrical power cord in which the different wires have different
colors (black, white, red) that signify what they do and how they
should be connected. By visualizing living brain tissue in a dish,
Brainbow provides a method for examining changes in neural circuits
with the passage of time.
 In the future, Brainbow will prove useful for examining
populations of cells and their connections—for example, cells
implicated in specific brain diseases. In principle, Brain-bow could be
turned on at specific times, as an individual ages or solves problems,
for example (Rojczyk-Gołȩbiewska et al., 2015). Despite Brainbow’s
promise, challenges remain. Even the simplest brain contains
extraordinary numbers of neurons and fibers. Modifications in
Brainbow that restrict visualization to only a few cells and fibers at a
time are necessary for their connections to be understood.

Cell bodies
Axons

Livet, Draft, Sanes, and Lichtman, Harvard University

 Terminal buttons

Scientists continue to fix, slice, and stain brain tissue and to improve
on ways of visualizing cells to provide insights into what cells do.
Visualization is aided not only by using dyes that either color an
individual cell completely; color some cellular components. such as its
proteins; or as described in Research Focus 3-2 , Brainbow: Rainbow
Neurons, color the cell only when it is engaged in a particular activity.
Scientists have developed other techniques of viewing living cells in
the nervous system or viewing cells that are cultured in a dish with
nurturing fluids. In doing so, they use staining techniques to produce an
image of the cell and to allow its activity to be viewed and controlled.
Investigators even implant tiny microscopes in the brain to view the
activity of its neurons (Chen et al., 2013). There remains, however, the
problem of making sense of what you see. Different brain samples can
yield different images, and different people can interpret the images in
different ways.
So began a controversy between two great scientists—the Italian
Camillo Golgi and the Spaniard Santiago Ramón y Cajal—that resulted in
defining neurons. Both men were awarded the Nobel Prize for medicine
in 1906. Imagine that you are Camillo Golgi, hard at work in your
laboratory staining and examining nervous system cells. You immerse a
thin slice of brain tissue in a solution containing silver nitrate and other
chemicals, a technique used at the time to produce black-and-white
photographs. A contemporary method, shown in Figure 3-1 A , produces
a color-enhanced microscopic image that resembles the images Golgi
saw.
(A)
 Biophoto Associates/Science Source/Photo Researchers

(B)
FIGURE 3-1Two Views of a Cell (A) Tissue preparation revealing human
pyramidal cells stained using the Golgi technique. (B) Cajal’s drawing of a single Purkinje
neuron made from Golgi-stained tissue. (B) Drawing from Histologie du système nerveux de l’homme et
des vertèbres, by S. Ramón y Cajal, 1909–1911, Paris: Maloine.

Golgi never revealed just how he came to develop his staining

technique.
The image is beautiful and intriguing, but what do you make of it? To
Golgi, this structure suggested that the nervous system is an
interconnected network of fibers. He thought that information flowed
around this “nerve net,” like water running through pipes, and so
produced behavior. His theory was reasonable, given what he saw.
But Santiago Ramón y Cajal came to a different conclusion. He used
Golgi’s stain to study chick embryos’ brain tissue. He assumed that their
developing nervous system would be simpler and easier to understand
than an adult’s. Figure 3-1 B shows an image he rendered from the neural
cells using the Golgi stain. Cajal concluded that the nervous system is
made up of such discrete cells, which begin life as a rather simple
structure that becomes more complex with age. When mature, each cell
consists of a main body with many extensions projecting from it.
The structure looks something like a plant, with branches coming out
of the top and roots coming out of the bottom. Cajal showed that neurons
come in many shapes and sizes. Cajal’s neuron theory —that neurons are
the nervous system’s functional units—is now universally accepted. The
neuron theory includes the ideas that the interactions between these
discrete cells enable behavior and that the more neurons an animal has,
the more complex its behavior.
Figure 3-2 shows the three basic subdivisions of a neuron. The core
region is called the cell body, or soma (Greek, meaning body ; the root of
words such as somatic ). A neuron’s branching extensions, or dendrites
(from Greek for tree ), collect information from other cells, and its main
root is the single axon (Greek for axle ), which carries messages to other
neurons. A neuron has only one axon, but most have many dendrites.
Some neurons have so many dendrites that they look like a garden hedge,
as Cajal’s drawing in Figure 3-1 B illustrates.
cell body (soma) Core region of the cell containing the nucleus and
other organelles for making proteins.
dendrite Branching extension of a neuron’s cell membrane; greatly
increases the cell’s surface area; collects information from other
cells.
axon Root, or single fiber, of a neuron that carries messages to other
neurons.
FIGURE 3-2 Basic Structure of a Neuron Dendrites gather information from
other neurons, the cell body (soma) integrates the information, and the axon sends the
information to other cells. Although a neuron may have many dendrites, it has only one
axon.

The human nervous system contains 86 billion neurons (Herculano-

Houzel et al., 2014). How can 86 billion cells cooperate, make
connections, and produce behavior? Fortunately, neurons have a common
plan: examining how one neuron works offers insights that we can
generalize to other neuron types. As you learn to recognize different types
of nervous system cells, you will begin to understand how their
specialized structures contribute to their functions in your body.

Neurons: The Basis of Information

Processing
As the information-processing units of the nervous system, neurons
acquire information, interpret it, and pass the information along to other
neurons that initiate a behavior. In engaging in this activity, neurons also
encode memories and produce our thoughts and emotions. At the same
time, they regulate body processes such as breathing, heartbeat, and body
temperature, to which we seldom give a thought.
Some scientists think that a specific function can be assigned to an
individual neuron. For example, many birds learn to sing during the
breeding season, and this learning is associated with the seasonal
development of new neurons (Bertram et al., 2014). To produce most
behaviors in most species, however, scientists think that neurons work
together in groups of many hundreds to many thousands. It is important,
then, to understand not only how neurons function but also how they
interconnect and influence one another.
Functional groups of neurons, or neural networks, connect wide areas
of the brain and spinal cord. The loss of a neuron or two from a network
is no more noticeable than the loss of one or two voices from a cheering
crowd. It is the crowd that produces the overall sound, not each person. In
much the same way, although neuroscientists call neurons the
information-processing units of the brain, they really mean that neural
networks serve this function. An ongoing effort aims to map the structural
connectivity—the physical wiring, or connectome —of the entire human
brain.
 neural network Functional group of neurons that connects wide
areas of the brain and spinal cord.
connectome Comprehensive map of all structural connectivity (the
physical wiring) in an organism’s nervous system.
Scientists also speak informally about a particular neuron’s structure as
if that structure never changes. But neurons are the essence of plasticity.
If you view fresh brain tissue through a microscope, the neurons reveal
themselves to be surprisingly active, producing new branches, losing old
ones, and making and losing connections with each other as you watch.
This dynamic activity underlies both the constancies and the changes in
our behavior.
Another important property of most neurons is their longevity. At a
few locations in the human nervous system, ongoing production of new
neurons does take place throughout life, and some behavior does depend
on the production of new neurons. But most of our CNS neurons are with
us for life. Although they change, they are not replaced when lost. For
this reason, if the brain or spinal cord is damaged, functional recovery is
often poor. In some nonhuman animal species, neurons can be replaced.
The variability in neuronal longevity and replacement are important
properties to scientists who study diseases of aging, disorders associated
with age-related changes in the nervous system, and diseases or injuries
that damage the nervous system.
Structure and Function of the Neuron
Figure 3-3 on page 78 details the external and internal features common
to neurons. The cell’s surface area is increased immensely by its
extensions into dendrites and an axon (Figure 3-3 A and B). The dendritic
area is further increased by many small protrusions called dendritic
spines (Figure 3-3C ). A neuron may have up to 20 dendrites, each may
have one to many branches, and the spines on the branches may number
in the thousands. Dendrites collect information from other cells, and the
spines are the points of contact with those neurons. The extent of a cell’s
branches and its spine number correspond to its information-processing
capacity.
dendritic spine Protrusion that greatly increases the dendrite’s
surface area; typical point of dendritic contact with the axons of other
cells.
 Each neuron has but a single axon to carry messages to other neurons.
The axon begins at one end of the cell body at an expansion known as the
axon hillock (little hill), shown in Figure 3-3 D. The axon may branch
out into one or many axon collaterals, which usually emerge from it at
right angles, as shown at the bottom of Figure 3-3 B.
axon hillock Juncture of soma and axon.
axon collateral Branch of an axon.
The axon’s lower tip may divide into multiple smaller branches
(telodendria, or end branches). At the end of each telodendrion is a knob
called an end foot, or terminal button. The terminal button sits very
close to but usually does not touch a dendritic spine or some other part of
another cell (Figure 3-3C ). This near-connection, called a synapse,
includes the surfaces of the end foot and the neighboring dendritic spine
as well as the space between them. The synapse is the information
transfer site between neurons.
terminal button (end foot) Knob at the tip of an axon that conveys
information to other neurons.
synapse Spatial junction between one neuron and another; forms the
information transfer site between neurons.
(A)
Ian Whishaw
FIGURE 3-3 Major Parts of a Neuron (A) Typical neuron Golgi-stained to reveal
its dendrites and cell body. (B) The neuron’s basic structures identified. (C) An electron
micrograph captures the synapse between an axon from another neuron and a dendritic
spine. (D) High-power light microscopic view inside the cell body. Note the axon hillock at
the junction of the soma and axon.
Ian Whishaw

Chapter 4 describes how neurons transmit information; here, we

simply generalize about neuronal function by examining shape. Imagine
looking down on a river system from an airplane. You see many small
streams merging to make creeks, which join to form tributaries, which
join to form the main river channel. As the river reaches its delta, it
breaks up into many smaller channels again before discharging its
contents into the sea.
The general shape of a neuron suggests that it works in a broadly
similar way to a river. As illustrated in Figure 3-4 , the neuron collects
information from many sources on its dendrites. It channels the
information to its axon, which can send out only a single message. The
eventual branching of the axon then allows the message to be sent to
many targets.
FIGURE 3-4 Information Flow Through a Neuron
Three Functions of Neurons
Neurons of varying shapes and sizes are structured to perform specialized
functions. Sensory neurons (Figure 3-5 A ) conduct information from
the sensory receptors in or on the body into the spinal cord and brain.
Interneurons (Figure 3-5 B) associate sensory and motor activity in the
CNS, and motor neurons (Figure 3-5C ) carry information from the brain
and spinal cord out to the body’s muscles.
sensory neuron Cell that detects or carries sensory information into
the spinal cord and brain.
interneuron Association cell interposed between a sensory neuron
and a motor neuron; in mammals, interneurons constitute most of the
brain’s neurons.
motor neuron Cell that carries efferent information from the brain
and spinal cord to make muscles contract.
(A) Sensory neurons
Bring information to the central nervous system
(B) Interneurons
Associate sensory and motor activity in the central nervous system

(C) Motor neurons

Send signals from the brain and spinal cord to muscles

FIGURE 3-5 Neuron Shape and Function (A) Sensory neurons

of many types detect stimulation or collect information and pass it on to (B)
an interneuron. The multibranched interneuron dendrites collect information
from varied sources and link to (C) motor neurons, which are distinctively
 large and which pass on commands to muscles to move. Cells are not
drawn to scale.

SENSORY NEURONS Sensory neurons are the simplest structurally. A

bipolar neuron found in the retina of the eye, for example, has a single
short dendrite on one side of its cell body and a single short axon on the
other side. Bipolar neurons transmit afferent (incoming) sensory
information from the retina’s light receptors to the neurons that carry
information into the brain’s visual centers.
bipolar neuron Sensory neuron with one axon and one dendrite.
A bit more structurally complicated is the somatosensory neuron,
which brings sensory information from the body into the spinal cord, a
long distance. Structurally, the somato-sensory dendrite connects directly
to its axon, so the cell body sits to one side of this long pathway.
somatosensory neuron Brain cell that brings sensory information
from the body into the spinal cord.
INTERNEURONS Also called association cells because they link up
sensory and motor neurons, interneurons branch extensively, the better to
collect information from many sources. Animals with large brains have
more interneurons, and their interneurons have more branches, than those
of small-brained animals. A specific type of interneuron, the stellate (star-
shaped) cell, is characteristically small, with many dendrites extending
around the cell body. Its axon is difficult to see in the maze of dendrites.
A pyramidal cell has a long axon, a pyramid-shaped cell body, and
two sets of dendrites. The apical set projects from the cell body apex, the
basal set from the base of its cell body. Pyramidal interneurons carry
information from the cortex to the rest of the brain and spinal cord. A
Purkinje cell (named for its discoverer) is a distinctive interneuron with
extremely branched dendrites that form a fan shape. It carries information
from the cerebellum to the rest of the brain and spinal cord.
pyramidal cell Distinctively shaped interneuron found in the
cerebral cortex.
Purkinje cell Distinctively shaped interneuron found in the
cerebellum.
MOTOR NEURONS To collect information from many sources, motor
neurons have extensive dendritic networks, large cell bodies, and long
axons that connect to muscles. Motor neurons reside in the lower
brainstem and spinal cord. All efferent (outgoing) neural information
must pass through them to reach the muscles.
Neuronal Networks
Sensory neurons collect afferent (incoming) information from the body
and connect to interneurons that process the information and pass it on to
motor neurons. The motor neurons’ efferent connections move muscles
and so produce behavior. These three organizational aspects of neurons
are thus features of neuronal networks: input, association, and output.
Neurons that project for long distances, such as somatosensory
neurons, pyramidal neurons, and motor neurons, are relatively large. In
general, neurons with a large cell body have long extensions, whereas
neurons with a small cell body, such as stellate interneurons, have short
extensions.
Long extensions carry information to distant parts of the nervous
system; short extensions are engaged in local processing. For example,
the dendrite tips of some somatosensory neurons are in your big toe,
whereas the target of their axons is at the base of your brain. These
sensory neurons send information over as much as 2 meters, even more in
very large animals. The axons of some pyramidal neurons must reach
from the cortex as far as the lower spinal cord, a distance that can be as
long as a meter. The imposing size of this pyramidal cell body therefore
accords with the work it must do in providing nutrients and other cellular
supplies for its axons and dendrites.
The Language of Neurons: Excitation and Inhibition
Neurons are networkers with elaborate interconnections, but how do they
communicate? Simply put, neurons either excite other neurons (turn them
on) or inhibit other neurons (turn them off). Like digital computers,
neurons send yes or no signals to one another; the yes signals are
excitatory, and the no signals are inhibitory. Each neuron receives up to
thousands of excitatory and inhibitory signals every second.
The neuron’s response to all those inputs is reasonably democratic: it
sums them. A neuron is spurred into action and sends messages to other
neurons if its excitatory inputs exceed its inhibitory inputs. If the reverse
occurs and inhibitory inputs exceed excitatory inputs, the neuron does not
communicate.
Principle 10: The nervous system works by juxtaposing excitatory
and inhibitory signals. Section 4-3 explains how neurons summate
 excitatory and inhibitory signals.
By exciting or inhibiting one another, a neuronal network can detect
sensory information and “decide” what kind of motor response to make to
that information. To confirm whether they understand how an entire
neural network produces behavior, scientists might make a model, such as
a robot, intended to function in the same way. Robots, after all, engage in
goal-oriented actions, just as animals do. A robot’s computer must
somehow sense the world, coordinate its actions in response, and perform
much as an animal’s nervous system performs.
Constructing humanlike machines is one scientific objective of
artificial intelligence (AI) research. Barbara Webb’s cricket robot,
constructed from Lego blocks, wires, and a motor ( Figure 3-6 , left), is
designed to mimic a female cricket, which listens for the source of a
male’s chirping song and travels to it (Reeve et al., 2007). This is the
beginning step in constructing intelligent robots (Figure 3-6 , right).
 James King-Holmes/Science Photo Library

Nervous System Mimics Left: Barbara Webb programmed rules

FIGURE 3-6
she developed from studying cricket behavior into her Lego cricket robot. Right: Social
roboticist Heather Knight conducts research on robot body language with her companion,
Marilyn Monrobot.
Kike Calvo via AP Images

In approaching a male, a female cricket must avoid open, well-lit

places where a predator could detect her. The female must often choose
between competing males, preferring, for example, the male that makes
the longest chirps. All of these behaviors must be wired into a successful
cricket robot, making sure that one behavior does not interfere with
another. In simulating cricket behavior in a robot, Webb is duplicating the
rules of a cricket’s nervous system, which are programmed by its genes.
The Procedure sections of Experiment 3-1 illustrate some ways that
neural inhibition and excitation might produce the cricket robot’s
behavior. The Results section confirms that this hypothetical arrangement
mimics the functions of sensory and motor neurons and the principle of
summating excitatory and inhibitory signals—but with only six neurons
and each neuron connected to only one other neuron! Today,
anthropomimetic robots, so-called because their parts are constructed to
mimic the parts of a human body, including its billions of neurons, are
being designed to model complex behavior (Wittmeier et al., 2013).

Five Types of Glial Cells

Another group of nervous system cell aids neurons in processing
information. Glial cells (from the Greek for glue ) are the nervous
system’s support cells. The human brain’s estimated 87 billion glial cells
reflect the typical nervous system ratio of roughly 1:1 between neurons
and glial cells (Herculano-Houzel et al., 2014). Although they do not
transmit information themselves, glial cells help neurons carry out this
task, binding them together (some do act as glue) and providing support,
nutrients, and protection, among other functions.
glial cell Nervous system cell that provides insulation, nutrients, and
support and that aids in repairing neurons and eliminating waste
products.
 EXPERIMENT 3-1

Question: Can the principles of neural excitation and

inhibition control the activity of a simple robot?
Procedure A
If we insert sensory neurons between the microphone for sound
detection on each side of this hypothetical robot and the motor on the
opposite side, we need only two rules to instruct the female robot to
seek out a chirping male cricket.

Rule 1 When a microphone detects a male cricket’s song, an excitatory

message is sent to the opposite wheel’s motor, activating it so the robot
turns toward the cricket.
Rule 2 If the chirp is coming from the robot’s left side, it will be
detected as being louder by the microphone on the left, which will
make the right wheel turn a little faster, swinging the robot to the left.
Procedure B
We add two more sensory neurons, coming from photoreceptors on the
robot. When activated, these light-detecting sensory neurons inhibit the
motor neurons leading to the wheels and prevent the robot from
moving toward a male cricket. Now the female cricket robot will move
only when it is dark and “safe.”
 Result
This hypothetical arrangement illustrates the biological function of
sensory and motor neurons and the neural principle of summating
excitatory and inhibitory signals.
Conclusion: A simple robot will operate on the principles of neural
excitation and inhibition. More neurons are necessary to make the
robot more “intelligent.”

Glia form the fatty coverings around neurons—the white matter in

brain images such as Figure 2-12 B and D.
Table 3-1 lists the five major types of glia along with their
characteristic structures and functions. Glial cells are different from
neurons in that new glial cells are produced, and errors in replication can
result in abnormal growths: brain tumors. Clinical Focus 3-3 , Brain
Tumors, describes the results of such uncontrolled glial cell growth.
Ependymal Cells
On the walls of the ventricles, the fluid-filled cavities inside your brain,
are ependymal cells, which produce and secrete the cerebrospinal fluid
that fills the ventricles. CSF is constantly being secreted, and it flows
through the ventricles toward the base of the brain, where it is absorbed
into the blood vessels. CSF serves several purposes. It acts as a shock
absorber when the brain is jarred, carries away waste products, assists
the brain in maintaining a constant temperature, and is a source of
nutrients for parts of the brain adjacent to the ventricles.
ependymal cell Glial cell that makes and secretes CSF; found on
the walls of the brain’s ventricles.
As CSF flows through the ventricles, it passes through some narrow
passages, especially from the cerebral aqueduct into the fourth ventricle,
which runs through the brainstem. If these passages are fully or partly
blocked, fluid flow is restricted. Because CSF is continuously being
produced, this blockage causes a buildup of pressure that begins to
expand the ventricles, which in turn push on the surrounding brain.
Figure 2-9 shows the location of the cerebral aqueduct and the four
ventricles.
If such a blockage develops in a newborn infant, before the skull
bones are fused, the pressure on the brain is conveyed to the skull, and
the baby’s head swells. This condition, called hydrocephalus (literally,
water brain ), can cause severe intellectual impairment, even death. To
treat it, doctors insert one end of a tube, called a shunt, into the blocked
ventricle and the other end into a vein, allowing excess CSF to drain into
the bloodstream.
hydrocephalus Buildup of fluid pressure in the brain and, in infants,
swelling of the head, if the flow of CSF is blocked; can result in
intellectual impairment.
TABLE 3-1 Types and Functions of Glial Cells
CLINICAL FOCUS 3-3

Brain Tumors
One day while watching a movie in a neuropsychology class, R. J., a
19-year-old college sophomore, collapsed on the floor, displaying
symptoms of a seizure. The instructor helped her to the university
clinic, where she recovered except for a severe headache. She
reported that she had repeated severe headaches.
A few days later, a computed tomography (CT) scan showed a
tumor over her left frontal lobe. The tumor was removed surgically,
and R. J. returned to classes after an uneventful recovery. Her
symptoms have not recurred.
A tumor is an uncontrolled growth of new tissue that is
independent of surrounding structures. No region of the body is
immune, but the brain is a site for the more than 120 kinds of
tumors. They are a common cause of brain cancer in children.
tumor Mass of new tissue that grows uncontrolled and
independent of surrounding structures.
The incidence of brain tumors in the United States is about 20 per
100,000, according to the Central Brain Tumor Registry of the
United States (Quinn et al., 2014). In adults brain tumors grow from
glia or other supporting cells rather than from neurons, but in infants,
tumors may grow from developing neurons. Rate of tumor growth
depends on the type of cell affected.
Some tumors are benign, as R. J.’s was, and not likely to recur
after removal. Others are malignant, likely to progress, to invade
other tissue, and apt to recur after removal. Both kinds can pose a
risk to life if they develop in sites from which they are difficult to
remove.
The earliest symptoms usually result from increased pressure on
surrounding brain structures. They can include headaches, vomiting,
mental dullness, changes in sensory and motor abilities, and seizures
such as R. J. had. Many symptoms depend on the tumor’s location.
The three major types of brain tumors are classified according to
how they originate:
1. Gliomas arise from glial cells. They are slow growing, not often
malignant, and relatively easy to treat if they arise from astrocytes.
Gliomas that arise from the precursor blast or germinal cells that
grow into glia are more often malignant, grow more quickly, and
often recur after treatment. U.S. Senator Edward Kennedy was
diagnosed with a malignant glioma in 2008 and died a year later.
As with R. J., his first symptom was an epileptic seizure.
2. Meningiomas, such as R. J.’s, attach to the meninges and so grow
entirely outside the brain, as shown in the accompanying CT scan.
These tumors are usually encapsulated (contained), and if the
tumor is accessible to surgery, chances of recovery are good.
3. Metastatic tumors become established when cells from one region
of the body transfer to another area (which is what metastasis
means). Typically, metastatic tumors are present in multiple
locations, making treatment difficult. Symptoms of the underlying
condition often first appear when the tumor cells reach the brain.

Dept. of Clinical Radiology, Salisbury District Hospital/Science Photo

Library/Science Source
 The red area in this false-color CT scan is a meningioma, a
noncancerous tumor arising from the meninges, which cover the
brain. Large meningiomas may compress the brain but usually
do not invade brain tissue.

Treatment for brain tumors is usually surgical, and surgery also

remains a main diagnostic tool. Chemotherapy is less successful in
treating brain tumors than tumors elsewhere in the body, because the
blood–brain barrier blocks the chemicals’ entry. Radiation therapy
(X-ray treatment) is more useful for destroying brain tumor cells.
Nevertheless, radiation has negative effects especially on the
developing brain and chemotherapy can affect brain function, a
condition referred to as Chemo Brain.
Recent approaches to treating brain tumors exploit biochemical
differences between tumors and healthy tissue, for example to
visualize a tumor for surgical removal. Chlorotoxin, a scorpion
venom that selectively binds to chloride channels in tumor cell
membranes, combined with a fluorescent dye, forms a tumor paint
(Butte et al., 2014). Injected into a vein, the paint crosses the blood–
brain barrier and coats a tumor, which then glows when exposed to
light in near-infrared wavelengths. Human trials began in 2015.
Nonsurgical tumor removal might also replace or aid
chemotherapy and radiation therapy. It combines chlorotoxin with a
poison to form a drug that kills tumor cells (Wang and Guo, 2015).

Astroglia
Astrocytes (star-shaped glia, shown in Table 3-1 ), also called astroglia,
provide structural support to the CNS. Their extensions attach to blood
vessels and to the brain’s lining, forming a scaffolding that holds neurons
in place. These same extensions provide pathways for certain nutrients to
move between blood vessels and neurons. Astrocytes also secrete
chemicals that keep neurons healthy and help them heal if injured.
astrocyte Star-shaped glial cell that provides structural support to
CNS neurons and transports substances between neurons and blood
vessels.
At the same time, astrocytes contribute to the structure of a protective
partition between blood vessels and the brain, the blood–brain barrier.
As shown in Figure 3-7 , the end feet of astrocytes attach to blood vessel
cells, causing the vessels to bind tightly together. These tight junctions
prevent an array of substances, including many toxins, from entering the
brain through the blood vessel walls.
blood–brain barrier Tight junctions between the cells that
compose blood vessels in the brain, providing a barrier to the entry
of an array of substances, including toxins, into the brain.

FIGURE 3-7 Blood–Brain Barrier Astrocyte processes attach to

neurons and to blood vessel cells to stimulate them to form tight junctions
and so form the blood–brain barrier. Astrocytes also move nutrients and
other chemicals between blood vessels and neurons, support brain
structures, and stimulate repair of damaged brain tissue.

The molecules (smallest units) of these substances are too large to

pass between the blood vessel cells unless the blood–brain barrier is
somehow compromised. The downside is that many useful drugs,
including antibiotics used to treat infections cannot pass through the
blood–brain barrier to enter the brain. As a result, brain infections are
very difficult to treat. Scientists can bypass the blood–brain barrier and
introduce drugs into the brain by inserting small tubes that allow the
delivery of a drug directly to a targeted brain region.
Yet another important function of astrocytes is to enhance brain
activity. When you engage in any behavior, whether it’s reading or
running, the neuronal network responsible for that behavior requires
more fuel in the form of oxygen and glucose. In response to neuron
activity, the blood vessels that supply it expand, allowing greater
oxygen- and glucose-carrying blood flow. What triggers the blood
vessels to dilate? This is where astrocytes come in. They receive signals
from the neurons, pass them on to the blood vessels, and so contribute to
increased blood flow and fuel supply (Rosenegger and Gordon, 2015).
Astrocytes also contribute to healing damaged brain tissue. If the
brain is injured by a blow to the head or penetrated by some object,
astrocytes form a scar to seal off the damaged area. Although the scar
tissue is beneficial in healing the injury, it can also act as a barrier to the
regrowth of damaged neurons. One experimental approach to repairing
brain tissue seeks to get the axons and dendrites of CNS neurons to grow
around or through a glial scar.
Microglia
Unlike other glial cells, which originate in the brain, microglia originate
in the blood as an offshoot of the immune system and migrate throughout
the nervous system, where they make up about 20% of all glial cells. The
brain is largely immune privileged, because the blood–brain barrier
prevents most immune system cells from entering. Microglia monitor the
health of brain tissue and play the role of its immune system. They
identify and attack foreign tissue, as illustrated in Figure 3-8 . When
brain cells are damaged, microglia invade the area to provide growth
factors that aid in repair.
microglia Glial cells that originate in the blood, aid in cell repair,
and scavenge debris in the nervous system.
Growth factors, described Section 8-2 , are chemicals that stimulate
and support growth, survival, and perhaps even brain cell plasticity
(see Section 14-4 ).
There are several kinds of microglia, which take different shapes
depending upon the role they are performing. Microglia engulf any
foreign tissue and dead brain cells, an immune process called
phagocytosis. When full they take on a distinctive appearance. The
stuffed and no-longer-functioning microglia can be detected as small
dark bodies, shown in Figure 3-8C , in and near damaged brain regions.
Because microglia are frontline players in protecting the nervous
system and removing its waste, considerable research is directed toward
the extent to which microglia are involved in protecting the nervous
system from disease. A characteristic of Alzheimer disease, the
degenerative brain disorder commonly associated with aging, is the
deposit of distinctive bodies called plaques in regions of damage.
Microglia may also play a harmful role, consuming inflamed tissue
rather than protecting it. They also interact with astrocytes in brain
healing. Although small, as their name suggests, microglia play a mighty
role in maintaining the brain’s health (Casano & Peri, 2015).
(A)

(B)
(C)
 Ian Whishaw

FIGURE 3-8 Detecting Brain Damage (A) Arrows indicate the red nucleus in a
rat brain. (B) Close-up of cresyl violet–stained neurons, the large dark bodies, in the
healthy red nucleus. (C) After exposure to a neurotoxin, only microglia, the small dark
objects in the micrograph, survive.

More on understanding and treating Alzheimer disease in Section

16-3 .
Oligodendroglia and Schwann Cells
Two kinds of glial cells insulate neuronal axons. Like the plastic
insulation on electrical wires, myelin prevents adjacent neurons from
short-circuiting. Myelinated neurons send information much faster than
neurons without myelin. Neurons that send messages over long distances
quickly, including sensory and motor neurons, are heavily myelinated to
increase their messaging speed.
 myelin Glial coating that surrounds axons in the central and
peripheral nervous systems; prevents adjacent neurons from short-
circuiting.
Section 4-2 , describes how myelin speeds up the neuron’s
information flow. Focus 4-2 describes effects of myelin damage.
Oligodendroglia myelinate axons in the brain and spinal cord by
sending out large, flat branches that enclose and separate adjacent axons
(the prefix oligo - means few and here refers to the fact that these glia
have few branches in comparison with astrocytes; see Table 3-1 ).
Schwann cells myelinate axons in the PNS. Each Schwann cell wraps
itself repeatedly around a part of an axon, forming a structure somewhat
like a bead on a string. In addition to myelination, Schwann cells and
oligodendroglia contribute to a neuron’s nutrition and functioning by
absorbing chemicals that the neuron releases and releasing chemicals
that the neuron absorbs.
oligodendroglia Glial cells in the CNS that myelinate axons.
Schwann cell Glial cell in the PNS that myelinates sensory and
motor axons.
Glial Cells and Neuron Repair
The multifaceted relations among neurons and glia provide insights into
nervous system diseases and into brain injury and recovery from brain
injury. Diseases that damage myelin impair a neuron’s ability to send
information. The consequences of damage to oligodendroglia and
Schwann cells can be as debilitating as damage to neurons themselves.
Damage to areas rich in neuron cell bodies can also be different from
damage to fiber pathways, because pathway damage includes both
neurons and myelin cells.
Glia can also aid in nervous system repair. A deep cut on your body—
on your arm or leg for instance—may cut the axons connecting your
spinal cord to muscles and to sensory receptors. Severing of motor
neuron axons will render you unable to move the affected part of your
body, whereas severing of sensory fibers will result in loss of sensation
from that body part. Cessation of both movement and sensation is
paralysis. Weeks to months after motor and sensory axons are severed,
movement and sensation will return. What mediates this recovery?
 paralysis Loss of sensation and movement due to nervous system
injury.
Both microglia and Schwann cells participate in repairing damage to
the peripheral nervous system. When a PNS axon is cut, it dies back to
the cell body, as shown at the top of Figure 3-9 . Microglia remove all of
the debris left by the dying axon. Meanwhile, the Schwann cells that
provided the axon’s myelin shrink and divide to form numerous smaller
glial cells along the path the axon formerly took. The cell body then
sends out axon sprouts that search for and follow the path formed by the
Schwann cells.
Eventually, one sprout reaches the intended target and becomes the
new axon; all other sprouts retract. The Schwann cells envelop the new
axon, forming new myelin and restoring function. In the PNS, then,
Schwann cells serve as signposts to guide axons to their appropriate end
points. Axons can get lost, however, as sometimes happens after
surgeons reattach a severed limb. If axons destined to innervate one
finger end up innervating another finger instead, the wrong finger will
move when a message is sent along that axon.

1 When a peripheral axon is cut, the axon dies.

2 Schwann cells first shrink and then divide, forming glial cells along the
axon’s former path.
3 The neuron sends out axon sprouts, one of which finds the Schwann-
cell path and becomes a new axon.
4 Schwann cells envelop the new axon, forming new myelin.
 FIGURE 3-9 Neuron Repair Schwann cells aid the regrowth of axons
in the somatic nervous system.

Sections 11-1 and 11-4 detail causes of and treatments for spinal
cord injury.
When the CNS is damaged, as happens, for example, when the spinal
cord is cut, regrowth and repair do not occur, even though the distance
that damaged fibers must bridge is short. The oligodendrocytes that
myelinate CNS cells do not behave like PNS Schwann cells to encourage
brain repair. They may actually play a role in inhibiting neuron regrowth
(Rusielewicz et al., 2014). That recovery should take place in the PNS
but not in the CNS is puzzling. Regrowth in the CNS may not occur in
part because as neuronal circuits mature, they become exquisitely tuned
to mediate individualized behavior and so are protected from the
proliferation of new cells or the regrowth of existing cells.
 3-1 REVIEW
Cells of the Nervous System
Before you continue, check your understanding.
1 . The two classes of nervous system cells are ___________, which in
humans number around ___________, and ___________, which in
humans number about ___________, reflecting the typical ratio.
2 . Neurons, the information-conducting units of the nervous system, act
either by ___________ or by ___________ one another through their
connecting synapses.
3 . The three types of neurons and their characteristic functions are
___________, which ___________; ___________, which
___________; and ___________, which ___________.
4 . The five types of glial cells are ___________, ___________,
___________, ___________, and ___________. Their functions
include ___________, ___________, ___________, ___________,
and ___________ neurons.
5 . What is the main obstacle to producing a robot with all of the
behavioral abilities displayed by a mammal?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 3-2 Internal Structure of a Cell
What is it about the structure of neurons that generates the remarkable
ability to receive, process, store, and send a seemingly limitless amount
of information? To answer this question, we must look inside a neuron to
see what its components are and understand what they do. Although
neurons are minuscule, when we view them with an electron microscope,
we find packed inside hundreds of interrelated parts that do the cell’s
work.
To a large extent, a cell’s proteins determine its characteristics and
functions. Each cell can manufacture thousands of proteins, which
variously take part in building the cell and in communicating with other
cells. When a neuron malfunctions or contains errors, proteins are
implicated and so are involved in many kinds of brain disease. In this
section, we explain how the different parts of a cell contribute to protein
manufacture, describe what a protein is, and detail some functions of
proteins.
Water, salts, and ions play prominent parts in the cell’s functions, as
you will learn in this and the next few chapters. If you already
understand the structure of water and you know what a salt is and what
ions are, read on. If you prefer a brief chemistry review first, turn to The
Basics: Chemistry Review, on pages 88 –89 .

The Cell as a Factory

We began Section 3-1 by comparing a cell to a miniature factory, with
work centers that cooperate to make and ship the cell’s products—
proteins. To investigate the cell’s internal parts—the organelles—and
how they function, we begin with a quick overview of the cell’s internal
structure.
Figure 3-10 displays many external and internal cellular components.
A factory’s outer wall separates it from the rest of the world and affords
some security. Likewise, a cell’s double-layered outer wall, or cell
membrane, separates the cell from its surroundings and allows it to
regulate what enters and leaves its domain. The cell membrane
envelopes the neuron’s contents and contributes to forming its cell body,
its dendrites and their spines, and its axon and terminals. It thus forms
the boundary around a continuous intracellular compartment.
 Very few substances can enter or leave a cell spontaneously, because
the cell membrane is virtually impermeable (impenetrable). Some
proteins made by the cell are embedded in the cell membrane, where
they facilitate the transport of substances into and out of the cell. These
proteins thus serve as the cellular factory’s gates.

FIGURE 3-10Typical Nerve Cell This view of the outside and inside
of a neuron reveals its overall structure and internal organelles and other
components.
 THE BASICS

Chemistry Review
The smallest unit of a protein or any other chemical substance is the
molecule. Molecules and the even smaller atoms of elements that
constitute them are the cellular factory’s raw materials.
Elements, Atoms, and Ions
Chemists represent each element, a substance that cannot be broken
down into another substance, by a symbol—for example, O for
oxygen, C for carbon, and H for hydrogen. The 10 elements listed
below in the table Chemical Composition of the Brain constitute
virtually the entire makeup of an average living cell. Many other
elements are vital to the cell but present only in minute quantities.
The smallest quantity of an element that retains the properties of
that element is an atom. Ordinarily, as shown opposite in part A of
the figure Ion Formation, atoms are electrically neutral: their total
positive and negative charges are equal.
Atoms of chemically reactive elements such as sodium and
chlorine can easily lose or gain negatively charged particles, or
electrons. When an atom gives up electrons, it becomes positively
charged; when it takes on extra electrons, it becomes negatively
charged, as illustrated in part B of Ion Formation. Either way, the
charged atom is now an ion. Ions’ positive or negative charges
allow them to interact. This property is central to cell function.
Chemical Composition of the Brain
Ions Critical to Neuronal Communication

(A) Atoms
Ion Formation
 Total positive (+) and negative (–) charges in atoms are equal.
The nucleus contains neutrons (no charge) and protons (positive
charge). Orbiting the nucleus are electrons (negative charge).

Molecules: Salts and Water

Salt crystals form bonds via the electrical attraction between ions.
The formula for table salt, NaCl (sodium chloride), means that this
molecule consists of one sodium ion and one chloride ion. KCl, the
formula for the salt potassium chloride, is composed of one
potassium ion (K+ ) and one chloride ion (Cl– ).
Atoms bind together to form molecules, the smallest units of a
substance that contain all of its properties. A water molecule (H2 O)
is the smallest unit of water that retains the properties of water.
Breaking down water any further would release its component
elements, the gases hydrogen and oxygen. The symbol H2 O
indicates that a water molecule is the union of two hydrogen atoms
and one oxygen atom.
Ionic bonds hold salt molecules together, but the atoms of water
molecules share electrons and electron sharing is not equal: H
electrons spend more time orbiting the O atom than orbiting each H
atom. As shown above in part A of Chemistry of Water, this
structure gives the oxygen region of the water molecule a slight
negative charge and leaves the hydrogen regions with a slight
positive charge. Like atoms, most molecules are electrically neutral,
but water is polar: it carries opposite charges on opposite ends, just
as Earth does at the North and South Poles.
(A) Water molecule
(B) Hydrogen bonds
 Chemistry of Water

Because water molecules are polar, they are attracted to other

electrically charged substances and to one another. Part B of
Chemistry of Water illustrates this attracting force, called a
hydrogen bond. Hydrogen bonding enables water to dissolve
electrically neutral salt crystals into their component ions. Salts thus
cannot retain their shape in water: they dissolve. As illustrated in
the figure Salty Water, the polar water molecules muscle their way
into the Na+ and Cl– lattice, surrounding and separating the ions.
Essentially, it is salty water that bathes our brain cells, provides
the medium for their activities, supports their communications, and
constitutes the brain’s CSF. Sodium chloride and many other
dissolved salts, including KCl (potassium chloride) and CaCl2
(calcium chloride) are among the constituents of the brain’s salty
water.
 Salty Water

Although neurons and glia appear to be packed tightly together, like

all cells, they are separated by extracellular fluid composed mainly of
water with dissolved salts and many other chemicals. A similar
intracellular fluid is found inside a cell. What’s important is the cell
membrane’s relative impermeability, which ensures that concentrations
of substances inside and outside the cell are different.
In the CNS, the extracellular fluid is CSF.
Within the cell shown in Figure 3-10 are membranes that surround its
organelles, similar to the work areas demarcated by a factory’s interior
walls. Each organelle membrane is also relatively impermeable and so
concentrates needed chemicals while keeping out unneeded ones.
The prominent nuclear membrane surrounds the cell’s nucleus.
Within the nucleus the genetic blueprints for the cell’s proteins are
stored, copied, then sent to the “factory floor,” the endoplasmic
reticulum. The ER is an extension of the nuclear membrane, and here the
cell’s protein products are assembled in accordance with instructions
from the nucleus. Once those proteins are assembled, many are packaged
and sent throughout the cell. The Golgi bodies are “mailrooms,” where
proteins are wrapped, addressed, and shipped.
Other cell components are tubules of several kinds. Some
(microfilaments ) reinforce the cell’s structure; others aid in the cell’s
movements. Still others (microtubules) form the transportation network
that carries proteins to their destinations, much as roads allow a factory’s
trucks and forklifts to deliver goods to their destinations.
Two other important parts of the cellular factory shown in Figure 3-10
are the mitochondria (sing. mitochondrion ), the cell’s power plants,
which supply its energy needs, and lysosomes, vesicles that transport
incoming supplies and remove and store wastes. Interestingly, more
lysosomes are found in old cells than in young ones. Cells apparently
have trouble disposing of all of their garbage, just as societies do.

Cell Membrane: Barrier and Gatekeeper

The cell membrane separates the intracellular from the extracellular
fluid, allowing the cell to function as an independent unit. The
membrane’s double-layered structure, shown in Figure 3-11 A ,
regulates the movement of substances into and out of the cell. One
regulated substance is water. If too much water enters a cell, it will burst;
if too much water leaves a cell, it will shrivel. The cell membrane’s
structure helps ensure that neither happens.

FIGURE 3-11 Bilayer Cell Membrane Structure (A) Double-

layered cell membrane close up. (B) Detail of a phospholipid molecule’s
polar head and electrically neutral tails. (C) Space-filling model shows why
the phosphate head’s polar regions (positive and negative poles) are
hydrophilic, whereas its nonpolar fatty acid tail is hydrophobic.

The cell membrane also regulates the differing concentrations of salts

and other chemicals on its inner and outer sides. This regulation is
important because, if its concentrations of chemicals are unbalanced, the
cell will not function normally. What properties of a cell membrane
allow it to regulate water and salt concentrations? One property is its
special molecular construction. These molecules, called phospholipids,
are named for their structure, shown close up in Figure 3-11 B.
Figure 3-11C shows a space-filling chemical model of the
phospholipid molecule’s structure. The molecule has a head containing
the element phosphorus (P) bound to some other atoms, and it has two
tails, which are lipids, or fat molecules. The head has a polar electrical
charge, with a positive charge in one location and a negative charge in
another, as do water molecules. The tails consist of hydrogen and carbon
atoms that tightly bind to one another by their shared electrons; hence,
the fatty tail has no polar regions.
The polar head and the nonpolar tails are the underlying reasons that a
phospholipid molecule can form cell membranes. The heads are
hydrophilic (Greek hydro, meaning water, and philia, meaning love ) and
so are attracted to one another and to polar water molecules. The
nonpolar lipid tails have no such attraction for water. They are
hydrophobic, or water hating (from the Greek word phobia, meaning
fear ).
Quite literally, then, the head of a phospholipid loves water and the
tails hate it. To avoid water, the tails of phospholipid molecules point
toward each other, and the hydrophilic heads align with one another and
point outward to the watery intracellular and extracellular fluid. In this
way, the cell membrane consists of a bilayer (two layers) of phospholipid
molecules (see Figure 3-11 A).
The bilayer cell membrane is flexible even as it forms a formidable
barrier to a wide variety of substances. It is impenetrable to intracellular
and extracellular water, because polar water molecules cannot pass
through the hydrophobic tails on the membrane’s interior. Ions in the
extracellular and intracellular fluid also cannot penetrate this membrane,
because they carry charges and thus cannot pass by the polar
phospholipid heads. In fact, only a few small molecules, such as oxygen
(O2 ), carbon dioxide (CO2 ), and the sugar glucose, can traverse a
phospholipid bilayer.

The Nucleus and Protein Synthesis

In our factory analogy, the nucleus is the cell’s executive office, where
the blueprints for making proteins are stored, copied, and sent to the
factory floor. These blueprints are called genes, segments of DNA that
encode the synthesis of particular proteins. Genes are contained within
the chromosomes, the double-helix structures that hold an organism’s
entire DNA library.
gene DNA segment that encodes the synthesis of a particular
protein.
The chromosomes have been likened to a book of blueprints. Each
chromosome contains thousands of genes. Each gene is the blueprint, or
code, for making one protein. The location of the chromosomes in the
cell nucleus, the appearance of a chromosome, and the structure of the
DNA within a chromosome are shown in Figure 3-12 .

Chromosome The nerve cell’s nucleus contains paired

FIGURE 3-12
chromosomes of double-stranded DNA molecules bound together by a
sequence of nucleotide bases.

This static picture of chromosomes does not represent the way they
look in living cells. Videos of the cell nucleus show that chromosomes
are constantly changing shape and moving in relation to one another,
jockeying to occupy the best locations within the nucleus. By changing
shape, chromosomes expose different genes to the surrounding fluid,
thus allowing the gene to begin the process of making a protein.
Chromosome means colored body ; they are so named because
chromosomes can be readily stained with certain dyes.
 A human somatic (body) cell has 23 pairs of chromosomes, or 46
chromosomes in all (in contrast, the 23 chromosomes within a
reproductive cell are not paired). Each chromosome is a double-stranded
molecule of deoxyribonucleic acid (DNA). The two strands of a DNA
molecule coil around each other, as shown in Figure 3-12 .
Each strand possesses a variable sequence of four nucleotide bases,
the constituent molecules of the genetic code: adenine (A), thymine (T),
guanine (G), and cytosine (C). Adenine on one strand always pairs with
thymine on the other, whereas guanine on one strand always pairs with
cytosine on the other. The two strands of the DNA helix are bound
together by the attraction between the two bases in each pair, as
illustrated in Figure 3-12 . Sequences of hundreds of nucleotide bases
within the chromosomes spell out the genetic code. Scientists represent
this code by the letters of the nucleotide bases, for example ATGCCG
and so forth.
A gene is a segment of a DNA strand. A gene’s code is its sequence
of thousands of nucleotide bases. Much as a sequence of letters spells out
a word, the sequence of ACTG base pairs spells out the order in which
amino acids, the constituent molecules of proteins, should be assembled
to construct a certain protein. To begin to make a protein, the appropriate
gene segment of the DNA strands first unwinds to expose its bases. The
exposed sequence of nucleotide bases on one of the DNA strands then
serves as a template to attract free-floating molecules called nucleotides.
The nucleotides, once attached, form a complementary strand of
ribonucleic acid (RNA), the single-stranded nucleic acid molecule
required for protein synthesis. This process, called transcription, is
shown in steps 1 and 2 of Figure 3-13 . (To transcribe means to copy, as
in copying part of a message you receive in a text.)
 FIGURE 3-13 Protein Synthesis Information in a cell flows from DNA
to mRNA to protein (peptide chain).

The Endoplasmic Reticulum and Protein

Manufacture
RNA produced through transcription is much like a single strand of
DNA except that the base uracil (U), which also is attracted to adenine,
takes the place of thymine. The transcribed strand of RNA is called
messenger RNA (mRNA) because it carries the protein code (the
message) out of the nucleus to the endoplasmic reticulum, where
proteins are manufactured.
Steps 3 and 4 in Figure 3-13 show that the ER consists of
membranous sheets folded to form numerous channels. A distinguishing
feature of the ER is that it may be studded with ribosomes, protein
structures that act as catalysts to facilitate the building of proteins. When
an mRNA molecule reaches the ER, it passes through a ribosome, where
its genetic code is read. In this process of translation, a particular
sequence of nucleotide bases in the mRNA is transformed into a
particular sequence of amino acids. Transfer RNA (tRNA) assists in
translating nucleotide bases into amino acids.
As shown in Figure 3-14 , each group of three consecutive nucleotide
bases along an mRNA molecule encodes one particular amino acid.
These sequences of three bases are called codons. For example, the
codon uracil, guanine, guanine (UGG) encodes the amino acid
tryptophan (Trp), whereas the codon uracil, uracil, uracil (UUU) encodes
the amino acid phenylalanine (Phe). The sequence of codons on the
mRNA strand determines the sequence of the resulting amino acid chain.

FIGURE 3-14 Transcription and Translation In protein

synthesis (see Figure 3-13 ), a particular sequence of nucleotide bases in
a strand of DNA (top) is transcribed into mRNA (center). Each sequence
of three nucleotide bases in the mRNA strand (a codon) encodes one
amino acid. In translation, the amino acids, directed by the codons, link
together to form a polypeptide chain (bottom). The amino acids are
tryptophan (Trp), phenylalanine (Phe), glycine (Gly), and serine (Ser).

Humans utilize 20 different amino acids, all structurally similar, as

illustrated in Figure 3-15 A . Each consists of a central carbon atom (C)
bound to a hydrogen atom (H), an amino group (NH3+ ), a carboxyl
group (COO– ), and a side chain (represented by the letter R). The side
chain varies in chemical composition from one amino acid to another.
Each amino group (NH3+ ) is bound to the carboxyl group (COO– ) of
the adjacent amino acid by a peptide bond, which gives amino acid
chains their alternative name, polypeptide chain (Figure 3-15 B).
 Just as a remarkable number of words can be made from the 26 letters
of the English alphabet, a remarkable number of polypeptide (meaning
many peptides ) chains can be made from the 20 amino acids. These
amino acids can form 400 (20 × 20) dipeptides (two-peptide
combinations), 8000 (20 × 20 × 20) tripeptides (three-peptide
combinations), and almost countless polypeptides.
In summary, the information flow driven by the genetic code is
conceptually quite simple: a gene (portion of a DNA strand) is
transcribed into a strand of mRNA, and ribosomes translate the mRNA
into a molecular chain of amino acids, a polypeptide chain. Thus the
sequence of events in building a protein:
DNA → mRNA → protein

Proteins: The Cell’s Product

A polypeptide chain and a protein are related, but they are not the same.
The relation is analogous to the relation between a length of ribbon and a
bow that can be made from the ribbon. Long polypeptide chains have a
strong tendency to twist into a helix (a spiral) or to form pleated sheets,
which in turn have a strong tendency to fold together to form more
complex shapes, as shown in Figure 3-16 . A protein is a folded-up
polypeptide chain that serves a particular function in the body.
protein Folded-up polypeptide chain that serves a particular
function in the body.
Any one neuron contains as many as 20,000 genes, and it can, in
principle, produce as many as 20,000 different protein molecules. The
number of proteins that can ultimately be produced by a neuron is far
larger than the number of its genes, however. Although each gene codes
for one protein, a protein can be cleaved into pieces—by enzymes, for
example—or combined with other proteins in a variety of cellular
processes to form still other proteins.
(A) Amino acid structure
(B) Polypeptide chain

FIGURE 3-15 Properties of Amino Acids (A) Each amino acid

consists of a central carbon atom (C) attached to an amine group (NH3+ ),
 a carboxyl group (COO– ), and a distinguishing side chain (R). (B) The
amino acids are linked by peptide bonds to form a polypeptide chain.

FIGURE 3-16Four Levels of Protein Structure Whether a

polypeptide chain forms a pleated sheet or a helix and what its three-
dimensional shape ultimately will be are determined by the amino acid
sequence in the primary structure. In rare circumstances, prion proteins
can misfold and wreak havoc; see Section 16-3 .

A protein’s shape and its ability to change shape and to combine with
other proteins are central to its function. Through their shapes and
changes in shape, proteins can combine with other proteins in chemical
reactions. They can modify the length and shape of other proteins and so
act as enzymes. Proteins embedded in a cell membrane form
passageways called channels, gates, and pumps that regulate the flow of
substances through the membrane. And proteins can be exported through
the axon terminal to travel to other cells and so act as messenger
molecules.

Golgi Bodies and Microtubules: Protein

Packaging and Shipment
Getting proteins to the right destination is the task of cellular
components that package, label, and ship them. These components
operate much like a postal or shipping service.
To reach their appropriate destinations, protein molecules that have
been synthesized in the cell are wrapped in membranes and marked with
addresses to indicate where they are to go. This wrapping and labeling
take place in the organelles called Golgi bodies. The packaged proteins
are then loaded onto motor molecules that move along the many micro-
tubules radiating through the cell, carrying each protein to its destination.
Protein export is illustrated in Figure 3-17 .
If a protein is destined to remain within the cell, it is unloaded into the
intracellular fluid. If it is to be incorporated into the cell membrane, it is
carried to the membrane, where it inserts itself. Some proteins are
expelled from the cell. In this process, called exocytosis, the membrane,
or vesicle, in which the protein is wrapped fuses with the cell membrane,
and the protein is excreted into the extracellular fluid. The roles proteins
play when embedded in the cell membrane or exported from the cell are
central to understanding how neurons process information and determine
behavior.

FIGURE 3-17 Protein Export Exporting a protein entails packaging,

transport, and assigning its fate at the destination.

Crossing the Cell Membrane: Channels,

Gates, and Pumps
Proteins embedded in the cell membrane serve many functions. One is
transporting substances across the membrane. We now consider how
three such membrane proteins—channels, gates, and pumps—perform
the transport function. In each case, the particular protein’s function is an
emergent property of its shape.
A protein’s shape and its ability to change shape both derive from the
precise amino acid sequence that composes the protein molecule. Some
proteins change shape when other chemicals bind to them; others change
shape as a function of temperature; and still others change shape in
response to changes in electrical charge. The protein molecule’s ability
to change shape is analogous to a lock in a door. When a key of the
appropriate size and shape is inserted into the lock and turned, the
locking device activates and changes shape, allowing the door to be
closed or opened.
Such a shape-changing protein is illustrated in Figure 3-18 . The
surface of this protein molecule has a groove, called a receptor,
analogous to a keyhole. Small molecules, such as glucose, or other
proteins can bind to a protein’s receptors and cause the protein to change
shape. Changes in shape allow the proteins to serve some new function.
FIGURE 3-18 Receptor Binding When substances bind to a protein’s receptors,
the protein changes shape, which may change its function.

Some membrane proteins form channels through which substances

can pass. Different-sized channels regulate the passage of different-sized
substances. Figure 3-19 A illustrates a protein with a particular shape
forming a channel large enough to pass potassium (K+ ) but not other
ions. Other protein channels allow sodium ions or chloride ions to pass
into or out of the cell. Still others allow the passage of various other
substances.
channel Opening in a protein embedded in the cell membrane that
allows the passage of ions.
Figure 3-19 B shows a protein molecule that acts as a gate to regulate
the passage of substances. Like the protein in Figure 3-18 , gates change
their shape in response to some trigger. The protein allows substances to
pass through when its shape forms a channel and prevents passage when
its shape leaves the channel closed.
gate Protein embedded in a cell membrane that allows substances to
pass through the membrane on some occasions but not on others.
Changes in protein shape can also allow it to act as a pump. Figure 3-
19C shows a protein that changes its shape to pump Na+ and K+ across
the membrane, exchanging the Na+ on one side for the K+ on the other.
pump Protein in the cell membrane that actively transports a
substance across the membrane.
Channels, gates, and pumps play an important role in allowing
substances to enter and leave a cell. This passage of substances is critical
in explaining how neurons send messages. Chapter 4 explores how
neurons use electrical activity to communicate.
(A) Channel
 (B) Gated channel

(C) Pump
FIGURE 3-19 Transmembrane Proteins Channels, gates, and
pumps are proteins embedded in the cell membrane.
 3-2 REVIEW
Internal Structure of a Cell
Before you continue, check your understanding.
1 . The constituent parts of the cell include the ___________,
___________, ___________, ___________, ___________, and
___________.
2 . The product of the cell is ___________. They serve many functions,
including acting at the cell membrane as ___________, ___________,
and ___________ to regulate movement of substances across the
membrane.
3 . The basic sequence of events in building a protein is that
___________ makes ___________ makes ___________.
4 . Once proteins are formed in the ___________, they are wrapped in
membranes by ___________ and transported by ___________ to their
designated sites in the neuron or its membrane or exported from the
cell by ___________.
5 . Why is a cell more than a protein factory?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 3-3 Genes, Cells, and Behavior
Your genotype (genetic makeup) influences your physical and behavioral
traits, which combine to form your phenotype (individual
characteristics). Genetic analysis conducted by the Human Genome
Project has cataloged the human genome—all 20,000 or so genes in our
species—and today individual genomes are routinely sequenced. (Recall
the Beery twins in Research Focus 3-1 .) James Watson, the codiscoverer
of DNA, was the first to have his genome sequenced.
Researchers have succeeded in sequencing the long-extinct
Neanderthal genome as well. The genomes of James Watson and the
Neanderthal are surprisingly similar, as you’d expect for close hominid
relatives. You can have your genome sequenced to reveal many aspects
of its coding functions, including your relationship to Neanderthals. The
cost is about $100. (Before you decide, you may want to check on any
required information sharing with employers and insurers.)
Figure 1-12 shows how a Neanderthal woman might have looked.
Studying how genes influence our traits is the objective of Mendelian
genetics, named for Gregor Mendel, whose research led to the concept of
the gene. Studying how the environment influences gene expression is
the objective of epigenetics. In this section we describe how both factors
influence our phenotypes.

Mendelian Genetics and the Genetic Code

The nucleus of each human somatic cell contains 23 pairs of
chromosomes, or 46 in all. One member of each pair comes from the
mother, and the other member comes from the father. The chromosome
pairs are numbered from 1 to 23, roughly according to size, with
chromosome 1 being the largest (Figure 3-20 ).
Chromosome pairs 1 through 22 are called autosomes, and they
contain the genes that contribute most to our physical appearance and
behavior. The twenty-third pair are the sex chromosomes, which
contribute to our physical and behavioral sexual characteristics. The two
mammalian sex chromosomes are referred to as X and Y because of their
appearance, shown at the right in Figure 3-20 . Ordinarily, female
mammals have two X chromosomes, whereas males have an X and a Y.
 Because all but your sex chromosomes are matched pairs, each cell
contains two copies of every gene, one inherited from your mother, the
other from your father. These two copies of a gene are called alleles. The
term matched here does not necessarily mean identical. The nucleotide
sequences in a pair of alleles may be either identical or different. If they
are identical, the two alleles are homozygous (homo- means the same ).
If they are different, the two alleles are heterozygous (hetero- means
different ).
allele Alternative form of a gene; a gene pair contains two alleles.
homozygous Having two identical alleles for a trait.
heterozygous Having two different alleles for the same trait.

FIGURE 3-20 Human Chromosomes The nucleus of a human cell

contains 23 chromosomes derived from the father and 23 from the mother.
Sexual characteristics are determined by the twenty-third pair, the X and Y
(sex) chromosomes.

The nucleotide sequence most common in a population is called the

wild-type allele, whereas a less frequently occurring sequence is called a
mutation. Any wild-type allele may have a number of mutations, some
beneficial, some neutral and some harmful.
mutation Alteration of an allele that yields a different version of its
protein.
Dominant and Recessive Alleles
If both alleles in a gene pair are homozygous, the two encode the same
protein, but if the two alleles in a pair are heterozygous, they encode
somewhat different proteins. Three possible outcomes attend the
heterozygous condition when these proteins express a physical or
behavioral trait: (1) only the allele from the mother may be expressed,
(2) only the allele from the father may be expressed, or (3) both alleles
may be expressed simultaneously.
A member of a gene pair that is routinely expressed as a trait is called
a dominant allele; a unexpressed allele is recessive. Alleles can vary
considerably in their dominance. In complete dominance, only the
allele’s own trait is expressed in the phenotype. In incomplete
dominance, the allele’s own trait is expressed only partially. In
codominance, both the allele’s own trait and that of the other allele in the
gene pair are expressed completely.
Each gene makes an independent contribution to the offspring’s
inheritance, even though the contribution may not always be visible in
the offspring’s phenotype. When paired with a dominant allele, a
recessive allele is often not expressed. Still, it can be passed on to future
generations and influence their phenotypes when not masked by the
influence of some dominant trait.
Genetic Mutations
The mechanism described in Section 3-2 for reproducing genes and
passing them on to offspring is fallible. Errors can arise in the nucleotide
sequence when reproductive cells make gene copies. The altered alleles
are mutations.
A mutation may be as small as a change in a single nucleotide base,
or single nucleotide polymorphism (SNP, pronounced snip ). This one
base change results in a change in a codon and a resulting change in one
amino acid in a protein. A single amino acid change is a mutation and is
often sufficient to alter the protein’s function.
Because the average gene has more than 1200 nucleotide bases, an
enormous number of SNPs as well as more complex losses and changes
in bases can occur on a single gene. For example, the BRCA1 (breast
cancer) gene, found on chromosome 17, is a caretaker gene that
contributes to preventing breast cancer and other cancers in both men
and women. More than 1000 mutations of this gene have already been
found. Thus, in principle, there are more than 1000 ways in which to
inherit a predisposition to a cancer just from this gene.
A mutation in a nucleotide or the addition of a nucleotide to a gene
sequence can be beneficial or disruptive or both. For example, a SNP in
which a T base is substituted for an A base in the HBB (hemoglobin)
gene on chromosome 11 causes sickle-cell anemia, a condition in which
blood cells take on an abnormal sickle shape. The sickle shape offers
some protection against malaria, but sickle cells also have poor oxygen-
carrying capacity, which weakens the person who possesses them.
Sickle-cell anemia is the most common genetic blood disease, affecting
millions of people worldwide, including 80,000 people in the United
States.

Al Lamme/Phototake
In this micrograph a sickle cell is surrounded by healthy blood cells.

Each of us carries a surprisingly large number of genetic mutations.

Because of cell division, different mutations may be localized in
different parts of our body and brain and may contribute to individual
variations in our organs, including the brain (Charney, 2012). While
mutations may be beneficial or seemingly neutral to the functioning of
the organism that carries them, most mutations have negative effects. If
not lethal, they produce in their carrier debilitating physical and
behavioral abnormalities.
Neuroscientists cannot yet explain human behavior in relation to
genes and neurons, but we know the severe behavioral consequences of
about 2000 genetic abnormalities that affect the nervous system. For
example, an error in a gene could produce a protein that should be an ion
channel but will not allow the appropriate substance to pass. It may
produce a pump that will not pump or a protein that the cell’s
transportation system refuses to transport.
Applying Mendel’s Principles
Gregor Mendel introduced the concept of dominant and recessive alleles
in the nineteenth century, when he studied pea plants. Today, scientists
study genetic variation to gain insight into how genes, neurons, and
behaviors are linked. This knowledge is directed toward explaining
healthy behavior and helping reduce the negative effects of genetic
abnormalities, perhaps someday even eliminating them.
Experiment 1-1 describes one of Mendel’s experiments.
Allele Disorders That Affect the Brain
Some disorders caused by mutant genes illustrate Mendel’s principles of
dominant and recessive alleles. One is Tay-Sachs disease, caused by a
dysfunctional protein that acts as the enzyme HexA (hexosaminidase A).
The outcome is that it fails to break down a class of lipids (fats) in the
brain.
Tay-Sachs disease Inherited birth defect caused by the loss of genes
that encode the enzyme necessary for breaking down certain fatty
substances; appears 4 to 6 months after birth and results in
intellectual disability, physical changes, and death by about age 5.
Scientists Warren Tay and Bernard Sachs first described the
disorder.
Symptoms usually appear a few months after birth and rarely at later
ages. The baby begins to have seizures, deteriorating eyesight, and
degenerating motor and mental abilities. Inevitably, the child dies within
a few years. Tay-Sachs mutations appear with high frequency among
certain ethnic groups, including Jews of European origin and French
Canadians, but the mutation in different populations can be different.
The dysfunctional Tay-Sachs HexA enzyme is caused by a recessive
allele of the HEXA (hexosaminidase) gene on chromosome 15.
Distinctive inheritance patterns result from recessive alleles, because two
copies (one from the mother and one from the father) are needed for the
disorder to develop. A baby can inherit Tay-Sachs disease only when
both parents carry the recessive allele. However, a number of causative
alleles exist, and even inheriting different mutant alleles, one from each
parent, can cause Tay-Sachs disease.
 Because both parents have survived to adulthood, both must also
possess a corresponding dominant wild-type HEXA allele for that
particular gene pair. The egg and sperm cells produced by this man and
woman will therefore contain a copy of the wild type or the mutation of
these two alleles. Which allele is passed on is determined completely by
chance.
wild type Typical allele (most common in a population).
In any child born of two Tay-Sachs carriers, then, this situation gives
rise to three possible gene combinations, as shown in Figure 3-21 A .
The child may have two wild-type alleles, in which case he or she will be
spared the disorder and cannot pass it on. The child may have one
normal and one Tay-Sachs allele, in which case he or she, like the
parents, will be a carrier. Or the child may have two Tay-Sachs alleles, in
which case he or she will develop the disease.
The chance of a child of two carriers being normal is 25 percent, the
chance of being a carrier is 50 percent, and the chance of having Tay-
Sachs disease is 25 percent. If one parent is a Tay-Sachs carrier and the
other is normal, any child has a 50-50 chance being normal or a carrier.
Such a couple has no chance of conceiving a baby with Tay-Sachs
disease.
 (A) Recessive gene carries Tay-Sachs allele

(B) Dominant gene carries Huntington’s allele

 FIGURE 3-21 Inheritance Patterns (A) Recessive condition: If a
parent has one mutant allele, the parent will not show symptoms of the
disease but will be a carrier. If both parents carry a mutant allele, each of
their offspring stands a 25 percent chance of developing the disease. (B)
Dominant condition: A person with a single allele will develop the disease.
If this person mates with a noncarrier, offspring have a 50-50 chance of
developing the disease. If both parents are carriers, both will develop the
disease, and offspring have a 75 percent chance of developing it.

The Tay-Sachs allele operates independently of the dominant allele.

As a result, it still produces the defective HexA enzyme, so the person
who carries it has a higher than normal lipid accumulation in the brain.
Because this person also has a normal allele that produces a functional
enzyme, the abnormal lipid accumulation is not enough to cause Tay-
Sachs disease.
Fortunately, a blood test can detect whether a person carries the Tay-
Sachs allele. People who find that they are carriers can make informed
decisions about conceiving children. If they avoid having children with
another Tay-Sachs carrier, none of their children will have the disorder,
although some will probably be carriers. Where genetic counseling has
been effective, the disease has been eliminated.
The normal dominant allele that a carrier of Tay-Sachs possesses
produces enough functional enzyme to enable the brain to operate in a
satisfactory way. That would not be the case if the normal allele were
recessive, however, as happens with the genetic disorder Huntington
disease. Here, the buildup of an abnormal version of the huntingtin
protein kills brain cells, especially in the basal ganglia and the cortex.
Huntington disease Hereditary disease characterized by chorea
(ceaseless involuntary jerky movements) and progressive dementia,
ending in death.
Symptoms can begin at any time from infancy to old age, but they
most often start in midlife and include abnormal involuntary movements,
which is why the disorder was once called a chorea (from the Greek
meaning dance ). Other symptoms are memory loss and eventually a
complete deterioration of behavior, followed by death. The abnormal
HTT (hunting-tin) allele is dominant, the recessive allele normal, so only
one defective allele is needed to cause the disease.
Figure 3-21 B illustrates the inheritance patterns associated with a
dominant allele on chromosome 4 that produces Huntington disease. If
one parent carries the defective allele, offspring have a 50 percent chance
of inheriting the disorder. If both parents have the defective allele, the
chance of inheritance increases to 75 percent. As discussed further in
Clinical Focus 3-4 , Huntington Disease, on page 100 , because the
abnormal huntingtin allele usually is not expressed until midlife, after the
people who possess it have had children, it is passed down even though it
is lethal.
As with the allele causing Tay-Sachs disease, a genetic test can
determine whether a person carries the allele that causes Huntington
disease. If so, the person can elect not to procreate. A decision not to
have children in this case will reduce the incidence of the abnormal
huntingtin allele in the human gene pool.
CLINICAL FOCUS 3-4

Huntington Disease
Woody Guthrie, whose protest songs made him a spokesman for farm
workers during the Great Depression of the 1930s, is revered among
the founders of American folk music. His best-known song is “This
Land Is Your Land.” Singer and songwriter Bob Dylan was
instrumental in reviving Guthrie’s popularity in the 1960s.
Guthrie died in 1967 after struggling with what was eventually
diagnosed as Huntington disease. His mother had died of a similar
condition, although her illness was never diagnosed. Two of Guthrie’s
five children from two marriages developed the disease, and his
second wife, Marjorie, became active in promoting its study.
Huntington disease is devastating, characterized by memory
impairment; choreas (abnormal, uncontrollable movements); and
marked changes in personality, eventually leading to nearly total loss
of healthy behavioral, emotional, and intellectual functioning. Even
before the onset of motor symptoms, Huntington disease impairs
theory of mind, a person’s ability to assess the behavior of others
(Eddy and Rickards, 2015).
The symptoms of Huntington disease result from neuronal
degeneration in the basal ganglia and cortex. Symptoms can appear at
any age but typically start in midlife. In 1983, the HTT (huntingtin)
gene responsible for forming the abnormal huntingtin protein was
found on chromosome 4.
The HTT gene has been a source of insights into the transmission
of genetic disorders. Part of the gene contains repeats of the base
sequence CAG. The CAG codon encodes the amino acid glutamine.
If the number of CAG repeats exceeds about 40, then the carrier, with
40 or more glutamine amino acids in the huntingtin protein, has an
increased likelihood of Huntington symptoms.
As the number of CAG repeats increases, the onset of symptoms
occurs earlier in life, and the disease progresses more rapidly.
Typically, non-Europeans have fewer repeats than do Europeans,
among whom the disease is more common. The number of repeats
 can also increase with transmission from the father but not from the
mother.
Investigations into why brain cells change in Huntington disease
and into potential treatments use transgenic animal models. Mice,
rats, and monkeys that have received the HTT gene feature the
abnormal huntingtin protein and display symptoms of Huntington
disease (Gu et al., 2015).

© MixPix/Alamy
Woody Guthrie, whose unpublished lyrics and artwork are
archived at woodyguthrie.org.

Chromosome Abnormalities
Genetic disorders are not caused solely by single defective alleles. Some
nervous system disorders are caused by copy number variations, that is,
aberrations in a part of a chromosome or even an entire chromosome.
Copy number variations are related to a variety of disorders, including
autism, schizophrenia, and learning disabilities. Often though, copy
number variation has little obvious consequence or is beneficial. For
example, humans average about 6 copies of the AMY1 (amylase) gene but
may have as many as 15 copies. The gene is an adaptation that improves
the ability to digest starchy foods (Mimori et al., 2015).
One condition due to a change in chromosome number in humans is
Down syndrome, which affects approximately 1 in 700 children. Down
syndrome is usually the result of an extra copy of chromosome 21. One
parent (usually the mother) passes on two copies of chromosome 21 to the
child rather than the normal single chromosome. Combining these two
with one chromosome from the other parent yields three chromosomes
21, an abnormal number called a trisomy ( Figure 3-22 ).
Down syndrome Chromosomal abnormality resulting in intellecutal
impairment and other abnormalities, usually caused by an extra
chromosome 21.
Although chromosome 21 is the smallest human chromosome, its
trisomy can dramatically alter a person’s phenotype. People with Down
syndrome have characteristic facial features and short stature. They are
susceptible to heart defects, respiratory infections, and intellecutal
impairment. They are prone to developing leukemia and Alzheimer
disease. Although people with Down syndrome usually have a much
shorter than normal life span, some live to middle age or beyond.
Improved educational opportunities for children with Down syndrome
shows that they can learn to compensate greatly for their mental
disabilities.
BSIP/Getty Images
© Everett Collection Inc/Alamy
FIGURE 3-22 Chromosome Aberration Left: Down syndrome, also known as
trisomy 21, is caused by an extra chromosome 21 (colored red, bottom row at left). Right:
Chris Burke, the first person with Down syndrome to play a leading role, on the television
series Life Goes On in the 1990s, is now in his fifties. He performs as a lead singer in a
band.

Genetic Engineering
Despite advances in understanding gene structure and function, the gap in
understanding how genes produce behavior remains wide. To investigate
gene structure and behavior relations, geneticists have invented methods
to influence the traits genes express. This approach collectively defines
the science of genetic engineering. In its simplest forms, genetic
engineering entails manipulating a genome, removing a gene from a
genome, or modifying or adding a gene to the genome. Its techniques
include selective breeding, cloning, and transgenics.
Selective Breeding
The oldest means of influencing genetic traits is the selective breeding of
animals and plants. Beginning with the domestication of wolves into dogs
more than 30,000 years ago, humans have domesticated many animal
species by selectively breeding males and females that display particular
traits. The selective breeding of dogs, for example, has produced the
species with the most diverse traits of all animal species: breeds that can
run fast, haul heavy loads, retrieve prey, dig for burrowing animals, climb
rocky cliffs in search of sea birds, herd sheep and cattle, or sit on an
owner’s lap and cuddle. Selective breeding especially influences dogs’
sociability with humans (Persson et al., 2015).
Maintaining spontaneous mutations is one objective of selective
breeding. Using this method, researchers produce whole populations of
animals possessing some unusual trait that originally arose as an
unexpected mutation in only one individual or in a few animals. In
laboratory colonies of mice, for example, multiple spontaneous mutations
have been discovered and maintained to produce over 450 different
mouse strains.
Some strains of mice make abnormal movements, such as reeling,
staggering, and jumping. Other strains have diseases of the immune
system; others are blind or cannot hear. Some mice are smart; some mice
are not; some have big brains;, some, small; and many display distinctive
behavioral traits. Many such genetic variations can also be found in
humans. As a result, the neural and genetic bases of the altered behavior
in the mice can be studied systematically to understand and treat human
disorders.
Unlike other animals, humans can consent to experimental
procedures. Section 7-7 frames debates on the benefits and ethics of
conducting research using nonhuman animals.
Cloning
More direct approaches to manipulating the expression of genetic traits
include altering early embryonic development. One such method is
cloning —producing an offspring that is genetically identical to another
animal.
Sections 7-1 and 7-5 review genetic methods used in neuroscience
research.
To clone an animal, scientists begin with a cell nucleus containing
DNA, usually from a living animal donor, place it in an egg cell from
which the nucleus has been removed, and after stimulating the egg to start
dividing, implant the new embryo in the uterus of a female. Because each
individual animal that develops from these cells is genetically identical to
the donor, clones can be used to preserve valuable traits, to study the
relative influences of heredity and environment, or to produce new tissue
or organs for transplant to the donor. Dolly, a female sheep, was the first
cloned mammal.
A team of researchers in Scotland cloned Dolly in 1996. As an adult,
she mated and bore a lamb.
Cloning has matured from an experimental manipulation to a
commercial enterprise. The first horse to be cloned was Charmayne
James’s horse Scamper, the mount she rode to 11 world championships in
barrel racing. The first cat to be cloned, shown in Figure 3-23 , was
called Copycat. The first rare species cloned was an Asian gaur, an animal
related to the cow. Investigators anticipate that cloning will be used to
reanimate extinct animals, a process called de-extinction. They propose
using preserved cells from the extinct passenger pigeon or from frozen
carcasses of the mastodon (an enclosure to house a de-extinct mastodon
has been prepared in Russia), an extinct elephant species, to clone those
animals.
Photos used with permission from Texas A&M College of Veterinary Medicine & Biomedical
Sciences.
FIGURE 3-23 A Clone and Her Mom Copycat (left) and Rainbow (right), the cat
that donated the cell nucleus for cloning. Although the cats’ genomes are identical, their
phenotypes, including fur color, differ. One copy of the X chromosome is randomly
inactivated in each cell, which explains the color differences. Even clones are subject to
phenotypic plasticity: they retain the capacity to develop into more than one phenotype.

Transgenic Techniques
Transgenic technology enables scientists to introduce genes into an
embryo or remove genes from it. For example, introducing a new gene
can enable cows or goats to produce medicines in their milk. The
medicines can be extracted from the milk to treat human disease.
Transgenic techniques used to take a mouse gene that affords resistance to
tuberculosis and insert it into cows has increased their resistance to TB
(Wu et al., 2015).
Chimeric animals are composites formed when an embryo of one
species receives cells from a different species. The resulting animal has
cells with genes from both parent species and behaviors that are a product
of those gene combinations. The chimeric animal may display an
interesting mix of the parent species’ behaviors. For example, chickens
that received Japanese quail cells in early embryogenesis display some
aspects of quail crowing behavior rather than chicken crowing behavior—
evidence for the genetic basis of the bird’s vocalization (Balaban, 2005).
The chimeric preparation provides an investigative tool for studying the
neural basis of crowing, because quail neurons can be distinguished from
chicken neurons when examined under a microscope.
Chimerism is common in humans (Giorgi, 2015). Twin zygotes
(fertilized eggs) may fuse into a single individual, twins may exchange
cells through placental circulation, and the fetus and the mother may
exchange cells with one another. Even organ transplant or stem cell
recipients may incorporate transplanted cells into other organs.
In knock-in technology, a number of genes or a single gene from one
species is added to the genome of another species, passed along, and
expressed in subsequent generations of transgenic animals. Brainbow
technology, described in Research Focus 3-2 , applies the knock-in
technique. Another application is in the study and treatment of human
genetic disorders. For instance, researchers have introduced into a line of
mice and a line of Rhesus monkeys the human HTT gene that causes
Huntington disease (Gill and Rego, 2009; see Focus 3-4). The mice
express the abnormal allele and display humanlike Huntington symptoms.
This mouse line is being used to study possible therapies for Huntington
disease in humans.
transgenic animal Product of technology in which one or more
genes from one species is introduced into the genome of another
species to be passed along and expressed in subsequent generations.
Knockout technology is used to inactivate a gene, for example so that a
line of mice fails to express it. The mouse line can then be examined to
determine whether the targeted gene is responsible for a specific function
or a human disorder and to examine possible therapies. It may be possible
to knock out genes related to certain kinds of memory, such as emotional
memory, social memory, or spatial memory. Knockout technology is a
useful way of investigating the neural basis of memory as well as clinical
conditions associated with learning impairments (Kusakari et al., 2015).
The neural basis of memory is the topic of Section 14-3 .

Phenotypic Plasticity and the Epigenetic

Code
Our genotype is not sufficient to explain our phenotype. We all know that
if we expose ourselves to the sun, our skin darkens; if we exercise, our
muscles enlarge; if we study, we learn. Our phenotype also changes with
our diet and as we age. In short, the extent of phenotypic variation, given
the same genotype, is remarkable.
Every individual has a capacity to develop into more than one
phenotype. This phenotypic plasticity is due in part to the genome’s
capacity to express a large number of phenotypes and in part to
epigenetics, the influence of environment and experience in phenotypic
expression.
Seemingly puzzling features in the expression of genomes in relation
to phenotypes are illustrated in strains of genetically identical mice, some
of which develop a brain with no corpus callosum ( Figure 3-24 ). The
absence of this hemispheric connector results from an epigenetic
influence on whether the trait is expressed in a particular mouse. It occurs
in the embryo at about the time the corpus callosum should form. This
lack of concordance (incidence of similar behavioral traits) is also
observed in patterns of disease incidence in human identical twins, who
share the same genome.
(A)
(B)

Advances in Behavioral Biology Volume 42, 1994, pp. 125–133; Defects of the
Fetal Forebrain in Acallosal Mice; Douglas Wahlsten, Hiroki S. Ozaki, © 1994
Plenum Press, New York, figure 1, with permission of Springer Science+Business
Media

FIGURE 3-24 Gene Expression Identical coronal sections through the

brain of mice with identical genotypes reveal frontal views of distinctly
 different phenotypes. (A) This mouse had a corpus callosum. (B) This
mouse did not.

The concordance rate between identical twins for a vast array of

diseases—including schizophrenia, Alzheimer disease, multiple sclerosis,
Crohn disease (a form of inflammatory bowel disease), asthma, diabetes,
and prostate cancer—is between 30 and 60 percent. For cleft palate and
breast cancer, identical twins’ concordance rate is about 10 percent. The
expectation from Mendelian genetics is 100 percent concordance. These
less than perfect concordance rates point to other contributing factors.
Phenotypic plasticity is in evidence not only in adult organisms but
also in cells. In Section 3-1 , we described the variety of neurons and glia
found in the nervous system. Each of these cells usually has the same
genotype. So also do the 248 other cell types of our body. How then do
they become so different?
The cloned mice shown in Figure 2-1 exemplify phenotypic
plasticity.
Applying the Epigenetic Code
The genes expressed in a cell are influenced by factors within the cell and
in the cell’s environment. Once a fertilized egg begins to divide, each new
cell finds itself in a somewhat different environment from that of its
parent cell. The cell’s environment will determine which genes are
expressed and so what kind of tissue it becomes, including what kind of
nervous system cell it becomes. Environmental influences do not end at
birth, of course. Our environment changes daily throughout our lives, as
does its influence on our genes.
The International Human Epigenome Consortium (IHEC) mandate is
to describe the epigenetic code, as the Human Genome Project has
described the genetic code.
Epigenetic mechanisms create phenotypic variation without altering
the base pair nucleotide sequence of the genes. Through these
mechanisms, experience and the environment can allow a gene to be
expressed or prevent its expression. Epigenetics is viewed as a second
code; the first code is the genome. Epigenetics describes how a single
genetic code produces each somatic cell type, explains how a single
genome can code for many phenotypes, and describes how cell functions
go astray to produce diseases ranging from cancer to brain dysfunction.
 Epigenetic mechanisms can influence protein production either by
blocking a gene to prevent transcription or by unlocking a gene so that it
can be transcribed. This is where experiential and environmental
influences come into play. To review, each of your chromosomes consists
of a long, double-stranded chain of nucleotide bases that forms your
DNA. Each gene on a chromosome is a segment of DNA that encodes the
synthesis of a particular protein (see Figure 3-13 ).
Chromosomes are wrapped around supporting molecules of a protein
called histone. Histone wrapping allows the many yards of a chromosome
to be packaged in a small space, as yards of thread are wrapped around a
spool. For any gene to be transcribed into messenger RNA, its DNA must
be unspooled from the histones. Once unspooled, each gene must be
instructed to transcribe mRNA. Then the mRNA must be translated into
an amino acid chain that forms the protein. Figure 3-25 illustrates some
ways that each step can be either enabled or blocked:

1 Histone modification A methyl group (CH3 ) or other molecules bind

to the tails of histones, either blocking them from opening (orange
circles) or allowing them to open for transcription (green squares).
 2 Gene (DNA) methylation Methyl groups (M) bind to CG base pairs to
block transcription.

3 mRNA modification ncRNA binds to mRNA, preventing

translation.

FIGURE 3-25 Epigenetic Mechanisms

1. Histone modification. DNA may unwrap or be stopped from
unwrapping from the histone. At the top of Figure 3-25 , a methyl
group (CH 3 ) or other molecule binds to the tails of histones to block
DNA from unspooling. Its genes cannot be exposed for transcription
with the block in place (left), but it can be opened for transcription
(right) if the block is absent or removed.
2. Gene (DNA) methylation. Transcription of DNA into mRNA may be
enabled or blocked. In Figure 3-25 at center, one or more methyl
groups bind to CG base pairs to block transcription.
gene (DNA) methylation Epigenetic process in which a methyl
group attaches to the DNA sequence, suppressing or enabling gene
expression.
Methylation dramatically alters gene expression during brain
development (see Sections 8-2 and 12-5 ) and can affect memory and
brain plasticity (see Section 14-4 ).
3. mRNA modification. mRNA translation may be enabled or blocked. In
Figure 3-25 , bottom, noncoding RNA (ncRNA) binds to mRNA,
blocking translation.
An environmental influence can either induce or remove one or more
blocks, thus allowing the environment to regulate gene expression
(Charney, 2012). It is through these epigenetic mechanisms that cells are
instructed to differentiate into various body tissues and that our unique
environment and experience induce changes in our brain that make us a
unique individual. Some experientially induced events can also be passed
from one generation to the next, as the following case study illustrates.
A Case of Inheriting Experience
The idea that traits are passed from parent to child through genes is a
cornerstone of Mendelian genetics. Mendel’s theory also predicts that
individual life experience cannot be inherited. Lars Olov Bygren and
colleagues (Kaati et al., 2007) found, however, that individuals’
nutritional experiences can affect their offspring’s health.
The investigators focused on Norrbotten, a sparsely populated northern
Swedish region. In the nineteenth century, Norrbotten was virtually
isolated from the outside world. If the harvest there was bad, people
starved. According to historical records, the years 1800, 1812, 1821,
1836, and 1856 saw total crop failure. The years 1801, 1822, 1828, 1844,
and 1863 brought good harvests and abundance.
Bygren and colleagues identified at random individuals who had been
subjected to famine or to plenty in the years just before they entered
puberty. Then the researchers examined the health records and longevity
of these people’s children and grandchildren.
The findings seem to defy logic. The descendants of the plenty group
had higher rates of cardiovascular disease and diabetes and had a life
expectancy more than seven years shorter than that of the famine group!
Notably, these effects were found only in male offspring of males and
female offspring of females.
Bygren and colleagues propose that diet during a critical period can
modify the genetic expression of sex chromosomes—the Y chromosome
in males and the X chromosome in females. Further, this change can be
passed on to subsequent generations. Dietary experience in the
prepubertal period, just before the onset of sexual maturity, is important:
this is the time at which gene expression on the sex chromosomes begins.
Section 8-4 examines critical periods, limited time spans during
which events have long-lasting influences on development.
Many other studies support Bygren and coworkers’ seminal findings.
Together, this body of research makes a strong argument for epigenetics
and for the idea that some epi-genetic influences can be passed on for at
least a few generations. Evidence that epigenetic influences play a
demonstrable role in determining gene expression is disclosing how our
experiences shape our brains to influence whom we become and how our
current environment might influence our descendants’ epigenetic
inheritance (Guerrero-Bosagna and Jensen, 2015).
 3-3 REVIEW
Genes, Cells, and Behavior
Before you continue, check your understanding.
1 . Each of our ___________ chromosome pairs contains thousands of
genes, and each gene contains the code for one ___________.
2 . The genes we receive from our parents may include slightly different
___________ of particular genes, which will be expressed in slightly
different ___________.
3 . Abnormalities in a gene, caused by a(n) ___________, can result in
an abnormally formed protein, hence in abnormal cell function.
Chromosome abnormality can result in abnormal functioning of many
genes. ___________, for example, is caused by an extra copy of
chromosome 21, a ___________.
4 . Tay-Sachs disease results from a(n) ___________ allele being
expressed; Huntington disease results from the expression of a(n)
___________ allele.
5 . ___________ is the oldest form of genetic manipulation. Genetic
engineering manipulates or alters the genome of an animal.
___________ produces an animal that is genetically identical to a
parent or sibling; ___________ animals contain new, altered, or
inactivated genes.
6 . ___________ is an epigenetic mechanism that either enables or
blocks transcription.
7 . What distinguishes Mendelian genetics from epigenetics?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 SUMMARY
3-1 Cells of the Nervous System
The nervous system is composed of two kinds of cells: neurons, which
transmit information, and glia, which support neuronal function. Sensory
neurons may act as receptors to convey information from the body to the
brain; motor neurons command muscles to move; and interneurons link
up sensory and motor neuron activities.
Like neurons, glial cells can be grouped by structure and function.
Ependymal cells produce CSF. Astrocytes structurally support neurons,
help to form the blood–brain barrier, and seal off damaged brain tissue.
Microglia aid in brain cell repair and waste removal. Oligodendroglia
and Schwann cells myelinate axons in the CNS and in the somatic
division of the PNS, respectively.
A neuron is composed of three parts: a cell body, or soma; multiple
branching extensions called dendrites, designed to receive information;
and a single axon that passes information along to other neurons.
Numerous dendritic spines greatly increase a dendrite’s surface area. An
axon may have branches (axon collaterals), which further divide into
telodendria, each ending at a terminal button (end foot). A synapse is the
almost connection between a terminal button and another cell’s
membrane.
 3-2 Internal Structure of a Cell
A surrounding cell membrane protects the cell and regulates what enters
and leaves it. Within the cell are a number of organelles, also enclosed in
membranes. These compartments include the nucleus (containing the
cell’s chromosomes and genes), the endoplasmic reticulum (where
proteins are manufactured), the mitochondria (where energy is gathered
and stored), the Golgi bodies (where protein molecules are packaged for
transport), and lysosomes (which break down wastes). A cell also
contains a system of tubules (microfilaments) that aid its movements,
provide structural support, and act as highways for transporting
substances.
To a large extent, the work of cells is carried out by proteins. The
nucleus contains chromosomes—long chains of genes, each encoding a
specific protein the cell needs. Proteins perform diverse tasks by virtue
of their diverse shapes. Some act as enzymes to facilitate chemical
reactions; others serve as membrane channels, gates, and pumps; still
others are exported for use in other parts of the body.
A gene is a segment of a DNA molecule made up of a sequence of
nucleotide bases. Through transcription, a copy of a gene is produced in
a strand of messenger RNA. The mRNA travels to the endoplasmic
reticulum, where a ribosome moves along the mRNA molecule,
translating it into a sequence of amino acids. The resulting amino acid
chain is a polypeptide. Polypeptides fold and combine to form protein
molecules with distinctive shapes that serve specific purposes in the
body.
 3-3 Genes, Cells, and Behavior
From each parent, we inherit one of each chromosome in the 23
chromosome pairs that constitute the human genotype. Because all but
the sex chromosomes are matched pairs, a cell contains two alleles of
every gene. Sometimes the paired alleles are homozygous (the same),
and sometimes they are heterozygous (different).
An allele may be dominant and expressed as a trait, recessive and not
expressed, or codominant and expressed along with the other allele in the
organism’s phenotype. One allele of each gene is designated the wild
type—the most common in a population—whereas the other alleles are
called mutations. A person might inherit any of these alleles from a
parent, depending on the parent’s genotype.
Genes have the potential to undergo many mutations—of a single
base pair, part of the chromosome, or the entire chromosome. Mutations
can be beneficial, harmful, or neutral in their effects on nervous system
structure and behavioral function. Genetic research seeks to prevent the
expression of genetic and chromosomal abnormalities and to find cures
for those that are expressed.
Selective breeding is the oldest form of genetic manipulation. In
genetic engineering, an animal’s genome is artificially altered. The
genetic composition of a cloned animal is identical to that of a parent or
sibling. In transgenic animals, a new or altered gene may be added or a
gene removed.
The genome encodes a range of phenotypes. The phenotype
eventually produced is determined by epigenetics and further influenced
by experience and the environment. Epigenetic mechanisms such as
DNA methylation can influence whether genes are transcribed or
transcription is blocked without changing the genetic code itself.
 KEY TERMS
allele, p. 97
astrocyte, p. 82
axon, p. 77
axon collateral, p. 77
axon hillock, p. 77
bipolar neuron, p. 79
blood–brain barrier, p. 82
cell body (soma), p. 77
channel, p. 95
connectome, p. 77
dendrite, p. 77
dendritic spine, p. 77
Down syndrome, p. 100
ependymal cell, p. 82
gate, p. 95
gene, p. 91
gene (DNA) methylation, p. 104
glial cell, p. 80
heterozygous, p. 97
homozygous, p. 97
Huntington disease, p. 98
hydrocephalus, p. 82
interneuron, p. 79
microglia, p. 85
motor neuron, p. 79
mutation, p. 97
myelin, p. 85
neural network, p. 77
oligodendroglia, p. 85
paralysis, p. 85
protein, p. 92
pump, p. 95
Purkinje cell, p. 79
pyramidal cell, p. 79
Schwann cell, p. 85
sensory neuron, p. 79
somatosensory neuron, p. 79
synapse, p. 77
Tay-Sachs disease, p. 98
terminal button (end foot), p. 77
transgenic animal, p. 102
tumor, p. 82
wild type, p. 98

Visit Launch Pad to access the e-Book, videos,

Learning Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

How Do Neurons Use

Electrical Signals to
Transmit Information?
 Katherine Streeter

CLINICAL FOCUS 4-1 EPILEPSY

4-1 SEARCHING FOR ELECTRICAL ACTIVITY IN THE
NERVOUS SYSTEM
EARLY CLUES THAT LINKED ELECTRICITY AND NEURONAL
ACTIVITY
THE BASICS ELECTRICITY AND ELECTRICAL STIMULATION
TOOLS FOR MEASURING A NEURON’S ELECTRICAL ACTIVITY
HOW ION MOVEMENT PRODUCES ELECTRICAL CHARGES
4-2 ELECTRICAL ACTIVITY OF A MEMBRANE
RESTING POTENTIAL
MAINTAINING THE RESTING POTENTIAL
GRADED POTENTIALS
ACTION POTENTIAL
NERVE IMPULSE
REFRACTORY PERIODS AND NERVE ACTION
SALTATORY CONDUCTION AND THE MYELIN SHEATH
CLINICAL FOCUS 4-2 MULTIPLE SCLEROSIS
4-3 HOW NEURONS INTEGRATE INFORMATION
EXCITATORY AND INHIBITORY POSTSYNAPTIC POTENTIALS
EXPERIMENT 4-1 QUESTION: HOW DOES STIMULATING A
NEURON INFLUENCE ITS EXCITABILITY?
SUMMATION OF INPUTS
VOLTAGE-SENSITIVE CHANNELS AND THE ACTION
POTENTIAL
THE VERSATILE NEURON
RESEARCH FOCUS 4-3 OPTOGENETICS AND LIGHT-
SENSITIVE ION CHANNELS
4-4 INTO THE NERVOUS SYSTEM AND BACK OUT
HOW SENSORY STIMULI PRODUCE ACTION POTENTIALS
HOW NERVE IMPULSES PRODUCE MOVEMENT
CLINICAL FOCUS 4-4 ALS: LOU GEHRIG’S DISEASE
CLINICAL FOCUS 4-1

Epilepsy
J. D. worked as a disc jockey for a radio station and at parties in his
off-hours. One evening, he set up on the back of a truck at a rugby
field to emcee a jovial and raucous rugby party. Between musical
sets, he made introductions, told jokes, and exchanged toasts.
About one o’clock in the morning, J. D. suddenly collapsed,
making unusual jerky motions, then passed out. He was rushed to a
hospital emergency room, where he gradually recovered. The
attending physician noted that he was not intoxicated, released him
to his friends, and recommended a series of neurological tests for the
next day. Neuroimaging with state-of-the-art brain scans can usually
reveal brain abnormalities (Bano et al., 2011), but it did not do so in
J. D. ’s case.

AJPhoto/Science Source
The EEG detects electrical signals given off by the brain in
various states of consciousness, as explained in Sections 7-2
and 13-3 . Section 16-3 details the diagnosis and treatment of
epilepsy.

When the electrical activity in J. D.’s brain was recorded while a

strobe light was flashed before his eyes, an electroencephalogram, or
EEG, displayed a series of abnormal electrical patterns characteristic
 of epilepsy. The doctor prescribed Dilantin (diphenylhydantoin), an
anti-seizure drug, and advised J. D. to refrain from drinking alcohol.
He was required to give up his driver’s license to prevent the
possibility of an attack while driving. And he lost his job at the radio
station.
After 3 uneventful months, medication was stopped and his
driver’s license was restored. J. D. convinced the radio station that he
could resume work, and subsequently he has remained seizure free.
Epilepsy is a common neurological disease marked by periods of
excessive neural synchrony called electrographic seizures. The
disease is electrical in nature. Electrographic seizures often follow
innocuous stimuli—events that would not typically cause seizures in
people who do not have epilepsy. The core concept is that the brain
of a person with epilepsy has a chronically low seizure threshold and
so is subject to recurrent seizures. About 4 in 10 cases of epilepsy
have been linked to specific neural causes, among them infections,
trauma, tumors, structural abnormalities, or genetic mutations in the
proteins that make up ion channels (Bhalla et al., 2011). But that
leaves the remaining 60% without a clear cause.
electrographic seizures Abnormal rhythmic neuronal
discharges; may be recorded by an electroencephalogram.
If seizures occur repeatedly and cannot be controlled by drug
treatment, as occurs in about 30% of people with epilepsy, other
options may include the high-fat–low-carbohydrate ketogenic diet,
deep brain stimulation, and surgical resection of the seizure focus
(Duncan et al., 2006). Removing this small area of brain tissue may
prevent seizures and keep them from spreading to other brain
regions. The brain is normally electrically active. If this activity
becomes abnormal, even infrequently, the consequences can be
severe.

The most reproduced drawing in behavioral neuroscience is

nearly 350 years old, predating our understanding of the electrical basis
of epilepsy by centuries. Taken from René Descartes’s book Treatise on
Man and reproduced in Figure 4-1 , it illustrates the first serious attempt
to explain how information travels through the nervous system.
Descartes proposed that the carrier of information was cerebrospinal
fluid flowing through nerve tubes.
 Descartes reasoned that when the fire burns the man’s toe, it stretches
the skin, which tugs on a nerve tube leading to the brain. In response to
the tug, a valve in a brain ventricle opens, and CSF flows down the tube,
filling the leg muscles and causing them to contract and pull the toe back
from the fire. The flow of fluid through other tubes to other muscles of
the body (not shown in Figure 4-1 ) causes the head to turn toward the
painful stimulus and the hand to rub the injured toe.
Descartes proposed the idea behind dualism—that the nonmaterial
mind controls body mechanics; see Section 1-2 .
Descartes’s theory was incorrect, yet it is remarkable because he
isolated the three basic questions that underlie a behavioral response to
stimulation:
1. How do our nerves detect a sensory stimulus and inform the brain
about it?
2. How does the brain decide what response to make?
3. How does the brain command muscles to move?
Descartes was trying to explain the very same things that scientists have
sought to explain in the intervening centuries. If not by stretched skin
tugging on a nerve tube initiating the message, the message must still be
initiated somehow. If not by opening valves to initiate the flow of CSF to
convey information, the information must still be sent. If not by filling
the muscles with fluid that produces movements, the muscles must
contract by some other mechanism.
These mechanisms are the subject of this chapter. We examine how
neurons convey information from the environment throughout the
nervous system and ultimately activate muscles to produce movement.
We begin by describing the clues and tools that explained the nervous
system’s electrical activity.
 Print Collector/Getty Images

FIGURE 4-1 Descartes’s Theory of Information Flow

 Searching for Electrical Activity in the
4-1

Nervous System
The first hints about how the nervous system conveys its messages came
in the eighteenth century, following the discovery of electricity. Early
discoveries about the nature of electricity quickly led to proposals that it
plays a role in conducting information in the nervous system. We
describe a few milestones that led from this idea to an understanding of
how the nervous system really conveys information. If you have a basic
understanding of how electricity works and how it is used to stimulate
neural tissue, read on. If you prefer to brush up on electricity and
electrical stimulation first, turn to The Basics: Electricity and Electrical
Stimulation on page 110 .

Early Clues That Linked Electricity and

Neuronal Activity
In a dramatic demonstration in 1731, Stephen Gray, an amateur English
scientist, rubbed a rod with a piece of cloth to accumulate electrons on
the rod. Then he touched the charged rod to the feet of a boy suspended
on a rope and brought a metal foil to the boy’s nose. The foil was
attracted to the boy’s nose and bent on approaching it, and as foil and
nose touched, electricity passed from the rod through the boy to the foil.
Yet the boy felt nothing. Therefore, Gray speculated that electricity
might be the messenger that spreads information through the nervous
system. Two other lines of evidence, drawn from electrical stimulation
and electrical recording studies, implicated electrical activity in the
nervous system’s flow of information.
Gray’s experiment resembles accumulating electrons by combing
your hair. Hold a piece of paper near the comb, and the paper bends
toward it. Negative charges on the comb push negative charges on
the paper to its backside, leaving the front side positively charged.
Because opposite charges attract, the paper bends toward the comb.
Electrical Stimulation Studies
When the Italian scientist Luigi Galvani, a contemporary of Gray,
observed that frogs’ legs hanging on a wire in a market twitched during a
lightning storm, he surmised that sparks of electricity from the storm
were activating the leg muscles. Investigating this possibility, he found
that if an electrical current is applied to a dissected nerve, the muscle
connected to that nerve contracts. While it was unclear how the process
worked, Galvani had discovered electrical stimulation: passing an
electrical current from the uninsulated tip of an electrode onto a nerve to
produce behavior—a muscular contraction.
electrical stimulation Passage of an electrical current from the
uninsulated tip of an electrode through tissue, resulting in changes in
the electrical activity of the tissue.
Among the many researchers who used Galvani’s technique to
produce muscle contraction, two mid-nineteenth-century Prussian
scientists, Gustave Theodor Fritsch and Eduard Hitzig, demonstrated that
electrical stimulation of the neocortex causes movement. They studied
several animal species, including rabbits and dogs, and may even have
stimulated the neocortex of a person whom they were treating for head
injuries sustained on a Prussian battlefield. They observed their subjects’
arm and leg movements in response to the stimulation of specific parts of
the neocortex.
In 1874, Roberts Bartholow, a Cincinnati physician, first described
the effects of human brain stimulation. His patient, Mary Rafferty, had a
skull defect that exposed part of her neocortex. Bartholow stimulated her
exposed brain tissue to examine the effects. In one of his observations he
wrote:
 THE BASICS

Electricity and Electrical

Stimulation
Electricity powers the lights in your home and the batteries that run
so many electronic gadgets, from smartphones to electric cars.
Electricity is the flow of electrons from a body that contains a higher
charge (more electrons) to a body that contains a lower charge
(fewer electrons). This electron flow can perform work—lighting an
unlit bulb, for instance. When biological tissue contains an electrical
charge, the charge can be recorded; if living tissue is sensitive to an
electrical charge, the tissue can be stimulated.
How Electricity Works
In Power Source, negatively charged electrons are attracted to the
positive pole because opposite charges attract. The electrons on the
negative pole have the potential to flow to the positive pole. This
electrical potential, or electrical charge, is the ability to do work
using stored electrical energy.
Electrical potential is measured in volts, the difference in charge
between the positive and the negative poles. These poles are
separated by an insulator. Thus, when not connected, the positive
and negative poles in a battery, like the poles in each wall socket in
your home, hold voltage between the poles.
Electrical Activity in Cells
If the bare tip of an insulated wire, or electrode, from each pole of a
battery comes into contact with biological tissue, current will flow
from the electrode connected to the negative pole into the tissue and
from the tissue into the electrode connected to the positive pole. The
stimulation comes from the electrode’s uninsulated tip.
Microelectrodes can record from or stimulate tissue as small as parts
of a single living cell.
Electrical stimulation, illustrated in part A of Studying Electrical
Activity in Animal Tissue, is most effective when administered in
brief pulses. A timer in the stimulator turns the current on and off to
produce the pulses. In electrical recording, voltage can be displayed
 by the dial on a voltmeter, a recording device that measures the
voltage of a battery or of biological tissue (part B).
Power Source
Current leaves the stimulator through a wire lead (red) that
attaches to an electrode. From the uninsulated tip of the
electrode, the current enters the tissue and stimulates it. The
current flows back to the stimulator through a second lead
(green) connected to a reference electrode.

1 A stimulating electrode delivers current (electrons) ranging

from 2 to 10 millivolts, intensities sufficient to produce a
response without damaging cells.

2 The reference electrode contacts a large surface area that

spreads out the current and thus does not excite the tissue here.

(A) Electrical stimulation

 (B) Electrical recording
Studying Electrical Activity in Animal Tissue
Passed an insulated needle into the left posterior lobe so that the non-insulated portion rested
entirely in the substance of the brain. The reference was placed in contact with the dura mater.
When the circuit was closed, muscular contraction in the right upper and lower extremities
ensued. Faint but visible contraction of the left eyelid, and dilation of the pupils, also ensued.
Mary complained of a very strong and unpleasant feeling of tingling in both right extremities,
especially in the right arm, which she seized with the opposite hand and rubbed vigorously.
Notwithstanding the very evident pain from which she suffered, she smiled as if much amused.
(Bartholow, 1874)

As you might imagine, Bartholow’s report was not well received! The
uproar after its publication forced him to leave Cincinnati. Despite the
questionable ethics of his experiment, Bartholow had demonstrated that
the brain of a conscious person could be stimulated electrically to produce
movement of the body.
By the 1960s, the scientific community had established ethical
standards for research on human and nonhuman subjects (see Section
7-7 ). Today, brain stimulation is standard in many neurosurgical
procedures (see Section 16-2 ).
Electrical Recording Studies
A less invasive line of evidence that information flow in the brain is
partly electrical came from the results of electrical recording experiments.
Richard Caton, a Scottish physician who lived a century ago, was the first
to measure the brain’s electrical currents with a sensitive voltmeter, a
device that measures the flow and the strength of electrical voltage by
recording the difference in electrical potential between two bodies. When
he placed electrodes on a human subject’s skull, Caton reported
fluctuations in his voltmeter recordings. Today, this type of brain
recording, the electroencephalogram (EEG), is a standard tool used,
among other things, to monitor sleep stages and to detect the excessive
neural synchrony that characterizes electrographic seizures, as described
in Clinical Focus 4-1 , Epilepsy.
voltmeter Device that measures the flow and the strength of
electrical voltage by recording the difference in electrical potential
between two bodies.
electroencephalogram (EEG) Graph that records electrical activity
from the brain and mainly indicates graded potentials of many
neurons.
Detail on these EEG applications appears in Sections 7-2 , 13-3 , and
16-3 .
These pioneering studies provided evidence that neurons send
electrical messages, but concluding that nerves and tracts carry the kind
of electrical current that powers your phone would be incorrect. Hermann
von Helmholtz, a nineteenth-century German scientist, stimulated a nerve
leading to a muscle and measured the time the muscle took to contract.
The nerve conducted information at only 30 to 40 meters per second,
whereas electricity flows along a wire about a million times faster.
Information flow in the nervous system, then, is much too slow to be a
flow of electricity (based on electrons). To explain the electrical signals of
a neuron, Julius Bernstein suggested in 1886 that neuronal chemistry
(based on ions) produces an electrical charge. He also proposed that the
charge can change and so act as a signal. Bernstein’s idea was that
successive waves of electrical change constitute the message conveyed by
the neuron.
Moreover, it is not the ions themselves that travel along the axon but
rather a wave of charge. To understand the difference, consider other
kinds of waves. If you drop a stone into a pool of still water, the contact
produces a wave that travels away from the site of impact, as shown in
Figure 4-2 . The water itself does not travel. Only the change in pressure
moves, shifting the height of the water surface and producing the wave
effect.
Similarly, when you speak, you induce pressure waves in air, and these
waves carry the sound of your voice to a listener. If you flick a towel, a
wave travels to the other end of the towel. Just as waves through the air
send a spoken message, Bernstein’s idea was that waves of chemical
change travel along an axon to deliver a neuron’s message.

© Fotosearch/Age Fotostock, Inc.

FIGURE 4-2Wave Effect Waves formed by dropping stones into still

water do not entail the water’s forward movement but rather pressure
differences that change the height of the water surface.

Tools for Measuring a Neuron’s Electrical

Activity
Waves that carry nervous system messages are minute and are restricted
to the surfaces of neurons. Still, we can produce these waves using
conventional electrical stimulation and measure them using electrical
recording techniques to determine how they are produced. When a single
axon is stimulated, it produces a wave of excitation. If an electrode
connected to a voltmeter is placed on a single axon, as illustrated in
Figure 4-3 , the electrode can detect a change in electrical charge on that
axon’s membrane as the wave passes.
 FIGURE 4-3 Wave of Information Neurons can convey information
as a wave induced by stimulation on the cell body traveling down the axon
to its terminal. A voltmeter detects the wave’s passage.

As simple as this process may seem, recording a wave and explaining

how it is produced require a neuron large enough to record, a recording
device sensitive enough to detect a tiny electrical impulse, and an
electrode small enough to be placed on the surface of a single neuron. The
fortuitous discovery of the giant axon of the squid, the invention of the
oscilloscope, and the development of microelectrodes met all these
requirements.
Giant Axon of the Squid
The neurons of most animals, including humans, are tiny, on the order of
1 to 20 micrometers (µm) in diameter, too small to be seen by the naked
eye. The British zoologist J. Z. Young, when dissecting the North Atlantic
squid, Loligo vulgaris, noticed that it has giant axons, as much as a
millimeter (1000 µm, or about a twenty-fifth of an inch) in diameter.
Figure 4-4 illustrates Loligo and the giant axons leading to its body wall,
or mantle, which contracts to propel the squid through the water.
1 micron (µm) = one-millionth of a meter or one-thousandth of a
millimeter (mm).
Loligo is not a giant squid. It is only about a foot long. But its axons
are giant, as axons go. Each is formed by the fusion of many smaller
axons. Because larger axons send messages faster than smaller axons do,
these giant axons allow the squid to jet-propel away from predators.
In 1936, Young suggested to Alan Hodgkin and Andrew Huxley,
neuroscientists at Cambridge University in England, that Loligo ’s axons
were large enough to be used for electrical recording studies. A giant
axon could be dissected out of the squid and kept functional in a bath of
salty liquid that approximates body fluids. In this way, Hodgkin and
Huxley (1939) described the neuron’s electrical activity. In 1963 they
received the Nobel Prize for their accomplishment.
 © Age Fotostock/Alamy
(A)

(B)

FIGURE 4-4 Laboratory Specimen (A) The North Atlantic squid

propels itself both with fins and by contracting its mantle to force water out
for propulsion. (B) The stellate ganglion projects giant axons to contract the
squid’s mantle.
 GIPhotostock/Science Source
(A)

(B)

FIGURE 4-5 Oscilloscope Recording (A) Basic wave shapes are

displayed on a digital oscilloscope, a versatile electronic instrument used to
visualize and measure electrical signals as they change. (B) On the graph
of a trace produced by an oscilloscope, S stands for stimulation. The
horizontal axis measures time, and the vertical axis measures voltage. By
convention, the axon voltage is represented as negative, in millivolts (mV).
On the right, one trace of two action potentials from an individual neuron as
displayed on a digital oscilloscope screen.

Oscilloscope
Hodgkin and Huxley’s experiments were made possible by the invention
of the oscilloscope, a voltmeter with a screen sensitive enough to display
the minuscule electrical signals emanating from a nerve or neuron over
time (Figure 4-5 A ). As graphed in Figure 4-5B , the units used when
recording the electrical charge from a nerve or neuron are millivolts (mV;
1 mV is one-thousandth of a volt) and milliseconds (ms; 1 ms is one-
thousandth of a second).
oscilloscope Device that serves as a sensitive voltmeter by
registering changes in voltage over time.
Microelectrodes
The final device needed to measure a neuron’s electrical activity is an
electrode small enough to place on or in an axon—a microelectrode.
Microelectrodes can deliver an electrical current to a single neuron or
record from it. One way to make a microelectrode is to etch the tip of a
piece of thin wire to a fine point about 1 µm in size and insulate the rest
of the wire. The tip is placed on or in the neuron, as shown in the image at
left in Figure 4-6 A .
microelectrode A microscopic insulated wire or a saltwater-filled
glass tube whose uninsulated tip is used to stimulate or record from
neurons.
Microelectrodes can also be made from a thin glass tube tapered to a
very fine tip (Figure 4-6 A, right image). The tip of a hollow glass
microelectrode can be as small as 1 µm. When the glass tube is filled with
salty water, a conducting medium (through which an electrical current can
travel), it acts as an electrode. A wire in the salt solution connects the
electrode to either a stimulating or a recording device.
Microelectrodes can record from axons in many ways. The tip of a
microelectrode placed on an axon provides an extracellular measure of
the electrical current from a tiny part of the axon. The tip of one electrode
can be placed on the surface of the axon and the tip of a second electrode
can be inserted into the axon. This technique measures voltage across the
cell membrane.
A still more refined use of a glass microelectrode is to place its tip on
the neuron’s membrane and apply a little suction until the tip is sealed to a
patch of the membrane, as shown in Figure 4-6B . This technique,
analogous to placing the end of a soda straw against a piece of plastic
wrapping and sucking, allows a recording to be made from only the small
patch of membrane sealed to the microelectrode tip.
Using the giant axon of the squid, an oscilloscope, and
microelectrodes, Hodgkin and Huxley recorded the electrical voltage on
an axon’s membrane and explained the nerve impulse as changes in ion
concentration across the cell membrane. The basis of electrical activity in
nerves is the movement of intracellular and extracellular ions, which
carry positive and negative charges across the cell membrane. To
understand Hodgkin and Huxley’s results, you first need to understand the
principles underlying the movement of ions.
(A)
(B)

FIGURE 4-6 Uses of Microelectrodes (A) A squid axon is larger

than the tip of either a wire (left) or a glass (right) microelectrode. Both can
be placed on an axon or in it. (Drawings are not to scale.) (B) A
microelectrode can record from only a small area of an axon by suctioning
the membrane up into the glass electrode.

How Ion Movement Produces Electrical

Charges
The intracellular fluid within a neuron and the extracellular fluid
surrounding it contain various ions, including Na+ (sodium) and K+
(potassium)—positively charged, as the plus signs indicate—and
negatively charged Cl– (chloride). These fluids also contain numerous
negatively charged protein molecules (A– ). Positively charged ions are
cations, and negatively charged ions, including protein molecules, are
anions. Three factors influence the movement of anions and cations into
and out of cells: diffusion, concentration gradient, and charge.
Because molecules move constantly, they spontaneously spread out
from a point of concentration. This spreading out is diffusion. Requiring
no work, diffusion results from the random motion of molecules as they
move and bounce off one another to gradually disperse in a solution.
When diffusion is complete, a dynamic equilibrium, with an equal
number of molecules everywhere, is the result.
diffusion Movement of ions from an area of higher concentration to
an area of lower concentration through random motion.
Smoke from a fire gradually diffuses through the air in a room until
every bit of air contains the same number of smoke molecules. Dye
poured into water diffuses in the same way—from its point of contact to
every part of the water in the container. Salts placed in water dissolve into
ions surrounded by water molecules. Carried by the random motion of the
water molecules, these ions diffuse throughout the solution to
equilibrium, when every part of the container has the same salt
concentration.
The Basics, pp. 88–89, covers ions. The illustration, Salty Water,
shows how water molecules dissolve salt crystals.
Concentration gradient describes the relative abundance of a
substance in space or in a solution. As illustrated in Figure 4-7 A , when
you drop a little ink into a beaker of water, the dye starts out concentrated
at the site of contact, then diffuses. The ink spreads out from a point of
concentration until it is equally distributed and all the water in the beaker
is the same color. A similar process takes place when a salt is put into
water. The salt is initially concentrated where it enters the water, but it
diffuses from that location until its ions are in equilibrium.
concentration gradient Difference in the relative abundance of a
substance among regions of a container; allows the substance to
diffuse from an area of higher concentration to an area of lower
concentration.
Because ions carry an electrical charge and because like charges repel
one another, ion movement can be described either by a concentration
gradient, the difference in the number of ions between two regions, or by
a voltage gradient, the difference in charge between two regions. Ions
will move down a voltage gradient from an area of higher charge to an
area of lower charge, just as they move down a concentration gradient
from an area of higher concentration to an area of lower concentration.
voltage gradient Difference in charge between two regions that
allows a flow of current if the two regions are connected.
(A) Concentrating gradient
(B) Voltage gradient
 FIGURE 4-7 Moving to Equilibrium
Figure 4-7B illustrates this process. When salt is dissolved in water, its
diffusion can be described either as movement down a concentration
gradient (for sodium and chloride ions) or movement down a voltage
gradient (for the positive and negative charges). In a container that allows
unimpeded movement of ions, the positive and negative charges
eventually balance.
A thought experiment will illustrate how a cell membrane influences
ion movement. Figure 4-8 A shows a container of water divided in half
by a solid, impermeable membrane. If we place a few grains of table salt
(NaCl) in the left half of the container, the salt dissolves. The ions diffuse
down their concentration and voltage gradients until the water in the left
compartment is in equilibrium.
The cell membrane is an insulator impermeable to salty solutions:
salt ions, surrounded by water molecules, will not pass through the
membrane’s hydrophobic tails (review Figure 3-11 ).
In the left side of the container, there is no longer a gradient for either
sodium or chloride ions because the water everywhere is equally salty.
There are no gradients for these ions on the other side of the container
either, because the solid membrane prevents the ions from entering that
side. But there are concentration and voltage gradients for both sodium
and chloride ions across the membrane—that is, from the salty side to the
freshwater side.
Transmembrane protein molecules embedded in a cell membrane form
channels, some with gates, and pumps that allow certain kinds of ions to
pass through the membrane. Returning to our thought experiment, we
place a few chloride channels in the membrane that divides the container
of water, making the membrane semipermeable, as illustrated at the left in
Figure 4-8B . Chloride ions will now diffuse across the membrane and
move down their concentration gradient on the side of the container that
previously had no chloride ions, shown in the middle of Figure 4-8B .
The sodium ions, in contrast, cannot cross through the chloride channels
or the cell membrane.
Dissolved sodium ions are smaller than chloride ions but more likely
to stick to water molecules and so are bulkier and will not pass
through a small chloride channel.
If the only factor affecting the movement of chloride ions were the
chloride concentration gradient, the efflux (outflow) of chloride from the
salty to the freshwater side of the container would continue until chloride
ions were in equilibrium on both sides. But this is not what happens.
Because opposite charges attract, the chloride ions, which carry a
negative charge, are attracted to the positively charged sodium ions they
left behind. Because they are pulled back toward the sodium ions, the
chloride ions cannot diffuse completely. Consequently, the concentration
of chloride ions remains higher in the left side of the container than in the
right, as illustrated at the right in Figure 4-8B .
In other words, the efflux of chloride ions down the chloride
concentration gradient is counteracted by the influx (inflow) of chloride
ions down the chloride voltage gradient. At some point, equilibrium is
reached: the chloride concentration gradient on the right side of the
beaker is balanced by the chloride voltage gradient on the left. In brief:
concentration gradient = voltage gradient
(A) Impermeable membrane
(B) Semipermeable membrane

FIGURE 4-8 Modeling the Cell Membrane

At this equilibrium, the differential concentration of the chloride ions
on the two sides of the membrane produces a difference in charge—
voltage. The left side of the container is positively charged because some
chloride ions have migrated, leaving a preponderance of positive (Na+ )
charges. The right side of the container is negatively charged because
some chloride ions have entered that chamber, where none were before.
The charge is highest on the surface of the semipermeable membrane, the
area at which positive and negative ions accumulate. Much the same
process happens in a real cell.
 4-1 REVIEW
Searching for Electrical Activity in the Nervous System
Before you continue, check your understanding.
1 . Although he was incorrect, ___________ was the first to seriously
attempt to explain how information travels through the nervous
system.
2 . Experimental results obtained over hundreds of years from electrical
___________ and more recently from electrical ___________
implicated electrical activity in the nervous system’s flow of
information.
3 . By the mid-twentieth century, scientists had solved three technical
problems in measuring the changes in electrical charge that travel like
a wave along an axon’s membrane: ___________, ___________, and
___________.
4 . The electrical activity of neuronal axons entails the diffusion of ions.
Ions may move down a(n) ___________ and down a(n) ___________.
5 . In what three ways does the semipermeable cell membrane affect the
movement of ions in the nervous system?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 4-2 Electrical Activity of a Membrane
Specific aspects of the cell membrane’s electrical activity interact to
convey information throughout the nervous system. The movement of
ions across neuronal membranes produces the electrical activity that
enables this information flow.

Resting Potential
Figure 4-9 shows how the voltage difference is recorded when one
microelectrode is placed on the outer surface of an axon’s membrane and
another is placed on its inner surface. In the absence of stimulation, the
difference is about 70 mV. Although the charge on the outside of the
membrane is actually positive, by convention it is given a charge of zero.
Therefore, the inside of the membrane at rest is –70 mV relative to the
extracellular side.
If we were to continue to record for a long time, the charge across the
unstimulated membrane would remain much the same. The charge can
change, given certain changes in the membrane, but at rest the difference
in charge on the inside and outside of the membrane produces an
electrical potential —the ability to use its stored power, analogous to a
charged battery. The charge is thus a store of potential energy called the
membrane’s resting potential.
resting potential Electrical charge across the insulating cell
membrane in the absence of stimulation; a store of potential energy
produced by a greater negative charge on the intracellular side
relative to the extracellular side.
 FIGURE 4-9 Resting Potential The electrical charge across a resting
cell membrane stores potential energy.

We might use the term potential in the same way to talk about the
financial potential of someone who has money in the bank—the person
can spend the money at some future time. The resting potential, then, is a
store of energy that can be used later. Most of your body’s cells have a
resting potential, but it is not identical on every axon. Resting potentials
vary from –40 to –90 mV, depending on neuronal type and animal
species.
Four charged particles take part in producing the resting potential:
ions of sodium (Na+ ), potassium (K+ ), chloride (Cl– ), and large protein
molecules (A– ). These are the cations and anions, respectively, defined
in Section 4-1 . As Figure 4-10 shows, these charged particles are
distributed unequally across the axon’s membrane, with more protein
anions and potassium ions in the intracellular fluid and more chloride
and sodium ions in the extracellular fluid. How do the unequal
concentrations arise, and how does each contribute to the resting
potential?

Ion Distribution Across the Resting

FIGURE 4-10

Membrane The number of ions distributed across the resting cell

membrane is unequal. Protein ions are represented by the label, A– .

Maintaining the Resting Potential

The cell membrane’s channels, gates, and pumps maintain the resting
potential. Figure 4-11 , which shows the resting membrane close up,
details how these three features contribute to the cell membrane’s resting
charge:
1. Because the membrane is relatively impermeable to large molecules,
the negatively charged proteins remain inside the cell.
2. Ungated potassium and chloride channels allow potassium and
chloride ions to pass more freely, but gates on sodium channels keep
out positively charged sodium ions.
3. Na + –K + pumps extrude Na + from the intracellular fluid and inject K
+.

Inside the Cell

Large protein anions are manufactured inside cells. No membrane
channels are large enough to allow these proteins to leave the cell, and
their negative charge alone is sufficient to produce transmembrane
voltage, or a resting potential. Because most cells in the body
manufacture these large, negatively charged protein molecules, most
cells have a charge across the cell membrane.
To balance the negative charge produced by large protein anions in
the intracellular fluid, cells accumulate positively charged potassium
ions to the extent that about 20 times as many potassium ions cluster
inside the cell as outside it. Potassium ions cross the cell membrane
through open potassium channels, as shown in Figure 4-11 . With this
high concentration of potassium ions inside the cell, however, the
potassium concentration gradient across the membrane limits the number
of potassium ions entering the cell. In other words, not all the potassium
ions that could enter do enter. Because the internal concentration of
potassium ions is much higher than the external potassium concentration,
potassium ions are drawn out of the cell by the potassium concentration
gradient.

FIGURE 4-11 Maintaining the Resting Potential Channels,

gates, and pumps in the cell membrane contribute to the transmembrane
charge.

A few residual potassium ions on the outside of the membrane are

enough to contribute to the charge across the membrane. They add to the
negative charge on the intracellular side of the membrane relative to the
extracellular side. You may be wondering whether you read the last
sentence correctly. If there are 20 times as many potassium ions inside
the cell as there are outside, why should the inside of the membrane have
a negative charge? Should not all those potassium ions in the
intracellular fluid give the inside of the cell a positive charge instead?
No, because not quite enough potassium ions are able to enter the cell to
balance the negative charge of the protein anions.
Think of it this way: if the number of potassium ions that could
accumulate on the intracellular side of the membrane were unrestricted,
the positively charged potassium ions inside would exactly match the
negative charges on the intracellular protein anions. There would be no
charge across the membrane at all. But the number of potassium ions that
accumulate inside the cell is limited, because when the intracellular K+
concentration becomes higher than the extracellular concentration,
further potassium ion influx is opposed by its concentration gradient.
Outside the Cell
The equilibrium of the potassium voltage and concentration gradients
results in some potassium ions remaining outside the cell. It is necessary
to have only a few potassium ions outside the cell to maintain a negative
charge inside the cell. As a result, potassium ions contribute to the
charge across the membrane.
Sodium (Na+ ) and chloride (Cl– ) ions also take part in producing the
resting potential. If positively charged sodium ions were free to move
across the membrane, they would diffuse into the cell and eliminate the
transmembrane charge produced by the unequal distribution of
potassium ions inside and outside the cell. This diffusion does not
happen, because a gate on the sodium ion channels in the cell membrane
is ordinarily closed (see Figure 4-11 ), blocking the entry of most sodium
ions. Still, given enough time, sufficient sodium ions could leak into the
cell to neutralize its membrane potential. The cell membrane has a
different mechanism to prevent this neutralization.
When sodium ions do leak into the neuron, they are immediately
escorted out again by the action of a sodium–potassium pump, a protein
molecule embedded in the cell membrane. A membrane’s many
thousands of pumps continually exchange three intra-cellular sodium
ions for two potassium ions, as shown in Figure 4-11 . The potassium
ions are free to leave the cell through open potassium channels, but
closed sodium channels slow the reentry of the sodium ions. In this way,
sodium ions are kept out to the extent that about 10 times as many
sodium ions reside on the outside of the axon membrane as on its inside.
The difference in sodium concentrations also contributes to the
membrane’s resting potential.
 Now consider the chloride ions. Unlike sodium ions, chloride ions
move in and out of the cell through open channels in the membrane. The
equilibrium point, at which the chloride’s concentration gradient equals
its voltage gradient, is approximately the same as the membrane’s resting
potential, and so chloride ions ordinarily contribute little to the resting
potential. At this equilibrium point, there are about 12 times as many
chloride ions outside the cell as inside it.
The cell membrane’s semipermeability and the actions of its channels,
gates, and pumps thus produce voltage across the cell membrane: its
resting potential ( Figure 4-12 ).

FIGURE 4-12 Resting Transmembrane Charge

Graded Potentials
The resting potential provides an energy store that can be used somewhat
like the water in a dam: small amounts can be released by opening gates
for irrigation or to generate electricity. If the concentration of any of the
ions across the unstimulated cell membrane changes, the membrane
voltage changes. These graded potentials are small voltage fluctuations
across the cell membrane.
graded potential Small voltage fluctuation across the cell
membrane.
Stimulating a membrane electrically through a microelectrode mimics
the way the membrane’s voltage changes to produce a graded potential in
the living cell. If the voltage applied to the inside of the membrane is
negative, the membrane potential increases in negative charge by a few
millivolts. As illustrated in Figure 4-13 A , it may change from a resting
potential of –70 mV to a slightly greater potential of –73 mV.
 This change is a hyperpolarization because the charge (polarity) of
the membrane increases. Conversely, if positive voltage is applied inside
the membrane, its potential decreases by a few millivolts. As illustrated
in Figure 4-13B , it may change from, say, a resting potential of –70 mV
to a slightly lower potential of –65 mV. This change is a depolarization
because the membrane charge decreases. Graded potentials usually last
only milliseconds.
hyperpolarization Increase in electrical charge across a membrane,
usually due to the inward flow of chloride or sodium ions or the
outward flow of potassium ions.
depolarization Decrease in electrical charge across a membrane,
usually due to the inward flow of sodium ions.
Hyperpolarization and depolarization typically take place on the soma
(cell body) membrane and on neuronal dendrites. These areas contain
gated channels that can open and close, changing the membrane potential
as illustrated in Figure 4-13 . Three channels—for potassium, chloride,
and sodium ions—underlie graded potentials:
 (A) Hyperpolarization

(B) Depolarization
 FIGURE 4-13 Graded Potentials (A) Stimulation (S) that increases
relative membrane voltage produces a hyperpolarizing graded potential.
(B) Stimulation that decreases relative membrane voltage produces a
depolarizing graded potential.

1. Potassium channels For the membrane to become hyperpolarized, its

extracellular side must become more positive, which can be
accomplished with an efflux of potassium ions. But if potassium
channels are ordinarily open, how can the efflux of potassium ions
increase? Apparently, even though potassium channels are open, some
resistance to the outward flow of potassium ions remains. Reducing
this resistance enables hyperpolarization.
2. Chloride channels The membrane can also become hyperpolarized if
an influx of chloride ions occurs. Even though chloride ions can pass
through the membrane, more ions remain on the outside than on the
inside, so a decreased resistance to Cl – flow can result in brief
increases of Cl – inside the cell.
3. Sodium channels Depolarization can be produced if normally closed
sodium channel gates open to allow an influx of sodium ions.
Evidence that potassium channels have a role in hyperpolarization
comes from the fact that the chemical tetraethylammonium (TEA),
which blocks potassium channels, also blocks hyperpolarization. The
involvement of sodium channels in depolarization is indicated by the fact
that the chemical tetrodotoxin (TTX), which blocks sodium channels,
also blocks depolarization. The puffer fish, considered a delicacy in
some countries, especially Japan, secretes this potentially deadly poison
to fend off potential predators. Skill is required to prepare this fish for
dinner. It can be lethal to the guests of careless cooks because its toxin
impedes the electrical activity of neurons.

The Photo Library—Sidney/Science Source

Puffer Fish

Action Potential
Electrical stimulation of the cell membrane at resting potential produces
local graded potentials. An action potential is a brief but large reversal
in an axon membrane’s polarity (Figure 4-14 A ). It lasts about 1 ms.
The voltage across the membrane suddenly reverses, making the
intracellular side positive relative to the extracellular side, then abruptly
reverses again to restore the resting potential. Because the action
potential is brief, many action potentials can occur within a second, as
illustrated in Figure 4-14B and C, where the time scales are compressed.
action potential Large, brief reversal in the polarity of an axon
membrane.
 An action potential occurs when a large concentration of first Na+ and
then K+ crosses the membrane rapidly. The depolarizing phase of the
action potential is due to Na+ influx, and the hyperpolarizing phase, to
K+ efflux. Sodium rushes in, then potassium rushes out. As shown in
Figure 4-15 , the combined flow of sodium and potassium ions underlies
the action potential.
An action potential is triggered when the cell membrane is
depolarized to about –50 mV. At this threshold potential, the membrane
charge undergoes a remarkable further change with no additional
stimulation. The relative voltage of the membrane drops to zero and
continues to depolarize until the charge on the inside of the membrane is
as great as +30 mV—a total voltage change of 100 mV. Then the
membrane potential reverses again, becoming slightly hyperpolarized—a
reversal of a little more than 100 mV. After this second reversal, the
membrane slowly returns to its resting potential at –70 mV.
threshold potential Voltage on a neural membrane at which an
action potential is triggered by the opening of sodium and potassium
voltage-sensitive channels; about –50 mV relative to extracellular
surround. Also called threshold limit.

(A)
 (B)

(C)

FIGURE 4-14 Measuring Action Potentials (A) Phases of a

single action potential. The time scales on the horizontal axes are
 compressed to chart (B) each action potential as a discrete event and (c)
the ability of a membrane to produce many action potentials in a short
time.

FIGURE 4-15 Triggering an Action Potential

The action potential normally consists of the summed current changes

caused first by the inflow of sodium and then by the outflow of
potassium on an axon. Experimental results reveal that if an axon
membrane is stimulated electrically while the solution surrounding the
axon contains the chemical TEA (to block potassium channels), the
result is a smaller-than-normal ion flow due entirely to an Na+ influx.
Similarly, if an axon’s membrane is stimulated electrically while the
solution surrounding the axon contains TTX (to block sodium channels),
a slightly different ion flow due entirely to the efflux of K+ is recorded.
Figure 4-16 illustrates these experimental results. The graphs in Figure
4-16 represent ion flow rather than voltage change.
Role of Voltage-Sensitive Ion Channels
What cellular mechanisms underlie the movement of sodium and
potassium ions to produce an action potential? The answer is the
behavior of a class of gated sodium and potassium channels sensitive to
the membrane’s voltage ( Figure 4-17 ). These voltage-sensitive
channels are closed when an axon’s membrane is at its resting potential:
ions cannot pass through them. When the membrane reaches threshold
voltage, the configuration of the voltage-sensitive channels alters: they
open briefly, enabling ions to pass through, then close again to restrict
ion flow. The sequence of actions:
voltage-sensitive channel Gated protein channel that opens or
closes only at specific membrane voltages.

FIGURE 4-16 Blocking an Action Potential

FIGURE 4-17 Voltage-Sensitive Potassium Channel
1. Both sodium and potassium voltage-sensitive channels are attuned to
the threshold voltage of about –50 mV. If the cell membrane changes
to reach this voltage, both types of channels open to allow ion flow
across the membrane.
2. The voltage-sensitive sodium channels are more sensitive than the
potassium channels and so open first. As a result, the voltage change
due to Na + influx takes place slightly before the voltage change due to
K + efflux can begin.
3. Sodium channels have two gates. Once the membrane depolarizes to
about +30 mV, one of the gates closes. Thus, Na + influx begins
quickly and ends quickly.
4. The potassium channels open more slowly than the sodium channels,
and they remain open longer. Thus, the efflux of K + reverses the
depolarization produced by Na + influx and even hyperpolarizes the
membrane.
Exceptions do exist: some CNS neurons discharge during the
repolarizing phase.
Action Potentials and Refractory Periods
There is an upper limit to how frequently action potentials occur, and
sodium and potassium channels are responsible for it. Stimulation of the
axon membrane during the depolarizing phase of the action potential will
not produce another action potential. Nor is the axon able to produce
another action potential when it is repolarizing. During these times, the
membrane is described as being absolutely refractory.
absolutely refractory The state of an axon in the repolarizing
period, during which a new action potential cannot be elicited (with
some exceptions), because gate 2 of sodium channels, which are not
voltage sensitive, are closed.
If on the other hand the axon membrane is stimulated during
hyperpolarization, another action potential can be induced, but the
second stimulation must be more intense than the first. During this
phase, the membrane is relatively refractory.
 relatively refractory The state of an axon in the later phase of an
action potential during which increased electrical current is required
to produce another action potential; a phase during which potassium
channels are still open.
Refractory periods result from the way gates of the voltage-sensitive
sodium and potassium channels open and close. Sodium channels have
two gates, and potassium channels have one gate. Figure 4-18 illustrates
the position of these gates before, during, and after the phases of the
action potential. We describe changes first in the sodium channels and
then in the potassium channels.

FIGURE 4-18 Phases of an Action Potential Initiated by

changes in voltage-sensitive sodium and potassium channels, an action
potential begins with a depolarization: gate 1 of the sodium channel opens
and then gate 2 closes. The slower-opening potassium channel gate
contributes to repolarization and hyperpolarization until the resting
membrane potential is restored.

During the resting potential, gate 1 of the sodium channel depicted in

Figure 4-18 is closed; only gate 2 is open. At the threshold level of
stimulation, gate 1 also opens. Gate 2, however, closes very quickly after
gate 1 opens. This sequence produces a brief period during which both
sodium gates are open. When both gates are open and when gate 2 is
closed, the membrane is absolutely refractory.
 The opening of the potassium channels repolarizes and eventually
hyperpolarizes the cell membrane. The potassium channels open and
close more slowly than the sodium channels do. The hyperpolarization
produced by a continuing efflux of potassium ions makes it more
difficult to depolarize the membrane to the threshold that reopens the
gates underlying an action potential. While the membrane is
hyperpolarizing, it is relatively refractory.
The action of a lever-activated toilet is analogous to some of the
changes in polarity that take place during an action potential. Pushing the
lever slightly produces a slight water flow that stops when the lever is
released. This activity is analogous to a graded potential. A harder lever
press brings the toilet to threshold and initiates flushing, a response that
is out of all proportion to the lever press. This activity is analogous to the
action potential.
During the flush, the toilet is absolutely refractory: another flush
cannot be induced at this time. During the refilling of the bowl, in
contrast, the toilet is relatively refractory, meaning that flushing again is
possible but harder. Only after the cycle is over and the toilet is once
again at rest can a full flush be produced again.

Nerve Impulse
Suppose you place two recording electrodes at a distance from one
another on an axon membrane, then electrically stimulate an area
adjacent to one electrode. That electrode would immediately record an
action potential. A similar recording would register on the second
electrode in a flash. An action potential has arisen near this second
electrode also, even though it is some distance from the original point of
stimulation.
Is this second action potential simply an echo of the first that passes
down the axon? No, it cannot be, because the action potential’s size and
shape are exactly the same at the two electrodes. The second is not just a
faint, degraded version of the first but is equal in magnitude. Somehow
the full action potential has moved along the axon. This propagation of
an action potential along an axon is called a nerve impulse.
nerve impulse Propagation of an action potential on the membrane
of an axon.
 Why does an action potential move? Remember that the total voltage
change during an action potential is 100 mV, far beyond the 20-mV
change needed to bring the membrane from its resting state of –70 mV to
the action potential threshold level of –50 mV. Consequently, the voltage
change on the part of the membrane where an action potential first
occurs is large enough to bring adjacent parts of the membrane to a
threshold of –50 mV.
When the membrane at an adjacent part of the axon reaches –50 mV,
the voltage-sensitive channels at that location pop open to produce an
action potential there as well. This second occurrence in turn induces a
change in the membrane voltage still farther along the axon, and so on
and on, down the axon’s length. Figure 4-19 illustrates this process. The
nerve impulse occurs because each action potential propagates another
action potential on an adjacent part of the axon membrane. The word
propagate means to give birth, and that is exactly what happens. Each
successive action potential gives birth to another down the length of the
axon.
FIGURE 4-19Propagating an Action Potential Voltage sufficient to open
+ +
Na and K channels spreads to adjacent sites of the axon membrane, inducing voltage-
sensitive gates to open. Here, voltage changes are shown on only one side of the
membrane.

Because they are propagated by gated ion channels acting on the

membrane in their own vicinity, action potentials on a nerve or tract are
the same magnitude wherever they occur. An action potential depends on
energy expended where it occurs, and the same amount of energy is
expended at every site along the membrane as a nerve impulse is
propagated.
As a result, action potentials do not dissipate: an action potential is
either generated completely or not generated at all. Action potentials are
all-or-none events. As the nerve’s impulse, or message, the action
potential maintains a constant size and arrives unchanged to every
terminal on the nerve that receives it.
Think of the voltage-sensitive channels along the axon as a series of
dominoes. When one falls, it knocks over its neighbor, and so on down
the line. There is no decrement in the size of the fall. The last domino
travels exactly the same distance and falls just as hard as the first one
did.
Essentially, the domino effect happens when voltage-sensitive
channels open. The opening of one channel produces a voltage change
that triggers its neighbor to open, just as one domino knocks over the
next. The channel-opening response does not grow any weaker as it
moves along the axon, and the last channel opens exactly like the first,
just as the domino action stays constant to the end of the line.
 The domino effect

Refractory Periods and Nerve Action

Refractory periods are determined by the position of the gates that
mediate ion flow in the voltage-sensitive channels. This limits the
frequency of action potentials to about 5 ms. The action potential’s
refractory phase thus has two practical uses for nerves that are
conducting information.
First, the maximum rate at which action potentials can occur is about
200 per second (1 s or 1000 ms/5 ms limit = 200 action potentials in 1 s).
The sensitivity of voltage-sensitive channels, which varies among kinds
of neurons, likewise affects firing frequency.
Second, although an action potential can travel in either direction on
an axon, refractory periods prevent it from reversing direction and
returning to its point of origin. Refractory periods thus produce a single,
discrete impulse that travels away from the initial point of stimulation.
When an action potential begins near the cell body, it usually travels
down the axon to the terminals.
To return to our domino analogy, once a domino falls, setting it back
up takes time. This is its refractory period. Because each domino falls as
it knocks down its neighbor, the sequence cannot reverse until the
domino is set upright again: the dominos can fall in only one direction.
The same principle determines the action potential’s direction.

Saltatory Conduction and the Myelin

Sheath
Because the giant axons of squid are so large, they can transmit nerve
impulses very quickly, much as a large-diameter pipe can rapidly deliver
a lot of water. But large axons take up substantial space: a squid cannot
accommodate many of them or its body would be too bulky. For us
mammals, with our many axons producing repertoires of complex
behaviors, giant axons are out of the question. Our axons must be
extremely slender because our complex behaviors require a great many
of them.
Our largest axons are only about 30 µm wide, so the speed with which
they convey information should not be especially fast. And yet, like most
vertebrate species, we humans are hardly sluggish creatures. We process
information and generate responses with impressive speed. How do we
manage to do so if our axons are so thin? The vertebrate nervous system
has evolved a solution that has nothing to do with axon size.
Glial cells play a role in speeding nerve impulses in the vertebrate
nervous system. Schwann cells in the human peripheral nervous system
and oligodendroglia in the central nervous system wrap around each
axon, forming the myelin sheath that insulates it ( Figure 4-20 ). Action
potentials cannot occur where myelin is wrapped around an axon. For
one thing, the myelin is an insulating barrier to ionic current flow. For
another, axonal regions that lie under myelin have few channels through
which ions can flow, and ion channels are essential to generating an
action potential.
(A)
(B)
 FIGURE 4-20 Myelination An axon is insulated by (A) oligodendroglia in
the CNS and (B) Schwann cells in the PNS. Each glial cell is separated by
a gap, or node of Ranvier.

To review glial cell types, appearance, and functions, see Table 3-1 .
But axons are not totally encased in myelin. Unmyelinated gaps
between successive glial cells are richly endowed with voltage-sensitive
channels. These tiny gaps in the myelin sheath, the nodes of Ranvier,
are sufficiently close to one another that an action potential at one node
can open voltage-sensitive gates at an adjacent node. In this way, a
relatively slow action potential jumps quickly from node to node, as
shown in Figure 4-21 . This flow of energy is called saltatory
conduction (from the Latin verb saltare, meaning to leap ).
node of Ranvier The part of an axon that is not covered by myelin.
saltatory conduction Fast propagation of an action potential at
successive nodes of Ranvier; saltatory means leaping.
 Myelin has two important consequences for propagating action
potentials. First, propagation becomes energetically cheaper, since action
potentials regenerate only at the nodes of Ranvier, not along the axon’s
entire length. Action potential conduction in unmyelinated axons, by
contrast, has a significant metabolic energy cost (Crotty et al., 2006).
The second consequence is that myelin improves the action potential’s
conduction speed.
Jumping from node to node speeds the rate at which an action
potential can travel along an axon, because the current flowing within the
axon beneath the myelin sheath travels very fast. While the current
moves speedily, the voltage drops quickly over distance. But the nodes
of Ranvier are spaced ideally to ensure sufficient voltage at the next node
to regenerate the action potential. On larger, myelinated mammalian
axons, nerve impulses can travel at a rate as high as 120 meters per
second. On smaller, uninsulated axons they travel only about 30 meters
per second.
Spectators at sporting events sometimes initiate a wave that travels
around a stadium. Just as one person rises, the next person begins to rise,
producing the wave effect. This human wave is like conduction along an
unmyelinated axon. Now think of how much faster the wave would
complete its circuit around the field if only spectators in the corners rose
to produce it. This is analogous to a nerve impulse that travels by
jumping from one node of Ranvier to the next. The quick reactions that
humans and other mammals are capable of are due in part to this
saltatory conduction in their nervous system.
Neurons that send messages over long distances quickly, including
sensory and motor neurons, are heavily myelinated. If myelin is
damaged, a neuron may be unable to send any messages over its axons.
In multiple sclerosis (MS ), the myelin formed by oligodendroglia is
damaged, which disrupts the functioning of neurons whose axons it
encases. Clinical Focus 4-2 , Multiple Sclerosis on page 126 , describes
the course of the disease.
multiple sclerosis (Ms) Nervous system disorder resulting from the
loss of myelin around axons in the CNS.
FIGURE 4-21 Saltatory Conduction Myelinated stretches of axons
are interrupted by nodes of Ranvier, rich in voltage-sensitive channels. In
saltatory conduction, the action potential jumps rapidly from node to node.
CLINICAL FOCUS 4-2

Multiple Sclerosis
One day J. O., who had just finished university requirements to
begin work as an accountant, noticed a slight cloudiness in her right
eye. It did not go away when she wiped her eye. Rather, the area
grew over the next few days. Her optometrist suggested that she see
a neurologist, who diagnosed optic neuritis, an indication that can be
a flag for multiple sclerosis (MS).
MS is caused by a loss of myelin produced by oligodendroglia
cells in the CNS (see illustration). It disrupts the affected neurons’
ability to propagate action potentials via saltatory conduction. This
loss of myelin occurs in patches, and scarring frequently results in
the affected areas.
Eventually, a hard scar, or plaque, forms at the site of myelin loss.
(MS is called a sclerosis from the Greek word meaning hardness. )
Associated with the loss of myelin is impairment of neuron function,
causing characteristic MS symptoms of sensory loss and difficulty in
moving.
Fatigue, pain, and depression are commonly associated with MS.
Bladder dysfunction, constipation, and sexual dysfunction all
complicate it. MS, about twice as common in women as in men,
greatly affects a person’s emotional, social, and vocational
functioning.
Multiple sclerosis is the most common of nearly 80 autoimmune
diseases, conditions in which the immune system makes antibodies
to a person’s own body (Rezania et al., 2012). Although MS patients
are treated with anti-inflammatory agents, it has no cure as yet.
autoimmune disease Illness resulting from an abnormal
immune response by the body against substances and tissues
normally present in the body.
J. O.’s eye cleared over the next few months, and she had no
further symptoms until after the birth of her first child 3 years later,
when she felt a tingling in her right hand. The tingling spread up her
arm, until gradually she lost movement in the arm for 5 months.
Then J. O.’s arm movement returned. But 5 years later, after her
second child was born, she felt a tingling in her left big toe that
spread along the sole of her foot and then up her leg, eventually
leading again to loss of movement. J. O. received corticosteroid
treatment, which helped, but the condition rebounded when she
stopped treatment. Then it subsided and eventually disappeared.
Since then, J. O. has had no major outbreaks of motor
impairment, but she reports enormous fatigue, takes long naps daily,
and is ready for bed early in the evening. Her sister and a female
cousin have experienced similar symptoms, and recently a third
sister began to display similar symptoms in middle age. One of J.
O.’s grandmothers was confined to a wheelchair, although the source
of her problem was never diagnosed.
MS is difficult to diagnose. Symptoms usually appear in
adulthood, their onset is quite sudden and their effects can be swift.
Initial symptoms may be loss of sensation in the face, limbs, or body
or loss of control over movements or loss of both sensation and
control. Motor symptoms usually appear first in the hands or feet.
Early symptoms often go into remission and do not appear again
for years. In some forms, however, MS progresses rapidly over just a
few years until the person is bedridden.
MS is common in the most northern and most southern latitudes,
so it may be related to a lack of vitamin D, which is produced by the
action of sunlight on the skin. The disease may also be related to
genetic susceptibility, as is likely in J. O.’s case. Many MS patients
take vitamin D3 and vitamin B12 .
It has been suggested that blood flow from the brain is reduced in
MS, allowing a buildup of toxic iron. Widening veins that drain
blood from the brain is suggested as a treatment. Clinical trials have
been initiated on the basis of reports from media and in response to
patient groups rather than on established scientific evidence. It has
been argued that methodological flaws and lack of evidence
disqualify both the venous cause of MS and venous widening as an
appropriate treatment (Valdueza et al., 2013).
Normal myelinated nerve fiber

Nerve affected by MS
 4-2 REVIEW
Electrical Activity of a Membrane
Before you continue, check your understanding.
1 . The ___________ results from the unequal distribution of ___________
inside and outside the cell membrane.
2 . Because it is ___________, the cell membrane prevents the efflux of
large protein anions and pumps sodium ions out of the cell to maintain a
slightly ___________ charge in the intracellular fluid relative to the
extracellular fluid.
3 . For a graded potential to arise, a membrane must be stimulated to the
point that the transmembrane charge increases slightly to cause a(n)
___________ or decreases slightly to cause a(n) ___________.
4 . The voltage change associated with a(n) ___________ is sufficiently
large to stimulate adjacent parts of the axon membrane to the threshold
for propagating it along the length of an axon as a(n) ___________.
5 . Briefly explain why nerve impulses travel faster on myelinated than on
unmyelinated axons.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 4-3 How Neurons Integrate Information
A neuron’s extensive dendritic tree is covered with spines, and through
them it can establish more than 50,000 connections from other neurons.
Lying between its dendritic tree and axon, a neuron’s cell body, too, can
receive multiple connections. Nerve impulses traveling from other
neurons to each of these synaptic locations bombard the receiving neuron
with excitatory and inhibitory inputs.
Neurons that receive more than one kind of input sum up the
information they get.
In the 1960s, John C. Eccles (1965) and his students performed
experiments that helped to answer the question, how does the neuron
integrate such an enormous array of inputs into a nerve impulse? Rather
than recording from the giant axon of a squid, Eccles recorded from the
cell bodies of large motor neurons in the vertebrate spinal cord. In doing
so, he refined the electrical stimulating and recording techniques first
developed for studying squid axons (see Section 4-1 ). Eccles received
the Nobel Prize in Physiology or Medicine in 1963.
Motor neurons, for example, receive input from multiple sources. A
spinal cord motor neuron has an extensive dendritic tree with as many as
20 main branches that subdivide numerous times and are covered with
dendritic spines. Input from the skin, joints, muscles, spinal cord, and
brain make motor cells ideal for studying how a neuron responds to
diverse inputs. Each motor neuron sends its axon directly to a muscle.
The motor neuron is the final common pathway the nervous system takes
to produce behavior.
Figure 2-29 A diagrams the human spinal cord in cross section.

Excitatory and Inhibitory Postsynaptic

Potentials
To study motor neuron activity, Eccles inserted a microelectrode into a
vertebrate’s spinal cord until the tip was in or right beside a motor
neuron’s cell body. He then placed stimulating electrodes on sensory
nerve fiber axons entering the spinal cord. By teasing apart the incoming
sensory fibers, he was able to stimulate one nerve fiber at a time.
 Experiment 4-1 diagrams the experimental setup Eccles used. As
shown at the left in the Procedures section, stimulating some incoming
sensory fibers produced a depolarizing graded potential (reduced the
charge) on the membrane of the motor neuron to which these fibers were
connected. Eccles called these graded potentials excitatory postsynaptic
potentials (EPSPs). As graphed at left in the Results section, EPSPs
reduce the charge on the membrane toward the threshold level and
increase the likelihood that an action potential will result.
excitatory postsynaptic potential (EPsP)
Brief depolarization of a neuron membrane in response to
stimulation, making the neuron more likely to produce an action
potential.
At the right in the Procedures section, when Eccles stimulated other
incoming sensory fibers, he produced a hyperpolarizing graded potential
(increased the charge) on the receiving motor neuron membrane. Eccles
called these graded potentials inhibitory postsynaptic potentials
(IPSPs). As graphed at the right in the Results section, IPSPs increase the
charge on the membrane away from the threshold level and decrease the
likelihood that an action potential will result.
inhibitory postsynaptic potential (IPsP)
Brief hyperpolarization of a neuron membrane in response to
stimulation, making the neuron less likely to produce an action
potential.
 EXPERIMENT 4-1

Question: How does stimulating a neuron influence its

excitability?
Procedure

Results

Conclusion: EPSPs increase the likelihood that an action potential will

result.
IPSPs decrease the likelihood that an action potential will result.

Both EPSPs and IPSPs last only a few milliseconds before they decay
and the neuron’s resting potential is restored. EPSPs are associated with
the opening of sodium channels, which allows an influx of sodium ions.
IPSPs are associated with the opening of potassium channels, which
allows an efflux of potassium ions (or with the opening of chloride
channels, which allows an influx of chloride ions).
Although the size of a graded potential is proportional to the intensity
of the stimulation, an action potential is not produced on the motor
neuron’s cell body membrane even when an EPSP is strongly excitatory.
The reason is simple: the cell body membrane of most neurons does not
contain voltage-sensitive channels. The stimulation must reach the initial
segment, the area near or overlapping the axon hillock, where the action
potential begins. The initial segment is rich in voltage-sensitive channels
(Bender & Trussel, 2012).
initial segment Area near or overlapping the axon hillock where the
action potential begins.
A brief video at www.youtube.com/watch?v=-qdH3WGL99Q
describes how the initial segment initiates an action potential.

Summation of Inputs
A motor neuron’s myriad dendritic spines can each contribute to
membrane voltage, via either an EPSP or an IPSP. How do these
incoming graded potentials interact at its membrane? What happens if
two EPSPs occur in succession? Does it matter if the time between them
increases or decreases? What happens when an EPSP and an IPSP arrive
together?

(A) EPSPs
Wide temporal spacing

(B) IPSPs
Wide temporal spacing
 FIGURE 4-22 Temporal Summation (A) Two depolarizing pulses
stimulation (S1 and S2 ) separated in time produce two EPSPs similar in
size. Pulses close together in time partly sum. Simultaneous EPSPs sum
as one large EPSP. (B) Two hyperpolarizing pulses (S1 and S2 ) widely
separated in time produce two IPSPs similar in size. Pulses coming fast
partly sum. Simultaneous IPSPs sum as one large IPSP.

Temporal Summation
If one excitatory pulse is followed some time later by a second excitatory
pulse, one EPSP is recorded and after a delay, a second identical EPSP is
recorded, as shown at the top left in Figure 4-22 . These two widely
spaced EPSPs are independent and do not interact. If the delay between
them is shortened so that the two occur in rapid succession, however, a
single large EPSP is produced, as shown in the left-center panel of
Figure 4-22 .
Here, the two excitatory pulses are summed—added together to
produce a larger depolarization of the membrane than either would
induce alone. This relation between two EPSPs occurring close together
or even at the same time (bottom left panel) is called temporal
summation. The right side of Figure 4-22 illustrates that equivalent
results are obtained with IPSPs. Therefore, temporal summation is a
property of both EPSPs and IPSPs.
temporal summation Addition of one graded potential to another
that occur close in time.
Spatial Summation
How does spacing affect inputs to the cell body membrane? By using
two recording electrodes (R1 and R2 ) we can see the effects of spatial
relations on the summation of inputs.
If two EPSPs are recorded at the same time but on widely separated
parts of the membrane (Figure 4-23 A ), they do not influence one
another. If two EPSPs occurring close together in time are also close
together on the membrane, however, they sum to form a larger EPSP
(Figure 4-23B ). This spatial summation occurs when two separate
inputs are very close to one another both on the cell membrane and in
time. Similarly, two IPSPs produced at the same time sum if they occur
at approximately the same place and time on the cell body membrane but
not if they are widely separated.
spatial summation Addition of one graded potential to another that
occur close in space.
Role of Ions in Summation
Summation is a property of both EPSPs and IPSPs in any combination.
These interactions make sense when you consider that ion influx and
efflux are being summed. The influx of sodium ions accompanying one
EPSP is added to the influx of sodium ions accompanying a second
EPSP if the two occur close together in time and space. If the two
influxes are remote in time or in space or in both, no summation is
possible.
 EPSPs produced at the same time, but on separate
parts of the membrane, do not influence each other.

%%%%%%
(A)

EPSPs produced at the same time, and close together, sum to

form a larger EPSP.
(B)
 FIGURE 4-23Spatial Summation The process for EPSPs. The process for
IPSPs is equivalent.

The same is true regarding effluxes of potassium ions. When they

occur close together in time and space, they sum; when they are far apart
in either or both ways, there is no summation. The patterns are identical
for an EPSP and an IPSP. The influx of sodium ions associated with the
EPSP is added to the efflux of potassium ions associated with the IPSP,
and the difference between them is recorded as long as they are spatially
and temporally close together. If, on the other hand, they are widely
separated in time or in space or in both, they do not interact and there is
no summation.
A neuron with thousands of inputs responds no differently from one
with only a few inputs. It democratically sums all inputs that are close
together in time and space. The cell body membrane, therefore, always
indicates the summed influences of multiple temporal and spatial inputs.
And so a neuron can be said to analyze its inputs before deciding what to
do. The ultimate decision is made at the initial segment, the region on the
axon that initiates the action potential.
FIGURE 4-24Triggering an Action Potential If the summated graded potentials—the
EPSPs and IPSPs—on the dendritic tree and cell body of a neuron charge the
membrane to threshold level at the initial segment, an action potential is initiated, and it
travels down the axon membrane.

Voltage-Sensitive Channels and the Action

Potential
Unlike the cell body membrane, the axon is rich in voltage-sensitive
channels, beginning at the initial segment (Figure 4-24 ). These
channels, like those on the squid axon, open at a particular membrane
voltage. The actual threshold voltage varies with the type of neuron, but
to keep things simple, we will stay with a threshold level of –50 mV.
To produce an action potential, the summed graded potentials—the
IPSPs and EPSPs—on the cell body membrane must depolarize the
membrane at the initial segment to –50 mV. If that threshold voltage is
obtained only briefly, voltage-sensitive channels open, and just one or a
few action potentials may occur. If the threshold level is maintained for a
longer period, however, action potentials will follow one another in rapid
succession, just as quickly as the gates on the voltage-sensitive channels
can reset. Each action potential is then repeatedly propagated to produce
a nerve impulse that travels from the initial segment down the length of
the axon.
Many neurons have extensive dendritic trees, but dendrites and
dendritic branches do not have many voltage-sensitive channels and
ordinarily do not produce action potentials. And distant branches of
dendrites may have less influence in producing action potentials initiated
at the initial segment than do the more proximal branches of the
dendrites. Consequently, inputs close to the initial segment are usually
much more influential than those occurring some distance away. Those
distant inputs usually have a modulating effect. As in all governments,
some inputs have more say than others (Debanne, 2011).
The hippocampus (from the Greek meaning seahorse because its
shape is similar) participates in aspects of memory and is vulnerable
to stress (see Section 6-5 ).

The Versatile Neuron

Dendrites collect information as graded potentials (EPSPs and IPSPs),
and the initial segment initiates discrete action potentials delivered to
other target cells via the axon. Exceptions to this picture of how a neuron
works do exist. For example, some cells in the developing hippocampus
can produce additional action potentials, called giant depolarizing
potentials, when the cell would ordinarily be refractory. It is thought that
giant depolarizing potentials aid in developing the brain’s neural
circuitry (Mohajerani & Cherubini, 2006).
Because the cell body membrane does not contain voltage-sensitive
channels, a typical neuron does not initiate action potentials on its
dendrites. In some neurons, however, voltage-sensitive channels on
dendrites do enable action potentials. The reverse movement of an action
potential from the initial segment into the dendritic field of a neuron is
called back propagation. Back propagation, which signals the dendritic
field that the neuron is sending an action potential over its axon, may
play a role in plastic changes in the neuron that underlie learning. For
example, back propagation may make the dendritic field refractory to
incoming inputs, set the dendritic field to an electrically neutral baseline,
or reinforce signals coming in to certain dendrites (Legenstein and
Maass, 2011).
back propagation Reverse movement of an action potential into the
soma and dendritic field of a neuron; postulated to play a role in
plastic changes that underlie learning.
We explore the neuronal basis of learning in Sections 5-4 and 14-4 .
The neurons of some nonmammalian species have no dendritic
branches. And some ion channels, rather than responding to voltage,
respond to light by opening and allowing ions to pass. The many
differences among neurons suggest that the nervous system capitalizes
on structural and functional modifications to produce adaptive behavior
in each species. In research to determine the neuron’s specific functions,
neuroscientists have incorporated into certain types of neurons ion
channels that respond to light, as described in Research Focus 4-3 ,
Optogenetics and Light-Sensitive Channels.
Section 7-1 describes the promise of optogenetics for neuroscience
research and for clinical applications.
RESEARCH FOCUS 4-3

Optogenetics and Light-Sensitive Ion

Channels
Membrane channels that are responsive to light have been
discovered in nonmammalian animal species. Using the transgenic
technique of optogenetics, researchers have successfully introduced
light-sensitive channels into worms, fruit flies, and mice.
optogenetics Transgenic technique that combines genetics and
light to excite or inhibit targeted cells in living tissue.
Optogenetics combines genetics and light to control targeted cells
in living tissue. Here we examine how introducing different light-
sensitive channels into a species excites the organism’s movements
with one wavelength and inhibits them with another wavelength.
One class of light-activated ion channels in the green alga
Chlamydomonas reinhardtii is channelrhodopsin-2. The ChR2
channel absorbs blue light and in doing so opens briefly to allow the
passage of cations, including sodium and potassium. These light-
sensitive channels allow the passage of Na+ and K+ when a cell is
illuminated with blue light. The resulting depolarization excites the
cell to generate action potentials.
Halorhodopsin (NpHR) is a light-driven ion pump, specific for
chlo-ride ions and found in phylogenetically ancient bacteria
(archaea) known as halobacteria. When illuminated with green-
yellow light, the halorhodopsin pumps chloride anions into the cell,
hyperpolarizing it and so inhibiting its activity.
The movements of worms, fruit flies, and mice with genetically
introduced light-sensitive channels have been controlled when their
nervous system cells were illuminated with appropriate wavelengths
of light. One such species, Caenorhabditis elegans, is a roundworm
about 1 millimeter long that lives in soil.
C. elegans is popular in neuroscience experiments because it is
trans-parent and has a simple nervous system. It is also the first
species to have all its neurons, synapses, and genome completely
described. The illustration shows (A) the normal movements of C.
elegans and the light-sensitive membrane channel responses that (B)
excite or (C) inhibit its movement.
Using optogenetic techniques, light-sensitive channels can be
incorporated into specific neural circuits so that light stimulation
controls only a subset of neurons. The promise is that investigating
specific neuron populations can provide insight into brain disease,
including conditions such as addiction (Cao et al., 2011).
Also encouraging are the results of a study suggesting that
impaired vision due to the loss of the light-sensitive retina of the eye
could be restored with light-sensitive channels (Fenno et al., 2011).

a
Sinclair Stammers/Science Source
(A) C. elegans
(B) Excitation
(C) Inhibition
Light-Sensitive Channels (A) Normal movements of C. elegans. (B) When
light-sensitive channelrhodopsin-2 ion channels are introduced into its
neurons, C. elegans becomes active and coils when exposed to blue light.
Information from Zhang et al., 2007. (c) With light-sensitive halorhodopsin ion
pumps introduced into its muscles, C. elegans elongates and becomes
immobile when exposed to green-yellow light. Information from Liewald et al.,
2008.
 4-2 REVIEW
How Neurons Integrate Information
Before you continue, check your understanding.
1 . Graded potentials that decrease the charge on the cell membrane,
moving it toward the threshold level, are called ___________ because
they increase the likelihood that an action potential will occur. Graded
potentials that increase the charge on the cell membrane, moving it
away from the threshold level, are called ___________ because they
decrease the likelihood that an action potential will result.
2 . EPSPs and IPSPs that occur close together in both ___________ and
___________ are summed. This is how a neuron ___________ the
information it receives from other neurons.
3 . The membrane of the ___________ does not contain voltage-
sensitive ion channels, but if summed inputs excite the ___________
to a threshold level, action potentials are triggered and then propagated
as they travel along the cell’s ___________ as a nerve impulse.
4 . Explain what happens during back propagation.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 4-4 Into the Nervous System and Back
Out
The nervous system allows us to respond to afferent sensory stimuli by
detecting them and sending messages about them to the brain. The brain
interprets the information, triggering efferent responses that contract
muscles and produce behavior. Until now, we have been dealing only
with the middle of this process—how neurons convey information to one
another, integrate the information, and generate action potentials. Now
we explore the beginning and end of the journey.
To fill in the missing pieces, we explain how a sensory stimulus
initiates a nerve impulse and how a nerve impulse produces a muscular
contraction. Once again, ion channels are vitally important, but in
muscles, the channels are different from those described so far.
For detail on how sensory receptors transduce external energy into
action potentials:
Hearing, Section 10-1
Sensation and perception, Section 9-1
Smell and taste, Section 12-2
Touch, pain, and balance, Section 11-4
Vision, Section 9-2

How Sensory Stimuli Produce Action

Potentials
We receive information about the world through bodily sensations (touch
and balance), auditory sensations (hearing), visual sensations (sight), and
chemical sensations (taste and olfaction). Each sensory modality has one
or more separate functions. In addition to touch, for example, the body
senses include pressure, joint sense, pain, temperature, and itch.
Receptors for audition and balance are modified touch receptors. The
visual system has receptors for light and for colors. And taste and
olfactory senses respond to a plethora of chemical compounds.
To process all these varied sensory inputs requires a remarkable array
of sensory receptors. But in all our sensory systems, the neurons related
to these diverse receptors have one thing in common: conduction of
information begins at ion channels. They initiate the chain of events that
produces a nerve impulse.
An example is touch. Each hair on the human body allows us to detect
even a very slight displacement. You can demonstrate this sensitivity to
yourself by selecting a single hair on your arm and bending it. If you are
patient and precise in your experimentation, you will discover that some
hairs are sensitive to displacement in one direction only, whereas others
respond to displacement in any direction. What enables this finely tuned
sensitivity?
The base of each hair is wrapped in a dendrite of a touch neuron.
When you bend a hair or otherwise mechanically displace it, the
encircling dendrite is stretched (Figure 4-25 ). The displacement opens
stretch-sensitive channels in the dendrite’s membrane. When open,
these channels allow an influx of sodium ions sufficient to depolarize the
dendrite to threshold. At threshold, the voltage-sensitive sodium and
potassium channels initiate a nerve impulse that conveys touch
information to your brain.
stretch-sensitive channel Ion channel on a tactile sensory neuron
that activates in response to stretching of the membrane, initiating a
nerve impulse.
Other kinds of sensory receptors have similar mechanisms for
transducing (transforming) the energy of a sensory stimulus into nervous
system activity. When displaced, the hair receptors that provide
information about hearing and balance likewise activate stretch-sensitive
channels. In the visual system, photons (light particles) strike opsin
proteins in receptors within specialized cells in the eye. The resulting
chemical change activates ion channels in relay neuron membranes. An
odorous molecule in the air that lands on an olfactory receptor and fits
itself into a specially shaped compartment opens chemical-sensitive ion
channels. When tissue is damaged, injured cells release chemicals that
activate channels on a pain nerve. The point here is that ion channels
originate conduction of information in all our sensory systems.
 FIGURE 4-25 Tactile Stimulation A hair’s touch receptor activated by
a feather results in a nerve impulse heading to the brain.

How Nerve Impulses Produce Movement

What happens at the end of the neural journey? After sensory
information has traveled to the brain and been interpreted, how does the
brain generate output—a behavioral response that includes muscle
contractions? Behavior, after all, is movement, and for movement to take
place, muscles must contract. Motor neurons in the spinal cord are
responsible for activating muscles. Without them movement becomes
impossible and muscles atrophy, as described in Clinical Focus 4-4 ,
ALS: Lou Gehrig’s Disease.
Motor neurons send nerve impulses to synapses on muscle cells.
These synapses are instrumental in making the muscle contract. Each
motor neuron axon makes one or a few synapses with its target muscle,
synapses similar to those neurons make with one another Figure 4-26 A
). The axon terminal contacts a specialized area of the muscle membrane
called an end plate. Onto the muscle’s end plate the axon terminal
releases the chemical transmitter acetylcholine.
end plate On a muscle, the receptor–ion complex that is activated
by the release of the neurotransmitter acetylcholine from the
 terminal of a motor neuron.
Acetylcholine does not enter the muscle but rather attaches to
transmitter-sensitive channels on the end plate (Figure 4-26B ). When
these channels open in response, they allow a flow of Na+ and K+ across
the muscle membrane sufficient to depolarize the muscle to the threshold
for its action potential. Yes, to contract, muscles generate action
potentials. At this threshold, adjacent voltage-sensitive channels open.
They in turn produce an action potential on the muscle fiber, as they do
in a neuron.
transmitter-sensitive channel Receptor complex that has both a
receptor site for a chemical and a pore through which ions can flow.
The transmitter-sensitive channels on muscle end plates are somewhat
different from the channels on axons and dendrites. A single end plate
channel is larger than two sodium and two potassium channels on a
neuron, combined. So when its transmitter- sensitive channels open, they
allow both Na+ influx and K+ efflux through the same pore. Generating a
sufficient depolarization on the end plate to activate neighboring voltage-
sensitive channels on the muscle membrane requires the release of an
appropriate amount of acetylcholine.
(A)
(B)
FIGURE 4-26 Muscle Contraction (A) When a motor neuron’s axon
collaterals contact a muscle fiber end plate, (B) acetylcholine attaches to
receptor sites on the end plate’s transmitter-sensitive channels, opening
them. These large membrane channels allow simultaneous influx of Na+
and efflux of K+ , generating current sufficient to activate voltage-sensitive
channels, triggering action potentials, and causing the muscle to contract.
CLINICAL FOCUS 4-4

ALS: Lou Gehrig’s Disease

In 1869, French physician Jean-Martin Charcot first described ALS,
amyotrophic lateral sclerosis. In North America, ALS is also known
as Lou Gehrig’s disease. Gehrig, a baseball legend who played for
the New York Yankees from 1923 until 1939, set a host of individual
records. He was an outstanding hitter, and his incredible durability
earned him the nickname the Iron Horse.
Gerhig played on many World Series championship teams, but
ALS sapped his strength, forcing him to retire from baseball at age
36. Amyotrophic means muscle weakness ; lateral sclerosis means
hardening of the lateral spinal cord. Gehrig’s condition deteriorated
rapidly. He died 2 years later. ALS strikes most commonly at age 50
to 75, although its onset can be as early as the teenage years.
While death often occurs within 5 years of diagnosis,
internationally renowned theoretical physicist and cosmologist
Stephen Hawking is a notable exception. Diagnosed at age 21,
Hawking has a rare early-onset and slowly progressing form of ALS.
As a doctoral student at Oxford, he grew increasingly clumsy, and
his speech was slightly slurred. In his late twenties he began to use
crutches. In his thirties his speech deteriorated until and only his
family and close friends understood him. Now in his seventies, and
confined to a wheelchair, Hawking, pictured at right, communicates
by using a single cheek muscle attached to a speech-generating
device.
Roughly 10 percent of people with ALS have a family history of
the disorder. About 5000 new cases are reported in the United States
each year. ALS is due primarily to the death of spinal motor neurons
but can affect brain neurons as well in some cases.
ALS typically begins with general weakness, at first in the throat
or upper chest and in the arms and legs. Gradually, walking becomes
difficult and falling common. ALS does not usually affect any
sensory systems, cognitive functions, bowel or bladder control, or
even sexual function. Even as his motor neurons continue to die,
 Stephen Hawking’s mind-blowing advancements continue to enrich
our understanding of the universe.
At present, no cure for ALS exists, although some newly
developed drugs appear to slow its progression and offer some hope
for future treatments. In 2014 the ALS Ice Bucket Challenge
appeared on YouTube to promote awareness of ALS and encourage
donations to research. The Challenge went viral.

Rex Features via AP Images

Sections 5-2 and 5-3 describe the varieties of chemical transmitters

and how they function.
Should the acetylcholine receptors on muscle end plates be blocked,
acetylcholine released from the motor neuron cannot properly exert its
depolarizing effect. This prevents muscular contraction in conditions
such as the autoimmune disease myasthenia gravis. In affected
individuals the thymus, an immune system gland that normally produces
antibodies to foreign material like viruses, makes antibodies to the
acetylcholine receptors on muscles, causing weakness and fatigue
(Figure 4-27 ).
 Unlike MS, another autoimmune disease, myasthenia gravis is usually
well controlled by treatments including drugs that suppress the immune
system or inhibit acetylcholine breakdown, extending the time it can act,
and by removal of the thymus gland (thymectomy).
The actions of membrane channels can explain a wide range of neural
events. Some channels generate the transmembrane charge. Others
mediate graded potentials. Still others trigger the action potential.
Sensory stimuli activate channels on neurons to initiate a nerve impulse,
and the nerve impulse eventually activates channels on motor neurons to
produce muscle contractions.
These various channels and their different functions evolved over a
long time in the same way that new species of animals and their
behaviors evolve. We have not described all the different ion channels
that neural membranes possess, but you will learn about some additional
ones in subsequent chapters.

Courtesy of Y. Harati, M.D./Baylor College of Medicine, Houston, Texas

FIGURE 4-27Myasthenia Gravis Asked to look up (1), this patient’s eyelids
quickly become fatigued and droop (2, 3). After a few minutes of rest her
eyelids open normally (4).
 4-2 REVIEW
Into the Nervous System and Back Out
Before you continue, check your understanding.
1 . Different sensory stimuli initiate nerve impulses for each
___________ in a similar way.
2 . A(n) ___________ membrane contains a mechanism for transducing
sensory energy into changes in ion channels. In turn, the channels
allow ion flow to alter the membrane voltage to the point that
___________ channels open, initiating a nerve impulse.
3 . Sensory stimuli activate ion channels to initiate a nerve impulse that
activates channels on ___________ neurons, which in turn contract
___________.
4 . In myasthenia gravis, a(n) ___________ disease, the thymus gland
produces antibodies to ___________ receptors on muscles, causing
weakness and fatigue.
5 . Why have so many kinds of ion channels evolved on cell
membranes?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 SUMMARY
4-1 Searching for Electrical Activity in the Nervous
System
Electrical stimulation studies dating as far back as the eighteenth century
show that stimulating a nerve with electrical current induces a muscle
contraction. In more recent recording studies, the brain’s electrical
current, measured using an oscilloscope, shows that electrical activity in
the nervous system is continuous.
In the twentieth century, researchers used giant axons of the squid to
measure the electrical activity of a single neuron. Using microelectrodes
that they could place on or in the cell, they recorded small, rapid
electrical changes with an oscilloscope. Today, digital oscilloscopes and
computers record these measurements.
A neuron’s electrical activity is generated by ions flowing across the
cell membrane. Ions flow both down a concentration gradient (from an
area of relatively high concentration to an area of lower concentration)
and down a voltage gradient (from an area of relatively high voltage to
an area of lower voltage). The opening, closing, and pumping of ion
channels in neural cell membranes also affect ion distribution.
4-2 Electrical Activity of a Membrane
Unequal ion distribution on a cell membrane’s two sides generates the
neuron’s resting potential. At rest, the intracellular membrane registers
about –70 mV relative to the extracellular side. Negatively charged
protein anions are too large to leave the neuron, and the cell membrane
actively pumps out positively charged sodium ions. Unequal
distributions of potassium cations and chloride anions contribute to the
resting potential as well.
Graded potentials, short-lived small increases or decreases in
transmembrane voltage, result when the neuron is stimulated. Voltage
changes affect the membrane’s ion channels and in turn change the
cross-membrane ion distribution. An increase in transmembrane voltage
causes hyperpolarization; a decrease causes depolarization.
An action potential is a brief but large change in axon membrane
polarity triggered when the transmembrane voltage drops to a threshold
level of about –50 mV. During an action potential, transmembrane
voltage suddenly reverses—the intracellular side becomes positive
relative to the extracellular side—and abruptly reverses again. Gradually,
the resting potential is restored. These membrane changes result from
voltage-sensitive channels—sodium and potassium channels sensitive to
the membrane’s voltage.
When an action potential is triggered at the initial segment, it can
propagate along the axon as a nerve impulse. Nerve impulses travel more
rapidly on myelinated axons because of saltatory conduction: the action
potentials leap between the nodes separating the glial cells that form the
axon’s myelin sheath.
4-3 How Neurons Integrate Information
Inputs to neurons from other cells can produce both excitatory
postsynaptic potentials and inhibitory postsynaptic potentials. The
membrane sums their voltages both temporally and spatially to integrate
the incoming information. If the summed EPSPs and IPSPs move the
membrane voltage at the initial segment to threshold, the axon generates
an action potential.
The neuron is a versatile kind of cell. Some species’ ion channels
respond to light rather than to voltage changes, an attribute that genetic
engineers are exploiting. Most of our neurons do not initiate action
potentials on dendrites, because the cell body membrane does not
contain voltage-sensitive channels. But some voltage-sensitive channels
on dendrites do enable action potentials. Back propagation, the reverse
movement of an action potential from the initial segment into the
dendritic field of a neuron, may play a role in plastic changes that
underlie learning.
4-4 Into the Nervous System and Back Out
Sensory receptor cells convert sensory energy to graded potentials. These
changes, in turn, alter transmembrane voltage to trigger an action
potential and propagate a nerve impulse that transmits sensory
information to relevant parts of the nervous system.
Ion channels come into play to activate muscles as well, because the
chemical transmitter acetylcholine, released at the axon terminal of a
motor neuron, activates channels on the end plate of a muscle cell
membrane. The subsequent ion flow depolarizes the muscle cell
membrane to the threshold for its action potential. In turn, this
depolarization activates voltage-sensitive channels, producing an action
potential on the muscle fiber, hence the muscle contractions that enable
movement. In myasthenia gravis, antibodies to the acetylcholine receptor
prevent muscle depolarization, which is the basis of weakness and
fatigue.
 KEY TERMS
absolutely refractory, p. 122
action potential, p. 120
autoimmune disease, p. 127
back propagation, p. 130
concentration gradient, p. 114
depolarization, p. 119
diffusion, p. 114
electrical stimulation, p. 109
electroencephalogram (EEG), p. 111
electrographic seizures, p. 109
end plate, p. 132
excitatory postsynaptic potential (EPSP), p. 127
graded potential, p. 119
hyperpolarization, p. 119
inhibitory postsynaptic potential (IPSP), p. 127
initial segment, p. 128
microelectrode, p. 113
multiple sclerosis (MS), p. 125
nerve impulse, p. 122
node of Ranvier, p. 125
optogenetics, p. 130
oscilloscope, p. 113
relatively refractory, p. 122
resting potential, p. 116
saltatory conduction, p. 125
spatial summation, p. 128
stretch-sensitive channel, p. 132
temporal summation, p. 128
threshold potential, p. 120
transmitter-sensitive channel, p. 132
voltage gradient, p. 114
voltage-sensitive channel, p. 122
voltmeter, p. 111

Visit Launch Pad : to access the e-Book, videos,

Learning Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

How Do Neurons
Communicate and
Adapt?
 Katherine Streeter

RESEARCH FOCUS 5-1 THE BASIS OF NEURAL

COMMUNICATION IN A HEARTBEAT
5-1 A CHEMICAL MESSAGE
EXPERIMENT 5-1 QUESTION: HOW DOES A NEURON PASS ON
A MESSAGE?
CLINICAL FOCUS 5-2 PARKINSON DISEASE
STRUCTURE OF SYNAPSES
NEUROTRANSMISSION IN FOUR STEPS
VARIETIES OF SYNAPSES
EXCITATORY AND INHIBITORY MESSAGES
EVOLUTION OF COMPLEX NEUROTRANSMISSION SYSTEMS
5-2 VARIETIES OF NEUROTRANSMITTERS AND
RECEPTORS
FOUR CRITERIA FOR IDENTIFYING NEUROTRANSMITTERS
FOUR CLASSES OF NEUROTRANSMITTERS
CLINICAL FOCUS 5-3 AWAKENING WITH L-DOPA
VARIETIES OF RECEPTORS
5-3 NEUROTRANSMITTER SYSTEMS AND BEHAVIOR
NEUROTRANSMISSION IN THE SOMATIC NERVOUS SYSTEM
DUAL ACTIVATING SYSTEMS OF THE AUTONOMIC NERVOUS
SYSTEM
ENTERIC NERVOUS SYSTEM AUTONOMY
FOUR ACTIVATING SYSTEMS IN THE CENTRAL NERVOUS
SYSTEM
CLINICAL FOCUS 5-4 THE CASE OF THE FROZEN ADDICT
5-4 ADAPTIVE ROLE OF SYNAPSES IN LEARNING AND
MEMORY
HABITUATION RESPONSE
EXPERIMENT 5-2 QUESTION: WHAT HAPPENS TO THE GILL
RESPONSE AFTER REPEATED STIMULATION?
SENSITIZATION RESPONSE
EXPERIMENT 5-3 QUESTION: WHAT HAPPENS TO THE GILL
RESPONSE IN SENSITIZATION?
LEARNING AS A CHANGE IN SYNAPSE NUMBER
RESEARCH FOCUS 5-5 DENDRITIC SPINES: SMALL BUT
MIGHTY
RESEARCH FOCUS 5-1

The Basis of Neural Communication in a

Heartbeat
Discoveries about how neurons communicate stem from experiments
designed to study what controls an animal’s heart rate. As with any
animal, your heartbeat quickens if you are excited or exercising; if
you are resting, it slows. Heart rate changes to match energy
expenditure—that is, to meet the body’s nutrient and oxygen needs.
Heartbeat undergoes a most dramatic change when you dive
beneath water: it slows almost to stopping. This drastic slowing,
called diving bradycardia, conserves the body’s oxygen when you
are not breathing. Bradycardia (brady-, meaning slow, and -cardia,
meaning heart ) is a useful survival strategy. This energy-conserving
response under water is common to many animals. But what controls
your heartbeat?
Otto Loewi, a great storyteller, recounted that his classic
experiment, which earned him a Nobel Prize in 1936, came to him
in a dream. As shown in the Procedure section of Experiment 5-1
. Loewi first maintained a frog’s heart in a salt bath, then
electrically stimulated the vagus nerve—the cranial nerve that
leads from the brain to the heart. At the same time, he channeled
some of the fluid bath from the vessel containing the stimulated
heart through a tube to another vessel in which a second heart was
immersed but not electrically stimulated.
Loewi recorded both heart rates. His findings are represented in
the Results section of Experiment 5-1 . The electrical stimulation
decreased the rate of the first heart, but more important, the second
heartbeat also slowed. This result indicated that the fluid transferred
from the first to the second container carried instructions to slow
down.
Where did the message come from originally? Loewi reasoned
that a chemical released from the stimulated vagus nerve must have
diffused into the fluid bath to influence the second heart. His
 experiment therefore demonstrated that the vagus nerve contains a
chemical that tells the heart to slow its rate.
Loewi subsequently identified the messenger chemical. Later, he
also identified a chemical that tells the heart to speed up. The heart
adjusts its rate in response to at least two different messages: an
excitatory message that says speed up and an inhibitory message that
says slow down.

Helgiskulason/Getty Images
Puffins fish by diving underwater, propelling themselves by
flapping their short, stubby wings as if flying. During these
dives, their heart displays the diving bradycardia response, just
as our heart does. Here, a puffin emerges from a dive, fish in
beak.

In this chapter, first we explain how neurons communicate with

one another using excitatory and inhibitory signals. Next we describe
how chemicals carried by one neuron signal receptors on receiving
neurons to produce a response. We conclude the chapter by exploring the
neural bases of learning —that is, how neural synapses adapt physically
as a result of an organism’s experience.
 5-1 A Chemical Message
Loewi’s successful heartbeat experiment, diagrammed in Experiment 5-
1 , marked the beginning of research into how chemicals carry
information from one neuron to another in the nervous system. Loewi
was the first to isolate a chemical messenger. We now know that
chemical as acetylcholine (ACh), the same transmitter that activates
skeletal muscles, as described in Section 4-4 . Yet here, ACh acts to
inhibit heartbeat, to slow it down. It turns out that ACh activates skeletal
muscles in the somatic nervous system and may either excite or inhibit
various internal organs in the autonomic system. And, yes, acetylcholine
is the chemical messenger that slows the heart in diving bradycardia.
acetylcholine (Ach) First neurotransmitter discovered in the PNS
and CNS; activates skeletal muscles in the SNS; may either excite or
inhibit internal organs in the ANS.
In further experiments modeled on his procedure in Experiment 5-1 ,
Loewi stimulated another nerve to the heart, the accelerator nerve, and
heart rate increased. The fluid that bathed the accelerated heart also
speeded the beat of a second heart that was not electrically stimulated.
Loewi identified the chemical that carries the message to speed up heart
rate in frogs as epinephrine (EP; epi -, above ; nephron, kidney ), also
known as adrenaline. Adrenaline (Latin) and epinephrine (Greek) are the
same substance, produced by the adrenal glands located atop the kidneys.
Adrenaline is the name more people know, in part because a drug
company used it as a trade name, but epinephrine is common parlance in
the science community.
epinephrine (EP, or adrenaline) Chemical messenger that acts as a
neurotransmitter in the CNS and as a hormone to mobilize the body
for fight or flight during times of stress.
Three-dimensional space-filling models contrast the molecular structure of ACh, which
inhibits heartbeat, to EP and NE, which excite the heart in frogs and humans,
respectively.
 EXPERIMENT 5-1

Question: How does a neuron pass on a message?

Conclusion: The message is a chemical released by the nerve.

Further experimentation eventually demonstrated that in mammals,

the chemical that accelerates heart rate is norepinephrine (NE; also
noradrenaline ), a chemical closely related to EP. The results of Loewi’s
complementary experiments showed that acetylcholine from the vagus
nerve inhibits heartbeat, and epinephrine from the accelerator nerve
excites it.
norepinephrine (NE, or noradrenaline) Neurotransmitter that
accelerates heart rate in mammals; found in the brain and in the
sympathetic division of the ANS.
The vagus nerve influences the heart and other internal body
processes; see Figure 2-29 .
 Chemical messengers released by a neuron onto a target to cause an
excitatory or inhibitory effect are neurotransmitters. Outside the central
nervous system, many of the same chemicals, epinephrine among them,
circulate in the bloodstream as hormones. Under control of the
hypothalamus, the pituitary gland releases hormones into the
bloodstream to excite or inhibit targets such as the organs and glands in
the autonomic and enteric nervous systems. In part because hormones
travel throughout the body to distant targets, their action is slower than
that of CNS neurotransmitters prodded by the lightning-quick nerve
impulse. But the real difference between neurotransmitters and hormones
is the distances they travel before they encounter their receptors.
neurotransmitter Chemical with an excitatory or inhibitory effect
when released by a neuron onto a target.
Section 6-5 explains how hormones influence the brain and
behavior.
Loewi’s discoveries led to the search for more neurotransmitters and
their functions. The actual number of transmitters is an open question,
with 100 posited as the maximum. The confirmed number is 60. Whether
a chemical is accepted as a neurotransmitter depends on the extent to
which it meets certain criteria. As this chapter unfolds, you will learn
those criteria along with the names and functions of many
neurotransmitters. You will also learn how groups of neurons form
neurotransmitter systems throughout the brain to modulate, or temper,
aspects of behavior. The three Clinical Focus boxes in this chapter tell
the fascinating story of how one such neurotransmitter system has
yielded deep insight into brain function. When depleted in a particular
brain area, this neurotransmitter is associated with a specific neurological
disorder. The story begins with Clinical Focus 5-2 , Parkinson Disease.
CLINICAL FOCUS 5-2

Parkinson Disease
Case VI: The gentleman … is seventy-two years of age…. About
eleven or twelve, or perhaps more, years ago, he first perceived
weakness in the left hand and arm, and soon after found the
trembling to commence. In about three years afterwards the right
arm became affected in a similar manner: and soon afterwards the
convulsive motions affected the whole body and began to interrupt
speech. In about three years from that time the legs became affected.
(James Parkinson, 1817/1989)
In the 1817 essay from which this case study is taken, British
physician James Parkinson reported similar symptoms in six patients,
some of whom he had observed only in the streets near his clinic.
Shaking was usually the first symptom, and it typically began in a hand.
Over a span of years, the shaking spread to include the arm and then
other parts of the body.
As the disease progressed, patients had a propensity to lean forward
and walk on the balls of their feet. They also tended to run forward to
prevent themselves from falling. In the later stages, patients had
difficulty eating and swallowing. They drooled, and their bowel
movements slowed. Eventually, the patients lost all muscular control
and were unable to sleep because of the disruptive tremors.
More than 50 years after James Parkinson’s descriptions, French
neurologist Jean-Martin Charcot named the condition Parkinson’s
disease, known today as Parkinson disease. Three findings have
helped researchers understand its neural basis:
Parkinson disease Motor system disorder correlated with
dopamine loss in the substantia nigra; characterized by tremors,
muscular rigidity, and reduction in voluntary movement.
1. In 1919, Constantin Tréatikoff (1974) studied the brains of nine
Parkinson patients on autopsy and found that the substantia nigra, a
small midbrain nucleus, had degenerated. In the brain of one patient
who had parkinsonian symptoms only on one side of the body, the
substantia nigra had degenerated on the side opposite that of the
symptoms.
2. Chemical examination of the brains of Parkinson patients showed
that disease symptoms appear when the level of dopamine, then a
proposed neurotransmitter, was reduced to less than 10 percent of
normal in the basal ganglia (Ehringer & Hornykiewicz, 1960/1974).
dopamine (DA) Amine neurotransmitter involved in coordinating
movement, attention, learning, and in reinforcing behaviors.
3. Confirming the role of dopamine in a neural pathway connecting the
substantia nigra to the basal ganglia, Urban Ungerstedt found in 1971
that injecting a neurotoxin called 6-hydroxydopamine into rats
selectively destroyed these dopamine-containing neurons and
produced symptoms of Parkinson disease.
Researchers have now linked the loss of dopamine-containing
substantia nigra neurons to an array of causes, including genetic
predisposition, the flu, pollution, insecticides, herbicides, and toxic
drugs. Dopamine itself in other brain areas has been linked not only to
motor behavior but also to some forms of learning and to neural
structures that mediate reward and addiction. This remarkable series of
discoveries, initiated by James Parkinson, has yielded tremendous
insight into brain function.
Universal Pictures/Photofest
Photo by Mike Coppola/Getty Images for the Michael J. Fox Foundation for Parkinson’s
Research
Actor Michael J. Fox gained wide fame in the 1980s for his starring role in the
Back to the Future film series, which included his rendition of Chuck Berry’s pop
classic, “Johnny B. Goode” (left). In 1991, at age 30, Fox was diagnosed with
young-onset Parkinson disease. When he performed the song 20 years later to
 benefit the Michael J. Fox Foundation for Parkinson’s Research, he labored but
still had the moves (right).

Structure of Synapses
Loewi’s discovery about the chemical messengers that regulate heart rate
was the first of two seminal findings that form the foundation for current
understanding of how neurons communicate. The second had to wait nearly
30 years, for the invention of the electron microscope. Shown at the right in
Figure 5-1 , it enables scientists to see the structure of a synapse.
Biophoto Associates/Science Source
Light microscope
Joseph F. Gennaro Jr./Science Source, Colorization by: Mary Martin
Electron microscope
FIGURE 5-1 Microscopic Advance Whereas an observer can use a light microscope
(left) to see the general features of a cell, an electron microscope (right) allows the observer
to examine the cell’s organelles in detail.

The electron microscope uses some principles of a light microscope,

shown at the left in Figure 5-1 , and an oscilloscope. The light microscope
illuminates the tissue and magnifies the image. The electron microscope
projects a beam of electrons through a very thin slice of tissue. The tissue’s
varying structures scatter the electron beam onto a reflective surface, where
they leave an image, or shadow, of the tissue. Electron waves are smaller
than light waves and scatter much less when the beam strikes tissue,
allowing for much higher resolution.
Figure 4-5 describes how a digital oscilloscope measures voltage in
biological tissue.
To see how much finer an electron microscope’s resolution is relative to
that of a light microscope, compare the images at the bottom of Figure 5-1 .
An electron microscope’s resolution can be much higher than a light
microscope because electron waves are smaller than light waves, so much
less scatter attends the beam striking the tissue. When tissue is stained with
a substance that reflects electrons, vanishingly fine structural details
emerge.
Chemical Synapses
The first good electron micrographs, made in the 1950s, revealed synaptic
structure for the first time. In the center of the micrograph in Figure 5-2 A ,
the upper part of the synapse is the axon terminal, or end foot; the lower
part is the receiving dendrite. The round granular substances in the terminal
are the synaptic vesicles, containing neurotransmitter.
synaptic vesicle Membranous compartment that encloses a quantum of
neurotransmitter.
Dark patches on the axon terminal membrane are proteins that serve
largely as ion channels to signal the release of the transmitters or as pumps
to recapture the transmitter after its release. The dark patches on the
dendrite consist mainly of receptor molecules also made up of proteins that
receive chemical messages. The terminal and the dendrite are separated by
a small space, the synaptic cleft. The synaptic cleft is central to synapse
function, because neurotransmitter chemicals must bridge this gap to carry a
message from one neuron to the next.
synaptic cleft Gap separating the neuronal presynaptic membrane
from the postsynaptic membrane.
 You can also see in the micrograph that the synapse is sandwiched by
many surrounding structures, including glial cells, other axons and dendritic
processes, and other synapses. The surrounding glia contribute to chemical
neurotransmission in several ways—by supplying the building blocks for
neurotransmitter synthesis, by confining the movement of neurotransmitters
to the synapse, and by mopping up excess neurotransmitter molecules, for
example.

Joseph F. Gennaro Jr./Science Source, Colorization by: Mary Martin

(A)
 (B)
FIGURE 5-2 Chemical Synapse (A) Surrounding the central synapse
in this electron micrograph are glial cells, axons, dendrites, other synapses,
and a synaptic cleft. (B) Within a chemical synapse, storage granules hold
vesicles containing neurotransmitter that travel to the presynaptic membrane
in preparation for release. Neurotransmitter is expelled into the synaptic cleft
by exocytosis, crosses the cleft, and binds to receptor proteins on the
postsynaptic membrane.

Figure 5-2 B details the process of neurotransmission at a chemical

synapse, the junction where messenger molecules are released from one
neuron to interact with the next neuron. Here the presynaptic membrane
forms the axon terminal, the postsynaptic membrane forms the dendritic
spine, and the space between the two is the synaptic cleft. Within the axon
terminal are specialized structures, including mitochondria, the organelles
that supply the cell’s energy needs; storage granules, large compartments
that hold several synaptic vesicles; and microtubules, which transport
substances, including neurotransmitter, to the terminal.
chemical synapse Junction at which messenger molecules are released
when stimulated by an action potential.
presynaptic membrane Axon terminal membrane on the transmitter,
or output, side of a synapse.
postsynaptic membrane Membrane on the transmitter, or input, side
of a synapse.
storage granule Membranous compartment that holds several vesicles
containing a neurotransmitter.
FIGURE 5-3 Gap Junction
Electrical Synapses
Chemical synapses are the rule in mammalian nervous systems, but they are
not the only kind of synapse. Some neurons influence each other
electrically through a gap junction, or electrical synapse, where the cell
membranes of two neurons come into direct contact (Figure 5-3 ). Ion
channels in one cell membrane connect to ion channels in the other
membrane, forming a pore that allows ions to pass from one neuron to the
other in both directions.
gap junction (electrical synapse) Area of contact between adjacent
cells in which ion channels form a pore that allows ions to pass directly
from one cell to the next.
This fusion eliminates the brief delay in information flow—about 5
milliseconds per synapse—of chemical transmission (compare Figure 5-3
with Figure 5-2 B). For example, the crayfish’s gap junctions activate its
tail flick, a response that provides quick escape from a predator. Gap
junctions are found in the mammalian brain, where in some regions they
allow groups of interneurons to synchronize their firing rhythmically. Gap
junctions also allow glial cells and neurons to exchange substances (Dere &
Zlomuzica, 2012).
Why, if chemical synapses transmit messages more slowly, do mammals
rely on them more than on gap junctions? The answer is that chemical
synapses flexibly control whether a message is passed from one neuron to
the next; they can amplify or diminish a signal sent from one neuron to the
next; and they can change with experience to alter their signals and so
mediate learning.

Neurotransmission in Four Steps

The four-step process of transmitting information across a chemical synapse
is illustrated in Figure 5-4 . In brief, the neurotransmitter must be
1. synthesized somewhere inside the neuron and stored at the axon terminal.
2. transported to the presynaptic membrane and released into the cleft in
response to an action potential.
3. able to bind to and activate receptors on the postsynaptic membrane.
4. inactivated, so it will not continue to work indefinitely.
 FIGURE 5-4 Synaptic Transmission
For a refresher on protein export, review Figure 3-17 .
Step 1: Neurotransmitter Synthesis and Storage
Neurotransmitters are derived in two general ways, and these origins define
two broad classes of neurotransmitters. Some are synthesized in the cell
body according to instructions in the neuron’s DNA, packaged in
membranes on the Golgi bodies, and transported on microtubules to the
axon terminal. Cellderived neurotransmitters may also be manufactured
within the presynaptic terminal from mRNA transported to the terminal.
Other neurotransmitters are synthesized in the axon terminal from
building blocks derived from food. Transporters, protein molecules that
pump substances across the cell membrane, absorb the required precursor
chemicals from the blood supply. (Sometimes transporter proteins absorb
the neurotransmitter ready-made.) Mitochondria in the axon terminal
provide the energy needed both to synthesize precursor chemicals into the
neurotransmitter and to wrap them in membranous vesicles.
transporter Protein molecule that pumps substances across a
membrane.
Regardless of their origin, neurotransmitters in the axon terminal can
usually be found in three locations, depending on their type. Some vesicles
are warehoused in granules, some are attached to microfilaments (a type of
microtubule; see Figure 5-2 B) in the terminal, and still others are attached
to the presynaptic membrane. These sites are the steps by which a
transmitter is transported from a granule to the membrane, ready to be
released into the synaptic cleft.
Step 2: Neurotransmitter Release
Synaptic vesicles loaded with neurotransmitters must dock near release sites
on the presynaptic membrane. Then the vesicles are primed to prepare them
to fuse rapidly in response to calcium (Ca2+ ) influx. When an action
potential reaches the presynaptic membrane, voltage changes on the
membrane set the release process in motion. Calcium cations play a critical
role. The presynaptic membrane is rich in voltage-sensitive calcium
channels, and the surrounding extracellular fluid is rich in Ca2+ . As
illustrated in Figure 5-5 , the action potential’s arrival opens these calcium
channels, allowing an influx of calcium ions into the axon terminal.
Primed vesicles fuse with the presynaptic membrane quickly in response
to the calcium influx and empty their contents into the synaptic cleft by
exocytosis. The vesicles from storage granules and on filaments then move
up to replace the vesicles that just emptied their contents.
Step 3: Receptor-Site Activation
After its release from vesicles on the presynaptic membrane, the
neurotransmitter diffuses across the synaptic cleft and binds to specialized
protein molecules embedded in the postsynaptic membrane. These
transmitter-activated receptors have binding sites for the transmitter,
which we elaborate on in Section 5-3 . Depending on the properties of
receptors on the postsynaptic membrane, the postsynaptic cell may be
affected in one of three ways. The receptor and its associated ion channel or
intracellular messenger system may
transmitter-activated receptor Protein that has a binding site for a
specific neurotransmitter and is embedded in the membrane of a cell.
1. depolarize the postsynaptic membrane and so have an excitatory action
on the postsynaptic neuron.
2. hyperpolarize the postsynaptic membrane and so have an inhibitory
action on the postsynaptic neuron.
3. initiate other chemical reactions that modulate either effect, inhibitory or
excitatory, or that influence other functions of the receiving neuron.
In addition to interacting with the postsynaptic membrane’s receptors, a
neurotransmitter may interact with receptors on the presynaptic membrane:
it may influence the cell that just released it. That is, a neurotransmitter may
activate presynaptic receptors called autoreceptors (selfreceptors) to
receive messages from their own axon terminals.
autoreceptor Self-receptor in a neuronal membrane; that is, it
responds to the same transmitter released by the neuron.
How much neurotransmitter is needed to send a message? Bernard Katz
was awarded a Nobel Prize in 1970 for providing an answer. Recording
electrical activity from the postsynaptic membranes of muscles, he detected
small, spontaneous depolarizations now called miniature postsynaptic
potentials. The potentials varied in size, but each size appeared to be a
multiple of the smallest potential.
Katz concluded that the smallest postsynaptic potential is produced by
the release of the contents of just one synaptic vesicle. This amount of
neurotransmitter is called a quantum. To produce a postsynaptic potential
large enough to initiate a postsynaptic action potential requires the
simultaneous release of many quanta from the presynaptic cell.
quantum (pl. quanta) Amount of neurotransmitter, equivalent to the
content of a single synaptic vesicle, that produces a just-observable
change in postsynaptic electric potential.
The results of subsequent experiments show that the number of quanta
released from the presynaptic membrane in response to a single action
potential depends on two factors: (1) the amount of Ca2+ that enters the
axon terminal in response to the action potential and (2) the number of
vesicles docked at the membrane, waiting to be released. Both factors are
relevant to synaptic activity during learning, which we consider in Section
5-4 .
 FIGURE 5-5 Neurotransmitter Release
Step 4: Neurotransmitter Deactivation
Chemical transmission would not be an effective messenger system if a
neurotransmitter lingered within the synaptic cleft, continuing to occupy
and stimulate receptors. If this happened, the postsynaptic cell could not
respond to other messages sent by the presynaptic neuron. Thus, after a
neurotransmitter has done its work, it is quickly removed from receptor
sites and from the synaptic cleft. Deactivation is accomplished in at least
four ways:
1. Diffusion. Some of the neurotransmitter simply diffuses away from the
synaptic cleft and is no longer available to bind to receptors.
2. Degradation. Enzymes in the synaptic cleft break down the transmitter.
3. Reuptake. Membrane transporters specific to that transmitter may bring
it back into the presynaptic axon terminal for reuse. The by-products of
degradation by enzymes also may be taken back into the terminal to be
used again in the cell.
reuptake Deactivation of a neurotransmitter when membrane
transporter proteins bring the transmitter back into the presynaptic
axon terminal for reuse.
4. Astrocyte uptake. Some neurotransmitters are taken up by neighboring
astrocytes. Potentially, the astrocytes can also store transmitters for re-
export to the axon terminal.
Table 3-1 describes astrocytes and other types of glial cells and their
functions.
Highlighting the flexibility of synaptic function, an axon terminal has
chemical mechanisms that enable it to respond to the frequency of its own
use. If the terminal is very active, the amount of neurotransmitter made and
stored there increases. If the terminal is not often used, however, enzymes
within the terminal buttons may break down excess transmitter. The by-
products are then reused or excreted from the neuron. Axon terminals may
even send messages to the neuron’s cell body requesting increased supplies
of the neurotransmitter or the molecules with which to make it.

Varieties of Synapses
So far we have considered a generic chemical synapse, with features
possessed by most synapses. Synapses vary widely in the nervous system.
Each type is specialized in location, structure, function, and target. Figure
5-6 illustrates this diversity on a single hypothetical neuron.
You have already encountered two kinds of synapses. One is the
axomuscular synapse, in which an axon synapses with a muscle end plate,
releasing acetylcholine. The other synapse familiar to you is the
axodendritic synapse, detailed in Figure 5-2 B, in which the axon terminal
of a neuron synapses with a dendrite or dendritic spine of another neuron.
Figure 4-26 shows both microscopic and schematic views of an
axomuscular synapse
Figure 5-6 diagrams axon terminals at the axodendritic synapse as well
as the axosomatic synapse, at a cell body; the axoaxonic synapse, on
another axon; and the axosynaptic synapse, on another presynaptic terminal
—that is, at the synapse between some other axon and its target.
Axoextracellular synapses have no specific targets but instead secrete their
transmitter chemicals into the extracellular fluid. In the axosecretory
synapse, a terminal synapses with a tiny blood vessel, a capillary, and
secretes its transmitter directly into the blood. Finally, synapses are not
limited to axon terminals. Dendrites also may send messages to other
dendrites through dendrodendritic synapses.
This wide variety of connections makes the synapse a versatile chemical
delivery system. Synapses can deliver transmitters to highly specific sites or
diffuse locales. Through connections to the dendrites, cell body, or axon of
a neuron, transmitters can control the neuron’s actions in different ways.
Through axosynaptic connections, they can also exert exquisite control
over another neuron’s input to a cell. By excreting transmitters into
extracellular fluid or into the blood, axoextracellular and axosecretory
synapses can modulate the function of large areas of tissue or even the
entire body. Many transmitters secreted by neurons act as hormones
circulating in your blood, with widespread influences on your body.
Gap junctions, shown in Figure 5-3 , further increase the signaling
diversity between neurons. Such interneuronal communication may occur
via dendrodendritic and axoaxonic gap junctions. Gap junctions also allow
neighboring neurons to synchronize their signals through somatosomatic
(cell body to cell body) connections, and they allow glial cells, especially
astrocytes, to pass nutrient chemicals to neurons and to receive waste
products from them.
More about hormones in Section 6-5 .

FIGURE 5-6 The Versatile Synapse

Excitatory and Inhibitory Messages
A neurotransmitter can influence a neuron’s functioning through a
remarkable variety of mechanisms. In its direct actions in influencing a
neuron’s electrical activity, however, a neurotransmitter acting through its
receptors has only one of two effects. It influences transmembrane ion flow
either to increase or to decrease the likelihood that the cell with which it
comes in contact will produce an action potential. Thus, despite the wide
variety of synapses, they all convey messages of only these two types,
excitatory or inhibitory. To be precise, neurotransmitters themselves do not
determine excitation or inhibition. The receptor makes the call.
Each neuron receives thousands of excitatory and inhibitory signals
every second. The nervous system works by juxtaposing these signals.
Excitatory and inhibitory synapses differ in their appearance and are
generally located on different parts of the neuron. As shown in Figure 5-7 ,
excitatory synapses are typically on the shafts or spines of dendrites,
whereas inhibitory synapses are typically on the cell body. Excitatory
synapses have round synaptic vesicles; the vesicles in inhibitory synapses
are flattened. The material on the presynaptic and postsynaptic membranes
is denser in an excitatory synapse than it is in an inhibitory synapse, and the
excitatory synaptic cleft is wider. Finally, the active zone on an excitatory
synapse is larger than that on an inhibitory synapse.
Behaviors are lost when a disorder prevents excitatory instructions and
released when a disorder prevents inhibitory instructions.
The differing locations of excitatory and inhibitory synapses divide a
neuron into two zones: an excitatory dendritic tree and an inhibitory cell
body. Think of excitatory and inhibitory messages as interacting from these
two different perspectives. Viewed from an inhibitory perspective, you can
picture excitation coming in over the dendrites and spreading past the axon
hillock to trigger an action potential at the initial segment. If the message is
to be stopped, it is best stopped by inhibiting the cell body close to the
initial segment. In this model of excitatory–inhibitory interaction, inhibition
blocks excitation by a “cut ’em off at the pass” strategy.
Another way to conceptualize excitatory–inhibitory interaction is to
picture excitation overcoming inhibition. In fact, excitatory synaptic inputs
that are farther away from the soma are larger, to counteract the loss of
signal that occurs over distance (Magee & Cook, 2000). If the cell body is
typically in an inhibited state, the only way to generate an action potential is
to reduce cell body inhibition. In this “open the gates” strategy, the
excitatory message is like a racehorse ready to run down the track, but first
the inhibitory starting gate must be removed.

FIGURE 5-7 Excitatory and Inhibitory Zones Excitatory synapses

typically occupy spines and dendritic shafts on a neuron. Inhibitory synapses
are typically found on the cell body.

Evolution of Complex Neurotransmission

Systems
Considering all the biochemical steps required for getting a message across
a synapse and the variety of synapses, you might well wonder why—and
how—such a complex communication system ever evolved. How did
chemical transmitters originate?
To make the origin of chemical secretions for neuronal communication
easier to imagine, think about the feeding behaviors of simple single-celled
creatures. The earliest unicellular creatures secreted juices onto bacteria to
immobilize and prepare them for ingestion. These digestive juices were
probably expelled from the cell body by exocytosis: a vacuole or vesicle
attaches itself to the cell membrane then opens into the extracellular fluid to
discharge its contents. The prey thus immobilized is captured through the
reverse process of endocytosis.
The exocytosis mechanism for digestion in a single-celled organism
parallels its use to release a neurotransmitter for communication in more
complex creatures. Quite possibly, evolution long ago adapted these
primordial digestive processes into processes of neural communication in
more complex organisms.
 5-1 REVIEW
A Chemical Message
Before you continue, check your understanding.
1 . In mammals, the principal form of communication between neurons
occurs via ___________, even though this structure is slower and
more complex than the fused ___________.
2 . The principal benefit of chemical synapses over electrical synapses is
that they can change with ___________ to alter their signals and so
mediate ___________.
3 . The nervous system has evolved a variety of synapses:
___________ between axon terminals and dendrites,
___________ between axon terminals and cell bodies,
___________ between axon terminals and muscles,
___________ between axon terminals and other axons,
___________ between axon terminals and other synapses.
A(n) ___________ synapse releases chemical transmitters into
extracellular fluid, a(n) ___________ synapse releases transmitter into
the bloodstream as hormones, and still another, the ___________
synapse, connects dendrites to other dendrites.
4 . Excitatory synapses are usually located on a(n) ___________,
whereas inhibitory synapses are usually located on a(n) ___________.
5 . Describe the four steps in chemical neurotransmission.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Varieties of Neurotransmitters and
5-2

Receptors
Subsequent to Otto Loewi’s 1921 discovery that excitatory and inhibitory
chemicals control heart rate, many researchers thought that the brain must
work under much the same type of dual control. They reasoned that
norepinephrine and acetylcholine were the transmitters through which
excitatory and inhibitory brain cells worked. They did not imagine what
we know today: the human brain employs a dazzling variety of
neurotransmitters and receptors. The neurotransmitters operate in even
more versatile ways: some may be excitatory at one location and
inhibitory at another, for example, and two or more may team up in a
single synapse so that one makes the other more potent. Moreover, each
neurotransmitter may interact with several varieties of receptors, each
with a somewhat different function.
In this section, you will learn how neurotransmitters are identified and
how they fit within four broad categories on the basis of their chemical
structure. The functional aspects of neurotransmitters interrelate and are
intricate, with no simple one-to-one relation between a single
neurotransmitter and a single behavior. Furthermore, receptor variety is
achieved by the unique combination of protein molecules that come
together to form a functional receptor.

Four Criteria for Identifying

Neurotransmitters
Among the many thousands of chemicals in the nervous system, which
are neurotransmitters? Figure 5-8 presents four identifying criteria:
1. The chemical must be synthesized in the neuron or otherwise be
present in it.
2. When the neuron is active, the chemical must be released and produce
a response in some target.
 FIGURE 5-8 Criteria for Identifying Neurotransmitters
3. The same response must be obtained when the chemical is
experimentally placed on the target.
4. A mechanism must exist for removing the chemical from its site of
action after its work is done.
These identifying criteria are fairly easy to apply for examining the
somatic nervous system, especially at an accessible nerve–muscle
junction with only one main neurotransmitter, acetylcholine. But
identifying chemical transmitters in the CNS is not so easy. In the brain
and spinal cord, thousands of synapses are packed around every neuron,
preventing easy access to any single synapse and its activities.
Consequently, multiple techniques, including staining, stimulating, and
collecting, are used to identify substances thought to be CNS
neurotransmitters. A suspect chemical that has not yet been shown to
meet all the criteria is called a putative (supposed) transmitter.
 Figure 4-6 illustrates the use of a glass microelectrode.
Researchers trying to identify new CNS neurotransmitters can use
microelectrodes to stimulate and record from single neurons. A glass
microelectrode is small enough to be placed on specific neuronal targets.
It can be filled with a chemical of interest, and when a current is passed
through the electrode, the chemical can be ejected into or onto the neuron
to mimic neurotransmitter release onto the cell.
Many staining techniques can identify specific chemicals inside the
cell. Methods have also been developed for preserving nervous system
tissue in a saline bath while experimenters determine how the neurons in
the tissue communicate. The use of such tissue slices simplifies the
investigation by allowing the researcher to view a single neuron through a
microscope while stimulating it or recording from it.
Acetylcholine was not only the first substance identified as a
neurotransmitter but also the first substance identified as a CNS
neurotransmitter. A logical argument that predicted its presence even
before experimental proof was gathered greatly facilitated the process.
All motor neuron axons leaving the spinal cord use acetylcholine as a
transmitter. Each axon has an axon collateral within the spinal cord that
synapses on a nearby CNS interneuron. The interneuron, in turn, synapses
on the motor neuron’s cell body. This circular set of connections, called a
Renshaw loop after the researcher who first described it, is shown in
Figure 5-9 .
Because the main axon to the muscle releases acetylcholine,
investigators suspected that its axon collateral also might release
acetylcholine. For two terminals of the same axon to use different
transmitters seemed unlikely. Knowing what chemical to look for made it
easier to find and obtain the required evidence that ACh is in fact a
neurotransmitter in both locations.
The loop made by the axon collateral and the interneuron in the spinal
cord forms a feedback circuit that enables the motor neuron to inhibit
itself from overexcitation, should it receive a great many excitatory inputs
from other parts of the CNS. Follow the positive and negative signs in
Figure 5-9 to see how the Renshaw loop works. If the loop is blocked, as
can be done with the toxin strychnine, motor neurons become overactive,
producing convulsions that can choke off respiration and so cause death.
The term neurotransmitter is used more broadly now than it was when
researchers began to identify these chemicals. Today, the term applies to
chemicals that
• carry a message from the presynaptic membrane of one neuron to
another by influencing postsynaptic membrane voltage.
• change the structure of a synapse.
• communicate by sending messages in the opposite direction. These
retrograde (reversedirection) messages influence the release or reuptake
of transmitters on the presynaptic side.

Four Classes of Neurotransmitters

We can impose some order on the diversity of neurotransmitters by
classifying them into four groups based on their chemical composition:
(1) small-molecule transmitters, (2) peptide transmitters, (3) lipid
transmitters, and (4) gaseous transmitters.

FIGURE 5-9 Renshaw Loop Left: Some spinal cord motor neurons
project to the rat’s forelimb muscles. Right: In a Renshaw loop the main
 motor axon (green) projects to a muscle, and its axon collateral remains in
the spinal cord to synapse with a Renshaw interneuron (red). The
Renshaw interneuron contains the inhibitory transmitter glycine, which acts
to prevent motor neuron overexcitation. Both the main motor axon and its
collateral terminals contain acetylcholine. When the motor neuron is highly
excited, it can modulate its activity level through the Renshaw loop (plus
and minus signs).

Small-Molecule Transmitters
The first neurotransmitters identified are the quick-acting small-molecule
transmitters, such as acetylcholine. Typically, they are synthesized from
dietary nutrients and packaged ready for use in axon terminals. When a
small-molecule transmitter has been released from a terminal button, it
can quickly be replaced at the presynaptic membrane.
small-molecule transmitter Quick-acting neurotransmitter
synthesized in the axon terminal from products derived from the diet.
Because small-molecule transmitters or their main components are
derived from the food we eat, diet can influence their abundance and
activity in our bodies. This fact is important in the design of drugs that act
on the nervous system. Many neuroactive drugs are designed to reach the
brain by the same route that small-molecule transmitters or their
precursor chemicals follow: the digestive tract.
Taking drugs orally is easy and comparatively safe, but not all drugs
can traverse the digestive tract. Section 6-1 explains.
Table 5-1 lists some of the best-known and most extensively studied
small-molecule transmitters. In addition to acetylcholine, four amines
(related by a chemical structure that contains an NH group, or amine )
and three amino acids are included in this list. A few other substances,
including histamine, also are classified as small-molecule transmitters.
Among its many functions, which include control of arousal and of
waking, the transmitter histamine (H) can cause the constriction of
smooth muscles. When activated in allergic reactions, histamine
contributes to asthma, a constriction of the airways. You are probably
familiar with antihistamine drugs used to treat allergies.
histamine (H) Neurotransmitter that controls arousal and waking;
can cause the constriction of smooth muscles; when activated in
allergic reactions, constricts airway and contributes to asthma.
ACETYLCHOLINE SYNTHESIS Acetylcholine is present at the junction of
neurons and muscles, including the heart, as well as in the CNS. Figure
5-10 illustrates how ACh molecules are synthesized from choline and
acetate by two enzymes, then broken down. Choline is among the
breakdown products of fats in foods such as egg yolk, avocado, salmon,
and olive oil; acetate is a compound found in acidic foods, such as
vinegar and lemon juice.
As depicted in Figure 5-10 , inside the cell, acetyl coenzyme A (acetyl
CoA) carries acetate to the synthesis site, and a second enzyme, choline
acetyltransferase (ChAT), transfers the acetate to choline to synthesize
acetylcholine. After ACh has been released into the synaptic cleft and
diffuses to receptor sites on the postsynaptic membrane, a third enzyme,
acetylcholinesterase (AChE), reverses the process, breaking down the
transmitter by detaching acetate from choline. The breakdown products
can then be taken back into the presynaptic terminal for reuse.
Acetylcholine (ACh)

Histamine (H)

Amines

Dopamine (DA)

Norepinephrine (NE, or noradrenaline, NA)

Epinephrine (EP, or adrenaline)

Serotonin (5-HT)

Amino acids

Glutamate (Glu)

Gamma-aminobutyric acid (GABA)

Glycine (Gly)

TABLE 5-1 Small-molecule Neurotransmitters

FIGURE 5-10 Chemistry of Acetylcholine Two enzymes combine the dietary
precursors of ACh within the cell, and a third breaks them down in the synapse for
reuptake.

AMINE SYNTHESIS Some transmitters grouped together in Table 5-1 have

common biochemical pathways to synthesis and so are related. You are
familiar with the amines dopamine (DA), norepinephrine (NE), and
epinephrine (EP). To review, DA loss figures in Parkinson disease, EP is
the excitatory transmitter at the amphibian heart, and NE is the excitatory
transmitter at the mammalian heart.
Figure 5-11 charts the biochemical sequence that synthesizes these
amines in succession. The precursor chemical is tyrosine, an amino acid
abundant in food. (Hard cheese and bananas are good sources.) The
enzyme tyrosine hydroxylase (enzyme 1 in Figure 5-11 ) changes tyrosine
into L -dopa, which other enzymes convert into dopamine, then
norepinephrine, and, finally, epinephrine.
Interestingly, the supply of the enzyme tyrosine hydroxylase is limited.
Consequently, so is the rate at which dopamine, norepinephrine, and
epinephrine can be produced, regardless of how much tyrosine is present
or ingested. This rate-limiting factor can be bypassed by the oral
administration of L -dopa, which is why L -dopa is a medication used in
treating Parkinson disease, as described in Clinical Focus 5-3 ,
Awakening with L -Dopa, on page 152 .
rate-limiting factor Any chemical in limited supply that restricts the
pace at which another chemical can be synthesized.
SEROTONIN SYNTHESIS The amine transmitter serotonin (5-HT, for 5-
hydroxy-tryptamine) is synthesized from the amino acid L -tryptophan.
Tryptophan is abundant in pork, turkey, milk, and bananas, among other
foods. Serotonin plays a role in regulating mood and aggression, appetite
and arousal, respiration, and pain perception.
serotonin (5-Ht) Amine neurotransmitter; helps to regulate mood
and aggression, appetite and arousal, perception of pain, and
respiration.
AMINO ACID SYNTHESIS Two amino acid transmitters, glutamate (Glu)
and gamma-aminobutyric acid (GABA), are closely related. GABA is
formed by a simple modification of the glutamate molecule, as shown in
Figure 5-12 . These two transmitters are the workhorses of the brain
because so many synapses use them.
 glutamate (Glu) Amino acid neurotransmitter; typically excites
neurons.
gamma-aminobutyric acid (GABA) Amino acid neurotransmitter;
typically inhibits neurons.
In the forebrain and cerebellum, glutamate is the main excitatory
transmitter and GABA is the main inhibitory transmitter. Thus, glutamate
is a neurotransmitter in excitatory synapses, and GABA is a
neurotransmitter in inhibitory synapses. So a synapse’s appearance
provides information about the neurotransmitter and its function (review
Figure 5-7 ). Interestingly, glutamate is widely distributed in CNS
neurons, but it becomes a neurotransmitter only if it is appropriately
packaged in vesicles in the axon terminal. The amino acid transmitter
glycine (Gly) is a much more common inhibitory transmitter in the
brainstem and spinal cord, where it acts within the Renshaw loop, for
example (review Figure 5-9 ).

FIGURE 5-11 Sequential Synthesis of Three Amines A

different enzyme is responsible for each successive molecular modification
in this biochemical sequence of amine neurotransmitters. The twins
featured in Focus 3-1 lack an enzyme that enhances DA production.

Peptide Transmitters
More than 50 short amino acid chains of various lengths (fewer than 100)
form the families of peptide transmitters, or neuropeptides, listed in
Table 5-2 . Synthesized through the translation of mRNA from
instructions contained in the neuron’s DNA, neuropeptides are
multifunctional chains of amino acids that act as neurotransmitters.
neuropeptide Short (fewer than 100), multifunctional amino acid
chain; acts as a neurotransmitter and can act as a hormone; may
contribute to learning.
In some neurons, peptide transmitters are made in the axon terminal,
but most are assembled on the neuron’s ribosomes, packaged in a
membrane by Golgi bodies, and transported by the microtubules to the
axon terminals. The entire process of neuropeptide synthesis and
transport is relatively slow compared with the nearly ready-made small-
molecule neurotransmitters. Consequently, peptide transmitters act slowly
and are not replaced quickly.
 Figure 3-15 diagrams peptide bonding and Figure 3-17 , protein
export.
Neuropeptides, however, perform an enormous range of functions in
the nervous system, as might be expected from their large numbers. They
act as hormones that respond to stress, enable a mother to bond with her
infant, regulate eating and drinking and pleasure and pain, and probably
contribute to learning.
Opium and related synthetic chemicals such as morphine, long known
both to produce euphoria and to reduce pain, appear to mimic the actions
of endogenous brain opioid neuropeptides: enkephalins, dynorphins, and
endorphins. (The term enkephalin derives from the phrase in the
cephalon, meaning in the brain or head, whereas the term endorphin is a
shortened form of endogenous morphine. )
FIGURE 5-12 Amino Acid Transmitters Top: Removal of a carboxyl (COOH)
group from the bottom of the glutamate molecule produces GABA. Bottom: Their different
shapes, illustrated by three-dimensional space-filling models, thus allow these amino acid
transmitters to bind to different receptors.

A part of the amino acid chain in each of these naturally occurring

opioid peptides is structurally similar to the others, as illustrated for two
of them in Figure 5-13 . Presumably, opium mimics this part of the chain.
The discovery of naturally occurring opium-like neuropeptides suggested
that one or more of them might have analgesic properties and take part in
pain perception. It turns out that beta-endorphin, released in response to
exercise and thought responsible for runner’s high, has many times the
analgesic potency of morphine.
Some CNS peptides take part in specific periodic behaviors, each
month or each year perhaps. For instance, in female deer, neuropeptide
transmitters act as hormones (luteinizing hormone) that prepare her for
the fall mating season. Come winter, a different set of biochemicals
facilitates the developing deer fetus. When the mother gives birth in the
spring, yet another set of highly specific neuropeptide hormones—such as
oxytocin, which enables her to bond to her fawn, and prolactin, which
enables her to nurse—takes control.
The same neuropeptides serve similar specific hormonal functions in
humans. Others, such as neuropeptide growth hormones, perform far
more general functions in regulating growth. Unlike small-molecule
transmitters that bind to ion channels, neuropeptides have no direct
effects on postsynaptic membrane voltage. Instead, peptide transmitters
activate synaptic receptors that indirectly influence cell structure and
function. Digestive processes degrade neuropeptide amino acid chains, so
they generally cannot be taken orally as drugs, as small-molecule
transmitters can.
 FIGURE 5-13 Opioid Peptides Parts of the amino acid chains of some
neuropeptides that act on brain centers for pleasure and pain are
structurally similar and also share similarities to drugs such as opium and
morphine, which mimic their functions (see Section 6-2 ).

Sections 12-4 and 12-5 explain hormonal influence over human

emotional and motivated behavior.
TABLE 5-2 Peptide Neurotransmitters
Family Examples

Opioids Met-enkephalin, dynorphin, beta-endorphin

Neurohypophyseals Vasopressin, oxytocin

Secretins Secretin, motilin, glucagon, growth hormone–releasing factor

Insulins Insulin, insulin growth factors

Gastrins Gastrin, cholecystokinin

Somatostatins Somatostatin

Tachykinins Neurokinin A, neurokinin B, substance P

Lipid Transmitters
Predominant among the lipid neurotransmitters are the
endocannabinoids (endogenous cannabinoids), a class of lipid
neurotransmitters synthesized at the postsynaptic membrane to act on
receptors at the presynaptic membrane. The endocannabinoids include
anandamide and 2-AG (2-arachidonoylglycerol), both derived from
arachidonic acid, an unsaturated fatty acid. Poultry and eggs are
especially good sources. Endocannabinoids participate in a diverse set of
physiological and psychological processes that affect appetite, pain, sleep,
mood, memory, anxiety, and the stress response. Their scientific history is
brief but illustrates how science can progress, punctuated by short steps.
endocannabinoid Class of lipid neurotransmitters, including
anandamide and 2-AG, synthesized at the postsynaptic membrane to
act on receptors at the presynaptic membrane; affects appetite, pain,
sleep, mood, memory, anxiety, and the stress response.
CLINICAL FOCUS 5-3

Awakening with L-Dopa

He was started on L -dopa in March 1969. The dose was slowly
raised to 4.0 mg a day over a period of three weeks without
apparently producing any effect. I first discovered that Mr. E. was
responding to L -dopa by accident, chancing to go past his room at
an unaccustomed time and hearing regular footsteps inside the
room. I went in and found Mr. E., who had been chair bound since
1966, walking up and down his room, swinging his arms with
considerable vigor, and showing erectness of posture and a
brightness of expression completely new to him. When I asked
him about the effect, he said with some embarrassment: “Yes! I felt
the L -dopa beginning to work three days ago—it was like a wave
of energy and strength sweeping through me. I found I could stand
and walk by myself, and that I could do everything I needed for
myself—but I was afraid that you would see how well I was and
discharge me from the hospital.” (Sacks, 1976)
In this case history, neurologist Oliver Sacks describes
administering L -dopa to a patient who had acquired parkinsonism as
an aftereffect of severe influenza in the 1920s. The relation between
the influenza and the parkinsonian symptoms suggests that the flu
virus had entered the brain and selectively attacked dopamine
neurons in the substantia nigra. By increasing the amount of DA in
remaining synapses, L -dopa relieved the patient’s symptoms.
Two separate groups of investigators independently gave L -dopa
to Parkinson patients beginning in 1961 (Birkmayer & Hornykiewicz,
1961; Barbeau et al., 1961). Both research teams knew that the
chemical is catalyzed into dopamine at DA synapses (see Figure 5-11
). The L -dopa turned out to reduce the patients’ muscular rigidity.
This work was the first demonstration that a neurological
condition can be relieved by a drug that aids in increasing the amount
of a neurotransmitter. L -Dopa has since become a standard treatment
for Parkinson disease. Its effects have been improved by the
administration of drugs that prevent L -dopa from being converted to
dopamine in the body before it passes through the blood–brain barrier
and gets to dopa-mine neurons in the brain.
 L -Dopa is not a cure. Parkinson disease still progresses during
treatment, and as more and more dopamine synapses are lost, the
treatment becomes less and less effective. Eventually, L -dopa begins
to produce dyskinesias —involuntary, unwanted movements, such as
ballistic (throwinglike) or choreic (dancelike) movements. When
these side effects eventually become severe, the treatment must be
discontinued.

Everett Coll
The movie Awakenings recounts the L -dopa trials conducted by
Oliver Sacks and described in his book of the same title.

Fatty acid molecules that contribute to forming the cell membrane

likewise are hydrophobic. See Figure 3-11 .
Because endocannabinoids are lipophilic (fat-loving) molecules, they
are not soluble in water and are not stored in vesicles. Rather,
investigators hypothesize that endocannabinoids are synthesized on
demand after a neuron has depolarized and calcium has entered. Calcium
activates the enzyme transacylase, the first step in producing anandamide.
Once anandamide or 2-AG is synthesized, it diffuses across the synaptic
cleft and interacts with its receptor on the presynaptic membrane. Thus,
both molecules act as retrograde neurotransmitters, for a time reducing
the amount of small-molecule transmitter being released. In this way, the
postsynaptic neuron has some control over the amount of incoming neural
signal.
The CB1 receptor is the target of all cannabinoids, whether generated
by the body (endocannabinoids), from plants (phytocannabinoids), or
synthetically. CB1 receptors are found at both glutamate and GABA
synapses, and so cannabinoids act as neuromodulators to inhibit release
of glutamate and GABA. Cannabinoids thus dampen both neuronal
excitation and inhibition.
Cannabis is among the psychotropic drugs discussed in Section 6-2 .
Phytocannabinoids are obtained from the hemp plants Cannabis sativa
and Cannabis indica. These plants have been used medically and
recreationally for thousands of years, but only recently was an extract
from cannabis synthesized. Early in the last century, many constituents of
cannabis, including cannabidiol and tetrahydrocannabinol (THC), were
isolated and their chemical structure determined. In 1964, Yehiel Gaoni
and Raphael Mechoulam reported the structure of the THC molecule, the
main psychoactive constituent in cannabis. Next, investigators
determined how THC is metabolized. (The process is quite slow, which
explains why THC can be detected in urine for weeks after cannabis use.)
Research on the physiological and psychological effects of THC in
animals and people, which began after its isolation and purification, is
ongoing. Twenty-four years after the structure of the THC molecule was
determined, the first cannabinoid receptor (CB1 ) was found. Typically,
receptors are activated by endogenous molecules, which motivated
researchers to look for endogenous cannabinoids. Four years later, in
1992, anandamide was isolated and its structure determined, but it took
another couple of decades to figure out that endocannabinoids act as
retrograde transmitters (Mechoulam et al., 2014).
Gaseous Transmitters
The gases nitric oxide (NO), carbon monoxide (CO), and hydrogen
sulfide (H2 S) further expand the biochemical strategies that transmitter
substances display. As water-soluble gases, they are neither stored in
synaptic vesicles nor released from them; instead, the cell synthesizes
them on demand. After synthesis, each gas diffuses away, easily crossing
the cell membrane and immediately becoming active. Both NO and CO
activate metabolic (energyexpending) processes in cells, including
processes modulating the production of other neurotransmitters. H2 S
prevents oxygen from binding in the mitochondria and thus functions to
slow down metabolism.
nitric oxide (NO) Gaseous neurotransmitter; acts, for example, to
dilate blood vessels, aid digestion, and activate cellular metabolism.
 carbon monoxide (CO) Gaseous neurotransmitter; activates cellular
metabolism.
hydrogen sulfide (H 2 s) Gaseous neurotransmitter; slows cellular
metabolism.
All three gaseous transmitters serve as chemical messengers in many
parts of the body. NO and H2 S control intestinal wall muscles and dilate
blood vessels in active brain regions, allowing these regions to receive
more blood. Because NO and H2 S also dilate blood vessels in the sexual
organs, both are active in producing penile erections. Drugs used to treat
erectile dysfunction in men, such as Viagra and Cialis, act by enhancing
the chemical pathways influenced by NO. NO does not of itself produce
sexual arousal.

Varieties of Receptors
Each of the two general classes of receptor proteins produces a different
effect: one directly changes the postsynaptic membrane’s electrical
potential, and the other induces cellular change indirectly. A dazzling
array of receptor subtypes allows for subtle differences in receptor
function.
Two Classes of Receptors
When a neurotransmitter is released from any of the wide varieties of
synapses onto a wide variety of targets, as illustrated in Figure 5-6 , it
crosses the synaptic cleft and binds to a receptor. What happens next
depends on the receptor type.
Structurally, ionotropic receptors resemble voltage-sensitive
channels, which propagate the action potential. See Figure 4-17 .
Ionotropic receptors allow the ions, such as Na1 , K1 , and Ca2 1, to
move across a membrane (the suffix -tropic means moving toward ). As
Figure 5-14 illustrates, an ionotropic receptor has two parts: (1) a binding
site for a neurotransmitter and (2) a pore, or channel. When the
neurotransmitter attaches to the binding site, the receptor quickly changes
shape, either opening the pore and allowing ions to flow through it or
closing the pore and blocking the ion flow. Thus, ionotropic receptors
bring about rapid changes in membrane voltage and are usually
excitatory: they trigger an action potential.
 ionotropic receptor Embedded membrane protein; acts as (1) a
binding site for a neurotransmitter and (2) a pore that regulates ion
flow to directly and rapidly change membrane voltage.
In contrast, a metabotropic receptor has a binding site for a
neurotransmitter but lacks its own pore through which ions can flow.
Through a series of steps, activated metabotropic receptors indirectly
produce changes in nearby membrane-bound ion channels or in the cell’s
metabolic activity. Figure 5-15 A shows the first of these two indirect
effects. The metabotropic receptor consists of a single protein that spans
the cell membrane, its binding site facing the synaptic cleft. Each receptor
is coupled to one of a family of guanyl nucleotide–binding proteins, G
proteins for short, shown on the inner side of the cell membrane in
Figure 5-15 A. When activated, a G protein binds to other proteins.
metabotropic receptor Embedded membrane protein with a binding
site for a neurotransmitter linked to a G protein; can affect other
receptors or act with second messengers to affect other cellular
processes, including opening a pore.
G protein Guanyl nucleotide–binding protein coupled to a
metabotropic receptor; when activated, binds to other proteins.

FIGURE 5-14 Ionotropic Receptor When activated, embedded

transmitter proteins bring about direct, rapid changes in membrane voltage.
 A G protein consists of three subunits: alpha, beta, and gamma. (A
subunit is a protein that assembles with other proteins.) The alpha
subunit detaches when a neurotransmitter binds to the G protein’s
associated metabotropic receptor. The detached alpha subunit can then
bind to other proteins within the cell’s membrane or its intracellular fluid.
If the alpha subunit binds to a nearby ion channel in the membrane, as
shown at the bottom of Figure 5-15 A, the channel structure changes,
modifying the flow of ions through it. If the channel is open, the alpha
subunit may close it or, if closed, it may open. Changes in the channel
and the ion flow across the membrane influence the membrane’s
electrical potential.
subunit Protein molecule that assembles with other protein
molecules.
The binding of a neurotransmitter to a metabotropic receptor can also
trigger more complicated cellular reactions, summarized in Figure 5-15
B. All these reactions begin when the detached alpha subunit binds to an
enzyme. The enzyme in turn activates a second messenger (the
neurotransmitter being the first messenger) that carries instructions to
other cellular structures. As illustrated at the bottom of Figure 5-15 B, the
second messenger can
second messenger Chemical that initiates a biochemical process
when activated by a neurotransmitter (the first messenger).
 FIGURE 5-15 Metabotropic Receptors When activated by a
neurotransmitter, embedded membrane receptor proteins trigger
associated G proteins, exerting indirect effects (A) on nearby ion channels
or (B) in the cell’s metabolic activity.

• bind to a membrane-bound channel, causing the channel to change its

structure and thus alter ion flow through the membrane.
• initiate a reaction that incorporates intracellular (within the cell) protein
molecules into the cell membrane, resulting, for example, in the
formation of new ion channels.
• bind to sites on the cell’s DNA to initiate or cease the production of
specific proteins.
Metabotropic receptors also allow for the possibility that a single
neurotransmitter’s binding to a receptor can activate an escalating
sequence of events called an amplification cascade. The cascade effect is
that many downstream proteins (second messengers or channels or both)
are activated or deactivated. Ionotropic receptors do not have such a
widespread amplifying effect.
 Recall that acetylcholine has an excitatory effect on skeletal muscles.
Here it activates an ionotropic receptor. Conversely, acetylcholine has an
inhibitory effect on the heart rate. Here it activates a metabotropic
receptor. Further, each transmitter may bind with several different kinds
of ionotropic or metabotropic receptors. Elsewhere in the nervous system,
for example, ACh may activate a wide variety of either receptor type.
Receptor Subtypes
While there are two general classes of receptors, ionotropic and
metabotropic, each neurotransmitter may interact with a number of
receptor subtypes specific to that neurotransmitter. Serotonin (5-HT), for
instance, has one ionotropic receptor subtype (5-HT3 ) and 12 subtypes of
metabotropic receptors. Table 5-3 lists the variety of small-molecule
neurotransmitter receptor subtypes.
How is this variety achieved? Alternative forms of each subunit can
assemble in unique combinations to make a functional receptor. For
instance, the functional NMDA receptor, an ionotropic receptor for
glutamate, is always composed of 4 subunits, but a total of 12 distinct
subunits are available to come together in various combinations to form
the functional receptor.
Why does the brain contain so many receptor subtypes for each
neurotransmitter? The answer seems to be that each subtype has slightly
different properties, which confer different activities. These activities can
include the presence or absence of binding sites for other molecules, how
long a channel remains open or closed, and the ability to interact with
intracellular signaling molecules.
Figure 14-18 diagrams how glutamate and the NMDA receptor
function in associative learning.
TABLE 5-3 Small-Molecule Transmitter Receptors *
Neurotransmitte lonotropic Metabotropic Receptors
r Receptors

Acetylcholine Nicotinic Muscarinic † M1, M2, M3, M4, M5

(ACh)

Dopamine (DA) — D1 , D2 , D3 , D4 , D5

GABA GABAA GABAB

Glutamate (Glu) NMDA, mGluR1 , mGluR2 , mGluR3 , mGluR4 , mGluR5 , mGluR6

AMPA,
 kainate , mGluR7

Glycine (Gly) Glycine, —

NMDA

Histamine (H) — H1 , H2 , H3

Norepinephrine — α 1a , α 1b , α 1c , α 1d , α 2a , α 2b , α 2c , α 2d , β 1 , β 2 , β
(NE) 3

Serotonin (5-HT) 5-HT3 5-HT1A , 5-HT1B , 5-HT1D , 5-HT1E , 5-HT1F , 5-HT2A , 5-

HT2B , 5-HT2C , 5-HT4 , 5-HT5 , 5-HT6 , 5-HT7

* Peptide neurotransmitters and the lipid neurotransmitters anandamide and 2-AG have
specific metabotropic-class receptors. Gaseous neurotransmitters do not have a specific
receptor.
† All metabotropic cholinergic receptors are muscarinic.

It should not be surprising that a brain such as ours, with its incredible
complexity, is built upon a vast array of units, including copious
neurotransmitter types and even more copious receptor types. All this,
and more, allows the human brain to function successfully.
 5-2 REVIEW
Varieties of Neurotransmitters and Receptors
Before you continue, check your understanding.
1 . Neurotransmitters are identified using four experimental criteria:
___________, ___________, ___________, and ___________.
2 . The four broad classes of chemically related neurotransmitters are
___________, ___________, ___________, and ___________.
3 . Acetylcholine is composed of ___________ and ___________. After
release into the synaptic cleft, ACh is broken down by ___________,
and the products can be recycled.
4 . Endocannabinoids are ___________ neurotransmitters, made on
demand and released from the ___________ membrane.
5 . Contrast the major characteristics of ionotropic and metabotropic
receptors.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Neurotransmitter Systems and
5-3

Behavior
When researchers began to study neurotransmission, they reasoned that
any given neuron would contain only one transmitter at all its axon
terminals. Newer methods of analysis revealed that this hypothesis isn’t
strictly accurate. A single neuron may use one transmitter at one synapse
and a different transmitter at another synapse. Moreover, different
transmitters may coexist in the same terminal or synapse. Neuropeptides
have been found to coexist in terminals with small-molecule transmitters,
and more than one small-molecule transmitter may be found in a single
synapse. In some cases, more than one transmitter may even be packaged
within a single vesicle.
All these findings allow for multiple combinations of
neurotransmitters and receptors for them. They caution as well against
assuming a simple cause-and-effect relation between a neurotransmitter
and a behavior. What are the functions of so many combinations? The
answer will likely vary, depending on the behavior that is controlled.
Generally, neurotransmission is simplified by concentrating on the
dominant transmitter within any given axon terminal. The neuron and its
dominant transmitter can then be associated with a function or behavior.
We now consider some links between neurotransmitters and behavior.
We begin by exploring the three peripheral nervous system divisions:
SNS, ANS, and ENS. Then we investigate neurotransmission in the
central nervous system.

Neurotransmission in the Somatic Nervous

System
Motor neurons in the brain and spinal cord send their axons to the body’s
skeletal muscles, including the muscles of the eyes and face, trunk,
limbs, fingers, and toes. Without these SNS neurons, movement would
not be possible. Motor neurons are also called cholinergic neurons
because acetylcholine is their main neurotransmitter. At a skeletal
muscle, cholinergic neurons are excitatory, producing muscular
contractions.
 cholinergic neuron Neuron that uses acetylcholine as its main
neurotransmitter; cholinergic applies to any neuron that uses ACh as
its main transmitter.
Just as a single main neurotransmitter serves the SNS, so does a
single main receptor, a transmitter-activated ionotropic channel called a
nicotinic acetylcholine receptor (nAChr). When ACh binds to this
receptor, its pore opens to permit ion flow, thus depolarizing the muscle
fiber. The nicotinic receptor pore is large enough to permit the
simultaneous efflux of K1 and influx of Na1 . The molecular structure of
nicotine, a chemical found in tobacco, activates the nAChr in the same
way that acetylcholine does, which is how this receptor got its name. The
molecular structure of nicotine is sufficiently similar to that of ACh that
nicotine acts as a mimic, fitting into acetylcholine receptor binding sites.
Acetylcholine is the primary neurotransmitter at skeletal muscles, but
other neurotransmitters also occupy these cholinergic axon terminals and
are released onto the muscle along with ACh. One is a neuropeptide
called calcitonin gene–related peptide (CGRP), which acts through
CGRP metabotropic receptors to increase the force with which a muscle
contracts.
Nicotinic ACh Receptor Research from J. E. Heuser and T. Reese, 1977, in E. R.
Kandel, ed, The Nervous System, vol. 1, Handbook of Physiology. Oxford University
Press, p. 266.
Dual Activating Systems of the Autonomic
Nervous System
The complementary ANS divisions, sympathetic and parasympathetic,
regulate the body’s internal environment. The sympathetic division
rouses the body for action, producing the fight-or-flight response. Heart
rate ramps up and digestive functions ramp down. The parasympathetic
division calms the body down, producing an essentially opposite restand-
digest response. Digestive functions ramp up, heart rate ramps down, and
the body is ready to relax.
Figure 5-16 shows the neurochemical organization of the ANS. Both
divisions are controlled by acetylcholine neurons that emanate from the
CNS at two levels of the spinal cord. The CNS neurons synapse with
parasympathetic neurons that also contain acetylcholine and with
sympathetic neurons that contain norepinephrine. In other words,
cholinergic neurons in the CNS synapse with sympathetic NE neurons to
prepare the body’s organs for fight or flight. Cholinergic neurons in the
CNS synapse with autonomic ACh neurons in the parasympathetic
division to prepare the body’s organs to rest and digest.
 Controlling Biological Functions in the
FIGURE 5-16

Autonomic Nervous System The neurotransmitter in all the

neurons leaving the spinal cord is acetylcholine. Left: In the sympathetic
division, ACh neurons activate autonomic norepinephrine neurons in the
sympathetic ganglia. NE stimulates organs required for fight or flight and
suppresses activity in organs used to rest and digest. Right: In the
parasympathetic division, ACh neurons from the spinal cord activate ACh
neurons in the parasympathetic ganglia near their target organs to
suppress activity in organs used for fight or flight and to stimulate organs
used to rest and digest. To review the ANS divisions and connections in
detail, see Figure 2-30 .

Which type of synapse is excitatory and which inhibitory depends on

the particular body organ’s receptors. During sympathetic arousal,
norepinephrine turns up heart rate and turns down digestive functions,
because NE receptors on the heart are excitatory, whereas NE receptors
on the gut are inhibitory. Similarly, acetylcholine turns down heart rate
and turns up digestive functions because its receptors on these organs are
reversed: on the heart, inhibitory; on the gut, excitatory. Neurotransmitter
activity, excitatory in one location and inhibitory in another, mediates the
sympathetic and parasympathetic divisions, forming a complementary
autonomic regulating system that maintains the body’s internal
environment under varying circumstances.

Enteric Nervous System Autonomy

The ENS can act without input from the CNS, which is why it has been
called the second brain. It uses all four classes of neurotransmitters, more
than 30 transmitters in total. Most are identical to those employed by the
CNS. Chief among the small-molecule neurotransmitters used by the
enteric nervous system are serotonin and dopamine.
Sensory ENS neurons detect mechanical and chemical conditions in
the system. Via intestinal muscles, motor neurons in the ENS control the
mixing of intestinal contents. Secretion of digestive enzymes is also
under ENS control.

Four Activating Systems in the Central

Nervous System
Just as there is an organization to the neurochemical systems of the PNS,
there is an organization of neurochemical systems in the CNS. These
systems are remarkably similar across a wide range of animal species,
which allowed for their identification, first in the rat brain and then in the
human brain (Hamilton et al., 2010).
For each of the four activating systems that we describe here, a
relatively small number of neurons grouped together in one or a few
brainstem nuclei send axons to widespread CNS regions, suggesting that
these nuclei and their terminals help to synchronize activity throughout
the brain and spinal cord. You can envision an activating system as
analogous to the power supply in a house. The fuse or breaker box is the
source of the power, and from it transmission lines go to each room.
activating system Neural pathways that coordinate brain activity
through a single neurotransmitter; its cell bodies lie in a brainstem
nucleus; axons are distributed through a wide CNS region.
Just as in the ANS, the precise action of the CNS transmitter depends
on the brain region that is innervated and on the types of receptors the
transmitter acts on at that region. To continue our analogy, precisely what
the activating effect of the power is in each room depends on the
electrical devices in that room.
Each of four small-molecule transmitters participates in its own neural
activating system—the cholinergic, dopaminergic, noradrenergic, and
serotonergic systems. Figure 5-17 locates each system’s nuclei, with
arrow shafts mapping the axon pathways and arrowheads indicating axon
terminal locales.
As summarized on the right in Figure 5-17 , each CNS activating
system is associated with numerous behaviors. Associations among
activating systems, behavior, and brain disorders are far less certain. All
these relations are subjects of ongoing research. Making definitive
correlations between activating systems and behavior or activating
systems and a disorder is difficult, because the axons of these systems
connect to almost every part of the brain and spinal cord. They likely
have both specific functions and modulatory roles. We detail some of the
documented relations between the systems and behavior and disorders
here and in many subsequent chapters.
 FIGURE 5-17 Major Activating Systems Each system’s cell
bodies are gathered into nuclei (shown as ovals) in the brainstem. Their
axons project diffusely through the CNS and synapse on target structures.
Each activating system is associated with one or more behaviors or
diseases.

Basal ganglia

FIGURE 5-18 Cholinergic Activation Drawing at left shows the

cortical location of the micrograph at right, stained to reveal AChE.
Cholinergic neurons in the rat’s basal forebrain project to the neocortex,
and the darkly stained bands in the cortex show areas rich in cholinergic
synapses. The darker central parts of the section, also rich in cholinergic
neurons, are the basal ganglia.

Cholinergic System
Figure 5-18 shows in cross section a rat brain stained for the enzyme
acetylcholinesterase (AChE), which breaks down ACh in synapses, as
diagrammed earlier in Figure 5-10 . The darkly stained areas have high
AChE concentrations, indicating the presence of cholinergic terminals.
AChE permeates the cortex and is especially dense in the basal ganglia.
Many of these cholinergic synapses are connections from ACh nuclei in
the brainstem, as illustrated in the top panel of Figure 5-17 .
The EEG detects electrical signals the brain emits during various
conscious states; see Sections 7-2 and 13-3 .
The cholinergic system participates in typical waking behavior,
attention, and memory. For example, cholinergic neurons take part in
producing one form of waking EEG activity. People affected by the
degenerative Alzheimer disease, which begins with minor forgetfulness,
progresses to major memory dysfunction, and later develops into
generalized dementia, show a profound loss of cholinergic neurons at
autopsy. One treatment strategy for Alzheimer disease is drugs that
stimulate the cholinergic system to enhance alertness. But the beneficial
effects of these drugs are minor at best (Herrmann et al., 2011). Recall
that ACh is synthesized from nutrients in food; thus, the role of diet in
maintaining acetylcholine levels also is being investigated.
Alzheimer disease Degenerative brain disorder related to aging;
first appears as progressive memory loss and later develops into
generalized dementia.
Focus 14-3 details research on Alzheimer disease. Section 16-3
reviews dementias’ causes and treatments.
The brain abnormalities associated with Alzheimer disease are not
limited to the cholinergic neurons, however. Autopsies reveal extensive
damage to the neocortex and other brain regions. As a result, what role,
if any, the cholinergic neurons play in the progress of the disorder is not
yet clear. Perhaps their destruction causes degeneration in the cortex or
perhaps the cause-and-effect relation is the other way around, with
cortical degeneration causing cholinergic cell death. Then too, the loss of
cholinergic neurons may be just one of many neural symptoms of
Alzheimer disease.
Dopaminergic System
Figure 5-17 maps the dopaminergic activating system’s two distinct
pathways. The nigrostriatal dopaminergic system plays a major role in
coordinating movement. As described throughout this chapter in relation
to parkinsonism, when dopamine neurons in the substantia nigra are lost,
the result is a condition of extreme muscular rigidity. Opposing muscles
contract at the same time, making it difficult for an affected person to
move.
Parkinson patients also exhibit rhythmic tremors, especially of the
limbs, which signals a release of formerly inhibited movement. Although
the causes of Parkinson disease are not fully known, it can actually be
triggered by the ingestion of certain toxic drugs, as described in Clinical
Focus 5-4 , The Case of the Frozen Addict. Those drugs may act as
selective neurotoxins that specifically kill dopamine neurons in the
substantia nigra.
Dopamine in the mesolimbic dopaminergic system may be the
neurotransmitter most affected in addiction—to food, to drugs, and to
other behaviors that involve a loss of impulse control. A common feature
of addictive behaviors is that stimulating the mesolimbic dopaminergic
system enhances responses to environmental stimuli, thus making those
stimuli attractive and rewarding. Indeed, some Parkinson patients who
take dopamine receptor agonists as medications show a loss of impulse
control that manifests in such behaviors as pathological gambling,
hypersexuality, and compulsive shopping (Moore et al., 2014).

Copyright Katsuyoshi Tanaka, courtesy of the Mark Morris Dance Group

Rhythmic movement helps Parkinson patients restore the balance
between neural excitation and inhibition—between the loss and the
release of behavior. Some patients participate in a specially designed
Dance for PD (http://danceforparkinsons.org/ ) class for people with
Parkinson’s (PwP). Participants at the Mark Morris Dance Center, pictured
here, report that moving to music helps them regain muscle control.
CLINICAL FOCUS 5-4

The Case of the Frozen Addict

Patient 1: During the first 4 days of July 1982, a 42-year-old man
used 4½ grams of a “new synthetic heroin.” The substance was
injected intravenously three or four times daily and caused a
burning sensation at the site of injection. The immediate effects
were different from heroin, producing an unusual “spacey” high
as well as transient visual distortions and hallucinations. Two days
after the final injection, he awoke to find that he was “frozen” and
could move only in “slow motion.” He had to “think through each
movement” to carry it out. He was described as stiff, slow, nearly
mute, and catatonic during repeated emergency room visits from
July 9 to July 11. (Ballard et al., 1985, p. 949)
Patient 1 was one of seven young adults hospitalized at about the
same time in California. All showed symptoms of severe Parkinson
disease that appeared very suddenly after drug injection. These
symptoms are extremely unusual in this age group. All who were
affected reportedly injected a synthetic heroin that was being sold on
the streets in the summer of 1982.
J. William Langston (2008) and his colleagues found that the
synthetic heroin contained a contaminant called MPTP (1-methyl-4-
phenyl-1,2,3,6-tetrahydropyridine) resulting from poor technique
during its synthesis. The results of experimental studies in rodents
showed that MPTP was not itself responsible for the patients’
symptoms but was metabolized into MPP1 (1-methyl-4-
phenylpyridinium), a neurotoxin.
The autopsy of one individual who was suspected of having died
of MPTP poisoning showed that the brain had selectively lost
dopamine neurons in the substantia nigra. The rest of the brain
appeared healthy. Injecting MPTP into monkeys, rats, and mice
produced similar symptoms and a similar selective loss of
dopaminergic neurons in the substantia nigra. Thus, the combined
clinical and experimental evidence indicates that a toxin can
selectively kill dopamine neurons and that the die-off can induce
Parkinson disease.
 In 1988, Patient 1 received an experimental treatment at
University Hospital in Lund, Sweden. Living dopamine neurons
taken from human fetal brains at autopsy were implanted into the
caudate nucleus and putamen (Widner et al., 1992). Extensive work
with rodents and nonhuman primates in a number of laboratories had
demonstrated that fetal neurons, before they develop dendrites and
axons, can survive transplantation, mature, and secrete
neurotransmitters.
Patient 1 had no serious postoperative complications and was
much improved 24 months after the surgery. He could dress and feed
himself, visit the bathroom with help, and make trips outside his
home. He also responded much better to medication. The
accompanying diagrams contrast DA levels in the brain of a
Parkinson patient before (left) and 2 years, 4 months after
implantation (right).
Transplantation of fetal neurons to treat Parkinson disease
typically does not work. Unlike the case of the frozen addict,
Parkinson disease is associated with a continuing, active process that
destroys dopaminergic neurons, including transplanted neurons, in
the substantia nigra. Because Parkinson disease can affect as many
as 20 people per 100,000, scientists continue to experiment with new
approaches to transplantation and with genetic approaches for
modifying remaining dopamine neurons (Lane et al., 2010).
DA levels before fetal DA cell implantation
 DA production at 2 years, 4 months after implantation
These diagrams represent PET scans that contrast DA levels in
a Parkinson patient’s brain before, and 28 months after,
implantation. Research from “Bilateral Fetal Mesencephalic Grafting
in Two Patients with Parkinsonism Induced by 1-Methyl-4-phenyl-
1,2,3,6-tetrahydropyradine (MPTP),” by H. Widner, J. Tetrud, S.
Rehngrona, B. Snow, P. Brundin, B. Gustavii, A. Bjorklund, O.
Lindvall, and J. W. Langston, 1992, New England Journal of
Medicine, 327, p. 151.

Sections 6-3 , 6-4 , and 12-3 describe drug effects on the mesolimbic
DA system. Sections 6-2 and 7-4 discuss schizophrenia’s possible
causes and Section 16-4 , its neurobiology.
Excessive mesolimbic dopaminergic activity is proposed as well to
play a role in schizophrenia, a behavioral disorder characterized by
delusions, hallucinations, disorganized speech, blunted emotion,
agitation or immobility, and a host of associated symptoms.
Schizophrenia is one of the most common and most debilitating
psychiatric disorders, affecting about 1 in 100 people.
 schizophrenia Behavioral disorder characterized by delusions,
hallucinations, disorganized speech, blunted emotion, agitation or
immobility, and a host of associated symptoms.
Noradrenergic System
Norepinephrine (noradrenaline) may participate in learning by
stimulating neurons to change their structure. Norepinephrine may also
facilitate healthy brain development and contribute to organizing
movements. A neuron that uses norepinephrine as its transmitter is
termed a noradrenergic neuron (derived from adrenaline, the Latin
name for epinephrine ).
noradrenergic neuron From adrenaline, Latin for epinephrine ; a
neuron containing norepinephrine.
In the main, behaviors and disorders related to the noradrenergic
system concern the emotions. Some symptoms of major depression —a
mood disorder characterized by prolonged feelings of worthlessness and
guilt, the disruption of typical eating habits, sleep disturbances, a general
slowing of behavior, and frequent thoughts of suicide—may be related to
decreased activity of noradrenergic neurons. Conversely, some
symptoms of mania (excessive excitability) may be related to increased
activity in these same neurons. Decreased NE activity has also been
associated both with hyperactivity and attention-deficit/hyperactivity
disorder (ADHD).
major depression Mood disorder characterized by prolonged
feelings of worthlessness and guilt, the disruption of normal eating
habits, sleep disturbances, a general slowing of behavior, and
frequent thoughts of suicide.
mania Disordered mental state of extreme excitement.
Serotonergic System
The serotonergic activating system maintains a waking EEG in the
forebrain when we move and thus participates in wakefulness, as does
the cholinergic system. Like norepinephrine, serotonin plays a role in
learning, as described next in Section 5-4 . Some symptoms of
depression may be related to decreased activity in serotonin neurons, and
drugs commonly used to treat depression act on 5-HT neurons.
Consequently, two forms of depression may exist, one related to
norepinephrine and another related to serotonin.
 Likewise, some research results suggest that various symptoms of
schizophrenia also may be related to increases in serotonin activity,
which implies that different forms of schizophrenia may exist. Decreased
serotonergic activity is related to symptoms observed in obsessive-
compulsive disorder (OCD), in which a person compulsively repeats
acts (such as hand washing) and has repetitive and often unpleasant
thoughts (obsessions). Evidence also points to a link between
abnormalities in serotonergic nuclei and conditions such as sleep apnea
and sudden infant death syndrome (SIDS).
obsessive-compulsive disorder (OcD) Behavior characterized by
compulsively repeated acts (such as hand washing) and repetitive,
often unpleasant, thoughts (obsessions).
Consult the Index of Disorders inside the book’s front cover for
more information on major depression, mania, ADHD, OCD, sleep
apnea, and SIDS.
 5-3 REVIEW
Neurotransmitter Systems and Behavior
Before you continue, check your understanding.
1 . Although neurons can synthesize more than one ___________, they
are usually identified by the principal ___________ in their axon
terminals.
2 . In the peripheral nervous system, the neurotransmitter at somatic
muscles is ___________; in the autonomic nervous system,
___________ neurons from the spinal cord connect with ___________
neurons for parasympathetic activity and with ___________ neurons
for sympathetic activity.
3 . The two principal small-molecule transmitters used by the enteric
nervous system are ___________ and ___________.
4 . The four main activating systems of the CNS are ___________,
___________, ___________, and ___________.
5 . How would you respond to the comment that a behavior is caused
solely by a chemical imbalance in the brain?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Adaptive Role of Synapses in
5-4

Learning and Memory

Among our most cherished abilities are learning and remembering.
Neuroplasticity is a requirement for learning and memory and a
characteristic of the mammalian brain. In fact, it is a trait of the nervous
systems of all animals, even the simplest worms. Larger brains with
more connections are more plastic, however, and thus likely to show
more adaptability in neural organization.
Experiment 2-1 demonstrates observational learning in the octopus
and the ubiquity of neuroplasticity.
Greater adaptability happens because experience can alter the
synapse. Not only are synapses versatile in structure and function, they
are plastic: they can change. The synapse, therefore, is the site for the
neural basis of learning, a relatively permanent change in behavior that
results from experience.
learning Relatively permanent change in behavior that results from
experience.
Donald O. Hebb (1949) was not the first to suggest that learning is
mediated by structural changes in synapses. But the change that he
envisioned in his book The Organization of Behavior was novel 65 years
ago. Hebb theorized, “When an axon of cell A is near enough to excite a
cell B and repeatedly or persistently takes part in firing it, some growth
process or metabolic change takes place in one or both cells such that A’s
efficiency, as one of the cells firing B, is increased” (Hebb, 1949, p. 62).
Simply put, cells that fire together wire together. A synapse that
physically adapts in this way is called a Hebb synapse today.
Hebb’s “cell-assembly” diagram appears at the end of Section 15-1 .
Eric Kandel was awarded a Nobel Prize in 2000 for his descriptions
of the synaptic basis of learning in a way that Hebb envisaged: learning
in which the conjoint activity of nerve cells serves to link them. Kandel’s
subject, the marine slug Aplysia californica, is an ideal subject for
learning experiments. Slightly larger than a softball and lacking a shell,
Aplysia has roughly 20,000 neurons. Some are quite accessible to
researchers, who can isolate and study circuits having few synapses.
 When threatened, Aplysia defensively withdraws its more vulnerable
body parts—the gill (through which it extracts oxygen from the water to
breathe) and the siphon (a spout above the gill that excretes seawater and
waste). By stroking or shocking the slug’s appendages, Kandel and his
coworkers (Bailey et al., 2015) produced enduring changes in its
defensive behaviors. They used these behavioral responses to study
underlying changes in Aplysia ’s nervous system.
We illustrate the role of synapses in two kinds of learning that Kandel
has studied: habituation and sensitization. For humans, both are called
unconscious because they do not depend on a person’s knowing precisely
when and how they occur.

Copyright © Earley, Steve/Animals Animals—All rights reserved.

Aplysia californica
Section 14-4 investigates the neural bases of brain plasticity in
conscious learning and in memory.

Habituation Response
In habituation, the response to a stimulus weakens with repeated
stimulus presentations. If you are accustomed to living in the country,
then move to a city, you might at first find the sounds of traffic and
people extremely loud and annoying. With time, however, you stop
noticing most of the noise most of the time. You have habituated to it.
habituation Learned behavior in which the response to a stimulus
weakens with repeated presentations.
 Habituation develops with all our senses. When you first put on a
shoe, you feel it on your foot, but very soon it is as if the shoe were not
there. You have not become insensitive to sensations, however. When
people talk to you, you still hear them; when someone steps on your foot,
you still feel the pressure. Your brain simply has habituated to the
customary background sensation of a shoe on your foot.
Aplysia habituates to waves in the shallow tidal zone where it lives.
These slugs are constantly buffeted by the flow of waves against their
body, and they learn that waves are just the background noise of daily
life. They do not flinch and withdraw every time a wave passes over
them. They habituate to this stimulus.
A sea slug that is habituated to waves remains sensitive to other touch
sensations. Prodded with a novel object, it responds by withdrawing its
siphon and gill. The animal’s reaction to repeated presentations of the
same novel stimulus forms the basis for Experiment 5-2 , studying its
habituation response.
Neural Basis of Habituation
The Procedure section of Experiment 5-2 shows the setup for studying
what happens to the withdrawal response of Aplysia ’s gill after repeated
stimulation. A gentle jet of water is sprayed on the siphon while gill
movement is recorded. If the water jet is presented to Aplysia ’s siphon
as many as 10 times, the gill withdrawal response is weaker some
minutes later, when the animal is again tested. The decrement in the
strength of the withdrawal is habituation, which can last as long as 30
minutes.
The Results section of Experiment 5-2 starts by showing a simple
representation of the pathway that mediates Aplysia ’s gill withdrawal
response. For purposes of illustration, only one sensory neuron, one
motor neuron, and one synapse are shown; in actuality, about 300
neurons may take part in this response. The water jet stimulates the
sensory neuron, which in turn stimulates the motor neuron responsible
for the gill withdrawal. But exactly where do the changes associated with
habituation take place? In the sensory neuron? In the motor neuron? In
the synapse between the two?
Habituation does not result from an inability of either the sensory or
the motor neuron to produce action potentials. In response to direct
electrical stimulation, both the sensory neuron and the motor neuron
retain the ability to generate action potentials even after habituation.
Electrical recordings from the motor neuron show that as habituation
develops, the excitatory postsynaptic potentials (EPSPs) in the motor
neuron become smaller.
The most likely way in which these EPSPs decrease in size is that the
motor neuron is receiving less neurotransmitter from the sensory neuron
across the synapse. And if less neurotransmitter is being received, then
the changes accompanying habituation must be taking place in the
presynaptic axon terminal of the sensory neuron.
 EXPERIMENT 5-2

Question: What happens to the gill response after repeated

stimulation?
Procedure

Results
Conclusion: The withdrawal response weakens with repeated presentation of water jet
(habituation) owing to decreased Ca2 1 influx and subsequently less neurotransmitter
release from the presynaptic axon terminal.

Reduced Sensitivity of Calcium Channels Underlies

Habituation
Kandel and his coworkers measured neurotransmitter output from a
sensory neuron and verified that less neurotransmitter is in fact released
from a habituated neuron than from a nonhabituated one. Recall from
Figure 5-5 that neurotransmitter release in response to an action potential
requires an influx of calcium ions across the presynaptic membrane. As
habituation takes place, that Ca2+ influx decreases in response to the
voltage changes associated with an action potential. Presumably, with
repeated use, voltage-sensitive calcium channels become less responsive
to voltage changes and more resistant to the passage of calcium ions.
The neural basis of habituation lies in the change in presynaptic
calcium channels. Its mechanism, which is summarized close up in the
Results section of Experiment 5-2 , is a reduced sensitivity of calcium
channels and a consequent decrease in neurotransmitter release. Thus,
habituation can be linked to a specific molecular change, as summarized
in the experiment’s Conclusion.

Sensitization Response
A sprinter crouched in her starting blocks is often hyperresponsive to the
starter’s gun: its firing triggers in her a rapid reaction. The stressful,
competitive context of the race helps to sensitize the sprinter to this sound.
Sensitization, an enhanced response to some stimulus, is the opposite of
habituation. The organism becomes hyperresponsive to a stimulus rather
than accustomed to it.
sensitization Learned behavior in which the response to a stimulus
strengthens with repeated presentations.
Sensitization occurs within a context. Sudden, novel stimulation
heightens our general awareness and often results in larger-than-typical
responses to all kinds of stimulation. If a loud noise startles you suddenly,
you become much more responsive to other stimuli in your surroundings,
including some to which you previously were habituated. In
posttraumatic stress disorder (PTSD), physiological arousal related to
recurring memories and dreams surrounding a traumatic event persist for
months or years after the event. One characteristic of PTSD is a
heightened response to stimuli, suggesting that the disorder is in part
related to sensitization.
posttraumatic stress disorder (PtsD) Syndrome characterized by
physiological arousal associated with recurrent memories and dreams
arising from a traumatic event that occurred months or years earlier.
Stress can foster and prolong PTSD effects. See Sections 6-5 and 12-
4 . Section 16-4 covers treatment strategies.
The same thing happens to Aplysia. Sudden, novel stimuli can heighten
a slug’s responsiveness to familiar stimulation. When attacked by a
predator, for example, the slug displays heightened responses to many
other stimuli in its environment. In the laboratory, a small electric shock to
Aplysia ’s tail mimics a predatory attack and effects sensitization, as
illustrated in the Procedure section of Experiment 5-3 . A single electric
shock to the slug’s tail enhances its gill withdrawal response for a period
that lasts for minutes to hours.
 EXPERIMENT 5-3

Question: What happens to the gill response in

sensitization?
Procedure

Results
Conclusion: Enhancement of the withdrawal response after a shock is due to increased
Ca2 1 influx and subsequently more neurotransmitter release from the presynaptic axon
terminal.

Neural Basis of Sensitization

The neural circuits participating in sensitization differ from those that
take part in a habituation response. The Results section of Experiment 5-
3 shows the sensory and motor neurons that produce the gill withdrawal
response and adds an interneuron that is responsible for sensitization.
An interneuron that receives input from a sensory neuron in Aplysia ’s
tail (and so carries information about the shock) makes an axoaxonic
synapse with a sensory neuron in the siphon. The interneuron’s axon
terminal contains serotonin. Consequently, in response to a tail shock,
the tail sensory neuron activates the interneuron, which in turn releases
5-HT onto the axon of the siphon sensory neuron. Information from the
siphon still comes through the sensory neuron to activate the motor
neuron leading to the gill muscle, but the interneuron’s action in
releasing 5-HT onto the sensory neuron’s presynaptic membrane
amplifies the gill withdrawal response.
At the molecular level, shown close up in Experiment 5-3 Results, the
serotonin released from the interneuron binds to a metabotropic
serotonin receptor on the siphon’s sensory neuron axon. This binding
activates second messengers in the sensory neuron. Specifically, the
serotonin receptor is coupled through its G protein to the enzyme adenyl
cyclase. This enzyme increases the concentration of second messenger
cyclic adenosine monophosphate (cAMP) in the presynaptic membrane
of the siphon’s sensory neuron.
Through several chemical reactions, cAMP attaches a phosphate
molecule (PO4 ) to potassium channels, rendering them less responsive.
The close-up in Experiment 5-3 sums it up. In response to an action
potential traveling down the axon of the siphon’s sensory neuron (such
as one generated by a touch to the siphon), the potassium channels on
that neuron are slower to open. Consequently, K1 ions cannot repolarize
the membrane as quickly as normal, so the action potential lasts longer
than it usually would.
Less-Responsive Potassium Channels Underlie Sensitization
The longer-lasting action potential that occurs because potassium
channels are slower to open prolongs Ca2+ inflow. Ca2+ influx is
necessary for neurotransmitter release. Thus, greater Ca2+ influx results
in more neurotransmitter being released from the sensory synapse onto
the motor neuron.
This increased neurotransmitter release produces greater activation of
the motor neuron and thus a larger-than-normal gill withdrawal response.
If the second messenger cAMP mobilizes more synaptic vesicles,
making more neurotransmitter ready for release into the sensory–motor
synapse, gill withdrawal may also be enhanced.
Sensitization, then, is the opposite of habituation at the molecular
level as well as at the behavioral level. In sensitization, more Ca2+ influx
results in more transmitter being released, whereas in habituation, less
Ca2+ influx results in less neurotransmitter being released. The structural
basis of cellular memory in these two forms of learning is different,
however. In sensitization, the change takes place in potassium channels,
whereas in habituation, the change takes place in calcium channels.

Learning as a Change in Synapse Number

Neural changes associated with learning must last long enough to
account for a relatively permanent change in an organism’s behavior.
The changes at synapses described in the preceding sections develop
quite quickly, but they do not last indefinitely, as memories often do.
How then, can synapses be responsible for the long-term changes
associated with learning and memory?
Repeated stimulation produces habituation and sensitization that can
persist for months. Brief training produces short-term learning; longer
training periods produce more enduring learning. If you cram for an
exam the night before you take it, you might forget the material quickly,
but if you study a little each day for a week, your learning may tend to
endure. What underlies this more persistent form of learning?
Researchers working with Eric Kandel (Bailey et al., 2015) found that
the number and size of sensory synapses change in well-trained,
habituated, and sensitized Aplysia. Relative to a control neuron, the
number and size of synapses decrease in habituated animals and increase
in sensitized animals, as represented in Figure 5-19 . Apparently,
synaptic events associated with habituation and sensitization can also
trigger processes in the sensory cell that result in the loss or formation of
new synapses.
A mechanism through which these processes can take place begins
with calcium ions that mobilize second messengers to send instructions
to nuclear DNA. The transcription and translation of nuclear DNA in
turn initiate structural changes at synapses, including the formation of
new synapses and new dendritic spines. Research Focus 5-5 , Dendritic
Spines: Small but Mighty, summarizes experimental evidence about
structural changes in dendritic spines.
The second messenger cAMP plays an important role in carrying
instructions regarding these structural changes to nuclear DNA. The
evidence for cAMP’s involvement comes from studies of the fruit fly
Drosophila. Two genetic mutations in the fruit fly can produce similar
learning deficiencies. Both render the second messenger cAMP
inoperative, but in opposite ways. One mutation, called dunce, lacks the
enzymes necessary to degrade cAMP, so the fruit fly has abnormally
high cAMP levels. The other mutation, called rutabaga, reduces levels
of cAMP below the normal range for Drosophila neurons.
Significantly, fruit flies with either mutation are impaired in acquiring
habituated and sensitized responses because their levels of cAMP cannot
be regulated. New synapses seem to be required for learning to take
place, and the second messenger cAMP seems to carry instructions to
form them. Figure 5-20 summarizes these research findings.
Control
Habituated
Sensitized
FIGURE 5-19 Physical Basis of Memory Relative to a control
neuronal connection (left), the number of synapses between Aplysia’s
sensory neuron and a motor neuron decline as a result of habituation
(center) and increase as a result of sensitization (right). Such structural
changes may underlie enduring memories.
RESEARCH FOCUS 5-5

Dendritic Spines: Small but Mighty

Dendritic spines, which protrude from the dendrite’s shaft, measure
about 1 to 3 micrometers (µm, one-millionth of a meter) long and
less than 1 µm in diameter. Each neuron can have many thousands of
spines. The number of dendritic spines in the human cerebral cortex
is estimated at 1014 .
Dendritic spines originate in filopodia (from the Latin file, for
thread, and the Greek podium, for foot ) that bud out of neurons,
especially at dendrites. Microscopic observation of dendrites shows
that filopodia are constantly emerging and retracting over times on
the order of seconds.
This budding of filopodia is much more pronounced in
developing neurons and in the developing brain (see Figure 8-13 ).
Because filo-podia can grow into dendritic spines, their budding
suggests that they are searching for contacts from axon terminals to
form synapses. When contact is made, some new synapses may have
only a short life; others will endure.
A permanent dendritic spine tends to have a large, mushroom-
shaped head, giving it a large contact area with a terminal button,
and a long stem, giving it an identity apart from that of its dendrite.
The heads of spines and the terminals of presynaptic connections
form functional compartments that can generate huge electrical
potentials and so influence the neuron’s electrical messages.
Dendritic spines mediate learning that lasts, including habituation
and sensitization. To mediate learning, each spine must be able to act
independently, undergoing changes that its neighbors do not
undergo.
Examination of dendritic spines in the nervous system shows that
some are simple and others complex. The cellular mechanisms that
allow synapses to appear on spines and to change shape include
microfilaments linked to the membrane receptors, protein transport
from the cell body, and the incorporation of nutrients from the extra-
cellular space.
 The variety suggests that all this activity changes the appearance
of both presynaptic and postsynaptic structures. The illustration
summarizes synaptic structures that can be measured and related to
learning and behavior and to structural changes that may subserve
learning.
Dendritic spines provide the structural basis for our behavior, our
individual skills, and our memories (Bosch & Hayashi, 2012).
Impairments in forming spines characterize some kinds of mental
disability, and the loss of spines is associated with the dementia of
Alzheimer disease.

Synaptic structures that may subserve learning.

More lasting habituation and sensitization are mediated by relatively

permanent changes in neuronal structure—by fewer or more synaptic
connections—and the effects can be difficult to alter. As a result of
sensitization, for example, symptoms of PTSD can persist indefinitely.
FIGURE 5-20 Genetic Disruption of Learning Either of two
mutations in the fruit fly Drosophila inactivates the second messenger
cAMP by moving its level either above or below the concentration range
the cell can regulate, thus disrupting learning.
 5-4 REVIEW
Adaptive Role of Synapses in Learning and Memory
Before you continue, check your understanding.
1 . Experience alters the ___________, the site of the neural basis of
___________, a relatively permanent change in behavior that results
from experience.
2 . Aplysia’s synaptic function mediates two basic forms of learning:
___________ and ___________.
3 . Changes that accompany habituation take place within the
___________ of the ___________ neuron, mediated by ___________
channels that grow ___________ sensitive with use.
4 . The sensitization response is amplified by ___________ that release
serotonin onto the presynaptic membrane of the sensory neuron,
changing the sensitivity of presynaptic ___________ channels and
increasing the influx of ___________.
5 . One characteristic of ___________, defined as physiological arousal
related to recurring memories and dreams surrounding a traumatic
event that persist for months or years after the event, is a heightened
response to stimuli. This suggests that the disorder is in part related to
___________.
6 . Describe the benefits and/or drawbacks of permanent habituation and
sensitization.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 SUMMARY
5-1 A Chemical Message
In the 1920s, Otto Loewi suspected that nerves to the heart secrete a
chemical that regulates its beat rate. His subsequent experiments with
frogs showed that acetylcholine slows heart rate, whereas epinephrine
increases it. This observation proved key to understanding the basis of
chemical neurotransmission.
The systems for chemically synthesizing an excitatory or inhibitory
neurotransmitter are in the presynaptic neuron’s axon terminal or its
soma, whereas the systems for neurotransmitter storage are in its axon
terminal. The receptor systems on which that neurotransmitter acts
typically are on the postsynaptic membrane. Such chemical
neurotransmission is dominant in the human nervous system.
Nevertheless, neurons also make direct connections with each other
through gap junctions, channel-forming proteins that allow direct sharing
of ions or nutrients.
The four major stages in the life of a neurotransmitter are (1)
synthesis and storage, (2) release from the axon terminal, (3) action on
postsynaptic receptors, and (4) inactivation. After synthesis, the
neurotransmitter is wrapped in a membrane to form synaptic vesicles in
the axon terminal. When an action potential is propagated on the
presynaptic membrane, voltage changes set in motion the vesicles’
attachment to the presynaptic membrane and neurotransmitter release by
exocytosis.
One synaptic vesicle releases a quantum of neurotransmitter into the
synaptic cleft, producing a miniature potential on the postsynaptic
membrane. To generate an action potential on the postsynaptic cell
requires simultaneous release of many quanta of transmitter. After a
transmitter has done its work, it is inactivated by such processes as
diffusion out of the synaptic cleft, breakdown by enzymes, and reuptake
of the transmitter or its components into the axon terminal (or sometimes
uptake into glial cells).
5-2 Varieties of Neurotransmitters and Receptors
Small-molecule transmitters, peptide transmitters, lipid transmitters, and
gaseous transmitters are broad classes for ordering the roughly 100
neurotransmitters that investigators propose might exist. Neurons
containing these transmitters make a variety of connections with other
neurons as well as with muscles, blood vessels, and extracellular fluid.
Functionally, neurons can be both excitatory and inhibitory, and they
can participate in local circuits or in general brain networks. Excitatory
synapses are usually on a dendritic tree, whereas inhibitory synapses are
usually on a cell body.
Some neurotransmitters are associated with both ionotropic and
metabotropic receptors. An ionotropic receptor quickly and directly
induces voltage changes on the postsynaptic cell membrane. Slower-
acting metabotropic receptors activate second messengers to indirectly
produce changes in the cell’s function and structure. A plethora of
receptors, formed from combinations of multiple types of proteins called
subunits, exist for most transmitters.
5-3 Neurotransmitter Systems and Behavior
Because neurotransmitters are multifunctional, scientists find it
impossible to isolate relations between a single neurotransmitter and a
single behavior. Rather, activating systems of neurons that employ the
same principal neurotransmitter influence various general aspects of
behavior. For instance, acetylcholine, the main neurotransmitter in the
SNS, controls movement of the skeletal muscles, whereas acetylcholine
and norepinephrine, the main neurotransmitters in the ANS, control the
body’s internal organs. In the ENS, dopamine and serotonin serve as the
main neurotransmitters regulating the gut’s functioning.
The CNS contains not only widely dispersed glutamate and GABA
neurons—its main neurotransmitters—but also neural activating systems
that employ acetylcholine, norepinephrine, dopamine, or serotonin. All
these systems ensure that wide areas of the brain act in concert, and each
is associated with various classes of behaviors and disorders.
5-4 Adaptive Role of Synapses in Learning and
Memory
Changes in synapses underlie the neural basis of learning and memory.
In habituation, a form of learning in which a response weakens as a
result of repeated stimulation, calcium channels become less responsive
to an action potential. Consequently, less neurotransmitter is released
when an action potential is propagated.
 In sensitization, a form of learning in which a response strengthens as
a result of stimulation, changes in potassium channels prolong the action
potential’s duration, resulting in an increased influx of calcium ions and
consequently, release of more neurotransmitter. With repeated training,
new synapses can develop, and both forms of learning can become
relatively permanent.
In Aplysia, the number of synapses connecting sensory neurons and
motor neurons decreases in response to repeated sessions of habituation.
Conversely, the number of synapses connecting sensory and motor
neurons increases in response to repeated sensitization sessions. These
changes in the numbers of synapses and dendritic spines are related to
long-term learning.
 KEY TERMS
acetylcholine (ACh), p. 139
activating system, p. 158
Alzheimer disease, p. 161
autoreceptor, p. 144
carbon monoxide (CO), p. 153
chemical synapse, p. 143
cholinergic neuron, p. 156
dopamine (DA), p. 141
endocannabinoid, p. 151
epinephrine (EP), p. 139
G protein, p. 155
gamma-aminobutyric acid (GABA), p. 151
gap junction (electrical synapse), p. 143
glutamate (Glu), p. 151
habituation, p. 163
histamine (H), p. 148
hydrogen sulfide (H 2 S), p. 153
ionotropic receptor, p. 153
learning, p. 163
major depression, p. 163
mania, p. 163
metabotropic receptor, p. 153
neuropeptide, p. 151
neurotransmitter, p. 139
nitric oxide (NO), p. 153
noradrenergic neuron, p. 163
norepinephrine (NE), p. 139
obsessive-compulsive disorder (OCD), p. 163
Parkinson disease, p. 141
postsynaptic membrane, p. 143
posttraumatic stress disorder (PTSD), p. 164
presynaptic membrane, p. 143
quantum (pl. quanta), p. 144
rate-limiting factor, p. 151
reuptake, p. 144
schizophrenia, p. 161
second messenger, p. 155
sensitization, p. 164
serotonin (5-HT), p. 151
small-molecule transmitter, p. 148
storage granule, p. 143
subunit, p. 155
synaptic cleft, p. 141
synaptic vesicle, p. 141
transmitter-activated receptor, p. 143
transporter, p. 143

Visit Launch Pad : to access the e-Book, videos,

Learning Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

How Do Drugs and

Hormones Influence the
Brain and Behavior?
 Katherine Streeter

CLINICAL FOCUS 6-1 COGNITIVE ENHANCEMENT

6-1 PRINCIPLES OF PSYCHOPHARMACOLOGY
DRUG ROUTES INTO THE NERVOUS SYSTEM
DRUG ACTION AT SYNAPSES: AGONISTS AND ANTAGONISTS
AN ACETYLCHOLINE SYNAPSE: EXAMPLES OF DRUG ACTION
TOLERANCE
EXPERIMENT 6-1 QUESTION: WILL THE CONSUMPTION OF
ALCOHOL PRODUCE TOLERANCE?
SENSITIZATION
EXPERIMENT 6-2 QUESTION: DOES THE INJECTION OF A
DRUG ALWAYS PRODUCE THE SAME BEHAVIOR?
6-2 GROUPING PSYCHOACTIVE DRUGS
GROUP I: ANTIANXIETY AGENTS AND SEDATIVE-HYPNOTICS
CLINICAL FOCUS 6-2 FETAL ALCOHOL SPECTRUM DISORDER
GROUP II: ANTIPSYCHOTIC AGENTS
GROUP III: ANTIDEPRESSANTS AND MOOD STABILIZERS
CLINICAL FOCUS 6-3 MAJOR DEPRESSION
GROUP IV: OPIOID ANALGESICS
GROUP V: PSYCHOTROPICS
6-3 FACTORS INFLUENCING INDIVIDUAL RESPONSES TO
DRUGS
BEHAVIOR ON DRUGS
ADDICTION AND DEPENDENCE
SEX DIFFERENCES IN ADDICTION
6-4 EXPLAINING AND TREATING DRUG ABUSE
WANTING-AND-LIKING THEORY
WHY DOESN’T EVERYONE ABUSE DRUGS?
TREATING DRUG ABUSE
 CAN DRUGS CAUSE BRAIN DAMAGE?
CLINICAL FOCUS 6-4 DRUG-INDUCED PSYCHOSIS
6-5 HORMONES
HIERARCHICAL CONTROL OF HORMONES
CLASSES AND FUNCTIONS OF HORMONES
HOMEOSTATIC HORMONES
GONADAL HORMONES
ANABOLIC–ANDROGENIC STEROIDS
GLUCOCORTICOIDS AND STRESS
CLINICAL FOCUS 6-1

Cognitive Enhancement
A new name for an old game? An article in the preeminent science
publication Nature floated the idea that certain “cognitive-
enhancing” drugs improve school and work performance in
otherwise healthy individuals by improving brain function (Greely et
al., 2008). The article was instigated in part by reports that up to 20
percent—and in some schools up to 80 percent—of high school and
university students were using the combination of Adderall (mainly
dextroamphetamine) and methylphenidate (Ritalin) as a study aid to
help meet deadlines and to cram for examinations.
Both drugs are prescribed as a treatment for attention-
deficit/hyperactivity disorder (ADHD), a developmental disorder
characterized by core behaviors: impulsivity, hyperactivity, and/or
inattention. Methylphenidate and dextroamphetamine are Schedule II
drugs, signifying that they carry the potential for abuse and require a
prescription when used medically. Their main illicit source is
through falsified prescriptions or purchase from someone who has a
prescription. Both drugs share the pharmacological properties of
cocaine: stimulating dopamine release and blocking its reuptake (see
Section 6-2 ).
attention-deficit/hyperactivity disorder (ADHD)
Developmental disorder characterized by core behavioral
symptoms, including impulsivity, hyperactivity, and/or
inattention.
The use of cognitive enhancers is not new. In his classic paper on
cocaine, Viennese psychoanalyst Sigmund Freud stated in 1884,
“The main use of coca [cocaine] will undoubtedly remain that which
the Indians [of Peru] have made of it for centuries … to increase the
physical capacity of the body.” Freud later withdrew his endorsement
when he realized that cocaine is addictive.
In 1937, an article in the Journal of the American Medical
Association reported that a form of amphetamine, Benzedrine,
improved performance on mental efficiency tests. This information
was quickly disseminated among students, who began using the drug
 as a study aid for examinations. In the 1950s, dextroamphetamine,
marketed as Dexedrine, was similarly prescribed for narcolepsy, a
sleep disorder, and used illicitly by students as a study aid.
The complex neural effects of amphetamine stimulants center on
learning at the synapse by means of habituation and sensitization.
With repeated use for nonmedicinal purposes, the drugs can also
begin to produce side effects, including sleep disruption, loss of
appetite, and headaches. Some people develop cardiovascular
abnormalities and/or become addicted to amphetamine.
Treating ADHD with prescription drugs is itself controversial,
despite their widespread use for this purpose. According to Aagaard
and Hansen (2011), assessing the adverse effects of cognitive
enhancement medication is hampered because many participants
drop out of studies and the duration of the studies is short.
Despite the contention that stimulant drugs can improve school
and work performance by improving brain function in otherwise
healthy individuals, evidence for their effectiveness, other than a
transient improvement in motivation, is weak.

Robert Stolarik/The New York Times

Psychopharmacology, the study of how drugs affect the

nervous system and behavior, is the subject of this chapter. We begin by
looking at the major ways drugs are administered, the routes they take to
reach the central nervous system, and how they are eliminated from the
body. We then group psychoactive drugs based on their major behavioral
effects and on how they act on neurons. Next we consider why different
people may respond differently to the same dose of a drug and why
people may become addicted to drugs. Many principles related to drugs
also apply to the action of hormones, the chapter’s final topic, which
includes a discussion of synthetic steroids that act as hormones.
psychopharmacology Study of how drugs affect the nervous
system and behavior.
Before we examine how drugs produce their effects on the brain for
good or for ill, we must raise a caution: the sheer number of
neurotransmitters, receptors, and possible sites of drug action is
astounding. Most drugs act at many sites in the body and brain and affect
more than one neurotransmitter system, and most receptors on which
drugs act display many variations. Individual differences—sex, genetic
makeup, age, height, and weight—all influence how drugs affect people.
Considering all the variables, psycho-pharmacological research has made
important advances in understanding drug action. Yet it remains safe to
say that neuroscientists do not know everything there is to know about
any drug.
 6-1 Principles of Psychopharmacology
Drugs are chemical compounds administered to bring about some desired
change in the body and brain. Drugs are usually used to diagnose, treat, or
prevent illness; to relieve pain and suffering; or to improve some adverse
physiological condition. In this chapter, we focus on psychoactive drugs
—substances that alter mood, thought, or behavior; are used to manage
neuropsychological illness; and may be abused. We also consider
psychoactive drugs that can act as toxins, producing sickness, brain
damage, or death.
psychoactive drug Substance that acts to alter mood, thought, or
behavior; is used to manage neuropsychological illness; or is abused.

Drug Routes into the Nervous System

To be effective, a psychoactive drug has to reach its target in the nervous
system. The way a drug enters and passes through the body to reach its
target is called its route of administration. Drugs can be administered
orally, inhaled into the lungs, administered rectally in a suppository,
absorbed from patches applied to the skin or mucous membranes, or
injected into the bloodstream, into a muscle, or even into the brain.
Figure 6-1 illustrates some of these routes of drug administration and
summarizes the characteristics of drugs that allow them to pass through
various barriers to reach their targets.
Oral administration is easy and convenient but is nonetheless a
complex route. To reach the bloodstream, an ingested drug must first be
absorbed through the lining of the stomach or small intestine. Drugs in
liquid form are absorbed more readily. Drugs taken in solid form are not
absorbed unless the stomach’s gastric juices can dissolve them. Some
drugs may be destroyed or altered by enzymes in the gastrointestinal
tract’s microbiome. Whether a drug is an acid or a base influences its
absorption.
Once absorbed by the stomach or intestine, the drug must enter the
bloodstream. This leg of the journey requires that the drug have additional
properties. Because blood has a high water concentration, the drug must
be water-soluble. It is then diluted by the approximately 6 liters of blood
that circulates through an adult body. When the drug leaves the
bloodstream, the body’s roughly 35 liters of extracellular fluid further
dilute it.
 Drugs administered as gases or aerosols penetrate the cell linings of
the respiratory tract easily and are absorbed across these membranes into
the bloodstream nearly as quickly as they are inhaled. Thus, they reach
the bloodstream by circumventing the barriers in the digestive system.
When administered as a gas or in smoke, drugs of abuse, including
nicotine, cocaine, and marijuana, are similarly absorbed.
Our largest organ, the skin, has three cell layers designed to be a
protective body coat. Some small-molecule drugs (e.g., nicotine in a
patch) penetrate the skin barrier almost as easily as they penetrate the
lungs. Still fewer obstacles confront a drug destined for the brain if that
drug is injected directly into the bloodstream. The fewest obstacles are
encountered if a psychoactive drug is injected directly into the brain.
With each obstacle eliminated en route to the brain, a drug’s dosage
can be reduced by a factor of 10. For example, 1000 micrograms (μg; 1
μg is equal to one-millionth of a gram) of amphetamine, a psychomotor
stimulant and major component of the drugs described in Clinical Focus
6-1 , Cognitive Enhancement, produces a noticeable behavioral change
when ingested orally. If inhaled into the lungs or injected into the blood,
circumventing the stomach, a dose of just 100 μg produces the same
results. If amphetamine is injected into the cerebrospinal fluid, bypassing
both the stomach and the blood, 10 μg is enough to produce an identical
outcome, as is merely 1 μg if dilution in the cerebrospinal fluid also is
skirted and the drug is applied directly to target neurons.
1000 μg = 1 mg (milligram)
 FIGURE 6-1 Routes of Drug Administration
This math is well known to sellers and users of illicit drugs. Drugs
prepared for inhalation or intravenous injection are much cheaper per
dose, because the amount required is so much smaller than that needed
for an effective oral dose.
Revisiting the Blood–Brain Barrier
The body presents barriers to the internal movement of drugs: cell
membranes, capillary walls, and the placenta. The passage of drugs across
capillaries in the brain is made difficult by the blood–brain barrier, the
tight junctions between the cells of blood vessels in the brain that block
passage of most substances. The blood–brain barrier protects the brain’s
ionic balance and denies neurochemicals from the rest of the body
passage into the brain, where they can disrupt communication between
neurons. It protects the brain from the effects of many circulating
hormones and from toxic and infectious substances. Injury or disease can
sometimes rupture the blood–brain barrier, letting pathogens through. For
the most part, however, the brain is well protected from harmful
substances.
Figures 4-7 and 4-8 illustrate ion diffusion and concentration and
voltage gradients.
 The brain has a rich capillary network. None of its neurons is farther
than about 50 micrometers (μm; 1 μm is equal to one-millionth of a
meter) from a capillary. As shown at the left in Figure 6-2 , like all
capillaries, brain capillaries are composed of a single layer of endothelial
cells. In most parts of the body, endothelial cells in capillary walls are not
fused, so substances can pass through the clefts between the cells. In most
parts of the brain, by contrast, endothelial cell walls are fused to form
tight junctions, so molecules of most substances cannot squeeze between
them.
Figure 6-2 also shows that brain capillaries’ endothelial cells are
surrounded by the end feet of astrocytes attached to the capillary wall,
covering about 80 percent of it. The glial cells provide a route for the
exchange of food and waste between capillaries and the brain’s
extracellular fluid and from there to other cells, shown at the right in
Figure 6-2 .
The cells of capillary walls in the three brain regions shown in Figure
6-3 lack a blood–brain barrier. The pituitary is a source of many
hormones secreted into the blood, and their release is triggered in part by
other hormones carried to the pituitary by the blood. The absence of a
blood–brain barrier in the lower brainstem’s area postrema allows toxic
substances in the blood to trigger vomiting. The pineal gland also lacks a
blood–brain barrier, enabling hormones to reach it and modulate the day–
night cycles it controls.
Section 13-2 details the pineal gland’s pacemaking function.

FIGURE 6-2 Blood–Brain Barrier Capillaries in most of the body

allow for substances to pass between capillary cell membranes, but those
 in the brain, stimulated by the actions of astrocytes, form the tight junctions
of the blood–brain barrier.

To carry out its work, the brain needs, among other substances, oxygen
and glucose for fuel and amino acids to build proteins. Fuel molecules
reach brain cells from the blood, just as carbon dioxide and other waste
products are excreted from brain cells into the blood. Molecules of these
vital substances cross the blood–brain barrier in two ways:
1. Small molecules such as oxygen and carbon dioxide can pass through
the endothelial membrane.
2. Complex molecules of glucose, amino acids, and other food
components are carried across the membrane by active transport
systems or ion pumps—transporter proteins specialized to convey a
particular substance.
Few psychoactive drug molecules are sufficiently small or have the
correct chemical structure to gain access to the CNS. An important
property possessed by those few drugs that have CNS effects, then, is an
ability to cross the blood–brain barrier.
How the Body Eliminates Drugs
After a drug is administered, the body soon begins to break it down
(catabolize) and remove it. Drugs are diluted throughout the body and are
sequestered in many regions, including fat cells. They are also catabolized
throughout the body, including in the kidneys and liver, and in the
intestine by bile. They are excreted in urine, feces, sweat, breast milk, and
exhaled air. Drugs developed for therapeutic purposes are usually
designed not only to increase their chances of reaching their targets but
also to enhance their survival time in the body.
The liver is especially active in catabolizing drugs. Owing to a family
of enzymes involved in drug catabolism, the cytochrome P450 enzyme
family (some are also present in the gastrointestinal tract microbiome), the
liver is capable of breaking down many different drugs into forms more
easily excreted from the body. Substances that cannot be catabolized or
excreted can build up in the body and become toxic. The metal mercury,
for instance, is not easily eliminated and can produce severe neurological
effects.
Catabolic processes break down; metabolic processes build up.
Drugs eliminated from the body and discharged into the environment
are extensive and problematic. They may be reingested, via food and
water, by many animal species, including humans (Brown et al., 2015).
Some may affect fertility, embryonic development, even the physiology
and behavior of adult organisms. The solution is redesigning waste
management systems to remove by-products eliminated by humans as
well as by other animals (Berninger et al., 2015).
FIGURE 6-3Barrier-Free Brain Sites The pituitary gland is a target for many
blood-borne hormones; the pineal gland, for hormones that affect circadian rhythms. The
area postrema initiates vomiting of noxious substances.

Drug Action at Synapses: Agonists and

Antagonists
Most drugs that produce psychoactive effects work by influencing
chemical reactions at synapses. So to understand how drugs work, we
must explore the ways they modify synaptic actions. Figure 6-4
summarizes seven major steps in neurotransmission at a synapse—each a
site of drug action:
1. Synthesis of the neurotransmitter can take place in the cell body, the
axon, or the terminal.
2. Storage of the neurotransmitter is in granules or in vesicles or in both.
3. Release of the transmitter is from the terminal’s presynaptic membrane
into the synapse.
4. Receptor interaction takes place in the postsynaptic membrane, as the
transmitter acts on an embedded receptor.
5. Inactivation of excess neurotransmitter occurs at the synapse.
6. Reuptake into the presynaptic terminal for reuse is one outcome.
7. Degradation of excess neurotransmitter by synaptic mechanisms and
removal of unneeded by-products from the synapse is the other
outcome.
 FIGURE 6-4 Points of Influence In principle, a drug can modify
seven major chemical processes, any of which results in enhanced or
reduced synaptic transmission, depending on the drug’s action as an
agonist or antagonist.

Ultimately, a drug that affects any of these synaptic functions either

increases or diminishes neurotransmission. Drugs that increase
neurotransmission are classified as agonists ; drugs that decrease
neurotransmission are classified as antagonists. To illustrate, consider a
typical synapse: the acetylcholine synapse between motor neurons and
muscles.
agonist Substance that enhances synapse function.
antagonist Substance that blocks synapse function.

An Acetylcholine Synapse: Examples of

Drug Action
Figure 6-5 shows how some drugs and toxins act as agonists or
antagonists at the ACh synapse on skeletal muscles. ACh agonists excite
muscles, increasing muscle tone, whereas ACh antagonists inhibit
muscles, decreasing muscle tone. Some of these substances may be new
to you, but you have probably heard of others. If you know their effects at
the ACh synapse, you can understand the relationships between these
substances’ neurochemical actions and their behavioral effects.
Figure 4-26 details the structure and action of ACh at a
neuromuscular synapse.
Figure 6-5 includes two toxins that influence ACh release from the
axon terminal. Black widow spider venom acts as an agonist by
promoting ACh release to excess. A black widow spider bite does not
inject enough drug to paralyze a person, though a victim may feel some
muscle weakness.
Botulinum toxin, or botulin, is the poisonous agent in improperly
processed canned goods. An antagonist, it blocks ACh release, an effect
that can last for weeks to months. Severe poisoning can paralyze both
movement and breathing and so cause death.
Botulin has medical uses. Injected into a muscle, it can selectively
paralyze the muscle. This action makes it useful for blocking excessive
and enduring muscular twitches or contractions, including the spasms that
make movement difficult, for example in people with cerebral palsy.
Under the trade name Botox, botulin is also used cosmetically to paralyze
facial muscles that cause wrinkling.
Focus 11-2 describes the causes and range of outcomes for cerebral
palsy.
Figure 6-5 also shows two drugs that act on ACh receptors. Nicotine’s
molecular structure is similar enough to that of ACh to allow nicotine to
fit into ACh receptors’ binding sites, where it acts as an agonist. Curare
acts as an ACh antagonist by occupying cholinergic receptors and so
preventing ACh from binding to them. Once introduced into the body,
curare acts quickly and is cleared from the body in a few minutes. Large
doses, however, arrest movement and breathing for a period sufficient to
result in death.
As illustrated in Section 5-3 , a single main receptor serves the
sympathetic nervous system: the nicotinic ACh receptor (nAChR).
 FIGURE 6-5 Acetylcholine Agonists and Antagonists
Drugs and nutrients can affect ACh transmission by altering its synthesis or
release or by binding to the postsynaptic receptor and affecting its
breakdown or inactivation.

Early European explorers of South America discovered that the

indigenous peoples living along the Amazon River in South America
killed small animals using arrowheads coated with curare prepared from
the seeds of a plant. The hunters did not poison themselves when eating
the animals, because ingested curare cannot pass from the gut into the
body. Many curarelike drugs have been synthesized. Some are used to
briefly paralyze large animals for examination or tagging for
identification. You have probably seen this use of these drugs in wildlife
videos. Skeletal muscles are more sensitive to curarelike drugs than are
respiratory muscles; an appropriate dose paralyzes an animal’s movement
temporarily but allows it to breathe.
The final drug action shown in Figure 6-5 is that of physostigmine, an
agonist that inhibits acetylcholinesterase (AChE), the enzyme that breaks
down ACh, thus increasing the amount available in the synapse.
Physostigmine, obtained from an African bean, is used as a poison by
hunters.
Figure 5-10 illustrates ACh synthesis and how AChE breaks it down.
Large doses of physostigmine can be toxic because they produce
excessive excitation of the neuromuscular synapse, disrupting movement
and breathing. In small doses, however, physostigmine is used to treat
myasthenia gravis, a condition of muscular weakness in which muscle
receptors are less than normally responsive to ACh. Physostigmine’s
action is short lived, lasting only a few minutes or at most a half hour.
In myasthenia gravis, muscle receptors lose their sensitivity to motor
neuron messages, as illustrated in Section 4-4 .
Organophosphate compounds bind irreversibly to AChE and
consequently allow a toxic buildup of ACh in the synaptic space. Many
insecticides and chemical weapons are organo-phosphates. Insects use
glutamate as a neurotransmitter at the nerve–muscle junction, but
elsewhere in their nervous system, they have nicotinic receptors. Thus,
organophosphates poison insects by acting centrally, but they poison
chordates by acting peripherally as well. The Chemical Weapons
Convention of 1993 banned one potent organophosphate agent, the lethal
nerve gas Sarin. That international ban did not restrain the governments
of Iraq, in 1999, and Syria, in 2013, from using Sarin against their own
citizens.
The Basics, Section 1-3 , charts nervous system evolution in the
animal kingdom.
Does a drug or toxin that affects neuromuscular synapses also affect
ACh synapses in the brain? That depends on whether the substance can
cross the blood–brain barrier. Physostigmine and nicotine readily pass the
barrier; curare cannot. Nicotine is the psychoactive ingredient in cigarette
smoke, and its actions on the brain account for its addictive properties
(see Section 6-4 ). Physostigminelike drugs reportedly have some
beneficial effects for memory disorders.

Tolerance
Tolerance is a decreased response to a drug with repeated exposure.
Harris Isbell and coworkers (1955) conducted an experiment that, while
questionable by today’s ethical standards, did suggest how tolerance
comes about. The researchers gave volunteers in a prison enough alcohol
daily in a 13-week period to keep them in a constant state of intoxication.
Yet they found that the participants did not remain drunk for 3 months
straight.
In tolerance, as in habituation, learning takes place when the
response to a stimulus weakens with repeated presentations (see
Experiment 5-2 ).
 tolerance Decrease in response to a drug with the passage of time.
When the experiment began, the participants showed rapidly rising
blood alcohol levels and behavioral signs of intoxication, as shown in the
Results section of Experiment 6-1 , on page 178 . Between the twelfth
and twentieth days of alcohol consumption, however, blood alcohol and
the signs of intoxication fell, even though the participants maintained
their alcohol intake. Thereafter, blood alcohol levels and signs of
intoxication fluctuated; one did not always correspond to the other. A
relatively high blood alcohol level was sometimes associated with a low
outward appearance of intoxication. Why?
The three results were the products of three kinds of tolerance, each
much more likely to develop with repeated drug use:
1. In metabolic tolerance, the number of enzymes needed to break down
alcohol in the liver, blood, and brain increases. As a result, any alcohol
consumed is metabolized more quickly, so blood alcohol levels fall.
2. In cellular tolerance, brain cell activities adjust to minimize the effects
of alcohol in the blood. Cellular tolerance can help explain why the
behavioral signs of intoxication may be so low despite a relatively high
blood alcohol level.
3. Learned tolerance explains a drop in outward signs of intoxication. As
people learn to cope with the demands of living under the influence of
alcohol, they may no longer appear intoxicated.
Does it surprise you that learning plays a role in alcohol tolerance? It
has been confirmed in many studies, including a description of the effect
first reported by John Wenger and his coworkers (1981). They trained rats
to prevent electric foot shocks as they walked on a narrow conveyor belt
sliding over an electrified grid. One group of rats received alcohol after
training in walking the belt; another group received alcohol before
training. A third group received training only, and a fourth group received
alcohol only.
After several days’ exposure to their respective conditions, all groups
received alcohol before a walking test. The rats that had received alcohol
before training performed well, whereas those that had received training
and alcohol separately performed just as poorly as those that had never
had alcohol or those that had not been trained. Despite alcohol
intoxication, then, animals can acquire the motor skills needed to balance
on a narrow belt. With motor experience, they can learn to compensate for
being intoxicated.
 EXPERIMENT 6-1

Question: Will the consumption of alcohol produce

tolerance?
Procedure

Results
 Conclusion: Because of tolerance, as the study progressed, much more
alcohol was required to obtain the same level of intoxication that was
produced at the beginning.
Information from H. Isbell, H. F. Fraser, A. Winkler, R. E. Belleville, and A. J.
Eisenman (1955). An experimental study of the etiology of “rum fits” and delirium
tremens. Quarterly Journal of Studies on Alcohol, 16, pp. 1–21.

Sensitization
Drug tolerance is much more likely to develop with repeated use than
with periodic use, but tolerance does not always follow repeated
exposure to a drug. Tolerance resembles habituation in that the response
to the drug weakens with repeated presentations. The drug user may have
the opposite reaction, sensitization—increased responsiveness to
successive equal doses. Whereas tolerance generally develops with
repeated drug use, sensitization is much more likely to develop with
periodic use.
To demonstrate drug sensitization, Terry Robinson and Jill Becker
(1986) isolated rats in observation boxes and recorded their reactions to
an injection of amphetamine, which stimulates dopamine receptors.
Every 3 or 4 days, the investigators injected the rats and found their
motor activities—sniffing, rearing, and walking—more vigorous with
each administration of the same drug dose, as graphed in Results 1 of
Experiment 6-2 .
The increased motor activity on successive tests was not due to the
animals becoming comfortable with the test situation. Control animals
that received no drug failed to display a similar escalation.
Administering the drug to rats in their home cages did not affect activity
in subsequent tests, either. Moreover, the sensitization to amphetamine
was enduring. Even when two injections were separated by months, the
animals still showed an escalation of motor behavior. Even a single
exposure to amphetamine produced sensitization.
Experiment 5-3 describes sensitization at the level of neurons and
synapses. Section 14-4 relates sensitization to neuroplasticity and
learned addictions.
 EXPERIMENT 6-2

Question: Does the injection of a drug always produce the

same behavior?
Procedure 1

In the Robinson and Becker study, animals were given periodic

injections of the same dose of amphetamine. Then the
researchers measured the number of times each rat reared in
its cage.
Results 1
Conclusion 1: Sensitization indicated by increased rearing, develops
with periodic repeated injections.
Procedure 2

In the Whishaw study, animals were given different numbers of

swims after being injected with Flupentixol. Then the
researchers measured their speed to escape to a platform in a
swimming pool.
Results 2
 Conclusion 2: Sensitization depends on the occurrence of a behavior:
the number of swims increases the time that it takes the rat to reach the
platform.
Left: Information from T. E. Robinson and J. B. Becker (1986). Enduring changes in
brain and behavior produced by chronic amphetamine administration: A review and
evaluation of animal models of amphetamine psychosis. Brain Research Reviews,
397, pp. 157–198. Right: Information from I. Q. Whishaw, G. Mittleman, and J. L.
Evenden (1989). Training-dependent decay in performance produced by the
narcoleptic cist(Z)-flupentixol on spatial navigation by rats in a swimming pool.
Pharmacology, Biochemistry, and Behavior, 32, pp. 211–220.

Sensitization is not always characterized by an increase in an elicited

behavior but may also manifest as a progressive decrease in behavior. Ian
Whishaw and his colleagues (1989) administered flupentixol, a drug that
blocks dopamine receptors, to rats that had been well trained in a
swimming task. As illustrated in Results 2 of Experiment 6-2 , the rats
displayed such a marked trial-dependent slowing in swimming speed
when escaping from the water that they completely stopped swimming
over successive trials. The trial-dependent decrease in swimming was
similar whether the trials were massed on the same day or spaced over
days or weeks.
The neural basis of sensitization lies in part in changes at the synapse.
Studies on the dopamine synapse after sensitization to amphetamine
show more dopamine released from the presynaptic terminal in
sensitized animals. Sensitization can also be associated with changes in
receptor numbers on the postsynaptic membrane, in the rate of
transmitter metabolism in the synaptic space, in transmitter reuptake by
the presynaptic membrane, and in the number and size of synapses.
Another basis of sensitization is learned. Animals show a change in
learned responses to environmental cues as sensitization progresses.
Consequently, sensitization is difficult to achieve in an animal tested in
its home cage. In the Whishaw group’s experiment, administering
flupentixol to rats left in their home environment did not influence their
performance in subsequent swim tests.
Sabina Fraioli and her coworkers (1999) gave amphetamine to two
groups of rats and recorded the behavioral responses to successive
injections. One group of rats lived in the test apparatus, so for that group,
home was the test box. The other group was taken out of their home cage
and placed in the test box for each day’s experimentation. The home
group showed no sensitization to amphetamine, whereas the out group
displayed robust sensitization.
At least part of the explanation of the home–out effect is that the
animals are accustomed to engaging in a certain behavioral repertoire in
their home environment, so it is difficult to get them to change their
response to home cues even when influenced by a drug. When subjects
are away from home, they receive novel out cues, which favor
conditioning of new responses.
Sensitization is relevant to understanding some
psychopharmacological effects of drugs:
1. Many drug therapies, including those for the psychiatric disorder
schizophrenia, must be taken for several weeks before they produce
beneficial effects. Possibly sensitization underlies the development of
these beneficial effects.
2. Sensitization is related to drug dependence. Before a person becomes
dependent on or addicted to a drug, he or she must be sensitized by
numerous experiences with the drug away from the home
environment.
3. Life experiences, especially stressful ones, can produce effects
resembling sensitization that prime the nervous system for addiction
(Roberts et al., 2015).
Focus 8-5 relates the possible origin of schizophrenia and its
progress.
 6-1 REVIEW
Principles of Psychopharmacology
Before you continue, check your understanding.
1 . ___________, substances that produce changes in behavior by acting
on the nervous system, are one subject of ___________, the study of
how drugs affect the nervous system and behavior.
2 . Perhaps the most important obstacle on a psychoactive drug’s journey
between its entry into the body and its action at a target is the
___________, which generally allows only substances needed for
nourishment to pass from the capillaries into the ___________.
3 . Most drugs that have psychoactive effects influence chemical
reactions at neuronal ___________. Drugs that influence
communication between neurons do so by acting either as
___________ (increasing the effectiveness of neurotransmission) or as
___________ (decreasing the effectiveness of neurotransmission).
4 . Behavior may change with the repeated use of a psychoactive drug.
These changes include ___________ and ___________, in which the
effect of the drug decreases or increases, respectively, with repeated
use.
5 . The body eliminates drugs through ___________, ___________,
___________, ___________, and ___________.
6 . Describe briefly how tolerance and sensitization might affect
someone who uses cognitive enhancers occasionally (a) at home or (b)
at work.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 6-2 Grouping Psychoactive Drugs
Did you know that most psychoactive drugs and their effects were
discovered by accident? Scientists and pharmaceutical companies have
experimented ever since, to explain drug action, to synthesize alternative
forms for therapeutic treatments, and to modify drugs to reduce side
effects. But the process is complex. Drugs with similar chemical
structure can have different effects, and drugs with different structure can
have similar effects. And a single drug usually acts on many
neurochemical systems and has many effects.
A full appreciation of any drug’s action requires a multifaceted
description, such as can be found in compendiums of drug action.
Unambiguously grouping psychoactive drugs is virtually impossible,
because most drugs influence many behaviors. Behavioral descriptions
undergo constant review, as illustrated by continuing revisions of the
Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
Published by the American Psychiatric Association and now in its fifth
edition, the DSM offers a classification system for diagnosing
neurological and behavioral disorders.
Table 6-1 groups psychoactive drugs based on their most pronounced
behavioral or psychoactive effects (Advokat et al., 2014). Each of the
five groups may contain a few to thousands of chemicals in its
subcategories. In the following sections we highlight drug actions, both
on neurochemical systems in the brain and on synaptic function.
Most psychoactive drugs have three names: chemical, generic, and
branded. The chemical name describes a drug’s structure; the generic
name is nonproprietary and is spelled lowercase; and the proprietary, or
brand, name, given by the pharmaceutical company that sells it, is
capitalized. Some psychoactive drugs also sport street names or are
known as club drugs.
TABLE 6-1 Grouping Psychoactive Drugs
Group 1: Antianxiety agents and sedative-hypnotics

Benzodiazepines: diazepam (Valium), alprazolam (Xanax), clonazepam (Klonopin)

Barbiturates (anesthetic agents); alcohol

Other anesthetics: gamma-hydroxybutyrate (GHB), ketamine (Special K),

phencyclidine (PCP, angel dust)
Group II: Antipsychotic agents

First generation: phenothiazines: chlorpromazine (Thorazine); butyrophenones:

haloperidol (Haldol)

Second generation: clozapine (Clozaril), aripiprazole (Abilify, Aripiprex)

Group III: Antidepressants and mood stabilizers

Antidepressants
MAO inhibitors
Tricyclic antidepressants: imipramine (Tofranil)
SSRIs (atypical antidepressants): fluoxetine (Prozac); sertraline
(Zoloft); paroxetine (Paxil, Seroxat)

Mood stabilizers
Lithium, sodium valproate, carbamazepine (Tegretol)

Group IV: Opioid analgesics

Opium derivatives: morphine, codeine, heroin

Endogenous opioid neuropeptides: enkephalins, dynorphins, endorphins

Group V: Psychotropics

Behavioral stimulants: amphetamine, cocaine

Psychedelic and hallucinogenic stimulants (listed by neurotransmitter)

Acetylcholine psychedelics: atropine, nicotine
Anandamide psychedelics: tetrahydrocannabinol (THC)
Glutamate psychedelics: phencyclidine (PCP, angel dust), ketamine (Special K)
Norepinephrine psychedelics: mescaline
Serotonin psychedelics: Lysergic acid diethylamide (LSD), psilocybin, MDMA
(Ecstasy)

General stimulants: caffeine

Group I: Antianxiety Agents and Sedative-

Hypnotics
At low doses, antianxiety drugs and sedative-hypnotics reduce anxiety;
at medium doses, they sedate; at high doses, they anesthetize or induce
coma. At very high doses, they can kill ( Figure 6-6 ). Even so,
antianxiety drugs are safer at high doses than sedative-hypnotics are.
Indeed, the prescribing of sedative-hypnotics for all purposes is
decreasing.
Many psychoactive drugs have sedative-hypnotic and antianxiety
actions. They include phencyclidine (PCP, angel dust) and two drugs—
gamma-hydroxybutyric acid (GHB) and ketamine (Special K)—that
gained notoriety as date rape drugs. Both are soluble in alcohol, act
quickly, and, like other sedative-hypnotics, impair memory of recent
events. Because they can be dissolved in a drink, partygoers and clubbers
should never accept drinks from anyone, drink from punch bowls, or
leave drinks unattended.

FIGURE 6-6 Behavioral Continuum of Sedation Increasing

doses of sedative-hypnotic and antianxiety drugs affect behavior: low
doses reduce anxiety and very high doses result in death.

Drug Action in the Brain

The best-known antianxiety agents, or minor tranquilizers, are the
benzodiazepines. One, diazepam, is marketed as the widely prescribed
brand-name drug Valium. Others are alprazolam (Xanax) and
clonazepam (Klonopin). Benzodiazepines are often used by people who
are having trouble coping with a major life stress, such as a traumatic
accident or a death in the family. They aid sleep and also are used as
presurgical relaxation agents.
 antianxiety agent Drug that reduces anxiety, including minor
tranquilizers such as benzodiazepines and sedative-hypnotic agents.
Sedative-hypnotics include alcohol and barbiturates. Both induce
sleep, anesthesia, and coma at doses only slightly higher than those that
sedate. Alcohol is well known to most people and widely consumed.
While sometimes prescribed as a sleeping medication, today barbiturates
are mainly used to induce anesthesia before surgery.
barbiturate Drug that produces sedation and sleep.
A characteristic feature of sedative-hypnotics is that the user who
takes repeated doses develops a tolerance for them. A larger dose is then
required to maintain the drug’s initial effect. Cross-tolerance results
when the tolerance for one drug is carried over to a different member of
the drug group.
cross-tolerance Reduction of response to a novel drug because of
tolerance to a chemically related drug.
Drug Action at the Synapse
Cross-tolerance suggests that antianxiety and sedative-hypnotic drugs act
on the nervous system in similar ways. One target common to both
alcohol and barbiturate drugs is a receptor for gamma-aminobutyric acid
(GABA), the inhibitory neurotransmitter that is widely distributed in the
CNS. The GABAA receptor, illustrated in Figure 6-7 , contains a
chloride ion channel.
GABA is an amino acid. Figure 5-12 shows its chemical structure.
Excitation of the GABAA receptor produces an influx of Cl– through
its pore. An influx of Cl– increases the concentration of negative charges
inside the cell membrane, hyper-polarizing it and making it less likely to
propagate an action potential. GABA therefore has its inhibitory effect
by decreasing a neuron’s firing rate. Widespread reduction of neuronal
firing underlies the behavioral effects of drugs that affect the GABAA
synapse.
The GABAA receptor illustrated in Figure 6-7 has different binding
sites for GABA, barbiturates, and benzodiazepines. Activation of each
site promotes an influx of Cl– , but in different ways. Because the effects
of actions at these three sites summate, sedative-hypnotics, including
alcohol and antianxiety drugs, should not be consumed together.
Combined doses of drugs reportedly contribute to as many deaths as
occur annually from automobile accidents in the United States. Such was
the case in 2012, when singer Whitney Houston drowned.
The GABAA receptor also has binding sites that block the ion pore
when active, reducing the flow of Cl– and increasing the target neuron’s
excitability. Picrotoxin, a compound that blocks the pore, produces
epileptic discharges in postsynaptic neurons. Administering GABAA
agonists can block picrotoxin’s action. Sedative-hypnotic and antianxiety
drugs are thus useful in treating epileptic discharges.
Drugs that act on GABA receptors may affect brain development,
because GABA is one of the substances that regulate brain development.
Clinical Focus 6-2 , Fetal Alcohol Spectrum Disorder, explores alcohol’s
potentially devastating effects on developing fetuses.
FIGURE 6-7 Drug Effects at the GABA A Receptor Sedative-hypnotics
act at the barbiturate site (left), and antianxiety agents act at the benzodiazepine site
(center). Taken together (right), these two types of drugs can be lethal.
CLINICAL FOCUS 6-2

Fetal Alcohol Spectrum Disorder

The term fetal alcohol syndrome (FAS) was coined in 1973 to
describe a pattern of physical malformation and intellectual disability
observed in some children born to alcoholic mothers. It is now called
fetal alcohol spectrum disorder (FASD) to acknowledge the range
of its effects. Children with FASD may have abnormal facial
features, such as unusually wide spacing between the eyes. Their
brains display a range of abnormalities, from small size with
abnormal gyri to abnormal clusters of cells and misaligned cells in
the cortex.
fetal alcohol spectrum disorder (FASD) Range of physical
and intellectual impairments observed in some children born to
alcoholic parents.
Related to these brain abnormalities are certain behavioral
symptoms that children with FASD tend to have in common. They
display varying degrees of learning disabilities and low intelligence
test scores as well as hyperactivity and other social problems.
Individuals with FASD are 19 times as likely to be incarcerated as
those without it (Popova et al., 2011).
The offspring of approximately 6 percent of alcoholic mothers
have pronounced FASD. In major cities, its incidence is about 1 in
700 births and is especially high among Native Americans on
reservations in Canada, some other minority groups, and single
mothers (Mead & Sarkar, 2014).
A major problem is that women who are most at risk for bearing
FASD babies are poor and not well educated, their alcohol
consumption problems predate pregnancy, and they have little access
to prenatal care. It is often difficult to inform these women about the
dangers that alcohol poses to a fetus and to encourage them to
abstain from drinking before and while they are pregnant.
Alcohol-induced abnormalities can vary from hardly noticeable
physical and psychological effects to full-blown FASD. The severity
of effects is related to when, how much, and how frequently alcohol
is consumed over the course of pregnancy. The effects are worse if
alcohol is consumed in the first trimester, a time when many women
do not yet realize that they are pregnant.
Severe FASD is also more likely to coincide with binge drinking,
which produces high blood alcohol levels. Other factors related to a
severe outcome are poor nutritional health of the mother and the
mother’s use of other drugs, including nicotine. In addition, alcohol
use by mothers and fathers before conception can change the
methylation status of some genes that contribute to disabilities found
on the spectrum (Lee et al., 2015).
A major question raised by FASD is how much alcohol is too
much to drink during pregnancy. To be completely safe, it is best not
to drink at all in the months preceding as well as during pregnancy.
This conclusion is supported by findings that as little as a single
drink of alcohol per day during pregnancy can lead to a decrease in
children’s intelligence test scores.

Courtesy of Sterling K. Clarren, M.D., Professor of Pediatrics, University of British

Columbi Faculty of Medicine.
 (Top) Characteristic facial features that indicate FASD. Effects
are not merely physical; many children endure severe
intellectual disabilities. (Bottom) The convolutions characteristic
of the brain of a healthy child at age 6 weeks (left) are grossly
underdeveloped in the brain of a child with FASD (right).

Group II: Antipsychotic Agents

The term psychosis is applied to behavioral disorders such as
schizophrenia, which is characterized by hallucinations (false sensory
perceptions) and delusions (false beliefs), among a host of symptoms.
The use of antipsychotic drugs has improved the functioning of
schizophrenia patients. Since 1955, when psychoactive drugs were
introduced into widespread therapeutic use, resident patient populations
in state and municipal mental hospitals in the United States have
decreased dramatically.
The success of antipsychotic agents is an important therapeutic
achievement, because the incidence of schizophrenia is high—about 1 in
every 100 people. Although antipsychotic agents make mental disorders
manageable, they do not constitute cures. In fact, according to the
National Institute on Disability and Rehabilitation Research, although
the number of people in mental institutions remains relatively low, as
many as 75% of the homeless and 50% of incarcerated people have
mental health issues. According to Human Rights Watch, in 2015, 10
times as many mentally ill people were incarcerated as resided in mental
institutions.
 Antipsychotic agents have been widely used since the mid-1950s,
beginning with the development of what are now called first-generation
antipsychotics (FGAs). They include the drug classes phenothiazines
(e.g., chlorpromazine, Thorazine) and butyrophenones (e.g., haloperidol,
Haldol). FGAs act mainly by blocking the dopamine D2 receptor.
Beginning in the 1980s, newer drugs such as clozapine (Clozaril) and
several other compounds emerged as the second-generation
antipsychotics (SGAs). SGAs weakly block dopamine D2 receptors but
also block serotonin 5-HT2 receptors. Antipsychotic drugs now in
development will likely form a third generation.
Antipsychotic agents’ therapeutic actions are not understood fully,
and these drugs can produce many unwanted side effects. Joint
experimentation by patients and physicians with different drugs and
doses is common (Pouget et al., 2014). The dopamine hypothesis of
schizophrenia holds that some forms of the disease may be related to
excessive dopamine activity—especially in the frontal lobes. Other
support for the dopamine hypothesis comes from the schizophrenialike
symptoms of chronic users of amphetamine, a stimulant.
dopamine hypothesis of schizophrenia Idea that excess dopamine
activity causes symptoms of schizophrenia.
As Figure 6-8 shows, amphetamine is a dopamine agonist. It fosters
dopamine release from the presynaptic membrane of D2 synapses and
blocks dopamine reuptake from the synaptic cleft. The logic is that if
amphetamine causes schizophrenialike symptoms by increasing
dopamine activity, perhaps naturally occurring schizophrenia is related to
excessive dopamine action too. Both FGAs and SGAs block the D2
receptor, which immediately reduces motor activity and alleviates the
excessive agitation of some schizophrenia patients. Because
schizophrenia involves more than just D2 receptors, changes in dopa-
mine synapses do not completely explain the disorder or the effects of
antipsychotic agents.
 FIGURE 6-8 Drug Effects at D 2 Receptors The antipsychotic
agent chlorpromazine can lessen schizophrenia symptoms, and
amphetamine or cocaine abuse can produce them. This suggests that
schizophrenia is related to excessive activity at the D2 receptor.

Group III: Antidepressants and Mood

Stabilizers
Major depression —a mood disorder characterized by prolonged
feelings of worthlessness and guilt, disruption of normal eating habits,
sleep disturbances, a general slowing of behavior, and frequent thoughts
of suicide—is rather common. At any given time, about 6 percent of the
U.S. adult population has major depression, and in the course of a
lifetime, 30 percent may have at least one episode that lasts for months
or longer. Depression is diagnosed in twice as many women as men.
 Inadequate nutrition, stress from difficult life conditions, acute
changes in neuronal function, and damage to brain neurons are among
the factors implicated in depression. These factors may be related:
nutritional deficiencies may increase vulnerability to stress; stress may
change neuronal function; and if unrelieved, altered neuronal function
may lead to neuron damage. Section 6-5 offers more information on
stress.
Among the nutrient deficiencies that may be related to depression
(Smith et al., 2010) are folic acid and other B vitamins and omega-3 fatty
acids, a rich source of vitamin D obtained from fish. Our skin
synthesizes vitamin D on exposure to sunlight, but our body cannot store
it. Vitamin D deficiency is reportedly widespread in people living in
northern climates because they don’t eat enough fish and they lack
exposure to sunlight in winter. Although vitamin D deficiency is
associated with depressive symptoms, little is known about the relations
among long-term deficiencies in nutrients, depression and associated
brain changes, and the effectiveness of dietary supplements (Kerr et al.,
2015).
Not surprisingly, alongside improved nutrition, a number of
pharmacological approaches to depression are available. They include
normalizing stress hormones, modifying neuronal responses, and
stimulating neuronal repair.
Section 12-4 explores the neuroanatomy of emotional disorders such
as depression and Section 16-4 its neurobiology and treatments for
it.
Antidepressant Medications
Three types of drugs have antidepressant effects: the monoamine
oxidase (MAO) inhibitors ; the tricyclic antidepressants, so called
because of their three-ring chemical structure; and the second-
generation antidepressants, sometimes called atypical antidepressants
(see Table 6-1 ). Second-generation antidepressants lack a three-ring
structure but do share some similarities to the tricyclics in their actions.
monoamine oxidase (mAO) inhibitor Antidepressant drug that
blocks the enzyme monoamine oxidase from degrading such
neurotransmitters as DA, NE, and 5-HT.
tricyclic antidepressant First-generation antidepresasant; its
chemical structure, characterized by three rings, blocks 5-HT
 reuptake transporter proteins.
second-generation antidepressant Drug that acts similarly to
tricyclics (first-generation antidepressants) but more selectively on
5-HT reuptake transporter proteins; also called atypical
antidepressant.
Antidepressants are thought to act by improving chemical
neurotransmission at serotonin, noradrenaline (norepinephrine),
histamine, and acetylcholine synapses, and perhaps at dopamine
synapses as well. Figure 6-9 shows the actions of MAO inhibitors and
second-generation antidepressants at a 5-HT synapse, on which most
research is focused. MAO inhibitors and the tricyclic and second-
generation antidepressants all act as agonists but have different
mechanisms for increasing serotonin availability.
MAO inhibitors provide for more serotonin release with each action
potential by inhibiting monoamine oxidase, an enzyme that breaks down
serotonin in the axon terminal. In contrast, the tricyclics and second-
generation antidepressants block the reuptake transporter that takes
serotonin back into the axon terminal. The second-generation
antidepressants are thought to be especially selective in blocking
serotonin reuptake; consequently, some are also called selective
serotonin reuptake inhibitors (SSRIs). Because the transporter is
blocked, serotonin remains in the synaptic cleft, prolonging its action on
post-synaptic receptors.
Reuptake is part of transmitter deactivation, the last of the four steps
of neurotransmission (see Figure 5-4 ).
selective serotonin reuptake inhibitor (ssri) Tricyclic
antidepressant drug that blocks 5-HT reuptake into the presynaptic
terminal.
Although these drugs begin to affect synapses very quickly, their
antidepressant actions take weeks to develop. One explanation is that
antidepressants, especially SSRIs, stimulate second messengers in
neurons to activate the repair of neurons damaged by stress. Of interest
in this respect, one SSRI, fluoxetine (Prozac), increases the production of
new neurons in the hippocampus, a limbic structure in the temporal
lobes. As detailed in Section 6-5 , the hippocampus is vulnerable to
stress-induced damage, and its restoration by fluoxetine is proposed to
underlie one of the drug’s antidepressant effects (Hill et al., 2015).
 Most people recover from depression within a year of its onset. If left
untreated, however, depression’s incidence of suicide is high, as
described in Clinical Focus 6-3 , Major Depression, on page 186 . Of all
psychological disorders, major depression is one of the most treatable,
and cognitive and intrapersonal therapies are as effective as drug
therapies (Comer, 2011).
Even so, about 20 percent of patients with depression fail to respond
to antidepressant drugs. Accordingly, depression likely can have many
other causes, including dysfunction in other transmitter systems and even
brain damage, including frontal lobe damage. Some people have
difficulty tolerating the side effects of antidepressants—increased
anxiety, sexual dysfunction, sedation, dry mouth, blurred vision, and
memory impairment among them.

FIGURE 6-9 Drug Effects at 5-HT Receptors Different

antidepressant drugs act on the serotonin synapse in different ways to
increase its availability.
CLINICAL FOCUS 6-3

Major Depression
P. H. was a 53-year-old high school teacher who, although popular
with his students, was deriving less and less satisfaction from his
work. His marriage was foundering because he was growing apathetic
and no longer wanted to socialize or go on vacations. He was having
difficulty getting up in the morning and arriving at school on time.
P. H. eventually consulted a physician, complaining of severe chest
pains, which he feared signaled an impending heart attack. He
informed his doctor that a heart attack would be a welcome relief
because it would end his problems. The physician concluded that P.
H. had depression and referred him to a psychiatrist.
Since the 1950s, depression has been treated with antidepressant
drugs, a variety of cognitive-behavioral therapies (CBTs), and
electro-convulsive therapy (ECT), in which electrical current is
passed briefly through one hemisphere of the brain. Of the drug
treatments available, tricyclic antidepressants and SSRIs are favored.
The risk of suicide and self-injurious behaviors is high in major
depression, especially among depressive adolescents who are resistant
to treatment with SSRIs (Asarnow et al., 2011). Even for patients who
do respond positively to SSRI treatment, the benefits may not occur
for weeks.
The glutamate antagonist ketamine, when given in smaller than
anesthetic doses, can produce rapid beneficial effects that last for
weeks, even in patients who are resistant to SSRI medication
(Reinstatler and Youssef, 2015). Ketamine is thus proposed to be
useful as an acute treatment for patients with major depression who
are at risk for suicide and even for patients with bipolar depression
who are at risk for suicide.
Prompted by complaints from family members that antidepressant
drug treatments have caused suicide, especially in children, the U.S.
Food and Drug Administration has advised physicians to monitor the
side effects of SSRIs, including fluoxetine (Prozac), sertraline
(Zoloft), and paroxetine (Paxil, Seroxat). Findings from several
studies show no difference in the suicide rate between children and
 adolescents who receive SSRIs and a placebo, and the incidence of
suicide after prescriptions were curtailed subsequent to the FDA
warning actually increased (Isacsson and Rich, 2014).
David Braun/Masterfile

Depressed? Virtually everyone who exercises will tell you that it

can work wonders to brighten your mood.

Mood Stabilizers
Bipolar disorder, once referred to as manic-depressive psychosis, is
characterized by periods of depression alternating with normal periods
and periods of intense excitation, or mania. According to the National
Institute of Mental Health, bipolar disorder may affect as much as 2.6%
of the adult population of the United States.
bipolar disorder Mood disorder characterized by periods of
depression alternating with normal periods and periods of intense
excitation, or mania.
The difficulty in treating bipolar disorder with drugs relates to the
difficulty in understanding how a disease produces symptoms that appear
to be opposites: mania and depression. Consequently, bipolar disorder
often is treated with numerous drugs, each directed toward a different
symptom. Mood stabilizers, which include the salt lithium, mute the
intensity of one pole of the disorder, thus making the other less likely to
occur. Lithium does not directly affect mood and so may act by
stimulating mechanisms of neuronal repair, such as the production of
neuron growth factors.
 mood stabilizer Drug for treating bipolar disorder; mutes the
intensity of one pole of the disorder, thus making the other pole less
likely to recur.
A variety of drugs for epilepsy (carbamazepine, valproate) have
positive effects; perhaps they mute the excitability of neurons during the
mania phase. And antipsychotic drugs that block D2 receptors effectively
control the hallucinations and delusions associated with mania. It is
important to remember, though, that all these treatments have side effects:
enhancing beneficial effects while minimizing side effects is a major
focus of new drug development (Grande and Vieta, 2015).

Group IV: Opioid Analgesics

An opioid is any compound that binds to a group of morphine-sensitive
brain receptors. The term narcotic analgesic was first used to describe
these drugs because opioid analgesics have sleep-inducing (narcotic) and
pain-relieving (analgesic) properties. There are two natural sources of
opioids.
opioid analgesic Drug such as morphine, with sleep-inducing
(narcotic) and pain-relieving (analgesic) properties; originally called
narcotic analgesic.
One source is opium, an extract of the seeds of the opium poppy,
Papaver somniferum, shown at left in Figure 6-10 . Opium has been used
for thousands of years to produce euphoria, analgesia, sleep, and relief
from diarrhea and coughing. In 1805, German chemist Friedrich Sertürner
synthesized two chemicals from opium: codeine and morphine. Codeine
is often an ingredient in prescription cough medicine and pain relievers.
The liver converts it to morphine. Morphine, shown at center in Figure 6-
10 and named for Morpheus, the Greek god of dreams, is a powerful pain
reliever. Despite decades of research, no other drug has been found that
exceeds morphine’s effectiveness as an analgesic.
The second natural source of opioids is the brain. In the 1970s, several
groups of scientists injected radioactive opioids into the brain of
experimental animals and identified receptors there to which opioids bind.
At roughly the same time, other groups of investigators identified several
brain peptides as the neurotransmitters that naturally affect these
receptors. The peptides in the body that have opioidlike effects are
collectively called endorphins (endogenous morphines).
 endorphin Opioid peptide that acts as a neurotransmitter and may be
associated with feelings of pain or pleasure; mimicked by opioid
drugs such as morphine, heroin, opium, and codeine.
Peptides, including the endorphins illustrated in Figure 5-13 , are
molecular amino acid chains connected by peptide bonds. Table 5-2
lists the families of peptide neurotransmitters.
Research has identified four classes of opioid peptides: endorphins,
enkephalins, dynorphins, and endomorphins. The three receptors on
which each endorphin is relatively specific are, respectively, mu, kappa,
and delta. All endorphins and their receptors occur in many CNS regions
as well as in other areas of the body, including the enteric nervous system.
Morphine most closely mimics the endomorphins and binds most
selectively to the mu receptors.
In addition to the natural opioids, synthetic opioids such as heroin
affect mu receptors. Heroin, shown at right in Figure 6-10 , is synthesized
from morphine. It is more fat-soluble than morphine and penetrates the
blood–brain barrier more quickly, allowing it to produce very rapid but
shorter-acting pain relief. Heroin is a legal drug in some countries but is
illegal in others, including the United States. Notwithstanding, in some
parts of the country, heroin use is on the rise.
Among the synthetic opioids prescribed for clinical use in pain
management are hydro-morphone, levorphanol, oxymorphone,
methadone, meperidine, oxycodone, and fentanyl. All opioids are potently
addictive, and abuse of prescription opioids is growing more common.
Opioids are also illegally modified, manufactured, and distributed. People
who use opioids for relief of chronic pain and take them when they are
not in pain can become addicted; some obtain multiple prescriptions and
sell them illicitly.
Many drugs, including nalorphine (Lethidrone, Nalline) and naloxone
(Narcan, Nalone), act as antagonists at opioid receptors. These drugs are
competitive inhibitors : they compete with opioids for neuronal
receptors. Because they can enter the brain quickly, they rapidly block the
actions of morphine and so are essential aids in treating morphine
overdoses. Many people addicted to opioids carry a competitive inhibitor
as a treatment for overdosing. Because they can also be long-acting,
competitive inhibitors can be used to treat opioid addiction after the
addicted person has recovered from withdrawal symptoms.
competitive inhibitor Drug, such as nalorphine and naloxone, that
acts quickly to block opioid action by competing with the opioid for
binding sites; used to treat opioid addiction.

Eye Ubiquitous/Corbis
 Science Source
Bonnie Kamin/PhotoEdit
 FIGURE 6-10 Potent Poppy Opium is obtained from the seeds of the
opium poppy (left). Morphine (center) is extracted from opium, and heroin
(right) is in turn synthesized from morphine.

Researchers have extensively studied whether opioid peptides

produced in the brain can be used as drugs to relieve pain without
morphine’s addictive effects. The answer so far is mixed, and one of the
objectives of pain research, producing an analgesic that does not produce
addiction, may be difficult to realize.
Feeling and treating pain are topics in Section 11-4 . Focus 12-1
reports that emotional pain activates the same neural areas as
physical pain.
Opioid drugs, such as heroin, are addictive and are abused worldwide.
The hypodermic needle was developed in 1853 and used in the American
Civil War for the intravenous injection of morphine for pain treatment.
This practice is said to have produced 400,000 cases of the “Soldier’s
Disease,” morphine addiction. Morphine has many routes of
administration, but intravenous injection is preferred because it produces
a euphoria described as a rush. Morphine does not readily cross the
blood–brain barrier, but heroin does and is even more likely to produce a
rush.
If opioids are used repeatedly, they produce tolerance such that within
a few weeks the effective dose may increase tenfold. Thereafter, many
desired effects with respect to both pain and addiction no longer occur.
An addicted person cannot simply stop using the drug: a severe sickness
called withdrawal results if drug use is abruptly stopped.
Because morphine results in both tolerance and sensitization, the
morphine user is always flirting with the possibility of overdosing. The
unreliability of appropriate information on the purity of street forms of
morphine contributes to the risk. A lack of sterile needles for injections
also leaves the morphine user at risk for many other diseases, including
AIDS (acquired immunodeficiency syndrome) and hepatitis.
Opioid ingestion produces wide-ranging physiological changes in
addition to pain relief, including relaxation and sleep, euphoria, and
constipation. Other effects include respiratory depression, decreased
blood pressure, pupil constriction, hypothermia, drying of secretions (e.g.,
dry mouth), reduced sex drive, and flushed, warm skin. Withdrawal is
characterized by symptoms that are physiologically and behaviorally
opposite those produced by the drug. A major part of the addiction
syndrome, then, is the drive to prevent withdrawal symptoms.

Group V: Psychotropics
Psychotropic drugs are stimulants that mainly affect mental activity,
motor activity, arousal, perception, and mood. Behavioral stimulants
affect motor activity and mood. Psychedelic and hallucinogenic
stimulants affect perception and produce hallucinations. General
stimulants mainly affect mood.
Behavioral Stimulants
Behavioral stimulants increase motor behavior as well as elevating mood
and alertness. Rapid administration of behavioral stimulants is most likely
to be associated with addiction. As shown in Figure 6-1 , the quicker a
drug reaches its target—in this case, the brain—the quicker it takes effect.
Further, with each obstacle eliminated en route to the brain, drug dosage
can be reduced by a factor of 10, making it cheaper per dose. Two
behavioral stimulants are amphetamine and cocaine.
 Amphetamine is a synthetic compound. It was discovered in attempts
to synthesize the CNS neurotransmitter epinephrine, which also acts as a
hormone to mobilize the body for fight or flight in times of stress (see
Figure 6-20 ). Both amphetamine and cocaine are dopamine agonists that
act first by blocking the dopamine reuptake transporter. Interfering with
the reuptake mechanism leaves more dopamine available in the synaptic
cleft. Amphetamine also stimulates dopamine release from presynaptic
membranes. Both mechanisms increase the amount of dopamine available
in synapses to stimulate dopa-mine receptors. As noted in Focus 6-1,
amphetamine-based drugs are widely prescribed to treat ADHD.
amphetamine Drug that releases the neurotransmitter dopamine into
its synapse and like cocaine, blocks dopamine reuptake.
Section 5-1 describes experiments Otto Loewi performed to identify
epinephrine, or adrenaline. Section 7-7 details symptoms and
outcomes of ADHD and the search for an animal model of the
disease.
Timothy Ross/The Image Works
 Gregory G. Dimijian/Science Source
Tek Image/Science Photo Library/Science Source
 FIGURE 6-11 Behavioral Stimulant Cocaine (left) is obtained from
the leaves of the coca plant (center). Crack cocaine (right) is chemically
altered to form rocks that vaporize when heated at low temperatures.

One form of amphetamine was first used as an asthma treatment:

Benzedrine was sold in inhalers as a nonprescription drug through the
1940s. Soon people discovered that they could open the container and
ingest its contents to obtain an energizing effect. Amphetamine was
widely used in World War II—and is still used today to help troops and
pilots stay alert, increase confidence and aggression, and boost morale—
and also was used then to improve wartime workers’ productivity. Today,
amphetamine is also used as a weight loss aid. Many over-the-counter
compounds marketed as stimulants or weight loss aids have
amphetaminelike pharmacological actions.
An illegal amphetamine derivative, methamphetamine (also known as
meth, speed, crank, smoke, or crystal ice) continues in widespread use.
Lifetime prevalence of methamphetamine use in the U.S. population,
once estimated to be as high as 8 percent (Durell et al., 2008), is related to
its ease of manufacture in illicit laboratories and to its potency, thus
making it a relatively inexpensive, yet potentially devastating, drug.
Cocaine is a powder extracted from the Peruvian coca shrub, both
shown in Figure 6-11 . The indigenous people of Peru have chewed coca
leaves through the generations to increase their stamina in the harsh
environment and high elevations where they live. Refined cocaine powder
can either be sniffed (snorted) or injected. Cocaine users who do not like
to inject cocaine intravenously or cannot afford it in powdered form sniff
or smoke rocks, or crack, a potent, highly concentrated form shown at
right in Figure 6-11 . Crack is chemically altered so that it vaporizes at
low temperatures, and the vapors are inhaled.
Sigmund Freud (1974) popularized cocaine in the late 1800s as an
antidepressant. It was once widely used in soft drinks and wine mixtures
promoted as invigorating tonics. It is the origin of the trade name of
Coca-Cola, which once contained cocaine ( Figure 6-12 ). Its addictive
properties soon became apparent, however.
Freud also recommended that cocaine be used as a local anesthetic.
Cocaine did prove valuable for this purpose, and many derivatives, such
as xylocaine (often called Novocain), are used today. These local
anesthetic agents reduce a cell’s permeability to sodium ions and so
reduce nerve conduction.
The Granger Collection
FIGURE 6-12 Warning Label Cocaine was once an ingredient in such invigorating
beverages as Coca-Cola.

Psychedelic and Hallucinogenic Stimulants

Psychedelic drugs alter sensory perception and cognitive processes and
can produce hallucinations. We categorize the major groups of
psychedelics by their actions on specific neurotransmitters, here and in
Table 6-1 on page 181 .
psychedelic drug Drug that can alter sensation and perception;
examples are lysergic acid diethylamide (LSD), mescaline, and
psilocybin.
ACETYLCHOLINE PSYCHEDELICS These drugs either block (atropine) or
facilitate (nicotine) transmission at ACh synapses.
ANANDAMIDE PSYCHEDELICS Results from numerous lines of research
suggest that the endogenous neurotransmitter anandamide enhances
forgetting. Anandamide prevents the brain’s memory systems from being
overwhelmed by all the information to which we are exposed each day.
Tetrahydrocannabinol (THC) is one of 84 cannabinoids and the main
psychoactive constituent in marijuana, obtained from the hemp plant
Cannabis sativa, shown in Figure 6-13 . THC alters mood primarily by
interacting with the anandamide CB1 receptor found on neurons, and it
also binds with the anandamide CB2 receptors found on glial cells and in
other body tissues. THC has low toxicity but may have a detrimental
effect on memory as well as a positive effect on mental overload.
Anandamide (from Sanskrit, meaning joy or bliss ) acts on a receptor
that naturally inhibits adenyl cyclase, part of a second messenger
system active in sensitization (see Section 5-4 ).
Evidence points to the usefulness of THC, or other cannabinoids, as a
therapeutic agent for a number of disorders. It relieves nausea and emesis
(vomiting) in patients undergoing cancer chemotherapy who are not
helped by other treatments and stimulates the appetite in AIDS patients
with anorexia–cachexia (wasting) syndrome. THC has been found helpful
for treating chronic pain through mechanisms that appear to be different
from those of the opioids. It has also proved useful for treating glaucoma
(increased pressure in the eye), for spastic disorders such as multiple
sclerosis, for disorders associated with spinal cord injury, and for
epilepsy. THC may also have some neuroprotective properties (see
Section 6-4 ). Many people self-prescribe THC for a wide range of
ailments, including PTSD (Roitman et al., 2014).
Synthetic and derived forms of THC have been developed in part to
circumvent legal restrictions on its use. Nevertheless, legal restrictions
against THC use hamper investigations into its useful medicinal effects.
Phil Schermeister/Stone/Getty Images

FIGURE 6-13 Cannabis sativa The hemp plant, an annual herb, grows
over a wide range of altitudes, climates, and soils. Hemp has myriad uses,
including in manufacturing rope, cloth, and paper.

GLUTAMATE PSYCHEDELICS PCP (angel dust) and ketamine (Special K)

can produce hallucinations and out-of-body experiences. Both drugs,
formerly used as anesthetics (see Table 6-1 , Group I), exert part of their
action by blocking glutamate NMDA receptors involved in learning.
Other NMDA receptor antagonists include dextromethorphan and nitrous
oxide (NO).
 Although PCP’s primary psychoactive effects last for a few hours, its
total elimination rate from the body can extend its action for 8 days or
longer. That psychotropic drugs, including PCP and ketamine, can
produce schizophrenialike symptoms, including hallucinations and out-of
-body experiences, suggests the involvement of excitatory glutamate
synapses in schizophrenia.
Glutamate is the main excitatory neurotransmitter in the forebrain
and cerebellum. Section 14-4 describes how Glu and NMDA
receptors affect long-term learning.
NOREPINEPHRINE PSYCHEDELICS Mescaline, obtained from the peyote
cactus, is legal in the United States for use by Native Americans for
religious practices. Mescaline produces pronounced psychic alterations,
including a sense of spatial boundlessness and visual hallucinations. The
effects of a single dose last up to 10 hours.
SEROTONIN PSYCHEDELICS The synthetic drug lysergic acid diethylamide
(LSD) and naturally occurring psilocybin (obtained from various
mushrooms) stimulate some 5-HT receptors and block the activity of
other serotonergic neurons through 5-HT autoreceptors.
Serotonin psychedelics may stimulate other transmitter systems,
including norepinephrine receptors. MDMA (Ecstasy), one of several
synthetic amphetamine derivatives, induces a sense of well-being and
disembodiment as well as visual distortions. Repeated MDMA use is
associated with sleep, mood, and anxiety disorders and may also be
associated with memory and attention deficits. Drug models of
schizophrenia include LSD, which produces hallucinations and is a
serotonin agonist that acts at the 5-HT2 receptor. Again, that
hallucinations are a symptom of schizophrenia suggests that excess 5-HT
action can be involved.
General Stimulants
General stimulants cause an overall increase in cells’ metabolic activity.
Caffeine, a widely used stimulant, inhibits an enzyme that ordinarily
breaks down the second messenger cyclic adenosine monophosphate
(cAMP). The resulting increase in cAMP leads to increased glucose
production, making more energy available and allowing higher rates of
cellular activity.
A cup of coffee contains about 100 mg of caffeine; many common soft
drinks contain almost as much; and some energy drinks pack as much as
500 mg. You may be using more caffeine than you realize. Excessive
levels can lead to the jitters. Regular caffeine users who quit may have
headaches, irritability, and other withdrawal symptoms.
Caffeine boosts cAMP concentrations, action potentials last longer
than usual, and we get the coffee jitters.
 6-2 REVIEW
Grouping Psychoactive Drugs
Before you continue, check your understanding.
1 . Because of their diverse actions, it is useful to group drugs in terms of
their most pronounced ___________ or ___________ effects.
2 . Antianxiety and sedative-hypnotic drugs affect the ___________
receptor, which through ___________ influx hyperpolarizes neurons.
3 . Among the antidepressant drug types, ___________ increase the
amount of 5-HT available in the presynaptic terminal, while
___________ block 5-HT reuptake at the synapse.
4 . Opioids mimic the action of ___________ by binding to the same
receptors.
5 . Amphetamine stimulates ___________ and cocaine blocks
___________ at the ___________ synapse.
6 . On which neurotransmitters do drugs that produce psychotropic
effects act?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Factors Influencing Individual
6-3

Responses to Drugs
Many behaviors trigger predictable results. You strike the same piano
key repeatedly and hear the same note each time. You flick a light switch
today, and the bulb glows exactly as it did yesterday. This cause-and-
effect consistency does not extend to the effects of psycho-active drugs.
Individuals respond to drugs in remarkably different ways at different
times.

Behavior on Drugs
Ellen is a healthy, attractive, intelligent 19-year-old university freshman
who knows the risks of unprotected sexual intercourse. She learned
about HIV and other sexually transmitted diseases (STDs) in her high
school health class. A seminar about the dangers of unprotected sexual
intercourse was part of her college orientation: seniors provided the
freshmen in her residence free condoms and safe sex literature. Ellen and
her former boyfriend were always careful to use latex condoms during
intercourse.
At a homecoming party in her residence hall, Ellen has a great time,
drinking and dancing with her friends and meeting new people. She is
particularly taken with Brad, a sophomore at her college, and the two of
them decide to go back to her room to order a pizza. One thing leads to
another, and Ellen and Brad have sexual intercourse without using a
condom. The next morning, Ellen wakes up, dismayed and surprised at
her behavior and concerned that she may be pregnant or may have
contracted an STD. She is terrified that she may have AIDS (MacDonald
et al., 2000).
What happened to Ellen? What is it about drugs, especially alcohol,
that make people sometimes do things they would not ordinarily do?
Alcohol links to many harmful behaviors that are costly both to
individuals and to society. These harmful behaviors include not only
unprotected sexual activity but also driving while intoxicated, date rape,
spousal or child abuse and other aggressive behaviors, and crime.
Among the explanations for alcohol’s effects are disinhibition, learning,
and behavioral myopia.
Disinhibition and Impulse Control
An early and still widely held explanation of alcohol’s effects is
disinhibition theory. It holds that alcohol has a selective depressant
effect on the cortical brain region that controls judgment while sparing
subcortical structures, those responsible for more instinctual behaviors,
such as desire. Stated differently, alcohol depresses learned inhibitions
based on reasoning and judgment while releasing the “beast” within.
disinhibition theory Explanation holding that alcohol has a
selective depressant effect on the brain’s frontal cortex, which
controls judgment, while sparing subcortical structures responsible
for more instinctual behaviors, such as desire.
A variation of disinhibition theory argues that the frontal lobes check
impulsive behavior. According to this idea, impulse control is impaired
after drinking alcohol because of a higher relative sensitivity of the
frontal lobes to alcohol. A person may then engage in risky behavior
(Hardee et al., 2014).
Proponents of these theories often excuse alcohol-related behavior,
saying for example, “She was too drunk to know better” or “The boys
had a few too many and got carried away.” Do disinhibition and impulse
control explain Ellen’s behavior? Not entirely. Ellen had used alcohol in
the past and managed to practice safe sex despite its effects. Neither
theory explains why her behavior was different on this occasion. If
alcohol is a disinhibitor, why is it not always so?
Learning
Craig MacAndrew and Robert Edgerton (1969) questioned disinhibition
theory along just these lines in their book Drunken Comportment. They
cite many instances in which behavior under the influence of alcohol
changes from one context to another. People who engage in polite social
activity at home when consuming alcohol may become unruly and
aggressive when drinking in a bar.
Even behavior at the bar may be inconsistent. Take Joe, for example.
While drinking one night at a bar, he acts obnoxious and gets into a fight.
On another occasion, he is charming and witty, even preventing a fight
between two friends; on a third occasion, he becomes depressed and
worries about his problems. MacAndrew and Edgerton also cite
examples of cultures in which people are disinhibited when sober only to
become inhibited after consuming alcohol and cultures in which people
are inhibited when sober and become more inhibited when drinking.
What explains all these differences in alcohol’s effects?
MacAndrew and Edgerton suggested that behavior under the effects
of alcohol is learned. Learned behavior is specific to culture, group, and
setting and can in part explain Ellen’s decision to sleep with Brad. Where
alcohol is used to facilitate social interactions, behavior while intoxicated
is a time-out from more conservative rules regarding dating.
Behavioral Myopia
But Ellen’s lapse in judgment regarding safe sex is more difficult to
explain by learning theory. Ellen had never practiced unsafe sex before
and had never made it a part of her time-out social activities. So why did
she engage in it with Brad?
A different explanation for alcohol-related lapses in judgment,
behavioral myopia (nearsightedness), is the tendency for people under
the influence of (in this case) alcohol to respond to a restricted set of
immediate and prominent cues while ignoring more remote cues and
possible consequences. Immediate and prominent cues are very strong
and obvious and close at hand (Griffin et al., 2010).
behavioral myopia “Nearsighted” behavior displayed under the
influence of alcohol: local and immediate cues become prominent;
remote cues and consequences are ignored.
In an altercation, the person with behavioral myopia will be quicker
than usual to throw a punch, because the fight cue is so strong and
immediate. At a raucous party, the myopic drinker will be more eager
than usual to join in, because the immediate cue of boisterous fun
dominates his or her view. Once Ellen and Brad arrived at Ellen’s room,
the sexual cues at the moment were far more immediate than concerns
about long-term safety. As a result, Ellen responded to those immediate
cues and behaved atypically.
Oliver Furrer/Brand X/Corbis
 People who enjoy high-risk adventure may be genetically predisposed to
experiment with drugs, but people with no interest in risk taking are just as
likely to use drugs. Section 6-4 discusses genetic influences on drug
taking.

Behavioral myopia can explain many lapses in judgment that lead to

risky behavior—aggression, date rape, and reckless driving while
intoxicated. Individuals who have been drinking may also have poor
insight into their level of intoxication: they may assume that they are less
impaired than they actually are (Sevincer and Oettingen, 2014).

Addiction and Dependence

B. G. started smoking when she was 13 years old. She has quit many
times without success. After successfully abstaining from cigarettes by
using a nicotine patch for more than 6 months, B. G. began smoking
again. Because the university where she works has a no smoking policy,
she has to leave campus and stand across the street to smoke. Her voice
has developed a rasping sound, and she has an almost chronic “cold.”
She says that she used to enjoy smoking but does not any more. Concern
about quitting dominates her thoughts.
B. G. has a drug problem. She is one of the 25 percent or so of North
Americans who smoke. Like B. G., most smokers realize that it is a
health hazard, have experienced unpleasant side effects from it, and have
attempted to quit but cannot. B. G. is exceptional only in her white-collar
occupation. Today, most smokers are found in blue-collar occupations
rather than among professional workers. And the use of electronic
cigarettes (e-cigarettes) by young people is on the rise (Czoli et al.,
2015). The health hazards posed by nicotine delivery via e-cigarettes are
unknown.
Substance abuse is a pattern of drug use in which people rely on a
drug chronically and excessively, allowing it to occupy a central place in
their life. In a more advanced state of substance dependence, popularly
known as addiction, people are physically dependent on a drug in
addition to abusing it. They have developed tolerance for the drug and so
require increased doses to obtain the desired effect.
substance abuse is a pattern of drug use in which people rely on a
drug chronically and excessively, allowing it to occupy a central
place in their life.
addiction Desire for a drug; manifested by frequent use, leading to
physical dependence in addition to abuse; often associated with
tolerance and unpleasant, sometimes dangerous, withdrawal
symptoms on cessation. Per the DSM-5, called substance use
disorder.
Drug addicts may also experience unpleasant, sometimes dangerous
physical withdrawal symptoms if they suddenly stop taking the abused
drug. Symptoms can include muscle aches and cramps, anxiety attacks,
sweating, nausea, and even, for some drugs, convulsions and death.
Symptoms of alcohol or morphine withdrawal can begin within hours of
the last dose and tend to intensify over several days before they subside.
withdrawal symptom Physical and psychological behavior
displayed by an addict when drug use ends.
Although B. G. abuses nicotine, she is not physically dependent on it.
She smokes approximately the same number of cigarettes each day (she
has not developed tolerance to nicotine), and she does not get sick if she
is deprived of cigarettes (does not have severe withdrawal symptoms but
does display irritability, anxiety, increased appetite, and insomnia). B. G.
illustrates that the power of psychological dependence can be as
influential as the power of physical dependence.
To view the brain areas nicotine affects most, see Figure 12-30 .
Many abused or addictive drugs—including sedative-hypnotics,
antianxiety agents, opioids, and stimulants—have a common property:
they produce psychomotor activation in some part of their dose range.
That is, at certain levels of consumption, these drugs make the user feel
energetic and in control. This common effect has led to the hypothesis
that all abused drugs may act on the same target in the brain: dopamine
in the mesolimbic pathways of the dopaminergic activating system.
Drugs of abuse increase mesolimbic dopamine activity, either directly or
indirectly, and drugs that blunt abuse and addiction decrease mesolimbic
dopamine activity.
psychomotor activation Increased behavioral and cognitive
activity: at certain levels of consumption, the drug user feels
energetic and in control.

Sex Differences in Addiction

Vast differences in individual responses to drugs are due to differences in
age, body size, metabolism, and sensitivity to a particular substance.
Larger people, for instance, are generally less sensitive to a drug than
smaller people are: their greater volume of body fluids dilutes drugs
more. Old people may be twice as sensitive to drugs as young people are.
The elderly often have less effective barriers to drug absorption as well
as less effective processes for metabolizing and eliminating drugs from
their body. Individuals also respond to drugs in different ways at
different times.
Females are about twice as sensitive to drugs as are males, on
average, owing in part to their smaller size but also to hormonal
differences. The long-held general assumption that human males are
more likely to abuse drugs than are human females led investigators to
neglect researching drug use and abuse in human females. But the results
of recent research support quite the opposite view: females are less likely
to become addicted to some drugs than are males, but females are
catching up and for some drugs are surpassing males in the incidence of
addiction.
Although the general pattern of drug use is similar in males and
females, the sex differences are striking (Becker and Hu, 2008). Females
are more likely than males to abuse nicotine, alcohol, cocaine,
amphetamine, opioids, cannabinoids, caffeine, and PCP. Females begin
to regularly self-administer licit and illicit drugs of abuse at lower doses
than do males; females’ use escalates more rapidly to addiction; and
females are at greater risk for relapse after abstinence.
 6-3 REVIEW

Factors Influencing Individual

Responses to Drugs
Before you continue, check your understanding.
1 . Of the three explanations for alcohol’s effects on behavior,
___________ and ___________ are less explicative than
___________.
2 . ___________ is a condition in which people rely on drugs chronically
and to excess, whereas ___________ is a condition in which people
are physically dependent on a drug as well.
3 . The evidence that many abused or addictive drugs produce
___________, which makes the user feel energetic and in control,
suggests that activation in the ___________ plays a role in drug abuse
and addiction.
4 . Common wisdom is incorrect in suggesting that ___________ are
less likely to abuse drugs than ___________ are.
5 . Why can alcohol-related behavior vary widely in a single individual
from time to time?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 6-4 Explaining and Treating Drug Abuse
Why do people become addicted to drugs? Early explanations centered on
pleasure and dependence: habitual drug users initially feel pleasure but
then endure psychological and physiological withdrawal symptoms as the
drug wears off. They feel anxious, insecure, or just plain sick without the
drug, so they take it again to alleviate those symptoms. In this way, they
get hooked on the drug.
Although this dependency hypothesis may account for part of drug-
taking behavior, it has shortcomings as a general explanation. For
example, an addict may abstain from a drug for months, long after any
withdrawal symptoms have abated, yet still be drawn back to using it. In
addition, some psychoactive drugs, such as the tricyclic antidepressants,
produce withdrawal symptoms when discontinued, but these drugs are not
abused.

Wanting-and-Liking Theory
To account for all the facts about drug abuse and addiction, Terry
Robinson and Kent Berridge (2008) proposed the incentive sensitization
theory, also called the wanting-and-liking theory because wanting and
liking are produced by different brain systems. Their wanting is craving,
whereas liking is the pleasure the drug produces. With repeated use,
tolerance for liking develops, and the expression of liking (pleasure)
decreases as a consequence (Figure 6-14 ). In contrast, the system that
mediates wanting sensitizes, and craving increases.
wanting-and-liking theory Explanation holding that when a drug is
associated with certain cues, the cues themselves elicit desire for the
drug; also called incentive sensitization theory.
The first step on the proposed road to drug dependence is the initial
experience, when the drug affects a neural system associated with
pleasure. At this stage, the user may like the substance—including liking
to take it within a given social context. With repeated use, liking the drug
may decline from its initial level. At this stage, the user may also begin to
show tolerance to the drug’s effects and so may begin to increase the
dosage to increase liking.
With each use, the drug taker increasingly associates the cues related
to drug use—be it a hypodermic needle, the room in which the drug is
taken, or the people with whom the drug is taken—with the drug-taking
experience. The user makes this association because the drug enhances
classically conditioned cues associated with drug taking. Eventually,
these cues come to possess incentive salience: they induce wanting, or
craving, the drug-taking experience.
In classical (Pavlovian) conditioning, learning to associate a formerly
neutral stimulus (the sound of a bell) with a stimulus (food) elicits an
involuntary response (salivation).
The neural basis of addiction is proposed to involve multiple brain
systems. The decision to take a drug is made in the prefrontal cortex, an
area that participates in most daily decisions. When a drug is taken, it
activates opioid systems in the brainstem that are generally related to
pleasurable experiences. And wanting drugs may spring from activity in
the mesolimbic pathways of the dopaminergic activating system.
In these mesolimbic pathways, diagrammed in Figure 6-15 , the axons
of dopamine neurons in the midbrain project to structures in the basal
ganglia, to the frontal cortex, and to the limbic system. When drug takers
encounter cues associated with drug taking, the mesolimbic system
becomes active, releasing dopamine. Dopamine release is the neural
correlate of wanting.
Another brain system may be responsible for conditioning drug-related
cues to drug taking. Barry Everitt (2014) proposes that the repeated
pairing of drug-related cues to drug taking forms neural associations, or
learning, in the dorsal striatum, a region in the basal ganglia consisting of
the caudate nucleus and putamen. As the user repeatedly takes the drug,
voluntary control gives way to unconscious processes—a habit. The
result: drug users lose control of decisions related to drug taking, and the
wanting—the voluntary control over drug taking—gives way to the
craving of addiction.
When a rat is placed in an environment where it anticipates a favored
food or sex, investigators record dopamine increases in the striatum
(see Section 7-5 ).
Multiple findings align with the wanting-and-liking explanation of
drug addiction. Ample evidence confirms that abused drugs and the
context in which they are taken initially has a pleasurable effect and that
habitual users continue using their drug of choice, even when taking it no
longer produces any pleasure. Heroin addicts sometimes report that they
are miserable: their lives are in ruins, and the drug is not even pleasurable
anymore. But they still want it. What’s more, desire for the drug often is
greatest just when the addicted person is maximally high, not during
withdrawal. Finally, cues associated with drug taking—the social
situation, the sight of the drug, and drug paraphernalia—strongly
influence decisions to take, or continue taking, a drug.
Notwithstanding support for a dopamine basis for addiction, recent
research suggests more than one type of addiction. Some rats become
readily conditioned to cues associated with reinforcement, for example a
bar that delivers a reward when pressed. Other animals ignore the bar’s
incentive salience but are attracted to the location where they receive
reinforcement. Animals that display the former behavior are termed sign
trackers and the other group, goal trackers. Sign trackers exposed to
addictive drugs appear to attribute incentive salience to drug-associated
cues. Their drug wanting is dependent upon the brain’s dopamine
systems. Goal trackers may also become addicted, possibly via different
neural systems. Such findings imply at least two types of addiction (Yager
et al., 2015).

Peter Dokus/Stone
FIGURE 6-14 Wanting-and-Liking Theory With repeated drug
use, wanting a drug and liking the drug progress in opposite directions.
Wanting (craving) is associated with drug cues.
 FIGURE 6-15 Mesolimbic Dopamine Pathways Axons of
neurons in the midbrain ventral tegmentum project to the basal ganglia,
prefrontal cortex, and hippocampus.

We can extend wanting-and-liking theory to many life situations. Cues

related to sexual activity, food, and even sports can induce wanting,
sometimes in the absence of liking. We frequently eat when prompted by
the cue of other people eating, even though we may not be hungry and
derive little pleasure from eating at that time. The similarities between
exaggerating normal behaviors and drug addiction suggest that they
depend on the same learning and brain mechanisms. For this reason, any
addiction is extremely difficult to treat.

Why Doesn’t Everyone Abuse Drugs?

Observing that some people are more prone than others to drug abuse and
dependence, scientists have investigated and found three lines of evidence
suggesting a genetic contribution to differences in drug use. First, if one
identical twin (same genotype) abuses alcohol, the other twin is more
likely to abuse it than if the twins are fraternal (have only some genes in
common). Second, people adopted shortly after birth are more likely to
abuse alcohol if their biological parents were alcoholic, even though they
have had almost no contact with those parents. Third, although most
animals do not care for alcohol, selective breeding of mice, rats, and
monkeys can produce strains that consume large quantities of it.
Each line of evidence presents problems, however. Perhaps identical
twins show greater concordance rates (incidence of similar behavioral
traits) for alcohol abuse because their environments are more similar than
those of fraternal twins. And perhaps the link between alcoholism in
adoptees and their biological parents has to do with nervous system
changes due to prenatal exposure to the drug. Finally, the fact that
animals can be selectively bred for alcohol consumption does not mean
that all human alcoholics have a similar genetic makeup. The evidence
for a genetic basis of alcohol abuse will become compelling only when a
gene or set of genes related to alcoholism is found.
Epigenetics offers another explanation of susceptibility to addiction
(Hillemacher et al., 2015). Addictive drugs may reduce the transcriptional
ability of genes related to voluntary control and increase the
transcriptional ability of other genes related to behaviors susceptible to
addiction. Epigenetic changes in an individual’s gene expression may be
relatively permanent and can be passed along, perhaps through the next
few generations. For these reasons, epigenetics can account both for the
enduring behaviors that support addiction and for the tendency of drug
addiction to be inherited.
Less-than-perfect concordance rates between identical twins for
diseases ranging from schizophrenia to asthma point to epigenetic
inheritance of behaviors by the next generation (see Section 3-3 ).

Treating Drug Abuse

Figure 6-16 charts the relative incidence of drug use in the United States
—people aged 12 and older who reported using at least one psychoactive
drug during the year preceding in a national survey conducted by the U.S.
Department of Health and Human Services in 2013. The two most-used
drugs, alcohol and tobacco, are legal. The drugs that carry the harshest
penalties, cocaine and heroin, are used by far fewer people. But
criminalizing drugs clearly is not a solution to drug use or abuse, as
illustrated by the widespread use of marijuana, the third most used drug
on the chart. In response to its widespread use, several states have
legalized marijuana to some degree, but it remains illegal under federal
law.
Treating drug abuse is difficult in part because legal proscriptions are
irrational. In the United States, the Harrison Narcotics Act of 1914 made
heroin and a variety of other drugs illegal and made the treatment of
addicted people by physicians in their private offices illegal. The Drug
Addiction Treatment Act of 2000 partly reversed this prohibition,
allowing the treatment of patients but with a number of restrictions. In
addition, legal consequences attending drug use vary greatly with the
drug and the jurisdiction.
From a health standpoint, tobacco has much higher proven health risks
than does marijuana. Moderate use of alcohol is likely benign. Moderate
use of opioids is likely impossible. Social coercion is useful in reducing
tobacco use: witness the marked decline in smoking as a result of
prohibitions against smoking in public places. Medical intervention is
necessary to provide methadone and other drug treatment of opioid
abusers.
The numerous approaches to treating drug abuse vary, depending on
the drug. Many online sites support self-help groups and professional
groups that address the treatment of various drug addictions. Importantly,
because addiction is influenced by unconscious conditioning to drug-
related cues and by a variety of brain changes, relapse remains an
enduring risk for people who have apparently kicked their habit.
Neuroscience research will continue to lead to a better understanding
of the neural basis of drug use and to better treatment. The best approach
to any drug treatment likely recognizes that addiction is a lifelong
problem for most people. Thus, drug addiction must be treated in the
same way as chronic behavioral addictions and medical problems—
analogous to recognizing that controlling weight with appropriate diet
and exercise is a lifelong struggle for many people.

FIGURE 6-16 Drug Use in the United States, 2013 Results

from an annual national survey of Americans aged 12 and older who
reported using at least one psychoactive drug during the past year.
Percentages for alcohol, tobacco, and marijuana are rounded to the
nearest whole number. Data from the 2013 National Survey on Drug Use and Health:
Summary of National Findings, U.S. Department of Health and Human Services, Substance
Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and
Quality. Available for download at www.hhs.gov .
Micrograph from NeuroScience Associates
 FIGURE 6-17 Neurotoxicity Domoic acid damage in this rat’s
hippocampus and to a lesser extent in many other brain regions, indicated
by the darkest coloring. Domoic acid, a Glu antagonist, is the causative
agent in amnesic shellfish poisoning, which can result in permanent short-
term memory loss, brain damage, and in severe cases, death.

Can Drugs Cause Brain Damage?

Many natural substances can act as neurotoxins; Table 6-2 lists some of
them. Ongoing investigations of the neurotoxicity of these substances and
other drugs in animal models show that many cause brain damage.
Whether drugs of abuse cause brain damage in humans—especially
whether they can do so at the doses that humans take—is more difficult to
determine. It is difficult to sort out other life experiences from drug
taking. It is also difficult to obtain the brains of drug users for
examination at autopsy. Nevertheless, there is evidence that the
developing brain can be particularly sensitive to drug effects, especially
in adolescence, a time when drug experimentation is common (Teixeira-
Gomes, 2015).
In the late 1960s, many reports linked monosodium glutamate, MSG, a
salty-tasting, flavor-enhancing food additive, to headaches in some
people. In investigating this effect, scientists placed large doses of MSG
on cultured neurons, which died. Subsequently, they injected MSG into
the brains of experimental animals, where it also killed neurons.
This line of research led to the discovery that many glutamatelike
substances, including domoic acid and kainic acid, both toxins in
seaweed, and ibotenic acid, which is found in some poisonous
mushrooms, similarly kill neurons (Figure 6-17 ). Some drugs, such as
PCP and ketamine, also act as glutamate agonists, leaving open the
possibility that at high doses they too can cause neuronal death.
TABLE 6-2 Some Neurotoxins, Their Sources, and Their
Actions
Substance Origin Action

Tetrodotoxin Puffer fish Blocks membrane permeability to Na+

Magnesium Natural element Blocks Ca2+ channels

Reserpine Tree Destroys storage granules

Colchicine Crocus plant Blocks microtubules

Caffeine Coffee bean Blocks adenosine receptors, blocks Ca2+ channels

Spider venom Black widow spider Stimulates ACh release

Botulin Spoiled food Blocks ACh release

Curare Berry Blocks ACh receptors

Rabies virus Infected animal Blocks ACh receptors

Ibotenic acid Mushroom Similar to domoic acid, mimics glutamate

Strychnine Plant Blocks glycine

Apamin Bees and wasps Blocks Ca2+ channels

Monosodium glutamate (MSG)

 Glutamate

Glutamatelike drugs are toxic because they act on glutamate receptors.

Glutamate receptor activation results in an influx of Ca2+ into the cell,
which through second messengers activates a suicide gene leading to
apoptosis (cell death). This discovery shows that a drug might be toxic
not only because of its general effect on cell function but also as an agent
that activates normal cell processes related to apoptosis.
We must add that there is no evidence that moderate consumption of
MSG is harmful.
 What about the many recreational drugs that affect the nervous
system? Are any neurotoxic? Sorting out the effects of the drug itself
from the effects of other factors related to taking the drug is a major
problem. Chronic alcohol use, for instance, can be associated with
damage to the thalamus and limbic system, producing severe memory
disorders. Alcohol, however, does not directly cause this damage.
Alcoholics typically obtain low amounts of thiamine (vitamin B1 ) in their
diet, and alcohol interferes with the intestine’s absorption of thiamine.
Thiamine plays a vital role in maintaining cell membrane structure.
Similarly, among the many reports of people who have a severe
psychiatric disorder subsequent to abusing certain recreational drugs, in
most cases determining whether the drug initiated the condition or
aggravated an existing problem is difficult. Exactly determining whether
the drug itself or some contaminant in it caused a harmful outcome also is
difficult. With the increasing sensitivity of brain imaging studies,
however, evidence is increasing that many drugs used recreationally can
cause brain damage and cognitive impairments.
Focus 5-4 reports the chilling case of heroin addicts who developed
Parkinson disease after using synthetic heroin, owing to a
contaminant (MPTP) in the drug.
The strongest evidence comes from the study of the synthetic
amphetaminelike drug MDMA, also called Ecstasy, and in pure powdered
form, Molly (Büttner, 2011). Although MDMA is structurally related to
amphetamine, it produces hallucinogenic effects and is called a
hallucinogenic amphetamine. Findings from animal studies show that
doses of MDMA approximating those taken by human users result in the
degeneration of very fine serotonergic nerve terminals. In monkeys,
significant terminal loss may be permanent, as shown in Figure 6-18 .
Memory impairments and damage in MDMA users revealed by brain
imaging may be a result of similar neuronal damage (Cowan et al., 2008).
MDMA may also contain a contaminant, paramethoxymethamphetamine
(PMMA). This notoriously toxic amphetamine is often called Dr. Death
because the difference between a dose that causes behavioral effects and a
dose that causes death is minuscule (Vevelstad et al., 2012).
Contamination by unknown compounds can occur in any drug purchased
on the street.
The psychoactive properties of cocaine are similar to those of
amphetamine, and so cocaine also is suspect with respect to brain
damage. Cocaine use is related to the blockage of cerebral blood flow and
other changes in blood circulation. Brain imaging studies suggest that
cocaine use can be toxic to neurons, because several brain regions are
reduced in size in cocaine users (Liu et al., 2011).
Chronic marijuana use has been associated with psychotic attacks.
Clinical Focus 6-4 , Drug-Induced Psychosis, describes one. The
marijuana plant contains at least 400 chemicals, 60 or more of which are
structurally related to its active ingredient, tetrahydrocannabinol.
Determining whether a psychotic attack is related to THC or to some
other chemical in marijuana is almost impossible.
Focus 7-3 explores the hypothesis that genetic vulnerability
predisposes some adolescents to develop a psychosis when exposed
to cannabis.
Whether or not THC can cause psychosis, there is no evidence that the
disease is a result of brain damage. Indeed, beyond the therapeutic
applications of TCH cited in Section 6-2 , recent studies suggest that
THC may have neuroprotective properties. It can aid brain healing after
traumatic brain injury and slow the progression of diseases associated
with brain degeneration, including Alzheimer disease and Huntington
disease (Nguyen et al., 2014).
CLINICAL FOCUS 6-4

Drug-Induced Psychosis
At age 29, R. B. S. smoked marijuana chronically. For years, he had
been selectively breeding a potent strain of marijuana in anticipation
of the day when it would be legalized. R. B. S. made his living as a
pilot, flying small freight aircraft into coastal communities in the
Pacific Northwest.
One evening, R. B. S. had a sudden revelation: he was no longer
in control of his life. Convinced that a small computer had been
implanted in his brain when he was 7 years old and was
manipulating his behavior, he confided in a close friend, who urged
him to consult a doctor. R. B. S. insisted that he had undergone the
surgery when he participated in an experiment at a local university.
He also claimed that all the other children who participated in the
experiment had been murdered.
The doctor told R. B. S. that the computer implantation was
unlikely but called the psychology department at the university and
got confirmation that children had in fact taken part in an experiment
conducted years before. The records of the study had long since been
destroyed. R. B. S. believed that this information completely
vindicated his story. His delusional behavior persisted and eventually
cost him his pilot’s license.
R. B. S. seemed to compartmentalize the delusion. When asked
why he could no longer fly, he intently recounted the story of the
implant and the murders, asserting that its truth had cost him the
medical certification needed for a license. Then he happily and
appropriately discussed other topics.
R. B. S. had a mild focal psychosis: he was losing contact with
reality. In some cases, this break is so severe and the capacity to
respond to the environment so impaired and distorted that the person
can no longer function. People in a state of psychosis may
hallucinate, may have delusions, or may withdraw into a private
world isolated from people and events around them.
 A variety of drugs can produce psychosis, including LSD,
amphetamine, cocaine, and, as shown by this case, marijuana. At low
doses THC, the active ingredient in marijuana, has mild sedative-
hypnotic effects similar to those of alcohol. At the high doses that R.
B. S. used, THC can produce euphoria and hallucinations.
Marijuana comes from the leaves of the hemp plant, Cannabis
sativa. Humans have used hemp for thousands of years to make rope,
paper, cloth, and a host of other products. And marijuana has a
number of beneficial medical effects. In the Pacific Northwest,
marijuana is the largest agricultural crop and makes a larger
contribution to the economy than does forestry. In some states
marijuana can legally be purchased for personal use, and in many
states its medical use is legal. Under federal law, however, it remains
illegal everywhere in the United States.
R. B. S.’s heavy marijuana use certainly raises the suspicion that
the drug had some influence on his delusional condition (Wilkinson
et al., 2014). Cannabis use has been reported to moderately increase
the risk of psychotic symptoms in young people and has a much
stronger effect in those with a predisposition for psychosis,
especially if potent strains are used (Di Forti et al., 2015). Although
there is evidence that heavy marijuana use may be associated with
alterations in brain development, it is unclear whether brain
abnormalities are a result of marijuana use or a causal factor in its
use (Lubman et al., 2015).
Jim Wilson/The New York Times/Redux
Employees fill prescriptions at a medical marijuana clinic in San
Francisco. At this writing California is one of more than 20
states that have decriminalized the use of medical marijuana.
 6-4 REVIEW
Explaining and Treating Drug Abuse
Before you continue, check your understanding.
1 . The wanting-and-liking theory of addiction suggests that with
repeated use, ___________ of the drug decreases as a result of
___________, while ___________ increases as a result of
___________.
2 . At the neural level, the decision to take a drug is made in the brain’s
___________. Once taken, the drug activates opioid systems related to
pleasurable experiences in the ___________. Drug cravings may
originate in the ___________, and the repeated pairing of drug-related
cues and drug taking forms neural associations in the ___________
that loosen voluntary control over drug taking.
3 . As an alternative to explanations of susceptibility to addiction based
on genetic ___________, ___________ can account both for the
enduring behaviors that support addiction and for the tendency of drug
addiction to be inherited.
4 . It is hard to determine whether recreational drugs cause brain damage
in humans because it is difficult to distinguish the effects of
___________ from the effects of ___________.
5 . Briefly describe the basis for a reasonable approach to treating drug
addiction.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 6-5 Hormones
In 1849, European scientist A. A. Berthold removed a rooster’s testes
and found that it no longer crowed, nor did it engage in sexual or
aggressive behavior. Berthold then reimplanted one testis in the rooster’s
body cavity. The rooster began crowing and displaying normal sexual
and aggressive behavior again. The reimplanted testis did not establish
any nerve connections, so Berthold concluded that it must release a
chemical into the rooster’s circulatory system that influenced the
animal’s behavior.
Berthold’s experiment demonstrated that hormones —chemicals
released by endocrine glands into the bloodstream—circulate to a
body target and affect it. The endocrine glands operate under CNS
and ANS influence (see Figure 2-30 ).
That chemical, we now know, is testosterone, the sex hormone
secreted by the testes and responsible for the distinguishing
characteristics of the male. The effect Berthold produced by reimplanting
the rooster’s testis mimics the effect of administering testosterone to a
castrated rooster, or capon. The hormone is sufficient to make the capon
behave like a rooster.
testosterone Sex hormone secreted by the testes that produces the
distinguishing characteristics of the male.
We now know that many hormones affect the sexual characteristics
and reproductive behavior of animals, including us humans. Hormonal
effects are not limited to sexual behavior but also influence eating and
drinking, growth, stress responses, and other bodily functions. Hormones
are secreted by glands in the body and by the brain. Interacting brain and
body hormones form feedback loops that regulate their activity.
Hormonal influences change across the life-span, influencing
development and body and brain function (Nugent et al., 2012). In many
respects, hormone systems are like neurotransmitter-activating systems
except that hormones use the bloodstream as a conveyance. Indeed,
many hormones act as neurotransmitters, and many neurotransmitters act
as hormones.
Intact rooster
Capon (rooster with gonads removed)
Hierarchical Control of Hormones
Many hormones operate in a feedback system that includes the brain and
the body. Figure 6-18 shows how the hypothalamus produces
neurohormones that stimulate the pituitary gland to secrete releasing
hormones into the circulatory system. The pituitary hormones in turn
influence the remaining endocrine glands to release appropriate
hormones into the bloodstream to act on various targets in the body and
send feedback to the brain about the need for more or less hormone
release.
Hormones not only affect body organs but also target virtually all
aspects of brain function. Almost every neuron in the brain contains
receptors on which various hormones can act. In addition to influencing
sex organs and physical appearance, hormones affect neurotransmitter
function, especially in neurons that influence sexual development and
behavior (Barth et al., 2015). Hormones can influence gene expression
by binding to special receptors on or in the cell, then being transported to
the nucleus to influence gene transcription. Transcription in turn
influences the synthesis of proteins needed for a variety of cellular
processes. Thus, hormones influence brain and body structure and
behavior.

FIGURE 6-18 Hormonal Hierarchy

Although many questions remain about how hormones produce or
contribute to complex behavior, the diversity of their functions clarifies
why the body uses hormones as messengers: their targets are so
widespread that the best possible way of reaching all of them is to travel
in the bloodstream, which goes everywhere in the body.
Consult the entry Hormonal Disorders inside the book’s front cover
for more information.

Classes and Functions of Hormones

Hormones can be used as drugs to treat or prevent disease. People take
synthetic hormones as replacement therapy if the glands that produce the
hormones are removed or malfunction. People also take hormones,
especially sex hormones, to counteract the effects of aging, to increase
physical strength and endurance, and to gain an advantage in sports. In
the human body, as many as 100 hormones are classified chemically as
either steroids or peptides.
Steroid hormones, such as testosterone and cortisol, are synthesized
from cholesterol and are lipid (fat) soluble. Steroids diffuse away from
their site of synthesis in glands, including the gonads, adrenal cortex, and
thyroid. They bind to steroid receptors on the cell membrane or in the
cell and frequently act on cellular DNA to influence gene transcription.
steroid hormone Fat-soluble chemical messenger synthesized from
cholesterol.
Peptide hormones, such as insulin, growth hormone, and the
endorphins, are made by cellular DNA in the same way other proteins
are made. They influence their target cell’s activity by binding to
metabotropic receptors on the cell membrane, generating a second
messenger that affects the cell’s physiology or gene transcription.
peptide hormone Chemical messenger synthesized by cellular
DNA that acts to affect the target cell’s physiology.
To refresh your understanding of metabotropic receptors, review
Figure 5-15 .
Steroid and peptide hormones fall into one of three main functional
groups with respect to behavior, and they may function in more than one
group:
1. Homeostatic hormones maintain a state of internal metabolic balance
and regulate physiological systems. Mineralocorticoids (e.g.,
aldosterone) control both the concentration of water in blood and cells
and the levels of sodium, potassium, and calcium in the body, and they
promote digestive functions.
homeostatic hormone One of a group of hormones that maintain
internal metabolic balance and regulate physiological systems in an
organism.
2. Gonadal (sex) hormones control reproductive functions. They
instruct the body to develop as male (testosterone) or female
 (estrogen); influence sexual behavior and conception; and in women,
control the menstrual cycle (estrogen and progesterone), birthing of
babies, and release of breast milk (prolactin, oxytocin). These
hormones, especially oxytocin, influence mother–infant bonding, and
in some species, including sheep, are essential for bonding to occur.
gonadal (sex) hormone One of a group of hormones, such as
testosterone, that control reproductive functions and bestow sexual
appearance and identity as male or female.
3. Glucocorticoids (e.g., cortisol and corticosterone), a group of steroid
hormones secreted in times of stress, are important in protein and
carbohydrate metabolism and in controlling blood sugar levels and
cellular absorption of sugar. Hormones activated in psychologically
challenging events or emergencies prepare the body to cope by
fighting or fleeing.
glucocorticoid One of a group of steroid hormones, such as cortisol,
secreted in times of stress; important in protein and carbohydrate
metabolism.

Homeostatic Hormones
Homeostatic hormones are essential to life. The body’s internal
environment must remain within relatively constant parameters for us to
function. An appropriate balance of sugars, proteins, carbohydrates,
salts, and water is necessary in the blood, in the extracellular
compartments of muscles, in the brain and other body structures, and in
all cells. The internal environment must be maintained regardless of a
person’s age, activities, or conscious state. As children or adults, at rest
or in strenuous work, when we have overeaten or when we are hungry, to
survive we need a relatively constant internal environment.
Homeostasis comes from the Greek words stasis (standing ) and
homeo (in the same place ).
A typical homeostatic function is controlling blood sugar level. After
a meal, digestive processes result in increased glucose in the blood. One
group of cells in the pancreas releases insulin, a homeostatic hormone
that instructs the enzyme glycogen synthase in liver and muscle cells to
start storing glucose in the form of glycogen. The resulting decrease in
glucose decreases the stimulation of pancreatic cells so that they stop
producing insulin, and glycogen storage stops. When the body needs
glucose for energy, another hormone in the liver, glucagon, acts as a
countersignal to insulin. Glucagon stimulates another enzyme, glycogen
phosphorylase, to initiate glucose release from its glycogen storage site.
Normal glucose concentration in the bloodstream varies between 80
and 130 mg per 100 milliliters (about 3.3 oz) of blood.
Diabetes mellitus is caused by a failure of the pancreatic cells to
secrete enough insulin, or any at all. As a result, blood sugar levels can
fall (hypoglycemia) or rise (hyperglycemia). In hyperglycemia, blood
glucose levels rise because insulin does not instruct body cells to take up
glucose. Consequently, cell function, including neuronal function, can
fail through glucose starvation, even in the presence of high glucose
levels in the blood. Chronic high blood glucose levels cause damage to
the eyes, kidneys, nerves, heart, and blood vessels.
In hypoglycemia, inappropriate diet can lead to low blood sugar
severe enough to cause fainting. Eric Steen and his coworkers (2005)
propose that insulin resistance in brain cells may be related to Alzheimer
disease. They raise the possibility that Alzheimer disease may be a third
type of diabetes.
Hunger and eating are influenced by a number of homeostatic
hormones, including leptin and ghrelin. Leptin (from the Greek for thin ),
secreted by adipose (animal fat) tissue, inhibits hunger and so is called
the satiety hormone. Ghrelin (from the Indio-European gher, meaning to
grow ), secreted by the gastrointestinal tract, regulates growth hormones
and energy use. Ghrelin also induces hunger. It is secreted when the
stomach is empty; secretion stops when the stomach is full. Leptin and
ghrelin act on receptors on the same neurons of the arcuate nucleus of
the hypothalamus and so contribute to energy homeostasis by managing
eating.

Gonadal Hormones
We are prepared for our adult reproductive roles by the gonadal
hormones that give us our sexual appearance, mold our identity on the
continuum of male to female, and allow us to engage in sex-related
behaviors. Sex hormones begin to act on us even before we are born and
continue their actions throughout our lives.
The male Y chromosome contains a gene called the sex-determining
region Y, or SRY, gene. If cells in the undifferentiated gonads of the early
embryo contain an SRY gene, they develop into a testis, and if they do
not, they develop into an ovary. In the male, the testes produce
testosterone, which masculinizes the body and the brain.
Section 8-4 explains how gonadal hormones participate in brain
development.
The organizational hypothesis proposes that hormone action in the
course of development alters tissue differentiation. Thus, testosterone
masculinizes the brain early in life, having been taken up in brain cells,
where it is converted into estrogen by the enzyme aromatase. Estrogen
then acts on estrogen receptors to initiate a chain of events that includes
activating certain genes in the cell nucleus. These genes contribute to the
masculinization of brain cells and their interactions with other brain
cells.
organizational hypothesis Proposal that hormonal action during
development alters tissue differentiation; for example, testosterone
masculinizes the brain.
That estrogen, a hormone usually associated with the female,
masculinizes the male brain may seem surprising. Estrogen does not
have the same effect on the female brain, because females have a blood
enzyme that binds to estrogen and prevents its entry into the brain.
Hormones play a somewhat lesser role in producing the female body and
brain, but they control the mental and physical aspects of menstrual
cycles, regulate many facets of pregnancy and birth, and stimulate milk
production for breastfeeding. In males, gonadal hormones demethylate,
and so release, genes in the preoptic area of the hypothalamus to become
active. The expression of these genes influences male sexual
characteristics and behavior. Thus, active methylation of male sex–
related genes maintains the female pheno-type (Nugent et al., 2015).
Gonadal hormones contribute to surprising differences in the brain
and in cognitive behavior and play a role in male–female differences in
drug dependence and addiction (see Section 6-3 ). The male brain is
slightly larger than the female brain after corrections are made for body
size, and the right hemisphere is somewhat larger than the left in males.
The female brain has a higher rate both of cerebral blood flow and of
glucose utilization. Differences in size appear in different brain regions,
including nuclei in the hypothalamus related to sexual function, parts of
the corpus callosum that are larger in females, and a somewhat larger
language region in the female brain.
 Section 12-5 describes gonadal hormones’ effects on sexual
behavior. Section 15-5 recounts sex differences in thinking patterns.
Three lines of evidence, summarized by Elizabeth Hampson and
Doreen Kimura (2005), support the conclusion that sex-related cognitive
differences result from these anatomical brain differences and that these
cognitive differences also depend in part on the continuing circulation of
the sex hormones. The evidence:
1. Spatial and verbal tests given to females and males in many different
settings and cultures show that males tend to excel in spatial tasks and
females in verbal tasks.
2. Results of similar tests given to female participants in the course of
the menstrual cycle show fluctuations in these test scores with phases
of the cycle. During the phase in which the female sex hormones
estradiol (metabolized from estrogen) and progesterone are at their
lowest levels, women perform comparatively better on spatial tasks;
during the phase in which levels of these hormones are high, women
do comparatively better on verbal tasks.
3. Tests comparing premenopausal and postmenopausal women, women
in various stages of pregnancy, and females and males with varying
levels of circulating sex hormones all provide some evidence that
hormones affect cognitive function.
Sex hormone–related differences in cognitive function are not huge.
Performance scores between males and females overlap broadly. Yet
statistically, the differences are reliable. Similar influences of sex
hormones on behavior are found in other species. Berthold’s rooster
experiment described earlier shows the behavioral effects of testosterone.
Findings from many studies demonstrate that motor skills in female
humans and other animals improve at estrus, a time when progesterone
levels are high.

Anabolic–Androgenic Steroids
A class of synthetic hormones related to testosterone has both muscle-
building (anabolic) and masculinizing (androgenic) effects. Commonly
known simply as anabolic steroids, they were synthesized originally to
build body mass and enhance endurance. Russian weight lifters were the
first to use them, in 1952, to enhance performance and win international
competitions.
 anabolic steroid Class of synthetic hormones related to testosterone
that have both muscle-building (anabolic) and masculinizing
(androgenic) effects; also called anabolic–androgenic steroid.
Synthetic steroid use rapidly spread to other countries and sports,
eventually leading to a ban from track and field and then from many
other sports, enforced by drug testing. Testing policy has led to a cat-
and-mouse game in which new anabolic steroids and new ways of taking
them and masking them are devised to evade detection.
Today, the use of anabolic steroids is about equal among athletes and
nonathletes. More than 1 million people in the United States have used
anabolic steroids not only to enhance athletic performance but also to
enhance physique and appearance. Anabolic steroid use in high schools
may be as high as 7 percent for males and 3 percent for females.
The use of anabolic steroids carries health risks. Their administration
results in the body reducing its manufacture of testosterone, which in
turn reduces male fertility and spermatogenesis. Muscle bulk is increased
and so is aggression. Cardiovascular effects include increased risk of
heart attack and stroke. Liver and kidney function may be compromised,
and the risk of tumors may increase. Male-pattern baldness may be
enhanced. Females may have an enlarged clitoris, acne, increased body
hair, and a deepened voice.
Anabolic steroids have approved clinical uses. Testosterone
replacement is a treatment for hypogonadal males. It is also useful for
treating muscle loss subsequent to trauma and for the recovery of muscle
mass in malnourished people. In females, anabolic steroids are used to
treat endometriosis and fibrocystic disease of the breast.

Glucocorticoids and Stress

Stress is a term borrowed from engineering to describe a process in
which an agent exerts a force on an object. Applied to humans and other
animals, a stressor is a stimulus that challenges the body’s homeostasis
and triggers arousal. Stress responses, behavioral as well as
physiological, include both arousal and attempts to reduce stress. A
stress response can outlast a stress-inducing incident and may even occur
in the absence of an obvious stressor. Living with constant stress can be
debilitating.
Activating a Stress Response
Surprisingly, the body’s response is the same whether the stressor is
exciting, sad, or frightening. Robert Sapolsky (2004) uses the vivid
image of a hungry lion chasing down a zebra to illustrate the stress
response. The chase elicits divergent behavior in the two animals, but
their physiological responses are identical. The stress response begins
when the body is subjected to a stressor and especially when the brain
perceives a stressor and responds with arousal, directed from the brain by
the hypothalamus. The response consists of two separate sequences, one
fast and the other slow.
THE FAST RESPONSE Shown at left in Figure 6-19 , the sympathetic
division of the ANS is activated to prepare the body and its organs for
fight or flight. The parasympathetic division for rest and digest is turned
off. The sympathetic division stimulates the medulla on the interior of
the adrenal gland to release epinephrine. The epinephrine surge (often
called the adrenaline surge after epinephrine’s original name) prepares
the body for a sudden burst of activity. Among its many functions,
epinephrine stimulates cell metabolism, readying the body’s cells for
action.
THE SLOW RESPONSE As shown at right in Figure 6-19 , the slow response
is controlled by the steroid cortisol, a glucocorticoid released from the
outer layer (cortex) of the adrenal gland. Activating the cortisol pathway
takes anywhere from minutes to hours. Cortisol has wide-ranging
functions, which include turning off all bodily systems not immediately
required to deal with a stressor. For example, cortisol turns off insulin so
that the liver starts releasing glucose, thus temporarily increasing the
body’s energy supply. It also shuts down reproductive functions and
inhibits the production of growth hormone. In this way, it concentrates
the body’s energy on dealing with the stress.
 FIGURE 6-19 Activating a Stress Response Two pathways to
the adrenal gland control the body’s stress response. The fast-acting
pathway primes the body immediately for fight or flight. The slow-acting
pathway both mobilizes the body’s resources to confront a stressor and
repairs stress-related damage. CRH, corticotropin-releasing hormone;
ACTH, adrenocorticotropic hormone.

Ending a Stress Response

Normally, stress responses are brief. The body mobilizes its resources,
deals with the challenge physiologically and behaviorally, and shuts
down the stress response. Just as the brain is responsible for turning on
the stress reaction, it is also responsible for turning it off. Consider what
can happen if the stress response is not shut down:
• The body continues to mobilize energy at the cost of energy storage.
• Proteins are used up, resulting in muscle wasting and fatigue.
• Growth hormone is inhibited, so the body cannot grow.
• The gastrointestinal system remains shut down, reducing the intake and
processing of nutrients to replace used resources.
• Reproductive functions are inhibited.
• The immune system is suppressed, contributing to the possibility of
infection or disease.
Sapolsky (2005) argues that the hippocampus plays an important role
in turning off the stress response. The hippocampus contains a high
density of cortisol receptors, and it has axons that project to the
hypothalamus. Consequently, the hippocampus is well suited to detecting
cortisol in the blood and instructing the hypothalamus to reduce blood
cortisol levels.

FIGURE 6-20 Vicious Circle Unrelieved stress promotes excessive

release of cortisol, which damages hippocampal neurons. The damaged
neurons cannot detect cortisol and therefore cannot signal the adrenal
gland to stop producing it. The resulting feedback loop enhances cortisol
secretion, further damaging hippocampal neurons.

There may, however, be a more insidious relation between the

hippocampus and blood cortisol levels. Sapolsky observed wild-born
vervet monkeys that had become agricultural pests in Kenya and had
therefore been trapped and caged. He found that some monkeys sickened
and died of a syndrome that appeared to be related to stress. Those that
died seemed to have been subordinate animals housed with particularly
aggressive dominant monkeys. Autopsies showed high rates of gastric
ulcers, enlarged adrenal glands, and pronounced hippocampal
degeneration. The hippocampal damage may have been due to prolonged
high cortisol levels produced by the unremitting stress of being caged
with the aggressive monkeys.
Cortisol levels are usually regulated by the hippocampus, but if these
levels remain elevated because a stress-inducing situation continues,
cortisol eventually damages the hippocampus, reducing its size. The
damaged hippocampus is then unable to do its work of reducing the level
of cortisol. Thus, a vicious circle is set up in which the hippocampus
undergoes progressive degeneration and cortisol levels are not controlled
(Figure 6-20 ). Interestingly, other research with rats suggests that
following similar stress, the size of the amygdala is increased (Bourgin et
al., 2015).
Because stress response circuits in rats and monkeys are similar to
those in humans, it is possible that excessive stress in humans can lead to
similar brain changes. Because the hippocampus is thought to play a role
in memory, stress-induced hippocampal damage is postulated to result in
impaired memory. Because the amygdala is thought to play a role in
emotion, stress-induced changes are postulated to result in increased
emotional responses. This pattern of behavioral changes resembles
posttraumatic stress disorder. People with PTSD feel as if they are
reliving the trauma, and the accompanying physiological arousal
enhances their belief that danger is imminent.
PTSD, introduced in Section 5-4 in relation to sensitization, is
among the anxiety disorders detailed in Section 12-4 . Focus 16-1
and Section 16-4 consider treatments.
Research has not yet determined whether the cumulative effects of
stress damage the human hippocampus. For example, research on
women who were sexually abused in childhood and were diagnosed with
PTSD yields some reports of changes in memory or in hippocampal
volume, as measured with brain imaging techniques. Other studies report
no differences in abused and nonabused subjects (Landré et al., 2010).
The fact that such apparently similar studies can obtain different results
can be explained in several ways.
First, the amount of damage to the hippocampus that must occur to
produce a stress syndrome is not certain. Second, brain imaging
techniques may not be sensitive to subtle changes in hippocampal cell
function or to moderate cell loss. Third, wide individual and
environmental differences influence how people respond to stress.
Fourth, neonatal stress can influence hippocampal neurogenesis (Lajud
and Torner, 2015). The long-term consequence is a smaller hippocampus
and increased susceptibility to stress.
Finally, humans are long-lived and gather many life experiences that
complicate simple extrapolations from a single stressful event.
Nevertheless, Patrick McGowan and his coworkers (2009) report that the
density of glucocorticoid receptors in the hippocampus of people who
committed suicide after sexual abuse in childhood was lower than that of
both controls and suicide victims who had not been abused.
The decrease in receptors and in glucocorticoid mRNA suggests that
childhood abuse induces epigenetic changes in the expression of
glucocorticoid genes. The decrease in glucocorticoid receptors
presumably renders the hippocampus less able to depress stress
responses. The importance of the McGowan study is its suggestion of a
mechanism through which stress can influence hippocampal function
without necessarily being associated with a decrease in hippocampal
volume. This study further underscores the point that stress likely
produces many changes in many brain regions. It is unlikely that all have
been described or are understood (Clauss et al., 2015).
 6-5 REVIEW
Hormones
Before you continue, check your understanding.
1 . The hypothalamus produces ___________ that stimulate the
___________ to secrete ___________ into the circulatory system.
Hormone levels circulating in the bloodstream send feedback to the
___________.
2 . Hormones are classified chemically as ___________ or
___________.
3 . Broadly speaking, ___________ hormones regulate metabolic
balance; ___________ hormones regulate reproduction; and
___________ regulate stress.
4 . One class of synthetic hormones is ___________, which increase
___________ and have ___________ effects.
5 . The stress response has a fast-acting pathway mediated by the release
of ___________ and a slow-acting pathway mediated by the release of
___________.
6 . Describe the proposed relationship among stress, cortisol, and the
hippocampus.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
SUMMARY
6-1 Principles of Psychopharmacology
Psychoactive drugs—substances that alter mood, thought, or behavior—
produce their effects by acting on neuronal receptors or on chemical
processes in the nervous system, especially on neurotransmission at
synapses. Drugs act either as agonists to stimulate neuronal activity or as
antagonists to depress it. Psychopharmacology is the study of drug
effects on the brain and behavior.
Drugs are administered by mouth, by inhalation, by absorption
through the skin, rectally by suppository, and by injection. To reach a
nervous system target, a psychoactive drug must pass through numerous
barriers posed by digestion and dilution, the blood–brain barrier, and cell
membranes. Drugs are diluted by body fluids as they pass through
successive barriers, are metabolized in the body, and are excreted
through sweat glands and in feces, urine, breath, and breast milk.
A common misperception about psychoactive drugs is that they act
specifically and consistently, but learning also affects individual
responses to drugs. The body and brain may rapidly become tolerant of
(habituated to) many drugs, so the dose must increase to produce a
constant effect. Alternatively, people may become sensitized to a drug:
the same dose produces increasingly strong effects. These forms of
unconscious learning also contribute to a person’s behavior under a
drug’s influence.
 6-2 Grouping Psychoactive Drugs
Psychoactive drugs can be organized according to their major behavioral
effects into five groups: antianxiety agents and sedative-hypnotics,
antipsychotic agents, antidepressants and mood stabilizers, opioid
analgesics, and psychotropics. Each group, summarized in Table 6-1 on
page 181 , contains natural or synthetic drugs or both, and they may
produce their actions in different ways.
 6-3 Factors Influencing Individual Responses to
Drugs
A drug does not have a uniform action on every person. Physical
differences—in body weight, sex, age, or genetic background—influence
a given drug’s effects on a given person, as do behaviors, such as
learning, and cultural and environmental contexts.
The influence of drugs on behavior varies widely with the situation
and as a person learns drug-related behaviors. Behavioral myopia, for
example, can influence a person to focus primarily on prominent
environmental cues. These cues may encourage the person to act in
uncharacteristic ways.
Females are more sensitive to drugs than males are and may become
addicted more quickly than males to lower doses of drugs. The incidence
of female abuse of many kinds of drugs equals or exceeds male abuse of
those drugs.
 6-4 Explaining and Treating Drug Abuse
The neural mechanisms implicated in addiction are the same neural
systems responsible for wanting and liking more generally. So anyone is
likely to be a potential drug abuser. Addiction develops in a number of
stages as a result of repeated drug taking.
Initially, drug taking produces pleasure (liking), but with repeated use
the behavior becomes conditioned to associated objects, events, and
places. Eventually, the conditioned cues motivate the drug user to seek
them out (wanting), which leads to more drug taking. These subjective
experiences become associated with prominent cues, and drug seeking
promotes craving for the drug. As addiction proceeds, the subjective
experience of liking decreases while wanting increases.
Treatment varies with the drug. Whatever the treatment approach,
success likely depends on permanent lifestyle changes. Considering how
many people use tobacco, drink alcohol, use recreational drugs, or abuse
prescription drugs, to find someone who has not used a drug when it was
available is probably rare. But because of either genetic or epigenetic
influences, some people do seem particularly vulnerable to drug abuse
and addiction.
Excessive alcohol use can be associated with damage to the thalamus
and hypothalamus, but the damage is caused by poor nutrition rather than
the direct actions of alcohol. Cocaine can produce brain damage by
reducing blood flow or by bleeding into neural tissue. MDMA (Ecstasy)
use can result in the loss of fine axon collaterals of serotonergic neurons
and associated impairments in cognitive function.
Psychedelic drugs, such as marijuana and LSD, can be associated
with psychotic behavior. Whether this behavior is due to the drugs’ direct
effects or to the aggravation of preexisting conditions is not clear.
 6-5 Hormones
Steroid and peptide hormones produced by endocrine glands circulate in
the bloodstream to affect a wide variety of targets. Interacting to regulate
hormone levels is a hierarchy of sensory stimuli and cognitive activity in
the brain that stimulates the pituitary gland through the hypothalamus.
The pituitary stimulates or inhibits the endocrine glands, which send
feedback to the brain via other hormones.
Homeostatic hormones regulate the balance of sugars, proteins,
carbohydrates, salts, and other substances in the body. Gonadal
hormones regulate the physical features and behaviors associated with
sex characteristics and behaviors, reproduction, and parenting.
Glucocorticoids are steroid hormones that regulate the body’s ability to
cope with stress—with arousing and challenging situations.
The hippocampus plays an important role in ending the stress
response. Failure to turn stress responses off after a stressor has passed
can contribute to susceptibility to PTSD and other psychological and
physical diseases. Stress may activate epigenetic changes that modify the
expression of genes regulating hormonal responses to stress and may
produce brain changes persisting long after the stress-provoking incident
has passed.
Synthetic anabolic steroids, used by athletes and others alike, mimic
the effects of testosterone and so increase muscle bulk, stamina, and
aggression but can have deleterious side effects.
KEY TERMS
addiction, p. 193
agonist, p. 177
amphetamine, p. 189
anabolic steroid, p. 204
antagonist, p. 177
antianxiety agent, p. 182
attention-deficit/hyperactivity disorder (ADHD), p. 173
barbiturate, p. 182
behavioral myopia, p. 193
bipolar disorder, p. 187
competitive inhibitor, p. 187
cross-tolerance, p. 182
disinhibition theory, p. 191
dopamine hypothesis of schizophrenia, p. 184
endorphin, p. 187
fetal alcohol spectrum disorder (FASD), p. 182
glucocorticoid, p. 203
gonadal (sex) hormone, p. 203
homeostatic hormone, p. 201
major depression, p. 184
monoamine oxidase (MAO) inhibitor, p. 184
mood stabilizer, p. 187
opioid analgesic, p. 187
organizational hypothesis, p. 203
peptide hormone, p. 201
psychedelic drug, p. 189
psychoactive drug, p. 173
psychomotor activation, p. 193
psychopharmacology, p. 173
second-generation antidepressant, p. 184
selective serotonin reuptake inhibitor (SSRI), p. 184
steroid hormone, p. 201
substance abuse, p. 193
testosterone, p. 201
tolerance, p. 177
tricyclic antidepressant, p. 184
wanting-and-liking theory, p. 194
withdrawal symptom, p. 193

Visit Launch Pad to access the e-Book, videos,

Learning Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

How Do We Study the

Brain’s Structures and
Functions?
 Katherine Streeter

RESEARCH FOCUS 7-1 TUNING IN TO LANGUAGE

7-1 MEASURING AND MANIPULATING BRAIN AND
BEHAVIOR
LINKING NEUROANATOMY AND BEHAVIOR
EXPERIMENT 7-1 QUESTION: DO HIPPOCAMPAL NEURONS
CONTRIBUTE TO MEMORY FORMATION?
METHODS OF BEHAVIORAL NEUROSCIENCE
MANIPULATING BRAIN–BEHAVIOR INTERACTIONS
7-2 MEASURING THE BRAIN’S ELECTRICAL ACTIVITY
RECORDING ACTION POTENTIALS FROM SINGLE CELLS
EEG: RECORDING GRADED POTENTIALS FROM THOUSANDS
OF CELLS
MAPPING BRAIN FUNCTION WITH EVENT-RELATED
POTENTIALS
CLINICAL FOCUS 7-2 MILD HEAD INJURY AND DEPRESSION
MAGNETOENCEPHALOGRAPHY
7-3 ANATOMICAL IMAGING TECHNIQUES: CT AND MRI
7-4 FUNCTIONAL BRAIN IMAGING
FUNCTIONAL MAGNETIC RESONANCE IMAGING
OPTICAL TOMOGRAPHY
POSITRON EMISSION TOMOGRAPHY
7-5 CHEMICAL AND GENETIC MEASURES OF BRAIN AND
BEHAVIOR
MEASURING BRAIN CHEMISTRY
MEASURING GENES IN BRAIN AND BEHAVIOR
CLINICAL FOCUS 7-3 CANNABIS USE, PSYCHOSIS, AND
GENETICS
EPIGENETICS: MEASURING GENE EXPRESSION
7-6 COMPARING NEUROSCIENCE RESEARCH METHODS
 7-7 USING ANIMALS IN BRAIN–BEHAVIOR RESEARCH
BENEFITS OF ANIMAL MODELS OF DISEASE
ANIMAL WELFARE AND SCIENTIFIC EXPERIMENTATION
RESEARCH FOCUS 7-4 ATTENTION-DEFICIT/HYPERACTIVITY
DISORDER
RESEARCH FOCUS 7-1

Tuning In to Language
The continuing search to understand the organization and operation
of the human brain is driven largely by emerging technologies. Over
the past decade, neuroscience researchers have developed dramatic
new noninvasive ways to image the brain’s activity in people who
are awake. One technique, functional near-infrared spectroscopy
(fNIRS), gathers light transmitted through cortical tissue to image
oxygen consumption in the brain. NIRS, a form of optical
tomography, is detailed in Section 7-4 .
functional near-infrared spectroscopy (fNIRs) Noninvasive
technique that gathers light transmitted through cortical tissue to
image oxygen consumption; form of optical tomography.
fNIRS allows investigators to measure oxygen consumption as a
surrogate marker of neuronal activity in relatively select cortical
regions, even in newborn infants. In one study (May et al., 2011),
newborns (0–3 days old) wore a mesh cap containing the NIRS
apparatus, made up of optical fibers, as they listened to a familiar or
unfamiliar language.
 “Language and the newborn brain: does prenatal language experience shape
the neonate neural response to speech?” by L. May, K. Byers-Heinlein, J.
Gervain, and J.F. Werker, 2011. Frontiers in Psychology, 2, 1–9. Photo by
Krista Byers-Heinlein
Newborn with probes placed on the head.

When newborns listened to a familiar language, their brain

showed a general increase in oxygenated hemoglobin; when they
heard an unfamiliar language, oxygenated hemoglobin decreased
overall. But when the babies heard the same sentences played
backward, there was no difference in brain response to either
language.
The opposing responses to familiar and unfamiliar languages
mean that prenatal language experience shapes how the newborn
brain responds to familiar and unfamiliar tongues. This finding leads
to many questions. Among them: How does prenatal exposure to
language influence later language learning? Do children who are
exposed to multiple languages prenatally show better language
acquisition than those exposed to just one? How much prenatal
 language exposure is necessary, and do premature infants show the
same results as full-term babies?
Whatever the answers, this study shows that the prenatal brain is
tuned in to the language environment into which it will be born.

“Language and the newborn brain: does prenatal language experience shape
the neonate neural response to speech?” by L. May, K. Byers-Heinlein, J.
Gervain, and J.F. Werker, 2011. Frontiers in Psychology, 2, 1–9. Image by
Judit Gervain.
Probe configurations overlaid on schematics of an infant’s left and
right hemispheres. Red dots indicate light-emitting fibers; blue dots
indicate light detectors. The light detectors in the outer strips in both
hemispheres sit over regions specialized for language in adults.

The simple, noninvasive nature of fNIRS likely will

yield new insights not only into brain development but also into adult
brain function. Over the coming decades, our understanding of the brain–
behavior relationship will continue to be driven in large part by new and
better technologies and by cleverly exploiting existing ones.
To understand how far neuroscience research methods have
progressed, imagine that it is the year 1800. You are a neurologist
interested in studying how the brain works. The challenge is how to
begin. The two most obvious choices are to dissect the brains of dead
people and other animals or to study people who have sustained a brain
injury. Indeed, this was how the relationship between brain and behavior
was studied well into the twentieth century.
Techniques for studying the brain’s physiological processes emerged
in the years between World War I and World War II. One breakthrough
was the electroencephalograph (EEG), developed for humans by Hans
Berger in the 1930s. Advances in understanding genetics and the
analysis of behavior in the early 1950s set the stage for phenomenal
advances in neuroscience knowledge. Scientists recognize that new
technologies allow for novel insights, lead to more questions, and can
dramatically advance their discipline. A large number of Nobel Prizes
have been awarded for the development and implementation of new
technologies.
Section 4-1 reviews how the EEG enabled investigators to explain
electrical activity in the nervous system.
Today, brain–behavior analyses combine the efforts of anatomists and
geneticists, psychologists and physiologists, chemists and physicists,
endocrinologists and neurologists, pharmacologists and psychiatrists,
engineers and biologists. For the aspiring brain researcher in the twenty-
first century, the range of available research methods is breathtaking.
We begin this chapter by reviewing how investigators measure
behavior in both human and nonhuman subjects and how neuroscientists
can manipulate behavior by perturbing the brain. We then consider
electrical techniques, including the EEG, for recording brain activity;
noninvasive procedures, such as fNIRS, that image the brain; and
chemical and genetic methods for measuring brain and behavior. After
comparing these methods at the chapter’s end, we review some issues
surrounding the use of nonhuman animals in research.
 Measuring and Manipulating Brain
7-1

and Behavior
During a lecture at a meeting of the Anthropological Society of Paris in
1861, Ernest Auburtin, a French physician, argued that language
functions are located in the brain’s frontal lobes. Five days later a fellow
French physician, Paul Broca, observed a brain-injured patient who had
lost his speech and was able to say only “tan” and utter a swear word.
The patient soon died. Broca and Auburtin examined the man’s brain and
found the focus of his injury in the left frontal lobe.
By 1863 Broca had collected eight similar cases and concluded that
speech is located in the third frontal convolution of the left frontal lobe—
a region now called Broca’s area. Broca’s findings attracted others to
study brain–behavior relationships in patients. The field that developed is
what we now call neuropsychology, the study of the relations between
brain function and behavior with a particular emphasis on humans.
Today, measuring brain and behavior increasingly includes noninvasive
imaging, complex neuroanatomical measurement, and sophisticated
behavioral analyses.
neuropsychology Study of the relations between brain function and
behavior, especially in humans.
Section 10-4 explores the anatomy of language and music and
describes Broca’s contributions.

Linking Neuroanatomy and Behavior

At the beginning of the twentieth century, neuroanatomy’s primary tools
were histological: brains were sectioned postmortem and the tissue
(histo - in Greek) stained with various dyes. As shown in Figure 7-1 ,
staining sections of brain tissue can identify cell bodies in the brain
viewed with a light microscope (A), and selectively staining individual
neurons reveals their complete structure (B). An electron microscope (C)
makes it possible to view synapses in detail.
By 1905, light microscopic techniques allowed researchers such as
Korbinian Brodmann to divide the cerebral cortex into many distinct
zones based on the characteristics of neurons in those zones.
Investigators presumed that cortical zones had specific functions. By the
dawn of the twenty-first century, dozens of techniques had developed for
labeling neurons and their connections, as well as glial cells.
Contemporary techniques allow researchers to identify molecular,
neurochemical, and morphological (structural) differences among
neuronal types and ultimately to relate these characteristics to behavior.
One fast-developing technique, shown in Figure 7-1 D, uses a
multiphoton microscope that makes it possible to image living brain
tissue in three dimensions.
Compare Brodmann’s map of the cortex, based on staining, shown
in Figure 2-23 .
Connections between anatomy and behavior can be seen in studies of
animals trained on various types of learning tasks, such as spatial mazes.
Such learning can be correlated with a variety of neuronanatomical
changes, such as modifications in the synaptic organization of cells in
specific cortical regions—the visual cortex in animals trained in visually
guided mazes is one example—or in the number of newly generated cells
that survive in the hippocampus. The hippocampus is necessary, in
mammals, for remembering the context in which we encounter
information.
(A) Light microscope, low magnification
 Bryan Kolb
Bryan Kolb
Douglas Bray, University of Lethbridge
N. Kasthuri and JW Lichtman, Harvard University

(B) Light microscope, high magnification

(C) Electron microscope
 (D) Multiphoton microscope
FIGURE 7-1 Staining Cerebral Neurons Viewed through a light
microscope, (A) Nissl-stained section of parietal cortex shows all cell
bodies but no cell processes (axons and dendrites). (B) At higher
magnification, an individual Golgi-stained pyramidal cell from the parietal
cortex is visible. The cell body (dark triangular shape at center) and spiny
dendrites (A and B) are visible in detail at right. (C) The view through an
electron microscope shows neuronal synapses in detail. (D) Multiple
images from a multiphoton microscope, merged to generate a three-
dimensional image of living tissue.

Although changes in synaptic organization or cell survival have not

yet been proved to be the basis of the new learning, experimental
evidence reveals that preventing the growth of new hippocampal neurons
leads to memory deficits. To test the idea that hippocampal neurons
contribute to memory formation, researchers tested healthy rats and
ADX rats—rats with adrenal glands removed, which eliminates the
hormone corticosterone. Without corticosterone, neurons in the
hippocampus die.
 Corticosterone, a steroid hormone secreted in times of stress, is
important in protein and carbohydrate metabolism (see Section 6-5
).
Procedure 1 in Experiment 7-1 contrasts the appearance of a healthy
rat hippocampus (left) and neuronal degeneration in an ADX rat after
surgery (right). The behavior of healthy and ADX rats was studied in the
object–context mismatch task diagrammed in Procedure 2. During the
training phase, the rats were placed in two distinct contexts, A and B, for
10 minutes on each of 2 days. Each context contained a different type of
object. On the test day, the rats were placed in either context A or context
B but with two different objects, one from that context and a second
from the other context.
As noted in the Results section of the experiment, when healthy rats
encounter objects in the correct context, they spend little time
investigating because the objects are familiar. If, however, they
encounter an object in the wrong context, they are curious and spend
about three-quarters of their time investigating, essentially treating the
mismatched object as new. But the ADX rats with hippocampal cell loss
treated the mismatched and in-context objects the same, spending about
half of their investigation time with each object.
 EXPERIMENT 7-1

Question: Do hippocampal neurons contribute to memory

formation?
Procedure 1
Rat hippocampus before (left) and after (right) surgical removal of the
adrenal glands. Arrows point to neuronal degeneration resulting from a
lack of corticosterone.

Spanswick S.C., Sutherland R.J. (2010). Object-context specific memory deficits

associated with loss of hippocampal granule cells after adrenalectomy in rats.
Learning and Memory, 17:241–245.
Healthy rat hippocampus

ADX-induced hippocampal degeneration

Procedure 2
The behavior of healthy and ADX rats was studied in an object–
context mismatch task in which two distinct contexts each contained a
different type of object.

Results
Healthy rats investigate the mismatch object more than the object that
is in context, but the ADX rats performed at chance. The rats in
another ADX group were given treatments known to increase neuron
generation in the hippocampus (enriched housing and exercise in
running wheels). The rats with hippocampal regeneration were not
impaired at the mismatch task.
The confocal photo at right shows a rat hippocampus. A specific
stain was used to identify new neurons, which appear yellow.
 Courtesy Bryan Kolb

Conclusion: Hippocampal neurons are necessary for the contextual

learning.
Information from S. Spanswick & R. J. Sutherland (2010). Object/context-specific
memory deficits associated with loss of hippocampal granule cells after
adrenalectomy in rats. Learning and Memory, 17, 241–245. Information from S.
Spanswick, H. Lethman, & R. J. Sutherland (2011). A novel animal model of
hippocampal cognitive deficits, slow neurodegeneration, and neuroregeneration.
Journal of Biomedicine and Biotechnology. Article ID 527201.

Another group of ADX rats given treatment known to increase neuron

generation in the hippocampus—enriched housing and exercise in
running wheels—was unimpaired at the context mismatch task.
Experiment 7-1 concludes that cellular changes in the hippocampus and
behavioral changes are closely linked: hippocampal neurons are
necessary for contextual learning.

Methods of Behavioral Neuroscience

The brain’s ultimate function is to produce behavior (movement). It
follows that brain dysfunction should alter behavior in some way. The
study of brain–behavior relationships in both humans and laboratory
animals is behavioral neuroscience, the study of the biological bases of
behavior.
behavioral neuroscience Study of the biological bases of behavior
in humans and other animals.
A major challenge to behavioral neuroscientists is developing
methods for studying both typical and atypical behavior. Measuring
behavior in humans and laboratory animals differs in large part because
humans speak: investigators can ask them about their symptoms. It is
also possible to use both paper-and-pencil and computer-based tests to
identify specific symptoms in people.
Measuring behavior in laboratory animals is more complex.
Researchers must learn to speak “ratese” with rat subjects or
“monkeyese” with monkeys. In short, researchers must develop ways to
enable the animals to reveal their symptoms. The development of the
fields of animal learning and ethology, the objective study of animal
behavior, especially under natural conditions, provided the basis for
modern behavioral neuroscience (see Whishaw & Kolb, 2005). To
illustrate the logic of behavioral neuroscience, we describe some
measurement tools used with humans and some used with rats.
Table 7-2 on page 239 summarizes selected brain measurement
techniques, their goals, and examples.
Neuropsychological Testing of Humans
The brain has exquisite control of an amazing array of functions ranging
from movement control and sensory perception to memory, emotion, and
language. As a consequence, any analysis of behavior must be tailored to
the particular function(s) under investigation. Consider the analysis of
memory.
People with damage to the temporal lobes often complain of memory
disturbance. But memory is not a single function; rather, multiple as well
as independent memory systems exist. We have memory for events,
colors, names, places, and motor skills, among other categories, and each
must be measured separately. It would be rare indeed for someone to be
impaired in all forms of memory. Neuropsychological tests of three
distinct forms of memory are illustrated in Figure 7-2 .
 Sections 14-1 through 14-3 analyze the varied categories of
memory.

The examiner taps out a sequence of blocks.

The block numbers are visible on the examiner’s side of the board but
not on the participant’s side.

Examiner’s view
(A) Corsi block-tapping test
(B) Mirror-drawing task
 (C) Test of recent memory

FIGURE 7-2 Neuropsychological Tests of Memory

The Corsi block-tapping test shown in Figure 7-2 A requires
participants to observe an experimenter tap a sequence of blocks—
blocks 4, 6, 1, 8, 3, for instance. The task is to repeat the sequence
correctly. The subject does not see numbers on the blocks but rather must
remember the location of the tapped blocks.
The Corsi test provides a measure of short-term recall of spatial
position, an ability we can call block span. The test can be made more
difficult by determining the maximum block span of an individual (say, 6
blocks) and then adding one (span + 1 ). By definition, the participant
will fail on the first presentation, but given the span + 1 repeatedly, will
eventually learn it.
 Span + 1 identifies a different form of memory from block span.
Different types of neurological dysfunction interfere differentially with
tasks that superficially appear quite similar. Block span measures the
short-term recall of information, whereas the span + 1 task reflects the
learning and longer-term memory storage of information.
The mirror-drawing task (Figure 7-2 B) requires a person to trace a
pathway, such as a star, by looking in a mirror. This motor task initially
proves difficult because our movements appear backward in the mirror.
With practice, participants learn how to accomplish the task accurately,
and they show considerable recall of the skill when retested days later.
Curiously, patients and subjects with certain types of memory problems
have no recollection of learning the task on the previous day but
nevertheless perform it flawlessly.
In this book, we refer to healthy human volunteers in research
studies as participants and to people or animals that have a brain or
behavioral impairment as patients or subjects.
In the recency memory task (Figure 7-2C ), participants are shown a
long series of cards, each bearing two stimulus items that are words or
pictures. On some trials a question mark appears between the items. The
subjects’ task is to indicate whether they have seen the items before and
if so, which item they saw most recently. People may be able to recall
that they have seen items before but be unable to recall which was most
recent. Conversely, they may not be able to identify the items as being
familiar, but when forced to choose the most recent one, they can
identify it correctly.
The latter, counterintuitive result reflects the need for behavioral
researchers to develop ingenious ways of identifying memory abilities. It
is not enough simply to ask people to recall information verbally,
although this too measures a form of memory.
Focus 15-4 compares effects of injuries to particular brain regions
on performance of particular neuropsychological tasks.
Behavioral Analysis of Rats
Over the past century, psychologists interested in the neural basis of
memory have devised a vast array of mazes and other tests and tasks to
investigate different forms of memory in laboratory animals. Figure 7-3
illustrates three tests based on a task devised by Richard Morris in 1980.
Researchers place rats in a large swimming pool where an escape
platform lies just below the water surface, invisible to the rats.
In one version of the task, place learning, the rat must find the
platform from any starting location in the pool (Figure 7-3 A). The only
cues available are outside the pool, so the rat must learn the relation
between several cues in the room and the platform’s location. In a second
version of the task, matching-to-place learning, the rat has already
learned that a platform always lies somewhere in the pool but is moved
to a different location every day. The rat is released and searches for the
platform (Figure 7-3 B). Once the rat finds the platform, the animal is
removed from the pool and after a brief delay (such as 10 seconds) is
released again. The rat’s task is to swim directly to the platform.
The challenge for the rat in the matching-to-place test is to develop a
strategy for finding the platform consistently: it is always in the same
location on each trial each day, but each new day brings a new location.
In the landmark version of the task, the platform’s location is identified
by a cue on the pool wall (Figure 7-3C ). The platform moves on every
trial, but the relation to the cue is constant. In this task the brain is
learning that the distant cues outside the pool are irrelevant; only the
local cue is relevant. Rats with different neurological perturbations are
selectively impaired in the three versions of the swimming pool task.
Another type of behavioral analysis in rats is related to movement. A
major problem facing people with stroke is a deficit in controlling hand
and limb movements. The prevalence of stroke has prompted
considerable interest in devising ways to analyze such motor behaviors
for the purpose of testing new therapies for facilitating recovery. Ian
Whishaw (Whishaw & Kolb, 2005) has devised both novel tasks and
novel scoring methods to measure the fine details of skilled reaching
movements in rats.
A rat placed in the pool at various starting locations must learn to find
a hidden platform. The rat can do this only by considering the
configuration of visual cues in the room—windows, wall decorations,
potted plants, and the like.
(A) Place-learning task
 The rat is again put into the pool at random locations, but
the hidden platform is in a new location on each test day.
The animal must learn that the location where it finds the
platform on the first trial each day is its location for all
trials on that day.
(B) Matching-to-place task

The rat must ignore the room cues and learn that only the cue on the
wall of the pool signals the location of the platform. The platform and
cue are moved on each trial, so the animal is penalized for using room
cues to try to solve the problem.
 (C) Landmark-learning task

FIGURE 7-3 Swimming Pool Tasks General arrangement of the

swimming pool used in three visuospatial learning tasks for rats. Red lines
in parts A, B, and C mark the rat’s swimming path on each trial (T). (A)
Information from R. G. M. Morris (1981). Spatial localization does not
require the presence of local cues. Learning and Motivation, 12, 239–260.
(B) Information from I. Q. Whishaw (1989). Dissociating performance and
learning deficits in spatial navigation tasks in rats subjected to cholinergic
muscarinic blockade. Brain Research Bulletin, 23, 347–358. (C)
Information from Kolb, B., and Walkey, J. (1987). Behavioural and
anatomical studies of the posterior parietal cortex of the rat. Behavioural
Brain Research, 23, 127–145.

In one test, rats are trained to reach through a slot to obtain a piece of
sweet food. The movements, which are remarkably similar to the
movements people make in a similar task, can be broken down into
segments. Investigators can score the segments separately, as they are
differentially affected by different types of neurological perturbation.
Experiments in Chapter 14 demonstrate fear conditioning in rats,
plasticity in the monkey’s motor cortex, and neuronal effects of
amphetamine sensitization in rats.
 The photo series in Figure 7-4 details how a rat orients its body to the
slot (A), puts its hand through the slot (B), rotates the hand horizontally
to grasp the food (C), then rotates the hand vertically and withdraws it to
obtain the food (D). Contrary to reports common in neurology textbooks,
primates are not the only animals to make fine digit movements, but
because the rat’s hand is small and moves so quickly, digit dexterity can
be seen in rodents only with use of high-speed videography.

Bryan Kolb
(D)
(A)
(B)
(C)
 FIGURE 7-4 Skilled Reaching in Rats Movement series
displayed by rats trained to reach through a narrow vertical slot to obtain
sweet food: (A) aim the hand, (B) reach over the food, (C) grasp the food,
(D) withdraw and move food to the mouth.

Manipulating Brain–Behavior Interactions

One strategy for studying brain–behavior relationships is to manipulate
some aspect of brain function and see how behavior changes.
Investigators do so to develop hypotheses about how the brain affects
behavior, then to test those hypotheses.
Neuroscientists hypothesize about the functions of brain regions by
studying how removing or inhibiting them affects behavior. Broca
studied patients with naturally occurring injuries and made inferences
about language organization. Similarly, Parkinson patients have motor
disturbances and associated cell death in the substantia nigra (Figure 7-5
). It is a small step experimentally to injure specific brain regions in
laboratory animals, then study their behavior. Such studies tell
investigators not only about the injured region’s function but also what
the remaining brain can do in the absence of the injured region.
Neuroscientists also study brain region functions to form hypotheses, for
example, on how exciting a region affects behavior. Certain drugs and
stimulation techniques that increase brain region activity result in
behavioral change.
Focus features 5-2, 5-3, and 5-4 detail many aspects of Parkinson
disease.
A second reason to manipulate the brain is to develop animal models
of neurological and psychiatric disorders. The general presumption in
neurology and psychiatry is that it ought to be possible to restore at least
some healthy functioning by pharmacological, behavioral, or other
interventions. A major hurdle for developing such treatments is that, like
most new medical treatments, they must be tested in nonhuman subjects
first. (In Section 7-7 , we take up scientific and ethical issues
surrounding the use of animals in research.)
Table 7-1 on page 238 summarizes selected brain manipulation
techniques, their goals, and examples.
For brain disorders, researchers must develop models of diseases
before they can be treated. Consider dementia, a progressive memory
impairment that appears to be related to neuronal death in specific brain
regions. The goal for treatment is to reverse or prevent cell death, but
developing effective treatments requires an animal model that mimics
dementia.
Brains can be manipulated in various ways, the precise manner
depending on the specific research question being asked. Researchers
can manipulate the whole animal by exposing it to differing diets, social
interactions, exercise, sensory stimulation, and a host of other
experiences. For brain manipulation, the principal direct techniques are
to inactivate the brain via lesion or with drugs or to activate it with
electrical stimulation, drugs, or light.
 FIGURE 7-5 Pathology in Parkinson Disease A variety of
motor disturbances appear when enough dopamine-producing cells in the
substantia nigra die. Information from healthguide.howstuffworks.com/substantia-nigra-
and-parkinsons-disease-picture.htm

Brain Lesions
The first—and the simplest—technique used was to ablate (remove or
destroy) tissue. Beginning in the 1920s, Karl Lashley, a pioneer of
neuroscience research, used ablation, and for the next 30 years he tried
to find the site of memory in the brain. He trained monkeys and rats on
various mazes and motor tasks, then removed bits of cerebral cortex with
the goal of producing amnesia for specific memories.
To his chagrin, Lashley failed in his quest. He observed instead that
memory loss was related to the amount of tissue he removed. The only
conclusion Lashley could reach was that memory is distributed
throughout the brain and not located in any single place. Subsequent
research strongly indicates that specific brain functions and associated
memories are indeed localized to specific brain regions. Ironically, just
as Lashley was retiring, William Scoville and Brenda Milner (1957)
described a patient from whose brain Scoville had removed both
hippocampi as a treatment for epilepsy. The surgery rendered this patient
amnesic. During his ablation research, Lashley had never removed the
hippocampi because he had no reason to believe the structures had any
role in memory. And because the hippocampus is not accessible on the
brain’s surface, other techniques had to be developed before subcortical
lesions could be used.
Scoville’s patient, H. M., profiled in Section 14-2 , became the
most-studied case in neuroscience.
The solution to accessing subcortical regions is to use a stereotaxic
apparatus, a device that permits a researcher or a neurosurgeon to target
a specific part of the brain for ablation, as shown in Figure 7-6 . The
head is held in a fixed position, and because the location of brain
structures is fixed in relation to the junction of the skull bones, it is
possible to visualize a three-dimensional brain map.
stereotaxic apparatus Surgical instrument that permits the
researcher to target a specific part of the brain.
Rostral–caudal (front to back) measurements, corresponding to the x -
axis in Figure 7-6 , are made relative to the junction of the frontal and
parietal bones (the bregma ). Dorsal–ventral (top to bottom)
measurements, the y -axis, are made relative to the surface of the brain.
Medial–lateral measurements, the z -axis, are made relative to the
midline junction of the cranial bones. Atlases of the brains of humans
and laboratory animals have been constructed from postmortem tissue so
that the precise location of any structure can be specified in three-
dimensional space.
Review the brain’s anatomical locations and orientations in The
Basics, in Section 2-1 . The brain atlas in Figure 8-14 tracks cortical
thickness over time.
Consider the substantia nigra. To ablate this region to induce a rat to
display symptoms of Parkinson disease, the structure and its three-
dimensional location in the brain atlas is located. A small hole is then
drilled in the skull, as shown in Figure 7-6 , and an electrode lowered to
the substantia nigra. If a current is passed through the electrode, the
tissue in the region of the electrode tip is killed, producing an electrolytic
lesion.

FIGURE 7-6 Stereotaxic Apparatus This instrument allows the

precise positioning of electrodes for lesioning or for stimulating brain
regions.

A problem with electrolytic lesions: not only are the neurons of the
targeted tissue killed but so are any nerve fibers passing through the
region (in this case, substantia nigra). One solution is to lower a narrow
metal tube (a cannula) instead of an electrode, infuse a neuron-killing
chemical, and thus produce a neurotoxic lesion. (Figure 7-22 diagrams
this procedure.) A selective toxin can be injected that kills only neurons,
sometimes only certain types of neurons, and spares the fibers.
To make a rat parkinsonian, a toxin can be injected that is selectively
taken up by dopaminergic neurons; this leads to a condition that mimics
human Parkinson pathology. Animals with such neurotoxic lesions have
a variety of motor symptoms including hypokinesia (slowness or
absence of movement), short footsteps, and tremor. Drugs such as L -
dopa, an agonist that enhances dopamine production, and atropine, an
antagonist that blocks acetylcholine production, relieve these symptoms
in Parkinson patients. Ian Whishaw and his colleagues (Schallert et al.,
1978) thus were able to selectively lesion the substantia nigra in rats to
produce a behavioral model of Parkinson disease.
hypokinesia Slowness or absence of movement.
The invasive techniques described so far result in permanent brain
damage. With time, the research subject will show compensation, the
neuroplastic ability to modify behavior from that used prior to the
damage. To avoid compensation following permanent lesions,
researchers have also developed temporary and reversible lesion
techniques such as regional cooling, which prevents synaptic
transmission. A hollow metal coil is placed next to a neural structure;
then chilled fluid is passed through the coil, cooling the brain structure to
about 18°C (Lomber & Payne, 1996). When the chilled fluid is removed
from the coil, the brain structure quickly warms, and synaptic
transmission is restored. Another technique involves local administration
of a GABA agonist, which increases local inhibition and in turn prevents
the brain structure from communicating with other structures.
Degradation of the GABA agonist reverses the local inhibition and
restores function.
compensation Following brain damage, neuroplastic ability to
modify behavior from that used prior to the damage.
 Ian Whishaw
Shuffling gait of a parkinsonian rat, captured in prints left by its ink-stained
hind feet.

Brain Stimulation
The brain operates on both electrical and chemical energy, so it is
possible to selectively turn brain regions on or off by using electrical or
chemical stimulation. Wilder Penfield, in the mid-twentieth century, was
the first to use electrical stimulation directly on the human cerebral
cortex during neurosurgery. Later researchers used stereotaxic
instruments to place an electrode or a cannula in specific brain locations.
The objective: enhancing or blocking neuronal activity and observing the
behavioral effects.
Read more about Penfield’s dramatic discoveries in Sections 10-4
and 11-2 .
Perhaps the most dramatic research example comes from stimulating
specific regions of the hypothalamus. Rats with electrodes placed in the
lateral hypothalamus will eat whenever the stimulation is turned on. If
the animals have the opportunity to press a bar that briefly turns on the
current, they quickly learn to press the bar to obtain the current, a
behavior known as electrical self-stimulation. It appears that the
stimulation is affecting a neural circuit that involves both eating and
pleasure.
Figure 12-12 diagrams hypothalamus anatomy. Section 12-3 details
its role in motivated and emotional behavior.
Brain stimulation can also be used as a therapy. When the intact
cortex adjacent to cortex injured by a stroke is stimulated electrically, for
example, it leads to improvement in motor behaviors such as those
illustrated in Figure 7-4 . Cam Teskey and his colleagues (Brown et al.,
2011) successfully restored motor deficits in a rat model of Parkinson
disease by electrically stimulating a specific brain nucleus.
Deep-brain stimulation (DBS) is a neurosurgical technique.
Electrodes implanted in the brain stimulate a targeted area with a low-
voltage electrical current to facilitate behavior. DBS to subcortical
structures—for example, the globus pallidus in the basal ganglia of
Parkinson patients—makes movements smoother. Medications can often
be reduced dramatically. DBS using several neural targets is an approved
treatment for obsessive-compulsive disorder. Experimental trials are
underway to identify the brain regions optimal for DBS to be used as a
treatment for intractable psychiatric disorders such as major depression
(Schlaepfer et al., 2013), schizophrenia, and possibly for epilepsy; also
for stimulating recovery from TBI.
deep-brain stimulation (DBs) Neurosurgical technique: electrodes
implanted in the brain stimulate a targeted area with a low-voltage
electrical current to produce or facilitate behavior.
View DBS in place in Figure 1-6 .
(A)
 Marcello Massimini/University of Milan.

Composite MRI and PE T scan from Dr. Tomáš Paus, Rotman Research Institute,
Baycrest Centre for Geriatric Care
(B)
FIGURE 7-7 Transcranial Magnetic Stimulation (A) In
clinical therapy for depression, TMS influences neural activity in a
localized region. (B) Composite photo shows how TMS works.

Electrical stimulation of the brain is invasive: holes must be drilled in

the skull and an electrode lowered into the brain. Researchers have taken
advantage of the relation between magnetism and electricity to develop a
noninvasive technique, transcranial magnetic stimulation (TMS). A
small wire coil is placed adjacent to the skull, as illustrated in Figure 7-7
A . A high-voltage current pulsed through the coil produces a rapid
increase and subsequent decrease in the magnetic field around the coil.
The magnetic field easily passes through the skull and causes a
population of neurons in the cerebral cortex to depolarize and fire
(Figure 7-7 B).
transcranial magnetic stimulation (TMS) Procedure in which a
magnetic coil is placed over the skull to stimulate the underlying
brain; used either to induce behavior or to disrupt ongoing behavior.
If the motor cortex is stimulated, movement is evoked, or if a
movement is in progress, it is disrupted. Similarly, if the visual cortex is
stimulated, the participant sees dots of light (phosphenes ). The effects of
brief pulses of TMS do not outlive the stimulation, but repetitive TMS
(rTMS), or continuous stimulation for up to several minutes, produces
more long-lasting effects. TMS and rTMS can be used to study brain–
behavior relationships in healthy participants, and rTMS has been tested
as a potential treatment for a variety of behavioral disorders. A growing
body of research also supports its antidepressant actions.
Research Focus 16-2 describes use of rTMS to treat depression and
other behaviorral disorders.
Drug Manipulations
Brain activity can also be stimulated by administration of drugs that pass
into the bloodstream and eventually enter the brain or, through an
indwelling cannula (illustrated in Figure 7-22 ), that allows direct
application of them to specific brain structures. Drugs can influence the
activity of specific neurons in specific brain regions. For example, the
drug haloperidol, used to treat schizophrenia, reduces dopaminergic
neuron function and makes healthy rats dopey and inactive (hypokinetic
).
In contrast, drugs that increase dopaminergic activity, such as
amphetamine, produce hyperkinetic rats —rats that are hyperactive. The
advantage of administering drugs is that their effects wear off in time as
the drugs are metabolized. It thus is possible to study drug effects on
learned behaviors, such as skilled reaching (see Figure 7-4 ), and then to
reexamine the behavior after the drug effect wears off.
 Claudia Gonzalez and her colleagues (2006) administered nicotine to
rats as they learned a skilled reaching task, then studied their later
acquisition of a new skilled reaching task. The researchers found that the
earlier nicotine-enhanced motor learning impaired the later motor
learning. This finding surprised the investigators, but it now appears that
repeated exposure to psychomotor stimulants such as amphetamine,
cocaine, and nicotine can produce long-term effects on the brain’s later
plasticity, its ability to change in response to experience, including
learning specific tasks.
Optogenetics and Chemogenetics
Within the span of a decade, synthetic biology, the design and
construction of biological devices, systems, and machines not found in
nature, has transformed how neuroscientists manipulate brain cells.
Techniques include inserting a genetic sequence into the genome of a
living organism. The transgenic technique of optogenetics, for example,
combines genetics and light to control targeted cells in living tissue. A
sequence that codes for a light-sensitive protein associated with an ion
channel enables investigators to use light to change the shape
(conformation) of the channel.
synthetic biology Design and construction of biological devices,
systems, and machines not found in nature.
optogenetics Transgenic technique that combines genetics and light
to control targeted cells in living tissue.
Excitation
Inhibition
Lighting Up Neurons Optogenetics allows precise temporal control of cell
firing and is rapidly reversible. Specific wavelengths activate light-sensitive proteins
expressed in neurons. At bottom left, when blue light illuminates a cell in which ChR2
has been incorporated, its firing rate increases dramatically. At right, when green-yellow
light illuminates a cell in which NpHR is incorporated, its firing rate decreases
dramatically. See more at https://www.youtube.com/watch?v=I64X7vHSHOE .
 Optogenetics is based on the discovery that light can activate certain
proteins that occur naturally and have been inserted into cells of model
organisms. For example, opsins, proteins derived from microorganisms,
combine a light-sensitive domain with an ion channel. The first opsin
used for the optogenetic technique was channelrhodopsin-2 (ChR2).
When ChR2 is expressed in neurons and exposed to blue light, the ion
channel opens and immediately depolarizes the neuron, causing
excitation. In contrast, stimulation of halorhodopsin (NpHR) with a
green-yellow light activates a chloride pump, hyperpolarizing the neuron
and causing inhibition. A fiber-optic light can be delivered to selective
brain regions such that all genetically modified neurons exposed to the
light respond immediately (Haubensak et al., 2010).
Optogenetics has tremendous potential as a research tool.
Investigators can insert light-sensitive proteins into specific neuron
types, such as pyramidal cells, and use light to selectively activate a
single cell type. Researchers hail optogenetics for its high spatial and
temporal (time) resolution. Ion channels can be placed into specific cell
lines and turned on and off on millisecond time scales. Optogenetics also
finds application in behavioral studies. Within the limbic system, for
example, the amygdala is a key structure in generating fear in animals. If
it is targeted with opsins then exposed to an inhibitory light, rats
immediately show no fear and wander about in a novel open space. As
soon as the light is turned off, they scamper back to a safe hiding place.
Figure 2-25 diagrams the limbic structures.
In the transgenic technique, chemogenetics, the inserted synthetic
genetic sequence codes for a G protein–coupled receptor engineered to
respond exclusively to a synthetic small-molecule “designer drug.”
Chemogenetics is best known by the acronym DREADD (designer
receptor exclusively activated by designer drugs). Its principle advantage
is that the drug will activate only the genetically modified receptors, and
the receptors will be activated only by the designer drug, not by
endogenous molecules (Wess et al., 2013). Thus, specificity is high, but
temporal resolution is much lower than with optogenetics because
receptors are activated by drugs rather than by light.
chemogenetics Transgenic technique that combines genetics and
synthetic drugs to activate targeted cells in living tissue.
DREADD does not employ the sort of designer drug that may come
to mind. Rather than synthetic versions of controlled substances
(e.g., heroin), these synthetic drugs interact with a synthetic
receptor.
 7-1 REVIEW
Measuring and Manipulating Brain and Behavior
Before you continue, check your understanding.
1 . Behavioral neuroscience, the study of relations between ___________
and ___________, employs memory tests such as ___________ in
nonhuman animals such as rats.
2 . Anatomical studies rely on techniques such as ___________ tissue
postmortem or visualizing living tissue using a ___________.
3 . Methods developed to manipulate the brain include ___________,
___________, ___________, and ___________.
4 . Outline the various brain stimulation methods that either activate or
inhibit neural activity.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Measuring the Brain’s Electrical
7-2

Activity
The brain is always electrically active, even when we sleep. Electrical
measures of brain activity are important for studying brain function, for
medical diagnosis, and for monitoring the effectiveness of therapies used
to treat brain disorders. The four major techniques for tracking the
brain’s electrical activity are single-cell recording,
electroencephalography (EEG), event-related potentials (ERPs), and
magnetoencephalography (MEG).
In part, these techniques are used to record electrical activity from
different parts of neurons. The electrical behavior of cell bodies and
dendrites, which give rise to graded potentials, tends to be much more
varied and slower than that of axons, which conduct action potentials.
Figure 4-11 diagrams a cell membrane at rest, Figure 4-13 during
graded potentials, and Figure 4-15 generating the action potential.

Recording Action Potentials from Single

Cells
By the early 1950s it was becoming possible to record the activity of
individual cells by measuring a single neuron’s action potentials with
fine electrodes inserted into the brain. These microelectrodes can be
placed next to cells (extracellular recording ) or inside cells
(intracellular recording ). Modern extracellular recording techniques
make it possible to distinguish the activity of as many as 40 neurons at
once. Intracellular recording allows direct study and recording of a single
neuron’s electrical activity. The two disadvantages of inserting an
electrode into a cell are (1) it can kill the cell, and (2) it cannot be done
in awake, freely moving animals. Single-cell recording is therefore
confined to neurons grown in a dish or, for short periods (hours), from
neurons in living brain slices.
Figure 4-6 illustrates the structure and use of microelectrodes.
See, for example, Seeing Shape and Seeing Color in Section 9-4 and
Processing Language in Section 10-4 .
We now know that cells recorded extracellularly in the brain’s sensory
regions are highly specific to what excites them. Some cells in the visual
system fire vigorously to specific wavelengths of light (a color) or to
specific orientations of bars of light (vertical, for example). Other cells
respond to more complex patterns, such as faces or hands. Similarly,
cells in the auditory system respond to specific sound frequencies (a low
or high pitch) or to more complex sound combinations, such as speech
(the syllable ba, for example).
But certain cells have a far more complex nature that reveals much
about brain–behavior relationships. John O’Keefe and his colleagues
(O’Keefe & Dostrovsky, 1971) showed that neurons in the rat and mouse
hippocampus vigorously fire when an animal is in a specific place in the
environment. These place cells, illustrated in Figure 7-8 , code the
spatial location of the animal and contribute to a spatial map of the world
in the brain. The Nobel Prize in Physiology or Medicine 2014 was
awarded to John O’Keefe, May-Britt Moser, and Edvard I. Moser “for
their discoveries of cells that constitute a positioning system in the
brain.”
place cells Neurons maximally responsive to specific locations in
the world.
Section 13-4 discusses how place cells help to store memories.

Courtesy of John O’Keefe.

(A) Place cell
(B) Place-by-direction cell

(C) Head-direction cell

(D) Grid cell

Classes of Spatially Related Cells in the
FIGURE 7-8

Hippocampal Formation (A and B) Place cells discharge when

a rat is at a spatial location, irrespective of its orientation. (C) Head-
direction cells discharge to indicate where the rat’s head points,
irrespective of its location. (D) Grid cells discharge at many locations,
forming a virtual grid that is invariant in the face of changes in the rat’s
 direction, movement, or speed. At right in each part, xy coordinates
indicate the directional selectivity of the cell recorded at left.

O’Keefe’s group (Cacucci et al., 2008) also demonstrated that, in

mice with a genetically engineered mutation that produces deficits in
spatial memory, place cells lack specificity: the cells fire to a very broad
region of their world. As a result, these mice have difficulty finding their
way around, much as human patients with dementia tend to get lost. One
reason may be that a change, similar to the engineered mutation in mice,
takes place in human brain cells.

EEG: Recording Graded Potentials from

Thousands of Cells
In the early 1930s, Hans Berger discovered that the brain’s electrical
activity could be recorded simply by placing electrodes on the scalp. In
Berger’s words, recording these “brain waves” produces an “electrical
record from the head”—an electroencephalogram. The EEG measures
the summed graded potentials from many thousands of neurons. EEG
waves, shown in Figure 7-9 , are recorded by computer. In
electrocorticography, or ECoG, a method used during neurosurgery,
electrodes are placed directly on the cerebral cortex.
electrocorticography (ECoG) Graded potentials recorded with
electrodes placed directly on the brain’s surface.
EEGs reveal some remarkable features of the brain’s electrical
activity. The EEG recordings in Figure 7-10 illustrate three:

2 …to record their electrical activity. This EEG indicates a relaxed

person.
Southern Illinois University/Science Source

1 Electrodes attached to the scalp correspond to specific brain areas…

 Michael Rosenfeld/Maximilian Stock Ltd./Getty Images

Recording EEG Waves A simple, noninvasive

FIGURE 7-9
method for recording the brain’s electrical activity, EEG waves recorded
 via computer (see Figure 4-5 ) can match wave activity to specific brain
regions.

1. EEG changes as behavior changes.

2. An EEG recorded from the cortex displays an array of patterns, some
rhythmical.
3. The living brain’s electrical activity is never silent, even when a
person is asleep or comatose.
When a person is aroused, excited, or even just alert, the EEG pattern
has a low amplitude and a fast frequency, as shown in Figure 7-10 A.
This pattern is typical of an EEG taken from anywhere on the skull of an
alert subject, not only humans but other animals too. In contrast, when a
participant is calm and quietly relaxed, especially with eyes closed, the
rhythmical brain waves shown in Figure 7-10 B often emerge. These
alpha rhythms are extremely regular, with a frequency of approximately
11 cycles per second and amplitudes that wax and wane as the pattern is
recorded. In humans, alpha rhythms are generated in the region of the
visual cortex at the back of the brain. If a relaxed person is disturbed,
performs mental arithmetic, or opens his or her eyes, the alpha rhythms
abruptly stop.
alpha rhythm Regular wave pattern in an electroencephalogram;
found in most people when they are relaxed with eyes closed.
Amplitude is a recorded brain wave’s height. Frequency is the
number of brain waves recorded per second.

(A) Awake or excited

(B) Relaxed, eyes closed, alpha rhythms generated

(C) Drowsy—slowed frequency, increased-amplitude waves

 (D) Asleep—slower, higher-amplitude waves

(E) Deep sleep—even slower and higher-amplitude waves

(F) Coma—further slowing

FIGURE 7-10 Characteristic EEG Recordings Brain wave
patterns reflect different states of consciousness in humans. Data from W.
Penfield & H. H. Jasper (1954). Epilepsy and the functional anatomy of the human brain (p. 12).
Boston: Little, Brown.

EEG is a sensitive indicator of behaviors beyond simple arousal and

relaxation. Parts C, D, and E of Figure 7-10 illustrate EEG changes as a
person moves from drowsiness to sleep and finally into deep sleep. EEG
rhythms become progressively slower and larger in amplitude. Still
slower waves appear during anesthesia, after brain trauma, or when a
person is in a coma (shown in Figure 7-10 F). Only in brain death does
the EEG permanently become a flat line.
These distinctive brain wave patterns make EEG a reliable tool for
monitoring sleep stages, estimating the depth of anesthesia, evaluating
the severity of head injury, and searching for brain abnormalities. In
epilepsy, for example, brief periods of impaired awareness or
responsiveness and involuntary movements associated with spiking
patterns in the EEG characterize electrographic seizures.
Section 13-3 describes how EEG measures sleep and dreaming.
Focus features 4-1 and 10-3 detail epilepsy diagnoses and Section
16-3 , treatments.
 The important point here is that EEG recording provides a useful tool
both for research and for diagnosing brain dysfunction. EEG can also be
used in combination with the brain-imaging techniques described in
Sections 7-3 and 7-4 to provide more accurate identification of the
source of the large and highly synchronized EEG waves in epilepsy.

Mapping Brain Function with Event-Related

Potentials
Brief changes in an EEG signal in response to a discrete sensory stimulus
produce complex electroencephalographic waveforms called event-
related potentials (ERPs). ERPs are largely the graded potentials on
dendrites that a sensory stimulus triggers. You might think that they
should be easy to detect, but they are not.
event-related potential (ERP) Complex electroencephalographic
waveform related in time to a specific sensory event.
ERPs are mixed in with so many other electrical signals in the brain
that they are difficult to spot just by visually inspecting an EEG record.
One way to detect ERPs is to produce the stimulus repeatedly and
average the recorded responses. Averaging tends to cancel out any
irregular and unrelated electrical activity, leaving in the EEG record only
the potentials the stimulus generated.
To clarify this procedure, imagine throwing a small stone into a lake
of choppy water. Although the stone produces a splash, the splash is hard
to see among all the ripples and waves. Like the splash surrounded by
choppy water, the ERP caused by a sensory stimulus is hard to discern
from all the other electrical activity around it.
A solution is to throw a number of stones exactly the same size,
always hitting the same spot in the water, and producing the same splash
over and over. If a computer then calculates an average of the water’s
activity, random wave movements will tend to average one another out,
and you will see the splashes produced by the stones as clearly as a
single stone thrown into a pool of calm water.
Figure 7-11 shows an ERP record (top) that results when a person
hears a tone. The EEG record is highly irregular when the tone is first
presented. But after averaging over 100 stimulus presentations, a
distinctive wave pattern appears, as shown in the bottom panel of Figure
7-11 . This ERP pattern consists of a number of negative (N) and
positive (P) waves that occur within a few hundred milliseconds after the
stimulus.
The waves are numbered in time sequence. For instance, in Figure 7-
11 , N1 is a negative wave occurring about 100 milliseconds after the
stimulus, whereas P2 is a positive wave occurring about 200 milliseconds
after the stimulus. (The waves may also be labeled as N100 and P200.)
Not all these waves are unique to this particular stimulus. Some are
common to any auditory stimulus. Other waves, however, correspond to
important differences in specific tone. ERPs to spoken words even
contain distinctive peaks and patterns that differentiate such similar-
sounding words as cat and rat.
FIGURE 7-11 Detecting ERPs In the averaging process for an auditory ERP, a tone
is presented at time 0, and EEG activity in response is recorded. After many successive
presentations of the tone, the EEG wave sequence develops a distinctive shape that
becomes extremely clear after 100 responses are averaged (bottom panel). Positive and
negative waves that appear at different times after the stimulus presentation are used for
analysis.
 CLINICAL FOCUS 7-2

Mild Head Injury and Depression

When a pallet of boxed tools tipped and part of the load struck his
head, B. D., an industrial tool salesman, did not lose consciousness.
He did sustain a serious cut to his scalp and damage to two spinal
vertebrae. The attending physician at the hospital emergency room
suspected mild concussion but ordered no further neurological
workup at the time.
B. D.’s spinal symptoms gradually cleared, but irritability,
anxiety, and depression persisted even 2 years later. B. D. was unable
to work, and his behavioral change placed a major strain on his
family. His emotional problems led him to withdraw from the world,
only worsening his predicament.
A neuropsychological exam administered to B. D. about 2 years
after the injury found his general cognitive ability to be well above
average, with an IQ score of 115. But B. D. also had significant
attentional and short-term memory deficits. A subsequent magnetic
resonance image of his brain failed to find any injury that could
explain his symptoms. In fact, B. D.’s serious emotional symptoms
are common following mild head injury, even when no other
neurological or radiological signs of brain injury present themselves.
One tool for investigating brain functioning in such cases is ERP.
Reza and colleagues (2007) compared healthy controls to groups of
subjects with mild head injuries, with or without depression. The
investigators found that all subjects with head injury displayed a
delayed P3 wave, but only those who were depressed as well also
had a delayed N2 wave. These findings demonstrate that ERP can
identify cerebral processing abnormalities in people with depression
after mild head injury, even when MRI scans are negative. Such
evidence can be critical for people like B. D., who are seeking long-
term disability support following what appears to be a mild head
injury.

Among the many practical reasons for using ERPs to study the brain
is the advantage that this EEG technique is noninvasive. Electrodes are
placed on the scalp, not in the brain. Therefore, ERPs can be used to
study humans, including those most frequently used participants: college
students.
Another advantage is cost. Compared to other techniques, such as
brain imaging, EEG and ERP are inexpensive and can be recorded from
many brain areas simultaneously by pasting an array of electrodes
(sometimes more than 200) to different parts of the scalp. Because
certain brain areas respond only to certain sensory stimuli (e.g., auditory
areas respond to sounds and visual areas to sights), relative responses at
different locations can be used to map brain function.
Figure 7-12 shows a multiple-recording method that uses 128
electrodes simultaneously to detect ERPs at many cortical sites.
Computed averaging techniques reduce the masses of information
obtained to simpler comparisons between electrode sites. For example, if
the focus of interest is P3 , a positive wave occurring about 300
milliseconds after the stimulus, the computer can display a graph of the
skull showing only the amplitude of P3 . A computer can also convert the
averages at different sites into a color code, graphically representing the
brain regions most responsive to the signal.
ERPs not only can detect which brain areas are processing particular
stimuli but also can be used to study the order in which different regions
participate. This second use of ERPs is important because we want to
know the route that information takes as it travels through the brain. In
Figure 7-12 , the participant is viewing a picture of a rat that appears
repeatedly in the same place on a computer screen. The P3 recorded from
the posterior right side of the head is larger than any other P3 occurring
elsewhere, meaning that this region is a hot spot for processing the visual
stimulus. Presumably, this particular participant’s right posterior brain is
central in decoding the picture of the rat 300 milliseconds after it is
presented.
Many other interesting research areas benefit from using ERPs, as
described in Clinical Focus 7-2 , Mild Head Injury and Depression.
ERPs also can be used to study how children learn and process
information differently as they mature. ERPs can examine how a person
with a brain injury compensates for the impairment by using undamaged
brain regions. ERPs can even help reveal which brain areas are most
sensitive to aging and therefore contribute most to declining behavioral
functions among the elderly. This simple, inexpensive research tool can
address all these areas.
FIGURE 7-12 Using ERPs to Image Brain Activity

Magnetoencephalography
Passing a magnetic field across a wire induces an electrical current in the
wire. Conversely, current flowing along a wire induces a magnetic field
around the wire. The same is true in the brain. Neural activity, by
generating an electrical field, also produces a magnetic field. Although
the magnetic field produced by a single neuron is vanishingly small, the
field produced by many neurons is sufficiently strong to be recorded on
the scalp. The record of this phenomenon, a magnetoencephalogram
(MEG), is the magnetic counterpart of the EEG or ERP.
magnetoencephalogram (MEG) Magnetic potentials recorded
from detectors placed outside the skull.
Calculations based on MEG measurements not only describe neuronal
groups’ electrical activity but also localize the cell groups generating the
measured field in three dimensions. Magnetic waves conducted through
living tissue undergo less distortion than electrical signals do, so an
MEG can yield a higher resolution than an ERP. A major advantage of
the MEG over the EEG and ERP, then, is MEG’s ability to more
precisely identify the source of the activity being recorded. For example,
MEG has proved useful in locating the source of epileptic discharges.
MEG’s disadvantage is its high cost in comparison with the apparatus
used to produce EEGs and ERPs.
 7-2 REVIEW
Measuring the Brain’s Electrical Activity
Before you continue, check your understanding.
1 . The four major techniques for tracking the brain’s electrical activity
are ___________, ___________, ___________, and ___________.
2 . Single-cell recording measures ___________ from a single neuron.
3 . EEG measures ___________ on the cell membrane.
4 . Magnetoencephalography measures the ___________ and also
provides a ___________.
5 . What is the advantage of EEG techniques over MEG?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Anatomical Imaging Techniques: CT
7-3

and MRI
Until the early 1970s, the only way to actually image the living brain was
by using X-rays that produce static images of brain anatomy from one
angle. The modern era of brain imaging began in the early 1970s, when
Allan Cormack and Godfrey Hounsfield independently developed an X-
ray approach now called computed tomography : the CT scan.
Cormack and Hounsfield both recognized that a narrow X-ray beam
could be passed through the same object at many angles, creating many
images; the images could be combined with the use of computing and
mathematical techniques to produce a three-dimensional image of the
brain.
computed tomography (CT) X-ray technique that produces a static
three-dimensional image of the brain in cross section—a CT scan.
Tomo- comes from the Greek word for section, indicating that
tomography yields a picture through a single brain slice.
The CT method resembles the way in which our two eyes (and our
brain) work in concert to perceive depth and distance to locate an object
in space. The CT scan, however, coordinates many more than two
images, roughly analogous to our walking to several vantage points to
obtain multiple views. X-ray absorption varies with tissue density. High-
density tissue, such as bone, absorbs a lot of radiation. Low-density
material, such as ventricular fluid or blood, absorbs little. Neural tissue
absorption lies between these extremes. CT scanning software translates
these differences in absorption into a brain image in which dark colors
indicate low-density regions and light colors indicate high-density
regions.
 Neil Borden/Science Source
(A)
(B)
 (C)
FIGURE 7-13 CT Scan and Brain Reconstruction (A) Dorsal
view of a horizontal CT scan of a subject with Broca’s aphasia. The dark
region at the left anterior is the area of the lesion. (B) A schematic
representation of the horizontal section, with the area of the lesion shown
in blue. (C) A reconstruction of the brain, showing a lateral view of the left
hemisphere with the lesion shown in blue. Research from Damasio, H., & Damasio,
A. R. (1989). Lesion analysis in neuropsychology (p. 56). New York: Oxford University Press.

Figure 7-13 A shows a typical CT scan. The dense skull forms a

white border. The brain’s gray matter density does not differ sufficiently
from that of white matter for a CT scan to distinguish between the two
clearly, so the cortex and its underlying white matter show up as a more
or less homogeneous gray. Ventricles can be visualized, however,
because the fluid in them is far less dense: they, as well as some major
fissures in the cortex, are rendered darker in the CT scan. Each point on
the image in Figure 7-13 A represents about a 1-millimeter-diameter
circle of tissue, a resolution sufficient to distinguish two objects about 5
millimeters apart and appropriate for localizing brain tumors and lesions.
The lesion revealed in Figure 7-13 A is a damaged region where the
presence of fewer neurons and more fluid produces a contrast that
appears as a dark area in the CT scan. This subject presented with
symptoms of Broca’s aphasia, the inability to speak fluently despite
having average comprehension and intact vocal mechanisms. The
location of the lesion, in the left frontal cortex (adjacent to the butterfly-
shaped lateral ventricles), confirms this diagnosis. Figure 7-13 B, a
drawing of the same horizontal section, uses color to portray the lesion.
Figure 7-13C is a lateral view of the left hemisphere reconstructed from
a series of horizontal CT scans and showing the lesion’s extent.
Section 10-4 delves into aphasias that result from damaged speech
areas.
An anatomical alternative to the CT scan, magnetic resonance
imaging (MRI), is based on the principle that hydrogen atoms behave
like spinning bar magnets in the presence of a magnetic field. The MRI
procedure is illustrated in Figure 7-14 . The dorsal view of the brain
portrays density differences among the hydrogen atoms in different
neural regions as colors on the horizontal slice through the head.
magnetic resonance imaging (MRI) Technique that produces a
static three-dimensional brain image by passing a strong magnetic
field through the brain, followed by a radio wave, then measuring a
radio frequency signal emitted from hydrogen atoms.
Normally, hydrogen atoms point randomly in different directions, but
when placed in a large, static magnetic field, they line up in parallel as
they orient themselves with respect to the static field’s lines of force. In
an MRI scanner, radio pulses are applied to a brain whose atoms have
been aligned in this manner, and each radio pulse forms a second
magnetic field. The second field causes the spinning atoms to deviate
from the parallel orientation caused by the static magnetic field to a new
orientation.
As each radio pulse ends and the hydrogen atoms realign with the
static field, they emit a tiny amount of energy, and a coil detects this
realignment. Based on the signals from the coil, a computer re-creates
the position of the hydrogen nuclei, producing a magnetic resonance
image. MRI images may be based on the density of the hydrogen atoms
in different brain regions. Areas with high water (H2 O) content (cell
body–rich areas), for example, stand out from areas with lower water
content (axon-rich areas). Figure 7-15 shows such a magnetic resonance
image.
 © Bob Schatz
Gregory G. Dimijian/Science Source
Medical Body Scans/Science Source; Colorization by Matthew Bologna

FIGURE 7-14 Magnetic Resonance Imaging The subject is

placed in a long metal cylinder that has two sets of magnetic coils
arranged at right angles, as shown in the drawing. An additional
radiofrequency coil (not shown) surrounds the head, perturbing the static
magnetic fields to produce an MRI image of a horizontal section through
the head, shown in dorsal view. The density differences in hydrogen atoms
show up as colors in the image.
 FIGURE 7-15 Magnetic Resonance Image Electrical currents
emitted by wobbling atoms are recorded by MRI to represent different
types of tissue—cerebrospinal fluid, brain matter, and bone, for example—
as lighter or darker depending on the density of hydrogen atoms in the
tissue.

Diffusion tensor imaging (DTI) is an MRI method that detects the

directional movements of water molecules to image nerve fiber pathways
in the brain. Water can move relatively freely along the axon but less
freely across cell membranes. The direction of this water movement is
detected by a coil and interpreted by a computer. DTIs can delineate
abnormalities in neural pathways. They are also used to identify changes
in fiber myelination, such as the damage that leads to myelin loss in
multiple sclerosis.
diffusion tensor imaging (DTI) Magnetic resonance imaging
method that can image fiber pathways in the brain by detecting the
directional movements of water molecules.
Clinical Focus 4-2 describes how myelin loss in MS disrupts
neuronal function.
 Each scan in the series of DTIs shown in Figure 7-16 represents a
dorsal view at increasing depths through the brain. Although the images
appear to show real fibers, DTIs are virtual and based on computer
reconstructions of water movement along axons, which should
correspond to actual fibers. Nonetheless, DTI easily detects
abnormalities, such as those that occur in multiple sclerosis, stroke, or
concussion, in the imaged fiber pathways and in their myelin sheaths.
Focus 16-3 explores the relationship between concussion and
degenerative brain disease.

Zephyr/Science Source

FIGURE 7-16 Diffusion Tensor Imaging MRI can measure the

diffusion of water molecules in white matter, allowing the visualization of
nerve fiber tracts. The front of the brain is at the top in these scans of
sections through a healthy brain. The axons are colored according to
orientation: fibers running left–right are red, front–back are blue, and up–
down are green. Section 15-3 outlines how DTI is helping researchers
develop a brain connectome to map functional connections in the living
brain.

Magnetic resonance spectroscopy (MRS) is an MRI method that

uses the hydrogen proton signal to determine the concentration of brain
metabolites such as N -acetylaspartate (NAA) in brain tissue. This
measurement is especially useful for detecting persisting abnormalities in
brain metabolism in disorders such as concussion.
magnetic resonance spectroscopy (MRS) Magnetic resonance
imaging method that uses the hydrogen proton signal to determine
the concentration of brain metabolites.
 7-3 REVIEW
Anatomical Imaging Techniques: CT and MRI
Before you continue, check your understanding.
1 . The principal anatomical brain imaging methods are ___________
and ___________.
2 . Diffusion tensor imaging identifies ___________, whereas magnetic
resonance spectroscopy determines ___________.
3 . In addition to imaging the density of different brain regions, CT and
MRI can be used to assess ___________.
4 . Explain briefly how the development of the CT scan ushered in the
brain-imaging techniques used today in neuroscience research.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 7-4 Functional Brain Imaging
Advances in MRI and computing technologies led from anatomical to
functional brain-imaging techniques, which allow investigators to
measure the amount of blood, oxygen, and glucose the brain uses as
subjects or participants solve cognitive problems. When a brain region is
active, the amount of blood, oxygen, and glucose flowing to the region
increases. It therefore is possible to infer changes in brain activity by
measuring either blood flow or levels of the blood’s constituents, such as
oxygen, glucose, and iron. Three techniques developed from this logic
are functional MRI, optical tomography, and positron emission
tomography.

FIGURE 7-17 Imaging Changes in Brain Activity Functional

MRI sequence of a horizontal section at mid-occipital lobe (bottom of each
image) in a normal human brain during visual stimulation. A baseline
acquired in darkness (far left) was subtracted from the subsequent
images. The participant wore tightly fitting goggles containing light-emitting
diodes that were turned on and off as a rapid sequence of scans was
obtained over 270 seconds. Note the prominent activity in the visual cortex
when the light is on and the rapid cessation of activity when the light is off,
all measured in the graph of signal intensity below the images. “Dynamic
Magnetic Resonance Imaging of Human Brain Activity During Primary Sensory Stimulation,” by
K. K. Kwong et al., 1992, Proceedings of the National Academy of Sciences (USA), 89, 5678.

Functional Magnetic Resonance Imaging

As neurons become active, they use more oxygen, resulting in a
temporary dip in the blood oxygen level. At the same time, active
neurons signal blood vessels to dilate to increase blood flow and bring
more oxygen to the area. Peter Fox and colleagues (1986) discovered
that when human brain activity increases, the extra oxygen produced by
increased blood flow actually exceeds the tissue’s needs. As a result, the
amount of oxygen in an activated brain area increases.
Oxygen is carried on the hemoglobin molecule in red blood cells.
Changes in the ratio of oxygen-rich hemoglobin to oxygen-poor
hemoglobin alters the blood’s magnetic properties, because oxygen-rich
hemoglobin is less magnetic than oxygen-poor hemoglobin. In 1990,
Segi Ogawa and his colleagues showed that MRI could accurately match
these changes in magnetic properties to specific brain locations (Ogawa
et al., 1990). This process, functional magnetic resonance imaging
(fMRI), signals which areas are displaying changes in activity.
functional magnetic resonance imaging (fMRI) Magnetic
resonance imaging in which changes in elements such as iron or
oxygen are measured during the performance of a specific behavior;
used to measure cerebral blood flow during behavior or resting.
Figure 7-17 shows changes in the fMRI signal in the visual cortex of
a person who is being stimulated with light. When the light is turned on,
the visual cortex (bottom of the brain images) becomes more active than
during baseline (no light). In other words, functional changes in the brain
are inferred from increases and decreases in the MRI signal produced by
changes in oxygen levels.
When superimposed on MRI-produced anatomical brain images,
fMRI changes in activity can be attributed to particular structures. The
dense blood vessel supply to the cerebral cortex allows for a spatial
resolution of fMRI on the order of 1 millimeter, affording good spatial
resolution of the brain activity’s source. On the other hand, because
changes in blood flow take as long as a third of a second, the temporal
resolution of fMRI is not as precise as that obtained with EEG recordings
and ERPs.
fMRI also has the disadvantage that subjects must lie motionless in a
long, noisy tube, an experience that can prove claustrophobic. The
confined space and lack of mobility also restrict the types of behavioral
experiments that can be performed. Nonetheless, fMRI is a major tool in
cognitive neuroscience.
Figure 2-7 diagrams the extent of the major cerebral arteries.
The living brain is always active, and researchers have succeeded in
inferring brain function and connectivity by studying fMRI signals when
participants are resting, that is, not engaged in any specific task. This
signal, resting-state fMRI (rs-fMRI), is collected when participants are
asked to look at a fixation cross and to keep their eyes open.
resting-state fMRI (rs-fMRI) Magnetic resonance imaging method
that measures changes in elements such as iron or oxygen when the
individual is resting (not engaged in a specific task).
The scanner collects brain activity, typically for at least 4-minute
blocks. Researchers are attempting to shorten the period by increasing
the strength of the static magnetic field and developing more sensitive
coils. Statistical analysis of the data entails correlating activity in
different brain regions over time. Although rs-fMRI is still in its growth
phase, investigators already have identified many consistent networks of
brain activity and abnormalities in disease states such as dementia and
schizophrenia (Van den Heuvel & Hulshoff Pol, 2010).

Optical Tomography
Research Focus 7-1 , Tuning into Language, describes a brain-imaging
study that used functional near-infrared spectroscopy (fNIRS) to
investigate newborn infants’ responses to language. fNIRS is a form of
optical tomography, a functional imaging technique that operates on the
principle that an object can be reconstructed by gathering light
transmitted through it. One requirement is that the object at least partially
transmit light. Thus, optical tomography can image soft body tissue, such
as that in the breast or the brain.
In fNIRS, reflected infrared light is used to determine blood flow
because oxygen-rich hemoglobin and oxygen-poor hemoglobin differ in
their absorption spectra. By measuring the blood’s light absorption it is
possible to measure the brain’s average oxygen consumption. So fNIRS
and fMRI measure essentially the same thing but with different tools. In
fNIRS, an array of optical transmitter and receiver pairs are fitted across
the scalp, as illustrated in Figure 7-18 A.
The obvious advantage of fNIRS is that it is relatively easy to hook
subjects up repeatedly and record from them for short periods, from
infancy to senescence. The disadvantage is that the light does not
penetrate far into the brain, so researchers are restricted to measuring
cortical activity (Figure 7-18 B). The spatial resolution is also not as
good as with other noninvasive methods, although NIRS equipment now
uses over 100 light detectors on the scalp, which allows acceptable
spatial resolution in the image. NIRS has been used to differentiate
cancerous from noncancerous brain tissue. This advance should lead to
safe, extensive surgical removal of brain cancers and improved outcomes
(Kut et al., 2015).

Hitachi, Ltd. Research & Development Group. Photo by Atsushi Maki

(A)
 (B)
FIGURE 7-18 How NIRS Works (A) Light injectors (red) and
detectors (blue) are distributed in an array across the head. (B) Light
injected through the scalp and skull penetrates the brain to a depth of
about 2 centimeters. A small fraction of the light is reflected and captured
by a detector on the scalp surface. Light is reflected from as deep as 2
centimeters but also from the tissue above it, as illustrated by the banana
shape of the curves. Information from L. Spinney (2005). Optical topography and the color
of blood, The Scientist, 19, 25–27.

Positron Emission Tomography

Researchers use positron emission tomography (PET) to study the
metabolic activity of brain cells engaged in processing brain functions
such as language. PET imaging detects changes in the brain’s blood flow
by measuring changes in the uptake of compounds such as oxygen and
glucose (Posner & Raichle, 1997). A PET camera, like the one shown in
Figure 7-19 , is a doughnut-shaped array of radiation detectors that
encircles a person’s head. A small amount of water, labeled with
radioactive molecules, is injected into the bloodstream. The person
injected with these molecules is in no danger because those used,
including the radioactive isotope oxygen-15 (15 O), are very unstable.
They break down in just a few minutes and are quickly eliminated from
the body. (Most of the oxygen in air we breathe is the stable 16 O
molecule.)
 positron emission tomography (PET) Imaging technique that
detects changes in blood flow by measuring changes in the uptake of
compounds such as oxygen or glucose; used to analyze the
metabolic activity of neurons.
Tagged to a glucose molecule, fluorine-18 (18 F) acts as a marker for
metabolism and is used far more in PET than is 15 O. The methods are
essentially the same.

Radioactive 15 O molecules release tiny, positively charged subatomic

particles known as positrons (electrons with a positive charge). Positrons
are emitted from an unstable atom because it is deficient in neutrons. The
positrons are attracted to the negatively charged electrons in the brain,
and the collision of the two particles leads to annihilation of both, which
produces energy.
This energy, in the form of two photons (a unit of light energy), leaves
the head at the speed of light and is detected by the PET camera. The
photons leave the head in exactly opposite directions from the site of
positron–electron annihilation, so annihilation photon detectors can
detect their source, as illustrated in Figure 7-19 . A computer identifies
the coincident photons and locates the annihilation source to generate the
PET image.
The PET system enables blood flow measurement in the brain
because the unstable radioactive molecules accumulate there in direct
proportion to the rate of local blood flow. Local blood flow in turn is
related to neural activity because potassium ions released from
stimulated neurons dilate adjacent blood vessels. The more the blood
flow, the higher the radiation counts recorded by the PET camera.
Sophisticated computer imaging can map blood flow in the brain
when a person is at rest with closed eyes (Figure 7-20 ). The resting-
state map shows, in a series of frames, where blood flow is highest. Even
though the distribution of blood is not uniform, it is still difficult to
conclude much from such a map because the entire brain is receiving
oxygen and glucose.
 Science Source

FIGURE 7-19 PET Scanner and Image Subject lying in a PET

scanner, whose design is illustrated in the drawing. In the scan, the bright
red and yellow areas are regions of high blood flow.

M. E. Raichle, Mallinckrodt Institute of Radiology, Washington University School

of Medicine

FIGURE 7-20 Resting State PET images of blood flow obtained while
a single subject rested quietly with eyes closed. Each scan represents a
horizontal brain section, from the dorsal surface (1) to the ventral surface
(31). Development of rs-fMRI suggests that resting-state PET analysis
may emerge.

But PET researchers who are studying the link between blood flow
and mental activity use a subtraction procedure. They subtract the blood
flow pattern when the brain is in a carefully selected control state from
the pattern of blood flow imaged when the subject is engaged in the task
under study, as illustrated in the top row of Figure 7-21 . This
subtraction process images the change in blood flow between the two
states. The change can be averaged across subjects (middle row) to yield
a representative average image difference that reveals which brain areas
are selectively active during the task (bottom). PET does not measure
local neural activity directly; rather, it infers activity on the assumption
that blood flow increases where neuron activity increases.
A significant limitation of PET is that radiochemicals, including so-
called radiopharmaceuticals used in diagnosing human patients, must be
prepared in a cyclotron quite close to the scanner because their half-lives
are so short that transportation time is a severely limiting factor.
Generating these materials is very expensive. But in spite of the expense,
PET has important advantages over other imaging methods:
• PET can detect the decay of literally hundreds of radiochemicals,
which allows the mapping of a wide range of brain changes and
conditions, including changes in pH, glucose, oxygen, amino acids,
neurotransmitters, and proteins.
• PET can detect relative amounts of a given neurotransmitter, the
density of neurotransmitter receptors, and metabolic activities
associated with learning, brain poisoning, and degenerative processes
that might be related to aging.
 M. E. Raichle, Mallinckrodt Institute of Radiology, Washington University School
of Medicine

FIGURE 7-21 The Procedure of Subtraction In the upper row

of scans, the control condition, resting while looking at a static fixation
point (control), is subtracted from the experimental condition, looking at a
flickering checkerboard (stimulation). The subtraction produces a different
scan for each of five experimental subjects, shown in the middle row, but
all show increased blood flow in the occipital region. The difference scans
are averaged to produce the representative image at the bottom.

• PET is widely used to study cognitive function with great success. For
example, PET confirms that various brain regions perform differing
functions.
• There are now hybrid scanners for diagnostic imaging and they come in
different combinations in which the imaging modalities combines PET
with CT, PET with MRI and also PET with MRI and EEG. The
advantage of these hybrid scanners is that they can acquire high-quality
anatomical images and then overlay the functional/metabolic image
information, allowing for precise localization that was not available
before, and all within a single examination.
 7-4 REVIEW
Functional Brain Imaging
Before you continue, check your understanding.
1 . The principal methods of functional brain imaging are ___________,
___________, and ___________.
2 . PET uses ___________ to measure brain processes and to identify
___________ changes in the brain.
3 . fMRI and optical imaging measure changes in ___________.
4 . Why are resting-state measurements useful to researchers?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Chemical and Genetic Measures of
7-5

Brain and Behavior

Our focus so far has been on how neuroscientists study the individual
and collective activity of neurons and how neuronal activity relates to
behavior. Neurons are regulated by genes, DNA segments that encode
the synthesis of particular proteins within cells. Genes control the cell’s
production of chemicals, so it is possible to relate behavior to genes and
to chemicals inside and outside the cell. Chemical and genetic
approaches require sophisticated technologies that have seen major
advances in the past decade.
Section 3-2 investigates how neurons function. Section 3-3 relates
genes to cell function, genetic engineering, and epigenetic
mechanisms.

Measuring Brain Chemistry

The brain contains a wide mixture of chemicals ranging from
neurotransmitters and hormones to glucose and gases, among many
others. Abnormalities in amounts of these chemicals can cause serious
disruptions in behavior. Prime examples are Parkinson disease,
characterized by low dopamine levels in the substantia nigra, and
depression, correlated with low serotonin and/or noradrenaline
production. The simplest way to measure brain chemistry in such
diseases is to extract tissue postmortem from affected humans or
laboratory animals and undertake traditional biochemical techniques,
such as high-performance liquid chromatography (HPLC), to measure
specific chemical levels.
Fluctuations in brain chemistry are associated not only with
behavioral dysfunction but also with ongoing healthy behavior. For
example, research over at least the past 30 years shows that dopamine
levels fluctuate in the nucleus accumbens (a structure in the subcortical
basal ganglia) in association with stimuli related to rewarding behaviors
such as food and sex. Changes in brain chemistry can be measured in
freely moving animals using two methods, cerebral microdialysis and
cerebral voltammetry.
Section 12-6 explores neural effects of rewarding events.
 Microdialysis, which can determine the chemical constituents of
extracellular fluid, is widely used in the laboratory. The technique has
found clinical application over the past decade. A catheter with a
semipermeable membrane at its tip is placed in the brain, as illustrated in
Figure 7-22 . A fluid flows through the cannula and passes along the cell
membrane. Simple diffusion drives extracellular molecules across the
membrane along their concentration gradient.
microdialysis Technique used to determine the chemical
constituents of extracellular fluid in freely moving animals.
Section 4-1 explains diffusion and concentration gradients in detail.
Fluid containing the molecules from the brain exits through tubing to
be collected for analysis. The fluid is removed at a constant rate so that
changes in brain chemistry can be correlated with behavior. For example,
if a rat is placed in an environment in which it anticipates sex or a
favored food, microdialysis will record an increase in dopamine within
the basal ganglia regions of the caudate nucleus and putamen, known as
the striatum.
striatum Caudate nucleus and putamen of the basal ganglia.
This result mirrors wanting-and-liking theory described in Section
6-4 .
Microdialysis is used in some medical centers to monitor chemistry in
the injured brain. The effects of TBI or stroke can be worsened by
secondary events such as a drastic increase in the neurotransmitter
glutamate. Such biochemical changes can lead to irreversible cell
damage or death. Physicians are beginning to use microdialysis to
monitor such changes, which can then be treated.
Section 6-4 investigates why glutamate and similar chemicals can
act as neurotoxins.
Cerebral voltammetry works on a different principle. A small
carbon fiber electrode and a metal electrode are implanted in the brain,
and a weak current is passed through the metal electrode. The current
causes electrons to be added to or removed from the surrounding
chemicals. Changes in extracellular levels of specific neurotransmitters
can be measured as they occur.
cerebral voltammetry Technique used to identify the concentration
of specific chemicals in the brain as animals behave freely.
 Because different currents lead to changes in different compounds, it
is possible to identify levels of different transmitters, such as serotonin or
dopamine, and related chemicals. Voltammetry has the advantage of not
requiring the chemical analysis of fluid removed from the brain, as
microdialysis does, but it has the disadvantage of being destructive. That
is, the chemical measurements require the degradation of one chemical
into another. Thus this technique is not well suited to clinical uses.

Measuring Genes in Brain and Behavior

Most human behaviors cannot be explained by genetic inheritance alone,
but variations in gene sequences do contribute significantly to brain
organization. About 1 in 250 live births are identical twins, people who
share an identical genome. Identical twins often have remarkably similar
behavioral traits. Twin studies show strong concordance rates that
support genetic contributions to drug addiction and other psychiatric
disorders. But twin studies also show that environmental factors and life
experience must be involved: concordance for most behavioral disorders,
such as schizophrenia and depression, is far less than 100 percent. Life
experiences are acting epigenetically to alter gene expression.
Genetic factors can also be studied by comparing people who were
adopted early in life and usually would not have a close genetic
relationship to their adoptive parents. Here, a high concordance rate for
behavioral traits would imply a strong environmental influence on
behavior. Ideally, an investigator would be able to study both the
adoptive and biological parents to tease out the relative heritability of
behavioral traits.
FIGURE 7-22 Microdialysis Information from M. M. Tisdall & M. Smith (2006).
Cerebral microdialysis: Research technique or clinical tool. British Journal of Anaesthesia, 97,
18–25.
CLINICAL FOCUS 7-3

Cannabis Use, Psychosis, and Genetics

Cannabis is the most widely used illicit drug in the world. Because it
is nearly impossible to overdose, cannabis is usually considered safe,
but it is not completely free of side effects. A relationship has been
established between cannabis use and the emergence of psychosis,
especially with use in adolescence: earlier use is associated with both
an earlier onset and worse long-term prognosis of disease.
Given that most adolescents who use cannabis do not develop
psychosis, however, some genetic vulnerability likely predisposes
certain individuals to develop a psychotic condition when exposed to
it. Cannabis use thus may act more as a trigger for the onset of
schizophrenia than as the primary cause of the disease.
A working hypothesis contends that one culprit may be the
COMT gene, because COMT has been associated with
schizophrenia. The COMT gene product is an enzyme involved in
metabolizing dopamine in the synapse, and abnormalities in
dopaminergic activity are associated with psychosis. The hypothesis
predicts that adolescents who develop psychosis after cannabis use
have an abnormality in the COMT gene.
Avshalom Caspi and colleagues (2005) analyzed the COMT gene
in nearly a thousand 26-year-old adults who had participated in a
long-term health study in New Zealand. As shown in the nearby
figure, although no genotype was more likely to use cannabis in
adolescence, carriers of the Val allele were far more likely to develop
psychotic symptoms if they did use cannabis in adolescence (graph
on the left) but not if they used it in adulthood (graph on the right).
The Met/Met genotype showed no adverse effect of cannabis use in
adolescence.
These results show that genetic variations can predispose people
to show adverse effects of environmental experiences and that the
experiences may have age-related effects. Presumably these effects
relate to the significant development the brain undergoes during
adolescence.
Adolescent-onset cannabis use
 No adolescent cannabis use

Information from A. Caspi, T. E. Moffitt, M. Cannon, J. McClay, R.

Murray, et al. (2005). Moderation of the effect of adolescent-onset
cannabis use on adult psychosis by a functional polymorphism in the
catechol-O-methyltransferase gene: Longitudinal evidence of a gene
X environment interaction. Biological Psychiatry, 57, 1117–1122.

With the development of relatively inexpensive methods of

identifying specific genes in people, it is now possible to relate the
alleles (different forms) of specific genes to behaviors. A gene related to
the production of a compound called brain-derived neurotrophic factor
(BDNF) is representative. BDNF plays an important role in stimulating
neural plasticity, and low levels of BDNF have been revealed in mood
disorders such as depression. The two alleles of this gene are BDNF Val
66Met and BDNF Val 66Val.
Section 8-2 explains how neurotrophic factors, nourishing chemical
compounds, support growth and differentiation in developing
neurons.
Joshua Bueller and his colleagues (2006) showed that the Met allele is
associated with an 11 percent reduction in hippocampal volume in
healthy participants. Other studies have associated the Met allele with
poor memory for specific events (episodic memory ) and a high
incidence of dementia later in life. However, the Val allele is by no
means the better variant: although Val carriers have better episodic
memory, they also have a higher incidence of neuroticism and anxiety
disorders, as illustrated in Clinical Focus 7-3 , Cannabis Use, Psychosis,
and Genetics. The two alleles produce different phenotypes because they
influence brain structure and functions differently. Other genes that were
not measured also differed among Bueller’s participants and may have
contributed to the observed difference.
Sections 2-6 and 5-3 introduce factors that contribute to dementias.
Focus 14-3 describes research and Section 16-3 , treatments.
Focus 6-4 relates a case in which chronic cannabis use may have led
to psychosis.

Epigenetics: Measuring Gene Expression

An individual’s genotype exists in an environmental context fundamental
to gene expression, the way genes become active or not. While
epigenetic factors do not change the DNA sequence, the genes that are
expressed can change dramatically in response to environment and
experience. Epigenetic changes can persist throughout a lifetime and
even across multiple generations.
See A Case of Inheriting Experience in Section 3-3 .
Changes in gene expression can result from widely ranging
experiences, including chronic stress, traumatic events, drugs, culture,
and disease. A study by Mario Fraga and his colleagues (2005) stands as
a powerful example of gene–experience interactions. The investigators
examined epigenetic patterns in 40 pairs of identical twins by measuring
two molecular markers related to gene expression.
Although twins’ patterns of gene expression were virtually identical
when measured in childhood, 50-year-old twins exhibited differences so
remarkable as to make them as different epigenetically as young non-
twin siblings! The specific cause or causes of such differences are
unknown but thought to be related to lifestyle factors, such as smoking
and exercise habits, diet, stressors, drug use, and education, and to social
experiences, such as marriage and child rearing, among others. The
epigenetic drift in the twins supports the findings of less than 100 percent
concordance for diseases in identical twins.
The role of epigenetic differences can also be seen across populations.
Moshe Szyf, Michael Meaney, and their colleagues (e.g., 2008) have
shown, for example, that the amount of maternal attention mother rats
give to their newborn pups alters the expression of certain genes in the
adult hippocampus. These genes are related to the infants’ stress
response when they are adults. (Maternal attention is measured as the
amount and type of mother–infant contact; a difference of up to 6 hours
per day can exist between attentive and inattentive mothers.)
A subsequent study by the same group (McGowan et al., 2009)
examined epigenetic differences in hippocampal tissue obtained from
two groups of humans: (1) suicides with histories of childhood abuse and
(2) either suicides with no childhood abuse or controls who died of other
causes. The epigenetic changes found in the abused suicide victims
parallel those found in the rats with inattentive mothers, again suggesting
that early experiences can alter hippocampal organization and function
via changes in gene expression.
Experience-dependent changes in gene expression are probably found
not only in the hippocampus but throughout the brain as well. For
example, Richelle Mychasiuk and colleagues (2011) found that stressing
pregnant rat dams led to wide changes in gene expression in their
offspring, in both the frontal cortex and the hippocampus. However, the
investigators found virtually no overlap in the altered genes in the two
brain regions: the same experience changed different brain regions
differently.
Epigenetic studies promise to revolutionize our understanding of
gene–brain interactions in healthy brain development and brain function.
They will also help researchers develop new treatments for neurological
disorders. For example, specific epigenetic changes appear to be related
to the ability to make a functional recovery after stroke.
Consult the Index entry epigenetics to locate coverage throughout
the book.
 7-5 REVIEW
Chemical and Genetic Measures of Brain and Behavior
Before you continue, check your understanding.
1 . Concentrations of different chemicals in the brain can be measured in
postmortem tissue using a(n) _____________ assay or in vivo using
_____________ or _____________.
2 . Gene–environment interactions can be investigated in human
populations by comparing _____________ of behavioral traits in
identical twins and adopted children.
3 . The study of genes and behavior focuses on individual differences in
_____________, whereas the study of epigenetics and behavior
examines differences in _____________.
4 . Describe briefly how epigenetic studies have led to the recognition
that life experience and the environment can alter brain function.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Comparing Neuroscience Research
7-6

Methods
We have considered a wide range of research methods for manipulating
and measuring brain–behavior interactions. Tables 7-1 and 7-2
summarize these methods, including goals and examples of each method.
How do researchers choose among them all? Their main consideration is
their research question. Ultimately, that question is behavioral, but many
steps lie along the route to understanding behavior.
Some researchers focus on morphology (structure) in postmortem
tissue. This approach allows detailed analysis of both macro and micro
structure, depending on the method chosen. Identifying brain pathology,
as in Parkinson disease, can lead to insights about the causes and nature
of a disorder.
Other investigators focus more on the ways neurons generate electrical
activity in relation to behavior or on functional changes in brain activity
during specific types of cognitive processing. Both approaches are
legitimate: the goal is gaining an understanding of brain–behavior
relationships.
But investigators must consider practical issues, too. Temporal
resolution (how quickly the measurement or image is obtained); spatial
resolution (how accurate localization is in the brain); and the degree of
invasiveness all are pertinent. It is impractical to consider MRI-based
methods for studies of very young children, for example, because
although the images are highly accurate, the participants must remain
absolutely still for long periods.
Similarly, studies of brain-injured patients must take into account
factors such as the subject’s ability to maintain attention for long periods
—during neuropsychological testing or imaging studies, for example.
And practical problems such as motor or language impairment may limit
the types of methods that researchers can use.
Of course, cost is an ever-present practical consideration. Studying
brain and behavior linkages by perturbing the brain are generally less
costly than some imaging methods, many of which require expensive
machinery. EEG, ERP, and fNIRS are noninvasive and relatively
inexpensive to set up (less than $100,000). MRI-based methods, MEG,
and PET are very expensive (more than $2 million) and therefore
typically found only in large research centers or hospitals. Similarly,
epigenetic studies can be very expensive if investigators consider the
entire genome in a large number of biological samples.
TABLE 7-1 Manipulating Brain and Behavior
Method Goal Examples

Whole-animal Determine how an Diet, exercise, social interactions, sensory

manipulations environmental condition stimulation, drug usage
(Section 7-1) affects brain and
behavior

Brain lesions, Remove or destroy Knife cuts or aspirations Electrolytic lesions

permanent neural tissue to observe Neurotoxic lesions
(Section 7-1) behavioral changes

Brain lesions, Short-term silencing of Regional cooling to arrest synaptic

temporary and neural tissue to observe transmission Delivery of an agonist for
reversible behavioral changes GABA through a cannula to increase local
(Section 7-1) inhibition

Genetic lesions Remove genetic Knockout technology

(Section 3-3) material

Genetic Add genetic material Knock-in technology

stimulation
(Section 3-3)

Drug Determine receptor Use drugs to activate (agonists) or inactivate

manipulations system’s role in the CNS (antagonists) a receptor system
(Section 7-1)

Electrical and Excite tissue activity DBS

magnetic TMS
stimulation
(Section 7-1)

Optogenetics Use light to activate Insertion of specific light-sensitive proteins

(Section 7-1) specific ion channels
and relate to behavior

Chemogenetics Use specific synthetic Insertion of specific G protein-coupled

(Section 7-1) drugs to activate receptors
designer receptors

TABLE 7-2 Measuring Brain and Behavior

Method Goal Examples

Behavioral Observe behavior; generate tests to allow people and Naturalistic

analysis (Section lab animals to demonstrate behavioral capacities observation;
7-1) tests, mazes
Tissue analysis Identify cell types and connections; identify disease Stains
(Section 7-1) states

Record electrical Measure action potentials from individual neurons; Single cell
and magnetic measure graded potentials to assess coordinated recording;
activity (Section activity of thousands of neurons; measure magnetic EEG, ERP;
7-2) fields MEG

Anatomical brain Noninvasive examination of brain structures Miniature

imaging (Section microscopes;
7-3) X-ray; CT;
MRI; DTI

Functional brain Measure brain activity as specific behaviors are fMRI; fNIRS;
imaging (Section performed MRS; PET
7-4)

In vivo chemistry Relate fluctuations in transmitter release to behavior HPLC;

(Section 7-5) microdialysis,
voltammetry

Genetics (Section Determine presence of a gene and its products DNA, RNA,
7-5) protein
analysis

Epigenetics Discover effect of experience on gene expression, Gene

(Section 7-5) brain, and behavior expression
analysis
 7-6 REVIEW
Comparing Neuroscience Research Methods
Before you continue, check your understanding.
1 . Neuroscience measurements and imaging vary along the dimensions
of __________, __________, and __________.
2 . Relative to the expense of fMRI and PET imaging, noninvasively
perturbing the brain using methods such as __________ or
administering neuropsychological testing is __________.
3 . The main consideration for choosing a research method is the
question being asked. What is the fundamental goal of neuroscience
research?

Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Using Animals in Brain–Behavior
7-7

Research
A complete understanding of brain–behavior relationships is limited in
part by the voluntary ethical constraints investigators place upon
experimentation on humans and nonhuman species. Most individual
countries decide independently which experimental practices are
acceptable for humans, for other vertebrates, and for invertebrate species.
In general, the experimental methods acceptable for use on our species
are fewer than those employed on our most closely related primate
relatives. Thus, like most new treatments in medicine, a wide variety of
nonhuman species have been used to develop and test treatments for
human neurological or psychiatric disorders before they are tested on
humans.
Although the human and the nonhuman brain have obvious
differences with respect to language, the general brain organization
across mammalian species is remarkably similar, and the functioning of
basic neural circuits in nonhuman mammals appears to generalize to
humans. Thus, neuroscientists use widely varying animal species to
model human brain diseases as well as to infer typical human brain
functioning.
Two important issues surface in use of animal models to develop
treatments for brain and behavioral disorders. The first is whether
animals actually display neurological diseases in ways similar to
humans. The second surrounds the ethics of using animals in research.
We consider each separately.

Benefits of Animal Models of Disease

Some disorders—stroke, for example—seem relatively easy to model in
laboratory animals because it is possible to interrupt blood supply to a
brain area and induce injury and consequent behavioral change.
However, it is far more difficult to determine whether human behavioral
disorders can actually be induced in laboratory animals. Consider
attention-deficit/hyperactivity disorder (ADHD), a developmental
disorder characterized by core behavioral symptoms: impulsivity,
hyperactivity, and/or inattention. The most common issue for children
with ADHD is problems at school. Lab animals such as rats and mice do
not go to school, so how does one model ADHD in rodents?
ADHD has proved difficult to treat in children, and interest in
developing an animal model is high. One way to proceed is to take
advantage of the normal variance in the performance of rats on a variety
of tests of working memory and cognitive functioning—tests that require
attentional processes. The idea is that we can think of ADHD in people
or in rats as one extreme on a spectrum of behaviors that are part of a
normal distribution in the general population. Many studies show that
treating rats with the dopaminergic agonist methylphenidate (Ritalin), a
common treatment for children diagnosed with ADHD, actually
improves the performance of rats that do poorly on tests requiring
attentional processes.
Focus 6-1 reports on illicit use of prescription ADHD medications
to boost performance at school and at work. Section 15-4 explores
the nature of attention and disorders that result in deficits of
attention.
One rat strain, the Kyoto SHR rat, has proved an especially good
model for ADHD and is widely used in the lab. The strain presents
known abnormalities in prefrontal dopaminergic innervation that
correlate with behavioral abnormalities such as hyperactivity.
Dopaminergic abnormalities are believed to be one underlying symptom
of ADHD in children, as explained in Research Focus 7-4 , Attention-
Deficit/Hyperactivity Disorder. Methylphenidate can reverse behavioral
abnormalities, both in children with ADHD and in the SHR rats.

Animal Welfare and Scientific

Experimentation
Using nonhuman animals in scientific research has a long history, but
only in the past half-century have ethical issues surrounding animal
research gained considerable attention and laws been instituted. Just as
the scientific community has established ethical standards for research
on humans, it has also developed regulations governing experimentation
on animals. The governments of most developed nations regulate the use
of animals in research; most states and provinces have additional
legislation. Universities and other organizations engaged in research
have their own rules governing animal use, as do professional societies
of scientists and the journals in which they publish.
 We present experiments that predate current ethical standards.
Bartholow’s brain stimulation (Section 4-1 ), the inmate volunteers
in Experiment 6-1 , and Magendie’s studies with puppies (Focus 2-
4) are examples.
Here are four principles, used as guidelines in Canada, for reviewing
experimental and teaching protocols that will use animals:
1. The use of animals in research, teaching, and testing is acceptable only
if it promises to contribute to the understanding of environmental
principles or issues, fundamental biological principles, or development
of knowledge that can reasonably be expected to benefit humans,
animals, or the environment.
2. Optimal standards for animal health and care result in enhanced
credibility and reproducibility of experimental results.
RESEARCH FOCUS 7-4

Attention-Deficit/Hyperactivity Disorder
Together, attention-deficit/hyperactivity disorder (ADHD) and
attention-deficit disorder (ADD) are probably the most common
disorders of brain and behavior in children, with an incidence of 4
percent to 10 percent of school-aged children. Although it often goes
unrecognized, an estimated 50 percent of children with ADHD still
show symptoms in adulthood, where its behaviors are associated
with family breakups, substance abuse, and driving accidents.
The neurobiological basis of ADHD and ADD is generally
believed to be a dysfunction in the noradrenergic or dopaminergic
activating system, especially in the frontal basal ganglia circuitry.
Psychomotor stimulants such as methylphenidate (Ritalin) and
Adderall (mainly dextroamphetamine) act to increase brain levels of
noradrenaline and dopamine and are widely used for treating ADHD.
About 70 percent of children show improvement of attention and
hyperactivity symptoms with treatment, but there is little evidence
that drugs directly improve academic achievement. This is important
because about 40 percent of children with ADHD fail to get a high-
school diploma, even though many receive special education for
their condition.

Robin Nelson/Photo Edit

 In this mainstreamed first-grade classroom, a special education
student with ADHD uses the turtle technique to cope with
frustration and stress.

Stephen Faraone and coworkers (Lecendreux et al., 2015) have

challenged a common view, that ADHD is a cultural phenomenon
reflecting parents’ and teachers’ tolerance of children’s behavior.
These investigators conclude that the prevalence of ADHD
worldwide is remarkably similar when the same rating criteria are
used. Little is known about incidence in developing countries,
however. It is entirely possible that the incidence may actually be
higher in developing countries, given that the learning environment
for children is likely to be less structured than it is in developed
nations.
The cause of ADHD is unknown but probably involves dopamine
receptors in the forebrain. The most likely areas are the frontal lobe
and subcortical basal ganglia. Evidence of reduced brain volumes in
these regions in ADHD patients is growing, as is evidence of an
increase in the dopamine transporter protein. The dopamine
transporter increase would mean that dopamine reuptake into the
presynaptic neuron occurs faster than it does in the brain of people
without ADHD. The result is a relative decrease in dopamine. Ritalin
works by blocking dopamine reuptake.
ADHD is believed to be highly heritable, a conclusion supported
by twin studies showing a concordance of about 75 percent in
identical twins. Molecular genetic studies have identified at least
seven candidate genes, and several of them are related to the
dopamine synapse, in particular to the D4 receptor gene.

3. Acceptance of animal use in science critically depends on maintaining

public confidence in the mechanisms and processes used to ensure
necessary, humane, and justified animal use.
4. Animals are used only if the researcher’s best efforts to find an
alternative have failed. Researchers who use animals employ the most
humane methods on the smallest number of appropriate animals
required to obtain valid information.
Legislation concerning the care and use of laboratory animals in the
United States is set forth in the Animal Welfare Act, which includes laws
passed by Congress in 1966, 1970, 1976, and 1985. Legislation in other
countries is similar and in some European countries much stricter. The
U.S. act covers mammals, including rats, mice, cats, dogs, primates, and
birds, but it excludes farm animals that are not used in research. The U.S.
Department of Agriculture (USDA) administers the Act through
inspectors in the Animal Care section of the Animal and Plant Health
Inspection Service.
In addition, the Office of Human Research Protections of the National
Institutes of Health (NIH) administers the Health Research Extension
Act (passed in 1986). The act covers all animal uses conducted or
supported by the U.S. Public Health Service and applies to any live
vertebrate animal used in research, training, or testing. The Act requires
that each institution provide acceptable assurance that it meets all
minimum regulations and conforms with The Guide for the Care and
Use of Laboratory Animals (National Research Council, 2011) before
conducting any activity that includes animals. The typical method for
demonstrating conformance with the Guide is to seek voluntary
accreditation from the Association for Assessment and Accreditation of
Laboratory Animal Care International.
All accredited U.S. and Canadian universities that receive government
grant support are required to provide adequate treatment for all
vertebrate animals. Reviews and specific protocols for vertebrates,
including fish, amphibians, reptiles, birds, and mammals, to be used in
research, teaching, or testing are administered through the same process.
Anyone using animals in a U.S. or Canadian university submits a
protocol to the university’s institutional animal care and use committee,
composed of researchers, veterinarians, people who have some
knowledge of science, and laypeople from the university and the
community.
Companies that use animals for research are not required to follow
this process. In effect, however, if they do not, they will be unable to
publish the results of their research, because journals require that
research conform to national guidelines on animal care. In addition,
discoveries made using animals are not recognized by government
agencies that approve drugs for clinical trials with humans if they do not
follow the prescribed process. Companies therefore use Good Laboratory
Practice (GLP) standards, which are as rigorous as those used by
government agencies.
 Regulations specify that researchers consider alternatives to
procedures that may cause more than momentary or slight pain or
distress to animals. Most of the attention on alternatives has focused on
the use of animals in testing and stems from high public awareness of
some tests for pharmacological compounds, especially toxic compounds.
In the United States, the National Institute of Environmental Health
Sciences now regulates testing of such compounds.
In spite of the legislation related to animal use, considerable
controversy remains over using animals in scientific research. At the
extremes, people on one side approve any usage and people on the other
side disapprove of using animals for any form of research. Most fall
somewhere in between. The debate centers on issues of philosophy, law,
morals, custom, and biology.
Because researchers in many branches of science experiment with
animals to understand the functions of the human and nonhuman body,
brain, and behavior, the issues in this debate are important to them.
Because human and veterinary medicine benefit from this research, as
well as do people and other animals with diseases or damage of the
nervous system, this debate is important. Because many people are
philosophically opposed to using animals for work or food, this debate is
important to them. And because you, as a student, encounter many
experiments on animals in this book, these issues are important to you as
well.
 7-7 REVIEW
Using Animals in Brain–Behavior Research
Before you continue, check your understanding.
1 . Laboratory animals can model such human dysfunctions as
____________ and ____________.
2 . One difficulty in using lab animals as models of human disease is
determining ____________.
3 . Animal models provide a way to investigate both proposed
____________ and for ____________ behavioral disorders.
4 . Outline the controversies that surround the use of animals in scientific
research on brain and behavioral relationships.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 SUMMARY
7-1 Measuring and Manipulating Brain and Behavior
The brain’s primary function is to produce behavior, so the fundamental
research technique in behavioral neuroscience is to study the direct
relationship between brain and behavior. Investigators study healthy
humans and other animals as well as human patients and laboratory
animals with neurological problems.
Initially, scientists simply observed behavior, but they later developed
neuropsychological testing measures designed to study specific functions
such as fine movements, memory, and emotion. Today, researchers
correlate these behavioral outcomes with anatomical, physiological,
chemical, genetic, and other molecular measures of brain organization.
Brain and behavioral relations can be manipulated by altering brain
function, either permanently or temporarily. Permanent changes involve
damaging the brain directly by ablation or neurotoxins that remove or
destroy brain tissue. Transient changes in brain activity can be induced
either by use of a mild electrical or magnetic current, as in DBS or TMS,
or by administration of drugs. Optogenetics, a transgenic technique,
employs light-activated ion channels to excite or inhibit targeted cells in
living tissue. Chemogenetic stimulation combines designer receptors and
synthetic drugs to excite targeted cells in living tissue.
7-2 Measuring the Brain’s Electrical Activity
Recording from single or multiple cells shows that neurons employ a
code and that cortical neurons are organized into functional groups that
work as coordinated networks. Neurons in sensory areas respond to
specific characteristics of stimuli, such as color or pitch. Other neurons,
such as place cells in the hippocampal formation, can code for more
complex information, such as an object’s location in space.
Electroencephalographic or magnetoencephalographic recordings
measure electrical or magnetic activity from thousands of neurons at
once. EEG can reveal a gross relationship between brain and behavior, as
when a person is alert and displays the beta wave pattern versus when
the person is resting or sleeping, indicated by the slower alpha wave
patterns. Event-related potentials tell us, on the other hand, that even
though the entire brain is active during waking, certain parts are
momentarily much more active than others. ERP records how the
location of increased activity changes as information moves from one
brain area to another.
EEG and ERP are noninvasive methods that record from electrodes
on the scalp; in the case of MEG, from magnetic detectors above the
head. Electrocorticography, by contrast, records via electrodes attached
directly to the cortex. ECoG and single-cell recording techniques are
invasive.
7-3 Anatomical Imaging Techniques: CT and MRI
Computed tomography and magnetic resonance imaging are sensitive to
the density of brain structures, ventricles, nuclei, and pathways. CT is a
form of three-dimensional X-ray, whereas MRI works on the principle
that hydrogen atoms behave like spinning bar magnets in the presence of
a magnetic field.
Although CT scans are quicker and less expensive, MRI provides
exceptionally clear images, both of nuclei and of fiber pathways in the
brain. MRI also indicates that people’s brain structure varies widely.
Both CT and MRI can be used to assess brain damage from neurological
disease or injury, but MRI is more useful as a research tool.
Diffusion tensor imaging is a form of MRI that makes it possible to
identify normal or abnormal fiber tracts and myelin in the brain.
Magnetic resonance spectroscopy, another form of MRI, permits
practitioners to detect brain metabolites, such as those produced
following concussion.
7-4 Functional Brain Imaging
Metabolic imaging shows that any behavior requires the collaboration of
widespread neural circuits. Positron emission tomography records blood
flow and other metabolic changes in periods measured in minutes, and
requires complex subtraction procedures and the averaging of responses
across multiple subjects. Records of blood flow obtained using
functional magnetic resonance imaging can be combined with
anatomical MRI images to locate changes in the individual brain and to
complement ERP results. Resting-state fMRI allows investigators to
measure connectivity across brain regions.
Functional near-infrared spectroscopy is the form of optical
tomography usually used for functional brain imaging studies. It works
on the principle that an object, including brain tissue, can be
reconstructed by gathering light transmitted through the object. fNIRS is
much simpler to use than PET or fMRI, but because light does not
penetrate very far into the brain, it can be used only to study cortical
function.
7-5 Chemical and Genetic Measures of Brain and
Behavior
Analysis of changes in both genes and neurochemicals provides insight
into the molecular correlates of behavior. Although genes code all the
information needed to construct and regulate cells, epigenetic research
reveals that the environment and life experience can modify gene
expression. Even identical twins, who have an identical genome at birth,
in adulthood have widely differing patterns of gene expression and very
different brains.
7-6 Comparing Neuroscience Research Methods
The main consideration in neuroscience research is the question.
Whatever the approach, the goal is to understand brain–behavior
relationships. Tables 7-1 and 7-2 on pages 238 and 239 summarize the
manipulations and measurements used in behavioral neuroscience.
Among all the practical issues of measurement resolution and
invasiveness, cost may prove the ultimate consideration.
7-7 Using Animals in Brain–Behavior Research
Understanding brain function, in both the healthy and the disordered
brain, often benefits from animal models. Investigators develop animal
models to manipulate the brain—to determine how experiential factors
and neurological treatments affect brain function.
Because animal subjects cannot protect themselves from abuse,
governments and researchers have cooperated to develop ethical
guidelines for the use of laboratory animals. These guidelines are
designed to ensure that discomfort is minimized, as is the number of
animals used for invasive procedures.
 KEY TERMS
alpha rhythm, p. 224
behavioral neuroscience, p. 214
cerebral voltammetry, p. 234
chemogenetics, p. 220
compensation, p. 218
computed tomography (CT), p. 226
deep-brain stimulation (DBS), p. 218
diffusion tensor imaging (DTI), p. 228
electrocorticography (ECoG), p. 223
event-related potential (ERP), p. 224
functional magnetic resonance imaging (fMRI), p. 230
functional near-infrared spectroscopy (fNIRS), p. 211
hypokinesia, p. 218
magnetic resonance imaging (MRI), p. 226
magnetic resonance spectroscopy (MRS), p. 228
magnetoencephalogram (MEG), p. 226
microdialysis, p. 234
neuropsychology, p. 211
optogenetics, p. 220
place cells, p. 223
positron emission tomography (PET), p. 232
resting-state fMRI (rs-fMRI), p. 230
stereotaxic apparatus, p. 218
striatum, p. 234
synthetic biology, p. 220
transcranial magnetic stimulation (TMS), p. 220
 Visit Lounch Pad to access the e-Book, videos,
Learning Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

How Does the Nervous

System Develop and
Adapt?
 Katherine Streeter

RESEARCH FOCUS 8-1 LINKING SOCIOECONOMIC STATUS TO

CORTICAL DEVELOPMENT
8-1 THREE PERSPECTIVES ON BRAIN DEVELOPMENT
CORRELATING EMERGING BRAIN STRUCTURES WITH
EMERGING BEHAVIORS
CORRELATING EMERGING BEHAVIORS WITH NEURAL
MATURATION
IDENTIFYING INFLUENCES ON BRAIN AND BEHAVIOR
8-2 NEUROBIOLOGY OF DEVELOPMENT
GROSS DEVELOPMENT OF THE HUMAN NERVOUS SYSTEM
ORIGINS OF NEURONS AND GLIA
NEURONAL GROWTH AND DEVELOPMENT
CLINICAL FOCUS 8-2 AUTISM SPECTRUM DISORDER
UNIQUE ASPECTS OF FRONTAL LOBE DEVELOPMENT
GLIAL DEVELOPMENT
8-3 USING EMERGING BEHAVIORS TO INFER NEURAL
MATURATION
MOTOR BEHAVIORS
LANGUAGE DEVELOPMENT
DEVELOPMENT OF PROBLEM-SOLVING ABILITY
EXPERIMENT 8-1 QUESTION: IN WHAT SEQUENCE DO THE
FOREBRAIN STRUCTURES REQUIRED FOR LEARNING AND
MEMORY MATURE?
A CAUTION ABOUT LINKING CORRELATION TO CAUSATION
8-4 BRAIN DEVELOPMENT AND THE ENVIRONMENT
EXPERIENCE AND CORTICAL ORGANIZATION
RESEARCH FOCUS 8-3 INCREASED CORTICAL ACTIVATION
FOR SECOND LANGUAGES
EXPERIENCE AND NEURAL CONNECTIVITY
 CRITICAL PERIODS FOR EXPERIENCE AND BRAIN
DEVELOPMENT
ABNORMAL EXPERIENCE AND BRAIN DEVELOPMENT
HORMONES AND BRAIN DEVELOPMENT
CLINICAL FOCUS 8-4 ROMANIAN ORPHANS
GUT BACTERIA AND BRAIN DEVELOPMENT
INJURY AND BRAIN DEVELOPMENT
DRUGS AND BRAIN DEVELOPMENT
OTHER SOURCES OF ABNORMAL BRAIN DEVELOPMENT
CLINICAL FOCUS 8-5 SCHIZOPHRENIA
DEVELOPMENTAL DISABILITY
8-5 HOW DO ANY OF US DEVELOP A NORMAL BRAIN?
RESEARCH FOCUS 8-1

Linking Socioeconomic Status to Cortical

Development
Nobel Prize–winning American economist James Heckman has
argued passionately about one effective strategy for economic
growth: investing as early as possible in disadvantaged families
promotes optimal development of young children at risk. Heckman
notes that children from lower SES families typically develop gaps
in knowledge and ability relative to their more advantaged peers.
These gaps influence health and prosperity, and they persist
throughout life. Childhood SES correlates with cognitive
development, language, memory, social and emotional processing,
and ultimately with income and health in adulthood. One reason:
early experiences related to SES influence children’s cerebral
development.
To examine cerebral development, neuroimaging studies (as
shown in Figure 8-14 ) visualize differences in brain development
that relate to growing up in under-resourced environments. As the
brain grows throughout childhood and adolescence, the cortical
surface area expands before declining in adulthood (Schnack et al.,
2014). Cortical surface area reflects the amount of neural tissue
available for different behaviors and correlates positively with
cognitive ability. It should be possible to estimate the effect of early
experiences on brain and behavioral development by comparing the
cortical surface area and cognitive abilities of people raised in lower
or higher SES families.
Kimberly Noble and her colleagues (2015) used neuroimaging to
investigate the relationship between SES and cortical surface area in
more than 1000 participants aged 3 to 20. As shown in the
illustration, lower family income, independent of race or sex, was
associated with decreased cortical surface area in widespread regions
of frontal, temporal, and parietal lobes, the regions shown in red.
The investigators also measured participants’ cognitive
performance on tests of attention, memory, vocabulary, and reading.
 The larger the cortical surface area, the better the test outcomes. The
negative effects of low SES were especially dramatic at the lower
end of the family income spectrum, especially in families with
annual incomes less than $30,000.
Low SES is associated with poor nutrition, high stress, and
insufficient prenatal and infant care. Following on Heckman’s thesis,
investing in children from low-income families will increase societal
health and prosperity, because these children can optimize their brain
development and realize their developmental potential. Policies
aimed toward decreasing poverty can lead to clear improvements in
children’s cognitive and brain development.

Research from “Family income, parental education, and brain

structure in chil dren and adol escents” by K. G. Nobl., 2015,
NatureNeuroscience, online doi: 10.1038/nn.3983, Figure 2C, p.
4.

After adjusting for age, sex, race, and parental education, Noble and
colleagues associated family income with cortical surface area. Areal
brain regions shown in red were significantly smaller in children
from low-SES families.

To see how scientists go about studying the interconnected

processes of brain and behavioral development, think about all the
architectural parallels between how the brain is constructed and how a
house is built. House plans are drawn as blueprints; the plans for a brain
are encoded in genes. Architects do not specify every detail in a
blueprint, nor do genes include every instruction for brain assembly and
wiring.
The brain is too complex to be encoded entirely and precisely in
genes. This leaves the fate of billions of brain cells partly undecided,
especially in regard to the massive undertaking of forming appropriate
connections between cells.
If the structure and fate of each brain cell are not specified in advance,
what controls brain development? Many factors are at work, and as with
house building, brain development is influenced by the environment in
the course of the construction phase and by the quality of the materials.
As we saw in Research Focus 8-1 , Linking Socioeconomic Status to
Cortical Development, living in poverty can compromise children’s brain
development.
We can shed light on nervous system development by viewing its
architecture from different vantage points—structural, functional, and
environmental. In this chapter, we consider the neurobiology of
development first, explore behavioral correlates of developing brain
functions next, then explore how experiences and environments
influence neuroplasticity over the life-span.
 Three Perspectives on Brain
8-1

Development
Brain and behavior develop apace, and scientists thus reason that the two
are closely linked. Events that alter behavioral development should
similarly alter the brain’s structural development and vice versa. As the
brain develops, neurons become more and more intricately connected,
and these increasingly complex interconnections underlie increasingly
complex behaviors. These observations enable neuroscientists to study
the relation between brain and behavioral development from three
perspectives:
1. Structural development can be correlated with emerging behaviors.
2. Behavioral development can be predicted by the underlying circuitry
that must be emerging.
3. Research can focus on factors such as language, injury, or
socioeconomic status (SES) that influence both brain structure and
behavioral development.

Correlating Emerging Brain Structures with

Emerging Behaviors
We can look at the nervous system’s structural development and
correlate it with the emergence of specific behaviors. For example, the
development of certain brain structures links to the motor development
of, say, grasping or crawling in infants. As brain structures mature, their
functions emerge and develop, as manifested in behaviors we can
observe.
Neural structures that develop quickly—the visual system, for
instance—exhibit their functions sooner than do structures that develop
more slowly, such as those used for speech. Because the human brain
continues to develop well into adulthood, some abilities emerge or
mature rather late. Some cognitive behaviors controlled by the frontal
lobes are among the last to develop. One such behavior, the ability to
plan efficiently, is a skill vital to many complexities of life, including
organizing daily activities or making travel plans.
The Tower of Hanoi test, illustrated in Figure 8-1 , shows how
planning skills can be measured in the laboratory. The task is to plan how
to move colored discs one by one, in the minimum number of moves,
from one configuration to another. Most 10-year-olds can solve simple
configurations, but more difficult versions of the task, such as shown in
Figure 8-1 , cannot be performed efficiently until about age 15 to 17. No
surprise then that adolescents often appear disorganized: their ability to
plan has yet to mature.
Mature adults with acquired frontal lobe injuries also fail to perform
well on the Tower of Hanoi test. Such evidence reinforces the idea that
children are not miniature adults who simply need to learn the “rules” of
adult behavior. A child’s brain is vastly different from an adult’s, and the
brains of children at different ages are not really comparable either.

GOAL

Move discs on towers below one by one to match goal above.

FIGURE 8-1 Testing Cognitive Development The Tower of

Hanoi is a mathematical puzzle consisting of three rods and several
different-sized discs. The task is to match the goal in as few moves as
possible, obeying two rules: (1) only one disc may be moved at a time; (2)
no disc may be placed on top of a smaller disc.

Correlating Emerging Behaviors with

Neural Maturation
We can turn our observational sequence around and scrutinize behavior
for the emergence of new abilities, then, inferring underlying neural
maturation. For example, as language emerges in the young child, we
expect to find corresponding changes in neural structures that control
language. In fact, neuroscientists do find such changes.
At birth, children do not speak, and even extensive training would not
enable them to do so. The neural structures that control speech are not
yet ready. Thus, as language emerges, the speech-related structures in the
brain are undergoing the necessary maturation.
The same reasoning can be applied to frontal lobe development. As
frontal lobe structures mature through adolescence and into early
adulthood, we look for related changes in behavior. We can also do the
reverse: because we observe new abilities emerging in the teenage years
and even later, we infer that they must be controlled by late-maturing
neural structures and connections.

Identifying Influences on Brain and

Behavior
The third approach to developmental interrelations between brain and
behavior is to identify and study factors that influence both. From this
perspective, the mere emergence of a fully developed brain structure is
not enough. We must also know the events that shape how that structure
functions and produces behaviors. Some events that influence brain
function are sensory experience, injuries, and the actions of hormones
and genes.
Logically, if one factor influences behavior, then the brain structures
changed by that factor are those responsible for the behavioral outcomes.
For example, we might study how the abnormal secretion of a hormone
affects both a certain brain structure and a certain behavior. We can then
infer that because the observed behavioral abnormality results from the
abnormally functioning brain structure, the structure must typically play
some role in controlling the behavior.
 8-1 REVIEW
Three Perspectives on Brain Development
Before you continue, check your understanding.
1 . Structural brain development is correlated with the emergence of
___________.
2 . Behavioral development predicts the maturation of ___________.
3 . Three factors that influence brain function are ___________,
___________, and ___________.
4 . What important constraint determines when behaviors emerge?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
Salamander
Chick
 Human

FIGURE 8-2 Embryos and Evolution The physical similarity of embryos of

different species is striking in the earliest stages of development, as the salamander,
chick, and human embryos in the top row show. This similarity led to the conclusion that
embryos are not simply miniature versions of adults.
 8-2 Neurobiology of Development
Some 2000 years ago, the Roman philosopher Seneca the Younger
proposed that a human embryo is an adult in miniature, and thus the task
of development is simply to grow bigger. This idea of preformation was
so appealing that it was widely believed for centuries. Even with the
development of the microscope, the appeal of preformation proved so
strong that biologists claimed to see microscopic horses in horse semen.
By the mid-1800s, preformation began to lose ground as people
realized that embryos look nothing like the adults they become. In fact, it
was obvious that embryos of different species more closely resemble one
another than their respective parents. The top row of Figure 8-2 shows
the striking similarity among embryos of species as diverse as
salamanders, chickens, and humans, each shown in fetal form in the
bottom row.
As embryos, all vertebrate species have a similar-looking primitive
head, a region with bumps or folds, and a tail. Only as an embryo
develops does it acquire the distinctive characteristics of its species. The
similarity of young embryos is so great that many nineteenth-century
biologists saw it as evidence for Darwin’s view that all vertebrates arose
from a common ancestor millions of years ago.
The embryonic nervous systems of vertebrates are as similar
structurally as their bodies are. Figure 8-3 details the three-chambered
brain of a young vertebrate embryo: forebrain, midbrain, and hindbrain.
The remaining neural tube forms the spinal cord. How do these three
regions develop? We can trace the events as the embryo matures.
 FIGURE 8-3 Embryonic Vertebrate Nervous System
Forebrain, midbrain, and hindbrain are visible in the human embryo at
about 28 days, as is the remaining neural tube, which will form the spinal
cord.

Gross Development of the Human Nervous

System
When a sperm fertilizes an egg, the resulting human zygote consists of
just a single cell. But this cell soon begins to divide. By the fifteenth day
after fertilization, the emerging embryo resembles a fried egg ( Figure 8-
4 ), a structure formed by several sheets of cells with a raised area in the
middle called the embryonic disc— essentially the primitive body.
Day 1: Fertilization
 Day 2: Division

Day 15
FIGURE 8-4 From Fertilization to Embryo Development begins
at fertilization (day 1), with the formation of the zygote. On day 2, the
zygote begins to divide. On day 15, the raised embryonic disc begins to
form. Information from K. L. Moore (1998). The developing human: Clinically oriented
embryology (4th ed., p. 61). Philadelphia: Saunders.

By day 21, 3 weeks after conception, primitive neural tissue, the

neural plate, occupies part of the outermost layer of embryonic cells.
First the neural plate folds to form the neural groove, detailed in Figure
8-5 . The neural groove then curls to form the neural tube, much as you
can curl a flat sheet of paper to make a cylinder.
neural plate Primitive neural tissue that gives rise to the neural tube.
neural tube Structure in the early stage of brain development from
which the brain and spinal cord develop.
Prenatal Stages
Zygote Fertilization to 2 weeks

Embryo 2 to 8 weeks
Fetus 9 weeks to birth
 Prof. P.M. Motta/Science Source

FIGURE 8-5 Formation of the Neural Tube A long depression,

the neural groove, first forms in the neural plate. By day 21, the primitive
brain and neural groove are visible. On day 23, the neural tube is forming
as the neural plate collapses inward along the length of the embryo’s dorsal
surface. The embryo is shown in a photograph at 24 days.
(A) Day 9
(B) Day 10
(C) Day 11
FIGURE 8-6Neural Tube Development Scanning electron micrographs show
the neural tube closing in a mouse embryo. Reproduced with the permission of Prof. Dr. R. E.
Poelmann,D ept. Cardiology, Leiden University Medical Center, Institute of Biology IBL, University of Leiden,
Leiden, The Netherlands.

The cells that form the neural tube can be regarded as the nursery for
the rest of the central nervous system. The open region in the tube’s
center remains open and matures into the brain’s ventricles and the spinal
canal. The micrographs in Figure 8-6 show the neural tube closing in a
mouse embryo.
The human body and nervous system change rapidly in the next 3
weeks (Figure 8-7 ). By 7 weeks (49 days), the embryo begins to
resemble a miniature person. The brain looks distinctly human by about
100 days after conception, but it does not begin to form gyri and sulci
until about 7 months. By the end of the ninth month, the fetal brain has
the gross appearance of the adult human brain, but its cellular structure is
different.

Origins of Neurons and Glia

The neural tube is the brain’s nursery. Neural stem cells lining it have an
extensive capacity for self-renewal. When a stem cell divides, it produces
two stem cells; one dies and the other lives to divide again. This process
repeats again and again throughout life. In an adult human, neural stem
cells line the ventricles, forming the subventricular zone.
neural stem cell Self-renewing multipotential cell that gives rise to
any of the different types of neurons and glia in the nervous system.
subventricular zone Lining of neural stem cells surrounding the
ventricles in adults.
Adult stem cells that line the subventricular zone also are located in
the hippocampus, spinal cord, and retina.
If lining the ventricles were all that stem cells did throughout the
decades of a human life, they would seem very odd cells to possess. But
neural stem cells have a function beyond self-renewal: they give rise to
progenitor cells (precursor cells ), which also can divide. As shown in
Figure 8-8 , progenitor cells eventually produce nondividing cells known
as neuroblasts and glioblasts. In turn, neuroblasts and glioblasts mature
into neurons and glia. Neural stem cells, then, are multipotent : they give
rise to all the many specialized cell types in the CNS.
progenitor cell (precursor cell) Derived from a stem cell; it
migrates and produces a neuron or a glial cell.
neuroblast Product of a progenitor cell that gives rise to any of the
different types of neurons.
glioblast Product of a progenitor cell that gives rise to different types
of glial cells.
Sam Weiss and his colleagues (1996) discovered that stem cells remain
capable of producing neurons and glia not just into early adulthood but
even in an aging brain. This important discovery implies that neurons that
die in an adult brain should be replaceable. But neuroscientists do not yet
know how to instruct stem cells to replace them.
One possibility is to make use of signals that the brain typically uses to
control stem cell production in adults. For example, the level of the
neuropeptide prolactin increases when female mice are pregnant and
stimulates the fetal brain to produce more neurons (Shingo et al., 2003).
These naturally occurring hormonal signals have been shown to replace
lost neurons in brain-injured laboratory animals.
4 weeks
5 weeks
6 weeks
7 weeks
14 weeks
20 weeks
24 weeks
28 weeks
 32 weeks

Forebrain
Midbrain
Hindbrain
Neural tube (forms spinal cord)
36 weeks
FIGURE 8-7 Prenatal Brain Development The developing
human brain undergoes a series of embryonic and fetal stages. You can
identify the forebrain, midbrain, and hindbrain by color (review Figure 8-3 )
as they develop in the course of gestation. At 6 months, the developing
forebrain has enveloped the midbrain structures. Research from Cowan, W. M.
(1979). The development of the brain. Scientific American, 241(3), p. 116.
 FIGURE 8-8 Origin of Brain Cells Cells in the brain begin as
multipotential stem cells, develop into precursor cells, then produce blasts
that finally develop into specialized neurons or glia.

How does a stem cell know to become a neuron rather than a skin cell?
In each cell, certain genes are expressed (turned on) by a signal, and those
genes then produce a particular cell type. Gene expression means that a
formerly dormant gene is activated so that the cell makes a specific
protein. You can easily imagine that certain proteins produce skin cells,
whereas other proteins produce neurons.
The specific signals for gene expression are largely unknown but
probably are chemical, and they form the basis of epigenetics. A common
epigenetic mechanism that suppresses gene expression during
development is gene methylation, or DNA methylation. Here a methyl
group (CH3 ) attaches to the nucleotide base cytosine lying next to
guanine on the DNA sequence. It is relatively simple to quantify gene
methylation in different phenotypes, reflecting either an increase or a
decrease in overall gene expression.
Methylation alters gene expression dramatically during development.
Prenatal stress can reduce gene methylation by 10 percent. This means
that prenatally stressed infants express 2000 more genes (of the more than
20,000 in the human genome) than unstressed infants (Mychasiuk et al.,
2011). Other epigenetic mechanisms, such as histone modification and
mRNA modification, can regulate gene expression, but these mechanisms
are more difficult to quantify.
Thus, the chemical environment of a brain cell is different from that of
a skin cell: different genes in these cells are activated, producing different
proteins and different cell types. The chemical environments needed to
trigger cellular differentiation could be produced by the activity of
neighboring cells or by chemicals, such as hormones, that are transported
in the bloodstream.

Gene Methylation Figure 3-25 contrasts the mechanisms of

histone and mRNA modification to DNA methylation.

The differentiation of stem cells into neurons must require a series of

gene-activating signals. A chemical signal must induce stem cells to
produce progenitor cells; another chemical signal must induce the
progenitor cells to produce either neuroblasts or glioblasts. Finally, a
chemical signal—perhaps a set of signals—must induce the genes to
make a particular type of neuron.
Compounds that signal cells to develop in particular ways are
neurotrophic factors (-trophic means nourishing ). By removing stem
cells from an animal’s brain and placing those cells in solutions that keep
them alive, researchers can study how neurotrophic factors function. One
compound, epidermal growth factor (EGF), when added to the stem cell
culture stimulates production of progenitor cells. Another compound,
basic fibroblast growth factor (bFGF, or FGF-2), stimulates progenitor
cells to produce neuroblasts.
neurotrophic factor A chemical compound that supports growth
and differentiation in developing neurons and may act to keep certain
 neurons alive in adulthood.
At this point, the destiny of a given neuroblast is undetermined. The
blast can become any type of neuron if it receives the right chemical
signals. The body relies on a general-purpose neuron that matures into a
specific cell type in a particular location when exposed to certain
neurotrophic factors.
This flexibility makes brain development simpler than it would be if
each different cell type, as well as the number of cells of each type, had to
be specified precisely in an organ-ism’s genes. In the same way, building
a house from all-purpose two-by-fours that can be cut to any length as
needed is easier than specifying in a blueprint a precise number of precut
pieces of lumber that can be used only in a certain location.
TABLE 8-1 Stages of Brain Development
1 Cell birth (neurogenesis; gliogenesis)

2 Cell migration

3 Cell differentiation

4 Cell maturation (dendrite and axon growth)

5 Synaptogenesis (formation of synapses)

6 Cell death and synaptic pruning

7 Myelogenesis (formation of myelin)

Neuronal Growth and Development

The human brain requires approximately 10 billion (1010 ) cells to form
just the cortex that blankets a single hemisphere. This means it must
produce about 250,000 neurons per minute at the peak of prenatal brain
development. But as Table 8-1 shows, this rapid formation of neurons
(neurogenesis) and glia (gliogenesis) is just the first step in brain growth.
These new cells must travel to the correct destination (migration ), they
must differentiate into the right type of neuron or glial cell, and the
neurons then must grow dendrites and axons and form synapses.
The brain also prunes unnecessary cells and connections, sculpting
itself according to the particular person’s experiences and needs. We
consider these stages in brain development next, focusing on cortical
development, because neuroscientists know more about development of
the cortex than of any other area of the human brain. The principles
derived from our examination of the cortex, however, apply to neural
growth and development in other brain regions as well.
In Focus 8-1, investigators used cortical development as a measure
of SES’s effects.
Neuronal Generation, Migration, and Differentiation
Figure 8-9 shows that neurogenesis is largely complete after about 5
months of gestation. (Some growth continues until about 5 years of age.)
An important exception is the hippocampus, where new neurons continue
to develop throughout life.
Until after full-term birth, however, the fetal brain is especially
delicate and extremely vulnerable to injury, teratogens (chemicals that
cause malformations), and trauma. Apparently, the developing brain can
more easily cope with injury earlier, during neurogenesis, than it can
during the later stages of cell migration or cell differentiation, when cell
maturation begins (see Table 8-1 ). One reason may be that once
neurogenesis has slowed, it is very hard to start it up again. If
neurogenesis is still progressing at a high rate, more neurons can be made
to replace injured ones, or perhaps existing neurons can be allocated
differently. The absence of neurogenesis in adulthood, other than in the
hippocampus, also explains why adult brain tumors arise from glial cells,
which are generated throughout adulthood, rather than from neurons. In
contrast, brain tumors in young children are sometimes neuronal,
reflecting some lingering neurogenesis.
Focus 11-2 describes outcomes resulting from cerebral palsy, caused
by brain trauma acquired perinatally.
 Prenatal Development of the Human
FIGURE 8-9

Cerebral Cortex Brain weight and body weight increase rapidly and
in proportion. The cortex begins to form about 6 weeks after conception,
with neurogenesis largely complete by 25 weeks. Neural migration and cell
differentiation begin at about 8 weeks and are largely complete by about 29
weeks. Neuron maturation, including axon and dendrite growth, begins at
about 20 weeks and continues until well after birth. Information from M. Marin-
Padilla (1993). Pathogenesis of late-acquired leptomeningeal heterotopias and secondary
cortical alterations: A Golgi study. In A. M. Galaburda (Ed.), Dyslexia and development:
Neurobiological aspects of extraordinary brains.

Cell migration begins shortly after the first neurons are generated and
continues for about 6 weeks in the cerebral cortex (and throughout life in
the hippocampus). Cell differentiation, in which neuroblasts become
specific types of neurons, follows migration. Cell differentiation is
essentially complete at birth, although neuron maturation, which includes
the growth of dendrites, axons, and synapses, goes on for years and in
some parts of the brain may continue throughout adulthood.
The hippocampus (see Figure 2-25 ) is critical to memory (Section
14-3 ) and vulnerable to stress (Section 6-5 ).
The cortex is organized into layers distinctly different from one
another in their cellular makeup. How does this arrangement of
differentiated areas develop? Neuroscientist Pasko Rakic and his
colleagues (e.g., Geschwind & Rakic, 2013) have been finding answers to
this question for more than four decades. Apparently, the subventricular
zone contains a primitive cortical map that predisposes cells formed in a
certain ventricular region to migrate to a certain cortical location. One
subventricular region may produce cells destined to migrate to the visual
cortex; another might produce cells destined to migrate to the frontal
lobes, for example.
How do the migrating cells know where to find these different parts of
the cortex? They follow a path made by radial glial cells. A glial fiber
from each of these path-making cells extends from the subventricular
zone to the cortical surface, as illustrated in Figure 8-10 A . The close-up
views in Figure 8-10 B and C show that neural cells from a given
subventricular region need only follow the glial road to end up in the
correct location.
radial glial cell Path-making cell that a migrating neuron follows to
its appropriate destination.
(A)
(B)
(C)

FIGURE 8-10 Neuronal Migration (A) Neuroscientists hypothesize

that the cortical map is represented in the subventricular zone. (B) Radial
glial fibers extend from the subventricular zone to the cortical surface. (c)
Neurons migrate along the radial glial fibers that take them from the
protomap in the subventricular zone to the corresponding region in the
cortex. Information from P. Rakic (1974). Neurons in rhesus monkey cerebral cortex:
Systematic relation between time of origin and eventual disposition. Science, 183, p. 425.

As the brain grows, the glial fibers stretch but still go to the same
place. Figure 8-10 B also shows a cell moving across the radial glial
fibers. Although most cortical neurons follow the radial glial fibers, a
small number appear to migrate by seeking some type of chemical signal.
Researchers do not yet know why these cells function differently.
Cortical layers develop from the inside out, much like adding layers to
a tennis ball. The neurons of innermost layer VI migrate to their locations
first, followed by those destined for layer V and so on, as successive
waves of neurons pass earlier-arriving neurons to assume progressively
more exterior positions in the cortex. Cortex formation is a bit like
building a house from the ground up until you reach the roof. The
materials needed to build higher floors must pass through lower floors to
get to their destinations.
Figure 2-22 contrasts the sensory and motor cortices’ six distinct
layers and their functions.
To facilitate house construction, each new story has a blueprint-
specified dimension, such as 10 feet high. How do neurons determine
how thick a cortical layer should be? This is a tough question, especially
when you consider that the cortical layers are not all the same thickness.
Local environmental signals—chemicals produced by other cells—
likely influence the way cells form layers in the cortex. These
intercellular signals progressively restrict the choice of traits a cell can
express, as illustrated in Figure 8-11 . Thus, the emergence of distinct
cell types in the brain results not from the unfolding of a specific genetic
program but rather from the interaction of genetic instructions, timing,
and signals from other cells in the local environment.
Uncommitted precursor
Cells with some segregation of determinants
Further segregation of determinants
Intercellular environment
Diverse cells

FIGURE 8-11 Cellular Commitment As also shown in Figure 8-8 ,

precursor cells have unlimited possibilities, but as they develop, interacting
genetic, maturational, and environmental influences increasingly steer
them toward developing into a particular cell type.

Neuronal Maturation
After neurons migrate to their destination and differentiate, they begin to
mature by (1) growing dendrites to provide surface area for synapses with
other cells and (2) extending their axons to appropriate targets to initiate
synapse formation.
Two events take place in dendrite development: dendritic arborization
(branching) and the growth of dendritic spines. As illustrated in Figure 8-
12 , dendrites in newborn babies begin as individual processes protruding
from the cell body. In the first 2 years of life, dendrites develop
increasingly complex extensions that look much like leafless tree
branches: they undergo arborization. The dendritic branches then begin to
form spines, where most synapses on dendrites are located.
Although dendritic development begins prenatally in humans, it
continues for a long time after birth, as Figure 8-12 shows. Dendritic
growth proceeds at a slow rate, on the order of microns (µm, millionths of
a meter) per day. Contrast this with the development of axons, which
grow on the order of a millimeter per day, about a thousand times faster.

Age (months)
FIGURE 8-12 Neuronal Maturation in Cortical Language
Areas In postnatal cortical differentiation—shown here around Broca’s
area, which controls speaking—neurons begin with simple dendritic fields
that become progressively more complex until a child reaches about 2
years old. Brain maturation thus parallels a behavioral development: the
emergence of language. Figure from Biological Foundations of Language (pp. 160–161),
by E. Lenneberg, 1967, New York: Wiley.

The disparate developmental rates of axons and dendrites are

important, because the faster-growing axon can reach its target cell before
the cell’s dendrites are completely formed. Thus the axon may play a role
in dendritic differentiation and ultimately in neuron function—for
example, as part of the brain’s visual, motor, or language circuitry.
Abnormalities in the maturation rate can produce abnormalities in
patterns of neural connectivity, as explained in Clinical Focus 8-2 ,
Autism Spectrum Disorder.
CLINICAL FOCUS 8-2

Autism Spectrum Disorder

In the 1940s, Leo Kanner and Hans Asperger first used the term
autism (from the Greek autos, meaning self ) to describe children
who seem to live in their own world. Some were classified as
intellectually disabled; others seemed to function intellectually.
The contemporary term, autism spectrum disorder (ASD),
accommodates this behavioral range to include children with mild
and severe symptoms. Severe symptoms include greatly impaired
social interaction, a bizarre and narrow range of interests, marked
abnormalities in language and communication, and fixed, repetitive
movements.
autism spectrum disorder (ASD) Range of cognitive
symptoms from mild to severe that characterize autism; severe
symptoms include greatly impaired social interaction, a bizarre
and narrow range of interests, marked abnormalities in language
and communication, and fixed, repetitive movements.
The autism spectrum includes classic autism and related
disorders. Asperger syndrome, for example, is distinguished by an
obsessive interest in a single topic or object to the exclusion of
nearly any other. Children with Asperger are socially awkward and
also usually have delayed motor skill development. Rett syndrome,
characterized by poor expressive language and clumsy hand use,
almost exclusively affects girls.
The rate of ASD has been rising over the past four decades, from
fewer than 1 person in 2000 in 1980 to the 2014 estimate of the
Centers for Disease Control that as many as 1 in 68 children has
some form of autism. The actual incidence may be as high as 1 in 50
(Blumberg et al., 2013). The cause of this increased incidence is
uncertain. Suggestions include changes in diagnostic criteria,
diagnosis of children at a younger age, and epigenetic influences.
Although it knows neither racial nor ethnic nor social boundaries,
ASD is four times as prevalent in boys as in girls.
 The behavior of many children with ASD is noticeable from birth.
To avoid physical contact, these babies arch their backs and pull
away from caregivers or grow limp when held. But approximately
one-third of children develop typically until somewhere between 1
and 3 years of age, when symptoms of autism emerge.
Perhaps the most recognized characteristics of ASD are failure to
interact socially, repetitive rocking or hand flapping, impairments in
language development, and resistance to any change in routine.
Some children on the autism spectrum are severely impaired; others
learn to function quite well. Still others display savant syndrome, a
narrow range of exceptional abilities such as in music, art, or
mathematics, often accompanied by severe cognitive deficits.
The brains of children diagnosed with ASD look remarkably
typical. One emerging view is that these brains are characterized by
unusual neuronal maturation rates. MRI studies show that at about 6
months of age, the autistic brain’s growth rate accelerates to the point
that its total volume is 6 percent to 10 percent greater than that of
typical children.
Excessive brain volume is especially clear in the amygdala
(Nordahl et al., 2012) and in the temporal and frontal lobes, the latter
showing greater gray matter volume (see the review by Chen et al.,
2011). The subcortical amygdala plays an important role in
generating fear, and the social withdrawal component of ASD may
be related to the enlarged amygdala.
Accelerated brain growth associated with enlarged regions
suggests that connections between cerebral regions are atypical,
which would in turn produce atypical functioning. What leads to
such brain development? More than 100 genetic differences have
been described in children with ASD, so it is clear that no “autism
gene” is at work.
The mechanism that translates genetic irregularities into the
autistic brain is unknown but is likely to include epigenetic factors
that could be prenatal, postnatal, or both. Women have an increased
risk of giving birth to a child who develops ASD if they are exposed
to rubella (German measles) in the first trimester of pregnancy.
Researchers also suspect that industrial toxins can trigger autism, but
the cause or causes remain uncertain.
 No medical interventions exist for ASD. Behavioral therapies are
the most successful, provided they are intense (20 to 40 hours per
week) and the therapists are trained practitioners. The earlier
interventions begin, the better the prognosis. Neuroscience has so far
offered little insight into why behavioral therapies are effective,
although in an animal model of autism, Raza et al. (2015) showed
that tactile stimulation from birth until weaning reverses many
morphological abnormalities in cortical neurons, suggesting a
possible mechanism.
Autism may appear puzzling because no evolutionary advantage
for its symptoms is apparent, but perhaps one exists.
Characteristically, children with ASD are overly focused on specific
tasks or information. The ability to concentrate on a complex
problem for extended periods, it is suggested, is the basis for
humankind’s development and for cultural advances.. But too much
of such a good thing may lead to conditions such as ASD.

Kim Gunkel/Getty Images

Children with ASD often look typical, but some physical
anomalies do characterize the condition. The corners of the
mouth may be low compared with the upper lip (left), and the
tops of the ears may flop over (right). The ears may be a bit
lower than average and have an almost square shape.
 Courtesy of Dennis Bray
(A)

(B)
FIGURE 8-13 Seeking a Path (A) At the tip of this axon, nurtured in a
culture, a growth cone sends out filopodia seeking specific molecules to
guide the axon’s direction of growth. (B) Filopodia guide the growth cone
toward a target cell that is releasing cell adhesion or tropic molecules,
represented in the drawing by red dots.
 Axon-appropriate connections may be millimeters or even a meter
away in the developing brain, and the axon must find its way through
complex cellular terrain to make them. Axon connections present a
significant engineering problem for the developing brain. Such a task
could not possibly be specified in a rigid genetic program. Rather,
genetic–environmental interaction is at work again, as various molecules
that attract or repel the approaching axon tip guide the formation of
axonic connections.
Santiago Ramón y Cajal was the first scientist to describe this
developmental process a century ago. He called the growing tips of
axons growth cones. Figure 8-13 A shows that as growth cones extend,
they send out shoots, analogous to fingers reaching out to find a pen on a
cluttered desk. When one shoot, a filopod (pl. filopodia ), reaches an
appropriate target, the others follow.
growth cone Growing tip of an axon.
filopod (pl. filopodia) Process at the end of a developing axon that
reaches out to search for a potential target or to sample the
intercellular environment.
Growth cones are responsive to cues from two types of molecules
(Figure 8-13 B):
1. Cell adhesion molecules (CAMs) are cell-manufactured molecules
that either lie on the target cell’s surface or are secreted into the
intercellular space. Some provide a surface to which growth cones can
adhere, hence the name cellular adhesion molecule; others serve to
attract or repel growth cones.
cell adhesion molecule (CAM) A chemical molecule to which
specific cells can adhere, thus aiding in migration.
2. Tropic molecules, produced by the targets the axons’ growth cones
are seeking (- tropic means moving toward ; pronounced as trope, not
tropical ), essentially tell growth cones to come on over here. They
likely also tell other growth cones seeking different targets to keep
away.
tropic molecule Signaling molecule that attracts or repels growth
cones.
Do not confuse tropic (guiding) molecules with the trophic
(nourishing) molecules, discussed earlier, which support neuronal
 growth.
Although Ramón y Cajal predicted them more than 100 years ago,
tropic molecules have proved difficult to find. So far, only one group,
netrins (from Sanskrit for to guide ), has been identified in the brain.
Given the enormous number of brain connections and the great
complexity in wiring them, many other types of tropic molecules
undoubtedly will be found.
netrin Member of the only class of tropic molecules yet isolated.
Synaptic Development
The number of synapses in the human cerebral cortex is staggering, on
the order of 1014 , or 100,000 trillion. A genetic program that assigns
each synapse a specific location could not possibly determine each spot
for this huge number. As with all stages of brain development, only the
general outlines of neuronal connections in the brain are likely to be
genetically predetermined. The vast array of specific synaptic contacts is
then guided into place by a variety of local environmental cues and
signals.
A human fetus displays simple synaptic contacts in the fifth
gestational month. By the seventh gestational month, synaptic
development on the deepest cortical neurons is extensive. After birth,
synapse numbers increase rapidly. In the visual cortex, synaptic density
almost doubles between ages 2 months and 4 months and then continues
to increase until age 1 year.
Cell Death and Synaptic Pruning
To carve statues, sculptors begin with blocks of stone and chisel away
the unwanted pieces. The brain does something similar during cell death
and synaptic pruning. The chisel in the brain could be a genetic signal,
experience, reproductive hormones, stress, even SES. The effect of these
chisels can be seen in changes in cortical thickness over time, as
illustrated in Figure 8-14 , an atlas of brain images. The cortex actually
becomes measurably thinner in a caudal–rostral (back-to-front) gradient,
a process that is probably due both to synaptic pruning and to white
matter expansion. This expansion stretches the cortex, leading to
increased surface area, as illustrated in Research Focus 8-1 .
Gray-matter volume

Progressive Changes in Cortical

FIGURE 8-14

Thickness MRI scans track the maturation of gray matter in typical

development, revealing the length and pattern of maturation from the back
of the cortex to the front. Cortical thinning and increased surface area
 progress together. Courtesy Paul M Thompson/Laboratory of Neuro Imaging, Keck School
of Medicine of USC.

The graph in Figure 8-15 plots this rise and fall in synaptic density.
Pasko Rakic (1974) estimated that at the peak of synapse loss, a person
may lose as many as 100,000 per second. Synapse elimination is
extensive. Peter Huttenlocher (1994) estimated it at 42 percent in the
human cortex. We can only wonder what the behavioral consequence of
this rapid synaptic loss might be. It is probably no coincidence that
children, especially toddlers and adolescents, seem to change moods and
behaviors quickly.
How does the brain eliminate excess neurons? The simplest
explanation is competition, sometimes referred to as neural Darwinism.
Charles Darwin believed that one key to evolution is the variation it
produces in the traits possessed by a species. Those whose traits are best
suited to the local environment are most likely to survive. From a
Darwinian perspective, then, more animals are born than can survive to
adulthood, and environmental pressures weed out the less-fit ones.
Similar pressures cause neural Darwinism.
neural Darwinism Hypothesis that the processes of cell death and
synaptic pruning are, like natural selection in species, the outcome
of competition among neurons for connections and metabolic
resources in a neural environment.
What exactly causes this cellular weeding out in the brain? It turns out
that when neurons form synapses, they become somewhat dependent on
their targets for survival. In fact, deprived of synaptic targets, neurons
eventually die. They die because target cells produce neurotrophic
(nourishing) factors absorbed by the axon terminals that function to
regulate neuronal survival. Nerve growth factor (NGF), for example, is
made by cortical cells and absorbed by cholinergic neurons in the basal
forebrain.
If many neurons compete for a limited amount of a neurotrophic
factor, only some can survive. The death of neurons deprived of a
neurotrophic factor is different from the cell death caused by injury or
disease. When neurons are deprived of a neurotrophic factor, certain
genes seem to be expressed, resulting in a message for the cell to die.
This programmed process is called apoptosis.
apoptosis Genetically programmed cell death.
 Apoptosis accounts for the death of overabundant neurons, but it does
not account for the synaptic pruning from cells that survive. In 1976,
French neurobiologist Jean-Pierre Changeux proposed a theory for
synapse loss that also is based on competition (Changeux & Danchin,
1976). According to Changeux, synapses persist into adulthood only if
they have become members of functional neural networks. If not, they
are eventually eliminated from the brain. We can speculate that
environmental factors such as hormones, drugs, and experience would
influence active neural circuit formation and thus influence synapse
stabilization and pruning.
In addition to outright errors in synapse formation that give rise to
synaptic pruning, subtler changes in neural circuits may trigger the same
process. One such change accounts for the findings of Janet Werker and
Richard Tees (1992), who studied the ability of infants to discriminate
speech sounds taken from widely disparate languages, such as English,
Hindi (from India), and Salish (a Native American language). Their
results show that young infants can discriminate speech sounds of
different languages without previous experience, but their ability to do so
declines in the first year of life. An explanation for this declining ability
is that synapses encoding speech sounds not typically encountered in an
infant’s daily environment are not active simultaneously with other
speech-related synapses. As a result, they are eliminated.

FIGURE 8-15 Synapse Formation and Pruning Changes in

the relative density of synapses in the human visual cortex and prefrontal
cortex (its frontmost part) as a function of age. Data from J.-P. Bourgeois (2001).
Synaptogenesis in the neocortex of the newborn: The ultimate frontier for individuation?” In C.
 A. Nelson and M. Luciana (Eds.), Handbook of developmental cognitive neuroscience.
Cambridge, MA: MIT Press.

FIGURE 8-16 Gray Matter Thickness Brain maps showing the

statistical significance of yearly change in cortical thickness measures
taken from MRIs. Shading represents increasing (white) or decreasing
(red) cortical thickness. Research from E. R. Sowell, P. M. Thompson, and A. W. Toga
(2004). Mapping changes in the human cortex throughout the span of life. The Neuroscientist,
10, 372–392.

Synaptic pruning may also allow the brain to adapt more flexibly to
environmental demands. Human culture is probably the most diverse and
complex environment with which any animal must cope. Perhaps the
flexibility in cortical organization achieved by the mechanism of
selective synaptic pruning is a necessary precondition for successful
development in a cultural environment.
Synaptic pruning may also be a precursor related to different
perceptions that people develop about the world. Consider, for example,
the obvious differences in Eastern and Western philosophies about life,
religion, and culture. Given the cultural differences to which people in
the East and West are exposed as their brain develops, imagine how
different their individual perceptions and cognitions may be. Considered
together as a species, however, we humans are far more alike than we are
different.
An important and unique characteristic common to all humans is
language. As illustrated in Figure 8-14 , the cortex generally thins from
age 5 to 20. The sole exception: major language regions of the cortex
actually show an increase in gray matter. Figure 8-16 contrasts the
thinning of other cortical regions with the thickening of language-related
regions (O’Hare & Sowell, 2008). A different pattern of development for
brain regions critical in language processing makes sense, given
language’s unique role in cognition and the long learning time.
Unique Aspects of Frontal Lobe
Development
The imaging atlas in Figure 8-14 confirms that the frontal lobe is the last
brain region to mature. Since the atlas was compiled, neuroscientists
have confirmed that frontal lobe maturation extends far beyond its age
20 boundary, including in the dorsolateral prefrontal cortex. The
DLPFC, which comprises Brodmann areas 9 and 46, makes reciprocal
connections with posterior parietal cortex and the superior temporal
sulcus: it selects behavior and movement with respect to temporal
memory. Zdravko Petanjek and colleagues (2011) analyzed synaptic
spine density in the DLPFC in a large sample of human brains ranging in
age at death from newborn to age 91 years.
dorsolateral prefrontal cortex (DLPFC) Brodmann areas 9 and
46; makes reciprocal connections with posterior parietal cortex and
the superior temporal sulcus; responsible for selecting behavior and
movement with respect to temporal memory.
Three-dimensional atlases guide researchers to brain regions’
precise locations (Section 7-1 ). More in Sections 12-4 and 15-3 on
how the DLPFC functions.
The analysis confirms that dendritic spine density, a good measure of
the number of excitatory synapses, is two to three times greater in
children than in adults and that spine density begins to decrease during
puberty. The analysis also shows that dendritic spines continue to be
eliminated well beyond age 20, stabilizing at the adult level around age
30. Two important correlates attend slow frontal lobe development:
1. The frontal lobe is especially sensitive to epigenetic influences (Kolb
et al., 2012). In a study of more than 170,000 people, Robert Anda and
colleagues (Anda et al., 2006) show that such aversive childhood
experiences (ACEs) as verbal or physical abuse, a family member’s
addiction, or loss of a parent are predictive of physical and mental
health in middle age. People with two or more ACEs, for example, are
50 times more likely to acquire addictions or attempt suicide. Women
with two or more ACEs are 5 times more likely to have been sexually
assaulted by age 50. We hypothesize that early aversive experiences,
such as sexual assault, promote these ACE-related susceptibilities by
compromising frontal lobe development. Abnormal frontal lobe
 development would make a person less likely to judge such a situation
as dangerous.
You can view and answer the ACE questionnaire at
http://www.theannainstitute.org/Finding Your ACE Score.pdf
2. The trajectory of frontal lobe development correlates with adult
intelligence. Philip Shaw and his colleagues (2006) used a longitudinal
design, administering multiple structural MRIs to participants over
time. The results show that it is not the thickness of the frontal cortex
in adulthood that predicts IQ score but rather the change in trajectory
of cortical thickness ( Figure 8-17 ). Children who score highest in
intelligence show the greatest plastic changes in the frontal lobe over
time. These changes are likely to reflect strong epigenetic influences.

Glial Development
Astrocytes and oligodendrocytes begin to develop after most
neurogenesis is complete and continue to develop throughout life. CNS
axons can function before they are myelinated by oligodendria, but
healthy adult function is attained only after myelination is complete.
Consequently, myelination is a useful rough index of cerebral
maturation.
Astrocytes nourish and support neurons; oligodendroglia form
myelin in the CNS (see Table 3-1 ).
In the early 1920s, Paul Flechsig noticed that cortical myelination
begins just after birth and continues until at least 18 years of age. He also
noticed that some cortical regions were myelinated by age 3 to 4 years,
whereas others showed virtually no myelination at that time. Figure 8-18
shows one of Flechsig’s cortical maps with areas shaded according to
earlier or later myelination.
Flechsig hypothesized that the earliest-myelinating areas control
simple movements or sensory analyses, whereas the latest-myelinating
areas control the highest mental functions. MRI analyses of myelin
development in the cortex show that white matter thickness largely does
correspond to the progress of myelination, confirming Flechsig’s ideas.
Myelination continues until at least 20 years of age, as illustrated in
Figure 8-19 , which contrasts total brain volume, gray matter volume,
and white matter volume during brain development in females and
males.
FIGURE 8-17 Frontal Lobe Development and IQ Score
The trajectory of frontal lobe development from ages 7 to 16 years
correlates with dynamic changes in cortical thickness. Colors on the scans
scale to the magnitude of differences between individuals with average
and superior intelligence. Purple shows thinner cortex in the individuals
with higher IQ scores; red, yellow, and green show progressively
increasing cortical thickness in those individuals. At age 7, they have a
thinner frontal cortex that rapidly thickens to peak at age 13, then wanes
later in adolescence. P. Shaw, D. Greenstein, J. Lerch, L. Clasen, R. Lenroot et al.
Intellectual ability and cortical development in children and adolescents, Nature, 440, pp. 676–
679 Mar 30, 2006, permission conveyed through Copyright Clearance Center, Inc.
FIGURE 8-18 Progress of Myelination The fact that the light-
colored zones are very late to myelinate led Flechsig to propose that they
are qualitatively different in function from those that mature earlier.
FIGURE 8-19 Sex Differences in Brain Development Mean brain volume
by age in years for males (green) and females (orange). Arrows above the curves
indicate that females show more rapid growth than males, reaching maximum overall
volume (A) and gray matter volume (B) sooner. Decreasing gray matter corresponds to
cell and synaptic loss. Increasing white matter volume (c) largely corresponds to myelin
development. Information from R. K. Lenroot, N. Gogtay, D. K. Greenstein, E. M. Wells, G. L. Wallace, L. S.
Clasen, et al. (2007). Sexual dimorphism of brain development trajectories during childhood and adolescence.
NeuroImage, 36, 1065–1073.
 8-2 REVIEW
Neurobiology of Development
Before you continue, check your understanding.
1 . The central nervous system begins as a sheet of cells, which folds
inward to form the ___________.
2 . The growth of neurons is referred to as ___________, whereas
formation of glial cells is known as ___________.
3 . Growth cones are responsive to two types of cues: ___________ and
___________.
4 . The adolescent period is characterized by two ongoing processes of
brain maturation: ___________ and ___________.
5 . What is the functional significance of the prolonged development of
the frontal lobe?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Using Emerging Behaviors to Infer
8-3

Neural Maturation
As brain areas mature, a person’s behaviors correspond to the functions of
the maturing areas. Stated differently, behaviors cannot emerge until the
requisite neural machinery has developed. When that machinery is in
place, however, related behaviors develop quickly through stages and are
shaped significantly by epigenetic factors.
Researchers have studied these interacting changes in the brain and
behavior, especially in regard to the emergence of motor skills, language,
and problem solving in children. We now explore development in these
three areas.

Motor Behaviors
Developing locomotion skills are easy to observe in human infants. At
first, babies cannot move about independently, but eventually, they roll
over, then crawl, then walk.
Other motor skills develop in less obvious but no less systematic ways.
Shortly after birth, infants are capable of flexing their arms in such a way
that they can scoop something toward their body, and they can direct a
hand, as toward a breast when suckling. Between 1 and 3 months of age,
babies also begin to make spontaneous hand and digit movements
consisting of almost all the skilled finger movements they will make as an
adult, a kind of motor babbling.
These movements at first are directed toward handling parts of their
body and their clothes (Wallace & Whishaw, 2003). Only then are
reaching movements directed toward objects in space. Tom Twitchell
(1965) studied and described how the ability to reach for objects and
grasp them progresses in stages, illustrated in Figure 8-20 .
Between 8 and 11 months, infants’ grasping becomes more
sophisticated as the pincer grasp, employing the index finger and the
thumb, develops. The pincer grasp is significant developmentally: it
allows babies to make the very precise finger movements needed to
manipulate small objects. What we see then, is a sequence in the
development of grasping: first scooping, then grasping with all of the
fingers, then grasping with independent finger movements.
 If increasingly well-coordinated grasping depends on the emergence of
certain neural machinery, anatomical changes in the brain should
accompany the emergence of these motor behaviors. Such changes do
take place, especially in the development of dendritic arborizations and in
fiber connections between neocortex and spinal cord. And a correlation
has been found between myelin formation and the ability to grasp
(Yakovlev & Lecours, 1967).
A classic symptom of motor cortex damage, detailed in Section 11-1
, is permanent loss of the pincer grasp.
In particular, a group of axons from motor cortex neurons myelinate at
about the same time that whole-hand reaching and grasping develop.
Another group of motor cortex neurons known to control finger
movements myelinates at about the time that the pincer grasp develops.
MRI studies of changes in cortical thickness show that increased motor
dexterity is associated with decreased cortical thickness in the hand
region of the left motor cortex of right-handers (Figure 8-21 A ).
We can now make a simple prediction. If specific motor cortex
neurons are essential for adultlike grasping movements to emerge,
removing those neurons should make an adult’s grasping ability similar to
a young infant’s, which is in fact what happens.
2 months
4 months
 10 months
FIGURE 8-20 Development of the Grasping Response of
Infants Information from T. E. Twitchell (1965). The automatic grasping response of
infants. Neuropsychologia, 3, p. 251.

Language Development
The gradual series of developments that accompanies speech acquisition
has usually progressed significantly by age 3 or 4. According to Eric
Lenneberg (1967), children reach certain important speech milestones in
a fixed sequence and at constant chronological ages. Children start to
form a vocabulary by 12 months. This 5-to-10-word repertoire typically
doubles over the next 6 months. By 2 years, vocabulary will range from
200 to 300 words that include mostly everyday objects. In another year,
vocabulary approaches 1000 words and begins to include simple
sentences. At 6 years, children boast a vocabulary of about 2500 words
and can understand more than 20,000 words en route to an adult
vocabulary of more than 50,000 words.
 Although language skills and motor skills generally develop in
parallel, the capacity for language depends on more than the ability to
make controlled movements of the mouth, lips, and tongue. Precise
movements of the muscles controlling these body parts develop well
before children can speak. Furthermore, even when children have
sufficient motor skill to articulate most words, their vocabulary does not
rocket ahead but rather progresses gradually.
A small proportion of children (about 1 percent) have typical
intelligence and motor skill development, yet their speech acquisition is
markedly delayed. Such children may not begin to speak in phrases until
after age 4, despite an apparently healthy environment and the absence of
any obvious neurological signs of brain damage. Because the timing of
speech onset appears universal in the remaining 99 percent of children
across all cultures, something different has likely taken place in the brain
maturation of a child with late language acquisition. Specifying what that
difference is—that is hard.

(A)
(B)

(C)
Correlations Between Gray Matter
FIGURE 8-21

Thickness and Behavior (A) Red shading corresponds to

regions showing significant cortical thinning correlated with improved motor
skills. (B) White shading corresponds to regions showing significant cortical
thickening correlated with improved language skills. (c) Red shading shows
regions of decreased cortical thickness correlated with improved
vocabulary scores. (A) and (B) Research from L. H. Lu, C. M. Leonard, P. M. Thompson, E.
Kan, J. Jolley, et al. (2007). Normal developmental changes in inferior frontal gray matter are
associated with improvement in phonological processing: A longitudinal MRI analysis. Cerebral
Cortex, 17, pp. 1092–1099. (C) Research from Elizabeth R. Sowell, Paul M. Thompson,
Christiana M. Leonard, Suzanne E. Welcome, Eric Kan, and Arthur W. Toga. Longitudinal
 Mapping of Cortical Thickness and Brain Growth in Normal Children. J. Neurosci. 2004 24:
8223–8231. Figure 9.

Because the age of language onset is usually between 1 and 2 and

language acquisition is largely complete by age 12, the best strategy
considers how the cortex is different before and after these two
milestones. By age 2, cell division and migration are complete in the
language zones of the cerebral cortex. The major changes that take place
from age 2 to 12 are in neuronal connectivity and myelination of the
speech zones.
Changes in dendritic complexity in these areas are among the most
impressive in the brain. Recall from Figure 8-12 that the axons and
dendrites of the speech zone called Broca’s area are simple at birth but
grow dramatically denser at age 15 to 24 months. This neuronal
development correlates with an equally dramatic change in language
ability, given that a baby’s vocabulary starts to expand rapidly at about
age 2.
We can therefore infer that language development may be constrained,
at least in part, by the maturing language areas in the cortex. Individual
differences in the speed of language acquisition may be accounted for by
differences in this neural development. Children with early language
ability may have an early-maturating speech zone, whereas it may
develop later in children with delayed language onset.
Focus 7-1 describes research on newborns’ reactions to language.
Results of MRI studies of the language cortex show that, in contrast
with the thinning of motor cortex associated with enhanced dexterity
shown in Figure 8-21 A, a thickening of the left inferior frontal cortex
areas associated with enhanced phonological processing (under-standing
speech sounds), as shown in Figure 8-21 B. The unique association
between cortical thickening and phonological processing is not due to a
general relation between all language functions and cortical thickening,
however. Figure 8-21C shows significant thinning of diffuse cortical
regions associated with better vocabulary—regions outside the language
areas—and vocabulary is one of the best predictors of general
intelligence.

Development of Problem-Solving Ability

The first researcher to try to identify discrete stages of cognitive
development was Swiss psychologist Jean Piaget (1952). He realized that
he could infer children’s understanding of the world by observing their
behavior. For example, a baby who lifts a cloth to retrieve a hidden toy
shows an understanding that objects continue to exist even when out of
sight. This understanding of object permanence is revealed by the
behavior of the infant in the upper row of photographs in Figure 8-22 .
Doug Goodman/Science Source
 Copyright 2016 Macmillan; Photo by Ellie Miller

FIGURE 8-22Two Stages of Cognitive Development The

infant shows that she understands object permanence—that things
continue to exist when they are out of sight (top). This girl does not yet
understand the principle of conservation of liquid volume. Beakers with
 identical volumes but different shapes seem to her to hold different
amounts of liquid (bottom).

An absence of understanding also can be seen in children’s behavior,

as shown by the actions of the 5-year-old girl in the lower row of
photographs in Figure 8-22 . She was shown two identical beakers with
identical volumes of liquid, then watched as one beaker’s liquid was
poured into a shorter, wider beaker. When asked which beaker contained
more liquid, she pointed to the taller beaker, not understanding that the
amount of liquid remains constant despite the difference in appearance.
Children display an understanding of this principle, the conservation of
liquid volume, at about age 7.
By studying children engaged in such tasks, Piaget concluded that
cognitive development is a continuous process. Children’s strategies for
exploring the world and their understanding of it are constantly changing.
These changes are not simply the result of acquiring specific pieces of
new knowledge. Rather, at certain points in development, fundamental
changes take place in the organization of a child’s strategies for learning
about the world and for solving problems. With these developing
strategies comes new understanding.
Piaget identified four major stages of cognitive development,
summarized in Table 8-2 :
• Stage I is the sensorimotor period, from birth to about 18 to 24 months
of age. During this time, babies learn to differentiate themselves from
the external world, come to realize that objects exist even when out of
sight, and gain some understanding of cause and effect.
• Stage II, the preoperational period, takes place at age 2 to 6 years.
Children gain the ability to form mental representations of things in
their world and to represent those things in words and drawings.
• Stage III is the period of concrete operations, typically 7 to 11 years.
Children learn to mentally manipulate ideas about material (concrete)
things such as volumes of liquid, dimensions of objects, and arithmetic
problems.
• Stage IV, the period of formal operations, is attained sometime after age
11. Children are now able to reason in the abstract, not just in concrete
terms.
If we take Piaget’s stages as rough approximations of qualitative
changes that take place in children’s thinking as they grow older, we can
ask what neural changes might underlie them. One place to look for brain
changes is in the relative rate of brain growth.
After birth, brain and body do not grow uniformly but rather during
irregularly occurring periods commonly called growth spurts. In his
analysis of ratios of brain weight to body weight, Herman Epstein (1979)
found consistent spurts in brain growth between 3 and 10 months
(accounting for an increase of 30 percent in brain weight by age 18
months) as well as ages 2 to 4, 6 to 8, 10 to 12, and 14 to 16+ years. The
increments in brain weight were about 5 percent to 10 percent in each of
these 2-year periods.
growth spurt Sporadic period of sudden growth that lasts for a finite
time.
TABLE 8-2 Piaget’s Stages of Cognitive Development
Approximate Description of stage Developmental
typical age phenomena
range (yr)

0-2 I: Sensorimotor Object permanence

Stranger anxiety
Experiences the world through senses and
actions (looking, touching, mouthing)

2-6 II: Preoperational Pretend play

Egocentrism
Represents things with words and images but
Language
lacks logical reasoning
development

7-11 III: Concrete operational Conservation

Mathematical
Thinks logically about concrete events; grasps
transformations
concrete analogies and performs arithmetical
operations

12+ IV: Formal operational Abstract logic

Reasons abstractly Potential for mature
moral reasoning

From: PSYCHOLOGY 11e, by David G. Myers, Copyright 2015 by Worth Publishers.

Used with permission of the publisher.
EXPERIMENT 8-1

Question: In what sequence do the forebrain structures

required for learning and memory mature?
Procedure
I. Displacement task
II. Nonmatching-to-sample learning task

III. Concurrent-discrimination learning task

 Results
Both human and monkey infants learn the concurrent-discrimination
task at a younger age than the nonmatching-to-sample task.
Conclusion: Neural structures underlying the concurrent-
discrimination task mature sooner than those underlying the
nonmatching-to-sample task
Research from W. H. Overman, J. Bachevalier, M. Turner, and A. Peuster (1992). Object recognition versus
object discrimination: Comparison between human infants and infant monkeys. Behavioral Neuroscience,
106, p. 18.

Brain growth takes place without a concurrent increase in the number

of neurons, and so it is most likely due to the growth of glial cells, blood
vessels, myelin, and synapses. Although synapses themselves would be
unlikely to add much weight to the brain, their growth is accompanied by
increased metabolic demands that cause neurons to become larger, new
blood vessels to form, and new astrocytes to be produced for neuronal
support and nourishment.
We would expect such an increase in cortical complexity to generate
more complex behaviors, so we might predict significant, perhaps
qualitative, changes in cognitive function during each growth spurt. The
first four brain growth spurts Epstein identified coincide nicely with the
four main stages of cognitive development Piaget described. Such
correspondence suggests significant alterations in neural functioning
with the onset of each cognitive stage.
At the same time, differences in the rate of brain development, or
perhaps in the rate at which specific groups of neurons mature, may
account for individual differences in the age at which the various
cognitive advances identified by Piaget emerge. Although Piaget did not
identify a fifth stage of cognitive development in later adolescence, a
growth spurt that occurs then implies one.
Growth spurts are superficial measures of changes taking place in the
brain. To link them to cognitive development, we need to know at a
deeper level what neural events are contributing to brain growth and just
where they are taking place. A way to find out is to observe healthy
children’s attempts to solve specific problems that are diagnostic of
damage to discrete brain regions in adults. If children perform a
particular task poorly, then whatever brain region regulates that task
must not yet be mature. Similarly, if children can perform one task but
not another, the tasks apparently require different brain structures, and
these structures must mature at different rates.
William Overman and Jocelyne Bachevalier (Overman et al., 1992)
used this logic to study the development of forebrain structures required
for learning and memory in young children and in monkeys. The
Procedure section of Experiment 8-1 shows the three intelligence test
items presented to their participants. The first task was simply to learn to
displace an object to obtain a food reward. When participants had
learned the displacement task, they were trained in two more tasks
believed to measure temporal lobe and basal ganglia functioning,
respectively.
In the nonmatching-to-sample task, participants were shown an object
they could displace to receive a food reward. After a brief (15-second)
delay, two objects were presented: the first object and a novel object. The
participants then had to displace the novel object to obtain the food
reward. Nonmatching to sample is thought to measure object
recognition, which is a temporal lobe function. The participant can find
the food only by recognizing the original object and not choosing it.
In the third task, concurrent discrimination, participants were
presented with a pair of objects and had to learn that one object in that
pair was always associated with a food reward, whereas the other object
was never rewarded. The task was made more difficult by sequentially
giving participants 20 different object pairs. Each day, they were
presented with one trial per pair. Concurrent discrimination is thought to
measure trial-and-error learning of specific object information, a
function of the basal ganglia.
Adults easily solve both the nonmatching and the concurrent tasks but
report that the concurrent task is more difficult because it requires
remembering far more information. The key question developmentally is
whether there is a difference in the ages at which children (or monkeys)
can solve these two tasks.
It turns out that children can solve the concurrent task by about 12
months of age, but not until about 18 months can they solve what most
adults believe to be the easier nonmatching task. These results imply that
the basal ganglia, the critical area for the concurrent discrimination task,
mature more quickly than the temporal lobe, the critical region for the
nonmatching-to-sample task.

A Caution about Linking Correlation to

Causation
Throughout this section we have described research results implying that
changes in the brain cause changes in behavior. Neuroscientists assert
that by looking at behavioral development and brain development in
parallel, they can make some inferences regarding the causes of
behavior. Bear in mind, however, that the fact that two things correlate
(take place together) does not prove that one of them causes the other.
The correlation–causation problem raises red flags in brain and
behavior studies, because research in behavioral neuroscience, by its
very nature, is often based on correlations. Nevertheless, correlational
studies, especially of development, have proved a powerful source of
insight into the principles of brain and behavior.
 8-3 REVIEW
Using Emerging Behaviors to Infer Neural Maturation
Before you continue, check your understanding.
1 . The last stage in motor development in infants is the ability to make
____________.
2 . Language development is correlated with cortical thinning related to
____________ and cortical thickening related to ____________.
3 . Brain growth spurts correlate with ____________.
4 . The nonmatching-to-sample task is believed to measure the function
of the ____________; the concurrent-discrimination learning task is
believed to measure the function of the ____________.
5 . Describe a major challenge in inferring changes in brain development
from the emergence of behaviors.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Brain Development and the
8-4

Environment
Developing behaviors are shaped not only by the maturation of brain
structures but also by each person’s environment and experience.
Neuroplasticity suggests that the brain is pliable and can be molded, at
least at the microscopic level. Brains exposed to different environmental
experiences are molded in different ways. Culture is an important aspect
of the human environment, so culture must help to mold the human
brain. We would therefore expect people raised in widely differing
cultures to acquire brain structure differences that have lifelong effects
on their behavior.
Section 1-5 summarizes humanity’s acquisition of culture.
The brain is plastic in response not only to external events but also to
events within a person’s body, including the effects of hormones, injury,
and genetic mutations. The developing brain early in life is especially
responsive to these internal factors, which in turn alter how the brain
responds to external experiences. In this section, we explore a whole
range of external and internal environmental influences on brain
development. We start with a question: Exactly how does experience
alter brain structure?

Experience and Cortical Organization

Researchers can study the effects of experience on the brain and behavior
by placing laboratory animals in different environments and observing
the results. In one of the earliest such studies, Donald Hebb (1947) took
a group of young laboratory rats home and let them grow up in his
kitchen. A control group grew up in standard laboratory cages at McGill
University.
The Hebb synapse, diagrammed in Section 15-1 , visualizes his
predictions about synaptic plasticity. Section 14-4 elaborates Hebb’s
contributions to learning theory.
The home-reared rats had many experiences that the caged rats did
not, including being chased with a broom by Hebb’s less-than-
enthusiastic wife. Subsequently, Hebb gave both groups a rat-specific
intelligence test that consisted of learning to solve a series of mazes,
collectively known as Hebb–Williams mazes. Figure 8-23 shows a
sample maze. Home-reared rats performed far better on these tasks than
caged rats did. Hebb therefore concluded that experience must influence
intelligence.
On the basis of his research, Hebb reasoned that people reared in a
stimulating environment will maximize their intellectual development,
whereas people raised in impoverished or under-resourced environments,
such as those described in the SES study in Research Focus 8-1 , will not
reach their intellectual potential. Although a generalization, Hebb’s
reasoning seems logical. How do we define environments that may be
stimulating or impoverished?
People living in slums typically have few formal educational
resources—decidedly not an enriched setting—but that does not mean
that the environment offers no cognitive stimulation or challenge. On the
contrary, people raised in slums are better adapted for survival in a slum
than are people raised in upper-class homes. Does this adaptability make
them more intelligent in a certain way? Could it make them more
resilient?
Slum dwellers may not be well adapted for college life, however. This
is probably closer to what Hebb had in mind when he referred to a slum
environment as limiting intellectual potential. Indeed, Hebb’s logic led to
the development of preschool television programs, such as Sesame
Street, that offer enrichment for children who would otherwise have little
preschool exposure to reading.
At 36 months of age, on average, the vocabulary of children from a
low-SES environment is less than one-third that of high-SES children
(400 versus 1200 words). This difference grows wider as children
develop. It is hypothesized to result from less direct conversation with
caregivers and less reading to the children by caregivers. The weaker
language skills demonstrated by children of low SES is related to the size
of cortical language areas as early as age 5 years (Raizada et al., 2008).
Patricia Kuhl (2011) makes the important point that SES itself is not the
variable driving effects on language and brain development. Rather, SES
is likely a proxy for the opportunity to learn language, a point that takes
us back to James Heckman’s thesis in Research Focus 8-1 .
 FIGURE 8-23 Hebb–Williams Maze In this version of the maze, a
rat is placed in the start box (S) and must learn to find the food in the goal
box (G). Investigators can reconfigure the walls of the maze to set new
problems. Rats raised in complex environments solve such mazes much
faster than do rats raised in standard laboratory cages.

Seven decades ago, Hebb’s studies used complex stimulating

environments, but much simpler experiences can also influence brain
development. Tactile stimulation of human infants is important not only
for bonding with caregivers but also for stimulating brain development.
For example, tactile stimulation of premature infants in incubators
speeds their growth and allows for quicker release from the hospital.
Laboratory studies show that brushing infant rats for 15 minutes 3 times
per day for the first 3 weeks of life also speeds up growth and
development. The animals show enhanced motor and cognitive skills in
adulthood as well. Tactile stimulation also dramatically improves
recovery from brain injury incurred early in development.
 Laboratory housed
(A)
(B)
Complex-environment housed
FIGURE 8-24 Enriched Environment, Enhanced Development (A)
A complex environment for a group of about six rats allows the animals to move about
and to interact with one another and with toys that are changed weekly. (B)
Representative neurons from the parietal cortex of a laboratory-housed rat and a
complex-environment-housed rat; the latter has about 25 percent more dendritic space
for synapses.

The idea that early experience can change later behavior seems
sensible enough, but we are left to question why experience should make
such a difference. One reason is that experience changes neuronal
structure, which is especially evident in the cortex. Neurons in the brains
of animals raised in complex environments, such as that shown in Figure
8-24 A , are larger and richer in synapses than are those of animals
reared in barren cages (Figure 8-24 B). Similarly, 3 weeks of tactile
stimulation increases synapse numbers all over the cortex in adulthood.
Presumably, increased synapse numbers result from increased sensory
processing in a complex and stimulating environment. The brains of
animals raised in complex settings also display more (and larger)
astrocytes. Although complex-rearing studies do not address the effects
of human culture directly, making predictions about human development
on the basis of their findings is easy. We know that experience can
modify the brain, so we can predict that different experiences might
modify the brain differently. Take language development, for example,
as Research Focus 8-3 , Increased Cortical Activation for Second
Languages, on page 268 , explains.
Focus 5-5 describes some structural changes neurons undergo as a
result of learning.
Like early exposure to language during development, early exposure
to music alters the brain. Perfect (absolute) pitch, or the ability to re-
create a musical note without external reference is believed to require
musical training during an early period, when brain development is most
sensitive to this experience. Similarly, adults exposed only to Western
music since childhood usually find Eastern music peculiar, even
nonmusical, on first encountering it. Both examples demonstrate that
early exposure to music alters neurons in the auditory system (see
Levitin & Rogers, 2005).
Figure 15-11 shows enhanced nerve tract connectivity in people
with perfect pitch.
Such loss of plasticity does not mean that the adult human brain
grows fixed and unchangeable. Adults’ brains are influenced by
exposure to new environments and experiences, although more slowly
and less extensively than children’s brains are. In fact, evidence reveals
that experience affects the brain well into old age: good news for those
of us who are no longer children.
It is becoming clear as well that prenatal events can modify brain
development. The consensus is that perinatal adversity, such as
gestational stress at or near birth, is a significant risk factor for later
behavioral disorders (see Bock et al., 2014). Even events such as stress
or drug use that occur before conception can lead to epigenetic effects in
offspring. Examples include abnormalities in neural organization and
behavior (e.g., Harker et al., 2015). Although such effects are usually
presumed to come from maternal exposure before conception, increasing
evidence from research on humans points to paternal preconception
experience also modifying children’s brain development, perhaps
including acquisition of fetal alcohol spectrum disorder (FASD).
Focus 6-2 details FASD.
RESEARCH FOCUS 8-3

Increased Cortical Activation for Second

Languages
Most of the world’s population is bilingual, but people rarely learn
their second language as early as their first. Denise Klein and her
colleagues (2006) used both PET and fMRI to determine whether
native and second languages differ in cortical activation.
The two languages overlap greatly in neural representation, but
when participants are asked to repeat words, the second language
shows greater activation in motor regions such as the striatum and
cerebellum as well as in the frontal and temporal language regions.
The investigators speculate that the second language places greater
articulatory demands on the speaker. These demands correspond to
the increased neural involvement in motor as well as language areas,
as shown in the illustration.
Further support for Klein and colleagues’ conclusions from these
imaging studies comes from a review of cortical mapping studies of
bilingual patients undergoing neurosurgery. Carlo Giussani and his
colleagues (2007) conclude that although all studies show language
representation grossly located in the same cortical regions, distinct
language-specific areas exist in the frontal and temporoparietal
language regions. Section 15-6 concludes with updates on these
findings.
Ventral striatum
Caudate nucleus
Anterior insula
Ventral premotor
 Blue regions show increased activation in neural motor structures when the
person is speaking a second language. Copyright © 2005 Wiley-Liss, Inc. Word
and Nonword Repetition in Bilingual Subjects: A PET Study. Denise Klein, Kate E.
Watkins, Robert J. Zatorre, and Brenda Milner, Human Brain Mapping 27: 153–161
(2006). Permission conveyed through Copyright Clearance Center, Inc.

Experience and Neural Connectivity

Experience can actually sculpt the brain prenatally, as studies of the
developing visual system illustrate clearly. Consider the anatomical
challenge of connecting the eyes to the rest of the visual system. A simple
analogy will help. Imagine that students in a large lecture hall are each
viewing the front of the room (the visual field) through a small cardboard
tube, such as an empty paper towel roll. If each student looks directly
ahead, he or she will see only a small bit of the total visual field.
Essentially, this is how the photoreceptor cells in the eyes act. Each
cell sees only a small bit of the visual field. The problem is putting all of
the bits together to form a complete picture. To do so, analogously to
students sitting side by side, receptors that see adjacent views must send
their information to adjacent regions in the various parts of the brain’s
visual system, such as the midbrain. How do they accomplish this feat?
Section 9-2 describes visual system anatomy. Figure 2-18 details
midbrain structures.
Roger Sperry (1963) suggested the chemoaffinity hypothesis, the idea
that specific molecules in different cells in various midbrain regions give
each cell a distinctive chemical identity. Each cell has an identifiable
biochemical label. Presumably, incoming axons seek out a specific
chemical, such as the tropic factors discussed in Section 8-2 , and
consequently land in the correct general midbrain region.
chemoaffinity hypothesis Proposal that neurons or their axons and
dendrites are drawn toward a signaling chemical that indicates the
correct pathway.
Many experiments have shown this process to take place prenatally as
the eye and brain are developing. But the problem is that chemical affinity
directs incoming axons only to a general location. To return to our two
adjacent retinal cells, how do they now place themselves in the precisely
correct position?
Here is where postnatal experience comes in: fine-tuning of neural
placement is believed to be activity-dependent. Because adjacent
receptors tend to be activated at the same time, they tend to form synapses
on the same neurons in the midbrain after chemoaffinity has drawn them
to a general midbrain region. Figure 8-25 illustrates this process. Neurons
A and G are unlikely to be activated by the same stimulus, so they seldom
fire synchronously. Neurons A and B, in contrast, are apt to be activated
by the same stimuli, as are B and C. Through this simultaneous activity
and with the passage of time, cells eventually line up correctly in the
connections they form.
FIGURE 8-25 Chemoaffinity in the Visual System Neurons A through G
project from the retina to the tectum in the midbrain. The activities of adjacent neurons (C
and D, say) are more likely to coincide than are the activities of widely separated neurons
such as A and G. As a result, adjacent retinal neurons are more likely to establish
permanent synapses on the same tectal neurons. By using chemical signals, axons grow
to the approximate location in the tectum (top). The connections become more precise
with the passage of time (bottom).

Now consider what happens to axons coming from different eyes.

Although the neural inputs from the two eyes may be active
simultaneously, cells in the same eye are more likely to be active together
than are cells in different eyes. The net effect is that inputs from the two
eyes tend to organize themselves into neural bands, called columns, that
represent the same region of space in each eye, as shown on the left in
Figure 8-26 on page 270 . Formation of these segregated cortical
columns therefore depends on the patterns of coinciding electrical activity
on the incoming axons.
If experience is abnormal—if one eye is covered during a crucial time
in development, for example—then the neural connections will not be
guided appropriately by experience. As shown at the right in Figure 8-26 ,
the effect of suturing one eye closed has the most disruptive effect on
cortical organization in kittens between 30 and 60 days after birth. In a
child who has a lazy eye, visual input from that eye does not contribute to
fine-tuning the neural connections as it should. So the details of those
connections develop abnormally, much as if the eye had been covered.
The resulting loss of sharpness in vision is amblyopia.
amblyopia Condition in which vision in one eye is reduced as a
result of disuse; usually caused by a failure of the two eyes to look in
the same direction.
To summarize, an organism’s genetic blueprint is vague in regard to
exactly which connections in the brain go to exactly which neurons.
Experience fine-tunes neural connectivity by modifying those details.

Critical Periods for Experience and Brain

Development
The preceding examples of perfect pitch and visual connectivity show
that for healthy development, specific sensory experiences occurring at
particular times are especially important. A time during which brain
development is most sensitive to a specific experience is called either a
critical period or a sensitive period.
 critical period Developmental window during which some event has
a long-lasting influence on the brain; also, sensitive period.
The absence of appropriate sensory experience during a critical period
may result in abnormal brain development, leading to abnormal behavior
that endures even into adulthood. Our colleague Richard Tees offered an
analogy to help explain the concept. He pictured the developing animal as
a little train traveling past an environmental setting, perhaps the Rocky
Mountains. All the windows are closed at the beginning of the journey
(prenatal development), but at particular stages of the trip, the windows in
certain cars open, exposing the occupants (different parts of the brain) to
the outside world. Some windows open to expose the brain to specific
sounds, others to certain smells, others to particular sights, and so on.
This exposure affects the brain’s development, and the absence of any
exposure through an open window severely disturbs that development. As
the journey continues, the windows become harder to open until finally
they close permanently. This does not mean that the brain can no longer
change, but changes become much harder to induce.
Now imagine two different trains, one headed through the Rocky
Mountains and another, the Orient Express, traveling across Eastern
Europe. The views from the windows are very different, and the effects
on the brain are correspondingly different. In other words, not only is the
brain altered by the experiences it has during a critical period, but the
particular kinds of experiences encountered matter too.
 FIGURE 8-26 Ocular Dominance Columns Typically in the
postnatal development of the cat brain, axons from each eye enter the
cortex, where they grow large terminal arborizations. (L, left eye; R, right
eye).

An extensively studied, related behavior is imprinting, a critical

period during which an animal learns to restrict its social preferences to a
specific class of objects, usually the members of its own species. In birds,
such as chickens and waterfowl, the critical period for imprinting often
comes shortly after hatching. Typically, the first moving object a young
hatchling sees is a parent or sibling, so the hatchling’s brain appropriately
imprints to its own species.
imprinting Formation of an attachment by an animal to one or more
objects or animals at a critical period in development.
Appropriate imprinting is not inevitable. Konrad Lorenz (1970)
demonstrated that if the first animal or object that baby goslings
encounter is a person, the goslings imprint to that person as though he or
she were their mother. Figure 8-27 shows a flock of goslings that
imprinted to Lorenz and followed him wherever he went. Incorrect
imprinting has long-term consequences for the hatchlings. They often
direct their subsequent sexual behavior toward humans. A Barbary dove
that had become imprinted to Lorenz directed its courtship toward his
hand and even tried to copulate with the hand if it was held in a certain
orientation.
Birds can imprint not just to humans but also to inanimate objects,
especially moving objects. Chickens have been induced to imprint to a
milk bottle sitting on the back of a toy train moving around a track. But
the brain is not entirely clueless when it comes to selecting an imprinting
target. Given a choice, young chicks will imprint on a real chicken over
any other stimulus.
This quick acquisition and its permanent behavioral consequences
suggest that during imprinting, the brain makes a rapid change of some
kind, probably a structural change given the permanence of the new
behavior. Gabriel Horn and his colleagues at Cambridge University
(1985) tried to identify the changes in chicks’ brains during imprinting.
The results of Horn’s electron microscopic studies show that synapses in
a specific forebrain region enlarge with imprinting. Thus, imprinting
seems a good model for studying brain plasticity during development, in
part because the changes are rapid, related to specific experience, and
localized in the brain.
As noted in Section 8-3 , brain development can be affected by either
parent’s experiences before conception or those of the mother or fetus
during gestation. Because developmental events change so dramatically
and quickly in utero, we should not be surprised that the effects of fetal
experiences vary with the precise developmental stage. As a rule, the
CNS is especially sensitive during gestational weeks 4 to 8, as the neural
tube forms. It remains sensitive through the period of cerebral
neurogenesis, which continues until the end of the second trimester.
Robbin Gibb and her colleagues (2014) have shown that housing pregnant
rats in complex environments, as in Figure 8-24 A, results in the offspring
showing increased dendritic spine density in the cortex, as though the
animals had been placed in the environment in adulthood.
 Thomas D. McAvoy/Time & Life Pictures/Getty Images

FIGURE 8-27 Strength of Imprinting Ethologist Konrad Lorenz followed by

goslings that imprinted on him. He was the first object that the geese encountered after
hatching, so he became their “mother.”

Abnormal Experience and Brain

Development
If complex or enriched experiences can stimulate brain growth and
influence later behavior, severely restricted experiences seem likely to
retard both brain growth and behavior. To study the effects of such
restrictions, Donald Hebb and his colleagues (Clarke et al., 1951) placed
young Scottish terriers in the dark with as little stimulation as possible
and compared their behavior to that of dogs raised in a typical
environment.
When the dogs raised in the barren environment, obviously unethical
by today’s standards, were later removed from it, their behavior was
highly unusual. They showed virtually no reaction to people or other dogs
and appeared to have lost any pain sensation. Even sticking pins in them
(equally unethical) produced no response. When given a dog version of
the Hebb–Williams intelligence test for rats, these dogs performed terribly
and were unable to learn some tasks that dogs raised in more stimulating
settings learned easily.
Results of subsequent studies show specifically that depriving young
animals of visual input or of maternal contact has devastating
consequences for their behavioral development and presumably for their
brain development. Austin Riesen (1982) and his colleagues extensively
studied animals raised in the dark. They found that even though the
animals’ eyes still work, they may be functionally blind after early visual
deprivation. An absence of visual stimulation results in the atrophy of
dendrites on cortical neurons, essentially the opposite of the results
observed in the brains of animals raised in complex and stimulating
environments.
Not only does the absence of specific sensory inputs adversely affect
brain development; so do more complex atypical experiences. In the
1950s, Harry Harlow (1971) began the first systematic laboratory studies
of analogous deprivation in laboratory animals. Harlow showed that
infant monkeys raised without maternal (or paternal) contact develop
grossly atypical intellectual and social behaviors in adulthood.
 Harlow separated baby monkeys from their mothers shortly after birth
and raised them in individual cages. Perhaps the most stunning effect
occurred in adulthood, when these animals were totally unable to
establish normal relations with other animals. Unfortunately, Harlow did
not analyze the deprived monkeys’ brains. We would predict atrophy of
cortical neurons, especially in the frontal lobe regions related to social
behavior. Harlow’s student Stephen Suomi continues to study early
experiences in monkeys at the U.S. National Institute of Child Health and
Human Development. He has found a wide variety of hormonal and
neurological abnormalities among motherless monkeys, including
epigenetic changes (see the review by Suomi, 2011).
Children in a barren environment or abused or neglected are at a
serious disadvantage later in life. Proof is the hampered intellectual and
motor development displayed by children raised in dreadful
circumstances such as those described in Clinical Focus 8-4 , Romanian
Orphans, on page 272 . Although some argue that children can succeed in
school and in life if they really want to, abnormal developmental
experiences can clearly alter the brain irrevocably. As a society, we
cannot be complacent about the environment to which our children are
exposed.
Early exposure to stress, including prenatally, also has major effects on
a child’s later behavior. Stress can alter the expression of certain genes,
such as those related to serotonin (5-hydroxytryptamine, or 5-HT)
reuptake. Early alteration in serotonin activity can severely alter how the
brain responds to stressful experiences later in life.
Stress early in life may predispose people to develop behavioral
disorders, such as depression (Sodhi & Sanders-Bush, 2004). Early stress
can also leave a lasting imprint on brain structure: the amygdala is
enlarged and the hippocampus is small (Salm et al., 2004). Changes in
frontal lobe anatomy have been associated with the development of
depressive and anxiety disorders and may be linked to the epigenetic
effects described in Section 8-2 .
Section 6-5 explains the neurobiology of the stress response. Section
16-4 connects mood and reactivity to stress.
Prenatal experiences also can lead to abnormal behavior in children
and adults. Exposing the fetus to alcohol, especially in the first two
trimesters, can lead to FASD, as can excessive alcohol use by either
parent before conception. Similarly, children exposed in utero to radiation
in the aftermath of the 1986 accident at the Chernobyl nuclear power
plant later developed a range of cognitive disorders, including lowered IQ
scores. Effects were most severe if they had been exposed during
gestational weeks 8 to 25, the critical period of cerebral neurogenesis
(Nyagu et al., 1998).

Hormones and Brain Development

The determination of sex is largely genetic. In mammals, the Y
chromosome in males controls the process by which an undifferentiated,
primitive gonad develops into testes, illustrated in Figure 8-28 . The
genitals begin to form in the seventh week after conception, but they
appear identical (indifferent) in the two sexes at this early stage. No
sexual dimorphism, or structural difference, yet exists. The testes
subsequently secrete the sex hormone testosterone, which stimulates
development of male reproductive organs and later, in puberty, the
appearance of male secondary sexual characteristics such as facial hair
and deepening of the voice.
testosterone Sex hormone secreted by the testes and responsible for
the distinguishing characteristics of the male.
CLINICAL FOCUS 8-4

Romanian Orphans
In the 1970s, Romania’s Communist regime outlawed all forms of
birth control and abortion. The natural result was more than 100,000
unwanted children in state-run orphanages. The conditions were
appalling.
The children were housed and clothed but given virtually no
environmental stimulation. Mostly they were confined to cots with
few, if any, playthings and virtually no personal interaction with
overworked caregivers, who looked after 20 to 25 children at once.
Bathing often consisted of being hosed down with cold water.
After the Communist government fell, the outside world
intervened. Hundreds of these children were placed in adoptive
homes throughout the world, especially in the United States, Canada,
and the United Kingdom. Studies of these severely deprived children
on arrival in their new homes document malnourishment, chronic
respiratory and intestinal infections, and severe developmental
impairments.
A British study by Michael Rutter (1998) and his colleagues
assessed the orphans at two standard deviations below age-matched
children for weight, height, and head circumference (taken as a very
rough measure of brain size). Scales of motor and cognitive
development assessed most of the children in the impaired range.
The improvement these children showed in the first 2 years after
placement in their adoptive homes was nothing short of spectacular.
Average height and weight advanced to nearly normal, although head
circumference remained below normal. Many tested in the normal
range of motor and cognitive development. But a significant number
were still considered intellectually impaired. What caused these
individual differences in recovery from the past deprivation?
The key factor was age at adoption. Children adopted before 6
months of age did significantly better than those adopted later. In a
Canadian study by Elenor Ames (1997), Romanian orphans who were
adopted before 4 months of age and then tested at age 4½ had an
average Stanford–Binet IQ score of 98. Age-matched Canadian
controls had an average score of 109. Brain imaging studies showed
that children adopted at an older age had a smaller brain than normal.
Charles Nelson and his colleagues (Berens & Nelson, 2015;
Nelson et al., 2007; Smyke et al., 2012) analyzed cognitive and social
development as well as event-related potential (ERP) measures in a
group of children who had remained in Romania. Whether the
children had moved to foster homes or remained in institutions, the
studies reveal severe abnormalities at about 4 years of age. The age at
adoption was again important, but in the Nelson studies the critical
age appears to be before 24 months rather than 6 months, as in the
earlier studies.
The inescapable conclusion is that the human brain may be able to
recover from a brief period of extreme deprivation in early infancy,
but periods longer than 24 months produce significant developmental
abnormalities that cannot be overcome completely. The studies of
Romanian orphans make clear that the developing brain requires
stimulation for healthy development. Although the brain may be able
to catch up after a brief deprivation, severe deprivation lasting many
months results in a small brain and associated behavioral
abnormalities, especially in cognitive and social skills.

Cynthia Johnson/Liaison/Getty Images

Romanian orphans warehoused in the 1970s and 1980s endured
the conditions shown in this photograph. The utter absence of
stimuli hampered their normal brain development.
 Gonadal (sex) hormones change the genetic activity of certain cells,
most obviously those that form the genitals, but neural cells also respond
to them. Regions of the embryonic brain thus also may begin to show
sexual dimorphism as testosterone secretion begins, about 60 days after
conception. What does sexual differentiation have to do with brain
development? Although the answer is largely hormonal, genetic
influences contribute, too.
Testosterone stimulates sexual differentiation in male embryos. In its
absence, female embryos develop. Prenatal exposure to gonadal
hormones shapes male and female brains differently, because these
hormones activate different genes in the two sexes. Experience, then,
affects male and female brains differently. Clearly, genes and experience
begin to shape the developing brain very early.
Sections 6-5 and 12-5 detail the actions of gonadal hormones,
including testosterone.

Indifferent stage
FIGURE 8-28 Sexual Differentiation in the Human Infant
 Early in the indifferent stage, male and female human embryos are identical
(top). In the absence of testosterone, female structures emerge (left). In
response to testosterone, genitalia begin to develop into male structures at
about 60 days (right). Parallel changes take place in the embryonic brain in
response to the absence or presence of testosterone.

Gonadal Hormones and Brain Development

Testosterone, the best-known androgen (the class of hormones that
stimulates or controls masculine characteristics), is released during a brief
period of prenatal brain development. Subsequently, it alters the brain
much as it alters the sex organs. This process is masculinization.
androgen Class of hormones that stimulates or controls masculine
characteristics.
masculinization Process by which exposure to androgens (male sex
hormones) alters the brain, rendering it identifiably male.
Testosterone does not affect all body organs or all brain regions, but it
does affect many brain regions in many ways. It affects the number of
neurons formed in certain brain areas, reduces the number of neurons that
die, increases cell growth, increases or reduces dendritic branching and
synaptic growth, and regulates synaptic activity, among other effects.
Estrogens, the sex hormones responsible for the female’s
distinguishing characteristics, also probably influence postnatal brain
development. Jill Goldstein and her colleagues found sex differences in
the volume of cortical regions known to have differential levels of
receptors for testosterone (androgen receptors) and estrogen, respectively,
as shown in Figure 8-29 (Goldstein et al., 2001). Orange areas in the
figure are larger in females, and green areas are larger in males. Clearly, a
male brain and a female brain are not the same. Hormones alter brain
development, and clear sex differences appear in the rate of brain
development (see Figure 8-19 ).
estrogens Variety of sex hormones responsible for the distinguishing
characteristics of the female.
Testosterone’s effects on brain development were once believed
unimportant, because this hormone was thought primarily to influence
brain regions related to sexual behavior, not regions of higher functions.
This belief is false. Testosterone changes cell structure in many cortical
regions, with diverse behavioral consequences that include influences on
cognitive processes.
Lateral view

Medial view
FIGURE 8-29 Sex Differences in Brain Volume Cerebral areas
related to sex differences in the distribution of estrogen (orange) and
androgen (green) receptors in the developing brain correspond to areas of
 relatively larger cerebral volumes in adult women and men. Information from J.
M. Goldstein, L. J. Seidman, N. J. Horton, N. Makris, D. N. Kennedy et al. (2001). Normal sexual
dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging. Cerebral
Cortex, 11, 490–497.

Jocelyne Bachevalier adapted her method, shown in Experiment 8-1

on page 264 , by training infant male and female monkeys in the
concurrent discrimination task. The animal has to learn which of two
objects in a series of pairs conceals a food reward. Bachevalier also
trained the animals in another task, object reversal learning. The task is to
learn that one object always conceals a food reward, whereas another
object never does. After the animal learns this pattern, the reward
contingencies are reversed so that the particular object that has always
been rewarded is now never rewarded, and the formerly unrewarded
object now conceals the reward. When the animal learns this new pattern,
the contingencies are reversed again, and so on for five reversals.
Bachevalier found that 2½-month-old male monkeys were superior to
female monkeys on the object reversal task, but females did better on the
concurrent task. Apparently, the different brain areas required for these
two tasks mature at different rates in male and female monkeys.
Bachevalier later tested additional male monkeys whose testes had been
removed at birth and so were no longer exposed to testosterone. These
animals performed like females on the tasks, which implies that
testosterone was influencing the brain development rate in areas related to
certain cognitive behaviors.
Bachevalier and her colleague William Overman (Overman et al.,
1996) repeated the experiment with children 15 to 30 months old. The
results were the same: boys were superior at the object reversal task and
girls were superior at the concurrent task. The investigators found no such
male–female performance differences among children 32 to 55 months of
age. Presumably, the brain regions required for both tasks had matured in
both boys and girls. At the earlier age, however, gonadal hormones
seemed to influence the maturation rate in certain brain regions, just as
they had in the baby monkeys.
Lifelong Effects of Gonadal Hormones
Although gonadal hormones’ biggest effects on the brain may come
during early development, their role there is by no means finished in
infancy. Both testosterone and estrogen (which females’ ovaries produce
in large quantities) continue to influence brain structure throughout an
animal’s life. In fact, removal of the ovaries in middle-aged laboratory
rats leads to marked growth of dendrites and glial cells in the cortex. This
finding of widespread neural change in the cortex associated with
estrogen loss has implications for treating postmenopausal women with
hormone replacement therapy, which may reverse the plastic changes.
Gonadal hormones also affect how the brain responds to
environmental events. For instance, among rats housed in complex
environments, males show more dendritic growth in neurons of the visual
cortex than do females (Juraska, 1990). In contrast, females housed in this
setting show more dendritic growth in the hippocampus than males do.
Apparently, the same experience can affect the male and female brain
differently owing to the mediating influence of gonadal hormones.
As females and males develop, then, their brains continue to diverge
more and more, much like a fork in a road. After you set out on one path,
your direction is forever changed, as the roads increasingly course farther
apart.
To summarize, gonadal hormones alter basic neuronal development,
shape experience-dependent changes in the brain, and influence neuronal
structure throughout our lifetimes. Those who believe that behavioral
differences between males and females are solely the result of
environmental experiences must consider these neural effects of sex
hormones.
Details on sexual orientation and gender identity appear in Section
12-5 .
In part, it is true that environmental factors exert a major influence.
But one reason they do so may be that male and female brains are
different to start with. Even the same events experienced by structurally
different brains may lead to different effects on those brains. Evidence
shows that significant experiences, such as prenatal stress, produce
markedly different changes in gene expression in the frontal cortex of
male and female rats (Mychasiuk et al., 2011).
Another key question related to hormonal influences on brain
development is whether any sex differences in brain organization might
be independent of hormonal action. In other words, are differences in the
action of sex chromosome genes unrelated to sex hormones? Although
little is known about such genetic effects in humans, studies of birds
clearly show that genetic effects on brain cells may indeed contribute to
sex differentiation.
 Songbirds have an especially interesting brain dimorphism: in most
species, males sing and females do not. This behavioral difference
between the sexes is directly related to a neural birdsong circuit present in
males but not in females. Robert Agate and his colleagues (2003) studied
the brain of a rare gynandromorph zebra finch, shown in Figure 8-30 .
This bird exhibits physical characteristics of both sexes.
Genetic analysis shows that cells on one half of the bird’s brain and
body are genetically female and on the other half are genetically male.
The two sides of the gynandromorph’s body and brain were exposed to
the same hormones during prenatal development. Thus, the effect of male
and female genes on the birdsong circuit can be examined to determine
how the genes and hormones might interact.
If the sex difference in the birdsong circuit were totally related to the
presence of hormones prenatally, then the two sides of the brain should be
equally masculine or feminine. Agate’s results confirm the opposite: the
neural song circuit is masculine on the male side of the brain. Only a
genetic difference that was at least partly independent of hormonal effects
could explain such a structural difference in the brain.
FIGURE 8-30 Gynandromorph This rare zebra finch has dull female plumage on
one side of the body and bright male plumage on the other side. Neural, not gonadal, origin of
brain sex differences in a gynandromorphic finch. Agate RJ, Grisham W, Wade J, Mann S, Wingfield J, Schanen C,
Palotie A, Arnold AP. Proc Natl Acad Sci U S A. 2003 Apr 15; 100 (8): 4873-8. Copyright (2003) National Academy
of Sciences, U.S.A.

Adolescent Onset of Mental Disorders

Adolescence is a time of rapid brain change related both to pubertal
hormones and to psychosocial stress. Relationships with parents and peers
are among the prime stressors, as is school. Add to this the finding,
charted in Figure 8-31 , that the peak age of onset for any mental disorder
is estimated at 14 years (Paus et al., 2008).
Figure 8-31 reveals that age of onset differs across disorders. However,
anxiety disorders, psychoses (including schizophrenia), bipolar disorder,
depression, eating disorders, and substance abuse most commonly emerge
by or during adolescence. From an evolutionary perspective,
neurobiological and associated behavioral changes linked with the period
we define as adolescence are designed to optimize the brain for
challenges that lie ahead in adulthood. But the brain’s plasticity in
adolescence can also make it vulnerable to psychopathologies that can
endure for the rest of the individual’s life.
 Emergence of Mental Disorders in
FIGURE 8-31

Adolescence Data from T. Paus, M. Keshavan, and J. N. Giedd

(2008). Why do so many psychiatric disorders emerge during
adolescence? Nature Reviews Neuroscience, 9, pp. 947–957.

Gut Bacteria and Brain Development

We have emphasized factors that affect CNS development directly, but a
less direct route exerts itself via the enteric nervous system. The ENS
sends information to the brain that affects our mental state. The brain in
turn can modify gut function.
An important component of the ENS is the microbiome, the bacteria in
the gut with which the ENS interacts. About 1014 microbiota populate the
adult gut, which means that microbiota outnumber the host body cells by
a factor of 10. But in utero, the fetus’s gut is sterile. It is only at birth that
trillions of microbes from the mother’s vaginal and anal fluids, and later
from her skin, invade the baby’s body and start to grow.
Many neurodevelopmental disorders, including autism, may be related
to an atypical microbiome early in life (e.g., Finegold et al., 2012). Elaine
Hsiao and her colleagues (2013) studied a mouse model known to display
features of ASD. These mice produce few social auditory vocalizations,
about one-third the normal levels. Manipulation of their gut bacteria
restored the vocalizations to normal levels, demonstrating that gut
bacteria can alter behavior. Other neurodevelopmental disorders may
involve microbiome abnormalities as well.
Section 2-5 introduces the ENS and microbiome.
 FIGURE 8-32 Time-Dependent Effects Damage to the rat’s frontal
cortex on the day of birth leads to cortical neurons with simple dendritic
fields and sparse growth of spines in the adult (left). In contrast, damage to
the frontal cortex at 10 days of age leads to cortical neurons with expanded
dendritic fields and denser spines than normal in adults (right). Information
from B. Kolb and R. Gibb (1993). Possible anatomical basis of recovery of function after neonatal
frontal lesions in rats. Behavioral Neuroscience, 107, p. 808.

Injury and Brain Development

Dating to the late 1800s, infants and children were generally believed to
show better recovery from brain injury than adults. In the 1930s, Donald
Hebb studied children with major birth-related injuries to the frontal lobes
and found them to have severe and permanent behavioral abnormalities in
adulthood. He concluded that brain damage early in life can alter the
brain’s subsequent development and actually may be worse than injury
later in life.
 Have other studies confirmed Hebb’s conclusion? Few anatomical
studies of humans with early brain injuries exist, but we can make some
general predictions from studying laboratory animals. In general, early
brain injuries do produce atypical brains, especially at certain critical
periods in development.
For humans, the worst time appears to be in the last half of the
intrauterine period and the first couple of months after birth. Rats and cats
that are injured at a comparable time have a significantly smaller brain
than average, and their cortical neurons show general atrophy relative to
healthy brains, as illustrated on the left in Figure 8-32 . Behaviorally,
these animals appear cognitively deficient over a wide range of skills.
Injury to the developing brain is not always devastating. For example,
researchers have known for more than 100 years that children with brain
injuries in the first couple of years after birth almost never have the
severe language disturbances common to adults with equivalent injuries.
Animal studies help explain why.
Whereas damage to the rat brain in the developmental period
comparable to the last few months of gestation in humans produces
widespread cortical atrophy, damage at a time in rat brain development
roughly comparable to ages 6 months to 2 years in humans actually
produces more dendritic development in rats (Figure 8-32 at right).
Furthermore, these animals show dramatic recovery of functions, which
implies that during development the brain has a capacity to compensate
for injury. Parallel studies in cats have shown extensive reorganization of
cortex-to-cortex connections after early injury to the visual cortex (see the
review by Payne and Lomber, 2001).

Drugs and Brain Development

The U.S. National Institute on Drug Abuse (2012) estimates that 16
percent of babies born alive in the United States today are exposed to
nicotine in utero. Similar statistics on alcohol consumption by pregnant
mothers are not available, but the effects of alcohol on the fetus are well
documented. Even low doses of commonly prescribed drugs, including
antidepressants, antipsychotics, and pain-killers, appear to alter prenatal
neuron development in the prefrontal cortex. It manifests after birth in
abnormalities in behaviors controlled by the affected regions (see the
review by Halliwell et al., 2009).
 NIDA also estimates that 5.5 percent of expectant mothers,
approximately 221,000 pregnant women each year in the United States,
use an illicit drug at least once in the course of their pregnancy. Among
pregnant teenagers aged 15 to 17, that figure climbs to 16%, or about
14,000 women. And what about caffeine and nicotine? More than likely
most children were exposed to caffeine (from coffee, tea, cola, energy
drinks, and chocolate) in utero and about 16% were exposed to nicotine.
Laboratory animal studies have shown that prenatal exposure to nicotine
alters the brain’s response to complex housing: the brain appears less
plastic (e.g., Mychasiuk et al., 2014).
Section 6-3 reviews nicotine’s prominence as a gateway drug.
The precise effects of prenatal drug intake on brain development are
poorly understood, but the overall conclusion from current knowledge is
that children with prenatal exposure to a variety of psychoactive drugs
have an increased likelihood of later drug use (e.g., Minnes et al., 2014).
Although, again, childhood disorders are poorly studied, many experts
suggest that they—learning disabilities and ADHD are examples—may
be related to prenatal exposure to drugs such as nicotine or caffeine or
both. As Carl Malanga and Barry Kosofsky (2003) note poignantly,
society at large does not yet fully appreciate the impact that prenatal drug
exposure can have on the lives of its children.
Focus 7-4 details ADHD and Focus 14-1 details dyslexia.

Other Sources of Abnormal Brain

Development
The nervous system need not be damaged by external forces to develop
abnormally. Many genetic aberrations are believed to result in
abnormalities in brain development and ultimately brain structure. Spina
bifida, in which the genetic blueprint goes awry and the neural tube does
not close completely, leads to an incompletely formed spinal cord. After
birth, unless treated with folic acid, children with spina bifida usually
have serious motor problems.
Imagine what happens if some genetic aberration causes improper
closure of the front end of the neural tube. Because the front end of the
neural tube forms the brain (see Figure 8-5 ), this failure results in gross
abnormalities in brain development known as anencephaly. Affected
infants die soon after birth.
 anencephaly Failure of the forebrain to develop.
Atypical brain development can be much subtler than anencephaly. For
example, if cells do not migrate to their correct locations, and if these
mispositioned cells do not subsequently die, they can disrupt brain
function and may lead to disorders ranging from seizures to schizophrenia
(see review by Guerrini et al., 2007). In a variety of conditions, neurons
fail to differentiate normally. In certain cases, neurons fail to produce long
dendrites or spines, which results in abnormal brain connectivity and
developmental disabilities.
The opposite condition also is possible: neurons continue to make
dendrites and form connections with other cells until the neurons are
extraordinarily large. The functional consequences of all the newly
formed connections can be devastating. Excitatory synapses in the wrong
location effectively short-circuit a neuron’s function.
Subtle abnormal events also can be devastating, even terminal.
Sudden infant death syndrome (SIDS), the unexplained death while
asleep of a seemingly healthy infant less than 1 year old, kills about 2500
babies yearly in the United States alone. Postmortem studies reveal that
SIDS victims are more likely than other babies to have a particular gene
variation that makes the serotonin transporter unusually efficient.
Normally, the serotoninergic system helps to stimulate a respiratory
mechanism that responds to high carbon dioxide levels in the blood and
acts to expel the gas.
sudden infant death syndrome (siDs) Unexplained death while
asleep of a seemingly healthy infant less than 1 year old.
In babies who die of SIDS, serotonin is cleared from the synapse more
rapidly than normal. This action makes 5-HT less effective in regulating
life-threatening events such as carbon dioxide buildup during sleep.
Babies can breathe excessive levels of carbon dioxide that is trapped in
their bedding, for example, and suffocate.
In addition to the serotonin transporter abnormality, David Paterson
and his colleagues (2006) found an abnormally low occurrence of 5-HT1A
receptors in SIDS victims’ brains. The researchers found that boys have
significantly fewer 5-HT1A receptors than do females, a result consistent
with higher SIDS mortality in boys. Hannah Kinney (2009) speculates
that the primary defect is increased numbers of 5-HT cells, possibly
arising during fetal development and owing to unknown causes, but
augmented by adverse prenatal exposure to alcohol, nicotine, and/or other
factors. This defect leads to the changes in 5-HT1A receptors.
A curious consequence of abnormal brain development is that
behavioral effects may emerge only as the brain matures and the maturing
regions begin to play a greater role in behavior. This consequence is true
especially of frontal lobe injuries. The frontal lobes continue to develop
into early adulthood (see Figure 8-17 ), and often not until adolescence do
the effects of frontal lobe abnormalities become noticeable.
Schizophrenia is a disease characterized by its slow development,
usually not becoming obvious until late adolescence. Clinical Focus 8-5 ,
Schizophrenia on page 278 , relates disease progress and its possible
origin.
Section 16-4 describes the schizophrenic brain and Section 5-3 a
possible relation to excessive DA or 5-HT activity in that brain.
CLINICAL FOCUS 8-5

Schizophrenia
When Mrs. T. was 16 years old, she began to experience her first symptom of
schizophrenia: a profound feeling that people were staring at her. These bouts of self-
consciousness soon forced her to end her public piano performances. Her self-
consciousness led to withdrawal, then to fearful delusions that others were speaking about
her behind her back, and finally to suspicions that they were plotting to harm her.
At first Mrs. T.’s illness was intermittent, and the return of her intelligence, warmth,
and ambition between episodes allowed her to complete several years of college, to
marry, and to rear three children. She had to enter a hospital for her illness for the first
time at age 28, after the birth of her third child, when she began to hallucinate.
Now, at 45, Mrs. T. is never entirely well. She has seen dinosaurs on the street and live
animals in her refrigerator. While hallucinating, she speaks and writes in an incoherent,
but almost poetic way. At other times, she is more lucid, but even then the voices she
hears sometimes lead her to do dangerous things, such as driving very fast down the
highway in the middle of the night, dressed only in a nightgown…. At other times and
without any apparent stimulus, Mrs. T. has bizarre visual hallucinations. For example, she
saw cherubs in the grocery store. These experiences leave her preoccupied, confused, and
frightened, unable to perform such everyday tasks as cooking or playing the piano.
(Gershon & Rieder, 1992, p. 127)

It has always been easier to identify schizophrenic behavior than

to define schizophrenia. Perhaps the one universally accepted
criterion for its diagnosis is the absence of other neurological
disturbances or affective (mood) disorders that could cause a person
to lose touch with reality—a definition by default.
Symptoms of schizophrenia vary, suggesting that biological
abnormalities also vary from person to person. Most patients appear
to stay at a fairly stable level after the first few years of symptoms,
with little evidence of a decline in neuropsychological functioning.
Symptoms come and go, much as for Mrs. T., but the severity is
relatively constant after the first few episodes.
Numerous studies have investigated the brains of schizophrenia
patients, both in MRI and CT scans and in autopsies. Although the
results vary, most neuroscientists agree that schizophrenic brains
weigh less than normal and have enlarged ventricles. Research
findings also suggest that brains affected by schizophrenia have
smaller frontal lobes (or at least a reduction in the number of neurons
in the prefrontal cortex) and thinner parahippocampal gyri.
 Joyce Kovelman and Arnold Scheibel (1984) found abnormalities
in the orientation of hippocampal neurons in people with
schizophrenia. Rather than the consistently parallel orientation of
neurons in this region characteristic of healthy brains, schizophrenic
brains have a more haphazard organization, as shown in the
accompanying drawings.
Evidence is increasing that the abnormalities observed in
schizophrenic brains are associated with disturbances of brain
development. William Bunney and his colleagues (1997) suggested
that at least a subgroup of those with schizophrenia underwent either
environmental insults or some type of abnormal gene activity in the
fourth to sixth month of fetal development.
These events are thought to result in abnormal cortical
development, particularly in the frontal lobes. Later in adolescence,
as the frontal lobes approach maturity, the person begins to have
symptoms deriving from this abnormal prenatal development.

Organized (healthy) pyramidal neurons

 Disorganized (schizophrenic) pyramidal neurons
(A)

(B)
Pyramidal cell orientation in the hippocampus of (A) a healthy
brain and (B) a schizophrenic brain. Research from J. A. Kovelman and A.
B. Scheibel (1984.) A neurohistologic correlate of schizophrenia. Biological Psychiatry, 19,
p. 1613.
Developmental Disability
Impaired cognitive functioning accompanies abnormal brain
development. Impairment may range from mild, allowing an almost
normal lifestyle, to severe, requiring constant care. As summarized in
Table 8-3 , such developmental disability can result from chronic
malnutrition, genetic abnormalities such as Down syndrome, hormonal
abnormalities, brain injury, or neurological disease. Different causes
produce different abnormalities in brain organization, but the critical
similarity across all types of developmental disability is that the brain is
not normal.
Figure 3-22 illustrates trisomy, the chromosomal abnormality that
causes Down syndrome.
Dominique Purpura (1974) conducted one of the few systematic
investigations of developmentally disabled children’s brains. Purpura
used Golgi stain to examine the neurons of children who had died of
accident or disease unrelated to the nervous system. When he examined
the brains of children with various forms of intellectual disability, he
found that dendrite growth was stunted and the spines very sparse relative
to dendrites from children of typical intelligence, as illustrated in Figure
8-33 .
TABLE 8-3 Causes of Developmental Disability
Cause Example mechanism Example condition

Abnormal embryonic Exposure to a toxin FASD

development

Birth trauma Anoxia (oxygen deprivation) Cerebral palsy

Chronic malnutrition Abnormal brain development Kwashiorkor

Drugs (e.g., valproate) Neural tube defects Spina bifida ASD

Environmental Sensory deprivation Children in Romanian

abnormality orphanages

Genetic abnormality Error of metabolism Phenylketonuria Down

Chromosomal abnormality syndrome

Prenatal disease Infection Rubella (German measles)

Retardation
 The simpler neuronal structure probably indicates a marked reduction
in the number of brain connections, which presumably caused the
developmental disability. Variation in both the nature and the extent of
neuronal abnormality in different children would lead to different
behavioral syndromes.

Typical child
Developmentally disabled child
FIGURE 8-33 Neuronal Contrast Representative dendritic branches from cortical
neurons in a child of typical intelligence (left) and a developmentally disabled child (right),
whose neurons are thinner and have far fewer spines. Information from D. P. Purpura (1974).
Dendritic spine “dysgenesis” and mental retardation. Science, 186, p. 1127.
 8-4 REVIEW
Brain Development and the Environment
Before you continue, check your understanding.
1 . The idea that specific molecules in different cells in various midbrain
regions give each cell a distinctive chemical identity is known as the
__________.
2 . Subnormal visual stimulation to one eye during early development
can lead to a loss of acuity, known as __________.
3 . The hormone __________ masculinizes the brain during
development.
4 . The brain’s sensitivity to experience is highest during ___________.
5 . Why do so many mental disorders appear during adolescence?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 How Do Any of Us Develop a Normal
8-5

Brain?
When we consider the brain’s complexity, the less-than-precise process
of brain development, and the myriad factors—from SES to gut bacteria
—that can influence development, we are left to marvel at how so many
of us end up with brains that pass for normal. We all must have had
neurons that migrated to wrong locations, made incorrect connections,
were exposed to viruses or other harmful substances. If the brain were as
fragile as it might seem, to end up with a normal brain would be almost
impossible.
Apparently, animals have evolved a substantial capacity to repair
minor abnormalities in brain development. Most people have developed
in the range that we call normal because the human brain’s plasticity and
regenerative powers overcome minor developmental deviations. By
initially overproducing neurons and synapses, the brain gains the
capacity to correct errors that might have arisen accidentally.
These same plastic properties later allow us to cope with the ravages
of aging. Neurons are dying throughout our lifetime. By age 60,
investigators ought to see significant effects from all this cell loss,
especially considering the cumulative results of exposure to
environmental toxins, drugs, traumatic brain injuries, and other neural
insults. But this is not what happens.
Although some teenagers may not believe it, relatively few 60-year-
olds are demented. By most criteria, the 60-year-old who has been
intellectually active throughout adulthood is likely to be much wiser than
the 18-year-old whose brain has lost relatively few neurons. A 60-year-
old chess player will have a record of many more chess matches from
which to draw game strategies than does an 18-year-old, for example.
Clearly, some mechanism must enable us to compensate for loss and
minor injury to our brain cells. This capacity for plasticity and change,
for learning and adapting, is arguably the most important characteristic
of the human brain during development and throughout life.
We return to learning, memory, and neuroplasticity in Chapter 14 .
 SUMMARY
8-1 Three Perspectives on Brain Development
Nervous system development entails more than the unfolding of a
genetic blueprint. Development is a complex dance of genetic and
environmental events that interact to sculpt the brain to fit within a
particular cultural and environmental context. We can approach this
dance from three perspectives: (1) correlating emerging brain structures
with emerging behaviors, (2) correlating new behaviors with neural
maturation, and (3) identifying influences on brain and behavior.
8-2 Neurobiology of Development
Human brain maturation is a long process, lasting as late as age 30.
Neurons, the units of brain function, develop a phenotype, migrate, and,
as their processes elaborate, establish connections with other neurons
even before birth. The developing brain produces many more neurons
and connections than it needs and then prunes back in toddlerhood and
again in adolescence and early adulthood to a stable level maintained by
some neurogenesis throughout the lifespan. Experiences throughout
development can trigger epigenetic mechanisms, such as gene
methylation, that alter gene expression.
8-3 Using Emerging Behaviors to Infer Neural
Maturation
Throughout the world, across the cultural spectrum, from newborn to
adult, we all develop through similar behavioral stages. As infants
develop physically, motor behaviors emerge in a predictable sequence
from gross, poorly directed movements toward objects to controlled
pincer grasps to pick up objects as small as pencils by about 11 months.
Cognitive behaviors also develop through stages of logic and problem
solving. Beginning with Jean Piaget, researchers have identified and
characterized four or more distinct stages of cognitive development.
Each stage can be identified by specific behavioral tests.
Behaviors emerge as the neural systems that produce them develop.
Matching the median timetables of neurodevelopment with observed
behavior infers the hierarchical relation between brain structure and
brain function. Motor behaviors emerge in synchrony with maturating
motor circuits in the cerebral cortex, basal ganglia, and cerebellum, as
well as in the connections from these areas to the spinal cord. Similar
correlations between emerging behaviors and neuronal development
accompany the maturation of cognitive behavior as neural circuits in the
frontal and temporal lobes mature in early adulthood.
8-4 Brain Development and the Environment
The brain is most plastic during its development, and neuronal structures
and their connections can be molded by various factors throughout
development. The brain’s sensitivity to factors such as external events,
quality of environment, tactile stimulation, drugs, gonadal hormones,
stress, and injury varies over time. At critical periods in the course of
development, beginning prenatally, different brain regions are
particularly sensitive to different events.
Brain perturbations in the course of development from, say, anoxia,
trauma, or toxins can alter brain development significantly; can result in
severe behavioral abnormalities, including intellectual disability; and
may be related to such disorders as ASD or SIDS. Other behavioral
disorders emerge in adolescence, a time of prolonged frontal lobe
change.
8-5 How Do Any of Us Develop a Normal Brain?
The brain has a substantial capacity to repair or correct minor
abnormalities, allowing most people to develop normal behavioral
repertoires and to maintain brain function throughout life.
 KEY TERMS
amblyopia, p. 269
androgen, p. 273
anencephaly, p. 277
apoptosis, p. 256
autism spectrum disorder (ASD), p. 255
cell adhesion molecule (CAM), p. 256
chemoaffinity hypothesis, p. 269
critical period, p. 269
dorsolateral prefrontal cortex (DLPFC), p. 259
estrogens, p. 273
filopod (pl. filopodia), p. 256
glioblast, p. 251
growth cone, p. 256
growth spurt, p. 263
imprinting, p. 271
masculinization, p. 273
netrin, p. 256
neural Darwinism, p. 256
neural plate, p. 249
neural stem cell, p. 251
neural tube, p. 249
neuroblast, p. 251
neurotrophic factor, p. 253
progenitor cell (precursor cell), p. 251
radial glial cell, p. 253
subventricular zone, p. 251
sudden infant death syndrome (SIDS), p. 277
testosterone, p. 273
tropic molecule, p. 256

Visit Lounch Pad to access the e-Book, videos,

Learning Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

How Do We Sense,
Perceive, and See the
World?
 Katherine Streeter

CLINICAL FOCUS 9-1 MIGRAINES AND A CASE OF

BLINDSIGHT
9-1 NATURE OF SENSATION AND PERCEPTION
SENSORY RECEPTORS
NEURAL RELAYS
SENSORY CODING AND REPRESENTATION
PERCEPTION
9-2 THE VISUAL SYSTEM’S FUNCTIONAL ANATOMY
STRUCTURE OF THE RETINA
THE BASICS VISIBLE LIGHT AND THE STRUCTURE OF THE
EYE
PHOTORECEPTORS
CLINICAL FOCUS 9-2 VISUAL ILLUMINANCE
TYPES OF RETINAL NEURONS
VISUAL PATHWAYS
DORSAL AND VENTRAL VISUAL STREAMS
9-3 LOCATION IN THE VISUAL WORLD
CODING LOCATION IN THE RETINA
LOCATION IN THE LATERAL GENICULATE NUCLEUS AND
REGION V1
VISUAL CORPUS CALLOSUM
9-4 NEURONAL ACTIVITY
SEEING SHAPE
SEEING COLOR
RESEARCH FOCUS 9-3 COLOR-DEFICIENT VISION
NEURONAL ACTIVITY IN THE DORSAL STREAM
9-5 THE VISUAL BRAIN IN ACTION
INJURY TO THE VISUAL PATHWAY LEADING TO THE CORTEX
 INJURY TO THE WHAT PATHWAY
CLINICAL FOCUS 9-4 CARBON MONOXIDE POISONING
INJURY TO THE HOW PATHWAY
CLINICAL FOCUS 9-1

Migraines and a Case of Blindsight

D. B.’s recurring headaches began at about age 14. A visual aura
warned of a headache’s approach: an oval area of flashing
(scintillating) light appeared just left of center in his field of vision.
Over the next few minutes, the oval enlarged. After about 15
minutes, the flashing light vanished, and D. B. was blind in the
region of the oval.
D. B. described the oval as an opaque white area surrounded by a
rim of color. A headache on the right side of his head followed and
could persist for as long as 48 hours. D. B. usually fell asleep before
that much time elapsed. When he awakened, the headache was gone
and his vision was normal again.
D. B. was subject to severe migraine, a recurrent headache
usually on one side of the head. Migraines vary in severity,
frequency, and duration and are often accompanied by nausea and
vomiting. Migraine is perhaps the most common of all neurological
disorders, affecting some 5 to 20 percent of the population at some
time in their life.
Auras may be auditory or tactile as well as visual and may result
in an inability to move or to talk. After an aura passes, most have a
severe headache caused by a dilation of cerebral blood vessels. The
headache is usually limited to one side of the head, just as the aura is
on one side of the visual field. Left untreated, migraines may last for
hours or even days.
D. B.’s attacks continued at intervals of about 6 weeks for 10
years. After one attack, he was left with a small blind spot, or
scotoma, illustrated in the accompanying photographs. When D. B.
was 26 years old, a neurologist found that a collection of abnormal
blood vessels at the back of his right occipital lobe was causing the
migraine attacks—a most unusual cause.
By the time he was 30, the migraines had begun to interfere with
his family life, social life, and job. No drug treatment was effective,
so D. B. had the malformed blood vessels surgically removed. The
operation relieved his pain and generally improved his life, but a part
of his right occipital lobe, deprived of blood, had died. D. B. was
blind in the left half of his visual field: as he looks at the world
through either eye, he is unable to see anything left of the midline.
Lawrence Weizkrantz (1986) made a remarkable discovery about
D. B.’s blindness. D. B. could not identify objects in his blind area
but could very accurately tell whether a light had blinked on there
and even where the light was. Apparently, D. B.’s brain knew when a
light blinked and where it appeared. This phenomenon is called
blindsight. D. B.’s brain knew more than he was aware of
consciously. D. B.’s case provides an excellent example of the
parallel streams of visual processing in the cortex. His system for
processing objects was impaired, but his system for locating objects
in space was not.

Tyler Olson/Shutterstock
X = Fixation point
As a typical migraine scotoma develops, a person looking at the small
white × in the photograph at the far left would first see a small patch
of lines. This striped area continues growing outward, leaving an
 opaque area (scotoma) where the stripes were, almost completely
blocking the visual field within 15 to 20 minutes. Normal vision returns
shortly thereafter.

As you look at the photograph in Clinical Focus 9-1 , Migraines

and a Case of Blindsight, you see three people—two women and a man
—who appear to be walking and talking on a warm summer day. Trees
appear in the background, clearly behind the people. It is tempting to
believe that this visual image is transferred whole to the brain, where we
see it.
But how could the nervous system do this? There is no viewing
screen in the brain. Instead, the nervous system must construct the image
from bits of information, such as shape and color. Then the brain must
put it all together to form what we perceive as a complete image. The
neural reconstruction is not a passive image such as a TV screen
projects. Rather, the brain continuously employs memories, both to
interpret moment-to-moment sensory information and to predict the
immediate future.
D. B.’s case demonstrates that we are consciously aware of only part
of the visual information our brain is processing. This selective
awareness is an important working principle behind human sensation
and perception. Weizkrantz, a world-renowned visual neuroscientist at
Oxford University, detected it in the visual system only because of D.
B.’s injury.
We are in fact unaware of much of the sensory processing that takes
place in the neural pathways for vision, hearing, touch, taste, and smell.
All our senses convert energy into neural activity that has meaning for
us. We begin this chapter with a general summary of sensation and
perception that explores how this energy conversion takes place.
Vision is this chapter’s main topic; hearing is Chapter 10 ’s. Section
11-4 covers body senses and balance. Section 12-2 explains smell
and taste.
The ability to lose conscious visual perception while retaining
unconscious vision, as D. B. did, leads us to the chapter’s central
question: How do we see the world? We begin by overviewing visual
system anatomy. Next we consider the connections between the eyes and
the sections of the brain that process visual information.
 Turning to the perceptual experience of sight, we focus on how
neurons respond to visual input and enable the brain to perceive features
such as color, shape, and movement. At the chapter’s end, we explore
vision’s culmination: understanding what we see. How do we infuse light
energy with meaning to grasp the content of written words or to see the
beauty in a painting? Read on.
 9-1 Nature of Sensation and Perception
We may believe that we see, hear, touch, smell, and taste real things in a
real world. In fact, the only input our brain receives from the “real”
world is a series of action potentials passed along the neurons that form
our various sensory pathways. Although we experience visual and body
sensations as fundamentally different from one another, the nerve
impulses coursing in the neurons of these two sensory systems are quite
similar, as are the neurons themselves.
Neuroscientists understand how nerves can turn energy, such as light
waves, into nerve impulses. They also know the pathways those nerve
impulses take to reach the brain. But they do not know how we end up
perceiving one set of nerve impulses as what the world looks like and
another set as what makes us move.
How much of what you know comes through your senses? Taken at
face value, this question seems reasonable. At the same time, we realize
that our senses can deceive us—that two people can look at the same
optical illusion and see very different images, that a person dreaming
typically does not think that the dream images are real, that you often do
not think that a picture of you looks like you. Many scientists think that
much of what we know comes to us through our senses, but they also
think that our brains actively transform sensory information into forms
that help us to adapt and are thus behaviorally useful.
Our sensory systems appear to be extremely diverse: vision, audition,
touch, taste, and olfaction appear to have little in common at first glance.
Although our perceptions and behaviors in relation to them differ, each
sensory system is organized on a similar hierarchical plan. We now
consider the features common to the sensory systems—receptors, neural
relays between receptor and neocortex, sensory coding and
representation, and perception.
 SPL/Science Source
Vision begins in the photoreceptor cells, the rods and cones shown here.
Section 9-2 details how they work.

Sensory Receptors
Sensory receptor neurons are specialized to transduce (convert) sensory
energy—light, for example—into neural activity. If we put flour into a
sieve and shake it, the more finely milled particles fall through the holes,
whereas the coarser particles and lumps do not. Sensory receptors are
designed to respond only to a narrow band of energy—analogous to
particles of certain sizes—within each modality’s energy spectrum. Each
sensory system’s receptors are specialized to filter a different form of
energy:
• For vision, the photoreceptors in the retina convert light energy into
chemical energy, which is in turn converted into action potentials.
• In the auditory system, air pressure waves are first converted into
mechanical energy, which activates the auditory receptors that produce
action potentials in auditory receptor neurons.
• In the somatosensory system, mechanical energy activates receptors
sensitive to touch, pressure, or pain. These somatosensory receptors in
turn generate action potentials in somatosensory receptor neurons.
• For taste and olfaction, various chemical molecules in the air or in food
fit themselves into receptors of various shapes to activate action
potentials in the respective receptor neurons.
Were our visual receptors somewhat different, we would be able to
see in the ultraviolet as well as the visible parts of the electromagnetic
spectrum, as honeybees and butterflies can. Receptors in the human ear
respond to a wide range of sound waves, but elephants and bats can hear
and produce sounds far below and above, respectively, the range humans
can hear. In fact, in comparison with those of other animals, human
sensory abilities are about average.
Even our pet dogs have “superhuman” powers: they can detect trace
odors; hear low-range sounds, as elephants do; and see in the dark. We
can hold up only our superior color vision. Thus, for each species and its
individual members, sensory systems filter the inputs to produce an
idiosyncratic representation of reality.
An animal’s perception of the world depends on its nervous
system’s complexity and organization.
Receptive Fields
Every sensory receptor organ and cell has a receptive field, a specific
part of the world to which it responds. If you fix your eyes on a point
directly in front of you, for example, what you see of the world is the
scope of your eyes’ receptive field. If you close one eye, the visual world
shrinks. What the remaining eye sees is the receptive field for that eye.
receptive field Sensory region that stimulates a receptor cell or
neuron.
Each photoreceptor cell in the eye points in a slightly different
direction and so has a unique receptive field. You can grasp the
conceptual utility of the receptive field by considering that the brain uses
information from each sensory receptor’s receptive field not only to
identify sensory information but also to contrast the information each
receptor field is providing.
Receptive fields not only sample sensory information but also help
locate events in space. Because adjacent receptive fields may overlap,
the contrast between their responses to events help us localize sensations.
This spatial dimension of sensory information produces cortical patterns
and maps that form each person’s sensory reality.
Our sensory system is organized to tell us both what is happening in
the world around us and what in the world we are doing ourselves. When
you move, you change the perceived properties of objects, and you sense
things that have little to do with the external world. When we run, visual
stimuli appear to stream by us, a stimulus configuration called optic
flow. When you move past a sound source, you hear an auditory flow, a
gradual shift in sound intensity that takes place because of your changing
location. Optic flow and auditory flow are useful for telling us how fast
we are going, whether we are going in a straight line or up or down, and
whether we or an object in the world is moving.
optic flow Streaming of visual stimuli that accompanies an
observer’s movement through space.
auditory flow Change heard as a person and a source of sound
move relative to one another.
Try this experiment. Slowly move your hand back and forth before
your eyes and gradually increase its speed. Eventually, your hand will
get a little blurry, because your eye movements are not quick enough to
follow its movement. Now keep your hand still and move your head
back and forth. The image of your hand remains clear. When receptors in
the inner ear inform your visual system that your head is moving, the
visual system compensates for the head movements, and you observe the
hand as a stationary image.
 Tyler Olson/Shutterstock

Receptive Fields In vision, each photoreceptor neuron has a

unique receptive field that partially overlaps adjacent fields, diagrammed
for another class of retinal neurons in Figure 9-27 .

Receptor Density and Sensitivity

Receptor density is particularly important for determining a sensory
system’s sensitivity. For example, tactile receptors on the fingers are
numerous compared with those on the arm. The difference explains why
fingers can discriminate touch remarkably well and the arm cannot.
Our sensory systems use different receptors to enhance sensitivity
under different conditions. For example, the visual system uses different
sets of receptors to respond to light and color. Color photoreceptors are
small and densely packed to make sensitive color discriminations in
bright light. Receptors for black–white vision are larger and more
scattered, but their sensitivity to light—say, a lighted match at a distance
of 2 miles on a dark night—is truly remarkable.
Differences in density of sensory receptors determine many animals’
special abilities—dogs’ excellent olfactory ability and the excellent
tactile ability of raccoons’ digits. Variations in receptor density in the
human auditory receptor organ may explain such abilities as perfect
pitch, displayed by some musicians.
Craig Lovell/Eagle Visions Photography/Alamy
Section 10-4 explains how we perceive music.

Neural Relays
Inasmuch as receptors are common to each sensory system, all receptors
connect to the cortex through a sequence of three or four intervening
neurons. The visual and somatosensory systems have three relays, and
the auditory system has four. Information can be modified at various
stages in the relay, allowing the sensory system to mediate different
responses. Once again, this is very different from the sensory images on
a TV screen or from an audio system: information is being modified
repeatedly as the brain constructs the image or sound.
Neural relays also allow sensory systems to interact. There is no
straight-through point-to-point correspondence between one neural relay
and the next; rather, each successive relay recodes the activity. Sensory
neural relays are central to the hierarchy of motor responses in the brain.
Some of the three or four relays in each sensory system are in the
spinal cord; others, in the brainstem; and still others, in the neocortex. At
each level, the relay allows a sensory system to produce relevant actions
that define the hierarchy of our motor behavior. For example, the first
relay for pain receptors in the spinal cord is related to reflexes that
produce withdrawal of a body part from a painful stimulus. Thus, even
after section of the spinal cord from the brain, a limb still withdraws
from a painful stimulus.
Recall the principle from Section 2-6 : brain systems are organized
hierarchically and in parallel.
A dramatic effect of sensory interaction is the visual modification of
sound. If a person hears a speech syllable such as ba while observing
someone who is articulating ga, the listener hears not the actual sound ba
but a hybrid sound, da. The viewed lip movements modify the listener’s
auditory perception.
This interaction effect is potent: it highlights the fact that a speaker’s
facial gestures influence our perception of speech sounds. As Roy
Hamilton and his coworkers (2006) described, synchrony of gestures and
sounds is an important aspect of language acquisition. The difficulty of
learning a foreign language can relate to the difficulty of blending a
speaker’s articulation movements with the sounds the speaker produces.
Sensory Coding and Representation
After it has been transduced, all information from all sensory systems is
encoded by action potentials that travel along peripheral nerves in the
somatic nervous system until they enter the spinal cord or brain. From
there the action potentials travel on nerve tracts within the central
nervous system. Every bundle carries the same kind of signal. How do
action potentials encode different sensations? (How does vision differ
from touch?) How do they encode the features of particular sensations?
(How does purple differ from blue?)
Parts of these questions seem easy to answer; others pose a
fundamental challenge to neuroscience. The presence of a stimulus can
be encoded by an increase or decrease in a neuron’s discharge rate, and
the amount of increase or decrease can encode stimulus intensity. As
detailed in Section 9-4 , qualitative visual changes, such as from red to
green, can be encoded by activity in different neurons or even by
different levels of discharge in the same neuron. (For example, more
activity might signify redder and less activity, greener.)
Recall the principle from Section 2-6 : the nervous system works by
juxtaposing excitation and inhibition.
What is less clear is how we perceive such sensations as touch, sound,
and smell as different from one another. Part of the explanation is that
each sensation is processed in its own distinct cortical region. Also, we
learn through experience to distinguish them. Third, each sensory system
has a preferential link with certain reflexive movements, constituting a
separate wiring that helps keep each system distinct at all levels of neural
organization. For example, pain stimuli produce withdrawal responses,
and fine-touch and pressure stimuli produce approach responses.
 Sensory Homunculus (plaster), English School, (20th century)/Natural History
Museum, London, UK/The Bridgeman Art Library
This curious figure reflects the topographic map in the sensorimotor
cortex. Disproportionately large areas control body parts we use to make
the most-skilled movements. See Sections 11-2 and 11-6 . Section 15-6
details synesthesia.

The distinctions among the sensory systems, however, are not always
clear: some people hear in color or identify smells by how the smells
sound to them. This mixing of the senses is called synesthesia. Anyone
who has shivered when hearing a piece of music or at the noise chalk or
fingernails can make on a blackboard has felt sound.
In most mammals, the neocortex represents the sensory field of each
modality—vision, hearing, touch, smell, or taste—as a spatially
organized neural representation of the external world. This topographic
map is a neural–spatial representation of the body or of the areas of the
sensory world perceived by a sensory organ. All mammals have at least
one primary cortical area for each sensory system. Additional areas are
usually referred to as secondary, because most of the information that
reaches these areas is relayed through the primary area. Each additional
representation is probably dedicated to encoding one specific aspect of
the sensory modality. For vision, different additional representational
areas may take part in perceiving color, movement, and form.
topographic map Spatially organized neural representation of the
external world.

Perception
Sensation is far more than the simple registration of physical stimuli
from the environment by the sensory organs. Compared with the richness
of actual sensation, our description of sensory neuroanatomy and
function is bound to seem sterile. Part of the reason for the disparity is
that our sensory impressions are affected by the context in which they
take place, by our emotional state, and by our past. All these factors
contribute to perception, the subjective experience of sensation—how
we interpret what we sense. Perception is more interesting to
neuropsychologists than is sensation.
sensation Registration by the sensory organs of physical stimuli
from the environment.
perception Subjective interpretation of sensations by the brain.
Clear proof that perception is more than sensation lies in the fact that
different people transform the same sensory stimulation into totally
different perceptions. The classic demonstration is an ambiguous image
such as the well-known Rubin’s vase shown in Figure 9-1 A . This
image may be perceived either as a vase or as two faces. If you fix your
eyes on the center of the picture, the two perceptions will alternate, even
though the sensory stimulation remains constant.
Similarly, the photograph of two cheetahs in Figure 9-1 B is
ambiguous. Which head goes with which cheetah? As with the Rubin’s
vase, the two perceptions may alternate. Such ambiguous images and
illusions demonstrate the workings of complex perceptual phenomena
and enlighten our insight into our cognitive processes.
 © Gerry Lemmo

(A)
(B)
FIGURE 9-1 Perceptual Illusions (A) Edgar Rubin’s ambiguous
reversible image can be perceived as a vase or as two faces. (B) Likewise
ambiguous in the photo, each cheetah’s head can be perceived as
belonging to either cheetah’s body.
 9-1 REVIEW
Nature of Sensation and Perception
Before you continue, check your understanding.
1 . ___________ are energy filters that transduce incoming physical
energy into neural activity.
2 . ___________ fields locate sensory events. Receptor ___________
determines sensitivity to sensory stimulation.
3 . We distinguish one sensory modality from another by its
___________.
4 . Sensation registers physical stimuli from the environment by the
sensory organs. Perception is the ___________.
5 . How is the anatomical organization similar for each sense?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 The Visual System’s Functional
9-2

Anatomy
Our primary sensory experience is visual. Far more of the human brain is
dedicated to vision than to any other sense. Understanding the visual
system’s organization, then, is key to understanding human brain
function. To build this understanding, we begin by following the routes
visual information takes into and within the brain. This exercise is a bit
like traveling a road to discover where it goes. As you trace the route,
keep in mind the photograph in Focus 9-1 (page 284 ) and what the
different levels of the visual system are doing to capture that image in
the brain.

Structure of the Retina

Light energy travels from the outside world through the pupil and into
the eye, where it strikes a light-sensitive surface, the retina, at the back
of the eye ( Figure 9-2 ). From this stimulation of photoreceptor cells
on the retina, we begin to construct a visual world. If you are familiar
with the properties of the electromagnetic spectrum and with the
structure of the eye, read on. To refresh your knowledge of these topics,
read The Basics: Visible Light and the Structure of the Eye on pages 290
–291 before you continue.
retina Light-sensitive surface at the back of the eye consisting of
neurons and photoreceptor cells.
photoreceptor Specialized retinal neuron that transduces light into
neural activity.
Virtually all retinal neurons are insensitive to light so are unaffected
by light passing through them.
Figure 9-2 includes a photograph of the retina, which is composed of
photoreceptors beneath a layer of neurons connected to them. The
neurons lie in front of the photoreceptor cells, but they do not prevent
incoming light from being absorbed by those receptors, because the
neurons are transparent and the photoreceptors are extremely sensitive to
light. In addition, special glial cells in the retina called Müller cells span
from the retina’s inner membrane at the front to the photoreceptors at the
back of the retina and act as optical fibers, channeling light to the buried
photoreceptors.
Together, the photoreceptor cells and the retinal neurons perform
some amazing functions. They translate light into action potentials,
discriminate wavelengths so that we can distinguish colors, and work in
a range of light intensities from bright to dim. These cells afford visual
precision sufficient for us to see a human hair lying on the page of this
book from a distance of 18 inches.
As in a camera, the image of objects projected onto the retina is
upside down and backward. This flip-flopped orientation poses no
problem for the brain. Remember, the brain is constructing the outside
world, so it does not really care how the image is oriented initially. In
fact, the brain can make adjustments regardless of the orientation of the
images that it receives.
If for several days you were to wear glasses that invert visual images,
the world would first appear upside down but then would suddenly
appear right side up again because your brain would correct the
distortion (Held, 1968). Curiously, when you removed the glasses, the
world would temporarily seem upside down once more, because your
brain at first would be unaware that you had tricked it again. Eventually,
though, your brain would solve this puzzle too, and the world would flip
back to the correct orientation.
 SPL/Science Source

FIGURE 9-2 Central Focus This cross section through the retina (A) shows the
depression at the fovea—also shown in the scanning electron micrograph (B) —where
photoreceptors are packed most densely and where our vision is clearest.

Fovea
Try this experiment. Focus on the print at the left edge of this page. The
words will be clearly legible. Now, while holding your eyes still, try to
read the words on the right side of the page. It will be very difficult, even
impossible, even though you can see that words are there.
 THE BASICS

Visible Light and the Structure of the

Eye
The brain’s visual system analyzes visible light—the part of the
electromagnetic (EM) spectrum that the human eye evolved to
capture and focus.
Light: The Stimulus for Vision
Light can enter the eye directly from a source that produces it—a
lamp, for example, or the sun—or indirectly after reflecting from a
surface—the pages of a book, for example, or the surface of water.
As illustrated in Electromagnetic Spectrum, not all light waves are
the same length, and only a sliver of the EM spectrum is visible to
us. If our photoreceptors could detect light in the shorter ultraviolet
or longer infrared wavelengths, we would see additional colors.
Structure of the Eye
The range of light visible to humans is constrained not by the
properties of light waves but rather by the properties of our visual
receptors. How do photoreceptor cells in the retina absorb light
energy and initiate the processes leading to vision? How the Eye
Works illustrates the eye’s structure and shows how its design
captures and focuses light.
Optical Errors of Refraction
A web of muscles adjusts the shape of the eye’s lens to bend light to
greater or lesser degrees, which allows near or far images to be
focused on the retina. When images are not properly focused, we
need corrective lenses.
The eye, like a camera, works correctly only when sufficient
light passes through the lens and is focused on the receptor surface
—the retina in the eye or the light-sensitive material in the camera.
If the focal point of the light falls slightly in front of the receptor
surface or slightly behind it, a refractive error causes objects to
appear blurry. Refractive errors in the eye are of two basic types,
diagrammed in Refractive Errors.
 Myopia (nearsightedness) afflicts about 50 percent of young
people in the developed world. Hyperopia (farsightedness) is a less
common refractive error, but as people age, the lens loses its
elasticity and consequently becomes unable to refract light from
nearby objects correctly. This form of hyperopia, called presbyopia
(old-sightedness), is so common that you rarely find people older
than 50 who do not need glasses to see up close, especially for
reading.
It is also common to see young children wearing corrective
lenses. The incidence of myopia in the United States has doubled in
the past 40 years to about 42 percent. It is even higher in Northern
Europe (50 percent) and Asia (50 percent to 80 percent). Two
factors probably account for the increase.
First, more young people are attending school longer and thus
are doing more close work, especially reading. Close work strains
the eye muscles. Second, people are spending less and less time
outdoors in bright light. Bright light makes the pupil contract,
which improves visual depth of field: your eyes focus better.
Children should probably spend at least 2 hours each day outside in
bright light. Consider that myopia is less common in countries such
as Australia (17 percent), where bright light is plentiful.

The electromagnetic energy visible to humans varies in

wavelength from about 400 to 700 nanometers. We
perceive the shortest visible wavelengths as deep purple.
As wavelength increases, perceived color morphs from
violet to blue to green to yellow, orange, and red: the colors
of the rainbow.
Electromagnetic Spectrum
How the Eye Works

Refractive Errors
 FIGURE 9-3 Acuity Across the Visual Field Focus on the star
in the middle of the chart to demonstrate the relative sizes of letters legible
in the central field of vision compared with the peripheral field.

The lesson is that our vision is better in the center of the visual field
than at the margins, or periphery. Letters at the periphery must be much
larger than those in the center for us to see them as well. Figure 9-3
shows how much larger. The difference is due partly to the fact that
photoreceptors are more densely packed at the center of the retina, in a
region known as the fovea. Figure 9-2 shows that the retinal surface is
depressed at the fovea. This depression is formed because many optic
nerve fibers skirt the fovea to facilitate light access to its receptors.
fovea Central region of the retina specialized for high visual acuity;
its receptive fields are at the center of the eye’s visual field.
Blind Spot
Now try another experiment. Stand with your head over a tabletop and
hold a pencil in your hand. Close one eye. Stare at the edge of the table-
top nearest you. Now hold the pencil in a horizontal position and move it
along the edge of the table, with the eraser on the table. Beginning at a
point approximately below your nose, move the pencil slowly along the
table in the direction of the open eye.
When you have moved the pencil about 6 inches, the eraser will
vanish. You have found your blind spot, a small area of the retina also
known as the optic disc. This is the area where blood vessels enter and
exit the eye and where fibers leading from retinal neurons form the optic
nerve, which goes to the brain. There are therefore no photoreceptors in
this part of the retina. You can use Figure 9-4 to demonstrate the blind
spot in another way.
blind spot Retinal region where axons forming the optic nerve leave
the eye and blood vessels enter and leave; has no photoreceptors and
is thus said to be blind.
Fortunately, your visual system solves the blind spot problem: your
optic disc is in a different location in each eye. The optic disc is lateral to
the fovea in each eye, which means that it is left of the fovea in the left
eye and right of the fovea in the right eye. Because the two eyes’ visual
fields overlap, the right eye can see the left eye’s blind spot and vice
versa.
Using both eyes together, then, you can see the whole visual world.
For people blind in one eye, the sightless eye cannot compensate for the
blind spot in the functioning eye. Still, the visual system compensates for
the blind spot in several other ways, and so these people have no sense of
a hole in their field of vision.
The blind spot is of particular importance in neurology. It allows
neurologists to indirectly view the condition of the optic nerve while
providing a window on events in the brain. If intracranial pressure
increases, as occurs with a tumor or brain abscess (an infection), the
optic disc swells, leading to papilledema (swollen disc). The swelling
occurs in part because, like all neural tissue, the optic nerve is
surrounded by cerebrospinal fluid. Pressure inside the cranium can
displace CSF around the optic nerve, causing swelling at the optic disc.
Another cause of papilledema is inflammation of the optic nerve
itself, a condition known as optic neuritis. Whatever the cause, a person
with a swollen optic disc usually loses vision owing to pressure on the
optic nerve. If the swelling is due to optic neuritis, probably the most
common neurological visual disorder, the prognosis for recovery is good.
 FIGURE 9-4 Find Your Blind Spot Hold this book 30 centimeters
(about 12 inches) away from your face. Shut your left eye and look at the
cross with your right eye. Slowly bring the page toward you until the red
spot in the center of the yellow disc disappears and the entire disc
appears yellow. The red spot is now in your blind spot. Your brain replaces
the area with the surrounding yellow to fill in the image. Turn the book
upside down to test your left eye.

Photoreceptors
The retina’s photoreceptor cells convert light energy first into chemical
energy and then into neural activity. Light striking a photoreceptor
triggers a series of chemical reactions that lead to a change in membrane
potential (electrical charge) that in turn leads to a change in the release of
neurotransmitter onto nearby neurons.
 SPL/Science Source

FIGURE 9-5 Photoreceptor Cells Rods and cones are tubelike

structures, as the scanning electron micrograph at right shows. They differ,
especially in the outer segment that contains the light-absorbing visual
pigment. Rods are especially sensitive to broad-spectrum luminance; and
cones, to particular wavelengths of light.

Rods and cones, the two types of photoreceptors shown in Figure 9-5
, differ in many ways. They are structurally different. Rods are longer
than cones and cylindrical at one end, whereas cones have a tapered end.
Rods are more numerous than cones; are sensitive to low levels of
brightness (luminance), especially in dim light; and function mainly for
night vision (see Clinical Focus 9-2 , Visual Illuminance). Cones do not
respond to dim light, but they are highly responsive to bright light. Cones
mediate both color vision and our ability to see fine detail (visual acuity).
rod Photoreceptor specialized for functioning at low light levels.
cone Photoreceptor specialized for color and high visual acuity.
 Rods and cones are unevenly distributed over the retina. The fovea
has only cones, but their density drops dramatically beyond the fovea.
For this reason, our vision is not so sharp at the edges of the visual field,
as demonstrated in Figure 9-3 .
A final difference between rods and cones is in their light-absorbing
pigments. All rods have the same pigment. Each cone has one of three
pigments. These four pigments, one in the rods and three in the cones,
form the basis for our vision.
As shown on the spectrum in Figure 9-6 , the three cone pigments
absorb light across a range of visible frequencies, but each is most
responsive to a small range of wavelengths—short (bluish light),
medium (greenish light), and long (reddish light). As you can see on the
background spectrum in Figure 9-6 , however, if you were to look at
lights with wavelengths of 419, 531, and 559 nanometers (nm), they
would not appear blue, green, and red but rather blue-green, yellow-
green, and orange. Remember, though, that you are looking at the lights
with all three of your cone types and that each cone pigment responds to
light across a range of frequencies, not just to its frequency of maximum
absorption.
A nanometer (nm) is one-billionth of a meter.
Both the presence of three cone receptor types and their relative
numbers and distribution across the retina contribute to our perception of
color. As Figure 9-7 shows, the three cone types are distributed more or
less randomly across the retina, making our ability to perceive different
colors fairly constant across the visual field. The numbers of red and
green cones are approximately equal, but blue cones are fewer. As a
result, we are not as sensitive to wavelengths in the blue part of the
visible spectrum as we are to red and green wavelengths.
FIGURE 9-6 Range and Peak Sensitivity Our color perception
corresponds to the summed activity of the three cone types: S cones, M
cones, and L cones (for short, medium, and long wavelengths). Each type
is most sensitive to a narrow range of the visible spectrum. Rods (white
curve) prefer a range of wavelengths centered on 496 nm but do not
contribute to our color perception. Rod activity is not summed with the
cones in the color vision system.
CLINICAL FOCUS 9-2

Visual Illuminance
The eye, like a camera, works correctly only when sufficient light
passes through the lens and is focused on the receptor surface—the
retina of the eye or the light-sensitive surface in the camera. Too
little light entering the eye or the camera produces a problem of
visual illuminance : it is hard to see any image at all.
Visual illuminance is typically a complication of aging eyes, It
cannot be cured by corrective lenses. As we age, the eye’s lens and
cornea allow less light through, so less light strikes the retina. Don
Kline (1994) estimated that between ages 20 and 40, people’s ability
to see in dim light drops by 50 percent; and by a further 50 percent
over every 20 additional years. As a result, seeing in dim light
becomes increasingly difficult, especially at night.
The only solution to compensate for visual illuminance is to
increase lighting. Night vision is especially problematic. Not
surprisingly, statistics show a marked drop in the number of people
driving at night in each successive decade after age 40.

Photo Courtesy of Dr. Donald Kline, University of Calgary

 These photographs represent the typical drop in luminance between
age 20 (left) and age 60 (right).

FIGURE 9-7 Retinal Receptors The retinal mosaic of rods and three
cone types. This diagram represents the distribution near the fovea, where
cones outnumber rods. Red and green cones outnumber the blue.

Other species that have color vision similar to humans’ also have
three types of cones with three color pigments. Because of slight
variations in these pigments, the exact frequencies of maximum
absorption differ among species. For humans, the exact frequencies are
not identical with the numbers given earlier, which are an average across
mammals. They are actually 426 and 530 nm for the blue and green
cones, respectively, and 552 or 557 nm for the red cone. The two peak
sensitivity levels of red cones represent the two variants that humans
have evolved. The difference in these two red cones appears minuscule,
but it does make a functional difference in some females’ color
perception.
The gene for the red cone is carried on the X chromosome. Males
have only one X chromosome, so they have only one of these genes and
only one type of red cone. The situation is more complicated for females,
who possess two X chromosomes. Although most women have only one
type of red cone, those who have both are more sensitive than the rest of
us to color differences at the red end of the spectrum. We could say that
women who have both red cone types have a slightly rosier view of the
world: their color receptors construct a world with a richer range of red
experiences. But they also have to contend with seemingly peculiar color
coordination by others.

Types of Retinal Neurons

Photoreceptors are connected to two layers of retinal neurons. In the
procession from the rods and cones toward the brain shown in Figure 9-
8 , the first layer contains three cell types: bipolar, horizontal, and
amacrine. Horizontal cells link photoreceptors with bipolar cells,
whereas amacrine cells link bipolar cells with cells in the second neural
layer, the retinal ganglion cells (RGCs). RGC axons collect in a bundle
at the optic disc and leave the eye to form the optic nerve.
retinal ganglion cell (RGC) One of a group of retinal neurons with
axons that give rise to the optic nerve.

FIGURE 9-8 Retinal Cells Neurons in the retina—bipolar, horizontal,

amacrine, and ganglion cells—form two layers moving outward from the
rods and cones at the retinal surface. Light must pass through both
transparent neuron layers to reach the photoreceptors.

Retinal ganglion cells fall into two major categories, called M and P
cells in the primate retina. The designations derive from the distinctly
different cell populations in the visual thalamus to which these two
classes of RGCs send their axons. As shown in Figure 9-9 , one
population consists of magnocellular cells (hence M); the other consists
of parvocellular cells (hence P). The larger M cells receive their input
primarily from rods and so are sensitive to light but not to color. The
smaller P cells receive their input primarily from cones and so are
sensitive to color.
In Latin, magno means large and parvo means small.
magnocellular (M) cell Large visual system neuron sensitive to
moving stimuli.
parvocellular (P) cell Small visual system neuron sensitive to
differences in form and color.
M cells are found throughout the retina, including the periphery,
where we are sensitive to movement but not to color or fine detail. P
cells are found largely in the region of the fovea, where we are sensitive
to color and fine details. As we follow the ganglion cell axons into the
brain, you will see that these two categories of RGCs maintain their
distinctiveness throughout the visual pathways.

FIGURE 9-9 Visual Thalamus The optic nerves connect with the
lateral geniculate nucleus of the thalamus. The LGN has six layers: two
magnocellular layers, which receive input mainly from rods, and four
parvocellular layers, which receive input mainly from cones.

Visual Pathways
RGCs form the optic nerve, the road into the brain. This road forks off to
several places. The destinations of these branches give us clues to what
the brain is doing with visual input and how the brain constructs our
visual world.
Crossing the Optic Chiasm
We begin with the optic nerves, one exiting from each eye. Just before
entering the brain, the optic nerves partly cross, forming the optic
chiasm.
optic chiasm Junction of the optic nerves, one from each eye, at
which the axons from the nasal halves of the retinas cross to the
brain’s opposite side.
The optic chiasm gets its name from the shape of the Greek letter
chi (X) (pronounced ki ).
About half the fibers from each eye cross in such a way that the left
half of each optic nerve goes to the left side of the brain, and the right
half goes to the brain’s right side, as diagrammed in Figure 9-10 . The
medial path of each retina, the nasal retina, crosses to the opposite side.
The lateral path, the temporal retina, travels straight back on the same
side. Because light that falls on the right half of each retina actually
comes from the left side of the visual field, information from the left
visual field goes to the brain’s right hemisphere, and information from
the right visual field goes to the left hemisphere. Thus, half of each
retina’s visual field is represented on each side of the brain.
By connecting both eyes with both hemispheres, our visual system
represents the world seen through two eyes as a single perception.
 FIGURE 9-10 Crossing the Optic Chiasm This dorsal view
shows the visual pathway from each eye to the primary visual cortex of
each hemisphere. Information from the right side of the visual field (blue)
moves from the two left halves of the retinas, ending in the left
hemisphere. Information from the left side of the visual field (red) hits the
right halves of the retinas and travels to the right side of the brain.

Three Routes to the Visual Brain

Two main pathways lead to the visual cortex in the occipital lobe: the
geniculostriate pathway for processing the object’s image and the
tectopulvinar pathway for directing rapid eye movements. Another
smaller pathway tracks into the hypothalamus.
GENICULOSTRIATE SYSTEM On entering the brain, the RGC
axons separate, forming the two distinct pathways shown in Figure 9-11
. All of the P ganglion axons and some of the M ganglion axons form a
pathway called the geniculostriate system. This pathway goes from the
retina to the lateral geniculate nucleus (LGN) of the thalamus and then to
layer IV of the primary visual cortex in the occipital lobe.
 geniculostriate system Projections from the retina to the lateral
geniculate nucleus to the visual cortex.
When stained, the primary visual cortex shows a broad stripe across it
in layer IV and so is known as striate (striped) cortex ( Figure 9-12 ).
The geniculostriate system therefore bridges the thalamus (geniculate)
and the striate cortex. From the striate cortex, the axon pathway divides.
One route goes to vision-related regions of the parietal lobe, and another
route goes to vision-related regions of the temporal lobe.
striate cortex Primary visual cortex (V1) in the occipital lobe;
shows stripes (striations) on staining.
TECTOPULVINAR SYSTEM The second pathway leading from the
eye is formed by the axons of the remaining M ganglion cells. These
cells send their axons to the midbrain’s superior colliculus, which sends
connections to the pulvinar region of the thalamus. This pathway is
therefore known as the tectopulvinar system because it runs from the
eye through the midbrain tectum to the pulvinar (see Figure 9-11 ). The
pulvinar sends connections to the parietal and temporal lobes, bypassing
the occipital visual areas.
tectopulvinar system Projections from the retina to the superior
colliculus to the pulvinar (thalamus) to the parietal and temporal
visual areas.
RETINOHYPOTHALAMIC TRACT Between 1 percent and 3
percent of RGCs are unique in that they are photosensitive : they act as
photoreceptors. These pRGCs, which contain the pigment melanopsin,
absorb blue light at a wavelength (between 460 and 480 nm) different
from the wavelengths of rods or cones (see Figure 9-6 ). Axons of
pRGCs form a small third visual pathway, the retinohypothalamic
tract.
retinohypothalamic tract Neural route formed by axons of
photosensitive retinal ganglion cells (pRGCs) from the retina to the
suprachiasmatic nucleus; allows light to entrain the SCN’s rhythmic
activity.
The retinohypothalamic tract synapses in the tiny suprachiasmatic
nucleus (SCN) in the hypothalamus, next to the optic chiasm.
Photosensitive RGCs participates both in regulating circadian rhythms
and in the pupillary reflex that expands and contracts the pupil in
response to the amount of light falling on the retina. Farhan Zaidi and
colleagues (2007) studied two profoundly blind subjects who lack
functional rods and cones. The researchers found that stimulation with
480-nm (blue) light increases alertness and appears to play some
rudimentary role in visual awareness.
Figure 13-6 maps the retinohypothalamic tract into the SCN.

FIGURE 9-11 Main Visual Pathways into the Brain The

optic nerve follows (1) the geniculostriate path to the primary visual cortex
and (2) the tectopulvinar path to the temporal and parietal lobes. (The
LGN of the thalamus is part of the diencephalon, shown in Figure 2-19 ;
the superior colliculus in the tectum is part of the midbrain, shown in
Figure 2-18 .)

Dorsal and Ventral Visual Streams

The geniculostriate and tectopulvinar pathways extend into the visual
brain. Each eventually leads to either the parietal lobe or the temporal
lobe. Our next task is to determine the role each lobe plays in building
our visual world. As we look at the photograph in Clinical Focus 9-1 ,
we can identify objects, and we can point to them. Identifying and
pointing are different functions.

Bryan Kolb
 FIGURE 9-12 Striate Cortex Area V1 is also called the striate cortex
because sections appear striated (striped) when stained with either a cell
body stain (left) or a myelin stain (right). The sections shown here come
from a rhesus monkey’s brain.

Having identified the temporal lobe and parietal lobe visual pathways,
researchers went searching for their possible functions. Why would
evolution produce two different destinations for these neural pathways?
Each route must produce visual knowledge for a different purpose.
David Milner and Mel Goodale (2006) proposed that these two
purposes are to identify a stimulus (the what function) and to control
movement to or away from the stimulus (the how function). This what –
how distinction came from an analysis of the routes visual information
takes when it leaves the striate cortex. Figure 9-13 shows the two
distinct visual pathways that originate in the striate cortex, one
progressing to the temporal lobe and the other to the parietal lobe. The
pathway to the temporal lobe is the ventral stream, whereas the
pathway to the parietal lobe is the dorsal stream.
ventral stream Visual processing pathway from V1 to the temporal
lobe for object identification and perceiving related movements.
dorsal stream Visual processing pathway from V1 to the parietal
lobe; guides movements relative to objects.
Both the geniculostriate and the tectopulvinar pathways contribute to
the dorsal and ventral streams. To understand how the two streams
function, we return to the details of how visual input from the eyes
contributes to them.
 FIGURE 9-13 Visual Streaming Information travels from the occipital
visual areas to the parietal and temporal lobes, forming the dorsal (how )
and ventral (what ) streams, respectively.

Geniculostriate Pathway
The RGC fibers from the two eyes distribute their connections to the two
lateral geniculate nuclei (left and right) of the thalamus. At first glance,
this appears to be an unusual arrangement. As seen in Figure 9-10 , the
fibers from the left half of each retina go to the left LGN; those from the
right half of each retina go to the right LGN. But the fibers from each
eye do not go to exactly the same LGN location.
Each LGN has six layers, and the projections from the two eyes go to
different layers, as illustrated in anatomical context in Figure 9-9 and
diagrammed in Figure 9-14 . Layers 2, 3, and 5 receive fibers from the
ipsilateral eye (the eye on the same side), whereas layers 1, 4, and 6
receive fibers from the contralateral eye (the eye on the opposite side).
This arrangement provides both for combining the information from the
two eyes and for segregating the information from the P and M ganglion
cells.
Axons from the P cells go only to layers 3 through 6 (the
parvocellular layers). Axons from the M cells go only to layers 1 and 2
(the magnocellular layers). Because the P cells are responsive to color
and fine detail, LGN layers 3 through 6 must be processing information
about color and form. In contrast, the M cells mostly process information
about movement, so layers 1 and 2 must deal with movement.
Just as there are six layers in the thalamic LGN (numbered 1 through
6), there are also six layers in the striate cortex (numbered I through VI).
That there happen to be six layers in each location is an accident of
evolution found in all primate brains. Let us now see where these LGN
cells from the thalamus send their connections within the visual cortex.
Figure 2-22 maps layers I through VI in the primary motor and
sensory cortices.

FIGURE 9-14 Geniculostriate Pathway

Layer IV is the main afferent (incoming) layer of the cortex. In the
visual cortex, layer IV has several sublayers, two of which are known as
IVCα and IVCβ. LGN layers 1 and 2 go to IVCα, and layers 3 through 6
go to IVCβ. A distinction between the P and M functions thus continues
in the striate cortex.
As illustrated in Figure 9-15 , input from the two eyes also remains
separated in the cortex. The input from the ipsilaterally and
contralaterally connected parts of the LGN go to adjacent strips of
occipital cortex. These strips, which are about 0.5 mm across, are known
as cortical columns.
cortical column Anatomic organization that represents a functional
unit six cortical layers deep and approximately 0.5 mm square,
perpendicular to the cortical surface.
In summary, P and M retinal ganglion cells send separate pathways to
the thalamus, and this segregation continues in the striate cortex. The left
and right eyes also send separate pathways to the thalamus, and these
pathways, too, remain segregated in the striate cortex.
Tectopulvinar Pathway
To review, magnocellular RGCs found throughout the retina receive
input primarily from the rods and so are sensitive to light but not to
color. M cells in the periphery of the retina are sensitive to movement but
not to color or fine details. In the brain, some M cells join P cells to form
the geniculostriate pathway. The tectopulvinar pathway is formed by the
axons of the remaining M cells.
These M cells send their axons to the superior colliculus in the
midbrain’s tectum. One function of the tectum is to produce orienting
movements—to detect stimuli and shift the eyes toward them. The
superior colliculus sends connections to the pulvinar region of the
thalamus. The medial pulvinar sends connections to the parietal lobe, and
the lateral pulvinar sends connections to the temporal lobe. One type of
information that these connections are conveying is related to where.
Where is important in both the what and how visual streams.
Many textbooks emphasize the how pathway as a where function.
Because where is both a property of what a stimulus is and a cue for
how to control movement, we use Milner and Goodale’s what–how
distinction.
The where function of the tectopulvinar system is useful in
understanding D. B.’s blind-sight, described in Clinical Focus 9-1 . His
geniculostriate system was disrupted by surgery, but his tectopulvinar
system was not, which allowed him to identify the location of stimuli
(where ) that he could not identify (what ).
This diagram shows where signals from the eye are processed in
predictable regions of the LGN.
The LGN is shown with three regions: the left eye occupying regions on
the right and left, and the right eye occupying the center region. These
regions are separated vertically as we view the LGN.
The LGN is further separated into 6 layers. Layers 1 and 2 are the M
layers. Layers 3 to 6 are the P layers.
The cortical visual area 1 has corresponding layers, except that layer 4 is
divided in two parts. The layers are: I, II, III, IVCa, IVCβ, V, VI.
The LGN sends signals to specific places in layer IV of the cortical
visual area.
LGN layer 1 left eye signal goes to visual cortex area 1 layer IVCa.
LGN layer 4 left eye signal goes to visual cortex area 1 layer IVCβ.
LGN layer 6 left eye signal goes to visual cortex area 1 layer IVCβ.
LGN layer 2 right eye signal goes to visual cortex area 1 layer IVCa.
LGN layer 3 right eye signal goes to visual cortex area 1 layer IVCβ.
LGN layer 5 right eye signal goes to visual cortex area 1 layer IVCβ.
 FIGURE 9-15 Maintaining Separate Visual Input Left:
Information from the eyes is segregated by layers in the LGN, which
maintains this segregation in its projections from the thalamus to the
primary visual cortex. Information from each eye travels to adjacent
regions in cortical layer IV. Right: A horizontal plane through striate cortex
shows a zebralike effect of alternating left and right eye regions.

Occipital Cortex
Our route down the visual pathways has led us from the retina all the
way back to the occipital lobe and into the parietal and temporal lobes.
Now we explore how visual information proceeds from the striate cortex
through the rest of the occipital lobe to the dorsal and ventral streams.
(A) Medial view of functional areas
FIGURE 9-16 Visual Regions of the Occipital Lobe

(B) Lateral view of functional areas

V1 = Primary visual cortex
V2–V5 = Extrastriate cortex
 As shown in Figure 9-16 , the occipital lobe is composed of at least
six visual regions: V1, V2, V3, V3A, V4, and V5. The striate cortex is
region V1, the primary visual cortex. The remaining occipital visual
areas form the extrastriate cortex, with each region processing specific
features of visual information. Because each occipital region has a
unique cytoarchitecture (cellular structure) and unique inputs and
outputs, we can infer that each must be doing something different from
the others.
primary visual cortex (V1) Striate cortex in the occipital lobe that
receives input from the lateral geniculate nucleus.
extrastriate (secondary visual) cortex (V2–V5) Visual cortical
areas in the occipital lobe outside the striate cortex.
All mammals have at least one primary cortical area for each
sensory system. The primary area relays most information that
reaches secondary areas.
As shown in Figures 9-12 and 9-15 , a remarkable feature of region
V1 is its striations—its distinctly visible layers. When Margaret Wong-
Riley and her colleagues (1993) stained region VI for the enzyme
cytochrome oxidase, which has a role in cell metabolism, they found an
unexpected heterogeneity. So they sectioned the V1 layers in such a way
that each cortical layer was in one plane of section, much like peeling off
the layers of an onion and laying them flat on a table. The surface of
each flattened layer can then be viewed from above.
The heterogeneous cytochrome staining now appears as random blobs
in the V1 layers, as diagrammed in Figure 9-17 . These darkened regions
have in fact become known as blobs, the less-dark regions separating
them as interblobs. Blobs and interblobs serve different functions.
Neurons in the blobs take part in color perception; neurons in the
interblobs participate in perception of form and motion. Within region
V1, then, input arriving from the P cell and M cell pathways of the
geniculostriate system is segregated into three separate types of
information: color, form, and motion.
blob Region in V1 that contains color-sensitive neurons, as revealed
by staining for cytochrome oxidase.
All three types of information move from region V1 to the adjoining
region V2. Here, the color, form, and motion inputs remain segregated,
again seen through the pattern of cytochrome oxidase staining. But as
Figure 9-17 shows, the staining pattern in region V2 differs from that in
region V1. Region V2 has a pattern of thick and thin stripes intermixed
with pale zones. The thick stripes receive input from the movement-
sensitive neurons in region V1; the thin stripes receive input from V1’s
color-sensitive neurons; and the pale zones receive input from V1’s
form-sensitive neurons.

FIGURE 9-17 Heterogeneous Layering Blobs in region V1 and

stripes in region V2 are illustrated in this drawing of a flattened section
through the visual cortex of a monkey. The blobs and stripes are revealed
by a special stain for cytochrome oxidase, a marker for mitochondria, the
organelles in cells that gather, store, and release energy.

FIGURE 9-18 Charting the Visual Streams The dorsal stream,

which controls visual action (top), begins in region V1 and flows through
V2 to the other occipital areas and finally to the parietal cortex, ending in
 area PG. The ventral stream, which controls object recognition (bottom),
begins in region V1 and flows through V2 to the other occipital areas and
finally to the temporal cortex, ending in area TE. Information from the
blobs and interblobs in V1 flows to the thick, thin, and pale zones of V2
and then to regions V3 and V4 to form the ventral stream. Information in
the thick and pale zones goes to regions V3A and V5 to form the dorsal
stream.

As charted in Figure 9-18 , the visual pathways proceed from region

V2 to the other occipital regions and then to the parietal and temporal
lobes, forming the dorsal and ventral streams. Although many parietal
and temporal regions take part, the major regions are region G in the
parietal lobe (thus called region PG) and region E in the temporal lobe
(thus called region TE).
The simple records of color, form, and motion from the occipital
regions are assembled in the dorsal and ventral streams to produce a rich,
unified visual world of complex objects, such as faces and paintings, and
complex skills, such as bike riding and ball catching. We can think of the
complex representations of the dorsal and ventral streams as consisting
of how functions and what functions. How is looking at, reaching for,
and grasping; what is the spoon.
Vision Beyond the Occipital Cortex
Visual processing that begins in occipital cortex continues via the
ventral and dorsal streams into the temporal and parietal visual cortex.
Each region has multiple areas specialized for specific visual functions.
For example, Figure 9-19 A shows two regions on the ventral surface of
the temporal lobes. One is specialized for recognizing faces (fusiform
face area, or FFA), the other for analyzing landmarks such as buildings
or trees (parahippocampal place area, or PPA). As we gaze at the
photograph in Clinical Focus 9-1 (p. 284), then, the three faces activate
the FFA and the trees engage the PPA. Figure 9-19 B shows three regions
in the parietal lobe related to eye movements (lateral intraparietal area, or
LIP) and visual control of grasping (anterior intraparietal area, or AIP).
The parietal reach region (PRR) has a role in visually guided reaching
movements.

(A)
 (B)
FIGURE 9-19 Vision Beyond the Occipital Cortex (A) In the
temporal lobe, the fusiform face area (FFA) processes faces, and the
parahippocampal place area (PPA) processes scenes. (B) In the parietal
lobe, the lateral intraparietal area (LIP) contributes to eye movements; the
anterior intraparietal area (AIP) is involved in visual control of grasping;
and the parietal reach region (PRR) participates in visually guided
reaching. (A) Republished with permission of Hasson, U., Y. Nir, I. Levy, G. Fuhrmann, and
R. Malach. Intersubject synchronization of cortical activity during natural vision. Science
303:1634–1640, 2004, permission conveyed through Copyright Clearance Center, Inc.

Damage to these regions can produce surprisingly specific deficits.

For example, damage to the FFA leads to facial agnosia, or
prosopagnosia, a condition in which an individual cannot recognize
faces. We saw one patient with prosopagnosia so severe that she could
not recognize her identical twin sister’s face. Curiously, her other visual
functions seemed to be normal.
facial agnosia Face blindness—the inability to recognize faces; also
called prosopagnosia.
Literally, agnosia means not knowing. Section 15-7 ties conditions
like agnosia to the search for a neural basis of consciousness.
 9-2 REVIEW
The Visual System’s Functional Anatomy
Before you continue, check your understanding.
1 . Neurons that project into the brain from the retina and form the optic
nerve are called ___________.
2 . ___________ retinal ganglion cells receive input mostly from cones
and carry information about color and fine detail, whereas
___________ retinal ganglion cells receive input mostly from rods and
carry information about light but not color.
3 . The two major pathways from the retina into the brain are
___________ and ___________.
4 . Damage to the fusiform face area in the temporal lobe can produce
___________.
5 . Contrast the paths and functions of the dorsal and ventral streams.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
FIGURE 9-20 Visual-Field Demonstration As you focus on the
cross at center, information at the left of this focal point forms the left
visual field (red) and travels to the right hemisphere. Information to the
right of the focal point forms the right visual field (blue) and travels to the
left hemisphere. The visual field can be split horizontally as well:
information above the focal point is in the upper visual field and that below
the focal point is in the lower visual field.
 9-3 Location in the Visual World
As we move about from place to place, we encounter objects in specific
locations. If we had no awareness of location, the world would be a
bewildering mass of visual information. The next leg of our journey
down the neural roads traces how the brain constructs a spatial map. In
Clinical Focus 9-1 , the photograph has a left and a right, an up and a
down. All these elements must be coded separately in the brain.
Neural coding of location begins in the retina and is maintained
throughout all visual pathways. To understand how this spatial coding is
accomplished, imagine your visual world as seen by your two eyes.
Imagine the large red and blue rectangles in Figure 9-20 as a wall. Focus
your gaze on the black cross in the middle of the wall.
The part of the wall that you can see without moving your head is
your visual field. It can be divided into two halves, the left and right
visual fields, by drawing a vertical line through the middle of the black
cross. Now recall from Figure 9-10 that the left half of each retina looks
at the right side of the visual field, whereas the right half of each retina
looks at the visual field’s left side. Thus, input from the right visual field
goes to the left hemisphere, and input from the left visual field goes to
the right hemisphere.
visual field Region of the visual world seen by the eyes.
Therefore, the brain can easily determine whether visual information
lies to the left or right of center. If input goes to the left hemisphere, the
source must be in the right visual field; if input goes to the right
hemisphere, the source must be in the left visual field. This arrangement
tells you nothing about the precise location of an object in the left or
right side of the visual field, however. To understand how precise spatial
localization is accomplished, we must return to the retinal ganglion cells.

Coding Location in the Retina

Look again at Figure 9-8 and you can see that each RGC receives input
through bipolar cells from several photoreceptors. In the 1950s, Stephen
Kuffler, a pioneer in visual system physiology, made an important
discovery about how photoreceptors and retinal ganglion cells are linked
(Kuffler, 1952). By shining small spots of light on the receptors, he
found that each ganglion cell responds to stimulation on just a small
circular patch of the retina—the ganglion cell’s receptive field.
A ganglion cell’s receptive field is therefore the retinal region on
which it is possible to influence that cell’s firing. Stated differently, the
receptive field represents the outer world as seen by a single cell. Each
RGC sees only a small bit of the world, much as you would if you
looked through a narrow cardboard tube. The visual field is composed of
thousands of such receptive fields (illustrated on page 286 ).
Now let us consider how receptive fields enable the visual system to
interpret an object’s location. Imagine that the retina is flattened like a
piece of paper. When a tiny light shines on different parts of the retina,
different ganglion cells respond. For example, when a light shines on the
top left corner of the flattened retina, a particular RGC responds because
that light is in its receptive field. Similarly, when a light shines on the top
right corner, a different RGC responds.
Like a camera lens, the lens in the eye focuses light rays to project a
backward, inverted image on a light-receptive surface (see How the
Eye Works in The Basics, p 291).
By using this information, we determine the location of a light on the
retina by the ganglion cell it activates. Another location device is
determining where the light must come from to hit a particular place on
the retina. Light coming from above hits the bottom of the retina after
passing through the eye’s lens, and light from below hits the top of the
retina. Information at the top of the visual field stimulates ganglion cells
on the bottom of the retina; information at the bottom of the field
stimulates ganglion cells on the top of the retina.
 FIGURE 9-21 Receptive Field Projection Information from a
receptive field in the retina retains its spatial relation when sent to the
lateral geniculate nucleus. Information at the top of the visual field goes to
the top of the LGN; information from the bottom of the visual field goes to
the bottom of the LGN; and information from the left or right goes to the
left or right of the LGN, respectively.

Location in the Lateral Geniculate Nucleus

and Region V1
Now consider the connection from the ganglion cells to the lateral
geniculate nucleus. In contrast to the retina, the LGN is not a thin sheet;
it is shaped more like a sausage. We can compare it to a stack of sausage
slices, with each slice representing a layer of cells.
Figure 9-21 shows how the connections from the retina to the LGN
can represent location. A retinal ganglion cell that responds to light in
the top left region of the retina connects to the left side of the first card.
A retinal ganglion cell that responds to light in the bottom right region of
the retina connects to the right side of the last card. In this way, the
location of left–right and top–bottom information is maintained in the
LGN.
Like the ganglion cells, each LGN cell has a receptive field—the
region of the retina that influences its activity. If two adjacent retinal
ganglion cells synapse on a single LGN cell, the receptive field of that
LGN cell will be the sum of the two ganglion cells’ receptive fields. As a
result, the receptive fields of LGN cells are bigger than those of RGCs.
The LGN projection to the striate cortex (region V1) also maintains
spatial information. As each LGN cell, representing a particular place,
projects to region V1, a spatially organized neural representation—a
topographic map—is produced in the cortex. As illustrated in Figure 9-
22 , this representation is essentially a map of the visual world.
The central part of the visual field is represented at the back of the
brain, whereas the periphery is represented more anteriorly. The upper
part of the visual field is represented at the bottom of region V1 and the
lower part at the top of V1. The other regions of the visual cortex (such
as V3, V4, and V5) have topographical maps similar to that of V1. Thus
the V1 neurons must project to the other regions in an orderly manner,
just as the LGN neurons project to region V1 in an orderly way.
 FIGURE 9-22 Topographic Organization of Region V1
The fovea sends information to a disproportionately large part of the
occipital cortex, which is why visual acuity is best in the central part of the
visual field.

FIGURE 9-23 Receptive-Field Hierarchy

Within each visual cortical area, each neuron’s receptive field
corresponds to the part of the retina to which the neuron is connected. As
a rule of thumb, cells in the cortex have much larger receptive fields than
RGCs do. This large field size means that the receptive field of a cortical
neuron must be composed of the receptive fields of many RGCs, as
illustrated in Figure 9-23 .
One additional wrinkle pertains to the organization of topographic
maps. Harry Jerison (1973) proposed the principle of proper mass, which
states that the amount of neural tissue responsible for a particular
function is proportional to the amount of neural processing that function
requires. The more complex a function is, the larger a specific region
performing that function must be. The visual cortex provides some good
examples.
In Figure 1-14 , we apply Jerison’s ideas to relative differences in
overall brain size across mammals.
You can see in Figure 9-22 that not all parts of the visual field are
equally represented in region V1. The small central part of the visual
field seen by the fovea is represented by a larger area in the cortex than
the visual field’s periphery, even though the periphery covers a much
larger area. In accord with Jerison’s principle, we would predict more
processing of foveal information than of peripheral information in region
V1. This prediction makes intuitive sense because we can see more
clearly in the center of the visual field than at the periphery (see Figure
9-3 ). In other words, sensory areas that have more cortical
representation provide a more detailed construct of the external world.

Visual Corpus Callosum

Topographic mapping based on neuronal receptive fields is an effective
way for the brain to code object location. But if the left visual field is
represented in the right cerebral hemisphere and the right visual field is
represented in the left cerebral hemisphere, how are the two halves of the
visual field ultimately merged into a unified representation? After all, we
have the subjective impression not of two independent visual fields but
rather of a single, continuous field of vision.
The answer to how this unity is accomplished lies in the corpus
callosum, which binds the two sides of the visual field together at the
midline. Until the 1950s, its function was largely a mystery. Physicians
had occasionally cut the corpus callosum to control severe epilepsy or to
reach a very deep tumor, but patients did not appear much affected by
this surgery. The corpus callosum clearly linked the two hemispheres of
the brain, but exactly which parts were connected was not yet known.
 We now realize that the corpus callosum connects only certain brain
structures. As shown in Figure 9-24 , the frontal lobes have many
callosal connections, but the occipital lobes have almost none. If you
think about it, there is no reason for a neuron in the visual cortex that is
looking at one place in the visual field to be concerned with what another
neuron in the opposite hemisphere is looking at in another part of the
visual field.
Cells that lie along the midline of the visual field are an exception,
however. These cells look at adjacent places in the visual field, one
slightly to the left of center and one slightly to the right. Callosal
connections between such cells zip the two visual fields together by
combining their receptive fields to overlap at the midline. The two fields
thus become one.

Section 15-4 describes the revelations learned from studying split-brain

patients, whose corpus callosa have been severed.
FIGURE 9-24 Callosal Connections Darker areas show regions of
the rhesus monkey cortex that receive projections from the opposite
hemisphere through the corpus callosum.
 9-3 REVIEW
Location in the Visual World
Before you continue, check your understanding.
1 . The characteristic of visual receptive fields that allows us to detect
exactly where a light source is coming from is their ___________.
2 . List four types of cells that have visual receptive fields:
___________,___________,___________, and ___________.
3 . Inputs to different parts of cortical region V1 from different parts of
the retina essentially form a ___________ of the visual world within
the brain.
4 . The two sides of the visual world are bound together as one
perception by the ___________.
5 . How does Jerison’s principle of proper mass apply to the visual
system?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 9-4 Neuronal Activity
Individual neurons make up the visual system pathways. By studying
how these cells behave when their receptive fields are stimulated, we can
begin to understand how the brain processes the features of the visual
world beyond the location of a light. We first examine how neurons in
the ventral stream respond to objects’ shapes and colors, then briefly
consider how neurons in the dorsal stream direct vision for action.

Seeing Shape
Imagine a microelectrode placed near a neuron somewhere in the visual
pathway from retina to cortex. The microelectrode is recording changes
in the neuron’s firing rate. This cell occasionally fires spontaneously,
producing action potentials with each discharge. Assume that the neuron
discharges, on average, once every 0.08 second. Each action potential is
brief, on the order of 1 millisecond.
Figure 4-6 diagrams how microelectrodes work.
If we plot action potentials spanning 1 s, we see only spikes in the
record because the action potentials are so brief. Figure 9-25 A is a
single cell recording of 12 spikes in the span of 1 second. If the firing
rate of this cell increases, we see more spikes (Figure 9-25 B). If the
firing rate decreases, we see fewer spikes (Figure 9-25C ). The increase
in firing is the result of neuronal excitation, whereas the decrease
indicates inhibition. Excitation and inhibition, of course, are the principal
information transfer mechanisms in the nervous system.
Now suppose we present a stimulus to the neuron by illuminating its
receptive field in the retina, perhaps by shining a light on a blank screen
within the cell’s visual field. We might place before the eye a straight
line positioned at a 45° angle. The cell could respond to this stimulus
either by increasing or decreasing its firing rate. In either case, we would
conclude that the cell is generating information about the line.
The same cell could show excitation to one stimulus, inhibition to
another stimulus, and no reaction at all to a third. The cell could be
excited by lines oriented 45° to the left and inhibited by lines oriented
45° to the right. Similarly, the cell could be excited by stimulation in one
part of its receptive field (such as the center) and inhibited by stimulation
in another part (such as the periphery).
 Finally, we might find that the cell’s response to a particular stimulus
is selective. Such a cell would be telling us about the importance of the
stimulus to the animal. For instance, the cell might be excited when a
stimulus is presented with food but inhibited when the same stimulus is
presented alone. In each case, the cell is selectively sensitive to
characteristics in the visual world.
Neurons at each level of the visual system have distinctly different
characteristics and functions. Our goal is not to look at each neuron type
but rather to consider generally how some typical neurons at each level
differ from one another in their contributions to processing shape. We
focus on neurons in three areas: the ganglion cell layer of the retina, the
primary visual cortex, and the temporal cortex.
(A) Baseline (12 per second)

(B) Excitation

(C) Inhibition

FIGURE 9-25 Recording Neuronal Stimulation Each action

potential is represented by a spike. (A) In a 1-s period at this neuron’s
baseline firing rate, 12 spikes were recorded. (B) A firing rate over
 baseline signals excitation. (C) A firing rate under baseline signals
inhibition.

Processing in RGCs
Neurons in the retina do not detect shape, because their receptive fields
are minuscule dots. Each retinal ganglion cell responds only to the
presence or absence of light in its receptive field, not to shape. Shape is
constructed by processes in the cortex from the information that those
ganglion cells pass on about events in their receptive fields.
The receptive field of a ganglion cell has a concentric circle
arrangement, as illustrated in Figure 9-26 A . A spot of light falling in
the receptive field’s central circle excites some of these cells, whereas a
spot of light falling in the receptive field’s surround (periphery) inhibits
the cell. A spot of light falling across the entire receptive field weakly
increases the cell’s firing rate.
This type of neuron is called an on-center cell. Other RGCs, called
off-center cells, have the opposite arrangement, with light in the center of
the receptive field inhibiting, light in the surround exciting, and light
across the entire field producing weak inhibition (Figure 9-26 B). The
on–off arrangement of RGC receptive fields makes these cells especially
responsive to tiny spots of light.
This description of ganglion cell receptive fields might mislead you
into thinking that they form a mosaic of discrete little circles on the
retina. In fact, neighboring retinal ganglion cells receive their inputs
from an overlapping set of photoreceptors. As a result, their receptive
fields overlap, as illustrated in Figure 9-27 . In this way, a small spot of
light shining on the retina is likely to produce activity in both on-center
and off-center RGCs.
(A) On-center cell’s receptive field

(B) Off-center cell’s receptive field

FIGURE 9-26 On—Off Receptivity (A) In the receptive field of an
RGC with an on-center and off-surround, a spot of light shining on the
 center excites the neuron, but a spot of light in the surround inhibits it.
When the light in the surround is turned off, firing rate increases briefly—
an offset response. A light shining in both the center and the surround
would produce a weak increase in firing. (B) In the receptive field of an
RGC with an off-center and on-surround, light in the center produces
inhibition, light on the surround produces excitation, and light across the
entire field produces weak inhibition.

How can on-center and off-center ganglion cells tell the brain
anything about shape? The answer is that a ganglion cell tells the brain
about the amount of light hitting a certain spot on the retina compared
with the average amount of light falling on the surrounding retinal
region. This comparison is known as luminance contrast. Luminance is
the amount of visible light reflected to the eye from a surface, and
contrast is the difference in luminance between adjacent parts of that
surface. The photograph in Focus 9-1 (p. 284) shows us two clear
differences in luminance contrast. On the left, the woman’s pink top
contrasts sharply with her black slacks, but the sleeve on the right
contrasts far less with the background. It does not appear as bright.
luminance contrast Amount of light an object reflects relative to its
surroundings.
To understand how luminance contrast tells the brain about shape,
consider the hypothetical population of on-center ganglion cells
represented in Figure 9-28 . Their receptive fields are distributed across
the retinal image of a light–dark edge. Some of the ganglion cells’
receptive fields are in the dark area, others are in the light area, and still
others’ fields straddle the edge of the light.
The ganglion cells with receptive fields in the dark or light areas are
least affected because they receive either no stimulation or stimulation of
both the excitatory and the inhibitory regions of their receptive fields.
The ganglion cells most affected by the stimulus are those lying along
the edge. Ganglion cell B is inhibited because the light falls mostly on its
inhibitory surround, and ganglion cell D is excited because its entire
excitatory center is stimulated but only part of its inhibitory surround is.
FIGURE 9-27 Overlapping Receptive Fields

FIGURE 9-28 Activity at the Margins Responses of a hypothetical

population of on-center ganglion cells whose receptive fields (A–E) are
distributed across a light–dark edge. The activity of the cells along the
edge is most affected relative to those away from the edge. Information from
D. Purves, G. J. Augustine, D. Fitzpatrick, L. C. Katz, A.-S. LaMantia, & J. O. McNamara (Eds.).
(1997). Neuroscience, (1st ed., p. 195). Sunderland, MA: Sinauer.
 (A) Horizontally aligned preferred orientation

(B) Oblique preferred orientation

 FIGURE 9-29 Typical Receptive Fields for Simple V1
Cells Simple cells respond to a bar of light in a particular orientation,
such as (A) horizontal or (B) oblique. The position of the bar in the visual
field is important, because the cell either responds (ON) or does not
respond (OFF) to light in adjacent visual field regions.

Consequently, information transmitted from retinal ganglion cells to

the visual areas in the brain does not give equal weight to all visual field
regions. Rather, it emphasizes regions containing differences in
luminance—areas along the edges. So RGCs are really sending signals
about edges, and edges form shapes.

Complex cell’s receptive field

 FIGURE 9-30 Receptive Field of a Complex Cell Unlike a
simple cell’s on–off response pattern, a complex cell in V1 shows the
same response throughout its circular receptive field, responding best to
bars of light moving at a particular angle. The response is reduced or
absent with the bar of light at other orientations.

Processing Shape in the Primary Visual Cortex

Now consider cells in region V1 that receive their visual inputs from
LGN cells, which in turn receive theirs from retinal ganglion cells. As
you read on, think about how these cortical cells are responding to the
Clinical Focus 9-1 photograph. Because each V1 cell receives input from
multiple RGCs, the receptive fields of the V1 neurons are much larger
than those of retinal neurons. Consequently, V1 cells respond to stimuli
more complex than simply light on or light off. In particular, these cells
are maximally excited by bars of light oriented in a particular direction
rather than by spots of light. These V1 cells are therefore called
orientation detectors.
Like the ganglion cells, some orientation detectors have an on–off
receptive-field arrangement, but the arrangement is rectangular rather
than circular. Visual cortex cells with this property are known as simple
cells. Typical receptive fields for simple cells in V1 are shown in Figure
9-29 .
Simple cells are not the only kind of orientation detector in the
primary visual cortex; several functionally distinct types of neurons
populate region V1. For instance, the receptive fields of complex cells,
such as those in Figure 9-30 , are maximally excited by bars of light
moving in a particular direction through the visual field. A hypercomplex
cell, like a complex cell, is maximally responsive to moving bars but also
has a strong inhibitory area at one end of its receptive field. As illustrated
in Figure 9-31 , a bar of light landing on the right side of the
hypercomplex cell’s receptive field excites the cell; but if, for example,
the bar lands mainly on the inhibitory area to the left, the cell’s firing is
inhibited.

Hypercomplex cell’s receptive field

FIGURE 9-31 Receptive Field of a Hypercomplex Cell A

hypercomplex cell in V1 responds to a moving bar of light in a particular
orientation (horizontal, e.g.) anywhere in the excitatory (ON) part of its
 receptive field. If most of the bar extends into the inhibitory area (OFF),
however, the response is inhibited.

Each class of V1 neurons responds to bars of light in some way, yet

this response results from input originating in retinal ganglion cells that
respond maximally not to bars but to spots of light. How does this
conversion from responding to spots to responding to bars take place?
An example will help explain the process.
A thin bar of light falls on the retinal photoreceptors, striking the
receptive fields of perhaps dozens of retinal ganglion cells. The input to
a V1 neuron comes from a group of ganglion cells that happen to be
aligned in a row, as in Figure 9-32 . That V1 neuron is activated (or
inhibited) only when a bar of light hitting the retina strikes that particular
row of ganglion cells. If the bar of light shines at a slightly different
angle, only some of the retinal ganglion cells in the row are activated, so
the V1 neuron is excited only weakly.
Figure 9-32 illustrates the connection between light striking the retina
in a certain pattern and the activation of a simple cell in the primary
visual cortex, one that responds to a bar of light in a particular
orientation. Using the same logic, we can also diagram the retinal
receptive fields of complex or hypercomplex V1 neurons. Try it as an
exercise yourself by adapting the format in Figure 9-32 .
A characteristic of cortical structure is that the neurons are organized
into functional columns. The connectivity pattern in a column is vertical:
inputs arrive in layer IV, then connect with cells in the other layers.
Figure 9-33 shows such a column, a 0.5-mm-diameter strip of cortex
that includes representative neurons and their connections.
Neurons within a cortical column have similar functions. For
example, Figure 9-34 A shows that neurons within the same column
respond to lines oriented in the same direction. Adjacent columns house
cells responsive to different line orientations. Figure 9-34 B shows the
cortical columns of input coming from each eye, discussed earlier, called
ocular dominance columns. So V1 has both orientation columns
housing neurons of similar sensitivity and ocular dominance columns
with input from one eye or the other.
ocular dominance column Functional column in the visual cortex
maximally responsive to information coming from one eye.
FIGURE 9-32 V1 Receptivity A V1 cell responds to a row of ganglion
cells in a particular orientation on the retina. The bar of light strongly
activates a row of ganglion cells, each connected through the LGN to a V1
neuron. The activity of this V1 neuron is most affected by a bar of light at a
45° angle.
FIGURE 9-33 Neural Circuit in a Column in the Visual Cortex In this
three-dimensional view, sensory inputs enter the cortical column at layer VI (bottom) and
terminate on stellate cells in layer IV that synapse with pyramidal cells in layers III and V.
The information flow is vertical. Axons of the pyramidal cells leave the column to join
other columns or structures. Information from J. Szentagothai (1975). The “module-concept” in cerebral
architecture. Brain Research, 95, p. 490.

Processing Shape in the Temporal Cortex

Consider neurons along the ventral stream in temporal lobe region TE.
Rather than being responsive to spots or bars of light, TE neurons are
maximally excited by complex visual stimuli, such as faces (see Figure
9-19 A) or hands, and can be remarkably specific in their responsiveness.
They may be responsive to particular faces seen head-on, to faces viewed
in profile, to the posture of the head, or even to particular facial
expressions.
How far does this specialized responsiveness extend? Would it be
practical to have visual neurons in the temporal cortex specialized to
respond to every conceivable feature of objects? Keiji Tanaka (1993)
approached this question by presenting monkeys with many three-
dimensional representations of animals and plants to find stimuli that are
effective in activating particular neurons of the inferior temporal cortex.
Having identified stimuli that were especially effective, such as faces
or hands, he then wondered which specific features of those stimuli are
critical to stimulating the neurons. Tanaka found that most neurons in
area TE require rather complex features for their activation. These
features include a combination of characteristics such as orientation,
size, color, and texture. Furthermore, neurons with similar but not
identical responsiveness to particular features tend to cluster in columns,
as shown in Figure 9-35 .
Apparently, then, an object is represented not by the activity of a
single neuron but rather by the activity of many neurons with slightly
varying stimulus specificity. These neurons are grouped in a column.
This finding is important because it provides an explanation for stimulus
equivalence, recognizing an object as remaining the same despite being
viewed from different orientations.
Think of how the representation of objects by multiple neurons in a
column can produce stimulus equivalence. If each neuron in the column
module varies slightly in regard to the features to which it responds but
the effective stimuli largely overlap, the effect of small changes in
incoming visual images will be minimized and we will continue to
perceive an object as itself.
(A)
 (B)
FIGURE 9-34 Organization of Functional Columns in V1
The stimulus specificity of neurons in the inferior temporal cortex in
monkeys shows remarkable neuroplasticity. If monkeys are trained to
discriminate particular shapes to obtain a food reward, not only do they
improve their discriminatory ability but neurons in the temporal lobe also
modify their preferred stimuli to fire maximally to some of the stimuli
used in training. This result shows that the temporal lobe’s role in visual
processing is not determined genetically but is instead subject to
experience, even in adults.
We can speculate that this neuroplastic characteristic evolved because
it allows the visual system to adapt to a changing visual environment.
Think of how different the demands on your visual recognition abilities
are when you move from a dense forest to a treeless plain to a city street.
The visual neurons of your temporal cortex can adapt to these
differences (Tanaka, 1993). Experience-dependent visual neurons ensure
in addition that people can identify visual stimuli that were never
encountered as the human brain evolved.
The preferred stimuli of neurons in the primary visual cortex are not
modified by experience. This implies that the stimulus preferences of V1
neurons are genetically programmed. Regardless, the functions of the V1
neurons underlie the more complex and flexible characteristics of the
inferior temporal cortex neurons.

FIGURE 9-35 Columnar Organization of Area TE Neurons

with similar but slightly different pattern selectivity cluster in vertical
columns, perpendicular to the cortical surface.

(A)
Fritz Goro/Time & Life Pictures/Getty Images
 FIGURE 9-36 Color Mixing (A) Subtractive color mixing absorbs light
waves that we see as red, blue, or yellow. When all visible wavelengths
are absorbed, we see black. (B) Additive color mixing reflects light waves
that we see as red, blue, and green. When all visible wavelengths are
reflected, we see white.

Seeing Color
Scientists have long wondered why—and how—we see a world so rich
in color. One hypothesis on the why is that color vision evolved first in
the great apes, specifically in apes that eat fruit. Chimpanzees and
humans are members of this family. Over their evolution, both species
have faced plentiful competition for ripe fruits—from other animals,
insects, and each other. Scientists suspect that color vision gave the great
apes a competitive evolutionary advantage.
Section 1-4 recounts several ideas on how the primate lifestyle,
including diet, encouraged the evolution of complex nervous
systems.
An explanation of color vision has its roots in the Renaissance 600
years ago in Italy. Painters of the time discovered that they could obtain
the entire range of colors in the visual world by mixing only three colors
of paint (red, blue, and yellow). This is the process of subtractive color
mixing shown in Figure 9-36 A .
We now know that such trichromatic color mixing is a property of the
cones in the retina. Subtractive color mixing works by removing light
from the mix. This is why matte black surfaces reflect no light: the
darker the color, the less light it contains.
Conversely, additive color mixing increases light to make color
(Figure 9-36 B). The lighter the color, the more light it contains, which is
why a white surface reflects the entire visible spectrum. Unlike those of
paint, the primary colors of light are red, blue, and green. Light of
different wavelengths stimulates the three cone receptor types in
different ways. It is the ratio of activity of these three receptor types that
forms our impressions of colors.
Trichromatic Theory
According to the trichromatic theory, the color we see—say, blue at
short 400-nanometer wavelengths, green at medium 500 nm, and red at
long 600 nm—is determined by the relative responses of the
corresponding cone types (see Figure 9-6 ). If all three types are equally
active, we see white.
trichromatic theory Explanation of color vision based on the
coding of three primary colors: red, green, and blue.
Trichromatic theory predicts that if we lack one cone receptor type,
we cannot process as many colors as we could with all three. This is
exactly what happens when a person is born with only two cone types.
The colors this person cannot perceive depend on which receptor type is
missing, as illustrated in Research Focus 9-3 , Color-Deficient Vision.
RESEARCH FOCUS 9-3

Color-Deficient Vision
Most people’s retinas contain three cone types. These people have
trichromatic vision. But some people are missing one or more cone
types and are thus often mistakenly said to be color-blind.
Mistakenly, because people who have two types of cones still can
distinguish lots of colors, just not as many as people with three cones
can.
To have no color vision at all, one would have to have only one
type of photoreceptor, rods. This is a rare occurrence, but we do have
a friend who has no concept of color. It has led to a lifetime of
practical jokes, because others (especially his wife) must choose
clothing colors that coordinate for him to wear.
The complete lack of red cones leads to a condition called
protanopia; the lack of green cones is deuteranopia; the lack of blue
cones is tritanopia. The frequency of each condition is about 1
percent in men and 0.01 percent in women. Having only a partial
lack of one cone type, most commonly the green cone, also is
possible. This condition afflicts about 5 percent of men and 0.4
percent of women.
The illustration provides a simple approximation, compared with
trichromats (left), of what people with protanopia (center) or
deuteranopia (right) see. They still see plenty of color, but that color
is largely different from the color trichromats see. Many domestic
animals (dogs, cats, and horses among them) have deuteranopia,
which actually gives them an advantage in seeing objects that appear
camouflaged to trichro-mats. In fact, the military often use humans
with deuteranopia to help see through camouflage.
Image as viewed by a trichromat observer
Protanopia: image as viewed by an observer lacking red cones
 Dr. Terrace L. Waggoner/www.ColorVisionTesting.com
Deuteranopia: image as viewed by an observer lacking green cones

The mere presence of cones in an animal’s retina does not mean that
the animal has color vision. It simply means that the animal has
photoreceptors particularly sensitive to light. Many animals lack color
vision as we know it, but the only animal with eyes known to have no
cones at all is a fish, the skate.
Opponent Processes
Although the beginning of color perception in the cones follows the
trichromatic model, succeeding levels of color processing use a different
strategy. Try staring first at the red and blue box in Figure 9-37 for about
30 seconds then at the white box next to it. When you shift your gaze to
the white surface, you will see an afterimage in the colors opposite to red
and blue—green and yellow. Conversely, if you stare at a green and
yellow box and then shift to white, you will see a red and blue
afterimage. Such afterimages lead to the sense that there are actually four
basic colors (red, green, yellow, and blue).
FIGURE 9-37 Demonstrating Opposing Color Pairs Stare
at the rectangle on the left for about 30 seconds. Then stare at the white
 box on the right. You will see an afterimage of green on the red side and of
yellow on the blue side.

(A)

(B)

(C)

(D)

(E)
 FIGURE 9-38 Opponent-Color Contrast Response (A) A
red–green color-sensitive RGC responds weakly to white light on its center
and surround because red and green cones absorb white light to similar
extents, so their inputs cancel out. (B) The cell responds strongly to a spot
of red light in its center as well as to red’s paired wavelength, green, in the
surround. (C) It is strongly inhibited by a small spot of green in its center.
(D) The RGC responds very strongly to simultaneous illumination of the
center with red and the surround with green. (E) It is completely inhibited
by the simultaneous illumination of the center with green and the surround
with red.

A characteristic of RGCs explains the two opposing pairs of four

basic colors. Remember that RGCs have an on–off and center–surround
organization. Stimulation to the center of the cell’s receptive field is
either excitatory (in some cells) or inhibitory (in other cells), whereas
stimulation to the periphery of the receptive field has the opposite effect
(see Figure 9-26 ).
This arrangement can be adapted to produce color-opponent cells. If
one wavelength of light produced excitation and another inhibition, cells
would evolve that are excited by red and inhibited by green (or vice
versa), as would cells that are excited by blue and inhibited by yellow (or
vice versa). Red–green and blue–yellow would therefore be linked to
each other as color opposites, or opponents.
In fact, about 60 percent of human retinal ganglion cells are color-
sensitive in this way, with the center responsive to one wavelength and
the surround to another. The most common opponent-process pairing,
shown in Figure 9-38 , is medium-wavelength (green) versus long-
wavelength (red), but we also have blue versus yellow RGCs. Most
likely, opponent-process cells evolved to enhance the relatively small
differences in spectral absorption among the three cone types.
opponent process Explanation of color vision that emphasizes the
importance of the apparently opposing color pairs: red versus green
and blue versus yellow.
Cortical neurons in region V1 also respond to color in an opponent-
process manner reminiscent of retinal ganglion cells. Recall that color
inputs in the primary visual cortex go to the blobs that appear in sections
stained for cytochrome oxidase (see Figure 9-17 ). These blobs are where
the color-sensitive cells are found.
Figure 9-39 models how the color-sensitive cells in the blobs are
inserted amid the orientation-sensitive and ocular dominance columns.
The primary visual cortex thus appears to be organized into modules that
include ocular dominance and orientation-sensitive columns as well as
blobs. Think of V1 as composed of several thousand modules, each
analyzing color and contour for a particular visual region. This
organization allows the primary visual cortex to perform several
functions concurrently.
How do neurons in the visual system beyond V1 process color? You
have already learned that cells in region V4 respond to color, but in
contrast with the cells in region V1, these V4 cells do not respond to
particular wavelengths. Rather, they are responsive to different perceived
colors, with the center of the field being excited by a certain color and
the surround being inhibited.
 FIGURE 9-39 V1 Modules A model of striate cortex showing the
orientation-sensitive columns, ocular dominance columns, and color-
sensitive blobs as composed of two hypercolumns. Each consists of a full
set (red and blue) of orientation-sensitive columns spanning 180° of
preferred angle as well as a pair of blobs. All cells in the hypercolumn
share the same receptive field.

Speculation swirls about the function of these V4 cells. One idea is

that they are important for color constancy, the property of perception
whereby colors appear to remain the same relative to one another despite
changes in light. For instance, were you to look at a bowl of fruit through
light-green glasses, the fruit would take on a greenish tinge, but bananas
would still look yellow relative to red apples. If you removed all the fruit
except the bananas and looked at them through the tinted glasses, the
bananas would appear green because the color you perceive is isolated
relative to any other. Monkeys with V4 lesions lose color constancy,
though they can discriminate different color wavelengths.
color constancy Phenomenon whereby an object’s perceived color
tends to remain constant relative to other colors, regardless of
changes in illumination.

Wired.com via tumblr

Color Constancy Depending on the viewer, the dress in the center

photo is perceived as either white and gold or blue and black. The image
is color-balanced, at left, to show the dress as white and gold, at right, as
blue and black. Which is the original?

Neuronal Activity in the Dorsal Stream

A striking characteristic of many cells in the visual areas of parietal
cortex is that they are virtually silent to visual stimulation when a person
is under anesthesia. This is true of neurons in the posterior parietal
regions of the dorsal stream. In contrast, cells in the visual temporal
cortex do respond to visual stimulation when a person is anesthetized.
The silence on the part of neurons in the posterior parietal cortex
under anesthesia makes sense if their role is to process visual
information for action. In the absence of action when a person is
unconscious, there is no need for processing. Hence, the cells are
quiescent.
Cells in the dorsal stream are of many types, their details varying with
the nature of the movement in which a particular cell takes part. One
interesting cell category processes the visual appearance of an object to
be grasped. If a monkey is going to pick up an apple, for instance, these
cells respond even when the monkey is only looking at the apple. The
cells do not respond when the monkey encounters the same apple if no
movement is to be made.
These dorsal stream cells also respond if the monkey merely watches
another monkey making movements to pick up the apple. Apparently, the
cells have some understanding of what is happening in the external
world. But that understanding is always related to action performed with
respect to visually perceived objects. These cells led David Milner and
Mel Goodale (2006) to conclude that the dorsal stream is a how visual
system.
 9-4 REVIEW
Neuronal Activity
Before you continue, check your understanding.
1 . Neurons in the primary visual cortex respond to properties of shapes,
especially to ___________ oriented in a certain direction.
2 . Recognition of complex visual stimuli such as faces is completed in
the ___________ lobe.
3 . The idea that the color we see is determined by the relative responses
of the three cone types in the retina is called ___________.
4 . Retinal ganglion cells mediate color vision by ___________
processes.
5 . Describe the opponent process in the retinal ganglion cells.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
The blue and black dress at right is the original.
 9-5 The Visual Brain in Action
Anatomical and physiological studies of brain systems leave one key
question unanswered: How do all of the cells in these systems act
together to produce a particular function? One way to answer this
question is to evaluate what happens when parts of the visual system are
dysfunctional. Then we can see how these parts contribute to the
workings of the whole. We use this strategy to examine the
neuropsychology of vision—the study of the visual brain in action.
Glowimages/Getty Images
 FIGURE 9-40 Consequences of Lesions in Region V1
The shaded areas indicate regions of visual loss. (A) A complete lesion of
V1 in the left hemisphere results in hemianopia affecting the right visual
field. (B) A large lesion of the lower lip of the calcarine fissure produces
quadrantanopia that affects most of the upper right visual quadrant. (C) A
smaller lesion of the lower lip of the calcarine fissure results in a smaller
scotoma.

Injury to the Visual Pathway Leading to the

Cortex
What happens when parts of the visual pathway leading from the eye to
the cortex are injured? For instance, destruction of the retina or optic
nerve of one eye produces monocular blindness, the loss of sight in that
eye. Partial destruction of the retina or optic nerve produces a partial loss
of sight in one eye, restricted to the visual field region that has severed
connections to the brain.
Injuries to the visual pathway beyond the eye also produce blindness.
For example, complete cuts of the optic tract, the LGN, or cortical region
V1 result in homonymous hemianopia, blindness of one entire side of
the visual field, as shown in Figure 9-40 A . We encountered this
syndrome in Focus 9-1, the story of D. B.’s lesion in region V1. Should a
lesion in one of these areas be partial, as is often the case, the result is
quadrantanopia, destruction of only a part of the visual field, illustrated
in Figure 9-40 B.
 homonymous hemianopia Blindness of an entire left or right visual
field.
quadrantanopia Blindness of one quadrant of the visual field.
Figure 9-40C shows that small lesions in V1 often produce small
blind spots, or scotomas, in the visual field. Focus 9-1 observes that
scotomas can be a warning symptom for migraine sufferers. But brain-
injured people are often totally unaware of them. One reason is that the
eyes are usually moving.
scotoma Small blind spot in the visual field caused by migraine or
by a small lesion of the visual cortex.
We make tiny, involuntary eye movements almost constantly. Because
of this usually constant eye motion, called nystagmus, a scotoma moves
about the visual field, allowing the intact brain regions to perceive all the
information in that field. If the eyes are temporarily held still, the visual
system actually compensates for a scotoma through pattern completion—
filling in the hole, so to speak—so that the people and objects in the
visual world are perceived as whole. The result: a seemingly normal set
of perceptions.
The visual system may cover up a scotoma so successfully that its
presence can be demonstrated to the patient only by tricking the visual
system. The trick is to place an object entirely within the scotoma and
without allowing the patient to shift gaze, asking what the object is. If
the patient reports seeing nothing, to confirm the existence of a blind
area the examiner moves the object out of the scotoma so that it suddenly
appears in the intact region of the visual field.
This technique is similar to demonstrating the presence of the blind
spot that is due to the optic disc (as in Figure 9-4 ). When a person is
looking at an object with only one eye, the brain compensates for the
scotoma in the same way as for the optic disc’s blind spot. As a result,
the person does not notice the scotoma.
Thus the type of blindness offers clues about where in the visual
pathway the cause of the problem lies. If the loss of vision is in one eye
only, the problem must be in that eye or its optic nerve; if the vision loss
affects both eyes, the problem most likely is in the brain. Many people
have difficulty understanding why a person with damage to the visual
cortex has difficulty with both eyes. They fail to realize that the visual
field, not the eye, is represented in the brain.
 Beyond region V1, the nature of visual loss caused by injury is
considerably more complex. It is also very different in the ventral and
dorsal streams. We therefore look at each pathway separately.

Injury to the What Pathway

We have encountered an example of damage to the what pathway: the
case of D. B. in Focus 9-1. He appeared to be blind in his affected visual
field but could point to the location of blinking lights in that field,
suggesting that some part of his visual system was working. An even
more dramatic example of ventral stream injury comes from the case of
D. F., a 35-year-old woman who, while taking a shower, was poisoned by
carbon monoxide (CO) from a faulty gas-fueled water heater. The length
of her exposure is unclear, but when her roommate found her, the shower
was running cold. CO poisoning can cause several kinds of neurological
damage, as discussed in Clinical Focus 9-4 , Carbon Monoxide
Poisoning; the result for D. F. was an extensive lesion of the lateral
occipital region, including cortical tissue in the ventral visual pathway.
D. F.’s principal deficit was visual-form agnosia, an inability to
recognize objects, real or drawn (see Farah, 1990). Not only was D. F.
unable to recognize objects, especially line drawings of objects, she
could neither estimate their size and their orientation nor copy drawings.
Likewise, as Figure 9-41 illustrates, patient J. W. also fails to recognize
or copy simple drawings.
visual-form agnosia Inability to recognize objects or drawings of
objects.
Section 9-2 describes damage to the temporal lobe area that causes
facial agnosia.
CLINICAL FOCUS 9-4

Carbon Monoxide Poisoning

Brain damage from carbon monoxide (CO) poisoning is usually
caused either by a faulty furnace or by motor vehicle exhaust fumes.
The blood absorbs carbon monoxide gas, resulting in swelling and
bleeding of the lungs and anoxia (loss of oxygen) in the brain. The
cerebral cortex, hippocampus, cerebellum, and striatum are
especially sensitive to CO-induced anoxia.
Only a small proportion of people who are subjected to CO
poisoning have permanent neurological symptoms. Among those
who do, the symptoms are highly variable. Most common are
cortical blindness and various agnosias, as seen in case D. F. Many
also have language difficulties.
The peculiarities of the language difficulties are shown clearly in
a young woman whose case was described by Norman Geschwind
(1972). Geschwind studied this patient for 9 years after her
accidental poisoning. She required complete nursing care during this
time, never uttered spontaneous speech, and did not comprehend
spoken language. Nonetheless, she could repeat with perfect
accuracy sentences that had just been said to her.
She could also complete certain well-known phrases. For
example, if she heard “Roses are red,” she would say, “Roses are red,
violets are blue, sugar is sweet, and so are you.” She could also learn
new songs. She did not appear to understand the content of the
songs, yet with only a few repetitions, she began to sing along.
Eventually, she could sing the song spontaneously, making no errors
in either words or melody.
Postmortem examination of this woman’s brain found that
although the parietal and temporal lobes were damaged extensively,
as shown in the accompanying diagram, her speech areas were intact.
Geschwind proposed that she could not comprehend speech because
the words she heard did not arouse associations in other parts of her
cortex.
 She could, however, repeat sentences because the internal
connections of the speech regions were undamaged. Geschwind did
not comment on whether this woman had agnosia, but it is likely that
she did. The difficulty would be in diagnosing agnosia in a person
who is unable to communicate.

Areas damaged by carbon monoxide poisoning are shown in red in

this postmortem diagram of Geschwind’s patient’s brain.
 Marlene Behrmann, Director Cognitive Neuroscience Lab, Carnegie Mellon University
Original

J. W.’s copy
FIGURE 9-41 Injury to the Ventral Stream J. W. survived a severe heart
attack while exercising and later, anoxia. Subsequently, he was unable to recognize the
simple line drawings on the left and copied them poorly (right).

Clearly, D. F.’s lesion interfered with her ventral stream what

pathway. Remarkably, despite her inability to identify objects or to
estimate their size and orientation, D. F. retained the capacity, illustrated
in Figure 9-42 , to appropriately shape her hand when reaching out to
grasp something. Goodale, Milner, and their research colleagues (1991)
studied D. F. extensively for years and devised a way to demonstrate D.
F.’s skill at reaching for objects.
The middle column in Figure 9-43 shows the grasp patterns of a
control participant (S. H.) when she picks up something irregularly
shaped. S. H. grasps the object along whichever of the two axes makes it
easier to pick up. When D. F. is presented with the same task, shown in
the left-hand column, she is as good as S. H. at placing her index finger
and thumb on appropriately opposed grasp points.
Clearly, D. F. remains able to use the structural features of objects to
control her visually guided grasping movements, even though she is
unable to interpret these same features. This result demonstrates once
more that we are consciously aware of only a small part of the sensory
processing that goes on in the brain. Furthermore, D. F.’s ability to use
structural features of objects for guiding movement but not for
perceiving shapes again shows us that the brain has separate systems for
each type of visual operation.
D. F.’s lesion is quite far back in the ventral visual pathway. More
anterior lesions produce other deficits, depending on the exact location.
For example, J. I., described by Oliver Sacks and Robert Wasserman
(1987), was an artist who developed complete color deficiency owing to
a cortical lesion presumed to be in region V4. His principal symptom
was achromatopsia, or color agnosia. Despite his inability to distinguish
any colors whatsoever, J. I.’s vision appeared otherwise unaffected.
Similarly, L. M., a woman described by Josef Zihl and his colleagues
(1983), lost her ability to detect movement after a lesion presumed to be
in region V5. In her case, objects either vanished when they moved or
appeared frozen despite their movement. L. M. had particular difficulty
pouring tea into a cup, because the fluid appeared to be frozen in midair.
Yet she could read, write, and recognize objects, and she appeared to
have normal form vision—until objects moved.
These varied cases demonstrate that cortical injuries in the ventral
stream all somehow interfere with determining what things are or are
like or are doing. In each case, the symptoms are somewhat different,
however, which is thought to be indicative of damage to different
subregions or substreams of the ventral visual pathway.
 FIGURE 9-42 Visual Guidance You may consciously reach for an
object such as a pen or a mug, but your hand forms the appropriate
posture automatically, without your conscious awareness. Figure 11-1
details this type of sequentially organized movement.

Injury to the How Pathway

In 1909, R. Bálint described a rather peculiar set of visual symptoms
associated with a bilateral parietal lesion. The patient had full visual
fields and could recognize, use, and name objects, pictures, and colors
normally. But he had a severe deficit in visually guided reaching, even
though he could still make accurate movements directed toward his own
body (presumably guided by tactile or proprioceptive feedback from his
joints). Bálint called this syndrome optic ataxia.
optic ataxia Deficit in the visual control of reaching and other
movements.
Section 11-5 details the somatic senses, including proprioception, or
body awareness.
Since Bálint’s time, many descriptions of optic ataxia associated with
parietal injury have been recorded. Goodale has studied several such
patients, one of whom is a woman identified as R. V. (Milner & Goodale,
2006). In contrast with patient D. F.’s visual form agnosia, R. V.’s
perception of drawings and objects was normal, but she could not guide
her hand to reach for objects.

FIGURE 9-43 Grasp Patterns The Milner–Goodale experiments

confirm that the brain has different systems for visual object recognition
and visual guidance of movement. Information from A. D. Milner & M. A. Goodale
(1995). The Visual Brain in Action (p. 127). Oxford: Oxford University Press.

The rightmost column in Figure 9-43 shows that, when asked to pick
up the same irregularly shaped objects that D. F. could grasp normally,
R. V. often failed to place her fingers on the appropriate grasp points,
even though she could distinguish the objects easily. In other words,
although R. V.’s perception of an object’s features was normal for the
task of describing that object, her perception was not normal for the task
of visually guiding her hand to reach for the object.
To summarize, people with damage to the parietal cortex in the dorsal
visual stream can see perfectly well, yet they cannot accurately guide
their movements on the basis of visual information. Guidance of
movement is the dorsal stream’s function. In contrast, people with
damage to the ventral stream cannot perceive objects, because object
perception is a ventral stream function. Yet these same people can guide
their movements to objects on the basis of visual information.
The first kind of patient, like R. V., has an intact ventral stream that
analyzes the visual characteristics of objects. The second kind of patient,
like D. F., has an intact dorsal stream that visually directs movements.
Comparing the two types of cases enables us to infer the visual functions
of the dorsal and ventral streams.
 9-5 REVIEW
The Visual Brain in Action
Before you continue, check your understanding.
1 . Cuts completely through the optic tract, LGN, or V1 produce
___________.
2 . Small lesions of V1 produce small blind spots called ___________.
3 . Destruction of the retina or the optic nerve of one eye produces
___________.
4 . The effect of severe deficits in visually guided reaching is called
___________.
5 . Contrast the effects of injury to the dorsal stream and the effects of
injury to the ventral stream.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 SUMMARY
9-1 Nature of Sensation and Perception
Sensory systems allow animals, including ourselves, to adapt. Animals
adapted to different environments vary widely in their sensory abilities.
What is distinctive about humans is the extent to which we can transform
sensations into perceptual information to mediate aspects of language,
music, and culture. For each sense, mammals represent the world in
topographic maps that form neural–spatial representations in the cortex.
9-2 The Visual System’s Function Anatomy
Like all sensory systems, vision begins with receptor neurons. The visual
photoreceptors (rods and cones) at the back of the eye in the retina
transduce the physical energy of light waves into neural activity.
Rods are sensitive to dim light. Cones, which are sensitive to bright
light, mediate color vision. Each of the three cone types is maximally
sensitive to a different wavelength—short, medium, or long. We see
these wavelengths, respectively, as the colors blue, green, or red; thus the
short, medium, and long cone receptors often are referred to as blue,
green, or red.
Retinal ganglion cells receive input from photoreceptors through
bipolar cells and send their axons out from the retinas to form the optic
nerve. P ganglion cells receive input mostly from cones and convey
information about color and fine detail. M cells receive input from rods
and convey information about luminance and movement but not color.
The optic nerve forms two distinct major routes into the brain. The
geniculostriate pathway synapses first in the thalamic LGN nucleus, then
in V1. The tectopulvinar pathway synapses first in the midbrain’s tectum
(superior colliculus), then in the pulvinar of the thalamus, and finally in
the temporal and parietal visual cortex areas. A few optic nerve fibers
also form the retinohypothalamic tract, which functions in part to control
circadian rhythms.
Among the visual regions in the occipital cortex, V1 and V2 carry out
multiple functions; the remaining regions (V3, V3A, V4, and V5) are
specialized. Visual information flows from the thalamus to V1 and V2,
then divides to form the visual stream pathways. The unconscious dorsal
stream aids in guiding movements visually, whereas the conscious
ventral stream aids in visual object perception.
9-3 Location in the Visual World
At each step along the visual pathways, neuronal activities are distinctly
different; it is the summed neural activity in all regions that produces our
visual experience. Each functional column in the cortical visual regions
is about 0.5 mm in diameter and extends to the depth of the cortex. The
visual system cortical columns are specialized for processes such as
analyzing line orientation or comparing similar shapes as complex as
faces.
9-4 Neuronal Activity
Neurons in the ventral stream are selective for aspects of shape. Those in
the visual cortex are maximally responsive to lines of different
orientations. Upstream, cells in the inferior temporal cortex are
responsive to shapes, some abstract, and in other cases, to concrete forms
as complex as hands or faces.
Cones in the retina are maximally responsive to different light
wavelengths, roughly corresponding to colors we perceive as green, blue,
and red. At the next level, RGCs’ center–surround organization
facilitates their opponent-process function: the cells are excited by one
hue and inhibited by another, as for example, red versus green; blue
versus yellow.
Color-sensitive cells in V1, located in the blobs, also have opponent-
process properties. Cells in region V4 respond to colors that we perceive
rather than to particular visible light wavelengths. Both the luminance
and the color of nearby objects influence the colors we perceive.
9-5 The Visual Brain in Action
Upon entering the brain, information from the left and right visual fields
proceeds on the optic nerve to the brain’s right and to its left sides,
respectively. As a result of these contralateral connections, damage to the
visual areas on one side of the brain results in visual disturbance in both
eyes, because half of each retina’s visual field is represented on each side
of the brain.
Specific visual functions are localized to different brain regions, so
local damage results in the loss of a particular function. Damage to
region V4 produces a loss of color constancy, for example; damage to
regions in the parietal cortex inhibits the contralateral hand’s grasping
ability.
As summarized in the illustration, the visual streams perform distinct
functions: (A) object recognition (the what ) in the ventral stream and
(B) visual action (the how ) in the dorsal stream. We are largely
unconscious of the dorsal stream’s ongoing online analyses, that allow us
to make accurate movements in relation to objects.

(A) The ventral stream begins in V1 and flows through V2 to V3 and V4,
then into the temporal visual areas. (B) The dorsal stream begins in V1
and flows through V5 and V3A to the posterior parietal visual areas.
Double-headed arrows show information flow between the two streams—
between recognition and action, perception and behavior.
 KEY TERMS
auditory flow, p. 286
blind spot, p. 293
blob, p. 299
color constancy, p. 313
cone, p. 293
cortical column, p. 299
dorsal stream, p. 297
extrastriate (secondary visual) cortex (V2–V5), p. 299
facial agnosia, p. 301
fovea, p. 293
geniculostriate system, p. 297
homonymous hemianopia, p. 315
luminance contrast, p. 306
magnocellular (M) cell, p. 295
ocular dominance column, p. 309
opponent process, p. 313
optic ataxia, p. 316
optic chiasm, p. 295
optic flow, p. 286
parvocellular (P) cell, p. 295
perception, p. 289
photoreceptor, p. 289
primary visual cortex (V1), p. 299
quadrantanopia, p. 315
receptive field, p. 286
retina, p. 289
retinal ganglion cell (RGC), p. 295
retinohypothalamic tract, p. 297
rod, p. 293
scotoma, p. 315
sensation, p. 289
striate cortex, p. 297
tectopulvinar system, p. 297
topographic map, p. 289
trichromatic theory, p. 311
ventral stream, p. 297
visual field, p. 301
visual-form agnosia, p. 315

Visit Launch Pad to access the e-Book, videos, Learning

Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

10

How Do We Hear,
Speak, and Make
Music?
Katherine Streeter

RESEARCH FOCUS 10-1 EVOLUTION OF LANGUAGE AND

MUSIC
10-1 SOUND WAVES: STIMULUS FOR AUDITION
PHYSICAL PROPERTIES OF SOUND WAVES
PERCEPTION OF SOUND
PROPERTIES OF LANGUAGE AND MUSIC AS SOUNDS
10-2 FUNCTIONAL ANATOMY OF THE AUDITORY SYSTEM
STRUCTURE OF THE EAR
AUDITORY RECEPTORS
CLINICAL FOCUS 10-2 OTOACOUSTIC EMISSIONS
PATHWAYS TO THE AUDITORY CORTEX
AUDITORY CORTEX
RESEARCH FOCUS 10-3 SEEING WITH SOUND
10-3 NEURAL ACTIVITY AND HEARING
HEARING PITCH
DETECTING LOUDNESS
DETECTING LOCATION
DETECTING PATTERNS IN SOUND
10-4 ANATOMY OF LANGUAGE AND MUSIC
PROCESSING LANGUAGE
CLINICAL FOCUS 10-4 LEFT-HEMISPHERE DYSFUNCTION
PROCESSING MUSIC
CLINICAL FOCUS 10-5 CEREBRAL ANEURYSMS
RESEARCH FOCUS 10-6 THE BRAIN’S MUSIC SYSTEM
10-5 AUDITORY COMMUNICATION IN NONHUMAN
SPECIES
BIRDSONG
ECHOLOCATION IN BATS
 RESEARCH FOCUS 10-1
Evolution of Language and Music
The finding that modern humans (Homo sapiens ) made music
early on implies that music has been important in our evolution.
Behavioral scientists have shown that music plays as central a role in
our social and emotional lives as language does.
Thomas Geissmann (2001) noted that among most of the 26
species of singing primates, males and females sing duets. All
singing primates are monogamous, suggesting that singing may
somehow relate to sexual behaviors. Music may also play a role in
primates’ parenting behaviors.
The human brain is specialized for analyzing certain aspects of
music in the right temporal lobe, which complements the left
temporal lobe specialization for analyzing aspects of speech. Did
music and language evolve simultaneously in our species? Possibly.
Neanderthals (Homo neanderthalensis ) have long fascinated
researchers. The species originated about 300,000 years ago and
disappeared about 30,000 years ago. During some of that time they
coexisted in Europe and the Middle East with Homo sapiens, whom
they resembled in many ways because they shared a common
ancestor. In some locales, the two species may have shared resources
and tools.
Researchers long hypothesized that Neanderthal culture was
significantly less developed than that of early modern humans. Yet
Neanderthals had a brain as large as or larger than that of Homo
sapiens, with whom they appear to have shared many cultural
similarities. Neanderthals buried their dead with artifacts, which
implies that they held spiritual beliefs, but we have no conclusive
evidence that they made visual art. In contrast, Homo sapiens began
painting on cave walls some 30,000 years ago, near the end of the
Neanderthal era.
Anatomically, some skeletal analyses of the larynx suggest that
Neanderthals’ articulated language ability was less well developed
than their Homo sapiens contemporaries’. What about music? It
appears that Neanderthals did make music.
 Shown in the accompanying photo is the bone flute found in 1995
by Ivan Turk, a paleontologist at the Slovenian Academy of Sciences
in Ljubljana. Turk was excavating a cave in northern Slovenia used
by Neanderthals long ago as a hunting camp. Buried in the cave
among a cache of stone tools was the leg bone of a young bear that
looked as if it had been fashioned into a flute.
The bone has holes aligned along one side that could not have
been made by gnawing animals. Rather, the holes’ spacing resembles
positions found on a modern flute. But the bone flute is at least
43,000 years old—perhaps as old as 82,000 years. All the evidence
suggests that Neanderthals, not modern humans, made the
instrument.
Bob Fink, a musicologist, analyzed the flute’s musical qualities.
He found that an eight-note scale similar to a do-re-mi scale could be
played on the flute, but compared with the scale most familiar in
European music, one note was slightly off. That blue note, a staple of
jazz, is standard in musical scales throughout Africa and India today.
The similarity between Neanderthal and contemporary musical
scales encourages us to speculate about the brain that conceived this
ancient flute. Like modern humans, Neanderthals probably had
complementary hemispheric specialization for language and music.
This may have contributed to the two species cohabitating and to
interbreeding that led to 1 to 4 percent of alleles being of
Neanderthal origin in humans whose lineages, in the last 30,000
years, come from outside of Africa.
 Archive of the Institute of Archaeology ZRC SAZU, photo: Marko
Zaplatil
Ancient Bone Flute The hole alignment in this piece of bear femur,
found in a cave in northern Slovenia, suggests that Neanderthals
made a flute from the bone and made music with the flute.

Language and music are universal among humans. The oral language of
every known culture follows similar basic structural rules, and people in
all cultures make and enjoy music. Music and language allow us both to
organize and to interact socially. Like music, language probably
improves parenting. People who can communicate their intentions to one
another and to their children presumably are better parents.
Language is independent of making or perceiving sounds, as sign
language demonstrates. In this chapter, however, language refers to
speech.
Humans’ capacities for language and music are linked conceptually
because both are based on sound. Understanding how and why we
engage in speech and music is this chapter’s goal. We first examine the
physical energy that we perceive as sound, then how the human ear and
nervous system detect and interpret sound. We next examine the
complementary neuroanatomy of human language and music processing.
Finally, we investigate how two other species, birds and bats, interpret
and utilize auditory stimuli.
 10-1 Sound Waves: Stimulus for Audition
What we experience as sound is the brain’s construct, as is what we see.
Without a brain, sound and sight do not exist. When you strike a tuning
fork, the energy of its vibrating prongs displaces adjacent air molecules.
Figure 10-1 shows how, as one prong moves to the left, air molecules to
the left compress (grow more dense) and air molecules to the right
become more rarefied (grow less dense). The opposite happens when the
prong moves to the right. The undulating energy generated by this
displacement of molecules causes compression waves of changing air
pressure to emanate from the fork. These sound waves move through
compressible media—air, water, ground—but not through the vacuum of
outer space.
sound wave Mechanical displacement of molecules caused by
changing pressure that possesses the physical properties of
frequency, amplitude, and complexity. Also compression wave.
The top graph in Figure 10-2 represents waves of changing air
pressure emanating from a tuning fork by plotting air molecule density
against time at a single point. The bottom graph shows how the energy
from the right-hand prong of the tuning fork moves to make the air
pressure changes associated with a single cycle. A cycle is one complete
peak and valley on the graph—the change from one maximum or
minimum air pressure level of the sound wave to the next maximum or
minimum level, respectively.
The nervous system produces movement within a perceptual world
the brain constructs.
Section 9-4 explains how we see shapes and colors.

Physical Properties of Sound Waves

Light is electromagnetic energy we see; sound is mechanical energy we
hear. Sound wave energy has three physical attributes—frequency,
amplitude, and complexity— produced by the displacement of air
molecules and summarized in Figure 10-3 . The auditory system analyzes
each property separately, just as the visual system analyzes color and
form separately.
Sound Wave Frequency
Sound waves in air travel at a fixed speed of 1100 feet (343 meters) per
second and more than four times faster in water, but sound energy varies
in wavelength. Frequency is the number of cycles a wave completes in a
given amount of time. Sound wave frequencies are measured in cycles per
second, called hertz (Hz), for the German physicist Heinrich Rudolph
Hertz.
frequency Number of cycles a wave completes in a given time.
hertz (Hz) Measure of sound wave frequency (repetition rate); 1
hertz equals 1 cycle per second.
One hertz is 1 cycle per second, 50 hertz is 50 cycles per second, 6000
hertz is 6000 cycles per second, and so on. Sounds we perceive as low
pitched have fewer wave frequencies (fewer cycles per second), whereas
sounds that we perceive as high pitched have more wave frequencies
(many cycles per second), as shown in the top panel of Figure 10-3 .

FIGURE 10-1 How a Tuning Fork Produces Sound

Waves (A) The fork is still, and air molecules are distributed randomly.
(B) When struck, the fork’s right arm moves to the left; air on the leading
edge compresses and air on the trailing edge rarefies. (C) As the arm
rebounds, air to the right compresses and air to the left rarefies.
FIGURE 10-2 Visualizing a Sound Wave Air molecule density plotted against
time at a single point relative to the tuning fork’s right prong. Physicists call the resulting
cyclical waves sine waves.

FIGURE 10-3 Physical Dimensions of Sound Waves The

frequency, amplitude, and complexity of sound wave sensations
correspond to the perceptual dimensions of pitch, loudness, and timbre.

Just as we can perceive light only at visible wavelengths, we can

perceive sound waves only in the limited range of frequencies plotted in
Figure 10-4 . Healthy young adult humans’ hearing range is from about
20 to 20,000 hertz. Many animals communicate with sound: their auditory
system is designed to interpret their species-typical sounds. After all,
what is the point in making complicated songs or calls if other members
of your species cannot hear and interpret them?
The range of sound wave frequencies heard by different species varies
extensively. Some (such as frogs and birds) have a rather narrow hearing
range; others (such as dogs, whales, and humans) have a broad range.
Some species use extremely high frequencies (bats are off the scale in
Figure 10-4 ); others (fish, for example) use the low range.
The auditory systems of whales and dolphins are responsive to a
remarkably wide range of sound waves. Characteristics at the extremes of
these frequencies allow marine mammals to use them in different ways.
Very low frequency sound waves travel long distances in water. Whales
produce them for underwater communication over hundreds of miles.
High-frequency sound waves echo and form the basis of sonar. Dolphins
produce them in bursts, listening for the echoes that bounce back from
objects. The echoes help the dolphins to navigate and locate prey.
 Differences in sound wave frequencies become differences in pitch
when heard. Each note in a musical scale must have a different frequency,
because each has a different pitch. Middle C on the piano, for instance,
has a frequency of 264 hertz.
Most people can discriminate between one musical note and another,
but some can actually name any note they hear (A, B flat, C sharp, and so
forth). This perfect (or absolute ) pitch runs in families, suggesting a
genetic influence. On the side of experience, most people who develop
perfect pitch also receive musical training in matching pitch to note from
an early age.
Section 8-4 suggests a critical period in brain development most
sensitive to musical training. Figure 15-11 shows enhanced
connectivity in people with perfect pitch.
Sound Wave Amplitude
Sound waves vary not only in frequency, which causes differences in
perceived pitch, but also in amplitude (strength), which causes
differences in perceived intensity, or loudness. If you hit a tuning fork
lightly, it produces a tone with a frequency of, say, 264 hertz (middle C).
amplitude Stimulus intensity; in audition, roughly equivalent to
loudness, graphed by the increasing height of a sound wave.
 FIGURE 10-4 Hearing Ranges among Animals Frogs and
birds hear a relatively narrow range of frequencies; whales’ and dolphins’
ranges are extensive, as are dogs’. Humans’ hearing range is broad, yet
we do not perceive many sound frequencies that other animals can both
make and hear.

If you hit it harder, the frequency remains 264 hertz, but you also transfer
more energy into the vibrating prong, increasing its amplitude.
The fork now moves farther left and right but at the same frequency.
Increased air molecule compression intensifies the energy in a sound
wave, which amps the sound—makes it louder. Differences in amplitude
are graphed by increasing the height of a sound wave, as shown in the
middle panel of Figure 10-3 .
Sound wave amplitude is usually measured in decibels (dB), the
strength of a sound relative to the threshold of human hearing as a
standard, pegged at 0 decibels ( Figure 10-5 ). Typical speech sounds, for
example, measure about 40 decibels. Sounds that register more than about
70 dB we perceive as loud; those of less than about 20 dB we perceive as
soft, or quiet.
decibel (dB) Measure of the relative physical intensity of sounds.
 The human nervous system evolved to be sensitive to soft sounds and
so is actually blown away by extremely loud ones. People regularly
damage their hearing through exposure to very loud sounds (such as rifle
fire at close range) or even by prolonged exposure to sounds that are only
relatively loud (such as at a live concert). Prolonged exposure to sounds
louder than 100 decibels is likely to damage our hearing.
Rock bands, among others, routinely play music that registers higher
than 120 decibels and sometimes as high as 135 decibels. Drake-Lee
(1992) found that rock musicians had a significant loss of sensitivity to
sound waves, especially at about 6000 hertz. After a typical 90-minute
concert, this loss was temporarily far worse—as much as a 40-fold
increase in sound pressure was needed to reach a musician’s hearing
threshold. But rock concerts are not the only music venue that can
damage hearing. Teie (1998) reports that symphony orchestras also
produce dangerously high sound levels and that hearing loss is common
among symphony musicians. Similarly, prolonged listening through
headphones or earbuds to music played loudly on personal music players
is responsible for significant hearing loss in many young people (Daniel,
2007).

FIGURE 10-5 Sound Intensity

Sound Wave Complexity
Sounds with a single frequency wave are pure tones, much like those that
emanate from a tuning fork or pitch pipe, but most sounds mix wave
frequencies together in combinations called complex tones (see Figure 10-
3 , bottom panel). To better understand the blended nature of a complex
tone, picture a clarinetist, such as Don Byron in Figure 10-6 , playing a
steady note. The upper graph in Figure 10-6 represents the sound wave a
clarinet produces.
The waveform pattern is more complex than the simple, regular waves
visualized in Figures 10-2 or 10-3 . Even when a musician plays a single
note, the instrument is making a complex tone. Using a mathematical
technique known as Fourier analysis, we can break down this complex
tone into its many component pure tones, the numbered waves traced at
the bottom of Figure 10-6 .
Craig Lovell/Eagle Visions Photography/Alamy
FIGURE 10-6 Breaking Down a Complex Tone The waveform of a single
note (top) from Don Byron’s clarinet and the simple sound waves—the fundamental
frequency (middle) and overtones (bottom)—that make up the complex tone.

The fundamental frequency (wave 1) is the rate at which the complex

waveform pattern repeats. Waves 2 through 20 are overtones, a set of
higher-frequency sound waves that vibrate at whole-number (integer)
multiples of the fundamental frequency. Different musical instruments
sound unique because they produce overtones of different amplitudes.
Among the clarinet’s overtones, represented by the heights of the blue
waves in Figure 10-6 , wave 5 is low amplitude, whereas wave 2 is high
amplitude.
As primary colors blend into near-infinite variety, so pure tones blend
into complex tones. Complex tones emanate from musical instruments,
from the human voice, from birdsong, and from machines or repetitive
mechanisms that make rhythmic buzzing or humming sounds. A key
feature of complex tones, besides being made up of two or more pure
tones, is periodicity: the fundamental frequency repeats at regular
intervals. Sounds that are aperiodic, or random, we call noise.

Perception of Sound
Visualize what happens when you toss a pebble into a pond. Waves of
water emanate from the point where the pebble enters the water. These
waves produce no audible sound. But if your skin were able to convert the
water wave energy (sensation) into neural activity that stimulated your
auditory system, you would hear the waves when you placed your hand in
the rippling water (perception). When you removed your hand, the sound
would stop.
The pebble hitting the water is much like a tree falling to the ground,
and the waves that emanate from the pebble’s entry point are like the air
pressure waves that emanate from the place where the tree strikes the
ground. The frequency of the waves determines the pitch of the sound
heard by the brain, whereas the height (amplitude) of the waves
determines the sound’s loudness.
Our sensitivity to sound waves is extraordinary. At the threshold of
human hearing, we can detect the displacement of air molecules of about
10 picometers. We are rarely in an environment where we can detect such
a small air pressure change: there is usually too much background noise.
A quiet, rural setting is probably as close as we ever get to an
environment suitable for testing the acuteness of our hearing. The next
time you visit the countryside, take note of the sounds you can hear. If
there is no sound competition, you can often hear a single car engine
miles away.
In addition to detecting minute changes in air pressure, the auditory
system is also adept at simultaneously perceiving different sounds. As
you read this chapter, you can differentiate all sorts of sounds around you
—traffic on the street, people talking next door, your air conditioner
humming, footsteps in the hall. As you listen to music, you detect the
sounds of different instruments and voices.
You can perceive more than one sound simultaneously because each
frequency of change in air pressure (each different sound wave)
stimulates different neurons in your auditory system. Sound perception is
only the beginning of your auditory experience. Your brain interprets
sounds to obtain information about events in your environment, and it
analyzes a sound’s meaning. Your use of sound to communicate with
other people through both language and music clearly illustrate these
processes.
1 picometer = one-trillionth of a meter

Properties of Language and Music as

Sounds
Language and music differ from other auditory sensations in fundamental
ways. Both convey meaning and evoke emotion. Analyzing meaning in
sound is a considerably more complex behavior than simply detecting a
sound and identifying it. The brain has evolved systems that analyze
sounds for meaning, speech in the left temporal lobe and music in the
right.
Infants are receptive to speech and musical cues before they have any
obvious utility, which suggests both the innate presence of these skills and
the effects of prenatal experiences. Humans have an amazing capacity for
learning and remembering linguistic and musical information. We are
capable of learning a vocabulary of tens of thousands of words, often in
many languages, and a capacity for recognizing thousands of songs.
Language facilitates communication. We can organize our complex
perceptual worlds by categorizing information with words. We can tell
others what we think and know and imagine. Imagine the efficiency that
gestures and language added to the cooperative food hunting and
gathering behaviors of early humans.
All these benefits of language seem obvious, but the benefits of music
may seem less straightforward. In fact, music helps us to regulate our own
emotions and to affect the emotions of others. After all, when do people
most commonly make music? We sing and play music to communicate
with infants and put children to sleep. We play music to enhance social
interactions and gatherings and romance. We use music to bolster group
identification—school songs and national anthems are examples. Music
as we know it is unique to humans. Studies of nonhumans provide little
evidence for preferences for human music over other sounds.
Another characteristic that distinguishes speech and musical sounds
from other auditory inputs is their delivery speed. Nonspeech and
nonmusical noise produced at a rate of about five segments per second is
perceived as a buzz. (A sound segment is a distinct unit of sound.)
Normal speed for speech is on the order of 8 to 10 segments per second,
and we are capable of understanding speech at nearly 30 segments per
second. Speech perception at these higher rates is astounding, because the
input speed far exceeds the auditory system’s ability to transmit all the
speech segments as separate pieces of information.
Loomis Dean/Time Life Pictures/Getty Images
Elvis Presley’s memory for lyrics suits his legend: while serving in the U.S. Army, he
wagered all comers that he could sing any song they named. Elvis never lost a bet.

Properties of Language
Experience listening to a particular language helps the brain to analyze
rapid speech, which is one reason people who are speaking languages
unfamiliar to you often seem to be talking incredibly fast. Your brain does
not know where the foreign words end and begin, so they seem to run
together in a rapid-fire stream.
A unique characteristic of our perception of speech sounds is our
tendency to hear variations of a sound as if they were identical, even
though the sound varies considerably from one context to another. For
instance, the English letter d is pronounced differently in the words deep,
deck, and duke, yet a listener perceives the pronunciations to be the same
d sound.
The auditory system must therefore have a mechanism for categorizing
sounds as being the same despite small differences in pronunciation.
Experience must affect this mechanism, because different languages
categorize speech sounds differently. A major obstacle to mastering a
foreign language after age 10 is the difficulty of learning which sound
categories are treated as equivalent.
Auditory constancy is reminiscent of the visual system’s capacity for
object constancy; see Section 9-4 .
Properties of Music
As with other sounds, the subjective properties that people perceive in
musical sounds differ from one another. One subjective property is
loudness, the magnitude of the sound as judged by a person. Loudness is
related to the amplitude of a sound wave measured in decibels, but
loudness is also subjective. What is very loud music for one person may
be only moderately loud for another, whereas music that seems soft to one
listener may not seem at all soft to someone else. Your perception of
loudness also changes with context. After you’ve slowed down from
driving fast on a highway, for example, your car’s music system seems
louder. The reduction in road noise alters your perception of the music’s
loudness.
Another subjective property of musical sounds is pitch, the position of
each tone on a musical scale as judged by the listener. Although pitch is
clearly related to sound wave frequency, there is more to it than that.
Consider the note middle C as played on a piano. This note can be
described as a pattern of sound frequencies, as is the clarinet note in
Figure 10-6 .
Like the note played on the piano, any musical note is defined by its
fundamental frequency—the lowest frequency of the sound wave pattern,
or the rate at which the overall pattern repeats. For middle C, the
fundamental frequency is 264 Hertz, and the sound waves for notes C, E,
and G, as measured by a spectrograph, are shown in Figure 10-7 . Notice
that by convention sound wave spectrographs are measured in kilohertz
(kHz), or thousands of hertz. Thus, if we look at the fundamental
frequency for middle C, it is the first large wave on the left, at 0.264
kilohertz. The fundamental frequencies for E and G are 0.330 and 0.392
kilohertz, respectively.
An important feature of the human brain’s analysis of music is that
middle C is perceived as being the same note whether it is played on a
piano or on a guitar, even though the sounds of these instruments differ
widely. The right temporal lobe extracts pitch from sound, whether the
sound is speech or music. In speech, pitch contributes to the perceived
melodic tone of a voice, or prosody.
prosody Melodic tone of the speaking voice.
A final property of musical sound is quality, or timbre, the perceived
characteristics that distinguish a particular sound from all others of
similar pitch and loudness. We can easily distinguish the timbre of a
violin from that of a trombone, even if both instruments are playing the
same note at the same loudness. The quality of their sounds differs.

Courtesy Drew Rendall, University of New Brunswick

FIGURE 10-7 Fundamental Frequencies of Piano Notes
Waveforms of the notes C, E, and G as played on a piano and recorded on
a spectrograph. The first wave in each graph is the fundamental frequency;
the secondary waves are the overtones.
10-1 REVIEW
Sound Waves: Stimulus for Audition
Before you continue, check your understanding.
1 . The physical stimulus for audition, produced by changes in, is a form
of mechanical energy converted in the ear to neural activity.
2 . Sound waves have three physical attributes:, ___________, and
___________.
3 . Four properties of musical sounds are, ___________, ___________,
and ___________.
4 . Sound is processed in the lobes.
5 . What distinguishes speech and musical sounds from other auditory
inputs?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Functional Anatomy of the Auditory
10-2

System
To understand how the nervous system analyzes sound waves, we begin
by tracing the pathway sound energy takes to and through the brain. The
ear collects sound waves from the surrounding air and converts their
mechanical energy to electrochemical neural energy, which begins a long
route through the brainstem to the auditory cortex.
Before we can trace the journey from ear to cortex, we must ask what
the auditory system is designed to do. Because sound waves have the
properties frequency, amplitude, and complexity, we can predict that the
auditory system is structured to decode these properties. Most animals
can tell where a sound comes from, so some mechanism must locate
sound waves in space. Finally, many animals, including humans, not
only analyze sounds for meaning but also make sounds. Because the
sounds they produce are often the same as the ones they hear, we can
infer that the neural systems for sound production and analysis must be
closely related.
In humans, the evolution of sound-processing systems for both
language and music was accompanied by enhancement of specialized
cortical regions, especially in the temporal lobes. In fact, a major
difference between the human and the monkey cortex is a marked
expansion of auditory areas in humans.
 Monkey

Human

Structure of the Ear

The ear is a biological masterpiece in three acts: outer ear, middle ear,
and inner ear, all illustrated in Figure 10-8 .
Processing Sound Waves
Both the pinna, the funnel-like external structure of the outer ear, and the
external ear canal, which extends a short distance from the pinna inside
the head, are made of cartilage and flesh. The pinna is designed to catch
sound waves in the surrounding environment and deflect them into the
external ear canal. To enhance sound detection when we want to hear
better, we often cup a hand around the pinna.
Because it narrows from the pinna, the external canal amplifies sound
waves and directs them to the eardrum at its inner end. When sound
waves strike the eardrum, it vibrates, the rate of vibration varying with
the frequency of the waves. On the inner side of the eardrum, as depicted
in Figure 10-8 , is the middle ear, an air-filled chamber that contains the
three smallest bones in the human body, connected in a series.
These three ossicles are called the hammer, the anvil, and the stirrup
because of their distinctive shapes. The ossicles attach the eardrum to the
oval window, an opening in the bony casing of the cochlea, the inner ear
structure containing the auditory receptor cells.
ossicle Bone of the middle ear; includes malleus (hammer), incus
(anvil), and stapes (stirrup).
cochlea Inner ear structure containing the auditory receptor cells.
 FIGURE 10-8 Anatomy of the Human Ear Sound waves
gathered into the outer ear are transduced from air pressure into
mechanical energy in the middle ear ossicles then into electrochemical
activity in the inner ear cochlea. Inner hair cells embedded in the basilar
membrane (the organ of Corti) are tipped by cilia. Movements of the
basilar and tectorial membranes displace the cilia, leading to changes in
the inner hair cells’ membrane potentials and resultant activity of auditory
bipolar neurons.

These receptor cells and the cells that support them are collectively
called the organ of Corti, shown in detail in Figure 10-8 .
When sound waves vibrate the eardrum, the vibrations are transmitted
to the ossicles. The leverlike action of the ossicles amplifies the
vibrations and conveys them to the membrane that covers the cochlea’s
oval window. As Figure 10-8 shows, the cochlea coils around itself and
looks a bit like a snail shell. Inside its bony exterior, the cochlea is
hollow, as the cross-sectional drawing reveals.
The hollow cochlear compartments are filled with lymphatic fluid,
and floating in its midst is the thin basilar membrane. Embedded in a
part of the basilar membrane are outer and inner hair cells. At the tip of
each hair cell are several filaments called cilia, and the cilia of the outer
hair cells are embedded in the overlying tectorial membrane. The inner
hair cells loosely contact this tectorial membrane.
 basilar membrane Receptor surface in the cochlea that transduces
sound waves into neural activity.
hair cell Specialized neurons in the cochlea tipped by cilia; when
stimulated by waves in the cochlear fluid, the cilia bend and
generate graded potentials in inner hair cells, the auditory receptor
cells.
Pressure from the stirrup on the oval window makes the cochlear fluid
move because a second membranous window in the cochlea (the round
window ) bulges outward as the stirrup presses inward on the oval
window. In a chain reaction, the waves traveling through the cochlear
fluid bend the basilar and tectorial membranes, and the bending
membranes stimulate the cilia at the tips of the outer and inner hair cells.
Cochlea actually means snail shell in Latin.
Transducing Sound Waves into Neural Impulses
How does the conversion of sound waves into neural activity code the
various properties of sound that we perceive? In the late 1800s, the
German physiologist Hermann von Helmholtz proposed that sound
waves of different frequencies cause different parts of the basilar
membrane to resonate. Von Helmholtz was partly correct. Actually, all
parts of the basilar membrane bend in response to incoming waves of
any frequency. The key is where the peak displacement takes place
(Figure 10-9 ).

(A) Uncoiling of cochlea

 (B) Uncoiled cochlea
FIGURE 10-9 Anatomy of the Cochlea (A) The basilar membrane
is maximally responsive to frequencies mapped as the cochlea uncoils.
(B) Sound waves of different frequencies produce maximal displacement
of the basilar membrane (shown uncoiled) at different locations.

This solution to the coding puzzle was determined in 1960, when

George von Békésy observed the basilar membrane directly. He saw a
traveling wave moving along the membrane all the way from the oval
window to the membrane’s apex. The coiled cochlea in Figure 10-9 A
maps the frequencies to which each part of the basilar membrane is most
responsive. When the oval window vibrates in response to the vibrations
of the ossicles, shown beside the uncoiled membrane in Figure 10-9 B, it
generates waves that travel through the cochlear fluid. Békésy placed
little grains of silver along the basilar membrane and watched them jump
in different places to different frequencies of incoming waves. Higher
wave frequencies caused maximum peaks of displacement near the base
of the basilar membrane; lower wave frequencies caused maximum
displacement peaks near the membrane’s apex.
As a rough analogy, consider what happens when you shake a rope. If
you shake it quickly, the waves in the rope are small and short and the
peak of activity remains close to the base—the hand holding the rope.
But if you shake the rope slowly, with a broader movement, the longer
waves reach their peak farther along the rope—toward the apex. The key
point is that, although both rapid and slow shakes produce movement
along the rope’s entire length, the point of maximum displacement
depends on whether the wave movements are rapid or slow.
This same response pattern holds for the basilar membrane and sound
wave frequency. All sound waves cause some displacement along the
entire length of the membrane, but the amount of displacement at any
point varies with the sound wave’s frequency. In the human cochlea,
shown uncoiling in Figure 10-9 A, the basilar membrane near the oval
window is maximally affected by frequencies as high as about 20,000
hertz, the upper limit of our hearing range. The most effective
frequencies at the membrane’s apex register less than 100 hertz, closer to
our lower limit of about 20 Hz (see Figure 10-4 ).
Intermediate frequencies maximally displace points on the basilar
membrane between its ends, as shown in Figure 10-9 B. When a wave of
a certain frequency travels down the basilar membrane, hair cells at the
point of peak displacement are stimulated, resulting in a maximal neural
response in those cells. An incoming signal composed of many
frequencies causes several points along the basilar membrane to vibrate
and excites hair cells at all these points.
Not surprisingly, the basilar membrane is much more sensitive to
changes in frequency than is the rope in our analogy, because the basilar
membrane varies in thickness along its entire length. It is narrow and
thick at the base, near the oval window, and wider and thinner at its
tightly coiled apex. The combination of varying width and thickness
enhances the effect of small frequency differences. As a result, the
cochlear receptors can code small differences in sound wave frequency
as neural impulses.

Auditory Receptors
Two kinds of hair cells transform sound waves into neural activity.
Figure 10-8 (bottom left) shows the anatomy of the inner hair cells;
Figure 10-10 illustrates how sound waves stimulate them. A young
person’s cochlea has about 12,000 outer and 3500 inner hair cells. The
numbers fall off with age. Only the inner hair cells act as auditory
receptors, and their numbers are small considering how many different
sounds we can hear. As diagrammed in Figure 10-10 , both outer and
inner hair cells are anchored in the basilar membrane. The tips of the
cilia of outer hair cells are attached to the overlying tectorial membrane,
but the cilia of the inner hair cells only loosely touch that membrane.
Nevertheless, the movement of the basilar and tectorial membranes
causes the cochlear fluid to flow past the cilia of the inner hair cells,
bending them back and forth.
 FIGURE 10-10 Transducing Waves into Neural Activity
Movement of the basilar membrane produces a shearing force in the
cochlear fluid that bends the cilia, leading to the opening or closing of
calcium channels in the outer hair cells. An influx of calcium ions leads the
inner hair cells to release neurotransmitter, stimulating increased action
potentials in auditory neurons.

Animals with intact outer hair cells but no inner hair cells are
effectively deaf. That is, they can perceive only very loud, low-frequency
sounds via the somatosensory system. You may have experienced this
feeling when a sub-woofer or a passing truck caused vibrations in your
chest. Inner hair cells can be destroyed by prolonged exposure to intense
sound pressure waves, infections, diseases, or certain chemicals and
drugs. Inner hair cells do not regenerate; thus once the inner hair cells
have died hearing loss is permanent.
Outer hair cells function by sharpening the cochlea’s resolving power,
contracting or relaxing and thereby changing tectorial membrane
stiffness. That’s right: the outer hair cells have a motor function. While
we typically think of sensory input preceding motor output, in fact,
motor systems can influence sensory input. The pupil contracts or dilates
to change the amount of light that falls on the retina, and the outer hair
cells contract or relax to alter the physical stimulus detected by the inner
hair cells.
How this outer hair cell function is controlled is puzzling. What
stimulates these cells to contract or relax? The answer seems to be that
through connections with axons in the auditory nerve, the outer hair cells
send a message to the brainstem auditory areas and receive a reply that
causes the cells to alter tension on the tectorial membrane. In this way,
the brain helps the hair cells to construct an auditory world. The outer
cells are also part of a mechanism that modulates auditory nerve firing,
especially in response to intense sound pressure waves, and thus offers
some protection against their damaging effects.
A final question remains: How does movement of the inner hair cell
cilia alter neural activity? The neurons of the auditory nerve have a
spontaneous baseline rate of firing action potentials, and this rate is
changed by the amount of neurotransmitter the hair cells release. It turns
out that movement of the cilia changes the inner hair cell’s polarization
and its rate of neurotransmitter release. Inner hair cells continuously leak
calcium, and this leakage causes a small but steady amount of
neurotransmitter release into the synapse. Movement of the cilia in one
direction results in depolarization: calcium channels open and release
more neurotransmitter onto the dendrites of the cells that form the
auditory nerve, generating more nerve impulses. Movement of the cilia
in the other direction hyper-polarizes the cell membrane and transmitter
release decreases, thus decreasing activity in auditory neurons.
Inner hair cells are amazingly sensitive to the movement of their cilia.
A movement sufficient to allow sound wave detection is only about 0.3
nm, about the diameter of a large atom! Such sensitivity helps to explain
why our hearing is so incredibly sensitive. Clinical Focus 10-2 ,
Otoacoustic Emissions, describes a consequence of cochlear function.
Section 4-2 reviews phases of the action potential and its
propagation as a nerve impulse.
 RESEARCH FOCUS 10-2
Otoacoustic Emissions
While the ear is exquisitely designed to amplify and convert sound
waves into action potentials, it is unique among the sensory organs.
The ear also produces the physical stimulus it is designed to detect!
A healthy cochlea produces sound waves called otoacoustic
emissions.
otoacoustic emissions Spontaneous or evoked sound waves
produced within the ear by the cochlea and escape from the ear.
The cochlea acts as an amplifier. The outer hair cells amplify
sound waves, providing an energy source that enhances cochlear
sensitivity and frequency selectivity. Not all the energy the cochlea
generates is dissipated within it. Some escapes toward the middle
ear, which works efficiently in both directions, thus setting the
eardrum in motion. The eardrum then acts as a loudspeaker, radiating
sound waves—the otoacoustic emissions—out of the ear.
Sensitive microphones placed in the external ear canal can detect
both types of otoacoustic emissions, spontaneous and evoked. As the
name implies, spontaneous otoacoustic emissions occur without
external stimulation. Evoked otoacoustic emissions, generated in
response to sound waves, are important because evoked emissions
are useful for assessing hearing impairments.
A simple, noninvasive test can detect and evaluate evoked
otoacoustic emissions in newborns and children who are too young
to take conventional hearing tests, as well as in people of any age. A
small speaker and microphone are inserted into the ear. The speaker
emits a click sound, and the microphone detects the resulting evoked
emission without damaging the delicate workings of the inner ear.
Missing or abnormal evoked emissions predict a hearing deficit.
Many wealthy countries now sponsor universal programs to test the
hearing of all newborn babies using otoacoustic emissions.
Otoacoustic emissions serve a useful purpose, but even so, they
play no direct role in hearing. They are considered an
epiphenomenon— a secondary phenomenon that occurs in parallel
with or above (epi ) a primary phenomenon.
Pathways to the Auditory Cortex
Inner hair cells in the organ of Corti synapse with neighboring bipolar
cells, the axons that form the auditory (cochlear) nerve. The auditory
nerve in turn forms part of the eighth cranial nerve, the auditory
vestibular nerve that governs hearing and balance. Whereas ganglion
cells in the eye receive inputs from many receptor cells, bipolar cells in
the ear receive input from but a single inner hair cell receptor.
Cochlear-nerve axons enter the brainstem at the level of the medulla
and synapse in the cochlear nucleus, which has ventral and dorsal
subdivisions. Two nearby structures in the hindbrain (brainstem), the
superior olive (a nucleus in the olivary complex) and the trapezoid body,
receive connections from the cochlear nucleus, as charted in Figure 10-
11 . Projections from the cochlear nucleus connect with cells on the same
side of the brain as well as with cells on the opposite side. This
arrangement mixes the inputs from the two ears to form a single sound
perception.
Both the cochlear nucleus and the superior olive send projections to
the inferior colliculus in the dorsal midbrain. Two distinct pathways
emerge from the inferior colliculus, coursing to the medial geniculate
nucleus in the thalamus. The ventral region of the medial geniculate
nucleus projects to the primary auditory cortex (area A1), whereas the
dorsal region projects to the auditory cortical regions adjacent to area
A1.
medial geniculate nucleus Major thalamic region concerned with
audition.
primary auditory cortex (area A1) Asymmetrical structures within
Heschl’s gyrus in the temporal lobes; receive input from the ventral
region of the medial geniculate nucleus.
Analogous to the two distinct visual pathways—the ventral stream for
object recognition and the dorsal stream for visual control of movement
—a similar distinction exists in the auditory cortex (Romanski et al.,
1999). Just as we can identify objects by their sound characteristics, we
can direct our movements by the sound we hear. The role of sound in
guiding movement is less familiar to sight-dominated people than it is to
the blind. Nevertheless, the ability exists in us all. Imagine waking up in
the dark and reaching to pick up a ringing telephone or to turn off an
alarm clock. Your hand automatically forms the appropriate shape in
response to just the sound you have heard. That sound is guiding your
movements much as a visual image guides them.
Relatively little is known about the what–how auditory pathways in
the cortex. One appears to continue through the temporal lobe, much like
the ventral visual pathway, and plays a role in identifying auditory
stimuli. A second auditory pathway apparently goes to the posterior
parietal region, where it forms a dorsal route for the auditory control of
movement. It appears as well that auditory information can gain access
to visual cortex, as illustrated in Research Focus 10-3 , Seeing with
Sound.
Figure 2-27 lists and locates the cranial nerves, and in its caption is a
mnemonic for remembering them in order.
Figure 9-13 maps the visual pathways through the cortex.

Auditory Pathways Auditory inputs cross to the

FIGURE 10-11
hemisphere opposite the ear in the hindbrain and midbrain, then recross in
 the thalamus. In this way, the information from each ear reaches both
hemispheres. Multiple nuclei process inputs en route to the auditory
cortex, charted here for the left ear.

Auditory Cortex
In humans, the primary auditory cortex (A1) lies within Heschl’s gyrus,
surrounded by secondary cortical areas (A2), as shown in Figure 10-12
A . The secondary cortex lying behind Heschl’s gyrus is called the
planum temporale (Latin for temporal plane ).
In right-handed people, the planum temporale is larger on the left than
it is on the right side of the brain, whereas Heschl’s gyrus is larger on the
right side than on the left. The cortex of the left planum forms a speech
zone known as Wernicke’s area (the posterior speech zone), whereas
the cortex of the larger right-hemisphere Heschl’s gyrus has a special
role in analyzing music.
Wernicke’s area Secondary auditory cortex (planum temporale)
lying behind Heschl’s gyrus at the rear of the left temporal lobe;
regulates language comprehension. Also posterior speech zone.
These hemispheric differences mean that the auditory cortex is
anatomically and functionally asymmetrical. Although cerebral
asymmetry is not unique to the auditory system, it is most obvious here
because auditory analysis of speech takes place only in the left
hemisphere of right-handed people. About 70 percent of left-handed
people have the same anatomical asymmetries as right-handers, an
indication that speech organization is not strictly related to hand
preference. Language, including speech and other functions such as
reading and writing, also is asymmetrical, although the right hemisphere
also contributes to these broader functions.
The remaining 30 percent of left-handers fall into two distinct groups.
The organization in about half of these people is opposite that of right-
handers. The other half has some idiosyncratic bilateral speech
representation. That is, about 15 percent of all left-handed people have
some speech functions in one hemisphere and some in the other
hemisphere.
(A) Auditory cortex

(B) Insula
FIGURE 10-12 Human Auditory Cortex (A) The left hemisphere,
showing the lateral fissure retracted to reveal the primary auditory cortex
buried within Heschl’s gyrus; and adjacent secondary auditory regions. In
cross section, the posterior speech zone (Wernicke’s area) is larger on the
left, and Heschl’s gyrus is larger in the right hemisphere. (B) Frontal view
showing the extent of the multifunctional insular cortex buried in the lateral
fissure.
 RESEARCH FOCUS 10-3
Seeing with Sound
As detailed in Section 10-5 , echolocation, the ability to use sound to
locate objects in space, has been extensively studied in species such
as bats and dolphins. But it was reported more than 50 years ago that
some blind people also echolocate.
More recently, anecdotal reports have surfaced of blind people
who navigate around the world using clicks made with their tongues
and mouths then listening to the returning echoes. Videos, such as
the 45-minute documentary at https://www.youtube.com/watch?
v=AiBeLoB6CKE , show congenitally blind people riding a bicycle
down a street with silent obstacles such as parked cars. But how do
they do this, and what part of the brain enables it?
Behavioral studies of blind people reveal that echolocators make
short, spectrally broad clicks by moving the tongue backward and
downward from the roof of the mouth directly behind the teeth.
Skilled echo-locators can identify properties of objects that include
position, distance, size, shape, and texture (Teng & Whitney, 2011).
Thaler and colleagues (2011) investigated the neural basis of this
ability using fMRI. They studied two blind echolocation experts and
compared brain activity for sounds that contain both clicks and
returning echoes with brain activity for control sounds that did not
contain the echoes. The participants use echolocation to localize
objects in the environment, but more important, they also perceive
the object’s shape, motion—even its identity!
When the blind participants listened to recordings of their
echolocation clicks and echoes compared to silence, both the
auditory cortex and the primary visual cortex showed activity.
Sighted controls showed activation only in the auditory cortex.
Remarkably, when the investigators compared the controls’ brain
activity to recordings that contained echoes versus those that did not,
the auditory activity disappeared. By contrast, as illustrated in the
figure, the blind echolocators showed activity only in the visual
cortex when sounds with and without echoes were compared.
 Sighted controls (findings not shown) showed no activity in either
the visual or auditory cortex in this comparison.
These results suggest that blind echolocation experts process
click–echo information using brain regions typically devoted to
vision. Thaler and his colleagues propose that the primary visual
cortex is performing a spatial computation using information from
the auditory cortex.
Future research may determine how this process works. More
immediately, the study suggests that echolocation could be taught to
blind and visually impaired people to provide them increased
independence in their daily life.

Seeing with Sound When cortical activation for sound with and
without echoes is imaged in a blind echolocator, only the visual cortex
shows activation (left) relative to the auditory cortex (right). Research
from Thaler, L., Arnott, S. R., & Goodale, M. A. (2011), Neural
correlates of natural human echolocation in early and late blind
echolocation experts. PLoS ONE, 6, (5)e20162.
doi:10.1371/journal.pone.0020162

Localization of language on one side of the brain is an example of

lateralization. Note here simply that, in neuroanatomy, if one
hemisphere is specialized for one type of analysis—as, for example, the
left hemisphere is for language—the other hemisphere has a
complementary function: the right hemisphere appears to be lateralized
for music.
lateralization Localization of function primarily on one side of the
brain.
The temporal lobe sulci enfold a volume of cortical tissue far more
extensive than the auditory cortex (Figure 10-12 B). Buried in the lateral
fissure, cortical tissue called the insula contains not only lateralized
regions related to language but also areas controlling taste perception
(the gustatory cortex) and areas linked to the neural structures underlying
social cognition. As you might expect, injury to the insula can produce
such diverse deficits as disturbance of both language and taste.
insula Multifunctional cortical tissue located within the lateral
fissure; contains language-and taste perception–related regions and
neural structures underlying social cognition.
 10-2 REVIEW
Functional Anatomy of the Auditory System
Before you continue, check your understanding.
1 . Incoming sound wave energy vibrates the eardrum, which in turn
vibrates the ___________.
2 . The auditory receptors are the ___________, found in the
___________.
3 . The motion of the cochlear fluid causes displacement of the
___________ and ___________ membranes.
4 . The axons of bipolar cells from the cochlea form the ___________
nerve, which is part of the ___________ cranial nerve.
5 . The auditory nerve originating in the cochlea projects to various
nuclei in the brainstem; then it projects to the ___________ in the
midbrain and the ___________ in the thalamus.
6 . Describe the asymmetrical structure and functions of the auditory
cortex.
Answers appear at the back of the book

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 10-3 Neural Activity and Hearing
We now turn to the neuronal activity in the auditory system that produces
our perception of sound. Neurons at different levels in this system serve
different functions. To get an idea of what individual hair cells and
cortical neurons do, we consider how the auditory system codes sound
wave energy so that we perceive pitch, loudness, location, and pattern.

Hearing Pitch
Recall that perception of pitch corresponds to the frequency (repetition
rate) of sound waves measured in hertz (cycles per second). Hair cells in
the cochlea code frequency as a function of their location on the basilar
membrane. In this tonotopic representation, hair cell cilia at the base of
the cochlea are maximally displaced by high-frequency waves, which we
hear as high-pitched sounds; those at the apex are displaced the most by
low-frequency waves, which we hear as low-pitched sounds. Because
each bipolar-cell axon that forms the cochlear nerve is connected to only
one inner hair cell, the bipolar cells convey information about the spot on
the basilar membrane, from apex to base, that is being stimulated.
tonotopic representation In audition, structural organization for
processing of sound waves from lower to higher frequencies.
Recordings from single fibers in the cochlear nerve reveal that
although each axon transmits information about only a small part of the
auditory spectrum, each cell does respond to a range of sound wave
frequencies—if the wave is sufficiently loud. That is, each hair cell is
maximally responsive to a particular frequency and also responds to
nearby frequencies, but the sound wave’s amplitude must be greater
(louder) for those nearby frequencies to excite the receptor’s membrane
potential.
We can plot this range of hair cell responses to different frequencies at
different amplitudes as a tuning curve. As graphed in Figure 10-13 ,
each hair cell receptor is maximally sensitive to a particular wavelength
but still responds somewhat to nearby wavelengths.
Tonotopic literally means of a tone place.
A hair cell’s frequency range parallels a photoreceptor’s response to
light wavelengths. See Figure 9-6 .
 FIGURE 10-13 Tuning Curves Graphs plotted by the sound wave
frequency and amplitude energy required to increase the firing rate of two
axons in the cochlear nerve. The lowest point on each tuning curve is the
frequency to which that hair cell is most sensitive. The curve at left is
centered on a frequency of 1000 Hz, the midrange of human hearing; the
curve at right is centered on a frequency of 10,000 Hz, in the high range.

FIGURE 10-14 Tonotopic Representation of Area A1 A

retractor holds the lateral fissure open to reveal the underlying primary
auditory cortex. The anterior end of area A1 corresponds to the apex of
the cochlea, hence low frequencies. The posterior end corresponds to the
base of the cochlea, hence high frequencies.

Bipolar cell axons in the cochlea project to the cochlear nucleus in an

orderly manner (see Figure 10-11 ). Axons entering from the base of the
cochlea connect with one location; those entering from the middle
connect to another location; and those entering from the apex connect to
yet another. Thus the basilar membrane’s tonotopic representation is
reproduced in the hindbrain cochlear nucleus.
This systematic representation is maintained throughout the auditory
pathways and into the primary auditory cortex. Figure 10-14 shows the
distribution of projections from the base and apex of the cochlea across
area A1. Similar tonotopic maps can be constructed for each level of the
auditory system.
This systematic auditory organization has enabled the development of
cochlear implants —electronic devices surgically inserted in the inner
ear that serve as prostheses to allow deaf people to hear (see Loeb,
1990). Cochlear implants are no cure for deafness but rather are a
hearing substitute. In Figure 10-15 , a miniature microphonelike
processor secured to the skull detects the component frequencies of
incoming sound waves and sends them to the appropriate place on the
basilar membrane through tiny wires. The nervous system does not
distinguish between stimulation coming from this artificial device and
stimulation coming through the middle ear.
cochlear implant Electronic device implanted surgically into the
inner ear to transduce sound waves to neural activity and allow a
deaf person to hear.
As long as appropriate signals go to the correct locations on the
basilar membrane, the brain will hear. Cochlear implants work well,
allowing the deaf to detect even the fluctuating pitches of speech. Their
success corroborates the tonotopic representation of pitch in the basilar
membrane.

FIGURE 10-15 Tonotopic Technology A cochlear implant captures

incoming sound wave stimulation via a microphone worn behind the ear.
 An audio processor converts the frequencies into electric current and
stimulates the correct locations on the basilar membrane.

Even so, the quality of sound cochlear implants create is

impoverished relative to natural hearing. Adults who lose their hearing
and then get cochlear implants describe the sounds as “computerized”
and “weird.” Many people with implants find music unpleasant and
difficult to listen to. Graeme Clark (2015) developed a prototype high-
fidelity cochlear implant with 50 electrodes to increase basilar membrane
stimulation. His goal is achieving better music perception and enhanced
ability to discern specific voices in noisy rooms.
One minor difficulty with frequency detection is that the human
cochlea does not respond in a tonotopic manner to frequencies below
about 200 Hz, yet we can hear frequencies as low as 20 Hz. At its apex,
all the cells respond to movement of the basilar membrane, but they do
so in proportion to the frequency of the incoming wave (see Figure 10-9
B). Higher rates of bipolar cell firing signal a higher frequency, whereas
lower rates of firing signal a lower frequency.
Why the cochlea uses a different system to differentiate pitch within
this range of very low frequency sound waves is not clear. It probably
has to do with the physical limitations of the basilar membrane.
Discriminating among low-frequency sound waves is vital to animals
such as elephants and whales, which depend on these frequencies to
communicate. These species most likely have more neurons at the apex
of the basilar membrane than we humans do.

Detecting Loudness
The simplest way for cochlear (bipolar) cells to indicate sound wave
intensity is to fire at a higher rate when amplitude is greater, which is
exactly what happens. More intense air pressure changes produce more
intense basilar membrane vibrations and therefore greater shearing of the
cilia. Increased shearing leads to more neurotransmitter released onto
bipolar cells. As a result, the bipolar axons fire more frequently, telling
the auditory system that the sound is getting louder.

Detecting Location
Psychologist Albert Bregman devised a visual analogy to describe what
the auditory system is doing when it detects sound location:
 Imagine a game played at the side of a lake. Two small channels are
dug, side by side, leading away from the lake, and the lake water is
allowed to fill them up. Partway up each channel, a cork floats,
moving up and down with the waves. You stand with your back to the
lake and are allowed to look only at the two floating corks. Then you
are asked questions about what is happening on the lake. Are there
two motorboats on the lake or only one? Is the nearer one going from
left to right or right to left? Is the wind blowing? Did something heavy
fall into the water? You must answer these questions just by looking at
the two corks. This would seem to be an impossible task. Yet consider
an exactly analogous problem. As you sit in a room, a lake of air
surrounds you. Running off this lake, into your head, are two small
channels – your ear canals. At the end of each is a membrane (the ear
drum) that acts like the floating corks in the channels running off the
lake, moving in and out with the sound waves that hit it. Just as the
game at the lakeside offered no information about the happenings on
the lake except for the movements of the corks, the sound-producing
events in the room can be known by your brain only through the
vibrations of your two eardrums. (Bregman, 2005, p. 35)
We estimate the location of a sound both by taking cues derived from
one ear and by comparing cues received at both ears. The fact that each
cochlear nerve synapses on both sides of the brain provides mechanisms
for locating a sound source. In one mechanism, neurons in the brainstem
compute the difference in a sound wave’s arrival time at each ear—the
interaural time difference (ITD). Differences in arrival time need not be
large to be detected. If two sounds presented through earphones are
separated in time by as little as 10 microseconds, the listener will
perceive that a single sound came from the leading ear.
This computation of left-ear–right-ear arrival times is carried out in
the medial part of the superior olivary complex (see Figure 10-11 ).
Because these hindbrain cells receive inputs from each ear, they can
compare exactly when the signal from each ear reaches them.
Figure 10-16 shows how sound waves originating on the left reach
the left ear slightly before they reach the right ear. As the sound source
moves from the side of the head toward the middle, a person has greater
and greater difficulty locating it: the ITD becomes smaller and smaller
until there is no difference at all. When we detect no difference, we infer
that the sound is either directly in front of us or directly behind us. To
locate it, we turn our head, making the sound waves strike one ear
sooner. We have a similar problem distinguishing between sounds
directly above and below us. Again, we solve the problem by tilting our
head, thus causing the sound waves to strike one ear before the other.
Another mechanism used by the auditory system to detect the source
of a sound is the sound’s relative loudness on the left and the right—the
interaural intensity difference (IID). The head acts as an obstacle to
higher-frequency sound waves, which do not easily bend around the
head. As a result, higher-frequency waves on one side of the head are
louder than on the other. The lateral part of the superior olive and the
trapezoid body detect this difference. Again, sound waves coming from
directly in front or behind or from directly above or below require the
same solution: tilting or turning the head.
Head tilting and turning take time, which is important for animals,
such as owls, that hunt using sound. Owls need to know the location of a
sound simultaneously in at least two directions—right or left and above
or below. Owls, like humans, can orient in the horizontal plane to sound
waves by using ITD. Additionally, the owl’s ears have evolved to detect
the relative loudness of sound waves in the vertical plane. As
diagrammed in Figure 10-17 , owls’ ears are slightly displaced
vertically. This solution allows owls to hunt entirely by sound in the
dark. Bad news for mice.
 FIGURE 10-16 Locating a Sound Compression waves originating on
the left side of the body reach the left ear slightly before the right. The ITD
is small, but the auditory system can discriminate it and fuse the dual
stimuli so that we perceive a single, clear sound coming from the left.
Horizontal orienting is azimuth detection; vertical orienting is elevation
detection.

Detecting Patterns in Sound

Music and language are perhaps the primary sound wave patterns that
humans recognize. Perceiving sound wave patterns as meaningful units
thus is fundamental to our auditory analysis. Because music perception
and language perception are lateralized in the right and left temporal
lobes, respectively, we can guess that neurons in the right and left
temporal cortex take part in pattern recognition and analysis of both
auditory experiences. Studying the activities of auditory neurons in
humans is not easy, however.
Most of what neuroscientists know comes from studies of how
individual neurons respond in nonhuman primates. Both human and
nonhuman primates have a ventral and dorsal cortical pathway for
audition. Neurons in the ventral pathway decode spectrally complex
sounds—referred to by some investigators as auditory object recognition
—including the meaning of speech sounds for people and species-typical
vocalizations in monkeys (for a review, see Rauschecker, 2012). Less is
known about the properties of neurons in the dorsal auditory stream, but
this path clearly has a role in integrating auditory and somatosensory
information to control speech production. We could call it audition for
action.

Art Wolfe/Getty Images

Wayne Lynch/All Canada Photos/Getty Images
FIGURE 10-17 Hunting by Ear Left: In the dark, a barn owl aligns its
talons with the body axis of the mouse it is about to catch. Center: The
owl’s facial ruff collects and funnels sound waves into ear canal openings
through tightly feathered troughs above and below the eyes. The owl’s left
ear is more sensitive to sound waves from the left and below because the
ear canal is higher on the left side and the trough is tilted down. The right-
side ear canal is lower and the trough tilts up, making the right ear more
 sensitive to sound waves from the right and above. Right: The boreal owl’s
asymmetric skull produces a similar auditory asymmetry. Information
from E. I. Knudsen (1981). The hearing of the barn owl. Scientific
American, 245 (6), p. 115.

Audition for action parallels unconscious visually guided

movements by the dorsal stream; see Figure 9-42 .
 10-3 REVIEW

Neural Activity and Hearing

Before you continue, check your understanding.
1 . Bipolar neurons in the cochlea form ___________ maps that code
sound wave frequencies.
2 . Loudness is decoded by the firing rate of cells in the _____________.
3 . Detecting the location of a sound is a function of neurons in the
____________ and ____________ of the brainstem.
4 . The function of the dorsal auditory pathway can be described as
___________.
5 . Explain how the brain detects a sound’s location.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 10-4 Anatomy of Language and Music
This chapter began with the evolutionary implications of discovering a
flute made by Neanderthals (see Focus 10-1). That Neanderthals made
flutes implies not only that they processed musical sound wave patterns
but also that they made music. In our brain, musical ability is generally a
right-hemisphere specialization complementary to language ability,
lateralized to the left hemisphere in most people.
No one knows whether these complementary systems evolved
together in the hominid brain, but it is highly likely. Language and music
abilities are highly developed in the modern human brain. Although little
is known about how each is processed at the cellular level, electrical
stimulation and recording and blood flow imaging studies yield
important insights into the cortical regions that process them. We
investigate such studies next, focusing first on how the brain processes
language.
Section 7-4 surveys functional brain imaging methods; Section 7-2
reviews methods for measuring its electrical activity.

Processing Language
An estimated 5000 to 7000 human languages are spoken in the world
today, and probably many more have gone extinct in past millennia.
Researchers have wondered whether the brain has a single system for
understanding and producing any language, regardless of its structure, or
whether disparate languages, such as English and Japanese, are
processed differently. To answer this question, it helps to analyze
languages to determine just how fundamentally similar they are, despite
their obvious differences.
Uniformity of Language Structure
Foreign languages often seem impossibly complex to those who do not
speak them. Their sounds alone may seem odd and difficult to make. If
you are a native English speaker, for instance, Asian languages, such as
Japanese, probably sound especially melodic and almost without obvious
consonants to you, whereas European languages, such as German or
Dutch, may sound heavily guttural.
 Even within such related languages as Spanish, Italian, and French,
marked differences can make learning one of them challenging, even if
the student already knows another. Yet as real as all these linguistic
differences may be, they are superficial. The similarities among human
languages, although not immediately apparent, are actually far more
fundamental than their differences.
Noam Chomsky (1965) is usually credited as the first linguist to stress
similarities over differences in human language structure. In a series of
books and papers written over the past half-century, Chomsky has made
a sweeping claim, as have researchers such as Steven Pinker (1997) more
recently. They argue that all languages have common structural
characteristics stemming from a genetically determined constraint, and
these common characteristics form the basis of universal grammar
theory. Humans, apparently, have a built-in capacity for learning and
using language, just as we have for walking upright.
Chomsky was greeted with deep skepticism when he first proposed
this idea in the 1960s, but it has since become clear that the capacity for
human language is indeed genetic. An obvious piece of evidence:
language is universal in human populations. All people everywhere use
language.
A language’s complexity is unrelated to its culture’s technological
complexity. The languages of technologically unsophisticated peoples
are every bit as complex and elegant as the languages of postindustrial
cultures. Nor is the English of Shakespeare’s time inferior or superior to
today’s English; it is just different.
Another piece of evidence that Chomsky adherents cite for the genetic
basis of human language is that humans learn language early in life and
seemingly without effort. By about 12 months of age, children
everywhere have started to speak words. By 18 months, they are
combining words, and by age 3 years, they have a rich language
capability.
Perhaps the most amazing thing about language development is that
children are not formally taught the structure of their language, just as
they are not taught to crawl or walk. They just do it. As toddlers, they are
not painstakingly instructed in the rules of grammar. In fact, their early
errors—sentences such as “I goed to the zoo”—are seldom even
corrected by adults. Yet children master language rapidly. They also
acquire language through a series of stages that are remarkably similar
across cultures. Indeed, the process of language acquisition plays an
important role in Chomsky’s theory of its innateness—which is not to
say that language development is not influenced by experience.
At the most basic level, children learn the language or languages that
they hear spoken. In an English household, they learn English; in a
Japanese home, Japanese. They also pick up the language structure—the
vocabulary and grammar—of the people around them, even though that
structure can vary from one speaker to another. Children go through a
sensitive period for language acquisition, probably from about 1 to 6
years of age. If they are not exposed to language throughout this critical
period, their language skills are severely compromised. If children learn
two languages simultaneously, the two share the same part of Broca’s
area. In fact, their neural representations overlap (Kim et al., 1997).
Both its universality and natural acquisition favor the theory for a
genetic basis of human language. A third piece of evidence is the many
basic structural elements common to all languages. Granted, every
language has its own particular grammatical rules specifying exactly
how various parts of speech are positioned in a sentence (syntax), how
words are inflected to convey different meanings, and so forth. But an
overarching set of rules also applies to all human languages, and the first
rule is that there are rules.
For instance, all languages employ parts of speech that we call
subjects, verbs, and direct objects. Consider the sentence Jane ate the
apple. Jane is the subject, ate is the verb, and apple is the direct object.
Syntax is not specified by any universal rule but rather is a characteristic
of the particular language. In English, syntactical order (usually) is
subject, verb, object; in Japanese, the order is subject, object, verb; in
Gaelic, the order is verb, subject, object. Nonetheless, all have both
syntax and grammar.
The existence of these two structural pillars in all human languages is
seen in the phenomenon of creolization —the development of a new
language from what was formerly a rudimentary language, or pidgin.
Creolization took place in the seventeenth century in the Americas when
slave traders and colonial plantation owners brought together, from
various parts of West Africa, people who lacked a common language.
The newly enslaved needed to communicate, and they quickly created a
pidgin based on whatever language the plantation owners spoke—
English, French, Spanish, or Portuguese.
 A 1-year-old’s 5- to 10-word vocabulary doubles in the next 6
months and by 36 months mushrooms to 1000 words; see Section 8-
3.
Focus 8-3 describes how cortical activation differs for second
languages learned later in life and Section 15-6 , research on
bilingualism and intelligence.
The pidgin had a crude syntax (word order) but lacked a real
grammatical structure. The children of the slaves who invented this
pidgin grew up with caretakers who spoke only pidgin to them. Yet
within a generation, these children had developed their own creole, a
language complete with a genuine syntax and grammar.
Clearly, the pidgin invented of necessity by adults was not a learnable
language for children. Their innate biology shaped a new language
similar in basic structure to all other human languages. All creolized
languages seem to evolve in a similar way, even though the base
languages are unrelated. This phenomenon can happen only because
there is an innate biological component to language development.
Localizing Language in the Brain
Finding a universal basic language structure set researchers on the search
for an innate brain system that underlies language use. By the late 1800s,
it had become clear that language functions were at least partly localized
—not just within the left hemisphere but to specific areas there. Clues
that led to this conclusion began to emerge early in the nineteenth
century, when neurologists observed patients with frontal lobe injuries
who had language difficulties.
Then, in 1861, the French physician Paul Broca confirmed that certain
language functions are localized in the left hemisphere. Broca concluded,
on the basis of several postmortem examinations, that language is
localized in the left frontal lobe, in a region just anterior to the central
fissure. A person with damage in this area is unable to speak despite both
an intact vocal apparatus and normal language comprehension. The
confirmation of Broca’s area was significant because it triggered the
idea that the left and right hemispheres might have different functions.
Broca’s area Anterior left hemisphere speech area that functions
with the motor cortex to produce movements needed for speaking.
 Other neurologists of the time believed that Broca’s area might be
only one of several left-hemisphere regions that control language. In
particular, they suspected a relation between hearing and speech. Proving
this suspicion correct, Karl Wernicke later described patients who had
difficulty comprehending language after injury to the posterior region of
the left temporal lobe, identified as Wernicke’s area in Figure 10-18 .
Section 7-1 links Broca’s observations to his contributions to
neuropsychology.

(A)

(B)
 FIGURE 10-18 Neurology of Language (A) In Wernicke’s model of
speech recognition, stored sound images are matched to spoken words in
the left posterior temporal cortex, shown in yellow. (B) Speech is produced
through the connection that the arcuate fasciculus makes between
Wernicke’s area and Broca’s area.

In Section 10-2 we identified Wernicke’s area as a speech zone (see

Figure 10-12 A). Damage to any speech area produces some form of
aphasia, the general term for any inability to comprehend or produce
language despite the presence of otherwise normal comprehension and
intact vocal mechanisms. At one extreme, people who suffer Wernicke’s
aphasia can speak fluently, but their language is confused and makes
little sense, as if they have no idea what they are saying. At the other
extreme, a person with Broca’s aphasia cannot speak despite normal
comprehension and intact physiology.
aphasia Inability to speak or comprehend language despite the
presence of normal comprehension and intact vocal mechanisms.
Broca’s aphasia is the inability to speak fluently despite the
presence of normal comprehension and intact vocal mechanisms.
Wernicke’s aphasia is the inability to understand or to produce
meaningful language even though word production remains intact.
Wernicke went on to propose a model, diagrammed in Figure 10-18
A, for how the two language areas of the left hemisphere interact to
produce speech. He theorized that images of words are encoded by their
sounds and stored in the left posterior temporal cortex. When we hear a
word that matches one of those sound images, we recognize it, which is
how Wernicke’s area contributes to speech comprehension.
To speak words, Broca’s area in the left frontal lobe must come into
play, because the motor program to produce each word is stored in this
area. Messages travel to Broca’s area from Wernicke’s area through the
arcuate fasciculus, a fiber pathway that connects the two regions.
Broca’s area in turn controls articulation of words by the vocal apparatus,
as diagrammed in Figure 10-18 B.
Wernicke’s model provided a simple explanation both for the
existence of two major language areas in the brain and for the
contribution each area makes to the control of language. But the model
was based on postmortem examinations of patients with brain lesions
that were often extensive. Not until neurosurgeon Wilder Penfield’s
pioneering studies, begun in the 1930s, were the left hemisphere
language areas clearly and accurately mapped.
Auditory and Speech Zones Mapped by Brain Stimulation
It turns out, among Penfield’s discoveries, that neither is Broca’s area the
independent site of speech production nor is Wernicke’s area the
independent site of language comprehension. Electrical stimulation of
either region disrupts both processes.
Penfield took advantage of the chance to map the brain’s auditory and
language areas when he operated on patients undergoing elective surgery
to treat epilepsy unresponsive to antiseizure medication. The goal of this
surgery is to remove tissues where the abnormal discharges are initiated
without damaging the areas responsible for linguistic ability or vital
sensory or motor functioning. To determine the locations of these critical
regions, Penfield used a weak electrical current to stimulate the brain
surface. By monitoring the patient’s responses during stimulation in
different locations, Penfield could map brain functions along the cortex.
Typically, two neurosurgeons perform the operation under local
anesthesia applied to the skin, skull, and dura mater (Penfield is shown
operating in Figure 10-19 A ) as a neurologist analyzes the
electroencephalogram in an adjacent room. Patients, who are awake, are
asked to contribute during the procedure, and the effects of brain
stimulation in specific regions can be determined in detail and mapped.
Penfield placed tiny numbered tickets on different parts of the brain’s
surface where the patient noted that stimulation had produced some
noticeable sensation or effect, producing the cortical map shown in
Figure 10-19 B.
When Penfield stimulated the auditory cortex, patients often reported
hearing such sounds as a ringing that sounded like a doorbell, a buzzing
noise, or a sound like birds chirping. This result is consistent with later
single-cell recordings from the auditory cortex in non-human primates.
Findings in these later studies showed that the auditory cortex
participates in pattern recognition.
Penfield also found that stimulation in area A1 seemed to produce
simple tones—ringing sounds, and so forth—whereas stimulation in the
adjacent auditory cortex (Wernicke’s area) was more apt to cause some
interpretation of a sound—ascription of a buzzing sound to a familiar
source such as a cricket, for instance. There was no difference in the
effects of stimulation of the left or right auditory cortex, and the patients
heard no words when the brain was stimulated.
Section 7-1 describes brain stimulation techniques used in
neuroscience research.

(A)
 (B)
FIGURE 10-19 Mapping Cortical Functions (A) Neurosurgery for
eligible epilepsy patients who failed to respond to antiseizure medications.
The patient is fully conscious, lying on his right side, and kept comfortable
with local anesthesia. Wilder Penfield stimulates discrete cortical areas in
the patient’s exposed left hemisphere. In the background, a neurologist
monitors an EEG recorded from each stimulated area to help identify the
epileptogenic focus. The anesthetist (seated) observes the patient’s
responses to the cortical stimulation. (B) A drawing overlies a photograph
of the patient’s exposed brain. The numbered tickets identify points
Penfield stimulated to map the cortex in this patient’s brain. At points 26,
27, and 28, a stimulating electrode disrupted speech. Point 26 presumably
is in Broca’s area, 27 is the motor cortex facial control area, and 28 is in
Wernicke’s area.

Sometimes, however, stimulation of the auditory cortex produced

effects other than sound perceptions. Stimulation of one area, for
example, might cause a patient to feel deaf, whereas stimulation of
another area might produce a distortion of sounds actually being heard.
As one patient exclaimed after a certain region had been stimulated,
“Everything you said was mixed up!”
Penfield was most interested in the effects of brain stimulation not on
simple sound wave processing but on language. He and later researchers
used electrical stimulation to identify four important cortical regions that
control language. The two classic regions—Broca’s area and Wernicke’s
area—are left-hemisphere regions. Located on both sides of the brain are
the other two major language use regions: the dorsal area of the frontal
lobes and the areas of the motor and somatosensory cortex that control
facial, tongue, and throat muscles and sensations. Although the effects
on speech vary depending on the region, stimulating any of them disrupts
speech in some way.
 Clearly, much of the left hemisphere takes part in audition. Figure 10-
20 shows those areas that Penfield found engaged in some way in
processing language. In fact, Penfield mapped cortical language areas in
two ways, first by disrupting speech, then by eliciting speech. Not
surprisingly, damage to any speech area produces some form of aphasia.
DISRUPTING SPEECH Penfield expected that electrical current might
disrupt ongoing speech by effectively short-circuiting the brain. To test
his hypothesis, he stimulated different cortical regions while the patient
was speaking. In fact, the speech disruptions took several forms,
including slurring, word confusion, and difficulty in finding the right
word. Such aphasias are detailed in Clinical Focus 10-4 , Left-
Hemisphere Dysfunction.
Electrical stimulation of the supplementary speech area on the
dorsal surface of the frontal lobe (shown in Figure 10-20 ) can even stop
ongoing speech completely, a reaction that Penfield called speech arrest.
Stimulation of other cortical regions far removed from the temporal and
frontal speech areas has no effect on ongoing speech, with the exception
of motor cortex regions, shown in Figure 10-20 , that control facial
movements. This exception makes sense because talking requires
movement of facial, tongue, and throat muscles.
supplementary speech area Speech production region on the left
frontal lobe dorsal surface.
FIGURE 10-20 Cortical Regions That Control Language
This map, based on Penfield’s extensive study, summarizes the left-
hemisphere areas where direct stimulation may disrupt speech or elicit
vocalization. Information from W. Penfield & L. Roberts (1956). Speech
and brain mechanisms (p. 201). London: Oxford University Press.
 CLINICAL FOCUS 10-4
Left-Hemisphere Dysfunction
Susan S., a 25-year-old college graduate and mother of two, had
epilepsy. When she had a seizure, which was almost every day, she
lost consciousness for a short period during which she often engaged
in repetitive behaviors, such as rocking back and forth.
Medication can usually control such seizures, but the drugs were
ineffective for Susan. The attacks disrupted her life: they prevented
her from driving and restricted the types of jobs she could hold. So
Susan decided to undergo neurosurgery to remove the region of
abnormal brain tissue that was causing the seizures.
The procedure has a high success rate. Susan’s surgery entailed
removal of a part of the left temporal lobe, including most of the
cortex in front of the auditory areas. Although it may seem a
substantial amount of the brain to cut away, the excised tissue is
usually abnormal, so any negative consequences typically are minor.
After the surgery, Susan did well for a few days; then she started
to have unexpected and unusual complications. As a result, she lost
the remainder of her left temporal lobe, including the auditory cortex
and Wernicke’s area. The extent of lost brain tissue resembles that
shown in the accompanying MRI.
Susan no longer understood language, except to respond to the
sound of her name and to speak just one phrase: I love you. Susan
was also unable to read, showing no sign that she could even
recognize her own name in writing.
To find ways to communicate with Susan, Bryan Kolb tried
humming nursery rhymes to her. She immediately recognized them
and could say the words. We also discovered that her singing skill
was well within the normal range and she had a considerable
repertoire of songs.
Susan did not seem able to learn new songs, however, and she did
not understand messages that were sung to her. Apparently, Susan’s
musical repertoire was stored and controlled independently of her
language system.
 Courtesy of George Jall Johns Hopkins Hospital

Postoperative MRI of a patient who has lost most of the left

hemisphere.

ELICITING SPEECH The second way Penfield mapped language

areas was to stimulate the cortex when a patient was not speaking. Here
the goal was to see if stimulation caused the person to utter a speech
sound. Penfield did not expect to trigger coherent speech; cortical
electrical stimulation is not physiologically normal and so probably
would not produce actual words or word combinations. His expectation
was borne out.
Stimulation of regions on both sides of the brain—for example, the
supplementary speech areas—produces a sustained vowel cry, such as
Oooh or Eee. Stimulation of the facial areas in the motor and
somatosensory cortices produces some vocalization related to mouth and
tongue movements. Stimulation outside these speech-related zones
produces no such effects.
Auditory Cortex Mapped by Positron Emission Tomography
To study the metabolic activity of brain cells engaged in tasks such as
processing language, researchers use PET, a brain-imaging technique
that detects changes in brain blood flow. Among the many PET studies
of auditory stimulation, a series conducted by Robert Zatorre and his
colleagues (1992, 1996) serves as a good example. These researchers
hypothesized that simple auditory stimulation, such as bursts of noise,
are analyzed by area A1, whereas more complex auditory stimulation,
such as speech syllables, are analyzed in adjacent secondary auditory
areas.
The researchers also hypothesized that performing a discrimination
task for speech sounds would selectively activate left-hemisphere
regions. This selective activation is exactly what they found. Figure 10-
21 A shows increased activity in the primary auditory cortex in response
to bursts of noise, whereas secondary auditory areas are activated by
speech syllables (Figure 10-21 B and C).
Section 7-4 details procedures used to obtain a PET scan.

(A) Listening to bursts of noise

(B) Listening to words

(C) Discriminating speech sounds

FIGURE 10-21 Cortical Activation in Language-Related
Tasks (A) Passively listening to noise bursts activates the primary
 auditory cortex. (B) Listening to words activates the posterior speech
zone, including Wernicke’s area. (C) Making a phonetic discrimination
activates the frontal region, including Broca’s area.

Both types of stimuli produced responses in both hemispheres but

with greater activation in the left hemisphere for the speech syllables.
These results imply that area A1 analyzes all incoming auditory signals,
speech and nonspeech, whereas the secondary auditory areas are
responsible for some higher-order signal processing required for
analyzing language sound patterns.
As Figure 10-21C shows, the speech sound discrimination task
yielded an intriguing additional result: Broca’s area in the left
hemisphere was also activated. This frontal lobe region’s involvement
during auditory analysis may seem surprising. In Wernicke’s model,
Broca’s area is considered the storage area for motor programs needed to
produce words. It is not usually a region thought of as a site of speech
sound discrimination.
A possible explanation is that to determine that the g in bag and the
one in pig are the same speech sound, the auditory stimulus must be
related to how the sound is actually articulated. That is, speech sound
perception requires a match with the motor behaviors associated with
making the sound.
This role for Broca’s area in speech analysis is confirmed further
when investigators ask people to determine whether a stimulus is a word
or a nonword (e.g., tid versus tin or gan versus tan ). In this type of
study, information about how the words are articulated is irrelevant, and
Broca’s area need not be recruited. Imaging reveals that it is not.

Processing Music
Although Penfield did not study the effect of brain stimulation on
musical analysis, many researchers study musical processing in brain-
damaged patients. Clinical Focus 10-5 , Cerebral Aneurysms, describes
one such case. Collectively, the results of these studies confirm that
musical processing is in fact largely a right-hemisphere specialization,
just as language processing is largely a left-hemisphere one.
Localizing Music in the Brain
A famous patient, the French composer Maurice Ravel (1875–1937),
provides an excellent example of right-hemisphere predominance for
music processing. Boléro is perhaps Ravel’s best-known work. At the
peak of his career, Ravel had a left-hemisphere stroke and developed
aphasia. Yet many of his musical skills remained intact post-stroke
because they were localized to the right hemisphere. He could still
recognize melodies, pick up tiny mistakes in music he heard, and even
judge the tuning of pianos. His music perception was largely intact.
Skills that had to do with producing music, however, were among
those destroyed. Ravel could no longer recognize written music, play the
piano, or compose. This dissociation of music perception and music
production may parallel the dissociation of speech comprehension and
speech production in language. Apparently, the left hemisphere plays at
least some role in certain aspects of music processing, especially those
that have to do with making music.
 CLINICAL Focus 10-5
Cerebral Aneurysms
C. N. was a 35-year-old nurse described by Isabelle Peretz and her
colleagues (1994). In December 1986, C. N. suddenly developed
severe neck pain and headache. A neurological examination revealed
an aneurysm in the middle cerebral artery on the right side of her
brain.
An aneurysm is a bulge in a blood vessel wall caused by
weakening of the tissue, much like the bulge that appears in a bicycle
tire at a weakened spot. Aneurysms in a cerebral artery are
dangerous: if they burst, severe bleeding and consequent brain
damage result.
In February 1987, C. N.’s aneurysm was surgically repaired, and
she appeared to have few adverse effects. Postoperative brain
imaging revealed, however, that a new aneurysm had formed in the
same location but in the middle cerebral artery on the opposite side
of the brain. This second aneurysm was repaired 2 weeks later.
After her surgery, C. N. had temporary difficulty finding the right
word when she spoke, but more important, her perception of music
was deranged. She could no longer sing, nor could she recognize
familiar tunes. In fact, singers sounded to her as if they were talking
instead of singing. But C. N. could still dance to music.
A brain scan revealed damage along the lateral fissure in both
temporal lobes. The damage did not include the primary auditory
cortex, nor did it include any part of the posterior speech zone. For
these reasons, C. N. could still recognize nonmusical sound patterns
and showed no evidence of language disturbance. This finding
reinforces the hypothesis that nonmusical sounds and speech sounds
are analyzed in parts of the brain separate from those that process
music.
 To find out more about how the brain carries out the perceptual side
of music processing, Zatorre and his colleagues (1994) conducted PET
studies. When participants listened simply to bursts of noise, Heschl’s
gyrus became activated (Figure 10-22 A ), but perception of melody
triggers major activation in the right-hemisphere auditory cortex lying in
front of Heschl’s gyrus (Figure 10-22 B), as well as minor activation in
the same left-hemisphere region (not shown).
In another test, participants listened to the same melodies. The
investigators asked them to indicate whether the pitch of the second note
was higher or lower than that of the first note. During this task, which
necessitates short-term memory of what was just heard, blood flow in the
right frontal lobe increased (Figure 10-22C ). As with language, then, the
frontal lobe plays a role in auditory analysis when short-term memory is
required. People with enhanced or impaired musical abilities show
differences in frontal lobe organization, as demonstrated in Research
Focus 10-6 , The Brain’s Music System.
As noted earlier, the capacity for language is innate. Sandra Trehub
and her colleagues (1999) showed that music may be innate as well, as
we hypothesized at the beginning of the chapter.
(A) Listening to bursts of noise

(B) Listening to melodies

(C) Comparing pitches
FIGURE 10-22 Cortical Activation in Music-Related
Tasks (A) Passively listening to bursts of noise activates Heschl’s
gyrus. (B) Listening to a melody activates the secondary auditory cortex.
(C) Making relative pitch judgments about two notes in each melody
activates a right frontal lobe area.
 RESEARCH FOCUS 10-6
The Brain’s Music System
Nonmusicians enjoy music and have musical ability. Musicians show
an enormous range of ability: some have perfect pitch and some do
not, for example. About 4 percent of the population is tone deaf.
Their difficulties, characterized as amusia —an inability to
distinguish between musical notes—are lifelong.
amusia Tone deafness—inability to distinguish between
musical notes.
Robert Zatorre and his colleagues (Bermudez et al., 2009; Hyde et
al., 2007) have used MRI to look at differences among the brains of
musicians, nonmusicians, and amusics. MRIs of the left and right
hemispheres show that compared to nonmusicians, musicians’
cortical thickness is greater in dorsolateral frontal and superior
temporal regions. Curiously, musicians with perfect pitch have
thinner cortex in the posterior part of the dorsolateral frontal lobe.
Thinner appears to be better for some music skills.
Compared to nonmusicians then, musicians with thicker than
normal cortex must have enhanced neural networks in the right-
hemisphere frontal–temporal system linked to performing musical
tasks. But thicker than normal cortex can bestow both advantage and
impairment.
Analysis of amusic participants’ brains showed thicker cortex in
the right frontal area and in the right auditory cortex regions. Some
abnormality in neuronal migration during brain development is
likely to have led to an excess of neurons in the right frontal–
temporal music pathway of the amusics. Their impaired music
cognition is the result.
 Compared to nonmusicians and amusics, musicians’
thicker cortex, shown in the green, yellow, and red areas,
contributes to performance. Focus 14-5 describes how
playing music can affect sensorimotor maps in the cortex.
Research from P. Bermudez, J. P. Lerch, A. C. Evans,
& R. J. Zatorre (2009). Neuroanatomical correlates of
musicianship as revealed by cortical thickness and
voxel-based morphometry. Cerebral Cortex, 7, 1583–
1596.

Trehub found that infants show learning preferences for musical scales
versus random notes. Like adults, children are sensitive to musical
errors, presumably because they are biased for perceiving regularity in
rhythms. Thus, it appears that the brain is prepared at birth for hearing
both music and language, and presumably it selectively attends to these
auditory signals.
The brain may be tuned prenatally to the language it will hear at
birth; see Focus 7-1.
At: https://www.youtube.com/watch?v=eNpoVeLfMKg , watch as
Parkinson patients step to the beat of music to improve their gait
length and walking speed.
More on music as therapy in Focus 5-2 and the dance class for
Parkinson patients pictured on page 160 . Sections 16-2 and 16-3
revisit music therapy.
Music as Therapy
The power of music to engage the brain has led to its use as a therapeutic
tool for brain dys-functions. The best evidence of its effectiveness lies in
studies of motor disorders such as stroke and Parkinson disease
(Johansson, 2012). Listening to rhythm activates the motor and premotor
cortex and can improve gait and arm training after stroke. Musical
experience reportedly also enhances the ability to discriminate speech
sounds and to distinguish speech from background noise in patients with
aphasia.
Music therapy also appears to be a useful complement to more
traditional therapies, especially when there are problems with mood,
such as in depression or brain injury. This may prove important in the
treatment of stroke and traumatic brain injury, with which depression is a
common complication in recovery. Music therapy also has positive
effects following major surgery, both in adults and children, by reducing
both their pain perception and the amount of pain medication they use
(Sunitha Suresh et al., 2015). With all these applications, perhaps
researchers will decide to use noninvasive imaging to determine which
brain areas music therapy recruits.
 10-4 REVIEW

Anatomy of Language and Music

Before you continue, check your understanding.
1 . The human auditory system has complementary specialization for the
perception of sounds: left for _________ and right for ____________.
2 . The three frontal lobe regions that participate in producing language
are __________, and _________, _________.
3 . _________ area identifies speech syllables and words and stores their
representations in that location.
4 . _________ area matches speech sounds to the motor programs
necessary to articulate them.
5 . At one end of the spectrum for musical ability are people with
_________ and at the other are people who are _________.
6 . What evidence supports the idea that language is innate?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Auditory Communication in
10-5

Nonhuman Species
Sound has survival value. You will appreciate this if you’ve ever
narrowly escaped becoming an accident statistic by crossing a busy
intersection on foot while listening to a music player or talking on a cell
phone. Audition is as important a sense to many animals as vision is to
humans. Many animals also communicate with other members of their
species by using sound, as humans do.
Here we consider just two types of auditory communication in
nonhumans: birdsong and echolocation. Each provides a model for
understanding different aspects of brain–behavior relations in which the
auditory system plays a role.

Birdsong
Of about 8500 living bird species, about half are considered songbirds.
Birdsong has many functions, including attracting mates (usually
employed by males), demarcating territories, and announcing location or
even just presence. Although all birds of the same species have a similar
song, the song’s details vary markedly from region to region, much as
dialects of the same human language vary.
Parallels Between Birdsong and Language
Figure 10-23 shows sound wave spectrograms for the songs of male
white-crowned sparrows that live in three localities near San Francisco.
These songs differ markedly from region to region. The differences stem
from the fact that song development in young birds is influenced not just
by genes but also by early experience and learning. Young birds that
have a good tutor can acquire more elaborate songs than can other
members of their species (Marler, 1991).
These gene–experience interactions are the result of epigenetic
mechanisms. For example, brain areas that control singing in adult song
sparrows show altered gene expression in spring as the breeding—and
singing—season begins (Thompson et al., 2012). Such studies have not
yet targeted young birds, but it is safe to predict that researchers will find
parallel changes.
 Birdsong and human language have broad similarities beyond
regional variation. Both appear to be innate yet are sculpted by
experience. Both are diverse and can vary in complexity. Humans seem
to have a basic template for language that is programmed into the brain,
and experience adds a variety of specific structural forms to this
template.
If a young bird is not exposed to song until it is a juvenile and then
listens to recordings of birdsongs of various species, the young bird
shows a general preference for its own species’ song. This preference
must mean that each bird has a species-specific song template in the
brain. As for language, experience modifies the details of this birdsong
template.

FIGURE 10-23 Birdsong Dialects The songs of male white-crowned

sparrows recorded in three locales around San Francisco Bay are similar,
but sound wave spectrograms reveal that the dialects differ. Like humans,
birds acquire regional dialects. Information from P. Marler (1991). The
instinct to learn. In S. Carey & R. German (Eds.), The epigenesis of
mind: Essays on biology and cognition (p. 39), Hillsdale, NJ:
Erlbaum.

Another broad similarity between birdsong and human language is

their great diversity. Among birds, diversity is apparent in the sheer
number of songs that a species possesses. Species such as the white-
crowned sparrow have but a single song; the marsh wren has as many as
150.
The number of syllables in birdsong also varies greatly, ranging from
30 for the canary to about 2000 for the brown thrasher. Similarly, even
though all modern human languages are equally complex, they vary
significantly in the type and number of elements they employ. The
number of meaningful patterns in speech sounds in human languages
ranges from about 15 for some Polynesian languages to about 100 for
some dialects spoken in the Caucasus Mountains. English has 24.
A final broad similarity between birdsong and human language lies in
how they develop. In many bird species, song development is heavily
influenced by experience during a critical period, just as language
development is in humans. Birds also go through stages in song
development, just as humans go through stages in language
development. Hatchlings make noises that attract their parents’ attention,
usually for feeding, and human babies emit cries to signal hunger, among
other things.
The fledgling begins to make noises that Charles Darwin compared to
the prespeech babbling of human infants. These noises, called subsong,
are variable in structure, low in volume, and often produced as the bird
appears to doze. Presumably, subsong, like human babbling, is practice
for the later development of adult communication after the bird has left
the nest.
As a young bird matures, it starts to produce sound wave patterns that
contain recognizable bits of the adult song. Finally, the adult song
emerges. In most species, the adult song remains remarkably stable,
although a few species, such as canaries, can develop a new song every
year that replaces the previous year’s song.
Neurobiology of Birdsong
The neurobiology of birdsong has been a topic of intense research, partly
because it provides an excellent model of brain changes that accompany
learning and partly because it offers insight into how sex hormones
influence behavior. In the 1970s, Fernando Nottebohm and his
colleagues first identified the major structures controlling birdsong,
illustrated in Figure 10-24 (Nottebohm & Arnold, 1976). The largest
structures are the higher vocal control center (HVC) and the nucleus
robustus archistriatalis (RA). The axons of the HVC connect to the RA,
which in turn sends axons to the 12th cranial nerve. This nerve controls
the muscles of the syrinx, the structure that actually produces the song.
The HVC and RA have several important and some familiar
characteristics:
• The structures are asymmetrical in some bird species, with those in the
left hemisphere larger than those on the right. In many cases, this
asymmetry is similar to the lateralized control of language in humans:
 if the left-hemisphere pathways are damaged, the bird stops singing,
but similar injury in the right hemisphere has no effect on song.
• Birdsong structures are sexually dimorphic, that is, much larger in
males than in females. In male canaries, the structures are five times as
large as in the female. This sex difference is due to the hormone
testosterone in males. Injection of testosterone into female birds causes
the song-controlling nuclei to increase in size.
• The size of the birdsong-controlling nuclei is related to singing skill.
Unusually talented singers among male canaries tend to have larger
HVCs and RAs than do less-gifted singers.
Shown in Figure 8-30 , a rare gyandromorph zebra finch exhibits
physical characteristics of both sexes.
• The HVC and RA contain cells that produce birdsong as well as cells
responsive to hearing song, especially the song of a bird’s own species.
The same structures therefore play a role in both song production and
song perception. This avian neural anatomy is comparable to the
overlapping roles of Broca’s and Wernicke’s areas in language
perception and production in humans.
KEY
Cell groups specialized for vocal learning
Cell groups specialized for vocal learning and adult song
 FIGURE 10-24 Avian Neuroanatomy Lateral view of the canary
brain shows several left-hemisphere nuclei that control song learning. Two
that are necessary both for adult singing and for learning the song are the
higher vocal control center (HVC) and the nucleus robustus archistriatalis
(RA). Other regions necessary for learning the song during development
but not required for adult singing include the dorsal archistriatum (Ad), the
lateral magnocellular nucleus of the anterior neostriatum (LMAN), area X
of the avian striatum, and the medial dorsolateral nucleus of the thalamus
(DLM).

Echolocation in Bats
Next to rodents, bats are the most numerous mammalian order. The two
general groups, or suborders, are the smaller bats (Microchiroptera) and
the larger fruit-eating and flower-visiting bats (Megachiroptera),
sometimes called flying foxes. Each uses a form of echolocation. Using
their wings to make clicking sounds, Megachiroptera can detect large
surfaces and orient in complete darkness. This rudimentary form of
echolocation may be the forerunner of the highly evolved throat
(laryngeal) system used in a sophisticated way by the Microchiroptera to
navigate, hunt, and communicate using sound waves (Boonman et al.,
2014).
Most of the 680 species of Microchiroptera feed on insects. Others
live on blood (vampire bats), and some catch frogs, lizards, fishes, birds,
and small mammals. These bats’ auditory system is highly specialized to
use echolocation not only to locate targets in the dark but also to analyze
the targets’ features as well as environmental features in general.
Through echolocation, these bats identify prey, navigate through the
leaves of trees, and locate suitable landing surfaces. Echolocation in the
Microchiroptera works rather like sonar. The bat larynx emits bursts of
sound waves at ultrasonic frequencies. The waves bounce off objects and
return to the bat’s ears, allowing the animal to identify what is in the
surrounding environment. The bat, in other words, navigates by the
echoes it hears, differentiating among the various characteristics of the
echoes.
echolocation Identifying and locating an object by bouncing sound
waves off it.
Moving objects (such as insects) give off a moving echo, smooth
objects a different echo from rough objects, and so on. A key component
of the bats’ echolocation system is analysis of differences in echo return
times. Close objects return echoes sooner than more distant objects do,
and the textures of various objects’ surfaces impose minute differences
in return times.
A bat’s cries are short (ranging from 0.3 to 200 milliseconds) and
high frequency (12,000 to 200,000 Hz, charted in Figure 10-4 ). Most of
this range lies at too high a frequency for the human ear to detect.
Different bat species produce sound waves of different frequencies that
depend on the animal’s ecology. Bats that catch prey in the open use
different frequencies from those used by bats that catch insects in foliage
and from those used by bats that hunt prey on the ground.
The echolocation abilities of bats are phenomenal, as shown in Figure
10-25 . Bats in the wild can be trained to catch small food particles
thrown up into the air in the dark. These echolocating skills make the bat
a most efficient hunter. The little brown bat, for instance, can capture
tiny flying insects, such as mosquitoes, at the remarkable rate of two per
second.
Researchers have considerable interest in the neural mechanisms of
bat echolocation. Each species emits sound waves in a relatively narrow
frequency range, and a bat’s auditory pathway has cells specifically
tuned to echoes in its species’ frequency range. For example, the
mustached bat sends out sound waves ranging from 60,000 to 62,000 Hz,
and its auditory system has a cochlear fovea (a maximally sensitive area
in the organ of Corti) that corresponds to that frequency range.
In this way, more neurons are dedicated to the frequency range used
for echolocation than to any other range of frequencies. Analogously, our
visual system dedicates more neurons to the retina’s fovea, the area
responsible for our most detailed vision. In the cortex of the bat’s brain,
several distinct areas process complex echoic inputs. One area computes
the distance of given targets from the animal, for instance, whereas
another area computes the velocity of a moving target. This neural
system makes the bat exquisitely adapted for nighttime navigation.
Dolphins use an auditory strategy similar to bats, but in water. Focus
10-2 profiles human echolocators.

Microchiroptera
 Megachiroptera

Figure 9-2 details the fovea’s structure.

© Rolf Nussbaumer/imageBRO KER
FIGURE 10-25 Born with Sonar Based entirely on auditory
information, a bat with a 40-centimeter wingspan can navigate through
openings in a 14-by-14-centimeter mesh made of 80-millimeter nylon
thread while flying in total darkness.
 10-5 REVIEW

Auditory Communication in
Nonhuman Species
Before you continue, check your understanding.
1 . Song development in young birds is influenced both by genes and by
early experience and learning, interactions indicative of _________.
2 . In many bird species the control of song in the brain is lateralized to
the _________ hemisphere.
3 . Bats use _________ to locate prey in the dark. This system is much
like the _________ that ships use to locate underwater objects.
4 . What does the presence of dialects in birdsong in the same species
demonstrate?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
SUMMARY
Although we take language and music for granted, both play central roles
in our mental lives and in our social lives. Language and music provide
us ways to communicate with other people—and with ourselves. They
facilitate social identification, parenting, and cultural transmission.
10-1 Sound Waves: The Stimulus for Audition
The stimulus for the auditory system is the mechanical energy of sound
waves that results from changes in air pressure. The ear transduces three
fundamental physical qualities of sound wave energy: frequency
(repetition rate), amplitude (size), and complexity. Perceptually, neural
networks then translate these energies into the pitch, loudness, and
timbre of the sounds that we hear.
10-2 Functional Anatomy of the Auditory System
Beginning in the ear, mechanical and electrochemical systems combine
to transform sound waves into auditory perceptions—what we hear.
Changes in air pressure are conveyed in a mechanical chain reaction
from the eardrum to the bones of the middle ear to the oval window of
the cochlea and the cochlear fluid that lies behind it in the inner ear.
Movements of the cochlear fluid produce movements in specific regions
of the basilar membrane, leading to changes in the electrochemical
activity of the auditory receptors, the inner hair cells on the basilar
membrane that send neural impulses through the auditory nerve into the
brain.
10-3 Neural Activity and Hearing
The basilar membrane has a tonotopic organization. High-frequency
sound waves maximally stimulate hair cells at the base, whereas low-
frequency sound waves maximally stimulate hair cells at the apex,
enabling cochlear neurons to code sound frequencies.
Tonotopic organization analyzes sound waves at all levels of the
auditory system, which also detects both amplitude and location. The
firing rate of cochlear neurons codes sound amplitude, with louder
sounds producing higher firing rates than softer sounds do. Location is
detected by structures in the brainstem that compute differences in the
arrival times and loudness of a sound in the two ears.
 Cochlear hair cells synapse with bipolar neurons that form the
cochlear nerve, which in turn forms part of the eighth cranial nerve. The
cochlear nerve takes auditory information to three structures in the
hindbrain: the cochlear nucleus, the superior olive, and the trapezoid
body. Cells in these areas are sensitive to differences in both sound wave
intensity and arrival times at the two ears. In this way, they enable the
brain to locate a sound.
The auditory pathway continues from the hindbrain areas to the
inferior colliculus of the midbrain, then to the medial geniculate nucleus
in the thalamus, and finally to the auditory cortex. As for vision, dorsal
and ventral pathways exist in the auditory cortex, one for pattern
recognition and the other for controlling movements in auditory space.
Cells in the cortex are responsive to specific sound categories, such as
species-specific communication.
10-4 Anatomy of Language and Music
Despite differences in the patterns and structures of speech sounds, all
human languages have the same basic foundation: syntax and grammar,
which implies an innate template for creating language. Auditory areas
of the left hemisphere cortex play a special role in analyzing language-
related information, whereas those in the right hemisphere play a special
role in analyzing music-related information. The right temporal lobe also
analyzes prosody, the melodic qualities of speech.
Among several left-hemisphere language-processing areas,
Wernicke’s area identifies speech syllables and words and so is critically
engaged in speech comprehension. Broca’s area matches speech sound
patterns to the motor behaviors necessary to make them and so plays a
major role in speech production. Broca’s area also discriminates between
closely related speech sounds. Aphasias are an inability to speak
(Broca’s aphasia) or to comprehend language (Wernicke’s aphasia)
despite the presence of normal cognition and intact vocal mechanisms.
Auditory analysis of music draws more on right-hemisphere activity
than on the left. Nor is music production localized to the right
hemisphere: it recruits the left hemisphere as well. Music perception
engages both the right temporal and frontal regions.
Music’s power to engage both right- and left-hemisphere activity
makes it a powerful tool for engaging the injured or dysfunctioning
brain. Music therapy is playing an increasingly important role in
treatment.
10-5 Auditory Communication in Nonhuman Species
Nonhuman animals have evolved specialized auditory structures and
behaviors. Regions of songbirds’ brains are specialized for producing
and comprehending song. In many species, these regions are lateralized
to the left hemisphere, analogous in a way to how language areas are
lateralized to the left hemisphere in most humans. Similarities in the
development of song in birds and the development of language in
humans, as well as similarities in the neural mechanisms underlying both
the production and the perception of birdsong and language, are striking.
Both owls and bats can fly and catch prey at night using only auditory
information to guide their movement. Bats evolved a type of biosonar
that allows them to map the objects in their auditory world, as humans
map their visual worlds. Although some blind humans employ this
strategy, the mainly auditory reality of bats, dolphins, and other
echolocators is one most people can only try to imagine.
KEY TERMS
aphasia, p. 343
amplitude, p. 325
amusia, p. 348
basilar membrane, p. 331
Broca’s area, p. 343
cochlea, p. 329
cochlear implant, p. 337
decibel (dB), p. 325
echolocation, p. 351
frequency, p. 323
hair cell, p. 331
hertz (Hz), p. 323
insula, p. 335
lateralization, p. 335
medial geniculate nucleus, p. 333
ossicle, p. 329
otoacoustic emissions, p. 333
primary auditory cortex (area A1), p. 333
prosody, p. 329
sound wave, p. 323
supplementary speech area, p. 345
tonotopic representation, p. 337
Wernicke’s area, p. 335

Visit Launch Pad to access the e-Book, videos, Learning Cur

✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

11

How Does the Nervous

System Respond to
Stimulation and Produce
Movement?
Katherine Streeter

RESEARCH FOCUS 11-1 NEUROPROSTHETICS

11-1 A HIERARCHY OF MOVEMENT CONTROL
THE BASICS RELATING THE SOMATOSENSORY AND MOTOR
SYSTEMS
FOREBRAIN: INITIATING MOVEMENT
EXPERIMENTAL EVIDENCE FOR A MOVEMENT HIERARCHY
BRAINSTEM: SPECIES-TYPICAL MOVEMENT
EXPERIMENT 11-1 QUESTION: WHAT ARE THE EFFECTS OF
BRAINSTEM STIMULATION UNDER DIFFERENT CONDITIONS?
CLINICAL FOCUS 11-2 CEREBRAL PALSY
SPINAL CORD: EXECUTING MOVEMENT
CLINICAL FOCUS 11-3 SPINAL CORD INJURY
11-2 MOTOR SYSTEM ORGANIZATION
MOTOR CORTEX
MOTOR CORTEX AND SKILLED MOVEMENT
EXPERIMENT 11-2 QUESTION: HOW DOES THE MOTOR
CORTEX TAKE PART IN THE CONTROL OF MOVEMENT?
PLASTICITY IN THE MOTOR CORTEX
EXPERIMENT 11-3 QUESTION: WHAT IS THE EFFECT OF
REHABILITATION ON THE CORTICAL REPRESENTATION OF
THE FORELIMB AFTER BRAIN DAMAGE?
CORTICOSPINAL TRACTS
MOTOR NEURONS
CONTROL OF MUSCLES
11-3 BASAL GANGLIA, CEREBELLUM, AND MOVEMENT
BASAL GANGLIA AND THE FORCE OF MOVEMENT
CLINICAL FOCUS 11-4 TOURETTE SYNDROME
CEREBELLUM AND MOVEMENT SKILL
EXPERIMENT 11-4 QUESTION: DOES THE CEREBELLUM HELP
TO MAKE ADJUSTMENTS REQUIRED TO KEEP MOVEMENTS
ACCURATE?
11-4 SOMATOSENSORY SYSTEM RECEPTORS AND
PATHWAYS
SOMATOSENSORY RECEPTORS AND PERCEPTION
POSTERIOR ROOT GANGLION NEURONS
SOMATOSENSORY PATHWAYS TO THE BRAIN
SPINAL REFLEXES
FEELING AND TREATING PAIN
RESEARCH FOCUS 11-5 PHANTOM LIMB PAIN
VESTIBULAR SYSTEM AND BALANCE
11-5 EXPLORING THE SOMATOSENSORY CORTEX
SOMATOSENSORY HOMUNCULUS
RESEARCH FOCUS 11-6 TICKLING
EFFECTS OF SOMATOSENSORY CORTEX DAMAGE
SOMATOSENSORY CORTEX AND COMPLEX MOVEMENT
RESEARCH FOCUS 1-1

Neuroprosthetics
Most of us seamlessly control the approximately 650 muscles that
move our bodies. But if the motor neurons that control those muscles
no longer connect to them, as happens in amyotrophic lateral sclerosis
(ALS, or Lou Gehrig disease), movement, and eventually breathing,
become impossible.
This happened to Scott Mackler, a neuroscientist and marathon
runner, in his late 30s. Dependent on a respirator to breathe, he
developed locked-in syndrome: Mackler lost virtually all ability to
communicate.
ALS has no cure, and death often occurs within 5 years of diagnosis.
Yet Scott Mackler beat the odds: he survived for 17 years before he
died in 2013 at age 55. Mackler beat locked-in syndrome too, by
learning to translate his mental activity into movement. He returned to
work at the University of Pennsylvania, stayed in touch with family and
friends, and even gave an interview to CBS’s 60 Minutes in 2008.
Mackler was a pioneer in brain–computer interface (BCI)
technology. BCIs employ the brain’s electrical signals to direct
computer-controlled devices. BCIs are one area of neuroprosthetics,
development of computer-assisted devices to replace lost biological
function.
neuroprosthetics Field that develops computer-assisted devices to
replace lost biological function.
A computer –brain interface (CBI) employs electrical signals from a
computer to instruct the brain. Cochlear implants that deliver sound-
related signals to the inner ear to allow hearing are CBIs. Brain–
computer–brain interfaces (BCBIs) combine the BCI and CBI
approaches. BCBIs enable the brain to command robotic devices that
provide it sensory feedback.
In 2008, Mackler’s BCI took up to 20 s to execute a single
command. Today’s devices enhance processing speed and increase
signal precision by using electrodes placed directly adjacent to brain
cells in arrays that interface with thousands of cells. Experimental
approaches use optogenetics, incorporating light-sensitive channels into
cortical motor and sensory neurons. Light signals are faster than
electrical signals and produce less tissue damage.
BCBIs command robotic hands to grasp objects while tactile
receptors on the robot are delivering touch and other sensory
information to the user. BCBIs in development also control exoskeletal
devices that reach and walk and return touch, body position, and
balance information to guide movement. In essence, BCBIs use
variations in CNS activity to generate signals. It is unlikely, however,
that in doing so they employ the signaling codes normally used by the
brain in producing behavior (Daly & Huggins, 2015).
 © Lifehand2, PatriziaTocci
Brain–computer–brain interfaces such as the robotic limb shown here enable
the brain to command robotic devices that provide it sensory feedback.

Movement is a defining feature of animals, and this chapter explores how

the nervous system produces movement. The body senses are more closely
related to movement than are the other senses. This chapter also describes
how somatic sensation and movement interact at different levels of the
nervous system.
Section 1-1 offers a simple definition of behavior: any movement in a
living organism.
At the level of the spinal cord, somatosensory information contributes to
motor reflexes. In the brainstem, it contributes to movement timing and
control. In the cerebrum, it contributes to complex voluntary movements.
Indeed, for many functions, the other senses work through the
somatosensory system to produce movement. If the motor system is a
vehicle and the somatosensory system is the driver, the other sensory
systems act like backseat drivers.
We first consider how movement is organized in the central nervous
system, then turn to how the somatic senses contribute to movement and
balance. If you want to review how the motor system and somatic sensation
interact before you read on, turn to The Basics: Relating the Somatosensory
and Motor Systems, on pages 358 –359 .
We begin here with movement and end with sensation. Section 4-4
begins with sensation and ends with movement.
 11-1 A Hierarchy of Movement Control
Our movements feature at least two categories of action. First we decide
on a goal and choose how to achieve it; then we make moves to reach the
goal. As we move, we correct movement errors that direct us away from
our goal. What are the neural bases of these choices? What neural bases
enable the motor system to produce our movements?
The major components of our motor system are the cerebrum
(forebrain), the brainstem, and the spinal cord. The cerebrum contributes
to our conscious control of movement, while the brainstem and spinal
cord direct our movements. In the face of impaired brainstem or spinal
cord function, the forebrain can imagine movement but can no longer
produce it. Neuroprosthetic devices, described in Research Focus 11-1 ,
can replace the movement production function provided by the brainstem
and spinal cord and restore forebrain control.
Getting from decisions to movements involves most of our nervous
system. Figure 11-1 illustrates the stepwise sequence your CNS
performs in the seemingly simple act of directing your hand to pick up a
cup. Once you decide to pick it up, you visually inspect it to determine
what part to grasp. The visual cortex relays this information through the
cortical somatosensory regions to the motor regions that plan and initiate
the movement. Only then does the brain send instructions to the spinal
cord segments that control your arm and hand muscles.
As you grasp the cup’s handle, information from sensory receptors in
your fingers aids in adjusting your grip and sends information back
through the spinal cord to the somatosensory cortex and from there to the
motor cortex to confirm that the act is complete—you are holding the
cup. Other brain regions also participate in controlling the movement.
The subcortical basal ganglia help to produce the appropriate amount of
force for grasping the cup handle, while in the brainstem, the cerebellum
helps to regulate the movement‘s timing and accuracy.
Clearly, the movement involved in picking up a cup involves
widespread CNS regions. The action also requires that higher-function
regions, including those that participate in deciding to pick up the cup,
work through and influence the actions of lower functional areas.
Remarkably, once you have made the decision to pick up the cup, most
of the movement happens automatically, without conscious control. Few
of us can describe the sequence of actions or produce an accurate
pantomime of the movements we make to actually grasp a cup, although
we have performed the action thousands of times (Davarpanah et al.,
2015). To understand how these CNS regions work together to produce
decisions and movements, we now consider the major components of the
hierarchy, starting with the forebrain.
For now, remember that the entire sensorimotor system is organized
hierarchically. When you reach the chapter’s end, review Figure 11-
1 to reinforce what you’ve learned.

FIGURE 11-1 Sequentially Organized Movement

 THE BASICS

Relating the Somatosensory and

Motor Systems
The intimate relationship between the motor and somatosensory
systems is apparent in their close anatomical relationships. Afferent
somatosensory information travels from the body inward via the
somatic nervous system. Movement information travels out of the
central nervous system via a parallel efferent motor system.
As diagrammed in Information Flow, when you step on a tack,
the sensory signals transmitted by the SNS from the body through
the spinal cord and into the brain are afferent. Efferent signals from
the CNS trigger a motor response: you lift your foot.
The spinal cord connects the somatosensory and motor systems
throughout the CNS. Connections Between the Nerves and the Spine
shows the spinal cord in cross section. In the outer part, which
consists of white matter, posterior tracts are sensory and anterior
tracts are motor, with some exceptions. The inner cord is gray matter
composed largely of cell bodies and shaped like a butterfly.
SNS nerves entering the spinal cord’s posterior side carry
information inward from the body’s sensory receptors and merge
into a posterior root as the fibers enter a spinal cord segment of the
CNS. Fibers leaving the spinal cord’s anterior side carry information
out from the spinal cord to the muscles. They, too, bundle together
as the fibers exit the spinal cord, forming an anterior root. (Bundles
of nerve fibers within the CNS are called tracts; outside the CNS
they are called nerves. )
 Information Flow

Connections Between the Nerves and the Spine

The spinal cord lies within a series of small bones called

vertebrae categorized into the five anatomical regions diagrammed
on the left in Spinal Segments and Dermatomes. Each spinal
segment corresponds to a region of body surface called a dermatome
(literally, skin cut ), shown on the right. From top to bottom, the
cervical, thoracic, lumbar, sacral, and coccygeal regions are
identified by spinal segment number: C5 (cervical segment 5) at the
base of the neck, for example, and L2 in the lower back.
 Body and nervous system segmentation has a long evolutionary
history that can be seen in spineless worms as well as in vertebrates.
The cervical and lumbar dermatomes represent the human forelimbs
and hind limbs. Their arrangement is sequential if you imagine a
human on all fours.
Layering in the Neocortex plumbs the depths of the primary
motor cortex (shown in blue) and adjacent sensory (red) cortical
regions. Viewed through a microscope, the six cortical layers differ
in appearance, characteristics, and functions. Layer IV is relatively
thick in the sensory cortex but relatively thin in the motor cortex.
Layer V is relatively thick in the motor cortex and relatively thin in
the sensory cortex. Cortical layer IV is afferent and layer V is
efferent, and that makes sense: sensory regions have a large input
layer and motor regions, a large output layer.

Spinal Segments and Dermatomes

 Layering in the Neocortex

Recall the principle from Section 2-6 : The CNS functions on

multiple levels.

Forebrain: Initiating Movement

Complex movements consist of many acts. Consider playing
basketball. At every moment, players must make decisions and perform
actions. Dribble, pass, and shoot are different movement categories, and
each can be performed in many ways. Skilled players choose among the
categories effortlessly and blend them together seemingly without
thought.
An early explanation for control of such complex movements centered
on feedback: after we act, we wait for feedback about how well the action
has succeeded, then make the next movement. The pioneering
neuroscience researcher Karl Lashley (1951), in the article “The Problem
of Serial Order in Behavior,” found fault with this explanation.
Lashley experimented for three decades to find the location of
memory in the brain. He failed.
 Lashley realized that we perform skilled movements too quickly to
rely on feedback about one movement before shaping the next. The time
required to receive feedback about the first movement combined with the
time needed to develop a plan for the subsequent movement and send a
corresponding message to muscles is simply too long for effective action.
Lashley argued that movements must be performed as motor sequences,
with the next sequence held in readiness while the ongoing one is under
way.
motor sequence Movement modules preprogrammed by the brain
and produced as a unit.
All complex behaviors, including speaking, piano playing, and playing
basketball, require selecting and executing multiple movements as
sequences. Most of our motor learning is mastering sequences of action.
As one sequence is being executed, the next sequence is being prepared to
follow the first smoothly. The act of speaking illustrates this activity.
When people use complex rather than simple word sequences, they are
more likely to pause and make umm and ahh sounds, suggesting that it is
taking them more time than usual to organize their speech sequences.
Initiating a Motor Sequence
The frontal lobes are responsible for planning and initiating motor
sequences. Each frontal lobe is divided into several hierarchically
arranged motor regions, including the three illustrated in Figure 11-2 .
From front to back, they are prefrontal cortex, premotor cortex, and
primary motor cortex.
FIGURE 11-2 Initiating a Motor Sequence
PREFRONTAL CORTEX Atop the hierarchy, the prefrontal cortex
(PFC) plans our behavior. Deciding to get up at a certain hour to arrive at
work on time, to stop at the library to return a book, even whether a
behavior is right or wrong and whether it should be performed at all are
examples. Humans with PFC injury often break social and legal rules not
because they do not know the rules or the consequences of breaking them
but because their decision making is faulty. The PFC does not specify the
precise movements to be made. It simply specifies the goal.
PREMOTOR CORTEX To bring a plan to completion, the prefrontal
cortex sends instructions to the premotor cortex, which produces
movements coordinating many body parts. If the premotor cortex is
damaged, sequences cannot be coordinated and goals cannot be
accomplished. For example, the monkey on the right in Figure 11-3 has a
lesion in the dorsal premotor cortex. The monkey has been given the task
of extracting a piece of food wedged in a hole in a table (Brinkman,
1984).
Sections 12-4 and 15-2 explore cognitive deficits caused by frontal
lobe injury.
The monkey simply pushes the food with a finger. The food drops to
the floor and is lost. The monkey has to catch the food by holding a palm
beneath the hole as the food is being pushed out. But this brain-injured
animal is unable to make the two complementary movements together. It
can push the food with a finger and extend an open palm, but it cannot
coordinate the action of its two hands, as the healthy monkey on the left
can.
Recall the principle from Section 2-6 : Brain circuits process
information hierarchically and in parallel.
PRIMARY MOTOR CORTEX The primary motor cortex (area M1)
specializes in producing focal skilled movements, such as those involving
our arms, hands, and mouth. To understand its role, consider the rich
array of movements we can use to grasp objects. We can hold them in one
hand, with two hands, or between a hand and another part of the body, for
example.
In using the precision pincer grip (Figure 11-4 A ), we hold an object
between the thumb and index finger. We can perform many precision
grips using the thumb and other fingers in opposition. The pincer grip not
only allows us to pick up small objects easily but also allows us to use
them with considerable skill. In contrast, when using a power grip (Figure
11-4 B), we hold an object with all our fingers and with more power but
fewer skilled options.

FIGURE 11-3 Premotor Control On a task requiring both hands, the

healthy monkey can push the peanut out of a hole with one hand and catch
it in the other, but 5 months after receiving a lesion of the premotor cortex,
the brain-injured monkey cannot. Information from C. Brinkman (1984). Supplementary
motor area of the monkey’s cerebral cortex: Short- and long-term effects after unilateral ablation
and the effects of subsequent callosal section. Journal of Neuroscience, 4, p. 925.

(A) Pincer grip

(B) Whole-hand grip
Ian Whishaw

FIGURE 11-4 Getting a Grip Figure 8-20 illustrates the development of

grasping responses in infants, from the whole-hand to the pincer grip.

People with damage to M1 have difficulty performing reaching

movements and shaping their fingers correctly to perform various hand
grasps. They also have difficulty performing many skilled hand, arm, and
trunk movements, bringing the hand to the mouth to feed themselves, and
in talking (Lang & Schieber, 2004).
Experimental Evidence for a Movement
Hierarchy
The frontal lobe regions in each hemisphere that plan, coordinate, and
execute different kinds of movements are hierarchically related. After the
prefrontal cortex formulates a plan of action, it instructs the premotor
cortex to organize the appropriate movement sequence, which the primary
motor cortex executes. This hierarchy is supported by findings from
studies of cerebral blood flow, which serves as an indicator of neural
activity. Figure 11-5 shows the brain regions that were active as the
participants in one such study performed various tasks (Roland, 1993).
As the participants use a finger to push a lever, increased blood flow is
limited to the primary somatosensory and primary motor cortex (Figure
11-5 A). As the participants execute a sequence of finger movements,
blood flow also increases in the premotor cortex (Figure 11-5 B). And as
the participants use a finger to trace their way through a maze, a task that
requires coordinated movements in relation to a goal, blood flow
increases in the prefrontal cortex as well (Figure 11-5C ). Notice that as
the participants were performing these tasks, relative blood flow
increased most in the regions taking part in the required movements
rather than throughout the frontal lobe.
Section 7-4 describes imaging methods that record and measure
blood flow in the brain.
(A) Simple movement
(B) Movement sequence
(C) Complex movement
FIGURE 11-5 Hierarchical Movement Control in the Brain Research from
P. E. Roland (1993). Brain Activation (p. 63). New York: Wiley-Liss.

Brainstem: Species-Typical Movement

In a series of studies, the Swiss neuroscientist Walter Hess (1957)
found that the brainstem controls species-typical behaviors, actions
displayed by every member of a species—the pecking of a robin, the
hissing of a cat, or the breaching of a whale. Species-typical movements,
then, are mainly innate and organized by brainstem neurons. Hess
developed the technique of implanting electrodes into the brains of cats
and other animals and cementing them in place. These electrodes could
then be attached to stimulating leads in the freely moving animal without
causing it much discomfort.
Section 1-5 introduces species-typical behavior, noting that
evolutionary principles apply across species but not to individuals
within a species.
 EXPERIMENT 11-1

Question: What are the effects of brainstem stimulation

under different conditions?
Procedures
Results

Electrical stimulation alone produces restless behavior.

Results

Electrical stimulation in the presence of a fist produces slight

threats.
Electrical stimulation in the presence of a stuffed polecat (a
type of weasel) produces vigorous threat.

Continued electrical stimulation in the presence of the stuffed

polecat produces flight and screeching.
Conclusion: Stimulation of some brainstem sites produces behavior that
depends on context, suggesting that an important function of the
brainstem is to produce appropriate species-typical behavior.
Information from The Collected Papers of Erich von Holst (p. 121), translated by R. Martin,
1973, Coral Gables, FL: University of Miami Press.

By stimulating the brainstem, Hess elicited the innate movements that

the animal might be expected to make. A resting cat could be induced to
suddenly leap up with an arched back and erect hair as though
frightened, for example, by an approaching dog. The elicited movements
began abruptly when the stimulating current was turned on and ended
equally abruptly when it was turned off. An animal performed such
species-typical behaviors in a subdued manner when the stimulating
current was low and displayed increased vigor as the stimulating current
was turned up.
The actions varied, depending on the brainstem site that was
stimulated. Stimulating some sites produced head turning; others,
walking or running; and still others elicited displays of aggression or
fear. The animal’s response to a particular stimulus could be modified
accordingly. For instance, when shown a stuffed toy, a cat responded to
electrical stimulation of some brainstem sites by stalking it and to
stimulation of other sites by showing fear and withdrawing.
Hess’s experiments have been confirmed and expanded on by other
researchers using many animal species. Experiment 11-1 shows the
effects of brainstem stimulation on a chicken under various conditions
(von Holst, 1973). Notice the effect of context: how the neural site
stimulated interacts both with the object presented and with the
stimulation’s duration.
 With stimulation at a certain site alone, the chicken displays only
restless behavior. When a fist is displayed, the same stimulation elicits
slightly threatening behavior. When the display switches from a fist to a
stuffed polecat, the chicken responds with vigorous threats. Finally, with
continued stimulation in the presence of the polecat, the chicken flees,
screeching.
Such experiments show that producing complex patterns of adaptive
behavior is an important brainstem function. These adaptive patterns
include movements used in eating and drinking and in sexual behavior.
Animals can be induced to display survival-related behaviors when
certain brainstem areas are stimulated. An animal can even be induced to
eat nonfood objects, such as chips of wood, if the part of the brainstem
that triggers chewing is stimulated.
Grooming illustrates how the brainstem coordinates complex action
patterns (Kalueff et al., 2007). A grooming rat sits back on its haunches,
licks its paws, wipes its nose with its paws, then wipes its paws across its
face, and finally turns to lick the fur on its body. These movements are
always performed in the same order, from the face to the shoulders and
then toward the rear of the body. The next time you dry off after a
shower or swimming, note the grooming sequence you use. Humans’
grooming sequence is very similar to the one rats use.
The brainstem is also important for maintaining posture, standing
upright, coordinating limb movements, swimming and walking,
grooming the fur, and making nests. The effects of damage to brainstem
regions that organize many adaptive movements can be seen in the
effects of locked-in syndrome, similar to those Scott Mackler
experienced in connection with ALS (see Research Focus 11-1 ,
Neuroprosthetics). The patient with locked-in syndrome is aware and
awake but cannot move or communicate verbally because nearly all
voluntary muscles except those of the eyes are completely paralyzed.
Focus 4-4 details ALS.
The effects of brainstem damage on behavior can also be seen in
cerebral palsy (CP), a disorder primarily of motor function: making
voluntary movements becomes difficult, whereas many aspects of
conscious behavior controlled by the cortex may remain intact. CP is
often caused by brainstem trauma before or shortly after birth. As
described in Clinical Focus 11-2 , Cerebral Palsy, trauma leading to
cerebral palsy can sometimes happen in early infancy as well. Advances
in neuroprosthetic technology, touch-screen technology, and remotely
controlled computers all signal important steps toward allowing people
with physical disabilities to become more independent.
locked-in syndrome Condition in which a patient is aware and
awake but cannot move or communicate verbally because of
complete paralysis of nearly all voluntary muscles except the eyes.
cerebral palsy Group of disorders that result from brain damage
acquired perinatally (at or near birth).
connectome Comprehensive map of the structural connectivity (the
physical wiring) of an organism’s nervous system.
CLINICAL FOCUS 11-2

Cerebral Palsy
E. S. had a cold and infection when he was about 6 months old.
Subsequently, he had great difficulty coordinating his movements.
As he grew up, his hands and legs were almost useless and his
speech was extremely difficult to understand. E. S. was considered
intellectually disabled and spent most of his childhood in a custodial
school.
When E. S. was 13 years old, the school bought a computer. One
teacher attempted to teach E. S. to use it by pushing the keys with a
pencil held in his mouth. Within a few weeks, the teacher realized
that E. S. was extremely intelligent and could communicate and
complete school assignments on the computer. He eventually
received a motorized wheelchair that he could control with finger
movements of his right hand.
Assisted by the computer and the wheelchair, E. S. soon became
almost self-sufficient and eventually attended college, where he
achieved excellent grades and became a student leader. On
graduation with a degree in psychology, he became a social worker
and worked with children with cerebral palsy.
William Little, an English physician, first noticed in 1853 that
difficult or abnormal births could lead to later motor difficulties in
children. The disorder that Little described was cerebral palsy (also
called Little disease), a group of disorders that result from brain
damage acquired perinatally (at or near birth). Cerebral palsy is
common worldwide, with an incidence estimated to be 1.5 in every
1000 births. Among surviving babies who weigh less than 2.5
kilograms at birth, the incidence is much higher—about 10 in 1000.
The most common causes of cerebral palsy are birth injury,
especially due to anoxia, a lack of oxygen, and genetic defects.
Anoxia may result from a defect in the placenta, the organ that
allows oxygen and nutrients to pass from mother to child in utero, or
it may be caused by a tangled umbilical cord that reduces the oxygen
supply to the infant during birth. Other causes include infections,
 hydrocephalus, seizures, and prematurity. All may produce a defect
in the immature brain before, during, or just after birth.
Most children with cerebral palsy appear healthy in the first few
months of life, but as the nervous system develops, motor
disturbances become progressively more noticeable. Common
symptoms include spasticity, an exaggerated contraction of muscles
when they are stretched; dyskinesia, involuntary extraneous
movements such as tremors and uncontrollable jerky twists (athetoid
movements); and rigidity, or resistance to passive movement.
Everyday movements are abnormal, and the affected person may be
confined to a wheelchair.
As a means for investigating the relationship between brain
development and susceptibility to brain injury, investigators can use
an MRI-derived baby connectome that maps changing brain
connections during development. A connectome is a comprehensive
map of the structural connectivity (the physical wiring) of an
organism’s nervous system. The baby connectome can reveal
developmental abnormalities in brain connections even at very early
ages, thus expanding the time window to initiate therapeutic
strategies (Castellanos et al., 2014).

Many people with cerebral palsy have successful professional

careers.
Dr. John Melville, second from right, monitors a CT scan and
discusses the patient’s progress with a colleague. Cerebral
palsy has not impeded—and may have inspired—his medical
career.

Spinal Cord: Executing Movement

 The late actor Christopher Reeve, who portrayed Superman in three
1980s films, was thrown from a horse during a riding competition in
1995. Reeve’s spinal cord was severed near its upper end, at the C1–C2
level (see Spinal Segments and Dermatomes, page 359 ). The injury left
Reeve’s brain intact and functioning and his remaining spinal cord intact
and functioning too, but his brain and spinal cord were no longer
connected.
Other than head movements and slight movement in his shoulders,
Reeve’s body was completely paralyzed. He was even unable to breathe
without assistance. A century ago such a severe injury would have been
fatal, but modern and timely medical treatment allowed Reeve to survive
for nearly a decade.
A cut high on the spinal cord, such as Christopher Reeve survived,
entails paralysis and loss of sensation in the arms and legs, a condition
called quadriplegia. If the cut is low, paraplegia results: paralysis and
loss of sensation are confined to the legs and lower body, as described in
Clinical Focus 11-3 , Spinal Cord Injury, on page 365 . Christopher
Reeve and his late wife Dana founded the Christopher and Dana Reeve
Foundation for spinal cord research. It is dedicated to improving the life
and function of spinal cord–injured people and also to searching for
cures for spinal cord injury.
Far from being a mere relay between the body and brain, the spinal
cord contains complex motor programs. A spinal cord patient can walk
on a conveyor belt if the body is supported. Indeed, Christopher Reeve
was able to walk in a swimming pool, where his body was supported by
water.
When a spinal cord patient’s leg is moved backward on a conveyor
belt, causing the foot to lose support, the limb reflexively lifts off the belt
and swings forward underneath the body. As the foot touches the surface
of the belt again, tactile receptors initiate the reflex that causes the foot to
push against the surface and support the body’s weight. In this way,
several spinal reflexes work together to facilitate the complex movement
of walking. Walking’s reflexive organization can even be obtained in a
premature or newborn baby: when held upright, the baby will perform
stepping movements.
Among the complex reflexes observed in other vertebrates is the
scratch reflex. Here, an animal reflexively scratches a part of its body in
response to a stimulus from the body surface. The complexity of the
scratch reflex is revealed in the movement’s accuracy. Absent the brain’s
direction, the tip of a limb, usually a hind limb in a quadruped, can be
correctly directed to the irritated body part. Typically, itching is the
sensation that elicits scratching; it is likely that the sensory receptors on
the skin that produce itch evolved for detecting parasites and other
foreign objects. We return to itching sensations in Section 11-4 .
In humans and other animals with a severed spinal cord, spinal
reflexes still function, even though the spinal cord is cut off from
communication with the brain. As a result, the paralyzed limbs may
display spontaneous movements or spasms. But the brain can no longer
guide the timing of these movements. Consequently, reflexes related to
bladder and bowel control may have to be artificially stimulated by
caregivers.
The Kobal Collection at Art Resource
Pavel Wolberg/epa/Corbis
Christopher Reeve (left) portraying Superman in 1984 and (right) in 2004,
9 years after his spinal cord injury.
 Scratch reflex

quadriplegia Paralysis of the legs and arms due to spinal cord

injury.
paraplegia Paralysis of the legs due to spinal cord injury.
scratch reflex Automatic response in which an animal’s hind limb
reaches to remove a stimulus from the surface of its body.
CLINICAL FOCUS 11-3

Spinal Cord Injury

Each year, on average, about 11,000 people in the United States and
1000 people in Canada undergo spinal cord injury (as reported by the
Foundation for Spinal Cord Injury). Nearly 40 percent of these
injuries occur in traffic accidents and another 40 percent occur as a
result of falls. Often the spinal cord is completely severed, leaving an
individual with no sensation or movement from the site of the cut
downward.
Although 12,000 annual spinal cord injuries may seem like a large
number, it is small relative to the number of people in the United
States and Canada who undergo other kinds of nervous system
damage each year. To increase public awareness of their condition
and promote research into possible treatments, some, like
Christopher Reeve and Canadian Rick Hansen, have been especially
active.
Hansen’s paraplegia resulted from a lower thoracic spinal injury
in 1975. Twelve years later, to raise public awareness of the potential
of people with disabilities, he wheeled himself 40,000 kilometers
around the world to raise funds for the Man in Motion Legacy Trust
Fund. The fund contributes to rehabilitation, wheelchair sports, and
public awareness programs. In 2008 it sponsored the Blusson Spinal
Cord Centre in Vancouver, Canada, the largest institution in the
world dedicated to spinal cord research, housing over 300
investigators.
Spinal cord injury is usually due to trauma to the cord that results
in a number of secondary degenerative processes. These processes
increase the size of the lesion. Thereafter, the formation of scar
tissue, a cavity, and cysts block communication between the two
severed sides. Research on spinal cord injury is directed at
minimizing the acute changes that take place after the insult,
devising ways to facilitate neural communication across the injury,
and improving mobility and home care.
Nanotechnology, the science of making and using molecular-sized
tools, holds promise for both decreasing the acute effects of injury
and bridging the two sides of the injury. Nanotechnology works with
substances between 1 and 100 nanometers (nm) in size. (A
nanometer is one billionth, or 10–9 , of a meter.)
Nanotubes, or nanovesicles, can be engineered to transport drugs,
RNA, or new stem cells into the area of injury, where they can arrest
degenerative changes and help form neural bridges across the injury
(Sharma & Sharma, 2012). Nanotubes that can carry chemicals or
conduct electrical impulses can be threaded into the injury through
blood vessels and then into the very small capillaries within the
spinal cord. Or they can be injected as molecules that self-assemble
into scaffolding or tubes when they reach a target area.
Nanoscaffolding, introduced into the injury to form a bridge, can
aid the regrowth of axons across the injury (Imani et al., 2015).
Nanoaxons can be introduced into the region of injury to synapse
with neurons on both sides of the injury and to carry messages across
the injury. Because they are small, nanomedicinal substances can
interface with spinal cord cells on both sides of an injury.

Stacy Pearsall/Getty Images/Aurora Creative

 11-1 REVIEW
A Hierarchy of Movement Control
Before you continue, check your understanding.
1 . The motor system is organized as a ___________.
2 . The ___________ cortex plans movements, the ___________ cortex
organizes movement sequences to carry out the plan, and the
___________ cortex executes precise movements.
3 . The ___________ is responsible for species-typical movements, for
survival-related actions, and for posture and walking.
4 . In addition to serving as a pathway between the brain and the rest of
the body, the ___________ independently produces reflexive
movements.
5 . Explain what happens when the brain is disconnected from the
spinal cord and why.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5 e
 11-2 Motor System Organization
Although we humans tend to rely primarily on our hands for
manipulating objects, we can still learn to handle things with other body
parts, such as the mouth or a foot, if we have to. Some people without
arms become proficient at using a foot for writing or painting or even for
driving. What properties of the motor system allow such versatility in
carrying out such skilled movements? In this section we examine first
the organization of the motor cortex, then the descending pathways from
the motor cortex to the brainstem and spinal cord, and finally the motor
neurons that in turn connect with the body’s muscles.

Motor Cortex
In 1870, two Prussian physicians, Gustav Fritsch and Eduard Hitzig,
discovered that they could electrically stimulate the neocortex of an
anesthetized dog to produce movements of the mouth, limbs, and paws
on the opposite side of the dog’s body. They provided the first direct
evidence that the neocortex controls movement. Later researchers
confirmed the finding by experimenting with a variety of animals as
subjects, including rats, monkeys, and apes.
Section 4-1 describes the milestones that led to understanding how
the nervous system uses electrical charge to convey information.
Based on this research background, beginning in the 1930s Wilder
Penfield (Penfield & Boldrey, 1958) used electrical stimulation to map
the cortices of conscious human patients who were about to undergo
neurosurgery. Penfield’s aim was to use the results to assist in surgery.
He and his colleagues confirmed that movements in humans are
triggered mainly in response to stimulation of the premotor and primary
motor cortices.
Figure 10-19 shows Penfield using brain stimulation to map the
cortex.
Mapping the Motor Cortex
Penfield summarized his results by drawing cartoons of body parts to
represent the areas of the motor cortex that produce movement in those
parts. The result was a homunculus (pl. homunculi ; Latin for little
person ) that could be spread out across the primary motor cortex, as
illustrated in Figure 11-6 . Because the body is symmetrical, an
equivalent motor homunculus is discernible in the primary motor cortex
of each hemisphere, and each motor cortex mainly controls movement in
the opposite side of the body. Penfield also identified another, smaller
motor homunculus in the dorsal premotor area of each frontal lobe, a
region sometimes referred to as the supplementary motor cortex.
The striking feature of the homunculus shown in Figure 11-7 is the
disproportionate relative sizes of its body parts compared with the
relative sizes of actual parts of the human body. The homunculus has
huge hands with an especially large thumb. Its lips and tongue are also
prominent. By contrast, the trunk, arms, and legs—most of the area of a
real body—are small.
These distortions illustrate that extensive areas of M1 allow precise
regulation of the hands, fingers, lips, and tongue (see Figure 11-6 ). Body
areas over which we have relatively little motor control have a much
smaller representation in the motor cortex.
Another curious feature of the homunculus as laid out across the
motor cortex is that the body parts are discontinuous—arranged
differently from those of an actual body. The cortical area that produces
eye movements is in front of the homunculus head on the motor cortex
(see the top drawing in Figure 11-6 ), and the head is oriented with the
chin up and the forehead down (bottom drawing). The tongue is below
the forehead.
FIGURE 11-6 Penfield’s Homunculus Movements are topographically organized
in M1. Stimulation of dorsal medial regions produces movements in the lower limbs.
Stimulation in ventral regions of the cortex produces movements in the upper body,
hands, and face.

FIGURE 11-7 Homuncular Man An artist’s representation illustrates

the disproportionate areas of the sensory and motor cortices that control
different body parts.

Modeling Movement
The motor homunculus shows at a glance that relatively large areas of
the brain control the body parts we use to make the most skilled
movements—our hands, mouth, and eyes. This makes it useful for
understanding M1’s topographic organization (functional layout).
Debate over how the motor areas represented by Penfield’s homunculus
might produce movement has been considerable.
homunculus Representation of the human body in the sensory or
motor cortex; also any topographical representation of the body by a
 neural area.
topographic organization Neural spatial representation of the body
or areas of the sensory world perceived by a sensory organ.
An early idea was that each part of the homunculus controls muscles
in that part of the body. Information from other cortical regions could be
sent to the motor homunculus, and neurons in the appropriate part of the
homunculus could then activate body muscles required for producing the
movement. If you wanted to pick up a coin, for example, messages from
the M1 finger area would instruct the fingers. More recent experiments
suggest that the motor cortex represents not muscles but rather a
repertoire of fundamental movement categories (Grazaino, 2006).
The drawings in Figure 11-8 illustrate several movement categories
elicited in monkeys by electrical stimulation. They include (A) ascend,
descend, or jump, (B) reach to clasp,
(C) defensive posture or expression, (D) hand toward mouth, (E)
masticate or lick, (F) control centrally, and (G) control distally. Whole-
body movements are elicited from premotor cortex, and more precise
hand and mouth movements are elicited from M1. All these
movements occur only when the electrical stimulation lasts long
enough for the movement to take place.
Each observed movement has the same end regardless of the starting
location of a monkey’s limb or its other ongoing behavior. Electrical
stimulation that results in the hand coming to the mouth always recruits
the hand. If a weight is attached to the monkey’s arm, the evoked
movement compensates for the added load.
But categorized movements are inflexible: when an obstacle is placed
between the hand and the mouth, the hand hits the obstacle. If
stimulation continues after the hand has reached the mouth, the hand
remains there for the duration of the stimulation. Further, broad
movement categories—for example, reaching—cluster together on the
motor cortex, but reaching directed to different parts of space is elicited
from slightly different cortical points in the topographic reaching map.
 FIGURE 11-8 Natural Movement Categories Movement
categories evoked by electrical stimulation of the monkey cortex and the
primary motor and premotor regions from which the categories were
elicited. Research from M. S. A. Graziano and T. N. Aflalo (2007). Mapping behavioral
repertoire onto the cortex. Neuron 56 : Figure 5, p. 243.

MRI studies on human subjects suggest that the human motor cortex,
like the monkey motor cortex, is organized in terms of functional
movement categories (Meier et al., 2008). The motor cortex maps appear
to represent basic types of movements that learning and practice can
modify. In other words, the motor cortex encodes not muscle twitches
but a lexicon, or dictionary, of movements. As with words and sentences,
these few movements used in different combinations produce all the
movements you are capable of, even in activities as complex as playing
basketball.
 EXPERIMENT 11-2

Question: How does the motor cortex take part in the

control of movement?
Procedure

Results
Conclusion: The motor cortex takes part in planning movement,
executing movement, and adjusting the force and duration of a
movement.
Research from E. V. Evarts (1968). Relation of Pyramidal Tract Activity to Force Exerted
During Voluntary Movement. Journal of Neurophysiology, 31, p. 15.

Motor Cortex and Skilled Movement

In a study designed to investigate how neurons in the motor cortex
control movement, Edward Evarts (1968) used the simple procedure
illustrated in Experiment 11-2 . He trained a monkey to flex its wrist to
move a bar. Different weights could be attached to the bar. An electrode
implanted in the wrist region of the monkey’s motor cortex recorded the
activity of neurons there.
Evarts discovered that the neurons began to discharge even before the
monkey began the movement, as shown in the Results section of
Experiment 11-2 . Thus, they take part in planning the movement as well
as initiating it. The neurons continued to discharge as the wrist moved,
confirming that they play a role in producing the movement. Finally, the
neurons discharged at a higher rate when the bar was loaded with a
weight. This finding shows that motor cortex neurons increase a
movement’s force by increasing their firing rate and its duration, as
stated in the experiment’s Conclusion.
Evarts’s findings also reveal that the motor cortex has a role in
specifying the end point of a movement. Motor cortex neurons in the
wrist might discharge when the monkey flexed its wrist inward but not
when the wrist was extended back to its starting position. These on–off
neuronal responses are a simple way of coding a desired final position of
a movement. Evart’s finding that motor cortex neurons are involved in
planning movements is confirmed in much less formal situations. For
example, recordings of a monkey’s biceps muscle, which produces arm
flexion, and from motor cortex neurons that produce arm flexion when
stimulated, show correlated activity during a monkey’s spontaneous
behaviors.
The activity of motor neurons in freely moving monkeys suggests that
the neurons, depending upon their location, move the body or parts of the
body to specific positions (Aflalo & Graziano, 2007). For example, if
some neurons are very active when a hand is moved to a specific
location, they are progressively less active when the hand is moved away
from that position. Thus, the neurons in the motor cortex regions
illustrated in Figure 11-8 are responsible for configuring movements that
achieve the same end point produced when those same neurons are
electrically stimulated (Aflalo & Graziano, 2007).
Nevertheless, studies using human participants reveal situations in
which motor cortex neurons can be active even when no overt movement
occurs (Schieber, 2011). These situations include planning a movement,
withholding a movement on instruction, and mental imagery. Such
subthreshold activity in motor cortex neurons may underlie our ability to
imagine movements without actually producing them. Subthreshold
activity may also allow motor cortex neurons to control brain–computer
interfaces (see Research Focus 11-1 ). In keeping with this idea,
monkeys that are controlling an external device using brain activity are
described as displaying a nearly complete absence of movement.

Plasticity in the Motor Cortex

 An intimate relationship connects the activity of M1 neurons with
movement of the body. The studies just described show that flexibility is
part of the relationship. Flexibility underlies another property of the
motor cortex: its plasticity, which contributes both to motor learning and
to recovery after the motor cortex is damaged, as the following example
explains.
A study by Randy Nudo and his coworkers (1996), summarized in the
Procedure section of Experiment 11-3 , illustrates change due to cortical
damage. These researchers mapped the motor cortices of monkeys to
identify the hand and digit areas. They then surgically removed a small
part of the cortex that represents the digit area. After undergoing this
electrolytic lesion, the monkeys used the affected hand much less,
relying mainly on the good hand.
Section 14-4 explores how motor maps change in response to
learning.
Focus 2-3 describes motor disruptions that stroke causes; Section
16-3 reviews stroke treatments.
 EXPERIMENT 11-3

Question: What is the effect of rehabilitation on the cortical

representation of the forelimb after brain damage?

Conclusion: Rehabilitation prevents both a loss of movement in the

hand and a decrease in the hand’s cortical representation.
Research from R. J. Nudo, B. M. Wise, F. SiFuentes, & G. W. Milliken (1996). Neural
Substrates for the Effects of Rehabilitative Training on Motor Recovery after Ischemic Infarct.
Science, 272, p. 1793.

When the researchers stimulated the cortex of the monkeys 3 months

later, the animals were unable to produce many lower-arm movements—
including the wrist, hand, and digits—that they produced prior to the
lesion. Much of the area representing the hand and lower arm had
disappeared from the animals’ cortical maps. The shoulder, upper arm,
and elbow areas had spread out to take up what had formerly been space
representing the hand and digits. The Results section of Experiment 11-3
shows this topographic change.
The experimenters wondered whether the change could have been
prevented had they forced the monkeys to use the affected arm. To find
out, they used the same procedure on other monkeys, except that during
the postsurgery period they forced the animals to rely on the bad arm by
binding the good arm in a sling.
When the experimenters reexamined these monkeys’ motor maps 3
months later, they found that the hand and digit area retained its larger
size. Even though no neural activity occurred in the spot with the lesion,
the monkeys had gained some function in the digits that used to be
connected to the damaged spot. Apparently, the remaining cortical digit
area was now controlling the movement of these fingers.
Most likely, plasticity is promoted in the formation of new connections
and the strengthening of existing connections among different parts of the
motor homunculus. Humans who have had a stroke to the motor cortex
also display plasticity-mediated recovery. They may at first be completely
unable to use their contralateral forelimb, but with time and practice they
may recover a great deal of movement.
As Nudo’s monkey experiment illustrates, one way to enhance
recovery is to restrain the good limb. Constraint-induced therapy,
which forces use of the affected limb, is a major therapy for stroke-
induced limb paralysis. Its effectiveness depends on frustration of the
good limb, which promotes a concerted effort to use the bad limb and
promotes neural plasticity.
Section 7-1 describes ablation techniques used by neuroscience
researchers to manipulate the brain.
FIGURE 11-9 Left-Hemisphere Corticospinal Tract Nerve fibers descend
from the left-hemisphere motor cortex to the brainstem, where the tract branches into the
spinal cord. The lateral tract crosses the brainstem’s midline, descending into the right
side of the spinal cord to move limb and digit muscles on the body’s right side. The
anterior tract remains on the left side to move muscles at the body’s midline.

Corticospinal Tracts
The main efferent pathways from the motor cortex to the brainstem to the
spinal cord are the corticospinal tracts. The axons from these tracts
originate mainly in motor cortex layer V pyramidal cells but also extend
from the premotor cortex and the sensory cortex (see Layering in the
Neocortex on page 359 ). The axons descend into the brainstem, sending
collaterals to numerous brainstem nuclei, and eventually emerge on the
brainstem’s ventral surface, where they form a large bump on each side.
These bumps, or pyramids, give the corticospinal tracts their alternative
name, the pyramidal tracts.
At this point, some axons descending from the left hemisphere cross
over to the right side of the brainstem. Likewise, some axons descending
from the right hemisphere cross over to the left side of the brainstem. The
remaining axons stay on their original side. This division produces two
corticospinal tracts, one crossed and the other uncrossed, entering each
side of the spinal cord. Figure 11-9 illustrates the division of tracts
originating in the left-hemisphere cortex. The dual tracts on each side of
the brainstem descend into the spinal cord, forming the two spinal cord
tracts.
The cross section of a spinal cord in Figure 11-10 shows the location
of the two tracts, on the left and right sides. The fibers that cross to the
opposite side of the brainstem descend the spinal cord in a lateral (side)
position to form the lateral corticospinal tract. The fibers that remain on
their original side continue from the brainstem down the spinal cord in an
anterior (front) position, to form the anterior corticospinal tract.
Retracing the pathway, the corticospinal tracts originate in the
neocortex and terminate in the spinal cord. Within the spinal cord,
corticospinal fibers make synaptic connections with both interneurons and
motor neurons, but the motor neurons carry all nervous system commands
out to the muscles.
 FIGURE 11-10 Motor Tract Organization Interneurons and motor
neurons in the left and right anterior spinal cord tracts are topographically
arranged: the more lateral neurons innervate more distal parts of the limbs
(those farther from the midline), and the more medial neurons innervate
more proximal body muscles (those closer to the midline).

Motor Neurons
Spinal cord motor neurons are located in the anterior part of the spinal
cord, the anterior horns, which jut out from the anterior part of the spinal
cord. The anterior horns contain two kinds of neurons. Interneurons lie
just medial to the motor neurons and project onto them. The motor
neurons send their axons to the body muscles. The fibers from the
corticospinal tracts make synaptic connections with both the interneurons
and the motor neurons, but the motor neurons carry all nervous system
commands to the muscles.
Figure 11-10 shows that a homunculus of the body is represented again
in the spinal cord. The more lateral motor neurons project to muscles that
control the fingers and hands, whereas intermediate motor neurons project
to muscles that control the shoulders and arms. The most medial motor
neurons project to muscles that control the body’s trunk. Axons of the
lateral corticospinal tract connect mainly with the lateral interneurons and
motor neurons, and axons of the anterior corticospinal tract connect
mainly to the medial interneurons and motor neurons.
To visualize how the cortical regions responsible for different
movements relate to the motor neuron homunculus in the spinal cord,
look again at Figure 11-9 . Place your finger on the index finger region of
the motor homunculus on the left side of the brain. If you trace the axons
of the cortical neurons downward, your route takes you through the
brainstem, across its midline, and down the right lateral corticospinal
tract.
The journey ends at the interneurons and motor neurons in the most
lateral region of the spinal cord’s right anterior horn—the horn on the
opposite (contralateral) side of the nervous system from which you began.
Following the axons of these motor neurons, you find that they synapse
on muscles that move the right index finger.
If you repeat the procedure by tracing the pathway from the trunk area
of the motor homunculus, near the top on the left side of the brain, you
follow the same route through the upper part of the brainstem. You do not
cross over to the opposite side, however. Instead, you descend into the
spinal cord on the left side, the same (ipsilateral) side of the nervous
system on which you began, eventually ending up in the most medial
inter-neurons and motor neurons of the left side’s anterior horn. (At this
point, some of these axons also cross over to the other side of the spinal
cord.) Thus, if you follow these motor neuron axons, you end up at their
synapses with the muscles that move the trunk on both sides of the body.
This visualization can help you remember the routes taken by motor
system axons. The limb regions of the motor homunculus contribute most
of their fibers to the lateral cortico-spinal tract, the fibers that cross over
to the opposite side of the spinal cord. They activate motor circuits that
move the arm, hand, leg, and foot on the opposite side of the body. In
contrast, the trunk regions of the motor homunculus contribute their fibers
to the anterior corticospinal tract. Only a few of these fibers cross, close
to their termination in the spinal cord; most control the trunk and limbs on
the same side of the body.
If you are right-handed, the neurons your brain is using to carry out
this task are the same neurons that you are tracing.
constraint-induced therapy Procedure in which restraint of a
healthy limb forces a patient to use an impaired limb to enhance
 recovery of function.
corticospinal tract Bundle of nerve fibers directly connecting the
cerebral cortex to the spinal cord, branching at the brainstem into an
opposite-side lateral tract that informs movement of limbs and digits
and a sameside anterior tract that informs movement of the trunk;
also called pyramidal tract.
The interneurons and motor neurons of the spinal cord are envisioned
as a homunculus representing the muscles that they innervate.
Remember that the motor cortex is organized in terms of functional
movement categories, such as reaching or climbing (see Figure 11-8 ). A
similar template in the spinal cord ensures that instructions from the
motor cortex are reproduced faithfully. Presumably, lateral interneurons
produce acts of reaching or bringing the hand to the mouth, and the
medial interneurons and motor neurons produce whole-body movements,
including walking. Recall that a spinal cord isolated from the brain by a
cut is capable of many kinds of movements, and it is able to do so
because the movements are organized by its interneurons and motor
neurons.
In addition to the corticospinal pathways, about 24 other pathways
from the brainstem to the spinal cord carry instructions, such as
information related to posture and balance (see Section 11-4 ), and they
control the enteric nervous system as well as portions of the sympathetic
division of the ANS. Remember that for all these functions, the motor
neurons are the final common path.
 FIGURE 11-11 Coordinating Muscle Movement

Control of Muscles
Spinal cord motor neurons synapse on the muscles that control body
movements. For example, the biceps and triceps of the upper arm control
movement of the lower arm. Limb muscles are arranged in pairs, as
shown in Figure 11-11 . One member of a pair, the extensor, moves
(extends) the limb away from the trunk. The other member of the pair, the
flexor, moves (flexes) the limb in toward the trunk. Experiment 11-2 on
page 368 demonstrates the on–off responses of cortical motor neurons,
depending on whether the flexor or extensor muscle is being used.
Connections between spinal cord interneurons and motor neurons
ensure that the muscles work together so that when one muscle contracts,
the other relaxes. Thus, the spinal cord interneurons and motor neurons
not only relay instructions from the brain but also, through their
connections, cooperatively organize the movement of many muscles. As
you know, the neurotransmitter at the motor neuron–muscle junction is
acetylcholine.
Figure 4-26 illustrates ACh action at a motor neuron–muscle
junction.
 11-2 REVIEW
Motor System Organization
Before you continue, check your understanding.
1 . The ___________ organization of the motor cortex is represented by
a ___________, in which parts of the body that are capable of the most
skilled movements (especially the mouth, fingers, and thumbs) are
regulated by ___________ cortical regions.
2 . Change can take place in the cortical ___________ to aid in recovery
of function after motor cortex injury.
3 . Instructions regarding movement travel out from the motor cortex
through the ___________ tracts to terminate on interneurons that
project to motor neurons in the anterior horn of the spinal cord. Many
corticospinal-tract fibers cross to the opposite side of the spinal cord to
form the ___________ tracts; some stay on the same side to form the
___________ tracts.
4 . The anterior corticospinal tracts carry instructions for ___________
movements, whereas the lateral corticospinal tracts carry instructions
for ___________ and ___________ movements.
5 . Motor neuron axons in the spinal cord carry instructions to
___________ that are arranged in pairs. One ___________ a limb; the
other ___________ the limb.
6 . What does the plan of movements in the motor cortex as revealed by
electrical stimulation tell us about the brain’s representation of
movement?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Basal Ganglia, Cerebellum, and
11-3

Movement
The main evidence that the basal ganglia and the cerebellum perform
motor functions is that damage to either structure impairs movement.
Both have extensive connections with the motor cortex, which further
suggests their participation in movement. After an overview of each
structure’s anatomy, we look at some symptoms that arise after damage to
the basal ganglia or the cerebellum. Then we consider the roles each
structure plays in controlling movement.

Basal Ganglia and the Force of Movement

The neocortex connects extensively with the basal ganglia, a collection of
nuclei lying just beneath the cortex, as illustrated in Figure 11-12 . The
basal ganglia do not produce movement directly, but rather modulate the
activity of cortical motor systems. The nuclei participate in a wide range
of functions, including association or habit learning, motivation, and
emotion, as well as motor control.
FIGURE 11-12 Basal Ganglia Connections The caudate putamen in the basal
ganglia connects to the amygdala through the tail of the caudate nucleus. The lateral see-
through view shows the basal ganglia relative to surrounding structures, including the
substantia nigra, with which it shares reciprocal connections. The basal ganglia receive
input from most regions of the cortex and send input into the frontal lobes through the
subthalamic nucleus.

Anatomy of the Basal Ganglia

Among the nuclei forming the basal ganglia are the caudate nucleus and
the putamen, which together form the striatum (meaning striped body and
named for the fibers, including corticospinal fibers, running through it),
and the subthalamic nucleus and globus pallidus. As shown in Figure 11-
12 , the prominent striatum extends as a tail (caudate means having a tail
) into the temporal lobe, ending in the amygdala. There are three main
basal ganglia connections:
1. All areas of the neocortex and more primitive allocortex project to the
basal ganglia.
2. The basal ganglia project to the motor cortex via relays in the thalamus.
3. The basal ganglia receive connections from the dopamine cells of the
midbrain substantia nigra over the nigrostriatal pathway and also
project to the substantia nigra.
Through these connections, the basal ganglia form reciprocal circuits,
or loops, connecting all neocortical and allocortical regions to the motor
cortex. Other loops connect the basal ganglia and substantia nigra,
allowing the substantia nigra to modulate the subcortical–motor cortex
loops. Separate loops likely participate in selecting and producing skilled
movements for learned actions and emotional expression. Some of these
loops’ functions are revealed in behavioral deficits that follow damage to
the basal ganglia.
How the Basal Ganglia Control Movement Force
Two types of movement disorders—in many ways opposites—result from
basal ganglia damage. If cells of the caudate putamen are damaged,
unwanted writhing and twitching movements called dyskinesias result. In
Huntington disease, for example, characterized by involuntary,
exaggerated, and disjointed movements, striatal cells are destroyed. Other
involuntary movements related to striatal damage are the unwanted tics
and vocalizations peculiar to the topic of Clinical Focus 11-4 , Tourette
Syndrome.
 Figure 5-17 traces the nigrostriatal pathways in the dopaminergic
activating system and highlights their importance for maintaining
healthy motor behavior.
In addition to causing involuntary movements, or hyperkinetic
symptoms, as just described, basal ganglia damage can result in a loss of
motor ability, or hypokinetic symptoms that feature rigidity and
difficulty initiating and producing movements. Parkinson disease is
marked by hypokinetic symptoms caused by the loss of dopamine cells in
the substantia nigra that project into the basal ganglia.
The fact that both hyperkinetic and hypokinetic symptoms arise
subsequent to basal ganglia damage suggests that one function of these
nuclei is regulating movement force. The idea is that hyperkinetic
disorders such as Huntington disease result from errors of too much force
and so result in excessive movement. Hypokinetic disorders such as
Parkinson disease result from errors of too little force and so result in
insufficient movement.
In support of these ideas, in a reaching task, Huntington subjects
reached using too much force, thus seemingly flinging a limb. Parkinson
subject reached with too little force, thus producing slowed movement
(Moisello et al., 2011). An MRI study of basal ganglia activity in healthy
participants who, for a small monetary reward, considered how much
force to apply in a gripping task, showed more basal ganglia activity
when they contemplated using a more forceful grip and less activity when
contemplating a less forceful grip (Kurniawan et al., 2010). Together,
these studies suggest that the basal ganglia play a role not just in
producing force but also in computing the effortful costs of making
movements.
Focus 3-4 describes the genetic basis of Huntington disease.
Detailed coverage of Parkinson disease and its treatment appears in
Chapters 5 , 7 , and 16 .
hyperkinetic symptom Excessive involuntary movement, as seen in
Tourette syndrome.
hypokinetic symptom Paucity of movement, as seen in Parkinson
disease.
CLINICAL FOCUS 11-4

Tourette Syndrome
The neurological disorder Tourette syndrome (TS) was first
described in 1885 by Georges Gilles de la Tourette, a French
neurologist, who described the symptoms as they appeared in
Madame de D., one of his patients:
Madame de D., presently age 26, at the age of 7 was afflicted by convulsive movements
of the hands and arms. These abnormal movements occurred above all when the child
tried to write, causing her to crudely reproduce the letters she was trying to trace. After
each spasm, the movements of the hand became more regular and better controlled until
another convulsive movement would again interrupt her work. She was felt to be
suffering from over-excitement and mischief, and because the movements became more
and more frequent, she was subject to reprimand and punishment. Soon it became clear
that these movements were indeed involuntary and convulsive in nature. The
movements involved the shoulders, the neck, and the face, and resulted in contortions
and extraordinary grimaces. As the disease progressed, and the spasms spread to involve
her voice and speech, the young lady made strange screams and said words that made
no sense. (Friedhoff & Chase, 1982)

The statistical incidence of Tourette syndrome is about 1 in 1000

people. TS affects all racial groups and seems to be hereditary. The
age range of onset is 2 to 25 years.
The most frequent symptoms of Tourette syndrome are
involuntary tics and complex movements, such as hitting, lunging, or
jumping. People with TS may also emit sudden cries and other
vocalizations or inexplicably utter words that do not make sense in
the context, including coprolalia and swearing.
Tourette syndrome is thought to reflect an abnormality of the
basal ganglia, especially in the right hemisphere, because its
symptoms can be controlled with haloperidol, an antipsychotic drug
that blocks dopamine synapses in the basal ganglia. Using fMRI to
correlate resting activity with brain regions, Church and colleagues
(2009) documented cortical changes associated with TS. These
include increased connectivity, mainly in the parietal cortex of
Tourette patients, and decreased connectivity between parietal and
frontal cortex. This finding, diagrammed in the illustration, suggests
altered functioning in neural circuits that connect the posterior
sensory regions of the cortex to its anterior motor regions.
 The urge to make involuntary movements and vocalizations may
be similar to behaviors that have an urge-to-action feature, such as
yawning and stretching (Tinaz et al., 2015). Using fMRI, the
investigators suggest that an urge-to-action system in the brain
involves the right dorsal insula, a multifunctional cortical area that
integrates sensory and emotional awareness and is important for
interoception (self-awareness). Why particular movements and
vocalizations that characterize individuals with Tourette syndrome
should be caught up by this urge-to-act system remains a mystery.

In fMRI analyses of young adults with Tourette syndrome, brain

areas that show enhanced (green) or decreased (red)
connectivity suggest abnormalities in dorsal stream structures
linking the parietal cortex to the frontal cortex. Information from J. A.
Church, D. A. Fair, N. U. Dosenbach, et al. (2009). Control networks in paediatric Tourette
syndrome show immature and anomalous patterns of functional connectivity. Brain, 32,
pp. 225–238.

What features of the reciprocal basal ganglia loops allow for selecting
movements or modulating movement force? One theory holds that the
basal ganglia can influence whether movement occurs (Friend & Kravitz,
2014). As illustrated in Figure 11-13 , a pathway (green) from the
thalamus to the cortex to the spinal cord produces movement. The globus
pallidus (red) can inhibit this pathway at the level of the thalamus.
The globus pallidus is controlled by two basal ganglia pathways, one
indirect and one direct. If the globus pallidus is excited, it in turn inhibits
the thalamus and blocks movement. If it is inhibited, motor cortex
circuits that include the thalamus are able to produce movement. The
globus pallidus thus acts like a volume control. If it is turned down,
movement can occur; if it is turned up, movement is blocked. This model
proposes that diseases of the basal ganglia affecting its “volume control”
function impair movement so that it is either excessive or slowed.
The idea that the globus pallidus acts like a volume control is the
basis for several treatments for Parkinson disease. Consistent with the
volume hypothesis, recordings made from globus pallidus cells show
excessive activity, which inhibits movement in people with Parkinson
disease. If the globus pallidus or the subthalamic nucleus (a relay in the
indirect pathway) is partially surgically destroyed in Parkinson patients,
muscular rigidity is reduced and normal movement is improved.
Similarly, deep brain stimulation (DBS) of the globus pallidus
inactivates it, freeing movement.
Interestingly, impairments in the application of force may underlie
motor disorders of skilled movements such as writer’s cramp, one of a
number of impairments called selective dystonias. One such impairment,
the yips, is distorted execution of skilled movements by professional
athletes. For example, the yips have ended the career of many
professional golfers by ruining the player’s swing (Belton et al., 2014).
Another structure in the basal ganglia, the nucleus accumbens, is also
called the ventral striatum, because it is the most ventral basal ganglia
nucleus. The nucleus accumbens receives projections from dopamine
cells of the ventral tegmental area, a nucleus just medial to the substantia
nigra in the midbrain. Called the mesolimbic dopamine pathway, it is a
part of a loop that aids our perception of cues signaling reward.
 FIGURE 11-13 Regulating Movement Force Two pathways in
the basal ganglia modulate movements produced in the cortex. Green
pathways are excitatory; red are inhibitory. The indirect pathway excites
the globus pallidus internal, whereas the direct pathway has an inhibitory
effect. If activity in the indirect pathway dominates, the thalamus shuts
down, and the cortex is unable to produce movement. If direct-pathway
activity dominates, the thalamus can become overactive, amplifying
movement. Information from R. E. Alexander & M. D. Crutcher (1990). Functional
architecture of basal ganglia circuits: Neural Substrates of parallel processing. Trends in
Neuroscience, 13, p. 269.

Figure 1-6 shows electrodes implanted in the brain for DBS.

Cerebellum and Movement Skill

Musicians have a saying: “Miss a day of practice and you’re OK, miss
two days and you notice, miss three days and the world notices.”
Apparently, changes take place in the brain when we practice or neglect
to practice a motor skill. The cerebellum may be the affected component
of the motor system. Whether the skill is playing a musical instrument,
pitching a baseball, or texting, the cerebellum is critical for acquiring and
maintaining motor skills.
 The mesolimbic DA pathway (purple projections from ventral tegmentum)
is a substrate not only of reward but of addictive behavior as well. See
Section 6-4 .

Anatomy of the Cerebellum

The cerebellum, a large and conspicuous part of the motor system, sits
atop the brainstem, clearly visible just behind the cerebrum, and like the
cerebrum, is divided into two hemispheres ( Figure 11-14 ). A small
lobe, the flocculus, projects from its ventral, or inferior, surface.
Although smaller than the cerebrum, the cerebellum has many more gyri
and sulci, and for all us primates, contains about four times as many
neurons as does the cortex.
The elephant’s cerebellum, by contrast, contains 98.5% of its
neurons. Details in Focus 1-3.
 FIGURE 11-14 Cerebellar Homunculus The cerebellar
hemispheres control body movements, and the flocculus controls eye
movements and balance. In the cerebellum’s topographical organization,
relatively medial parts represent the body’s midline and relatively lateral
parts represent the limbs and digits.

As Figure 11-14 shows, the cerebellum can be divided into several

regions, each specialized for an aspect of motor control. At its base, the
flocculus receives projections from the middle ear vestibular system,
described in Section 11-4 , and takes part in controlling balance. Many
projections from the flocculus go to the spinal cord and to the motor
nuclei that control eye movements.
Just as the motor cortex has a homuncular organization and multiple
homunculi, the cerebellar hemispheres have at least two, as shown in
Figure 11-14 . The medial part of each homunculus controls the face and
the body’s midline. The more lateral parts connect to motor cortex areas
associated with movements of the limbs, hands, feet, and digits.
Pathways from the cerebellar hemispheres project to nuclei at the
interface of the cerebellum and spinal cord. These in turn project to other
brain regions, including the motor cortex.
To summarize the cerebellum’s topographic organization, the midline
of the homunculus is represented in its central part; the limbs and digits
are represented in the lateral parts. Tumors or damage to midline areas of
the cerebellum disrupt balance, eye movement, upright posture, and
walking but do not substantially disrupt other movements such as
reaching, grasping, and using the fingers. A person with medial damage
to the cerebellum may, when lying down, show few symptoms. Damage
to lateral parts of the cerebellum disrupts arm, hand, and finger
movements much more than movements of the body’s trunk.
The arrangement and connections of the cerebellum are built to a
common plan. The cerebellar cortex consists of three layers of cells, with
the distinctive Purkinje cells forming the second layer. Purkinje cells are
the output cells of the cerebellum. This plan suggests that the cerebellum
has a common function with respect to its control over other motor
system regions.
Ramón y Cajal’s drawing of a Purkinje cell, circa 1900.

How the Cerebellum Improves Movement Control

Attempts to understand how the cerebellum controls movement have
centered on two major ideas. Damage to the cerebellum (1) does not
abolish any movement but (2) does disrupt the timing and execution of
movement. Thus, the cerebellum must regulate the timing and flow of
movement as required for the situation.
Tom Thach (2007), in an intriguing experiment, illustrates how the
cerebellum helps make the adjustments needed to keep movements
accurate. Control participants and subjects with cerebellar damage threw
darts at a target, as shown in the Procedure section of Experiment 11-4 .
After a number of throws that allowed them to become reasonably
accurate, both groups donned glasses containing wedge-shaped prisms
that displaced the apparent location of the target to the left. Now when
they threw a dart, it landed to the left of the intended target.
Both groups showed this initial distortion in aim. But then came an
important difference, graphed in the Results section of Experiment 11-4 .
When controls saw the dart miss the mark, they adjusted each successive
throw until reasonable accuracy was restored. In contrast, subjects with
cerebellar damage could not correct for this error. Time after time, they
missed the target far to the left.
Next, the controls removed the prism glasses and threw a few more
darts. Again, a significant difference emerged. The first dart thrown by
each participant was much too far to the right (owing to the previous
adjustment they had learned to make), but soon each one adjusted once
again until his or her former accuracy was regained.
 EXPERIMENT 11-4

Question: Does the cerebellum help to make adjustments

required to keep movements accurate?
Procedure

Results

Conclusion: Many movements we make depend on moment-to-

moment learning and adjustments made by the cerebellum.
Information from W. T. Thach, H. P. Goodkin, & J. G. Keating (1992). The Cerebellum and the
Adaptive Coordination of Movement. Annual Review of Neuroscience, 15, p. 429.

In contrast, subjects with damage to the cerebellum showed no

aftereffects of wearing the prisms; they had never compensated for the
glasses to begin with. This experiment suggests that many movements
we make—whether throwing a dart or organizing a movement sequence
to shoot a basketball—depend on moment-to-moment learning and
adjustments made by the cerebellum.
 To examine the role of learning in this task, monkeys were trained on
a similar task to point a finger to a target on a computer screen. Once
they had mastered the task, they were required to perform it with prism
glasses. The monkeys displayed a displacement of pointing and an
aftereffect when the prism glasses were removed.
After 30 days of training with and without prisms, displacement and
aftereffect disappeared, and the monkeys were immediately accurate
when wearing the prisms and after they were removed. When the arm
region of the cerebellar homunculus was then anesthetized with
lidocaine, a local anesthetic agent, pointing without prisms was normal,
but the learned adaptation to prisms was abolished. This experiment
illustrates that the cerebellum is responsible not only for online
adjustments of movement but also for learning relatively permanent
movement skills (Norris et al., 2011). Using a somewhat similar task,
Hashimoto and associates (2015) obtained similar results using humans
who have cerebellar damage.
To better understand how the cerebellum improves motor skills by
adjusting movements, consider the model charted in Figure 11-15 .
Imagine throwing a dart. You aim at the bull’seye, throw the dart, and
find that it misses the board completely. You aim again, this time
adjusting your throw to correct for the original error. The model
illustrates that there are actually two versions of your action: (1) the
movement you intended to make and (2) the actual movement as
recorded by sensory receptors in your arm and shoulder. If you carry out
the intended movement successfully, you need make no correction on
your next try. But if you miss, and you frequently will, an adjustment is
called for.
The model illustrates that the cortex sends instructions to the spinal
cord to throw a dart at the target. A copy of the same instructions is sent
to the cerebellum through the inferior olive, a nucleus in the brainstem
that projects to the cerebellum. Then, when you throw the dart, the
sensory receptors in your arm and shoulder code the actual movement
you make and send a message about it back to the cerebellum through
the spinocerebellar tract. The cerebellum now has information about both
versions of the movement—what you intended to do and what you
actually did—and can calculate the error and inform the cortex how to
correct the movement. When you next throw a dart, you incorporate the
correction into your throw. If the cerebellum is damaged, the ability to
correct errors by comparing intended and actual movements is impaired
(Therrien & Bastian, 2015).
FIGURE 11-15 Intention, Action, and Feedback By comparing the message
for the intended movement with the movement that was actually performed, the
cerebellum sends an error message to the cortex to improve the accuracy of a
subsequent movement.
 11-3 REVIEW
Basal Ganglia, Cerebellum, and Movement
Before you continue, check your understanding.
1 . The ___________ contribute to motor control by adjusting the
___________ associated with each movement.
2 . Damage to the basal ganglia results either in unwanted involuntary
___________ movements (too much force exerted) or in such
___________ rigidity that movements are difficult to perform (too
little force exerted).
3 . The cerebellum contributes to motor control by improving movement
___________ and the learning of motor ___________.
4 . Describe how the cerebellum improves execution of motor skills.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Somatosensory System Receptors and
11-4

Pathways
The motor system produces movement, but without sensation, movement
would lack direction and quickly become impaired. The somatosensory
system is indispensable for movement. The body senses tell us about the
physical contact we make with the world as well as how successful our
physical interactions with the world are.
Somatic sensation is unique among sensory systems. For the most
part, it is distributed throughout the body, not localized in the head, as
are vision, hearing, taste, and smell. Somatosensory receptors found in
the skin, muscles, and internal organs, including the circulatory system,
feature specialized dendritic attachments on sensory neurons, or the
dendrites themselves are the sensory receptors. Somatosensory neurons
convey information to the spinal cord and brain. One part of the system,
however, is confined to a single organ. The inner ear houses the
vestibular system, which contributes to our sensations of balance and
head movement.
In considering the motor system, we started at the cortex and followed
the motor pathways out to the spinal cord (review Figures 11-9 and 11-
10 ). This efferent route follows the outward flow of neural instructions
regarding movement. As we explore the somatosensory system, we
proceed in the opposite direction, because afferent sensory information
flows inward, from the body’s sensory receptors through sensory
pathways in the spinal cord to the cortex.

Somatosensory Receptors and Perception

Our body is covered with somatosensory receptors. Receptors include
body hair, which is attached to the dendrites of sensory neurons. Many
receptor types are embedded in surface skin, in deeper layers of the skin,
and in muscles, tendons, and joints. Some receptors consist simply of a
sensory neuron dendrite. Others are specialized capsules or connective
tissue surrounding a dendrite, and still others include a dendrite attached
to the base of a hair.
The density of somatosensory receptors, which varies greatly
throughout the body, determines sensitivity to stimulation. Body parts
that are highly sensitive to touch—including the hands, feet, lips, and
tongue—have far more sensory receptors than less sensitive body parts
—the arms, back, and legs.
Humans have two kinds of skin, hairy skin and glabrous skin, which
includes the palms of the hands and feet, lips, and tongue. Glabrous skin
is hairless and exquisitely sensitive to a wide range of stimuli. It covers
the body parts that we use to explore objects—hence its heightened
sensitivity.
The skin’s touch sensitivity is often measured with a two-point
sensitivity test. By touching the skin with two sharp points
simultaneously, we can observe how close together the points can be
placed while still being detected by the participant as two points rather
than one. On glabrous skin, we can detect the two points when they are
as close as 3 millimeters apart.
On hairy skin, two-point sensitivity is weaker by a factor of about 10.
The two points seem to merge into one below a separation distance
ranging from 2 to 5 cm, depending on the exact body part tested. You
can confirm these differences in sensitivity on your own body by
touching two sharp pencil points to a palm and to a forearm, varying the
distances that you hold the points apart. Be sure not to look as you touch
each surface.

Classifying Somatosensory Receptors

The varied types of somatosensory receptors in the human body may
total as many as 20 or more, but they can all be classified into the three
functional groupings illustrated in Figure 11-16 as perceptions of
irritation, pressure, or movement.
 glabrous skin Skin that does not have hair follicles but contains
larger numbers of sensory receptors than do hairy skin areas.

FIGURE 11-16 Somatosensory Receptors Perceptions derived

from the body senses of nociception, hapsis, and proprioception depend
on various receptors in various parts of the skin, muscles, joints, and
tendons.

Figure 4-25 illustrates the cellular processes at work in a sensory

neuron dendrite when a touch receptor is activated.
IRRITATION Nociception is the perception of pain, temperature, or
itch. Most nociceptors are free nerve endings, the tips of sensory neuron
dendrites, as diagrammed at the top of Figure 11-16 . When damaged or
irritated, these endings secrete chemicals, usually peptides, that stimulate
the nerve to produce an action potential. The action potential then
conveys a message about pain, temperature, or itch to the central nervous
system.
PRESSURE Hapsis (from the Greek for touch ) is the ability to
discriminate objects on the basis of touch. Haptic receptors enable us to
perceive fine touch and pressure and to identify objects that we touch
and grasp. Haptic receptors occupy both superficial and deep skin layers
and are attached to body hairs as well.
As diagrammed in the center of Figure 11-16 , haptic receptors consist
of a dendrite attached to a hair, to connective tissue, or to a dendrite
encased in a capsule of tissue. Mechanical stimulation of the hair, tissue,
or capsule activates special ion channels on the dendrite, which in turn
initiate an action potential. Differences in the tissue forming the capsule
determine the kinds of mechanical energy transduced by the haptic
receptor to the nerve. For example, pressure that squeezes the capsule of
a Pacinian corpuscle is the necessary stimulus for initiating an action
potential conveying pressure information. Displacement of a hair is a
necessary stimulus for initiating action potentials conveying some other
types of touch information.
MOVEMENT Proprioception, or body awareness, is the perception of
body location and movement. Proprioceptors are encapsulated nerve
endings sensitive to the stretch of muscles and tendons and the
movement of joints. In the Golgi tendon organ shown at the bottom of
Figure 11-16 , for instance, an action potential is triggered when the
tendon moves, stretching the receptor attached to it.
Duration of Receptor Response
Somatosensory receptors are specialized to tell us when a sensory event
occurs and/or whether it is still occurring. Information about when a
stimulus occurs is handled mainly by rapidly adapting receptors,
which activate neurons when stimulation begins and when it ends. As
shown in Figure 11-16 , haptic receptors that respond to touch (Meissner
corpuscles), to fluttering sensations (Pacinian corpuscles), and to
vibration (Ruffini corpuscles) all are rapidly adapting receptors.
In contrast, slowly adapting receptors activate neurons as long as a
sensory event is present: they detect whether a stimulus is still occurring.
For instance, after you have put on an article of clothing and become
accustomed to how it feels, only slowly adapting haptic receptors (such
as Merkel receptors and hair receptors) remain active.
The difference between a rapidly adapting and a slowly adapting
receptor rests on two factors: how the receptor is stimulated and how the
ion channels in the membrane of its dendrite respond to mechanical
stimulation. The stimulation may be sharp or cold, fluttery or deep, a
stretch or a swerve.
nociception Perception of pain, temperature, and itch.
hapsis Perceptual ability to discriminate objects on the basis of
touch.
proprioception Perception of the position and movement of the
body, limbs, and head.
 rapidly adapting receptor Body sensory receptor that responds
briefly to the onset of a stimulus on the body.
slowly adapting receptor Body sensory receptor that responds as
long as a sensory stimulus is on the body.

Posterior Root Ganglion Neurons

The dendrites that carry somatosensory information into the CNS belong
to neurons whose cell body is just outside the spinal cord in posterior
root ganglia. Their axons enter the spinal cord. As illustrated in Figure
11-17 , such a posterior root ganglion neuron contains a single long
dendrite. Only the tip is responsive to sensory stimulation. This dendrite
is continuous with the somatosensory neuron’s axon, which enters the
spinal cord. The somatosensory cell body sits to one side of this long
pathway.
Every spinal cord segment is flanked by a posterior root ganglion that
contains many types of neurons. Each type responds to a particular kind
of somatosensory information. Within the spinal cord, the axons of
posterior root ganglion neurons may synapse with other neurons or
continue to the brain or do both.
The axons of posterior root ganglion neurons vary in diameter and
myelination. These structural features are related to the kind of
information the neurons carry. Proprioceptive information (location and
movement) and haptic information (touch and pressure) are carried by
posterior root ganglion neurons that have large, well-myelinated axons.
Nociceptive information (pain, temperature, itch) is mainly carried by
posterior root ganglion neurons that have smaller axons with little or no
myelin.
Because of their size and myelination, the larger neurons carry
information faster than the smaller neurons do. One possible reason
proprioceptive and haptic neurons are designed to carry messages
quickly is that their information requires rapid response. Imagine that
you’ve touched a hot stove. A myelinated pain fiber activates and
instructs the hand to withdraw quickly. A nonmyelinated pain fiber, less
hurried, will let you know for some time afterward that your finger has
been burned.
 Myelin is the fatty coating around axons, formed by glial
cells, that speeds neurotransmission. See Section 3-1 .

FIGURE 11-17 Haptic Neuron of the Posterior Root

Ganglion The dendrite and axon of this neuron of the posterior root
ganglion, which are contiguous, carry sensory information from the skin to
 the CNS. These large, myelinated ganglionic axons travel up the spinal
cord to the brain in the posterior column, whereas the small axons
synapse with neurons whose axons cross the spinal cord and ascend on
the other side (shown in Figure 11-19 ).

Disruption of Posterior Root Ganglion Function

We can support the claim that sensory information is essential for
movement by describing what happens when posterior root ganglion
cells do not function. A clue comes from a visit to the dentist. If you
have ever had a tooth frozen for dental work, you have felt the strange
effect of losing sensation on one side of your face. Not only do you lose
pain perception but you also seem to lose the ability to move your facial
muscles properly, making it awkward to talk and smile and downright
dangerous to chew. Similarly, if your hands or mouth become terribly
cold, disrupting receptor function, talking or making hand movements
becomes difficult. So even though only the sensory nerves are blocked,
movement is affected as well.
In much the same way, sensory nerve damage affects both sensory
perceptions and motor abilities. John Rothwell and his coworkers (1982)
described a patient, G. O., who was deafferentated (had lost afferent
sensory fibers) by a disease that destroyed somatosensory posterior root
ganglion neurons. G. O. received no sensory input from his hands. He
could not, for example, feel when his hand was holding something.
However, G. O. could still accurately produce a range of finger
movements, and he could outline figures in the air even with his eyes
closed. He could also move his thumb accurately through different
distances and at different speeds, judge weights, and match movement
force. Nevertheless, his hands were relatively useless to him in daily life.
Although G. O. could drive his old car, he was unable to learn to drive a
new one. He was also unable to write, to fasten shirt buttons, and to hold
a cup.
G. O. began movements quite normally, but as he proceeded, the
movement patterns gradually fell apart, ending in failure. Part of G. O.’s
difficulties lay in maintaining muscle force for any time. When he tried
to carry a suitcase, he would quickly drop it unless he continually looked
down to confirm that he was carrying it. Clearly, although only G. O.’s
sensory neurons were damaged, he also had severe motor disability,
including inability to learn new motor skills.
Disruption of Body Awareness
Movement abnormalities also result from more selective damage to
neurons that carry proprioceptive information about body location and
movement. Neurologist Oliver Sacks (1998) gives a dramatic example in
his description of a patient, Christina, whose proprioceptive sensory
fibers throughout her body were damaged after she took megadoses of
vitamin B6 . Christina was left with little ability to control her
movements and spent most of each day lying prone. Here is how she
describes what a loss of proprioception means:
“What I must do then,” she said slowly, “is use vision, use my eyes, in every situation where I
used—what do you call it?—proprioception before. I’ve already noticed,” she added,
musingly, “that I may lose my arms. I think they are in one place, and I find they’re in
another. This proprioception is like the eyes of the body, the way the body sees itself. And if
it goes, as it’s gone with me, it’s like the body’s blind. My body can’t see itself if it’s lost its
eyes, right? So I have to watch it—be its eyes.” (Sacks, 1998, p. 46)

Clearly, Christina’s motor system is intact, but with no sense of where

in space her body is and what it is doing, she is almost completely
immobilized. Jonathan Cole (1995) described the case of Ian Waterman,
who lost proprioception after a presumed viral infection at age 19. He is
the only person reported to have learned how to move again, and this
relearning took years. He was even able to drive. All his regained
movement was mediated by vision, however, without which he was as
helpless as Christina.
Oliver Sacks’s research informed scientific understanding of
conditions as diverse as Parkinson disease (Focus 5-3 and Section
16-3 ), ventral visual stream injury (Section 9-4 ), and thinking
(Section 15-1 ).

Somatosensory Pathways to the Brain

As the axons of somatosensory neurons enter the CNS in the spinal cord,
they divide, forming two pathways to the brain. The haptic-
proprioceptive axons for touch and body awareness ascend the spinal
cord ipsilaterally, whereas nociceptive (pain, temperature, itch) nerve
fibers synapse with neurons whose axons cross to the contralateral side
of the spinal cord before ascending to the brain. Figure 11-18 shows
these two routes through the spinal cord. The posterior haptic-
proprioceptive pathway is shown as a solid red line, the anterior
nociceptive pathway as a dashed red line.
 FIGURE 11-18 Dual Somatosensory Pathways to the
Brain As neurons from the posterior root ganglia enter the spinal cord,
the two somatosensory pathways to the brain diverge.

The Posterior Spinothalamic Tract

Haptic-proprioceptive axons, which lie in the posterior portion of the
spinal cord, form the posterior spinothalamic tract. These axons for
fine touch and pressure synapse in the posterior column nuclei at the
base of the brain. As shown in Figure 11-18 , axons of neurons in the
posterior column nuclei cross to the other side of the brainstem and
ascend as part of a pathway called the medial lemniscus.
These posterior column axons synapse in the ventrolateral thalamus,
the part of the thalamus that sends afferent information about body
senses on to the somatosensory cortex. Although ventrolateral thalamic
neurons send most of their axons to the somatosensory cortex, some do
go to the motor cortex. Thus, three relay neurons are required to carry
hapticproprioceptive information to the cortex: posterior root ganglia
neurons, posterior column nuclei neurons, and thalamic neurons.
Because posterior column neurons cross to the opposite hemisphere,
each hemisphere perceives the opposite side of the somatosensory world.
The Anterior Spinothalamic Tract
Most nociceptive axons take a different route to the brain. As shown in
Figure 11-18 , they first synapse with neurons in the anterior part of the
spinal cord’s gray matter, and in turn, these neurons send their axons
across to the other side of the spinal cord. There they form the anterior
spinothalamic tract, which carries afferent information about pain,
temperature, and itch to the thalamus. This tract joins the medial
lemniscus in the brainstem to continue on to the ventrolateral thalamus.
The thalamic neurons project to the somatosensory cortex. So again,
conveying information to the cortex requires three groups of relay
neurons: posterior root neurons, spinal cord gray matter neurons, and
ventrolateral thalamic neurons.
Ipsilateral connections lie on the side of the body on which they
enter; contralateral connections lie on the side opposite.
deafferentation Loss of incoming sensory input, usually due to
damage to sensory fibers; also loss of any afferent input to a
structure.
posterior spinothalamic tract Pathway that carries fine-touch and
pressure fibers.
ventrolateral thalamus Part of the thalamus that carries
information about body senses to the somatosensory cortex.
anterior spinothalamic tract Pathway from the spinal cord to the
thalamus that carries information about pain and temperature.
Effects of Unilateral Somatosensory System Damage
Unilateral damage dissociates the functions of the two somatosensory
pathways—haptic-proprioceptive and nociceptive. Because they enter
the spinal cord together, separate in the spinal cord, and finally join up
again in the brainstem, unilateral damage to the system results in
distinctive sensory losses, depending upon the site of injury.
Damage to the posterior roots produces global somatosensory deficits
in a particular part of the body. In contrast, as illustrated in Figure 11-19
, after unilateral spinal cord injury, loss of hapsis and proprioception
occurs unilaterally, to the side of the body below where the damage
occurred. Loss of nociception occurs contralaterally. This occurs because
hapsis and proprioception take different routes through the spinal cord.
Unilateral damage at the points where the pathways merge in the
brainstem, thalamus, and cortex again affects hapsis, proprioception, and
nociception together, because these parts of the pathways again lie in
close proximity.
 Effects of Unilateral Damage to the
FIGURE 11-19

Somatosensory System

Spinal Reflexes
Not only do somatosensory nerve fibers convey information to the
cortex, they also participate in behaviors mediated by the spinal cord and
brainstem. Spinal cord somatosensory axons, even those ascending the
posterior columns, give off axon collaterals that synapse with
interneurons and motor neurons on both sides of the spinal cord. The
circuits made between sensory neurons and muscles through these
connections mediate spinal reflexes.
The simplest spinal reflex is formed by a single synapse between a
sensory neuron and a motor neuron. Figure 11-20 illustrates such a
monosynaptic reflex, the knee jerk. It affects the quadriceps muscle of
the thigh, which is anchored to the leg bone by the patellar tendon. When
the lower leg hangs free and this tendon is tapped with a small hammer,
the quadriceps muscle is stretched, activating the stretch-sensitive
sensory receptors embedded in it.
The sensory receptors then send a signal to the spinal cord through
sensory neurons that synapse with motor neurons projecting to the same
thigh muscle. The discharge from the motor neurons stimulates the
muscle, causing it to contract to resist the stretch. Because the tap is
brief, the stimulation is over before the motor message arrives, and the
muscle contracts even though it is no longer stretched. This contraction
pulls the leg up, producing the knee jerk reflex.

FIGURE 11-20 Monosynaptic Reflex

This simplest of reflexes entails monosynaptic connections between
single sensory neurons and single motor neurons. Somatosensory
neurons receiving information from the skin make much more complex
connections with both interneurons and motor neurons. These
multisynaptic connections are responsible for more complex spinal
movements, such as those involved in standing and walking, actions that
include many muscles on both sides of the body.

Feeling and Treating Pain

As many as 30 percent of physician visits involve pain symptoms, as do
50 percent of emergency room visits. People have pain as a result of
acute injuries such as broken bones, chronic conditions such as cancer
and arthritis, and everyday conditions such as stiff muscles from
exercising. Women have pain during menstruation, pregnancy, and
childbirth. The incidence of living with pain increases as people age, and
for many people, pain is a constant companion.
Perceiving Pain
People can experience central pain in a part of the body that is not
obviously injured. One type of central pain is phantom limb pain. As
described in Research Focus 11-5 , Phantom Limb Pain on page 386 ,
phantom sensations are felt in a limb that has been lost, hence the term.
People in pain would happily dispense with it. But pain is necessary:
the rare person born without pain receptors has body deformities because
of failure to adjust posture and acute injuries because of failure to avoid
harm.
Pain perception results from synthesizing a plethora of sensory
information. There may be as many as eight kinds of pain fibers, judging
from the peptides and other chemicals released by these nerves when
irritated or damaged. Some of these chemicals irritate surrounding tissue,
stimulating it to release other chemicals to stimulate blood flow and to
stimulate the pain fibers themselves. These reactions contribute to pain,
redness, and swelling at the site of an injury.
Consider itch. We may feel itchy and consequently scratch a foreign
object on our body. We also frequently feel itch in the absence of an
obvious stimulus. Some drugs, including opioids, enhance itch
sensations in the absence of a physical stimulus at the itchy body part.
Haptic information also contributes to pain perception. For example,
people can accurately report the location and characteristics of various
kinds of pain, but in the absence of fine-touch and pressure information,
pain is more difficult to identify and localize.
The anterior spinothalamic tract, illustrated in Figure 11-18 , is the
main pain pathway to the brain, but as many as four other pathways may
carry pain information from the spinal cord to the brain. These pathways
are both crossed and uncrossed and project to the reticular formation of
the midbrain, where they produce arousal; to the amygdala, where they
produce emotional responses typically associated with pain; and to the
hypothalamus, where they activate hormonal and cardiovascular
responses.
 The existence of multiple pain pathways in the spinal cord makes it
difficult to treat chronic pain, even by selectively cutting the anterior
spinothalamic tract—one radical procedure used to control chronic pain.
It is likely that each pain pathway has its own function, whether for
sensation, arousal, emotional responses, or other physiological
responses.
Responding to Pain
Neuronal circuits in the spinal cord allow haptic-proprioceptive and
nociceptive pathways to interact. Such interactions may be responsible
for our puzzling and variable responses to pain. For example, people
who are engaged in combat or intense athletic competition may receive a
serious physical injury but start to feel the pain only much later.
monosynaptic reflex Reflex requiring one synapse between sensory
input and movement.
RESEARCH FOCUS 11-5

Phantom Limb Pain

Up to 80 percent of people who have had a limb amputated also
endure phantom limb phenomena, including pain and other
sensations and motor phantoms, such as phantom movement and
cramps (Kern et al., 2009). Phantom sensations and movements are
illusions that originate in the brain.
Various techniques used to minimize phantom limb pain include
drug-based pain management with opioids and the injection of pain
medications into the spinal cord. An innovative method devised by
V. S. Ramachandran (1996) assists the patient in setting up a
counter-illusion that the limb is intact and is providing normal
sensory input to the brain.
Ramachandran devised a mirror box into which a person who has
lost an arm inserts the intact arm and then observes its reflection in
the mirror. The reflection suggests that the missing arm is present
and can be controlled, as shown in the illustration. The perception of
the limb as intact counteracts phantom pain and cramps.
Inspired by Ramachandran’s mirror box, researchers have
developed other illusions to suggest that a missing limb is present
and can be controlled. One method uses virtual reality goggles.
Another uses the so-called rubber limb phenomenon to produce the
illusion that a missing limb is present. To induce this phenomenon,
the stump of the amputated limb is stimulated tactually while the
subject observes a prosthetic limb being touched.
All of the illusions lessen phantom limb pain and cramps by
suggesting that a normal limb is present. Using similar logic,
Hellman and associates (2015) suggest the possibility of developing
neuroprosthetic limbs that provide their users sensory information to
alleviate phantoms.
Alessandria and colleagues (2011) asked whether phantom limbs
and their associated sensations also occur during dreaming. They
awoke sleeping participants with amputations during rapid eye
movement, or REM, sleep and asked them to recount their dreams.
 In none of the dreams did the participants remember having an
amputated limb or phantom limb sensations.
This finding suggests that the integrity of brain regions associated
with a limb is preserved even though the limb is absent. When
awake, the loss of moment-to-moment sensory activity from the limb
results in the opportunity for phantom perceptions.

Section 6-2 notes similarities between the brain’s endogenous

opioids and opioid analgesic drugs.
A friend of ours was attacked by a grizzly bear while hiking and
received 200 stitches to bind his wounds. When friends asked if it hurt to
be bitten by a grizzly bear, he surprisingly answered no, explaining, “I
had read the week before about someone who was killed and eaten by a
grizzly bear. So I was thinking that this bear was going to eat me unless I
got away. I did not have time for pain. I was fighting for my life. It was
not until the next day that I started feeling pain.”
The primacy of our friend’s fear over his pain is related to the stress
he was under. Not feeling pain in a fight-or-flight situation is obviously
adaptive, as this story illustrates, and may be related to the activation of
endogenous opioid peptides. Treatments for pain include opioid drugs
(such as morphine), acupuncture (which entails the rapid vibration of
needles embedded in the skin), and simply rubbing the area surrounding
the injury. Psychological factors interact with pain treatments, and most
studies on pain management find that placebos can be as effective as
actual treatments. Pain is puzzling in the variety of ways that lessen it.
To explain both the perception of pain and how it can be suppressed
in so many ways, Ronald Melzack and Patrick Wall (1965) proposed a
gate theory of pain. Its essence as applied to pain perception is that
activities in different sensory pathways play off against each other and so
determine whether and how much pain is perceived as a result of an
injury. Melzack and Wall propose that haptic-proprioceptive stimulation
can reduce pain perception, whereas the absence of such stimulation can
increase pain perception through interactions at a pain gate.

FIGURE 11-21 Pain Gate A spinal cord interneuron receives excitatory

input (plus signs) from the fine-touch and pressure pathway; and inhibitory
input (minus signs) from the pain and temperature pathway. The
interneuron’s relative activity then determines whether pain and
temperature information ascends to the brain. Information from R. Melzack (1973).
The Puzzle of Pain (p. 154). New York: Basic Books.

A model of the pain gate, illustrated in Figure 11-21 , consists of a

haptic-proprioceptive fiber that conveys fine touch and pressure
information and a nociceptive fiber that conducts pain information. Each
fiber synapses with the same interneuron. Collaterals from the haptic-
proprioceptive pathway excite the interneuron, whereas collaterals from
the nociceptive pathway inhibit it. The interneuron, in turn, inhibits a
neuron that relays pain information from the spinal cord to the brain.
Consequently, when the haptic-proprioceptive pathway is active, the
interneuron is stimulated, inhibiting the secondary pain neuron, and the
interneuron acts as a gate, reducing the pain sensation.
Treating Pain
Gate theory helps to explain how so many pain treatments work (Foster
et al., 2015). When you stub your toe, for instance, you feel pain because
the pain pathway to the brain is open. Rubbing the toe activates the
haptic-proprioceptive pathway and reduces the information flow in the
pain pathway because the pain gate partly closes, relieving the pain by
crowding it out.
Similarly, a variety of pain treatments, including massage, warm
water immersion, and acupuncture, may produce pain-relieving effects
by selectively activating haptic and proprioceptive fibers relative to pain
fibers, thus closing the pain gate. For acupuncture, vibrating needles on
different body points presumably activate fine-touch and pressure fibers.
The pain gate model may also explain why opioid drugs influence pain.
The interneuron that is the gate uses an endogenous opioid as an
inhibitory neurotransmitter. Thus, opioids have one of their effects in
relieving pain by mimicking the actions of the endogenous opioid
neurotransmitter of the interneuron.
One of the most successful pain treatments is injecting small amounts
of morphine under the dura mater, the outer layer of the meninges. This
epidural anesthesia is mediated by the action of morphine on
interneurons in the spinal cord. Although morphine is a highly useful
pain treatment, its effects lessen with continued use. This form of
habituation may be related to changes that take place on the postsynaptic
receptors of pain neurons in the spinal cord and brain.
Gate theory also suggests an explanation for the pins and needles we
feel after sitting too long in one position. Loss of oxygen from reduced
blood flow first deactivates the large myelinated axons that carry touch
and pressure information, leaving the small unmyelinated fibers that
carry pain and temperature messages unaffected. As a result, ungated
sensory information flows in the pain and temperature pathway, leading
to the pins and needles.
Neural circuits resembling pain gates may be located in the brainstem
and cortex as well as the spinal cord. These gates help to explain how
cognition and emotion influence pain and how other approaches to pain
relief work. For example, researchers have found that feelings of severe
pain can be lessened when people can shift their attention from the pain
to other stimuli. Dentists have long used this technique by giving their
patients something soothing to watch or listen to during procedures.
Figure 2-4 diagrams the triple-layered meninges encasing the brain
and spinal cord.
pain gate Hypothetical neural circuit in which activity in fine-touch
and pressure pathways diminishes the activity in pain and
temperature pathways.
The brain can also influence the pain signal it receives from the spinal
cord. The cell bodies of periaqueductal gray matter (PAG) neurons
surround the cerebral aqueduct connecting the third and fourth ventricles.
Electrical stimulation of the PAG is effective in suppressing pain.
Neurons in the PAG produce their pain-suppressing effect by exciting
pathways (including serotonergic and noradrenergic pathways) in the
brainstem that project to the spinal cord. There they inhibit neurons that
form the ascending pain pathways. Activation in these inhibitory circuits
in part explains why pain sensation and perception ease during sleep.
Deep brain stimulation of the PAG by implanted microelectrodes is one
way of treating pain that proves resistant to all other therapies, including
treatment with opioid drugs.
Many internal organs, including the heart, kidneys, and blood vessels,
have pain receptors, but the ganglion neurons carrying information from
these receptors do not have their own pathway to the brain. Instead, they
synapse with spinal cord neurons that receive nociceptive information
from the body’s surface. Consequently, the spinal cord neurons that relay
pain and temperature messages to the brain receive two sets of signals:
one from the body’s surface and the other from the internal organs.
These spinal cord neurons cannot distinguish the two sets of signals—
nor can we. As a result, pain in body organs is felt as referred pain
coming from the body surface. For example, pain in the heart associated
with a heart attack is felt as pain in the left shoulder and upper arm (
Figure 11-22 ). Pain in the stomach is felt as pain in the midline of the
trunk; pain in the kidneys is felt as pain in the lower back. Pain in blood
vessels in the head is felt as diffuse pain that we call a headache.
(Remember, the brain has no pain receptors.)
The PAG is one nucleus in the midbrain’s tegmentum (floor), shown here
in cross section. DBS is pictured in Figure 1-6 .
 FIGURE 11-22 Referred Pain During a heart attack, pain from
receptors in the heart is commonly felt in the left shoulder and upper arm,
especially in men.

Vestibular System and Balance

The only localized part of the somatosensory system, the vestibular
system, consists of two organs, one in each inner ear. As Figure 11-23 A
shows, each vestibular organ consists of two groups of receptors: the
three semicircular canals and the otolith organs, the utricle and the
saccule. These vestibular receptors do two jobs: (1) they tell us the
position of the body in relation to gravity and (2) they signal changes in
direction and speed of head movement.
In Figure 11-23 A the semicircular canals are oriented in three planes
that correspond to the three dimensions in which we move through
space. Each canal furnishes information about movement in its particular
plane. The semicircular canals are filled with a fluid called endolymph.
Immersed in the endolymph is a set of hair cells.
When the head moves, the endolymph also moves, pushing against
the hair cells and bending the cilia at their tips. The force of the bending
is converted into receptor potentials in the hair cells that send action
potentials over auditory vestibular nerve axons to the brain. These axons
are normally quite active: bending the cilia in one direction increases
receptor potentials, consequently increasing vestibular nerve axon
activity; bending them in the other direction decreases vestibular afferent
axon activity. These responses are diagrammed in Figure 11-23 B.
Typically, when the head turns in one direction, the receptor message on
that side of the body increases neuronal firing. The message on the
body’s opposite side leads to decreased firing.
The utricle and saccule lie stacked just beneath the semicircular
canals, as shown at the right in Figure 11-23 A. These organs also
contain hair cells, but the receptors are embedded in a gelatinous
substance that contains otoconia ( sing. otoconium), small crystals of the
salt calcium carbonate. When you tilt your head, the gelatin and otoconia
press against the hair cells, bending them. The mechanical action of the
hair bending modulates the rate of action potentials in vestibular afferent
axons that convey messages about the head’s position in three-
dimensional space.
The receptors in the vestibular system tell us about our location
relative to gravity, about acceleration and deceleration of our
movements, and about changes in movement direction. They also allow
us to ignore the otherwise destabilizing influence that our movements
might have on us. When you are standing on a moving bus, for example,
even slight movements of the vehicle could potentially throw you off
balance, but they do not. Similarly, when you move, you easily avoid
tipping over, despite the constant shifting of your body weight. Your
vestibular system enables your stability.
Vestibular hair cells work on the same principles as cochlear hair
cells, which mediate hearing. See Section 10-2 .
Cranial nerve 8 conveys both hearing and balance information to the
brain. See Figure 2-27 .
FIGURE 11-23 The Vestibular System (A) The vestibular organs in
each inner ear contain hair cells sensitive to head movement and to
gravity. (B) A vestibular neuron is normally active. Its activity increases if
the cilia at the tips of its hair cell receptors bend in one direction but
decreases if the receptors bend in the opposite direction .
 11-4 REVIEW
Somatosensory System Receptors and Pathways
Before you continue, check your understanding.
1 . Body senses contribute to the perception of ___________ (touch and
pressure), ___________ (location and movement), and ___________
(temperature, pain, itch).
2 . Haptic-proprioceptive information is carried into the CNS by the
___________ spinothalamic tract; nociceptive information is carried in
by the ___________ spinothalamic tract.
3 . The two tracts interact in the spinal cord to regulate pain perception
via a ___________.
4 . In the midbrain, the ___________ suppresses pain by activating
neuromodulatory circuits that inhibit pain pathways.
5 . The only localized somatosensory system is the ___________ system,
which helps us to maintain ___________ by signaling information
about the head’s position and our movement through space.
6 . Explain how proprioception acts as the “eyes of the body.”
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 11-5 Exploring the Somatosensory Cortex
Somatosensory neurons do more than convey sensation to the brain: they
enable us to perceive things that we describe as pleasant or unpleasant,
the shape and texture of objects, the effort required to complete tasks,
and even our spatial environment. They also play a central role in
movement. Figure 11-24 illustrates the two main somatosensory areas in
the cortex.
Korbinian Brodmann numbered these areas more than a century ago
on his map of the cortex (see Figure 2-23 ).
The primary somatosensory cortex (S1), which receives projections
from the thalamus, consists of Brodmann areas 3-1-2 (all appear red in
Figure 11-24 ). The primary somatosensory cortex begins to construct
perceptions from somatosensory information. It mainly consists of the
postcentral gyrus in the parietal lobe, just behind the central fissure.
Thus, S1 lies adjacent to the primary motor cortex, on the other side of
the central fissure in the frontal lobe.
The secondary somatosensory cortex (Brodmann areas 5 and 7,
shaded orange and yellow in Figure 11-24 ) is located in the parietal lobe
just behind S1. The secondary somatosensory cortex (S2) refines
perceptual constructions in relation to potential movement and sends
information to the frontal cortex.

FIGURE 11-24 Somatosensory Cortex Stimulation of the primary

somatosensory cortex in the parietal lobe produces sensations that are
referred to appropriate body parts. Information from the primary
somatosensory cortex travels to the secondary somatosensory cortex for
further perceptual analysis.

Somatosensory Homunculus
In his studies of human patients undergoing brain surgery, Wilder
Penfield electrically stimulated the somatosensory cortex and recorded
patients’ responses. Stimulation at some sites elicited sensations in the
foot; stimulation of other sites produced sensations in a hand, the trunk,
or the face. By mapping these responses, Penfield was able to construct a
somatosensory homunculus in the cortex, shown in Figure 11-25 A . The
sensory homunculus looks nearly identical to the motor homunculus
shown in Figure 11-6 in that the most sensitive areas of the body are
accorded relatively large cortical areas.
Using smaller electrodes and more precise recording techniques in
monkeys, Jon Kaas (1987) found that Penfield’s homunculus could be
subdivided into a series of smaller homunculi. When Kaas stimulated
sensory receptors on the body and recorded the activity of cells in the
sensory cortex, he found that the somatosensory cortex comprises four
representations of the body. Each is associated with a class of sensory
receptors.
The progression of these representations across S1 from front to back
is shown in Figure 11-25 B. Area 3a cells are responsive to muscle
receptors; area 3b cells are responsive to slow-responding skin receptors.
Area 1 cells are responsive to rapidly adapting skin receptors, and area 2
cells are responsive to deep tissue pressure and joint receptors. In another
study, Hiroshi Asanuma (1989) and his coworkers found still another
sensory representation in the motor cortex (area 4) in which cells
respond to muscle and joint receptors.
(A) Penfield’s single-homunculus model

(B) Four-homunculus model

 Two Models of the Primary
FIGURE 11-25

Somatosensory Cortex
Perceptions constructed from elementary sensations depend on
combining the sensations. This combining takes place as areas 3a and 3b
project onto area 1, which in turn projects onto area 2. Whereas a cell in
area 3a or 3b may respond to activity in only a certain area on a certain
finger, for example, cells in area 1 may respond to similar information
from a number of fingers.
At the next level of synthesis, cells in area 2 respond to stimulation in
a number of locations on a number of fingers as well as to stimulation
from different kinds of somatosensory receptors. Thus, area 2 contains
multimodal neurons responsive to force, orientation, and direction of
movement. We perceive all these properties when we hold an object in
our hands and manipulate it.
 With each successive information relay, both the size of the pertinent
receptive fields and the synthesis of somatosensory modalities increase.
The segregation of sensory neuron types at the level of the cortex is
likely the basis for our ability to distinguish among different kinds of
sensory stimuli coming from different sources. For example, we
distinguish between tactile stimulation on the surface of the skin, which
is usually produced by some external agent, and stimulation coming
from muscles, tendons, and joints, which is usually produced by our own
movements.
At the same time, we perceive the combined sensory properties of a
stimulus. For instance, when we manipulate an object, we know the
object both by its sensory properties, such as temperature and texture,
and by the movements we make as we handle it. Thus, the cortex
provides for somatosensory synthesis too. The tickle sensation seems
rooted in an other-versus-us somatosensory distinction, as described in
Research Focus 11-6 , Tickling, on page 392 .
Research by Vernon Mountcastle (1978) shows that cells in the
somatosensory cortex are arranged in functional columns running from
layer I to layer VI, similar to the functional columns found in the visual
cortex. Every cell in a functional somatosensory cortical column
responds to a single class of receptors. Some columns are activated by
rapidly adapting skin receptors, others by slowly adapting skin receptors,
still others by pressure receptors, and so forth. All neurons in a
functional column receive information from the same local skin area. In
this way, neurons lying within a column seem to be an elementary
functional unit of the somatosensory cortex.
See Section 9-1 for details on receptive fields.
Figure 9-33 shows functional column organization in V1.
RESEARCH FOCUS 11-6

Tickling
Everyone knows the effects and consequences of tickling. The
perception is a curious mixture of pleasant and unpleasant
sensations. The two kinds of tickling are kinismesis, the sensation
from a light caress, and gargalesis, the pleasurable effect of hard
rhythmic probing.
The tickle sensation is felt not only by humans but also by other
primates and by cats, rats, and probably most mammals. Play in rats
is associated with 50-kilohertz vocalizations, and tickling body
regions that are targets of the rats’ own play also elicits 50-kilohertz
vocalizations (Panksepp, 2007).
Tickling is rewarding because people and animals solicit tickles
from others. They even enjoy observing others being tickled. Using a
robot and brain imaging techniques, Sarah Blakemore and her
colleagues (1998) explained why we cannot tickle ourselves.
Blakemore had participants deliver two kinds of identical tactile
stimuli to the palms of their hand. In one condition, the stimulus was
predictable and in the other a robot introduced an unpredictable
delay in the stimulus. Only the unpredictable stimulus was perceived
as a tickle. Thus, it is not the stimulation itself but its
unpredictability that accounts for the tickle perception. This is why
we cannot tickle ourselves. Yet Windt and associates (2015), using a
self-report method, find that during lucid dreams, the self–other
distinction is absent: people do dream that they tickle themselves.
One interesting feature of tickling is the distinctive laughter it
evokes. This laughter can be identified by sonograms (sound
analysis), and people can distinguish tickle-related laughter from
other forms of laughter.
Intrigued by findings that all apes appear to laugh during tickling,
Ross and coworkers (2009) compared tickle-related laughter in apes
and found that human laughter is more similar to chimpanzee
laughter than to the laughter of gorillas and other apes. We humans
 thus have inherited from our common ape ancestors both a
susceptibility to tickling and laughter as well.

LWA-Dann Tardif/CORBIS

Effects of Somatosensory Cortex Damage

Damage to S1 impairs the ability to make even simple sensory
discriminations and movements. Suzanne Corkin and her coworkers
(1970) demonstrated this effect by examining patients with cortical
lesions that included most of areas 3-1-2 in one hemisphere. The
researchers mapped the primary sensory cortex of these patients before
they underwent elective surgery for removal of a carefully defined piece
of that cortex, including the hand area. The patients’ sensory and motor
skills in both hands were tested on three occasions: before the surgery,
shortly after the surgery, and almost a year afterward.
The tests included pressure sensitivity, two-point touch
discrimination, position sense (reporting the direction in which a finger
was being moved), and haptic sense (using touch to identify objects,
such as a pencil, a coin, eyeglasses, and so forth). For all the sensory
abilities tested, the surgical lesions produced a severe and seemingly
permanent deficit in the contralateral hand. Sensory thresholds,
proprioception, and hapsis—all were greatly impaired.
 The results of other studies of both humans and other animals have
shown that damage to the somatosensory cortex also impairs simple
movements. For example, limb use in reaching for an object is impaired,
as is the ability to shape the hand to hold an object (Leonard et al., 1991).
Nevertheless, like the motor cortex, the somatosensory cortex is
plastic. Plasticity is illustrated by the reorganization of somatosensory
cortex after deafferentation. In 1991, Tim Pons and his coworkers
reported a dramatic change in the somatosensory maps of monkeys in
which the ganglion cells for one arm had been cut, deafferentating the
limb, a number of years earlier. The researchers had wanted to develop
an animal model of damage to sensory nerves that could offer insight
into human injuries, but they were interrupted by a legal dispute with an
animal advocacy group. Years later, as the health of the animals declined,
a court injunction allowed the mapping experiment to be conducted.
Section 7-7 considers debates over using laboratory animals in
brain–behavior research.
(A) Control monkey

(B) Deafferentated monkey

 FIGURE 11-26 Somatosensory Plasticity Information from T. P. Pons, P.
E. Garraghty, A. K. Ommaya, J. H. Kaas, & M. Mishkin (1991). Massive cortical reorganization
after sensory deafferentation in adult macaques. Science, 252, p. 1858.

Pons and his coworkers discovered that the area of somatosensory

cortex that had formerly represented the arm no longer did so. Light
touches on a monkey’s lower face now activated cells in what had
formerly been the cortical arm region. As illustrated in Figure 11-26 ,
the cortical facial area had expanded by as much as 10 to 14 millimeters,
virtually doubling its original size by entering the arm area.
This massive change was completely unexpected. The stimulus–
response patterns associated with the expanded facial area of the cortex
appeared indistinguishable from those associated with the original facial
area. Furthermore, the trunk area, which bounded the other side of the
cortical arm area, did not expand into the vacated arm area.
What could account for this expansion of the face area into the arm
area? There is evidence for preexisting axon collaterals that are not
normally active, but these collaterals would probably not be able to
extend far enough to account for all of the cortical reorganization.
Another possibility is that within the thalamic and brainstem relay
pathways, facial-area neurons project collaterals to arm-area neurons.
These neurons are close together, so the collaterals need travel only a
millimeter or so (Kambi et al., 2014). Whatever the mechanism, the
dramatic cortical reorganizations observed in the Pons study are helpful
in understanding other remarkable phenomena, including phantom limb
sensations. In humans who have lost a forelimb, touches to the face can
be felt as touches to the missing forearm.
Figure 14-23 diagrams this phenomenon.
Somatosensory Cortex and Complex
Movement
How are our abilities to move and to interpret stimulation on the body
related? Our somatosensory cortex actually makes an important
contribution to movement. Damage to the secondary somatosensory
cortex does not disrupt the plans for making movements, but it does
disrupt how the movements are performed, leaving their execution
fragmented and confused. This inability to complete a plan of action
accurately—to make a voluntary movement—is called apraxia. The
following case highlights its symptoms.
A woman with a biparietal lesion [damage on the left- and right-
hemisphere secondary somatosensory cortex] had worked for years as a
fish-filleter. With the development of her symptoms, she began to
experience difficulty in carrying on with her job. She did not seem to
know what to do with her knife. She would stick the point in the head of
a fish, start the first stroke, and then come to a stop. In her own mind she
knew how to fillet fish, but yet she could not execute the maneuver. The
foreman accused her of being drunk and sent her home for mutilating
fish.
The same patient also showed another unusual phenomenon that
might possibly be apraxic in nature. She could never finish an
undertaking. She would begin a job, drop it, start another, abandon that
one, and within a short while would have four or five uncompleted tasks
on her hands. This would cause her to do such inappropriate actions as
putting the sugar bowl in the refrigerator, and the coffeepot inside the
oven. (Critchley, 1953, pp. 158–159)
The somatosensory cortex contributes to movement by participating
in both the dorsal and the ventral visual streams. The dorsal (how)
stream, working without conscious awareness, provides vision for action,
as when we automatically shape a hand as we reach to grasp a cup (recall
Figure 11-1 ). Within this stream a number of channels specify the
movements—reaching, manipulating, bringing a hand to the mouth,
walking—that we should make in response not only to somatosensory
information but also to visual and auditory information. The ventral
(what) stream, in contrast, works with conscious awareness for
perception—that an object is a cup.
 As Figure 11-27 illustrates, the dorsal visual stream projects to the
secondary somatosensory cortex and then to the frontal cortex (Kaas et
al., 2012). In this way, visual information is integrated with
somatosensory information to produce unconscious movements
appropriately shaped and directed to their targets, as in reaching for a
cup. The secondary somatosensory area contributes perceptual
information to the ventral stream by providing conscious haptic
information about object identity and completed movements. From this
information the frontal cortex can imagine the consequence of a
movement and select the actions that appropriately follow from those
already completed.
Apraxia derives from the Greek words for no and action.

FIGURE 11-27 Visual Aid Section 9-4 explains how visual information
from the dorsal and ventral streams contributes to movement.
apraxia Inability to make voluntary movements in the absence of
paralysis or other motor or sensory impairment, especially an
inability to make proper use of an object.
 11-5 REVIEW
Exploring the Somatosensory Cortex
Before you continue, check your understanding.
1 . The ___________ somatosensory cortex, arranged as a series of
homunculi, feeds information to the ___________ somatosensory
cortex, which produces somatosensory perception.
2 . Damage to the secondary somatosensory cortex produces
___________, an inability to complete a series of movements.
3 . The somatosensory cortex provides information to the ___________
stream to produce unconscious movements and also provides
information to the ___________ stream for conscious recognition of
objects.
4 . Explain briefly what phantom limb pain tells us about the brain.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
SUMMARY
In the nervous system, the somatosensory and motor systems are
interrelated at all levels. At the level of the spinal cord, sensory
information contributes to motor reflexes; in the brainstem, sensory
information contributes to complex regulatory movements. At the level
of the neocortex, sensory information represents the sizes, shapes, and
positions of objects and records just-completed movements.
11-1 Hierarchy of Movement Control
Movement is organized hierarchically, using the entire nervous system
(review Figure 11-1 ). The forebrain plans, organizes, and initiates
movements, whereas the brainstem coordinates regulatory functions,
such as eating and drinking, and controls neural mechanisms that
maintain posture and produce locomotion. Many reflexes are organized
at the level of the spinal cord and occur without the brain’s involvement.
11-2 Motor System Organization
Maps produced by stimulating the primary motor cortex show that it is
organized topographically as a homunculus with different cortical areas
capable of producing different movements. Motor cortex neurons initiate
movement, produce movement, control movement force, and indicate
movement direction. Disuse of a limb, as might result from a motor
cortex injury, results in shrinkage of the limb’s cortical representation.
This shrinkage can be prevented, however, if the limb can be somehow
forced into use, as in constraint-induced therapy.
Two corticospinal pathways emerge from the motor cortex to the
spinal cord. Lateral corticospinal axons project from cortical areas that
control arm and hand movements. The lateral tract crosses from the
contralateral brain hemisphere to form synapses with spinal interneurons
and motor neurons located laterally in the spinal cord, and on the side
opposite the brain hemisphere where the lateral tract formed. Anterior
corticospinal tract axons project from the cortical motor regions that
produce whole-body movements. The anterior tract synapses with
interneurons and motor neurons located medially and ipsilaterally in the
spinal cord.
Spinal cord interneurons and motor neurons also are topographically
organized: lateral motor neurons project to digit, hand, and arm muscles
to produce arm and hand movements, and medial motor neurons project
to trunk muscles and mediate whole-body movements, including
locomotion.
11-3 Basal Ganglia, Cerebellum, and Movement
Movement abnormalities result from damage to the basal ganglia or to
the cerebellum. Both structures participate in movement control by
modulating the movements initiated by the cortex. The basal ganglia
regulate force; the cerebellum maintains accuracy and participates in
learning.
11-4 Somatosensory System Receptors and
Pathways
Distributed throughout the body, the somatosensory system consists of
more than 20 types of specialized sensory neurons and receptors, each
sensitive to a particular form of mechanical energy. Located in posterior
dorsal root ganglia, each of these neurons carries sensory information
into the spinal cord and the brain.
Neurons carrying proprioceptive (location and movement)
information and haptic (touch and pressure) information have axons that
ascend the spinal cord as the posterior spinothalamic tract. These fibers
synapse in the posterior column nuclei at the base of the brain. From
there axons cross to the other side of the brainstem to form the medial
lemniscus, which ascends to the ventrolateral thalamus. Most of the
ventrolateral thalamus cells project to the somatosensory cortex.
Nociceptive (pain, temperature, and itch) posterior root ganglion
neurons synapse on entering the spinal cord. Their relay neurons cross
the spinal cord to ascend to the thalamus as the anterior spinothalamic
tract.
Because the two somatosensory pathways take somewhat different
routes, unilateral spinal cord damage impairs proprioception and hapsis
ipsilaterally below the site of injury and nociception contralaterally
below the site.
11-5 Exploring the Somatosensory Cortex
The somatosensory system is represented topographically in parietal
areas 3-1-2. The most sensitive body parts are accorded the largest
somatosensory regions, as befits the body parts most capable of fine
movements.
A number of sensory homunculi represent various sensory modalities,
and these regions are hierarchically organized. If sensory input from
anywhere in the body is cut off from the cortex by damage to sensory
fibers, adjacent functional sensory cortex can expand into the now-
unoccupied region.
Through the dorsal visual stream, the somatosensory cortex
contributes to directing hand and body movements to visual targets. The
somatosensory cortex also contributes to the ventral visual stream to
produce perception of external objects, through which we can imagine
the consequences of our movements.
KEY TERMS
anterior spinothalamic tract, p. 383
apraxia, p. 394
cerebral palsy, p. 363
connectome, p. 363
constraint-induced therapy, p. 371
corticospinal tract, p. 371
deafferentation, p. 383
glabrous skin, p. 379
hapsis, p. 381
homunculus, p. 367
hyperkinetic symptom, p. 374
hypokinetic symptom, p. 374
locked-in syndrome, p. 363
Ménière disease, p. 389
monosynaptic reflex, p. 385
motor sequence, p. 359
neuroprosthetics, p. 357
nociception, p. 381
pain gate, p. 387
paraplegia, p. 364
periaqueductal gray matter (PAG), p. 389
posterior spinothalamic tract, p. 383
proprioception, p. 381
quadriplegia, p. 364
rapidly adapting receptor, p. 381
referred pain, p. 389
scratch reflex, p. 364
slowly adapting receptor, p. 381
topographic organization, p. 367
ventrolateral thalamus, p. 383
vestibular system, p. 389

Visit Launch Pad to access the e-Book, videos,

Learning Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

12

What Causes Emotional

and Motivated
Behavior?
 Katherine Streeter

RESEARCH FOCUS 12-1 THE PAIN OF REJECTION

12-1 IDENTIFYING THE CAUSES OF BEHAVIOR
BEHAVIOR FOR BRAIN MAINTENANCE
NEURAL CIRCUITS AND BEHAVIOR
12-2 THE CHEMICAL SENSES
OLFACTION
GUSTATION
12-3 EVOLUTION, ENVIRONMENT, AND BEHAVIOR
EVOLUTIONARY INFLUENCES ON BEHAVIOR
ENVIRONMENTAL INFLUENCES ON BEHAVIOR
INFERRING PURPOSE IN BEHAVIOR: TO KNOW A FLY
12-4 NEUROANATOMY OF MOTIVATED AND EMOTIONAL
BEHAVIOR
REGULATORY AND NONREGULATORY BEHAVIOR
REGULATORY FUNCTION OF THE HYPOTHALAMIC CIRCUIT
ORGANIZING FUNCTION OF THE LIMBIC CIRCUIT
EXECUTIVE FUNCTION OF THE FRONTAL LOBES
CLINICAL FOCUS 12-2 AGENESIS OF THE FRONTAL LOBES
STIMULATING AND EXPRESSING EMOTION
AMYGDALA AND EMOTIONAL BEHAVIOR
PREFRONTAL CORTEX AND EMOTIONAL BEHAVIOR
EMOTIONAL DISORDERS
CLINICAL FOCUS 12-3 ANXIETY DISORDERS
12-5 CONTROL OF REGULATORY AND NONREGULATORY
BEHAVIOR
CONTROLLING EATING
CLINICAL FOCUS 12-4 WEIGHT LOSS STRATEGIES
EXPERIMENT 12-1 QUESTION: DOES THE HYPOTHALAMUS
PLAY A ROLE IN EATING?
CONTROLLING DRINKING
CONTROLLING SEXUAL BEHAVIOR
CLINICAL FOCUS 12-5 ANDROGEN INSENSITIVITY
SYNDROME AND THE ANDROGENITAL SYNDROME
SEXUAL ORIENTATION, SEXUAL IDENTITY, AND BRAIN
ORGANIZATION
COGNITIVE INFLUENCES ON SEXUAL BEHAVIOR
12-6 REWARD
RESEARCH FOCUS 12-1

The Pain of Rejection

We use words like sorrow, grief, and heartbreak to describe a loss.
Loss evokes painful feelings, and the loss or absence of contact that
comes with social rejection leads to hurt feelings. Several
investigators have attempted to discover whether physically painful
and emotionally hurtful feelings are manifested in the same neural
regions.
Physical pain (say, hot or cold stimuli) is easy to inflict, but
inducing equivalently severe emotional, or affective, pain is more
difficult. Ethan Kross and colleagues (2011) performed an
experiment that may have succeeded in balancing participants’
degree of emotional and physical pain.
Using fMRI, they scanned 40 people who had recently gone
through an unwanted breakup. To compare brain activation, the
participants viewed two photographs: one of their ex-partner, to
evoke negative emotion, or the photo of a same-gender friend with
whom the participant shared a pleasant time at about the time of the
breakup. The picture order was randomized across participants.
Emotional cue phrases associated with each photograph directed
the participants to focus on a specific experience they shared with
each person. The physical stimulus employed by the researchers,
which was administered in a separate session, was either painfully
hot or painless warm stimulation of participants’ forearm.
The research question is, do physical pain and social pain have a
common neuroanatomical basis? The results, shown in the
illustration, reveal that four regions respond to both types of pain:
the insula, dorsal anterior cingulate cortex (dACC), somatosensory
thalamus, and secondary somatosensory cortex (S2). The conclusion:
Social rejection hurts in much the same way physical pain hurts.
Previous studies, including Eisenberger and colleagues, 2003,
2006, showed anterior cingulate activity during the experience of
both physical and emotional pain. But new results also showed
activity in cortical somatosensory regions related to physical pain.
 The results imaged by Kross and colleagues suggest that the brain
systems underlying emotional reactions to social rejection may have
developed by co-opting brain circuits that support the affective
component of physical pain. We hasten to point out, however, that
the overlapping activity in brain regions does not rule out unique
neural components of emotional experiences. Certainly our
subjective experiences are unique (e.g., Woo et al., 2014).
Another insight from the Kross study is that normalizing the
activity of these brain regions probably provides a basis for both
physical and mental restorative processes. Seeing the similarity in
brain activation during social pain and physical pain helps us
understand why social support can reduce physical pain, much as it
soothes emotional pain.

Overlapping Social Rejection and Physical Pain

These fMRIs result from averaging scans from 40 participants to
image the brain’s response to physical or emotional pain. We see
activation in the insula, dorsal anterior cingulate cortex (dACC),
somatosensory thalamus, and/or secondary somatosensory cortex
(S2). Research from E. Kross, M.G. Berman, W. Mischel, E.E. Smith, & T.D. Water,
“Social rejection shares somatosensory representations with physical pain,” 2011,
Proceedings of the National Academy of Sciences (USA), 108, 6270–6275.

Knowing that the brain makes emotional experience real—more than

mere metaphors of hurt or pain —how do we incorporate our thoughts
and reasons for behaving as we do? Clearly, our subjective feelings and
thoughts influence our actions. The cognitive interpretations of
subjective feelings are emotions —anger, fear, sadness, jealousy,
embarrassment, joy. These feelings can operate outside our immediate
awareness.
 emotion Cognitive interpretation of subjective feelings.
This chapter begins by exploring the causes of behavior. Sensory
stimulation, neural circuits, hormones, and reward are primary factors in
behavior. We focus both on emotion and on the underlying reasons for
motivation —behavior that seems purposeful and goal-directed. Like
emotion, motivated behavior is both inferred and subjective, and it can
occur without awareness or intent. It includes both regulatory behaviors,
such as eating, which are essential for survival, and nonregulatory
behaviors, such as curiosity, which are not required to meet an animal’s
basic needs.
motivation Behavior that seems purposeful and goal-directed.
Research on the neuroanatomy responsible for emotional and
motivated behavior focuses on a neural circuit formed by the
hypothalamus, the limbic system, and the frontal lobes. But behavior is
influenced as much by the interaction of our social and natural
environments and by evolution as it is by biology. To explain how all
these interactions affect the brain’s control of behavior, we concentrate
on two specific examples, feeding and sexual activity. Our exploration
leads us to revisit the idea of reward, which is key to explaining
emotional and motivated behaviors.
 12-1 Identifying the Causes of Behavior
We may think that the most obvious explanation for our behavior is
simply that that we act in a state of free will: we do what we want to, and
we always have a choice. But free will is not a likely cause of behavior.
Consider Roger. We first met 25-year-old Roger in the admissions
ward of a large mental hospital when Roger approached us and asked if
we had any snacks. We had chewing gum, which he accepted eagerly.
We thought little about this encounter until 10 minutes later, when we
noticed Roger eating the flowers from the stems in a vase on a table. A
nurse took the vase away but said little to Roger.
Later, as we wandered about the ward, we encountered a worker
replacing linoleum floor tiles. Roger was watching the worker, and as he
did, he dipped his finger into the pot of gluing compound and licked the
glue from his finger, as if he were sampling honey from a jar. When we
asked Roger what he was doing, he said that he was really hungry and
that this stuff was not too bad. It reminded him of peanut butter.
One of us tasted the glue and concluded that it did not taste like
peanut butter. It tasted awful. Roger was undeterred. We alerted a nurse,
who quickly removed him from the glue. Later, we saw him eating
flowers from another bouquet.
Neurological testing revealed that a tumor had invaded Roger’s
hypothalamus at the base of his brain. He was indeed hungry all of the
time and in all likelihood could consume more than 20,000 calories a day
if allowed to do so.
Would you say that Roger was exercising free will regarding his
appetite and food preferences? Probably not. Roger seemed compelled to
eat whatever he could find, driven by a ravenous hunger. The nervous
system, not an act of free will, produced this behavior and undoubtedly
produces many others.
If free will does not adequately explain why we act as we do, what
does? One obvious answer is that we do things that we find rewarding.
Rewarding experiences must activate brain circuits that make us feel
good. Consider the example of prey killing by domestic cats.
One frustrating thing about being a cat owner is that even well-fed
cats kill birds—often lots of birds. Most people are not much bothered
when their cats kill mice: they view mice as a nuisance. But birds are
different. People enjoy watching birds in their yard and garden. Many cat
owners wonder why their pets keep killing birds.
To provide an answer, we look to the activities of neural circuits. Cats
must have a brain circuit that controls prey killing. When this circuit is
active, a cat makes an “appropriate” kill. Viewed in an evolutionary
context, it makes sense for cats to have such a circuit: in the days when
doting humans did not keep cats as pets, cats did not have food dishes
that were regularly filled.
Why does this prey-killing circuit become active when a cat does not
need food? One explanation is that, to secure survival, the activity of
circuits like the prey-killing circuit are in some way rewarding—they
make the cat feel good. As a result, the cat will engage often in the
pleasure-producing behavior. This helps to guarantee that it will usually
not go hungry.
Many people find watching and sharing cute cat videos rewarding: it
makes them feel good, and they do it often.
In the wild, after all, a cat that did not like killing would probably be
dead. In the early 1960s, Steve Glickman and Bernard Schiff (1967) first
proposed the idea that behaviors such as prey killing are rewarding. We
return to reward in Section 12-6 because it is important in understanding
the causes of behavior.

FIGURE 12-1 Sensory Deprivation Experimenters record the EEG

of a participant lying on a bed in a dimly lit environmental cubicle 24 hours
a day, with time out only for meals and bathroom breaks. A translucent
plastic visor restricts the participant’s vision; a U-shaped pillow and the
noise of a fan and air conditioner limit hearing. Cotton gloves and long
 cardboard cuffs restrict the sense of touch. Information from W. Heron (1957). The
Pathology of Boredom. Scientific American, 197(4), p. 52.

Behavior for Brain Maintenance

Some experiences are rewarding; others are aversive, again because
brain circuits are activated to produce behaviors that reduce the aversive
experience. One example is the brain’s inherent need for stimulation.
Donald Hebb and his coworkers (Heron, 1957) studied the effects of
sensory deprivation, depriving people of nearly all sensory input. They
wanted to see how well-fed, physically comfortable college students who
were paid handsomely for their time would react if they did nothing, saw
nothing, and heard or touched very little 24 hours a day. Figure 12-1
shows the experimental setup.
sensory deprivation Experimental setup in which a participant is
allowed only restricted sensory input; participants generally have a
low tolerance for deprivation and may even hallucinate.
Each student lay on a bed in a small, soundproofed room with ears
enveloped by a hollowed-out pillow that muffled the monotonous hums
of a nearby fan and air conditioner. Cardboard tubes covered the hands
and arms, cutting off the sense of touch, and a translucent visor covered
the eyes, blurring the visual world. The participants were given food and
access to bathroom facilities on request. Otherwise, they were asked
simply to enjoy the peace and quiet. For doing so, they would receive
$20 per day—about four times what a student could earn 60 years ago,
even for a day’s hard labor.
Wouldn’t you think the participants would be ecstatic to contribute to
scientific knowledge in such a painless way? In fact, they were far from
happy. Most were content for perhaps 4 to 8 hours; then they became
increasingly distressed. They craved stimulation of almost any kind. In
one version of the experiment, the participants could listen, on request, to
a talk for 6-year-old children on the dangers of alcohol. Some of them
asked to hear it 20 times a day. Few lasted more than 24 hours in these
conditions.
What caused their distress? Why did they find sensory deprivation so
aversive? The answer, Hebb and colleagues concluded, must be that the
brain has an inherent need for stimulation.
 Psychologists Robert Butler and Harry Harlow (1954) came to a
similar conclusion through a series of experiments they conducted at
about the same time Hebb conducted his sensory deprivation studies.
Butler placed rhesus monkeys in a dimly lit room with a small door that
could be opened to view an adjoining room. As shown in Figure 12-2 ,
the researchers could vary the stimuli in the adjoining room so that the
monkeys could view different objects or animals each time they opened
the door.
Monkeys in these conditions spent a lot of time opening the door and
viewing whatever was on display, such as toy trains circling a track. The
monkeys were even willing to perform various tasks just for an
opportunity to look through the door. The longer they were deprived of a
chance to look, the more time they spent looking when finally given the
opportunity.
 University of Wisconsin

FIGURE 12-2 Brain Maintenance Monkeys quickly learn to solve puzzles or

perform other tricks to gain access to a door that looks out from their dimly lit quarters
into an adjacent room. A toy train is a strong visual incentive for the monkey peeking
through the door; a bowl of fruit is less rewarding. From R. A. Butler and H. F. Harlow (1954).
Persistence of Visual Exploration in Monkeys. Journal of Comparative and Physiological Psychology, 47, p. 260.

The Butler and Harlow experiments, together with Hebb and

colleagues’ research on sensory deprivation, show that in the absence of
stimulation, the brain will seek it out.

Neural Circuits and Behavior

Researchers have identified brain circuits for “reward” and discovered
that these circuits can modulate to increase or decrease activity.
Researchers studying the rewarding properties of sexual activity in
males, for example, found that a man’s frequency of copulation
correlates with his levels of androgens (male hormones). Unusually high
androgen levels are related to ultrahigh sexual interest; abnormally low
androgen levels are linked to low sexual interest or perhaps no interest at
all. The brain circuits are more difficult to activate in the absence of
androgens.
androgen Male hormone related to level of sexual interest.
Another way to modulate reward circuits comes via our chemical
senses, smell and taste. The odor of a mouse can stimulate hunting in
cats, whereas the odor of a cat will drive mice into hiding. Similarly, the
smell from a bakery can make us hungry, whereas foul odors can reduce
the rewarding value of our favorite foods. Although we tend to view the
chemical senses as relatively minor in our daily lives, they are central to
motivated and emotional behavior, as discussed next, in Section 12-2 .
Understanding the neural basis for motivated behavior has wide
application. For instance, we can say that Roger had a voracious and
indiscriminate appetite either because the brain circuits that initiate
eating were excessively active or because the circuits that terminate
eating were inactive. Similarly, we can say that Hebb’s participants were
highly upset by sensory deprivation because the neural circuits that
respond to sensory inputs were forced into abnormal underactivity. So
the main reason for a particular thought, feeling, or action lies in what is
going on in brain circuits.
 12-1 REVIEW
Identifying the Causes of Behavior
Before you continue, check your understanding.
1 . One reason cats kill when they may not be hungry is that the killing
behavior is ___________.
2 . A reason animals get bored and seek new things to do is to maintain
a(n) ___________.
3 . Which senses strongly modulate neural circuits?
4 . Why is free will inadequate to explain why we do the things we do?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 12-2 The Chemical Senses
Chemical reactions are central to nervous system activity, and
chemosignals (chemical signals) play a central role in motivated and
emotional behavior. Mammals identify group members by odor, mark
their territory with urine and other odorants, identify favorite and
forbidden foods by taste, and form associations among odors, tastes, and
emotional events.

Olfaction
Olfaction is the most puzzling sensory system. We can discriminate
thousands of odors, yet we have great difficulty finding words to describe
what we smell. We may like or dislike smells or compare one smell to
another, but we lack a vocabulary for olfactory perceptions.
Wine experts rely on olfaction to tell them about wines, but they must
learn to use smell to do so. Training courses in wine sniffing typically run
one full day per week for a year, and most participants still have great
difficulty passing the final test. This degree of difficulty contrasts with
that of vision and audition, senses designed to analyze the specific
qualities of sensory input, such as pitch in audition or color in vision. In
contrast, olfaction seems designed to discriminate whether information is
safe or familiar—is the smell from an edible food? from a friend or a
stranger?—or identifies a signal, perhaps from a receptive mate.
Receptors for Smell
Conceptually, identifying chemosignals is similar to identifying other
sensory stimuli (light, sound, touch). But rather than converting physical
energy such as light or sound waves into receptor potentials, scent
interacts with chemical receptors. This constant chemical interaction must
be tough on the receptors: in contrast with receptors for light, sound, and
touch, chemical receptors are constantly being replaced. The life of an
olfactory receptor neuron is about 60 days.
The receptor surface for olfaction, illustrated in Figure 12-3 , is the
olfactory epithelium in the nasal cavity. The epithelium is composed of
receptor cells and support cells. Each receptor cell sends a process ending
in 10 to 20 cilia into a mucous layer, the olfactory mucosa. Chemicals in
the air we breathe dissolve in the mucosa to interact with the cilia. If an
olfactory chemosignal affects the receptors, metabotropic activation of a
specific G protein leads to an opening of sodium channels and a change in
membrane potential.
Figure 5-15 A illustrates activity in such a metabotropic receptor.
The epithelial receptor surface varies widely across species. In
humans, this area is estimated to range from 2 to 4 square centimeters; in
dogs, about 18 square centimeters; and in cats, about 21 square
centimeters. No wonder our sensitivity to odors is less acute than that of
dogs and cats: they have 10 times as much receptor area as humans have!
Roughly analogous to the tuning characteristics of cells in the auditory
system, olfactory receptor neurons in vertebrates do not respond to
specific odors but rather to a range of odors.
How does a limited number of receptor types allow us to smell many
different odors? The simplest explanation is that any given odorant
stimulates a unique pattern of receptors, and the summed activity or
pattern of activity produces our perception of a particular odor.
Analogously, the visual system enables us to identify several million
colors with only three receptor types in the retina: the summed activity of
the three cones leads to our richly colored life.

FIGURE 12-3 Olfactory Epithelium

A fundamental difference, however, is that the olfactory system is
estimated to contain about 400 kinds of receptors compared with 4 (rods
plus the cones) in the visual system. Some researchers propose that
humans can discriminate up to 1 trillion smells. At present the true
number is unknown but likely more than commonly believed (Gerkin &
Castro, 2015).
Olfactory Pathways
Olfactory receptor cells project to the olfactory bulb, ending in ball-like
tufts of dendrites—the glomeruli shown in Figure 12-3 —where they
form synapses with the dendrites of mitral cells. Mitral cells send their
axons from the olfactory bulb to the broad range of forebrain areas
summarized in Figure 12-4 . Many olfactory targets, such as the
amygdala and pyriform cortex, have no connection through the thalamus,
as do other sensory systems. However, a thalamic connection (to the
dorsomedial nucleus) does project to the orbitofrontal cortex (OFC), the
prefrontal area behind the eye sockets (the orbits ) that receives
projections from this thalamic nucleus. In Section 12-4 we explain the
OFC’s central role in emotional and social behaviors as well as in eating.
orbitofrontal cortex (OFC) Prefrontal cortex behind the eye sockets
(the orbits ); receives projections from the dorsomedial nucleus of
the thalamus; central to a variety of emotional and social behaviors,
including eating; also called orbital frontal cortex.
Accessory Olfactory System
A unique class of odorants is pheromones, biochemicals released by one
animal that act as chemosignals and can affect the physiology or behavior
of another animal of the same species. For example, Karen Stern and
Martha McClintock (1998) found that when women reside together, their
estrous cycles begin to synchronize. Furthermore, the researchers found
that the synchronization of menstrual cycles, a phenomenon called the
Whitten effect, is stimulated by the odor of male urine.
pheromone Odorant biochemical released by one animal that acts as
a chemosignal and can affect the physiology or behavior of another
animal.
Pheromones appear able to affect more than sex-related behavior. A
human chemosignal, androstadienone, has been shown to alter glucose
utilization in the neocortex—that is, how the brain uses energy (Jacob et
al., 2001). Thus, a chemosignal appears to affect cortical processes even
though that signal was not consciously detected. The puzzle is why we
would evolve such a mechanism and how it might actually affect cerebral
functioning.
Pheromones are unique odors because they are detected by a special
olfactory receptor system, the vomeronasal organ, which is made up of a
small group of sensory receptors connected by a duct to the nasal passage.
The receptor cells in the vomeronasal organ send their axons to the
accessory olfactory bulb, which lies adjacent to the main olfactory bulb.
The vomeronasal organ connects primarily with the amygdala and
hypothalamus, via which it probably plays a role in reproductive and
social behavior.
It is likely that the vomeronasal organ participates not in general
olfactory behavior but rather in the analysis of pheromones, such as those
in urine. You may have seen bulls or cats engage in a behavior known as
flehmen, illustrated in Figure 12-5 . When exposed to novel urine from a
cat or human, cats raise their upper lip to close off the nasal passages and
suck air into the mouth. The air flows through the duct on the roof of the
mouth en route to the vomeronasal organ.
FIGURE 12-4 Olfactory Pathways
 Courtesy of Arthur Nonneman and Bryan Kolb

FIGURE 12-5 Response to Pheromones Left: A cat sniffs a urine-

soaked cotton ball. Center: It raises its upper lip to close off the nasal
passages. Right: It follows with the full gape response characteristic of
flehmen, a behavior mediated by the accessory olfactory system.

Human Olfactory Processing

Our ability to distinguish a surprisingly large number of odors upends the
common misperception that people have a miserable sense of smell
relative to other mammals. Still, our threshold for detecting many smells
is certainly inferior to that of our pet dogs, cats, and horses. Yet humans
have a surprisingly acute sensitivity to behaviorally significant smells.
Several studies show convincingly that people can identify their own
odor, the odor of kin versus not-kin, and the odor of friends versus
strangers with an accuracy well above chance (e.g., Olsson et al., 2006).
Johan Lundstrom and colleagues (2008) used PET scans to identify the
neural networks that process human body odors. They made two
surprising findings.
First, the brain analyzes common odors and body odors differently.
Although both activate primary olfactory regions, body odors also
activate structures not previously believed to participate in olfactory
processing, including the posterior cingulate cortex, occipital cortex, and
anterior cingulate cortex—regions also activated by visually emotional
stimuli. Considered in an evolutionary perspective, the ability to identify
human odors probably is uniquely important to safety.
Second, smelling a stranger’s odor activates the amygdala and insular
cortex, similar to activation observed for fearsome visual stimuli such as
masked or fearsome faces. The investigators also asked participants to
rate the intensity and pleasantness of odors; they found that strangers’
odors were rated as stronger and less pleasant than those of familiar
persons.
The insula contains regions related to language, taste perception, and
social cognition.
Lundstrom and colleagues conclude that processing body odors is
mostly unconscious. It represents an automatic process that matches odors
to a learned library of smells. Similar unconscious processes seem to
occur during visual and auditory information processing and to play an
important role in our emotional reactions.

Gustation
Research reveals significant differences in taste preferences both between
and within species. Humans and rats like sucrose and saccharin solutions,
but dogs reject saccharin and cats are indifferent to both, inasmuch as
they do not detect sweetness at all. The failure of cats to taste sweet may
not be surprising: they are pure carnivores, and nothing that they normally
eat is sweet.
Within the human species, clear differences in taste thresholds and
preferences are obvious. An example is the preference for or dislike of
bitter tastes—the flavor of brussels sprouts, for instance. People tend to
love them or hate them. Linda Bartoshuk (2000) showed absolute
differences among adults: some perceive certain tastes as very bitter,
whereas others are indifferent to them. Presumably, the latter group is
more tolerant of brussels sprouts.
Sensitivity to bitterness is related to genetic differences in the ability to
detect a specific bitter chemical (6-n-propylthiouracil, or PROP). PROP
bitterness associates with allelic variation in the taste receptor gene
TAS2R38. People able to detect minute quantities of PROP find the taste
extremely bitter; they are sometimes called supertasters. Those who do
not taste PROP as very bitter are nontasters. The advantage of being a
supertaster is that many bitter “foods” are poisonous. The disadvantage is
that supertasters avoid many nutritious fruits and vegetables that they find
bitter.
Valerie Duffy and her colleagues (2010) investigated sensitivity to
quinine (usually perceived as bitter) in participants who were assessed for
the TAS2R38 genotype. They estimated participants’ taste bud density by
counting the number of papillae (the little bumps on the tongue). Quinine
was reported as more bitter to those who tasted PROP as very bitter or to
those who had more taste buds. Thus, detection of bitterness is related
both to TAS2R38 and to tongue anatomy.
Nontasters, either by genotype or phenotype (for few taste buds),
reported greater consumption of vegetables, both bitter and not.
Nontasters with higher numbers of taste buds reported eating about 25%
more vegetables than the other groups. These data suggest that genetic
variation in taste can explain differences in overall consumption of all
types of vegetables. It also suggests that persuading supertasters to eat
more healthy foods—that is, vegetables—may prove difficult.
Differences in taste thresholds also emerge as we age. Children are
much more responsive to taste than adults and are often intolerant of
spicy foods because they have more taste receptors than adults have. It is
estimated that by age 20, humans have lost at least 50 percent of their
taste receptors. No wonder children and adults have different food
preferences.
Receptors for Taste
Taste receptors are found in taste buds on the tongue, under the tongue, on
the soft palate on the roof of the mouth, on the sides of the mouth, and at
the back of the mouth on the nasopharynx. Each of the five taste receptor
types responds to a different chemical component in food. The four most
familiar are sweet, sour, salty, and bitter. The fifth type, called the umami
receptor, is especially sensitive to glutamate, a neurotransmitter molecule,
and perhaps to nucleotides. (Nucleotide bases are the structural units of
nucleic acids such as DNA and RNA.)
Taste receptors are grouped into taste buds, each containing several
receptor types, as illustrated in Figure 12-6 . Gustatory stimuli interact
with the receptor tips, the microvilli, to open ion channels, leading to
changes in membrane potential. At its base, the taste bud contacts the
branches of afferent cranial nerve 7 (facial), 9 (glossopharyngeal), or 10
(vagus).
 FIGURE 12-6 Anatomy of a Taste Bud Information from D. V. Smith & G.
M. Shepherd (2003). Chemical senses: Taste and olfaction. In L. R. Squire, F. E. Bloom, S. K.
McConnell, J. L. Roberts, N. C. Spitzer, & M. J. Zigmond (Eds.), Fundamental Neuroscience
(2nd ed., pp. 631–667), New York: Academic Press.

Gustatory Pathways
Cranial nerves 7, 9, and 10 form the main gustatory nerve, the solitary
tract. On entering the brainstem, the tract splits, as illustrated in Figure
12-7 . One route (traced in red) travels through the posterior medulla to
the ventroposterior medial nucleus of the thalamus. This nucleus in turn
sends out two pathways, one to the primary somatosensory cortex (S1)
and the other to the primary gustatory cortex of the insula, a region just
rostral to the secondary somatosensory cortex (S2).
The gustatory region in the insula is dedicated to taste, whereas S1 is
also responsive to tactile information and is probably responsible both for
localizing tastes on the tongue and for our reactions to a food’s texture.
The gustatory cortex sends a projection to the orbital cortex in a region
near the input from the olfactory cortex. Neuroimaging studies suggest
that the mixture of olfactory and gustatory input in the orbital cortex gives
rise to our perception of flavor. Ambience, including music and light, also
affects this region of orbital cortex, increasing blood flow and so
enhancing our experience of flavor.
A meta-analysis of noninvasive imaging studies that demonstrate taste-
responsive brain regions, conducted by Maria Veldhuizen and colleagues
(2011), also shows a brain asymmetry. The investigators conclude that
areas in the right orbital cortex mediate the pleasantness of tastes,
whereas the same region in the left hemisphere mediates the
unpleasantness of tastes. Whereas the insula identifies the nature and
intensity of flavors, the OFC evaluates the affective properties of tastes.
The second pathway from the gustatory nerve (shown in blue in Figure
12-7 ) projects via the nucleus of the solitary tract in the brainstem to the
hypothalamus and amygdala. Researchers hypothesize that these inputs
somehow participate in feeding behavior, possibly evaluating the
pleasantness and strength of flavors.
FIGURE 12-7 Gustatory Pathways
 12-2 REVIEW
The Chemical Senses
Before you continue, check your understanding.
1 . The receptor surface for olfaction is the _________.
2 . Olfactory and gustatory pathways eventually merge in the
orbitofrontal cortex, leading to the perception of ___________.
3 . Chemosignals that convey information about the sender are called
___________.
4 . The perception of bitterness is related to both the ___________ and
the ___________.
5 . How do a relatively limited number of receptor types allow us to
smell a trillion different odors?
Answers appear at the back of the book.

For additional study tools, visit : Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Evolution, Environment, and
12-3

Behavior
Odor and taste play a fundamental role in the biology of emotional and
motivated behavior. Why does the sight or smell of a bird or a mouse
trigger stalking and killing in a cat? Why does the human body stimulate
sexual interest? We can address such questions by investigating the
evolutionary and environmental influences on brain circuit activity that
contribute to behavior.

Evolutionary Influences on Behavior

One evolutionary explanation hinges on the concept of innate releasing
mechanisms (IRMs), activators for inborn adaptive responses that aid an
animal’s survival. IRMs help an animal to feed, reproduce, and escape
predators. The concept is best understood by analyzing its parts.
innate releasing mechanism (IRM) Hypothetical mechanism that
detects specific sensory stimuli and directs an organism to take a
particular action.
IRMs are present from birth rather than acquired through experience,
as the term innate implies. These mechanisms have proved adaptive and
therefore have been maintained in the genome of the species. The term
releasing indicates that IRMs act as triggers for behaviors set in motion
by internal programs.
Let us return to prey killing by cats. The cat’s brain must have a built-
in mechanism that triggers stalking and killing in response to such a
stimulus as a bird or a mouse. A cat must also have a built-in mechanism
that triggers mating behavior in the presence of a suitable cat of the
opposite sex. Not all cat behaviors are due to IRMs, but you probably
can think of other innate releasing mechanisms that cats possess—
arching and hissing on encountering a threat, for example. For all these
IRMs, the animal’s brain must have a set of norms against which it can
match stimuli to trigger an appropriate response.
The following experiment suggests the existence of such innate,
internalized norms. Bryan Kolb and Arthur Nonneman allowed a litter of
6-week-old kittens to play in a room and become familiar with it. After
this adjustment period, they introduced a two-dimensional image of an
adult cat in a Halloween posture, as shown in Figure 12-8 A .
The kittens responded with raised fur, arched backs, and bared teeth,
all signs of being threatened by the image of the adult. Some even hissed
at the model. These kittens had no experience with any adult cat except
their mother, and there was no reason to believe that she had ever shown
them this behavior. Some sort of template of this posture must be
prewired in the kitten brain. Seeing the model that matched this
preexisting template automatically triggered a threat response. This
innate trigger is an IRM.
The IRM concept also applies to humans. In one study, Tiffany Field
and her colleagues (1982) had an adult display to young infants various
exaggerated facial expressions, such as happiness, sadness, and surprise.
As Figure 12-9 shows, the babies responded with very much the same
expressions the adults displayed. These newborns were too young to be
imitating the adult faces intentionally. Rather, babies must innately
match these facial expressions to internal templates, in turn triggering
some prewired program to reproduce the expressions in their own faces.
Such an IRM would have adaptive value if these facial expressions serve
as important social signals for humans.
(A)
(B)

Courtesy of Arthur Nonneman and Bryan Kolb

FIGURE 12-8 Innate Releasing Mechanism in Cats (A)

Displaying the Halloween cat image stimulates defensive responses in
cats—raised fur, arched backs, and bared teeth. This behavior appears at
about 6 weeks of age in kittens who have never seen such a posture
before. (B) The scrambled “Picasso cat” evokes no response at all.

Evidence for a prewired motor program related to facial expressions

also comes from study of congenitally blind children, who spontaneously
produce the very same facial expressions that sighted people do, even
though they have never seen them in others. IRMs are prewired into the
brain, but experience can modify them. Our cat Hunter’s stalking skills
were not inherited fully developed at birth but rather matured
functionally as she grew older. The same is true of many human IRMs,
such as those for responding to sexually arousing stimuli.
Different cultures may emphasize different stimuli as arousing. Even
within a single culture, what different people find sexually stimulating
varies. Nonetheless, some human attributes are universally sexually
arousing. For most human males, an example is the hip-to-waist ratio of
human females. This ratio is probably part of an IRM.
The IRM concept can be related to the Darwinian view of nervous
system evolution. Natural selection favors behaviors that prove adaptive
for an organism, and these behaviors are passed on to future generations.
Because behavior patterns are produced by the activity of neurons in the
brain, the natural selection of specific behaviors is really the selection of
particular brain circuits.
Animals that survive long enough to reproduce and have healthy
offspring are more likely to pass on their brain circuit genes than are
animals with traits that make them less likely to survive and successfully
reproduce. Thus, feral cats adept at stalking prey or responding fiercely
to threats are more likely to survive and produce many offspring, passing
on their adaptive brain circuits and behaviors to their young. In this way,
the behaviors become widespread in the species over time.
The Darwinian view seems straightforward when we consider how
cats evolved brain circuits for stalking prey or responding to threats. It is
less obvious when applied to complex human behaviors, however. Why,
for instance, have humans evolved the behavior of killing other humans?
At first glance, it seems counterproductive to the survival of the human
species. Why has it endured? For an answer, we turn to evolutionary
psychology, the field that applies principles of natural selection to
explanations of human behavior.
evolutionary psychology Discipline that seeks to apply principles
of natural selection to understand the causes of human behavior.
Evolutionary psychologists assume that any behavior, including
homicide, occurs because natural selection has favored the neural circuits
that produce it. When two men fight a duel, one commonsense
explanation might be that they are fighting over grievances. But
evolutionary psychologists would instead ask, why is a behavior pattern
that risks people’s lives sustained in a population? Their answer: fights
are about social status.
Men who fought and won duels passed on their genes to future
generations. Through time, therefore, the traits associated with
successful dueling—strength, aggression, agility—became more
prevalent among humans, as did dueling. Martin Daly and Margot
Wilson (1988) extended this evolutionary analysis to further account for
homicide. In their view, homicide may endure in our society despite its
severe punishment because it is related to behaviors that were adaptive in
the human past.
Suppose that natural selection favored sexually jealous males who, to
guarantee that they had fathered all offspring born of their mates,
intimidated their rivals and bullied their mates. Male jealousy would be a
prevalent motive for interpersonal violence, including homicide.
Homicide itself does not help a man produce more children. But men
who are apt to commit homicide are more likely to engage in other
behaviors (bullying and intimidation) that improve their social status and
therefore their reproductive fitness. Homicide therefore is related to
adaptive traits that have been selected through millennia.
David Buss (2014) has examined patterns of mate selection across
thousands of participants from 37 cultures, seeking to identify factors
beyond culture that influence mate selection. His conclusions after nearly
30 years of study are that women around the world value dependability,
stability, education, and intelligence in a long-term mate. Men, however,
value good looks, health, and a desire for home and children more than
women do.
Section 15-5 posits a genetic explanation for the evolution of sex-
related cognitive differences.
 FIGURE 12-9 Innate Releasing Mechanism in Humans
Facial expressions made by young infants in response to expressions
made by the experimenter. From M. Field, R. Woodson, R. Greenberg, D. Cohen,
“Discrimination and imitation of facial expression by neonates,” Science 8 October 1982: Vol.
218 no. 4568 pp. 179–181, Figure 1, permission conveyed through Copyright Clearance Center,
Inc.

Older men and younger women are most likely to exhibit the
mutually desired set of traits, which leads to a universal tendency for age
differences between mates. Although the idea is controversial, Buss
argues that these preferences are a product of natural selection in a Stone
Age environment, when women and men would have faced different
daily problems and thus would have developed separate adaptations
related to mating.
Evolutionary theory cannot account for all human behavior, perhaps
not even homicide or mate selection. By casting an evolutionary
perspective on the neurological bases of behavior, though, evolutionary
psychologists can generate intriguing hypotheses about how natural
selection might have shaped the brain and behavior.
Section 1-2 reviews Darwin’s theory, materialism, and
contemporary perspectives on brain and behavior.

Environmental Influences on Behavior

Many psychologists have emphasized learning as a cause of behavior.
No one would question that we modify our behavior as we learn, but the
noted behaviorist B. F. Skinner (1938) went much further. He believed
that behaviors are selected by environmental factors.
Skinner’s argument is simple. Certain events function as rewards, or
reinforcers. When a reinforcing event follows a particular response,
similar responses are more likely to occur. Skinner argued that
reinforcement can be manipulated to encourage the display of complex
behaviors.
reinforcer In operant conditioning, any event that strengthens the
behavior it follows.
The power of experience to shape behavior by pairing stimuli and
rewards is typified by one of Skinner’s experiments. A pigeon is placed
in a box that has a small disc on one wall (the stimulus). If the pigeon
pecks at the disc (the response), a food tray opens, and the pigeon can
feed (the reinforcement or reward). The pigeon quickly learns the
association between the stimulus and the response, especially if the disc
has a small spot on it. It pecks at the spot and within minutes it has
mastered the response needed to receive a reward.
Now the response requirement can be made more complex. The
pigeon might be required to turn 360 degrees before pecking the disc to
gain the reward. The pigeon can learn this response too. Other
contingencies might then be added, making the response requirements
even more complex. For instance, the pigeon might be trained to turn in
a clockwise circle if the disc is green, to turn in a counterclockwise circle
if the disc is red, and to scratch at the floor if the disc is yellow.
 If you suddenly came across this complex behavior in a pigeon, you
would probably be astounded. But if you understood the experience that
had shaped the bird’s behavior, you would understand its cause. The
rewards offered to the pigeon altered its behavior: its responses were
controlled by the color of the disc on the wall.
Skinner extended behavioral analysis to include actions of all sorts—
behaviors that at first do not appear easily explained. For instance, he
argued that understanding a person’s reinforcement history could account
for various phobias. Someone who once was terrified by a turbulent
plane ride thereafter avoids air travel and manifests a phobia of flying.
The avoidance of flying is rewarding because it lowers the person’s
anxiety level, maintaining the phobic behavior.
Skinner also argued against the commonly held view that much of
human behavior is under our own control. From Skinner’s perspective,
free will is an illusion, because behavior is controlled not by the
organism but rather by the environment, through experience. But what is
the experience actually doing? Increasing evidence suggests that
epigenetic changes regulate changes in memory circuits. Skinner was not
studying the brain directly, but it is becoming clear that epigenetics
supports his perspective. We learn many complex behaviors through
changes in memory-related genes that act to modify neural circuits (see
the review by Day and Sweatt, 2011).
Epigenetic mechanisms mediate synaptic plasticity, especially in
learning and memory. See Section 14-4 .
 Skinner box

The environment does not always change the brain. A case in point
can be seen again in pigeons. A pigeon in a Skinner box can quickly
learn to peck a disc to receive a bit of food, but it cannot learn to peck a
disc to escape from a mild electric shock to its feet. Why not? Although
the same simple pecking behavior is being rewarded, apparently the
pigeon’s brain is not prewired for this second kind of association. The
bird is prepared genetically to make the first association, for food, but
not prepared for the second. This makes adaptive sense: typically, it flies
away from noxious situations.
John Garcia and R. A. Koelling (1966) were the first psychologists to
demonstrate the specific nature of this range of behavior–consequence
associations that animals are able to learn. Garcia observed that farmers
in the western United States are constantly shooting at coyotes for
attacking lambs, yet despite the painful consequences, the coyotes never
seem to learn to stop killing lambs in favor of safer prey. The reason,
Garcia speculated, is that a coyote’s brain is not prewired to make this
kind of association.
 So Garcia proposed an alternative to deter coyotes from killing lambs
—an association that a coyote’s brain is prepared to make: the
connection between eating something that makes one sick and avoiding
that food in the future. Garcia gave the coyotes a poisoned lamb carcass,
which sickened but did not kill them. With only one pairing of lamb and
illness, most coyotes learned not to eat sheep for the rest of their lives.
Many humans have similarly acquired food aversions because a
certain food’s taste—especially a novel taste—was subsequently paired
with illness. This learned taste aversion is acquired even when the food
eaten is in fact unrelated to the later illness. As long as the taste and the
nausea are paired in time, the brain is prewired to connect them.
learned taste aversion Acquired association between a specific
taste or odor and illness; leads to an aversion to foods that have the
taste or odor.
One of us ate his first Caesar salad the night before coming down
with a stomach flu. A year later, he was offered another Caesar salad
and, to his amazement, felt ill just at the smell of it. Even though he
knew that the salad had not caused his earlier illness, he nonetheless had
formed an association between the novel flavor and the illness. This
strong and rapid associative learning makes adaptive sense. Having a
brain that is prepared to make a connection between a novel taste and
subsequent illness helps an animal avoid poisonous foods and so aids in
its survival. A curious aspect of taste aversion learning is that we are
unaware of having formed the association until we encounter the taste
and/or smell again.
Section 14-4 has more on how our brains are wired to link unrelated
stimuli.
The fact that the nervous system is often prewired to make certain
associations but not to make others has led to the concept of
preparedness in learning theories. Preparedness can help account for
some complex behaviors. For example, if two rats are paired in a small
box and exposed to a mild electric shock, they will immediately fight
with one another, even though neither was responsible for the shock.
Apparently, the rat brain is predisposed to associate injury with nearby
objects or other animals. The extent to which we might extend this idea
to explain such human behaviors as bigotry and racism is an interesting
topic to ponder.
 preparedness Predisposition to respond to certain stimuli
differently from other stimuli.

Inferring Purpose in Behavior: To Know a

Fly
We may tend to assume that behavior is intentional. A wonderful little
book, To Know a Fly, by Vincent Dethier (1962), disabuses this
assumption by illustrating the problems in inferring purpose from an
organism’s actions.
When a fly lands on a kitchen table, it wanders about, occasionally
stomping its feet. Eventually, it finds a bit of food and sticks its
proboscis (an extension like an elephant’s trunk) into the food and eats.
The fly may then walk to a nearby place and begin to groom by rubbing
its legs together quickly. Finally, it spends a long period motionless.
If you observed a fly engaged in these behaviors, it might appear to
have been searching for food because it was hungry. When it found food,
you might assume that it gorged itself until it was satisfied, then it
cleaned up and rested. In short, the fly’s behavior might seem to you to
be motivated—to have some purpose or intention.
Dethier studied flies for years to understand what a fly is actually
doing when it engages in these behaviors. His findings have little to do
with purpose or intention. When a fly wanders about a table, it is not
deliberately searching. Rather, it is tasting what it walks on.
As Figure 12-10 shows, a fly’s taste receptors are on its feet. Tasting
is automatic when a fly walks. An adult fly’s nervous system has a built-
in preference for sweet tastes and an aversion to sour, salty, and bitter
tastes. Therefore, when a fly encounters something sweet, it
automatically lowers its proboscis and eats—or drinks if the sweet is
liquid. The sweeter the food, the more a fly will consume. (Sweet foods
attract us humans too, as Clinical Focus 12–4, Weight Loss Strategies,
reports.)
 FIGURE 12-10Feeding System of the Fly After the fly samples
the surface using taste buds on its feet, it takes in food through the
proboscis and passes it through the esophagus to the gut. Stretch
receptors at the gut entrance determine when the esophagus is full. The
recurrent nerve alerts the brain to signal cessation of eating.

Why does a fly stop eating? A logical possibility is that its blood
sugar level rises to some threshold. If this were correct, injecting glucose
into the circulatory system of a fly would prevent the fly from eating.
But that does not happen. Blood glucose level has no effect on a fly’s
feeding. Furthermore, injecting food into the animal’s stomach or
intestine has no effect either. So what is left?
Flies have a nerve (the recurrent nerve) that extends from the neck to
the brain and carries information about whether any food is present in the
esophagus. If the recurrent nerve is cut, the fly is chronically hungry and
never stops eating. Such flies become so full and fat that their feet no
longer reach the ground, and they become so heavy that they cannot fly.
Even though a fly appears to act with a purpose in mind, a series of
very simple mechanisms actually control its behavior—mechanisms not
remotely related to our concept of thought or intent. Hunger is simply the
activity of the nerve. Clearly, we should not assume simply from
appearances that a behavior carries intent. Behavior can have very subtle
causes that do not include conscious purpose. How do we know that any
behavior is purposeful? That question turns out to be difficult to answer.
 12-3 REVIEW
Evolution, Environment, and Behavior
Before you continue, check your understanding.
1 . B. F. Skinner argued that behaviors could be shaped by ___________
in the environment.
2 . John Garcia used the phenomenon of ___________ to discourage
coyotes from killing lambs.
3 . The brain of a species is prewired to produce ___________ to
specific sensory stimuli selected by evolution to prompt certain
associations between events.
4 . When a fly wanders around on a table, it is not exploring so much as.
5 . Explain briefly how the concept of preparedness accounts for
puzzling human behaviors.
Answers appear at the back of the book.

For additional study tools, visit : Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Neuroanatomy of Motivated and
12-4

Emotional Behavior
The neural circuits that control behavior encompass regions at all levels
of the brain, but the critical neural structures in emotional and motivated
behavior are the hypothalamus and associated pituitary gland, the limbic
system, and the frontal lobes. The expression of emotions includes
physiological changes: in heart rate, blood pressure, and hormone
secretions. It also includes motor responses, especially movements of the
muscles that produce facial expressions (see Figure 12-9 ). So much of
human life revolves around emotions that understanding them is central to
understanding our humanness.
But emotions are not restricted to people. A horse that is expecting
alfalfa for dinner will turn its nose up at grass hay and may stomp its front
feet and toss its head. Two dogs that are in competition for attention may
snap at one another. Charles Darwin interpreted such behaviors as
emotions in his classic book The Expression of the Emotions in Man and
Animals, published in 1872. We now know that emotional expression in
all mammals is related to activity in the limbic system and frontal lobes.
Although the hypothalamus plays a central role in controlling
motivated behavior, it takes its instructions from the limbic system and
the frontal lobes. The limbic and frontal regions project to the
hypothalamus, which houses many basic neural circuits for controlling
behavior and for autonomic processes that maintain critical body
functions within a narrow, fixed range—that is, homeostatic
mechanisms.
homeostatic mechanism Process that maintains critical body
functions within a narrow, fixed range.
Section 6-5 explores hormonal regulation of homeostatic
mechanisms.
In Figure 12-11 , the neck of a funnel represents the hypothalamus,
and the limbic system and frontal lobes form the funnel’s rim. To produce
behavior, the hypothalamus sends axons to other brainstem circuits. But
not all behavior is controlled via the funnel to the hypothalamus. Many
other routes to the brainstem and spinal cord bypass the hypothalamus,
among them projections from the motor cortex to the brainstem and
spinal cord. Thus it is primarily motivated behaviors that require
hypothalamic involvement.

FIGURE 12-11 Funneling Signals In this model, many inputs from the
frontal lobes and limbic system funnel through the hypothalamus, which
sends its axons to control brainstem circuits that produce motivated
behaviors.

Regulatory and Nonregulatory Behavior

We seek mates, food, or sensory stimulation because of brain activity, but
we talk about such behavior as being motivated. Motivated behaviors are
not something in the brain that we can point to, however. Rather,
motivations are inferences we make about why someone, ourselves
included, engages in a particular behavior. The two general classes of
motivated behaviors are regulatory and nonregulatory. In this section we
explore both categories before exploring the neuroanatomy of motivation
and emotion.
Regulatory Behaviors
Regulatory behaviors —behaviors motivated by an organism’s survival
—are controlled by homeostatic mechanisms. By analogy, consider a
house whose thermostat is set at 18 degrees Celsius (°C). When the
temperature falls below a certain tolerable range (say, to 16°C), the
thermostat turns the furnace on. When the temperature rises above a
certain tolerable level (say, 20°C), the thermostat turns on the air
conditioner.
regulatory behavior Behavior motivated to meet the animal’s
survival needs.
Human body temperature is controlled in a somewhat similar manner
by a thermostat in the hypothalamus that holds internal temperature at
about 37°C, a temperature referred to as a set point. Even slight variations
cause us to engage in various behaviors to regain the set point. For
example, when body temperature drops slightly, neural circuits that
increase body temperature turn on. These neural circuits might induce an
involuntary response such as shivering or a seemingly voluntary behavior
such as moving closer to a heat source. Conversely, if body temperature
rises slightly, we sweat or move to a cooler place.
Similar mechanisms control many other homeostatic processes,
including the amount of water in the body, the balance of dietary
nutrients, and the blood sugar level. Control of many such homeostatic
systems is quite complex, requiring both neural and hormonal
mechanisms. In some way, however, all of the body’s homeostatic
systems involve hypothalamic activity.
Imagine that specific cells are especially sensitive to temperature.
When they are cool, they become very active; when they are warm, they
become less active. These cells could function as a thermostat, telling the
body when it is too cool or too warm. A similar set of cells could serve as
a glucostat, controlling the level of sugar in the blood, or as a hydrostat,
controlling the amount of water in the body. In fact, the body’s real
homeostatic mechanisms are slightly more complex than this imagined
one, but they work on the same general principle.
Mechanisms to hold conditions such as temperature constant have
evolved because the body, including the brain, is a chemical soup in
which thousands of reactions are taking place all the time. Maintaining
constant temperature is critical. When temperature changes, even by 2°C,
the rates at which chemical reactions take place change.
 Such changes might be tolerable, within certain limits, if all the
reaction times changed to the same extent. But they do not. Consequently,
an increase of 2°C might increase one reaction by 10 percent and another
by only 2 percent. Such uneven changes would wreak havoc with finely
tuned body processes such as metabolism and the workings of neurons.
A similar logic applies to maintaining homeostasis in other body
systems. For instance, cells require certain concentrations of water, salt,
and glucose to function properly. Wild fluctuations in the concentrations
cause a gross disturbance of metabolic balance and eventually biological
disaster.
Categories of Motivated Behavior
Some Regulatory Behaviors

Internal body temperature

Eating and drinking

Salt consumption

Waste elimination

Some Nonregulatory Behaviors

Sex

Parenting

Aggression

Food preference

Curiosity

Reading

Nonregulatory Behaviors
Unlike regulatory behaviors, such as eating or drinking, nonregulatory
behaviors are neither required to meet the basic survival needs of an
animal nor controlled by homeostatic mechanisms. Thus, nonregulatory
behaviors include everything else we do—from sexual intercourse to
parenting to such curiosity-driven activities as conducting psychology
experiments.
nonregulatory behavior Behavior unnecessary to the animal’s basic
survival needs.
 Some nonregulatory behaviors, such as sexual intercourse, entail the
hypothalamus, but most of them probably do not. Rather, such behaviors
entail a variety of forebrain structures, especially the frontal lobes.
Presumably, as the forebrain evolved and enlarged, so did our range of
nonregulatory behaviors.
Most nonregulatory behaviors are strongly influenced by external
stimuli. As a result, sensory systems must play some role in controlling
them. For example, the sexual behavior of most male mammals is
strongly influenced by the pheromone emitted by receptive females. If the
olfactory system is not functioning properly, we can expect abnormalities
in sexual behavior. We will return to sexual behavior in Section 12-5 , as
we investigate how a nonregulatory behavior is controlled. But first we
explore the brain structures that take part in motivated behaviors—
nonregulatory and regulatory.

Regulatory Function of the Hypothalamic

Circuit
The hypothalamus maintains homeostasis by acting on both the endocrine
system and the autonomic nervous system (ANS) to regulate our internal
environment. The hypothalamus also influences the behaviors selected by
the rest of the brain, especially by the limbic system. Although it
constitutes less than 1 percent of the human brain’s volume, the
hypothalamus controls an amazing variety of motivated behaviors,
ranging from heart rate to feeding and sexual activity.
Figure 2-30 diagrams ANS pathways and connections.
Hypothalamic Involvement in Hormone Secretions
A principal function of the hypothalamus is to control the pituitary
gland, which is attached to it by a stalk (Figure 12-12 A ). Figure 12-12
B diagrams the anatomic location of the hypothalamus in each
hemisphere, with the thalamus above and the optic tracts just lateral.
pituitary gland Endocrine gland attached to the bottom of the
hypothalamus; its secretions control the activities of many other
endocrine glands; associated with biological rhythms.
We can divide the hypothalamus into three regions, lateral, medial, and
periventricular, illustrated in frontal view in Figure 12-12 B. The lateral
hypothalamus, composed both of nuclei and of nerve tracts running up
and down the brain, connects the lower brainstem to the forebrain. The
principal tract, shown in Figure 12-13 , is the medial forebrain bundle
(MFB).
medial forebrain bundle (MFB) Tract that connects brainstem
structures with various parts of the limbic system; forms the
activating projections that run from the brainstem to basal ganglia
and frontal cortex.
The MFB connects brainstem structures with various parts of the
limbic system and forms the activating projections that run from the
brainstem to the basal ganglia and frontal cortex. Fibers that ascend from
the dopamine- and noradrenaline-containing cells of the lower brainstem
form a significant part of the MFB. The dopamine-containing MFB fibers
contribute to the control of many motivated behaviors, including eating
and sex. They also contribute to pathological behaviors, such as addiction
and impulsivity.
Section 6-4 elaborates on dopamine’s importance in experiences
related to drug use.
Each hypothalamic nucleus is anatomically distinct, and most have
multiple functions, in part because the cells in each nucleus contain a
different mix of peptide neurotransmitters. Each peptide participates in
different behaviors. For instance, transmitters in the cells in the
paraventricular nucleus may be vasopressin, oxytocin, or various
combinations of other peptides (such as enkephalin and neurotensin).
When peptide neurotransmitters act, we may experience a range of
feelings such as well-being (endorphins) or attachment (oxytocin and
vasopressin). For example, oxytocin is released during intimate moments
such as nurturing behavior, hugging, or sex, and thus is sometimes known
as the bonding hormone.
Section 5-2 reviews the structures and functions of peptide
neurotransmitters.
 (A)

(B)

FIGURE 12-12 Nuclei and Regions of the Hypothalamus

(A) Medial view shows the relation between the hypothalamic nuclei and
the rest of the brain. (B) Frontal view shows the relative positions of the
hypothalamus, thalamus, and—in the midline between the left and right
hemispheres—the third ventricle. Note the three principal hypothalamic
regions: periventricular, lateral, and medial.

The production of various neuropeptides hints at the special relation

between the hypothalamus and the pituitary. The pituitary consists of
distinct anterior and posterior glands, as shown in Figure 12-14 . The
posterior pituitary is composed of neural tissue and is essentially a
continuation of the hypothalamus.
Neurons in the hypothalamus make peptides (e.g., oxytocin and
vasopressin) that are transported down their axons to terminals lying in
the posterior pituitary. If these neurons become active, they send action
potentials to the terminals to release the peptides stored there. But rather
than affecting another neuron, as occurs at most synapses, capillaries (tiny
blood vessels) in the posterior pituitary’s rich vascular bed pick up these
peptides.
The peptides then enter the bloodstream, which carries them to distant
targets where they exert their effects. Vasopressin, for example, affects
water resorption by the kidneys, and oxytocin controls both uterine
contractions and the ejection of milk by mammary glands in the breasts.
Peptides can have multiple functions, depending on where their receptors
are. Thus, oxytocin not only controls milk ejection in females but also
performs a more general role in several forms of affiliative behavior,
including parental care, grooming, and sexual behavior in both men and
women (Insel & Fernald, 2004).

FIGURE 12-13 Medial Forebrain Bundle The activating projections

that run from the brainstem to the basal ganglia and frontal cortex are
major components of the MFB, a primary pathway for fibers connecting
various parts of the limbic system with the brainstem.
 FIGURE 12-14 Hypothalamus and Pituitary Gland The
anterior pituitary is connected to the hypothalamus by a system of blood
vessels that carry hormones from the hypothalamus to the pituitary. The
posterior pituitary receives input from axons of hypothalamic neurons. Both
regions respond to hypothalamic input by producing hormones that travel in
the bloodstream to stimulate target organs.

The glandular tissue of the anterior pituitary, by contrast, synthesizes

various hormones. The major hormones and their functions are listed in
Table 12-1 . The hypothalamus controls the release of these anterior
pituitary hormones by producing releasing hormones, peptides that act to
increase or decrease hormone release. Produced by hypothalamic cell
bodies, releasing hormones are secreted into capillaries that transport
them to the anterior pituitary, as Figure 12-14 shows.
releasing hormone Peptide released by the hypothalamus that
increases or decreases hormone release from the anterior pituitary.
TABLE 12-1 Major hormones Produced by the anterior Pituitary
Hormone Function

Adrenocorticotrophic hormone (ACTH) Controls secretions of the adrenal cortex

Thyroid-stimulating hormone (TSH) Controls secretions of the thyroid gland

Follicle-stimulating hormone (FSH) Controls secretions of the gonads

Luteinizing hormone (LH) Controls secretions of the gonads

Prolactin Controls secretions of the mammary glands

Growth hormone (GH) Promotes growth throughout the body

A releasing hormone can either stimulate or inhibit the release of an

anterior pituitary hormone. For example, the anterior pituitary produces
the hormone prolactin, but its release is controlled by a prolactin-
releasing factor and a prolactin release–inhibiting factor, both synthesized
in the hypothalamus. Hormone release by the anterior pituitary in turn
provides the brain a means for controlling what is taking place in many
other parts of the body. Three factors control hypothalamic hormone-
related activity: feedback loops, neural regulation, and experience-based
responses.
FEEDBACK LOOPS When the level of, say, thyroid hormone is low,
the hypothalamus releases thyroid-stimulating hormone–releasing
hormone (TSH-releasing hormone), which stimulates the anterior
pituitary to release TSH. TSH then acts on the thyroid gland to secrete
more thyroid hormone.
(A) Feedback loop
(B) Neural regulation
 FIGURE 12-15 Hypothalamic Controls (A) Releasing hormones
from the hypothalamus stimulate the anterior pituitary to release hormones.
The pituitary hormones stimulate target organs, such as the thyroid and
adrenal glands, to release their hormones. In the feedback loop, those
hormones in turn influence the hypothalamus to decrease its secretion of
the releasing hormones. (B) In the milk letdown response, oxytocin
released from the hypothalamus stimulates the mammary glands to release
milk. Milk letdown is enhanced by infant-related stimuli and inhibited by
maternal anxiety.

Receptors in the hypothalamus detect the thyroid hormone level. When

that level rises, the hypothalamus lessens its secretion of TSH-releasing
hormone. This type of system is essentially a form of homeostatic control
that works as a feedback mechanism, a system in which a neural or
hormonal loop regulates the initiation of neural activity or hormone
release, as illustrated in Figure 12-15 A .
The hypothalamus initiates a cascade of events that culminates in
hormone secretion, but it pays attention to how much hormone is
released. When a certain level is reached, it stops its hormone-stimulating
signals. Thus, the feedback mechanism in the hypothalamus maintains a
fairly constant circulating level of certain hormones.
NEURAL CONTROL Hormonal activities of the hypothalamus
necessitate regulation by other brain structures, such as the limbic system
and the frontal lobes. Figure 12-15 B diagrams this neural control in
relation to the effects of oxytocin released from the hypothalamus by the
paraventricular nucleus, which lies within the periventricular region
illustrated in Figure 12-12 . As stated earlier, one function of oxytocin is
to stimulate cells of the mammary glands to release milk. As shown in
Figure 12-15 B, when an infant suckles the breast, the tactile stimulation
causes hypothalamic cells to release oxytocin, which stimulates milk
letdown. In this way, the oxytocin cells participate in a fairly simple
reflex that is both neural and hormonal.
Other stimuli can influence oxytocin release, however, which is where
control by other brain structures comes in. For example, the sight, sound,
or even thought of her baby can trigger a lactating mother to eject milk.
Conversely, as diagrammed in Figure 12-15 B, feelings of anxiety in a
lactating woman can inhibit milk ejection. These excitatory and inhibitory
influences exerted by cognitive activity imply that the cortex can
influence neurons in the periventricular region. It is likely that projections
from the frontal lobes to the hypothalamus perform this role.
EXPERIENTIAL RESPONSES A third control on the hormonal
activities of the hypothalamus is the brain’s responses to experience:
neurons in the hypothalamus undergo structural and biochemical changes
just as cells in other brain regions do. In other words, hypothalamic
neurons are like neurons elsewhere in the brain in that they can be
changed by heavy demands on them.
Recall the principle of neuroplasticity from Section 2-6 .
Such changes in hypothalamic neurons can affect hormone output. For
instance, when a woman is lactating, the cells producing oxytocin
increase in size to promote oxytocin release and meet the increasing
demands of a growing infant for more milk. Through this control, which
is mediated by experience, a mother provides her baby with sufficient
milk over time.
 FIGURE 12-16 Generating Behavior When rats receive electrical
stimulation to the hypothalamus, they produce goal-directed behaviors.
This rat is stimulated to dig when and only when the electricity is on. If the
sawdust is removed (not shown), there is no digging.

Hypothalamic Involvement in Generating Behavior

Not only does the hypothalamus control hormone systems, it is also
central in generating behavior. This function was first demonstrated by
studies in which stimulating electrodes were placed in the hypothalamus
of various animals, ranging from chickens to rats and cats. When a small
electric current was delivered through a wire electrode, an animal
suddenly engaged in some complex behavior—eating, drinking, or
digging; displaying fear, attack, predatory, or reproductive behavior.
Which behavior depended on which site was stimulated. All the behaviors
were smooth, well integrated, and indistinguishable from typically
occurring ones. Furthermore, all were goal directed.
The onset and termination of these behaviors depended entirely on
hypothalamic stimulation. For example, if an electrode in a certain
location elicited feeding behavior, the animal ate as soon as the
stimulation was turned on and continued to eat until the stimulation was
turned off. If the food was removed, however, the animal would not eat
but might engage in other behaviors, such as drinking. Recall that Roger,
profiled in Section 12-1 , ate continuously if foodlike materials were
present, corresponding to the continuous hypothalamic activity caused by
a tumor.
Figure 12-16 illustrates the effect of stimulation at a site that elicits
digging. When no current is delivered, the animal sits quietly. When the
current is turned on, the animal vigorously digs in the sawdust; when the
current is turned off, the animal stops digging. If the sawdust is removed,
it does not dig.
Two more important characteristics of behaviors generated by
hypothalamic stimulation are related to (1) survival and (2) reward.
Animals apparently find the stimulation of these behaviors pleasant, as
suggested by the fact that they willingly expend effort, such as pressing a
bar, to trigger the stimulation. Recall that cats kill birds and mice because
the act of stalking and killing prey is rewarding to them. Similarly, we can
hypothesize that animals eat because eating is rewarding, drink because
drinking is rewarding, and mate because mating is rewarding.

Organizing Function of the Limbic Circuit

We now turn our attention to parts of the brain that interact with the
hypothalamus in generating motivated and emotional behaviors. These
brain structures evolved as a ring around the brainstem in early
amphibians and reptiles. Nearly 150 years ago, Paul Broca, impressed by
this evolutionary development, called these structures the limbic lobe.
The limbic circuit derives its name from the Latin limbus, meaning
border.
Known collectively as the limbic system today, these structures are
formed from a primitive three-layered cortex known as allocortex, which
lies adjacent to the six-layered neocortex. In mammals, the allocortex
encompasses the cingulate (meaning girdle ) gyrus and the hippocampal
formation, as shown in Figure 12-17 . The hippocampal formation
includes the hippocampus —a cortical structure important in species-
specific behaviors, memory, and spatial navigation and vulnerable to the
effects of stress—and the parahippocampal cortex adjacent to it.
hippocampus From the Greek word for seahorse ; distinctive
allocortical structure lying in the medial temporal lobe; participates
in species-specific behaviors, memory, and spatial navigation and is
vulnerable to the effects of stress.
Allocortex is found in the brain of mammals and other chordates,
especially birds and reptiles.

FIGURE 12-17 Limbic Lobe Encircling the brainstem, the limbic lobe as
described by Broca consists of the cingulate gyrus and hippocampal
formation (the hippocampus and parahippocampal cortex), the amygdala,
the mammillothalamic tract, and the anterior thalamus.

Organization of the Limbic Circuit

As anatomists began to study the limbic structures, connections to the
hypothalamus became evident. It also became apparent that the limbic
system has a role in emotion. For instance, in the 1930s, James Papez
observed that people with rabies display radically abnormal emotional
behavior, and postmortem examinations showed that the rabies had
selectively attacked the hippocampus. (Definitive proof of rabies remains
postmortem hippocampal examination.)
Papez concluded from his observations that the limbic lobe and
associated subcortical structures provide the neural basis of emotion. He
proposed a neural circuit, traced in Figure 12-18 A , now known as the
Papez circuit, whereby emotion could reach consciousness, presumed at
that time to reside in the cerebral cortex. In 1949, Paul MacLean
expanded Papez’s concept of the limbic circuit to include the amygdala
and prefrontal cortex. Figures 12-17 and 12-18A show the amygdala
lying adjacent to the hippocampus in the temporal lobe, with the
prefrontal cortex lying just anterior.
Figure 12-18 B charts the limbic circuit schematically. The
hippocampus, amygdala, and prefrontal cortex all connect with the
hypothalamus. The mammillary nucleus of the hypothalamus connects to
the anterior thalamus, which in turn connects with the cingulate cortex.
The cingulate cortex completes the circuit by connecting with the
hippocampal formation, amygdala, and prefrontal cortex. This anatomical
arrangement can be compared to the funnel in Figure 12-18C , which
shows the hypothalamus as the spout leading to motivated and emotional
behavior.
There is now little doubt that most limbic system structures, especially
the amygdala and hypothalamus, take part in emotional behaviors, as
detailed later in this section. But most limbic structures perform important
roles in various motivated behaviors as well, especially in motivating
species-typical behaviors such as feeding and sexual activity. The critical
structures for such motivated behaviors, as well as for emotion, are the
hypothalamus, which we have already considered, and the amygdala, to
which we turn now.
(A)
(B)
(C)

FIGURE 12-18 Limbic System (A) In this contemporary conception of the limbic
system, an interconnected network of structures—the Papez circuit—controls emotional
expression.(B) A schematic representation, coded to brain areas shown in part A by
color, charts the limbic system’s major connections. (C) A reminder that parts A and B
can be conceptualized as part of a funnel rim of outputs that, through the hypothalamus,
produce emotional and motivated behavior.

Amygdala
Named for the Greek word for almond because of its shape, the
amygdala consists of three principal subdivisions, the corticomedial area,
the basolateral area, and the central area. Like the hypothalamus, the
amygdala receives inputs from all sensory systems. But in contrast with
the hypothalamic neurons, more complex stimuli are necessary to excite
amygdalar neurons. Indeed, many amygdalar neurons are multimodal :
they respond to more than one sensory modality. In fact, some respond to
the entire sensory array: sight, sound, touch, taste, and smell. These
amygdalar cells must shape a rather complex image of the sensory world.
 Section 15-3 elaborates on multisensory integration and the binding
problem.
amygdala Almond-shaped collection of nuclei in the limbic system;
plays a role in emotional and species-typical behaviors.
The amygdala sends connections primarily to the hypothalamus and
the brainstem, where it influences neural activity associated with
emotions and species-typical behavior. For example, when the amygdala
of a person with epilepsy is electrically stimulated before brain surgery,
the person becomes fearful and anxious. We observed a woman who
responded with increased respiration and heart rate, saying that she felt as
if something bad was going to happen, although she could not specify
what.
Amygdala stimulation can also induce eating and drinking. We
observed a man who drank water every time the stimulation was turned
on. (There happened to be a pitcher of water on the table next to him.)
Within 20 minutes, he had consumed about 2 liters of water. When asked
if he was thirsty, he said, “No, not really. I just feel like drinking.”
The amygdala’s role in eating can be seen in patients with amygdalar
lesions. Like Roger as a result of his tumor, many of these patients lose
discrimination in their food choices, eating foods that were formerly
unpalatable to them. Lesions of the amygdala may also give rise to
hypersexuality.

Executive Function of the Frontal Lobes

The amygdala is intimately connected to the functioning of the frontal
lobes that constitute all cortical tissue anterior to the central sulcus. This
large area is made up of several functionally distinct regions mapped in
Figure 12-19 A .
Figure 11-2 charts the hierarchy of frontal lobe regions with regard to
movement.
The motor cortex controls fine movements, especially of the fingers,
hands, toes, feet, tongue, and face. The premotor cortex participates in
selecting appropriate movement sequences. For instance, a resting dog
may get up in response to its owner’s call, which serves as an
environmental cue for a series of movements processed by one region of
the premotor cortex. Or a dog may get up for no apparent reason and
wander about the yard, a sequence of actions in response to an internal
cue processed by a different premotor region.
(A) Lateral view

(B) Ventral view

(C) Medial view
 Gross Subdivisions of the Frontal Lobe
FIGURE 12-19

and Prefrontal Cortex

Prefrontal Anatomy and Connections
As shown in Figure 12-19 A, the prefrontal cortex (PFC) is anterior to
the premotor cortex. The PFC is key to controlling executive functions
such as planning movements. Its three primary areas are the dorsolateral
region; the orbitofrontal cortex (OFC), also shown from a ventral aspect
in Figure 12-19 B; and the ventromedial PFC. The anterior cingulate
cortex (ACC), shown in Figure 12-19C , is closely associated with the
PFC, although not strictly part of it.
prefrontal cortex (PFc) Extensive frontal lobe area anterior to the
motor and premotor cortex; key to controlling executive functions
such as planning.
Prefrontal literally means in front of the front.
The prefrontal cortex contributes to specifying the goals toward which
movement should be directed. It controls the processes by which we
select movements appropriate to the particular time and context. This
selection may be cued by internal information, such as memory and
emotion, or it may be made in response to context (environmental
information).
We focus here on the PFC and motivation and emotion. In Section
15-2 we turn to the PFC and cognition.
Like the amygdala, the frontal lobes receive highly processed
information from all sensory areas, and many neurons in the prefrontal
cortex, like those in the amygdala, are multimodal. As shown in Figure
12-20 , the prefrontal cortex receives input via connections from the
amygdala, dorsomedial thalamus, sensory association cortex, posterior
parietal cortex, and the dopaminergic cells of the ventral tegmental area.
Dopaminergic input is important for regulating how prefrontal neurons
react to stimuli, including emotional ones. Abnormalities in this
dopaminergic projection may account for some disorders, including
schizophrenia, in which people evince little emotional reaction to
typically arousing stimuli.
Section 16-4 elaborates on the causes of and treatments for
schizophrenia.
 Figure 12-20 also shows the areas to which the prefrontal cortex sends
connections—its output. The inferior prefrontal region projects axons to
the amygdala and the hypothalamus in particular. These PFC axons
provide a route for influencing the ANS and ENS, which control changes
in blood pressure, respiration, and other internal processes. The
dorsolateral prefrontal region sends its connections primarily to the
sensory association cortex, posterior parietal cortex, cingulate cortex,
basal ganglia, and premotor cortex.
PFC output influences movement (Section 11-1 ), memory (Section
14-3 ), and cognition (Section 15-2 ).
Prefrontal Functions
The prefrontal cortex takes part in selecting behaviors appropriate to the
particular time and place. Selection may be cued by internal information
or made in response to the environmental context. Disruption to this
selection function can be seen in people with injury to the dorsolateral
frontal lobe (see Figure 12-19 A). They become overly dependent on
environmental cues to determine their behavior. Like small children, they
can be easily distracted by what they see or hear. We have all experienced
a loss of concentration to some extent, but for a patient with frontal lobe
damage, the problem is exaggerated and persistent. Because the person
becomes so absorbed in irrelevant stimuli, he or she cannot act on
internalized information most of the time.
Inputs to prefrontal cortex

Outputs from prefrontal cortex

 FIGURE 12-20 Prefrontal Connections At left, the PFC receives
inputs (red arrows) and sends outputs (blue arrows) to the areas charted
on the right.

A good example is J. C., in whom bilateral damage to the dorsolateral

prefrontal cortex resulted from having a tumor removed. J. C. would lie in
bed most of the day fixated on television programs. He was aware of his
wife’s opinion of this behavior, but only the sound of the garage door
opening when she returned home from work in the evening would
stimulate him into action. Getting out of bed was controlled by this
specific environmental cue; without it, he seemed to lack motivation.
Television completely distracted him from acting on internal knowledge
of things that he could or should do.
Adapting behavior appropriately to the environmental context also is a
PFC function. Most people readily change their behavior to match the
situation at hand. We behave one way with our parents, another with our
friends, another with our children, and yet another with our coworkers.
Each set of people constitutes a different context, and we shift our
behaviors accordingly. Our tone of voice, our use of slang or profanity,
and the content of our conversations are quite different in different
contexts.
Even among our peers we act differently, depending on who is present.
We may be relaxed in the presence of some people and ill at ease with
others. It is therefore no accident that the size of the frontal lobes is
related to species’ sociability. Social behavior is extremely rich in
contextual information, and humans are highly social animals.
Controlling behavior in context requires detailed sensory information,
which is conveyed from all sensory regions to the frontal lobes. This
sensory input includes not only information from the external world but
also internal information from the ANS. People with damage to the
orbital prefrontal cortex, as is common in traumatic brain injuries, have
difficulty adapting their behavior to the context, especially the social
context. Consequently, they often make social gaffes.
Focus 1-1 and Section 1-2 recount behavioral effects of TBI; Section
14-5 details recovery; Section 16-3 explores TBI symptoms and
treatments.
In summary, the role of the frontal lobes in selecting behaviors is
important for considering what causes behavior. The frontal lobes act
much like a composer, but instead of selecting notes and instruments, they
select our actions. Not surprisingly, the frontal lobes are sometimes
described as housing the brain’s executive functions. To grasp the full
extent of frontal lobe control of behavior, see Clinical Focus 12-2 ,
Agenesis of the Frontal Lobe.
Section 15-2 considers the frontal lobes and the executive function of
planning.
CLINICAL FOCUS 12-2

Agenesis of the Frontal Lobes

The role of the frontal lobes in motivated behavior is perhaps best
understood by looking at J. P.’s case, described in detail by Stafford
Ackerly (1964). Born in December 1914, J. P. was a problem child.
Early on, he became a wanderer. Policemen would find him miles
from home, as he had no fear of being lost. Severe whippings by his
father did not deter him.
J. P.’s behavioral problems continued and expanded as he grew
older, and by adolescence, he was constantly in trouble. Yet J. P. also
had a good side. When he started school, his first-grade teacher was
so impressed with his polite manners that she began writing a letter
to his parents to compliment them on having such a well-mannered
child who was such a good influence in the class.
As she was composing the letter, she looked up to find J. P.
exposing himself to the class and masturbating. This juxtaposition of
polite manners and odd behavior characterized J. P.’s conduct
throughout his life. At one moment he was charming; at the next he
was engaged in socially unacceptable behavior.
J. P. developed no close friendships with people of either sex, in
large part because of his repeated incidents of public masturbation,
stealing, excessive boastfulness, and wandering. He was a person of
average intelligence who seemed unaffected by the consequences of
his behavior. Police officers, teachers, and neighbors all ascribed
intention to J. P.’s behavior: all believed that he was willfully
misbehaving and blamed his parents for not enforcing sufficiently
strict discipline.
Perhaps as a result, not until he was 19 years old was J. P.’s true
condition detected. To prevent him from serving a prison term for
repeated automobile theft, a lawyer suggested that J. P. undergo
psychiatric evaluation. The psychiatrist who examined him ordered
an X-ray (the only brain scan available at the time). The image
revealed that J. P. lacked a right frontal lobe, and his left frontal lobe
was about 50 percent of normal size. It is almost certain that his
frontal lobes simply failed to develop.
 Failure of a structure to develop is known as agenesis ; J. P.’s
condition was agenesis of the frontal lobes. His case offers an
unusual opportunity to study the role of the frontal lobes in
motivated behavior.
Clearly, J. P. lacked the bag of mental tricks that most people use
to come to terms with the world. Normally behavior is affected both
by its past consequences and by current environmental input. J. P.
did not seem much influenced by either factor. As a result, the world
was simply too much for him. He always acted childlike and was
unable to formulate plans or to inhibit many of his behaviors. He
acted on impulse. At home, he was prone to aggressive outbursts
about small matters, especially with regard to his mother.
Curiously, J. P. seemed completely unaware of his life situation.
Even though the rest of his brain was working fairly well—his IQ
score was in the normal range, and his language skills were very
good—the rest of his brain was unable to compensate for the absence
of frontal lobes.

Stimulating and Expressing Emotion

Emotion, like motivation, is intangible: it is an inferred state. But the
importance of emotion to our everyday lives is hard to exaggerate.
Emotion can motivate us. It inspires artistic expression, for example,
from poetry to filmmaking to painting. Many people enjoy the arts
simply because they evoke emotions. And while people find certain
emotions pleasant, severe and prolonged negative emotions, especially
anxiety and depression, can cause clinical disorders.
To explore neural control of emotions, we must first specify the types
of behavior we want to explain. Think of any significant emotional
experience you’ve had recently. Perhaps you had a serious disagreement
with a close friend. Maybe you just got engaged to be married.
A common characteristic of such experiences includes autonomic
responses such as rapid breathing, sweating, and dry mouth. Emotions
may also entail strong subjective feelings that we label as anger, fear, or
love, among others. Finally, emotions typically entail thoughts or plans
related to the experience itself and may take the form of replaying
conversations and events in your mind, anticipating what you might say
or do under similar circumstances in the future or in planning your
married life.
These three forms of emotional experience suggest the influence of
different neural systems. The autonomic component must include the
hypothalamus and associated structures, as well as the enteric nervous
system. The components of subjective feelings are more difficult to
localize but clearly include the amygdala and probably parts of the
frontal lobes. And thoughts and plans are likely to be cortical. What is
the relation between our cognitive experience of an emotion and the
associated physiological changes?
One view is that physiological changes (such as trembling and rapid
heartbeat) come first, and the brain then interprets these changes as an
emotion. This perspective implies that the brain (most likely the cortex)
produces a cognitive response to autonomic information. That response
varies with the context in which the autonomic arousal occurs, including
the effects on the gut via the ENS. In cases of extreme autonomic
activity, serotonin release surges in the gut, which can lead to diarrhea
and cramping. If we are frightened by a movie, we feel a weaker, shorter-
lived emotion than if we are frightened by a real-life encounter with a
gang of muggers. Variations of this perspective have gone by many
terms, beginning with the James–Lange theory, named for its originators,
but all assume that the brain concocts a story to explain bodily reactions.
Two lines of evidence support the James–Lange theory and similar
points of view. One is that the same autonomic responses can accompany
different emotions. That is, particular emotions are not tied to unique
autonomic changes. This line of evidence leaves room for interpreting
what a particular pattern of arousal means, even though particular
physiological changes may suggest only a limited range of possibilities.
The physiological changes experienced during fear and happiness are
unlikely to be confused.
The second line of evidence supporting the view that physiological
changes are the starting point for emotions comes from people with
reduced information about their own autonomic arousal, for example,
owing to spinal cord injury. Spinal injury results in a decrease in
perceived emotion, and its severity depends on how much sensory input
is lost. Figure 12-21 illustrates this relation. People with the greatest loss
of sensory input, which occurs with injuries at the uppermost end of the
spinal cord, also have the greatest loss of emotional intensity. In contrast,
people with low spinal injuries retain most of their visceral input and
have essentially typical emotional reactions.
After Christopher Reeve’s spinal cord was severed at the cervical
level (high), his emotions may have been blunted, but his motivation
clearly remained intact. See Section 11-1 .
somatic marker hypothesis Proposal that marker signals arising
from emotions and feelings act to guide behavior and decision
making, usually in an unconscious process.
Antonio Damasio (1999) emphasized an important additional aspect
of the link between emotional and cognitive factors in his somatic
marker hypothesis. When Damasio studied patients with frontal lobe
injuries, he was struck by how they could be highly rational in analyzing
the world yet still make decidedly irrational social and personal
decisions. The explanation, he argued, is that the neural machinery
underlying emotion no longer affects the reasoning of people with frontal
lobe injury, either consciously or unconsciously. Cut off from critical
emotional input, many social and personal decisions suffer.
FIGURE 12-21 Losing Emotion Spinal cord injury blunts the emotional experience.
Loss of emotionality is greatest when the lesion is high on the spine. Information from J.
Beatty (1995). Principles of Behavioral Neuroscience (p. 339). Dubuque, IA: Brown & Benchmark.

To account for these observations, Damasio proposed that emotions

are responses induced by either internal or external stimuli not normally
attended to consciously. For example, if you encounter a bear as you
walk down the street (presuming that you live in a place where this event
could take place), the stimulus is processed rapidly without conscious
appraisal. In other words, a sensory representation of the bear in the
visual cortex is transmitted directly to brain structures, such as the
amygdala, that initiate an emotional response.
The grizzly bear attack recounted in Section 11-4 confirms the
primacy of emotion—fear—over other factors, including pain.
This emotional response includes actions on structures in the
forebrain and brainstem and ultimately on the ANS. The amygdala has
connections to the frontal lobes, so the emotional response can influence
the frontal lobes’ appraisal. But if the frontal lobes are injured, emotional
information is excluded from cognitive processing, so the quality of
emotion-related appraisals suffers, and the response to the bear might be
inappropriate.
To summarize, Damasio’s somatic marker hypothesis proposes how
emotions are normally linked to a person’s thoughts, decisions, and
actions. In a typical emotional state, certain brain regions send messages
to many other brain areas and to most of the rest of the body through
hormones and the ANS. These messages produce a global change in the
organism’s state, and the altered state influences behavior, often
unconsciously.

Amygdala and Emotional Behavior

In addition to controlling certain species-typical behaviors, described
earlier, the amygdala influences emotion (Davis et al., 2003). Its role can
be seen most clearly in monkeys whose amygdala has been removed. In
1939, Heinrich Klüver and Paul Bucy reported an extraordinary result,
now known as Klüver–Bucy syndrome, that followed removal of the
amygdala and anterior temporal cortex of monkeys. The principal
symptoms included the following:
 Klüver–Bucy syndrome Behavioral syndrome, characterized
especially by hypersexuality, that results from bilateral injury to the
temporal lobe.
1. Tameness and loss of fear
2. Indiscriminate dietary behavior (eating many types of formerly
rejected foods)
3. Greatly increased autoerotic, homosexual, and heterosexual activity
with inappropriate object choice (e.g., the sexual mounting of chairs)
4. Tendency to attend to and react to every visual stimulus
5. Tendency to examine all objects by mouth
6. Visual agnosia, an inability to recognize objects or drawings of objects
Section 9-4 describes varieties of visual form agnosia in a range of
case studies.
Visual agnosia results from damage to the ventral visual stream in the
temporal lobe, but the other symptoms are related to the amygdalectomy.
Tameness and loss of fear are especially striking. Monkeys that normally
show a strong aversion to stimuli such as snakes show no fear of them
whatsoever. In fact, amygdalectomized monkeys may pick up live snakes
and even put them in their mouth.
Focus 2-2 examines some causes and symptoms of encephalitis.
Although Klüver–Bucy syndrome is not common in humans—
because bilateral temporal lobectomies are rare—its symptoms can be
seen in people with certain forms of encephalitis, a brain infection. In
some cases, encephalitis centered on the base of the brain can damage
both temporal lobes and produce many Klüver–Bucy symptoms,
including especially indiscriminate sexual behavior and the tendency to
examine objects by mouth.
The amygdala’s role in Klüver–Bucy syndrome points to its central
role in emotion. So does its electrical stimulation, which produces an
autonomic response (such as increased blood pressure and arousal) as
well as a feeling of fear. Fear produced by the brain in the absence of an
obvious threat may seem odd, but fear is basic to species’ survival. To
improve their chances of surviving, most organisms using fear as a
stimulus minimize their contact with dangerous animals, objects, and
places and maximize their contact with safe things.
 Throughout human history, exploiting fear has proved especially
effective in controlling group behavior.
Awareness of danger and of safety has both an innate and a learned
component, as Joe LeDoux (1996) emphasized. The innate component,
much as in the IRMs described in Section 12-3 , is the automatic
processing of species-relevant sensory information—inputs from the
visual, auditory, and olfactory systems. The importance of olfactory
inputs is not obvious to us humans. Our senses are dominated by vision.
But olfactory information connects directly to the amygdala in the
human brain (see Figure 12-17 ). For many other animals, olfactory cues
predominate.
A rat that has never encountered a ferret thus shows an immediate
fear response to the odor of ferret. Other novel odors (such as
peppermint or coffee) do not produce an innate fear reaction. The innate
response triggers in the rat an autonomic activation that stimulates
conscious awareness of danger.
In contrast, the learned component of fear consists of the avoidance of
specific animals, places, and objects that the organism has come to
associate with danger. The organism is not born with this avoidance
behavior prewired. In a similar way, animals learn to increase contact
with environmental stimuli that they associate with positive outcomes,
such as food or sexual activity or, in the laboratory, drugs. Damage to the
amygdala interferes with all these behaviors. The animal loses not only
its innate fears but also its acquired fears of and preferences for certain
environmental stimuli.
To summarize, a species’ survival requires a functioning amygdala. It
influences autonomic and hormonal responses through its connections to
the hypothalamus. It influences our conscious awareness of the positive
and negative consequences of events and objects through its connections
to the prefrontal cortex.

Prefrontal Cortex and Emotional Behavior

At about the same time that Klüver and Bucy began studying their
monkeys, Carlyle Jacobsen was studying the effects of frontal lobotomy
on the cognitive capacities of two chimpanzees. A frontal lobotomy
destroys substantial brain tissue as the result of inserting a sharp
instrument into the frontal lobes and moving it back and forth.
 In 1936, Jacobsen reported that one of the chimps was particularly
neurotic before being subjected to this procedure. It became more
relaxed afterward. Incredibly, a leading Portuguese neurologist of the
time, Egas Moniz, seized on this observation as a treatment for
behavioral disorders in humans, and the frontal lobotomy, illustrated in
Figure 12-22 , was initiated as the first technique of psychosurgery, or
neurosurgery intended to alter behavior.
psychosurgery Any neurosurgical technique intended to alter
behavior.
The use of psychosurgery grew rapidly in the 1950s. In North
America alone, nearly 40,000 people received frontal lobotomies as a
treatment for psychiatric disorders. Not until the 1960s was any
systematic research conducted into the effects of frontal lesions on social
and emotional behavior. By this time, the frontal lobotomy had virtually
vanished as a “treatment.” We now know that prefrontal lesions in
various species, including humans, severely affect social and emotional
behavior.
Agnes is a case in point. We met Agnes at the psychiatric hospital
where we met Roger (whose indiscriminate eating we described in
Section 12-1 ). At the time, Agnes, a 57-year-old woman, was visiting
one of the nurses. She had, however, once been a patient.
The first thing we noticed about Agnes was that she exhibited no
outward sign of emotion. She showed virtually no facial expression.
Agnes had been subjected to a procedure known as a frontal leukotomy
because her husband, an oil tycoon, felt that she was too gregarious.
Evidently, he felt that her “loose lips” were a detriment to his business
dealings. He convinced two psychiatrists that she would benefit from
psychosurgery, and her life was changed forever.
To perform a leukotomy, as illustrated in Figure 12-22 , a surgeon
uses a special knife called a leukotome to sever the connections of a
region of the orbitofrontal cortex (see Figure 12-19 ). In our
conversations with Agnes, we quickly discovered her considerable
insight into the changes brought about by the leukotomy. In particular,
she indicated that she no longer had any feelings about things or most
people, although, curiously, she was attached to her dog. She said that
she often just felt empty and much like a zombie.
FIGURE 12-22 Transorbital Leukotomy In this procedure, a leukotome is
inserted through the bone of the eye socket to disconnect the orbitofrontal cortex from
the rest of the brain.

Agnes’s only moment of real happiness in the 30 years since her

operation was the sudden death of her husband, whom she blamed for
ruining her life. Unfortunately, Agnes had squandered her dead
husband’s considerable wealth as a consequence of her inability to plan
or organize. This inability, we have seen, is another symptom of
prefrontal injury.
 The orbitofrontal area has direct connections with the amygdala and
hypothalamus. Its stimulation can produce autonomic responses, and as
we saw in Agnes, damage to the orbital region can produce severe
personality change characterized by apathy and loss of initiative or drive.
The orbital cortex is probably responsible for the conscious awareness of
emotional states produced by the rest of the limbic system, especially the
amygdala.
Agnes’s loss of facial expression is also typical of frontal lobe
damage. In fact, people with frontal lobe injuries and people who have
schizophrenia or autism spectrum disorder are usually impaired at both
producing and perceiving facial expressions, including a wide range of
expressions found in all human cultures—happiness, sadness, fear, anger,
disgust, and surprise. As with J. P.’s frontal lobe agenesis, described in
Clinical Focus 12-2 , it is difficult to imagine how such people can
function effectively in our highly social world without being able to
express their own emotions or to recognize others’.
ASD is the topic of Focus 8-2; schizophrenia, of Focus 8-5.
Although facial expression is a key to recognizing emotion, so is tone
of voice, or prosody. Patients with damage to the frontal lobe are devoid
of prosody, both in their own conversations and in understanding the
prosody of others. The lost ability to comprehend or produce emotional
expression in both faces and language partly explains those patients’
apathy. In some ways, they are similar to spinal cord patients who have
lost autonomic feedback and so can no longer feel the arousal associated
with emotion. These patients can no longer either read emotion in other
people’s faces and voices or express it in their own.
Some psychologists have proposed that our own facial expressions
provide us with important clues to what we are feeling. This idea has
been demonstrated in experiments reviewed by Pamela Adelmann and
Robert Zajonc (1989). In one such study, people were required to
contract their facial muscles by following instructions about which parts
of the face to move. Unbeknown to the participants, the movements
produced happy and angry expressions. Afterward, they viewed a series
of slides and reported how the slides made them feel.
They said that they felt happier when they were inadvertently making
a happy face and angrier when making the angry face. Patients with
frontal lobe damage presumably have no such feedback from their own
facial expressions, which could contribute to their emotional experiences
being dampened.
generalized anxiety disorder Persistently high levels of anxiety
often accompanied by maladaptive behaviors to reduce anxiety;
thought to be caused by chronic stress.

Emotional Disorders
Major depression, a highly disruptive emotional disorder, is
characterized by some or all the following: prolonged feelings of
worthlessness and guilt, the disruption of normal eating habits, sleep
disturbances, a general slowing of behavior, and frequent thoughts of
suicide. A depressed person feels severely despondent for a long time.
Major depression is common in our modern world, with a prevalence of
about 6 percent of the population at any given time.
Major depression, detailed in Focus 6-3, is among the most treatable
psychological disorders. Cognitive and intrapersonal therapies are as
effective as drugs. See Section 16-4 .
phobia Fear of a clearly defined object or situation.
Depression has a genetic component. It not only runs in families but
also frequently tends to occur in both members of a pair of identical
twins. The genetic component in depression implies a biological
abnormality, but the cause remains unknown. However, neuroscience
researchers’ interest in the role of epigenetic changes in depression is
increasing. One hypothesis is that early life stress may produce
epigenetic changes in the prefrontal cortex (see the review by Schroeder
et al., 2010).
Excessive anxiety is an even more common emotional problem than
depression. Anxiety disorders, including posttraumatic stress disorder
(PTSD), phobias, generalized anxiety disorder, panic disorder, and
obsessive-compulsive disorder (OCD), are estimated to affect 15 percent
to 35 percent of the population. As described in Clinical Focus 12-3 ,
Anxiety Disorders, symptoms include persistent fears and worries in the
absence of any direct threat, usually accompanied by various
physiological stress reactions, such as rapid heartbeat, nausea, and
breathing difficulty.
CLINICAL FOCUS 12-3

Anxiety Disorders
Animals typically become anxious at times, especially when they are in
obvious danger. But anxiety disorders are different. They are
characterized by intense feelings of fear or anxiety inappropriate for the
circumstances. People with an anxiety disorder have persistent and
unrealistic worries about impending misfortune. They also tend to have
multiple physical symptoms attributable to hyperactivity of the
sympathetic nervous system.
G. B.’s case is a good example. He was a 36-year-old man with two
college degrees who began to have severe spells initially diagnosed as a
heart condition. He would begin to breathe heavily, sweat, develop
heart palpitations, and sometimes feel pains in his chest and arms.
During these attacks, he was unable to communicate coherently and
would lie helpless on the floor until an ambulance arrived to take him to
an emergency room.
Extensive medical testing and multiple attacks over about 2 years
eventually led to the diagnosis of generalized anxiety disorder. Like
most of the 5 percent of the U.S. population who have an anxiety
disorder at some point in their life, G. B. was unaware that he was
overly anxious. The cause of generalized anxiety is difficult to pinpoint,
but one likely explanation is related to the cumulative effect of general
stress.
Although G. B. appeared outwardly calm most of the time, he had
been a prodemocracy activist in communist Poland, a dangerous
position. Because of the dangers, he and his family eventually escaped
from Poland to Turkey, and from there they went to Canada. G. B. may
have had continuing worries about the repercussions of his political
activities—worries (and stress) that eventually found expression in
generalized anxiety attacks.
The most common and least disabling type of anxiety disorders are
phobias. A phobia pertains to a clearly defined, dreaded object (such as
spiders or snakes) or situation (such as enclosed spaces or crowds).
Most people have a mild aversion to some types of stimuli. Such
aversion becomes a phobia only when a person’s feelings about a
disliked stimulus lead to overwhelming fear and anxiety.
 The incidence of disabling, that is, serious enough to interfere with
living well, phobias is surprisingly high—estimated to affect at least 1
in 10 people. Most people with a phobia control the emotional reaction
by avoiding what they dread. Others face their fears in controlled
settings, with the goal of overcoming them.
Panic disorder has an estimated incidence on the order of 3 percent
of the population. Symptoms include recurrent attacks of intense terror
that begin without warning and without any apparent relation to
external circumstances. Panic attacks usually last only a few minutes,
but the experience is always terrifying. Sudden activation of the
sympathetic nervous system leads to sweating, a wildly beating heart,
and trembling.
panic disorder Recurrent attacks of intense terror that come on
without warning and without any apparent relation to external
circumstances.
Although panic attacks may occur only occasionally, the victim’s
dread of another episode may be continual. Consequently, many people
with panic disorder also have agoraphobia, a fear of public places or
situations in which help might not be available. This phobia makes
some sense, because a person with a panic disorder may feel
particularly vulnerable about the possibility of having an attack in a
public place.
Freud believed that anxiety disorders are psychological in origin and
treatable with talking therapies in which people confront their fears.
Today, cognitive-behavioral therapies serve this purpose, as shown in
the accompanying photo. More recently, a behavioral therapy called
mindfulness, a form of meditation is proving effective in treating
anxiety disorders. Its effectiveness is correlated with suppressed
activity in the anterior cingulate region (Garrison et al., 2015). The
effect is greater in trained as opposed to novice meditators, which
supports the value of mindfulness training programs.
Pharmacologically, anxiety disorders are most effectively treated
with benzodiazepines such as diazepam (Valium), the best known.
Alprazolam (Xanax) is the most commonly prescribed drug for panic
attacks. Benzodiazepines act by augmenting GABA’s inhibitory effect
and are believed to exert a major influence on neurons in the amygdala.
Whether treatments are behavioral, pharmacological, or both, the
general goal is normalizing brain activity in the limbic system.
Lea Paterson/Science Source
 Up to 90 percent of people with an animal phobia overcome their fears in a
single exposure therapy session that lasts 2 or 3 hours.

As with depression, the root cause of anxiety disorders is unknown, but

the effectiveness of the drug treatments described in Clinical Focus 12-3
implies a biological basis. The most widely prescribed anxiolytic
(antianxiety) drugs are the benzodiazepines, such as Valium, Librium, and
Xanax. Why would the brain have a mechanism for benzodiazepine action?
It certainly did not evolve to allow us to take Valium. Probably this
mechanism is part of a system that both increases and reduces anxiety
levels. The mechanism for raising anxiety seems to entail a compound
known as diazepam-binding inhibitor, which appears to bind
antagonistically with the GABAA receptor, increasing anxiety.
Figure 6-7 illustrates antianxiety agents’ action at the GABAA
receptor.
Increased anxiety can be beneficial, especially if we are drowsy and need
to be alert to deal with a crisis. Impairment of this survival mechanism or
the one that reduces anxiety can cause serious emotional problems, even
anxiety disorders.
Section 16-4 further explores anxiety disorders and reviews treatments.
 12-4 REVIEW
Neuroanatomy of Motivated and Emotional Behavior
Before you continue, check your understanding.
1 . The two types of motivated behaviors are __________ behaviors,
which maintain homeostasis, and __________ behaviors,
encompassing basically all other behaviors.
2 . The brain’s homeostat for many functions is found in the
__________.
3 . The three brain structures housing the major behavioral circuitry
involved in motivation and emotion are __________, __________,
and __________.
4 . The prefrontal cortex has three main subdivisions: __________,
__________, and __________.
5 . Damage to the __________ is the primary cause of Klüver–Bucy
syndrome.
6 . The anterior pituitary gland produces __________.
7 . Contrast the functions of the limbic system and the frontal lobes.
Answers appear at the back of the book.

For additional study tools, visit : Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Control of Regulatory and
12-5

Nonregulatory Behavior
The two distinctly different types of motivated behaviors described in
Section 12-4 are regulatory behaviors, which maintain vital body system
balance, or homeostasis; and non-regulatory behaviors, those not
controlled by a homeostatic mechanism—basically all other behaviors.
In this section, we focus first on the control of two regulatory behaviors
in humans—eating and fluid intake. Then we explore the control of
human sexual behavior. While sexual behavior is nonregulatory; that is,
not essential for an individual organism’s survival, it is of enormous
psychological significance to humans.

Controlling Eating
Feeding behavior entails far more than sustenance alone. We must eat
and drink to live, but we also derive great pleasure from these acts. For
many people, eating is a focus of daily life, if not for survival, for its
centrality to social activities, from get-togethers with family and friends
to business meetings and even to group identification. Are you a
gourmet, a vegetarian, or a snack food junkie? Do you diet?
Control over eating is a source of frustration and even grief for many
people in the developed world. In 2000, the World Health Organization
identified obesity, the excessive accumulation of body fat, as a
worldwide epidemic. The United States is a case in point. From 1990 to
2010, the proportion of overweight people increased from about 50
percent to 65 percent of the population. The proportion of people
considered obese increased from about 12 percent in 1990 to 33 percent
in 2014.
obesity Excessive accumulation of body fat.
The increasing numbers of overweight and obese children and adults
persist despite a substantial decrease in fat intake in American diets.
What behaviors might cause persistent weight gain? One key to
understanding weight gain in the developed world is evolutionary. Even
40 years ago, much of our food was only seasonally available. In a world
with uncertain food availability, it makes sense to store excess body
calories in the form of fat to be used later when food is scarce. Down
through history and in many cultures today, plumpness was and is
desirable as a standard of beauty and a sign of health and wealth.
In postindustrial societies, where food is continuously and easily
available, overweight may not be the healthiest condition. People eat as
though food will be scarce and fail to burn off the extra calories by
exercising, and the result is apparent. About half of the U.S. population
has dieted at some point in their life. At any given time, at least 25
percent report that they are currently on a diet. For a comparison of how
some well-known dieting programs perform, see Clinical Focus 12-4 ,
Weight Loss Strategies, on page 428 .
Most Americans are overweight despite living in a culture obsessed
with slimness. The human control system for feeding has multiple
neurobiological inputs, including cognitive factors such as thinking
about food and the association between environmental cues (e.g.,
watching television or studying) and the act of eating. The constant
pairing of such cues with eating can result in the cues alone becoming a
motivation—an incentive to eat. We return to this phenomenon in the
discussion of reward and addiction in Section 12-6 .
Eating disorders entail being either overweight or underweight.
Anorexia nervosa is an eating disorder with a huge cognitive
component: self-image. A person’s body image is highly distorted in
anorexia. This misperception leads to an exaggerated concern with being
overweight. That concern spirals to excessive dieting, compulsive
exercising, and severe, potentially life-threatening weight loss. Anorexia
is especially prevalent among adolescent girls.
anorexia nervosa Exaggerated concern with being overweight that
leads to inadequate food intake and often excessive exercising; can
lead to severe weight loss and even starvation.
The neurobiological control of feeding behavior in humans is not as
simple as it is in the fly described in Section 12-3 . The multiple inputs to
the human control system for feeding come from three major sources:
the cognitive factors already introduced, the hypothalamus, and the
digestive system.
Digestive System and Control of Eating
As illustrated in Figure 12-23 , the digestive tract begins in the mouth
and ends at the anus. Digestion is controlled by the enteric nervous
system. As food travels through the tract, the digestive system extracts
three types of nutrients: lipids (fats), amino acids (the building blocks of
proteins), and glucose (sugar). Each nutrient is a specialized energy
reserve. Because we require varying amounts of these reserves
depending on what we are doing, the body has detector cells to keep
track of the level of each nutrient in the bloodstream.
Figure 2-31 diagrams the inner workings of the ENS and Section 5-
3 the main neurotransmitters it employs.
Glucose is the body’s primary fuel and virtually the only energy
source for the brain. Because the brain requires glucose even when the
digestive tract is empty, the liver acts as a short-term reservoir of
glycogen, a starch that acts as an inert form of glucose. When blood
sugar levels fall, as when we are sleeping, detector cells tell the liver to
convert glycogen into glucose for release into the bloodstream.
Thus the digestive system functions mainly to break down food, and
the body needs to be apprised of how this breakdown is proceeding.
Feedback mechanisms provide such information. When food reaches the
intestines, it interacts with receptors in the ENS to trigger the release of
at least 10 different peptide hormones, including cholecystokinin (CCK),
glucagonlike peptide 1 (GLP-1), and peptide YY (PYY). Each, by virtue
of its release as food, is absorbed and acts as a satiation or satiety signal
that inhibits food intake. For example, when CCK is infused into an
animal’s hypothalamus, the animal’s appetite diminishes.
CLINICAL FOCUS 12-4

Weight Loss Strategies

Among the wide range of diets and weight loss strategies on the market,
none has stopped the obesity epidemic facing the developed world.
Diets range widely in their recommended allowed proportions and
types of fats, carbohydrates, and proteins.
A study by Iris Shai and colleagues (2008) compared a low-fat diet,
a low-carbohydrate diet, and the Mediterranean diet high in fruits,
vegetables, legumes, and whole grains and including fish, nuts, and
low-fat dairy products (Panagiotakos et al., 2004). The Shai study
lasted 2 years and had relatively low dropout rates: 95.4 percent
remained on their diet at 1 year and 84.6 percent at 2 years.
Figure A shows that all three diets led to weight loss. The low-
carbohydrate diet produced the largest acute weight loss. Over the 2-
year period subjects gained back some weight, and in the second year
the low-carbohydrate and Mediterranean dieters achieved similar
weight loss.
The low-carbohydrate diet had more favorable effects on lipid
levels, whereas the Mediterranean diet provided better control of
glucose and insulin levels. Those who followed the low-fat diet lost
weight but fared less well than those on the other regimens.
The question of which foods are most likely to lead to weight gain
was studied in a 20-year prospective study of three cohorts totaling
about 120,000 U.S. women and men (Mozaffarian et al., 2011). None
were obese when the study began. Participants gained an average of 3.4
pounds during every 4-year period.
Shown graphically in Figure B, weight gain was most strongly
related to the intake of potato chips, potatoes, sugar-sweetened
beverages, and red meat. Weight loss was related to the intake of
vegetables, whole grains, fruits, nuts, and yogurt. Other lifestyle factors
related to weight change included the amount of television watching
(gain) and physical activity (loss).
Teresa Fung and her colleagues (2010) conducted a prospective
study of mortality over a 26-year period in 85,000 women and 45,000
men. They found that a low-carbohydrate diet based on animal food
sources was associated with higher mortality from all causes, whereas a
vegetable-based, low-carbohydrate diet was associated with lower
mortality from all causes.
Shai and her colleagues concluded that health care professionals
might suggest more than one dietary approach based on individual
preferences and metabolic needs, as long as the effort is sustained. At
present, the only certain formula for weight loss appears to include (1) a
permanent switch to a diet reduced in calories and fat and (2) increased
ingestion of high-fiber foods (e.g., beans, whole grains, greens)
combined with (3) increased physical activity. The results of the
Mozaffarian study suggest cutting back on foods and beverages with
high sugar content as well.

FIGURE A Benefits of Dieting Changes in body weight over a 2-year

period on three diets. Low-carbohydrate and Mediterranean diets were
equivalent after 1 year, and both led to more weight loss than did the
low-fat diet. Information from I. Shai, D. Schwarzfuchs, Y. Henkin, et al. (2008). Weight
loss with a low-carbohydrate, Mediterranean, or low-fat diet. New England Journal of
Medicine, 13, pp. 229–241.
 FIGURE B Foods Most Likely to Lead to Weight Gain or Loss Weight changes
recorded for each increase in daily serving of a food per 4-year period, based on the
diets and weights of nearly 125,000 people who were followed over 20 years. Information
from D. Mozaffarian, M. P. H. Tao Hao, E. B. Rimm, W. C. Willett, & F. B. Hu (2011). Changes in diet and
lifestyle and long-term weight gain in women and men. New England Journal of Medicine, 3654, pp. 2392–
2404.

FIGURE 12-23 The Digestive System

Hypothalamus and Control of Eating
Feeding behavior is influenced by hormones, including insulin, growth
hormone, and sex steroids, that stimulate and inhibit feeding and aid in
converting nutrients into fat and fat into glucose. The hypothalamus, which
controls hormone systems, is the key brain structure in feeding as well as in
satiety.
Section 6-5 reviews the general categories of hormones and how they
work.
Investigation into how the hypothalamus controls feeding began in the
early 1950s, when researchers discovered that damage to the lateral
hypothalamus in rats caused the animals to stop eating, a symptom known
as aphagia (in Greek, phagein means to eat ). In contrast, damage to the
ventromedial hypothalamus (VMH) caused the animals to overeat—display
hyperphagia. A VMH-lesioned rat that overate to the point of obesity is
shown in the Procedure section of Experiment 12-1 on page 430 . The
Results section reveals that the VMH-lesioned rat weighed more than 1
kilogram, three times the weight of her healthy sister, at 340 grams.
 aphagia Failure to eat; may be due to an unwillingness to eat or to
motor difficulties, especially with swallowing.
hyperphagia Overeating that leads to significant weight gain.
The researchers also found that electrical stimulation of the lateral
hypothalamus elicits feeding, whereas stimulation of the ventromedial
hypothalamus inhibits feeding. The opposing effects of injury and
stimulation to these two regions led to the idea that the lateral hypothalamus
signals turn eating on, whereas the VMH signals turn eating off. This model
quickly proved too simple.
Not only does the lateral hypothalamus contain cell bodies; fiber bundles
also pass through it. Damage to either the cell bodies or the fibers can
produce aphagia. Similarly, damage to fibers passing through the VMH
often causes injury as well to the paraventricular nucleus of the
hypothalamus (review Figure 12-12 A). But the role of the hypothalamus in
controlling feeding involves more than the activities of its lateral and
ventromedial structures alone.
In fact, another hypothalamic region, the arcuate nucleus, contains two
major classes of neurons, one that initiates eating (e.g., neurons expressing
genes for neuropeptide Y) and one that reduces eating behavior, the
principal transmitter being α-melanocyte–stimulating hormone (α-MSH).
Changes in hormone levels reflecting glucose (insulin) and lipid (leptin)
levels in the blood act to stimulate either the first class, which initiates
eating, or the second class, which acts to inhibit eating. Neurons of the
arcuate nucleus also connect to the paraventricular nucleus. Damage to this
region produces hyperphagia.
The summed activity of all such hypothalamic neurons constitutes a
complex homeostat that controls feeding. Figure 12-24 shows that this
homeostat receives inputs from three sources: the enteric nervous system
(such as information about blood glucose levels), hormone systems (such as
information about the level of appetite-diminishing CCK), and parts of the
brain that process cognitive factors. We turn to these cognitive factors next.
 EXPERIMENT 12-1

Question: Does the hypothalamus play a role in eating?

Procedure

Results
 Conclusion: The VMH plays a role in controlling the cessation of
eating. Damage to the VMH results in prolonged and dramatic weight
gain.

Cognitive Control of Eating

Pleasure and its absence are cognitive factors in controlling eating. Just
thinking about a favorite food can make many of us feel hungry. The
cognitive aspect to feeding includes not only images of food that we pull
from memory but also external sensations, especially food-related sights
and smells. Learned associations, such as the taste aversions discussed in
Section 12-3 , are also related to feeding.
Neural control of the cognitive factors important for controlling eating
in humans probably originates in multiple brain regions. Two structures
are clearly important: the amygdala and the orbital prefrontal cortex.
Damage to the amygdala alters food preferences and abolishes taste
aversion learning. These effects are probably related to the amygdala’s
efferent connections to the hypothalamus.
The amygdala’s role in regulating species-typical behaviors is well
established, but the role of the orbital PFC is more difficult to pin down.
Rats and monkeys with damage to the orbital cortex lose weight, in part
because they eat less. Humans with orbital injuries are invariably slim,
but we know of no formal studies on their eating habits. The orbital
prefrontal cortex receives projections from the olfactory bulb, and cells
in this region respond to smells. Because odors influence the taste of
foods, it is likely that damage to the orbital cortex decreases eating,
owing to diminished sensory responses to food odor and perhaps to taste.
An additional cognitive factor in control of eating is the pleasure we
derive from it, especially from eating foods with certain tastes. Think
chocolate. What pleasure is and how the brain produces it are discussed
in Section 12-6 in the context of reward.
Randy Seeley and Stephen Woods (2003) noted that in spite of
contemporary problems with weight gain, adult mammals do a masterful
job of matching their caloric intake to caloric expenditure. Consider that
a typical man eats 900,000 calories per year. To gain just one extra
pound requires him to eat 4000 calories more than he burned in that year.
This increase amounts to only 11 calories per day, equivalent to a single
potato chip. But people rarely eat just one chip. As Figure B in Clinical
Focus 12-4 illustrates, potato chips top the list of major food sources
linked to weight gain over time.

FIGURE 12-24 Modeling Control of Feeding Behavior

Controlling Drinking
Dissolved in the water that is 70 percent of the human body are
chemicals that participate in the hundreds of reactions necessary to
bodily functions. Essential homeostatic mechanisms control water levels
(and hence chemical concentrations) within rather narrow limits. The
rate of a chemical reaction is partly determined by the concentration of
the participating chemicals.
As with eating, we drink for many reasons. We consume some
beverages, such as coffee, wine, beer, and juice, for an energy boost or to
relax, as part of social activities, or just because they taste good. We
drink water for its health benefits, to help wash down a meal or to
intensify the flavor of dry foods. On a hot day, we drink water because
we are thirsty, presumably because we become dehydrated through
sweating and evaporation.
These examples illustrate the two kinds of thirst. Osmotic thirst
results from increased concentrations of dissolved chemicals, known as
solutes, in the body fluids. Hypovolemic thirst results from a loss of
overall fluid volume from the body.
osmotic thirst Thirst that results from a high concentration of
dissolved chemicals, or solutes, in body fluids.
hypovolemic thirst Thirst produced by a loss of overall fluid
volume from the body.
Osmotic Thirst
Solutes found inside and outside cells are ideally concentrated for the
body’s chemical reactions. Maintaining this concentration requires a kind
of homeostat, much like the mechanism that controls body temperature.
Deviations from the ideal solute concentration activate systems to
reestablish it.
When we eat salty foods, such as potato chips, the salt (NaCl) spreads
through the blood and enters the extracellular fluid between our cells.
This shifts the solute concentration away from the ideal. Receptors in the
hypothalamus along the third ventricle detect the altered solute
concentration and relay the message too salty to various hypothalamic
areas that in turn stimulate us to drink. Other messages are sent to the
kidneys to reduce water excretion.
Turning to sugar-sweetened beverages to quench thirst from eating
salty foods increases the likelihood of weight gain.
Water Intoxication
Eating too much leads to obesity. What happens when we drink too
much water? Our kidneys are efficient at processing water, but if we
drink a large volume all at once, the kidneys cannot keep up.
 The result is a condition called water intoxication. Body tissues swell
with the excess fluid, essentially drowning the cells in freshwater. At the
same time, the relative concentration of sodium drops, leading to an
electrolyte imbalance.
Water intoxication can produce widely ranging symptoms, from
irregular heartbeat to headache. In severe cases, people may act as
though they are drunk. The most likely way for an adult to develop water
intoxication is to sweat heavily, by running a marathon in hot weather,
for example, then drink too much water without added electrolytes.
Hypovolemic Thirst
Unlike osmotic thirst, hypovolemic thirst arises when the total volume of
body fluids declines, motivating us to drink more and replenish them. In
contrast with osmotic thirst, however, hypovolemic thirst encourages us
to choose something other than water, because water would dilute the
solute concentration in the blood. Rather, we prefer to drink flavored
beverages that contain salts and other nutrients.
Hypovolemic thirst and its satiation are controlled by a hypothalamic
circuit different from the one that controls osmotic thirst. When fluid
volume drops, the kidneys send a hormone signal (angiotensin) that
stimulates midline hypothalamic neurons. These neurons, in turn,
stimulate drinking.

Controlling Sexual Behavior

Individuals must feed and drink continually to survive. This is the
essence of regulatory behavior. But notwithstanding procreation, which
is essential to the survival of the species, sexual behavior is
nonregulatory: it is not essential for the individual organism’s survival.
That fact does nothing to convince most of us that sex is unimportant.
In Sigmund Freud’s psychodynamic theory, sexual drives are central
to human behavior. Sexual themes repeatedly appear in our art, literature,
and films. They bombard us via advertising and other sales pitches. Such
significance makes it all the more important to understand the control of
human sexual behavior in terms of both gonadal hormones and brain
circuits.
Effects of Sex Hormones on the Brain
During the fetal stage of prenatal development, a male’s Y chromosome
controls the differentiation of embryonic gonad tissue into testes, which
in turn secrete testosterone. This process is an organizing effect of
gonadal hormones. Testosterone masculinizes both the sex organs and
the brain during development. A major organizing effect of gonadal
hormones on the brain is in the hypothalamus, especially the preoptic
area of the medial hypothalamus. Organizing effects also operate in other
nervous system regions, notably the amygdala, the prefrontal cortex, and
the spinal cord.
Gonadal hormones produce enzymes necessary for epigenetic changes
such as gene methylation. One action of steroid hormones is to methylate
brain regions. For example, estrogen methylates the preoptic area of
females, leading to the suppression of male characteristics. Growing
evidence indicates that increased environmental levels of compounds,
such as agricultural pesticides, can interfere with hormone activity,
resulting in multigenerational epigenetic effects (e.g., McCarthy et al.,
2009). These effects may be linked to anxiety levels and obesity and
possibly to the organizational effects of gonadal hormones.
The case study in Section 3-3 describes such epigentic inheritance.
Sex-related differences in the nervous system make sense
behaviorally. After all, animal courtship rituals differ between the sexes,
as do copulatory behaviors, with females typically engaging in sexually
receptive responses and males in mounting ones. Producing these sex
differences in behaviors depends on the action of gonadal hormones on
the brain during development and in adulthood.
Hormonal actions on the adult brain are referred to as activating
effects, in contrast with developmental organizing effects. Next we
consider both, separately.
ORGANIZING EFFECTS OF SEX HORMONES During fetal
development, a male’s testes produce male hormones, the androgens. In
the developing rat, androgens are produced during the last week of fetal
development and the first week after birth. The androgens produced at
this time greatly alter both neural structures and later behavior. For
example, a male rat’s hypothalamus and prefrontal cortex differ
structurally from those of both female rats and of males that were not
exposed to androgens during development.
 Section 8-4 explains organizing influences of gonadal hormones and
critical periods in brain development.
Males with little exposure to the androgen testosterone during
development behave like genetically female rats in adulthood. If given
estrogen and progesterone, they become sexually receptive and display
typical female behaviors when mounted by males. Male rats castrated in
adulthood do not act in this way.
Sexual dimorphism, the differential development of brain areas in
the two sexes, arises from a complex series of steps. Cells in the brain
produce aromatase, an enzyme that converts testosterone into estradiol,
one of the class of female sex hormones called estrogens. That is, when
males produce testosterone, the brain converts it to an estrogen. Thus a
female hormone, estradiol, actually masculinizes the male brain.
sexual dimorphism Differential development of brain areas in the
two sexes.

Females are not masculinized by the presence of estrogens because

fetuses of both sexes produce a liver enzyme (alpha fetoprotein ) that
binds to estrogen, rendering it incapable of entering neurons.
Testosterone is unaffected by alpha fetoprotein: it enters neurons and is
converted into estradiol.
 The organizing effects of testosterone are clearly illustrated in the
preoptic area of the hypothalamus (see Figure 12-12 A), which plays a
critical role in male rats’ copulatory behavior. Comparing this area in
males and females, Roger Gorski (1984) and his colleagues found a
nucleus about five times as large in the males as in the females.
Significantly, manipulating gonadal hormones during development can
alter the sexual dimorphism of the preoptic area. Castrating male rats at
birth leads to a smaller preoptic area; treating infant females with
testosterone enlarges it.
The organizing effects of gonadal hormones are more difficult to
study in humans. However, John Money and Anke Ehrhardt (1972)
revealed an important role of these hormones in human development.
Clinical Focus 12-5 , Androgen Insensitivity Syndrome and
Androgenital Syndrome, describes this role.
CLINICAL FOCUS 12-5

Androgen Insensitivity Syndrome and the

Androgenital Syndrome
After the testes have formed in a male fetus, sexual development
depends on the actions of testicular hormones. Studying people with
androgen insensitivity syndrome makes this dependence crystal clear.
In this syndrome, an XY (genetic male) fetus produces androgens,
but the body cannot to respond to them.
Because androgen insensitivity syndrome does not affect estrogen
receptors, these people are still responsive to estrogen produced by
both the adrenal glands and the testes. As a result, they develop
female secondary sexual characteristics during puberty, even without
additional hormone treatment. A person with androgen insensitivity
syndrome is therefore a genetic male who develops a female
phenotype, that is, appears to be female, as shown in the photograph
on the left.
If no Y chromosome is present to induce the growth of testes, an
XX (genetic female) fetus develops ovaries and becomes a female. If
the adrenal glands of either the mother or the infant produces an
excessive amount of androgens, however, exposure of the female
fetus to them produces the androgenital syndrome (congenital
adrenal hyperplasia).
The effects vary, depending on when the androgens are produced
and on the level of exposure. In extreme cases, the clitoris enlarges
until it can be mistaken for a small penis, as shown in the photograph
on the right.
In less severe cases, no gross change in genital structure develops,
but there is a behavioral effect: these girls show a high degree of
tom-boyishness. In early childhood, they identify with boys and
prefer boys’ clothes, toys, and games. One explanation for this
behavioral effect is that the developing brain is masculinized, which
changes later behavior.
 John Money and Anke A. Ehrhardt/John’s Hopkins University Press
Left: In androgen insensitivity syndrome, a genetic male (XY) is insensitive to
gonadal androgens but remains sensitive to estrogens, which leads to the
development of a female phenotype. Right: In congenital adrenal hyperplasia, a
genetic female (XX) is exposed to androgens produced by the adrenal gland
embryonically, which leads to the partial development of male external genitalia.
Reprinted from J. Money & A. A. Ehrhardt (1972). Man and Woman, Boy and Girl (p. 116).
Baltimore: Johns Hopkins University Press.

ACTIVATING EFFECTS OF SEX HORMONES The sexual

behavior of both males and females also depends on the actions of
gonadal hormones on the adult brain. In most vertebrate species, female
sexual behavior varies in the course of an estrous cycle, during which the
levels of ovarian hormones fluctuate. The rat’s estrous cycle is about 4
days long, with sexual receptivity occurring only in the few hours during
which the production of the ovarian hormones estrogen and progesterone
peaks. These ovarian hormones alter brain activity, which in turn alters
behavior. In female rats, various chemicals released after mating inhibit
further mating behavior.
Section 6-5 details broader activating effects of sex hormones on
male and female behavior.
The activating effect of ovarian hormones can be seen clearly in
hippocampal cells. Figure 12-25 compares hippocampal pyramidal
neurons taken from female rats at two points in the estrous cycle: one
when estrogen levels are high and the other when they are low. When
estrogen levels are high, more dendritic spines and presumably more
synapses emerge. These neural differences during the estrous cycle are
all the more remarkable when we consider that cells in the female
hippocampus are continually changing their connections to other cells
every 4 days throughout the animal’s adulthood.
In males, testosterone activates sexual behavior in two distinct ways.
First, testosterone’s actions on the amygdala are related to the motivation
to seek sexual activity. Second, the actions of testosterone on the
hypothalamus are needed to produce copulatory behavior. We look at
both processes next.

FIGURE 12-25 Hormonal Effects A comparison of the dendrites of

hippocampal pyramidal neurons at high and low levels of estrogen in the
rat’s (4-day) estrous cycle reveals far fewer dendritic spines in the low
period. Information from C. S. Woolley, E. Gould, M. Frankfurt, & B. McEwen (1990). Naturally
occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. Journal
of Neuroscience, 10, p. 1289.

Hypothalamus, Amygdala, and Sexual Behavior

The hypothalamus is the critical structure controlling copulatory
behaviors in both male and female mammals. The ventromedial
hypothalamus controls the female mating posture, which in quadrupedal
animals is called lordosis : arching the back and elevating the rump
while the female otherwise remains quite still. Damage to the VMH
abolishes lordosis. The role of the VMH is probably twofold: it controls
the neural circuit that produces lordosis, and it influences hormonal
changes in the female during coitus.
In males, neural control of sexual behavior is somewhat more
complex. The medial pre-optic area, which is larger in males than in
females, controls copulation. Damage to this area greatly disrupts mating
performance, whereas its electrical stimulation activates mating,
provided that testosterone is circulating in the bloodstream. Curiously,
although destruction of the medial preoptic area stops male mammals
from mating, they continue to show interest in receptive females. For
instance, monkeys with lesions in the medial preoptic area will not mate
with receptive females, but they will masturbate while watching them
from across the room.
Barry Everitt (1990) designed an ingenious apparatus that allows
male rats to press a bar to deliver receptive females. After males were
trained to use this apparatus, shown in Figure 12-26 , lesions were made
in their medial preoptic areas. Immediately, their sexual behavior
changed. They would still press the bar to obtain access to females but
would no longer mate with them.
Apparently, the medial preoptic area controls mating but not sexual
motivation. The brain structure responsible for motivation appears to be
the amygdala. When Everitt trained male rats in the apparatus and then
lesioned their amygdala, they would no longer press the bar to gain
access to receptive females, but they would mate with receptive females
provided to them.
 It is not practical to discriminate small hypothalamic nuclei in fMRI
studies of humans. Studies have shown a bilateral increase in
hypothalamic activity when men view erotic video clips but not when
they view sports video clips (Figure 12-27 ). The degree of sexual
arousal is related to the increase in hypothalamic activity (e.g., Brunetti
et al., 2008).
In summary, the hypothalamus controls copulatory behavior in both
male and female mammals. In males, the amygdala influences sexual
motivation and probably plays a key role in female sexual motivation as
well, especially among females of species, such as humans, whose
sexual activity is not tied to fluctuations in ovarian hormones.
 Barry J. Everitt

FIGURE 12-26 Studying Sexual Motivation and Mating In

this experiment, a male rat must press the bar 10 times to gain access to a
receptive female who drops in through a trapdoor. The copulatory behavior
of the male rat illustrates mating behavior, whereas the bar pressing for
access to a female rat illustrates sexual motivation. Barry J. Everitt, Department
of Experimental Psychology and the MRCWellcome Behavioural and Clinical Neuroscience
Institute, University of Cambridge.

Sexual Orientation, Sexual Identity, and

Brain Organization
Does sexual orientation —a person’s sexual attraction to the opposite
sex or to the same sex or to both sexes—have a neural basis? Sexual
orientation appears to be determined during early development,
influenced by genetics and by epigenetic factors during prenatal brain
development. No solid evidence points to any postnatal experience
directing sexual orientation.
sexual orientation A person’s pattern of sexual attraction—to the
opposite sex or to the same sex or to both sexes.
Indeed, it appears virtually impossible to change a person’s sexual
orientation. Lesbian couples commonly rear heterosexual children, and
no evidence supports the notion that homosexuality is a lifestyle choice
or that it is an effect of social learning (Bao & Swaab, 2011). The place
to look for differences, therefore, is in the brain of people who identify
themselves as heterosexual and homosexual.
Like rats, humans have sex-related differences in the structure of the
hypothalamus and amygdala. Several hypothalamic nuclei are two to
three times larger in males (for a review, see Becker and colleagues,
2008). Sexual differentiation of the brain results from the effect of
testosterone and is complete by birth.
But sex differences in the brain are not simply a matter of hormones.
Epigenetics plays a role too, beginning early in development. In females,
for example, one of the two X chromosomes is largely silenced, but not
all its genes are silenced, which provides a basis for sex differences.
Furthermore, emerging evidence suggests that sex differences in the
hypothalamus result from differences in gene methylation (for a review,
see McCarthy and coworkers, 2009).
Among homosexuals, variations in epigenetic effects could lead to
differences in the architecture and function of the hypothalamus.
Differences in the hypothalamus of heterosexual and homosexual men
suggest that homosexual men form, in effect, a third sex because their
hypothalamus differs from that of both females and heterosexual males.
Architectural and functional differences in the hypothalamus may
form a basis for the spectrum of gender identity —a person’s degree of
feeling male or female. People who view themselves as transgender,
whose personal characteristics transcend traditional gender boundaries
and corresponding sexual norms, believe they were born the wrong sex.
Their desire to live as a member of the other sex can be so strong that
they undergo sex change surgery.
gender identity The degree to which a person feels male or female.
Several biological factors appear to influence the likelihood of
transgender identity—chromosomal abnormalities, polymorphisms of the
genes for the estrogen and androgen receptors, atypical gonadal hormone
levels, prenatal exposure to certain anticonvulsants, and immune system
activity directed toward the Y chromosome. These factors are
hypothesized to lead to changes in the architecture and function of brain
structures, especially the hypothalamus, which match transgender
peoples’ identities even while their sex organs do not (Bao & Swaab,
2011).
More evidence favoring a neural basis for gender identity, including
transgender identity, in Section 15-5 .
In summary, differences in sexual orientation and gender identity
appear to result from prenatal events that influence the organization and
function of the brain, not from postnatal social or environmental
experiences.

FIGURE 12-27 Hypothalamus and Sex in Males Red regions

on the left and right represent bilateral activity in the hypothalamus of men
viewing erotic film clips. This activity was absent as the men watched
sports clips. Republished from “The Hypothalamus, Sexual Arousal and Psychosexual
Identity in Human Males: A functional Magnetic Resonance Imaging Study,” by M. Brunetti, C.
Babiloni, A. Ferretti, C. Del Gratta, A. Merla, and M. Olivetti Belardino, 2008, European Journal
of Neuroscience, 27, 2922–2927, Figure 2, permission conveyed through Copyright Clearance
Center, Inc.

transgender Possessing personal characteristics that transcend

traditional gender boundaries and corresponding sexual norms; a
 person’s belief that he or she was born the wrong sex.

© Neal Preston/Corbis
Peter Brooker/Rex Features/Alamy
 NC P/Star Max/Getty Images
Before accepting the Arthur Ashe Courage Award at the 2015 ESPY
ceremony, Caitlyn Jenner was known worldwide as Bruce Jenner. Bruce
won Olympic Gold in the 1976 decathlon competition. Caitlyn began her
physical transition nearly four decades later. At left, Bruce in 1984 and at
center in 2003; at right, Caitlyn in 2015.

Cognitive Influences on Sexual Behavior

People think about sex, dream about sex, make plans about sex. These
behaviors may include activity in the amygdala or the hypothalamus, but
they must certainly also include the cortex. This is not to say that the
cortex is essential for sexual motivation and copulation.
In studies of rats whose entire cortex has been removed, both males
and females still engage in sexual activity, although the males are
somewhat clumsy. Nevertheless, the cortex must play a role in certain
aspects of sexual behavior. For instance, imagery about sexual activity
must include activity in the cortical ventral visual pathway. And thinking
about sexual activity and planning for it must require frontal lobe
participation.
As you might expect, these aspects of sexual behavior are not easily
studied in rats, and they remain uncharted waters in research on humans.
However, changes in the sexual behavior of people with frontal lobe
injury are well documented. And recall J. P.’s case, described in Clinical
Focus 12-2 . Although J. P. was uninhibited in his sexual behavior,
frontal lobe damage is just as likely to produce a loss of libido (sexual
interest). The wife of a man who 5 years earlier had a small tumor
removed from the medial frontal region complained that she and her
husband had since had no sexual contact whatever. He was simply not
interested, even though they were both still in their twenties.
The husband said that he no longer had sexual fantasies or sexual
dreams, and although he still loved his wife, he did not have any sexual
urges toward her or anyone else. Such cases clearly indicate that the
human cortex is important in controlling sexual behaviors. The exact
nature of its role remains poorly understood.
 12-5 REVIEW
Control of Regulatory and Nonregulatory Behavior
Before you continue, check your understanding.
1 . The three main hypothalamic regions that control feeding are
____________, ____________, and ____________.
2 . The key structures in the control of sexual behavior are the
____________ and the ____________.
3 . The two types of effects that hormones exert on the brain are
____________ and ____________.
4 . ____________ thirst results from an increase in the concentration of
dissolved chemicals; ____________ thirst results from a decline in the
total volume of body fluids.
5 . Describe why sex differences in the brain are not simply a matter of
hormones.
Answers appear at the back of the book.

For additional study tools, visit : Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 12-6 Reward
Throughout this chapter we have concluded repeatedly that animals
engage in a wide range of voluntary behaviors because those behaviors
are rewarding. That is, they increase the activity in neural circuits that
function to maintain an animal’s contact with certain environmental
stimuli, either in the present or in the future. Presumably, the animal
perceives the activity of these circuits as pleasant. This would explain
why reward can help maintain not only adaptive behaviors such as
feeding and sexual activity but also potentially nonadaptive behaviors
such as drug addiction. After all, evolution would not have prepared the
brain specifically for the eventual development of psychoactive drugs.
The first clue to the presence of a reward system in the brain came
with an accidental discovery by James Olds and Peter Milner in 1954.
They found that rats would perform behaviors such as pressing a bar to
administer a brief burst of electrical stimulation to specific sites in their
brain. This phenomenon is called intracranial self-stimulation or brain
stimulation reward.
Section 7-1 describes how electrical stimulation works both as a
treatment and as a research tool.
Typically, rats will press a lever hundreds or even thousands of times
per hour to obtain this brain stimulation, stopping only when they are
exhausted. Why would animals engage in such behavior when it has
absolutely no survival value to them or to their species? The simplest
explanation is that the brain stimulation is activating the system
underlying reward (Wise, 1996).
After more than a half-century of research on brain stimulation
reward, investigators now know that dozens of brain sites maintain self-
stimulation. Some especially effective regions are the lateral
hypothalamus and medial forebrain bundle (see Figures 12-12 and 12-13
). Stimulation along the MFB tract activates fibers that form the
ascending pathways from dopamine-producing cells of the midbrain
tegmentum, shown in Figure 12-28 . This mesolimbic dopamine
pathway sends terminals to sites that include especially the nucleus
accumbens in the basal ganglia and the prefrontal cortex.
Neuroscientists have several reasons to believe that the mesolimbic
dopamine system is central to circuits mediating reward:
1. Dopamine release shows a marked increase when animals are engaged
in intracranial self-stimulation.
2. Drugs that enhance dopamine release increase self-stimulation,
whereas drugs that decrease dopamine release also decrease self-
stimulation. It seems that the amount of dopamine released somehow
determines how rewarding an event is.
3. When animals engage in behaviors such as feeding or sexual activity,
dopamine release rapidly increases in locations such as the nucleus
accumbens.
4. Highly addictive drugs such as nicotine and cocaine increase the
dopamine level in the nucleus accumbens.
Even opioids appear to affect at least some of an animal’s actions
through the dopamine system. Animals quickly learn to press a bar to
obtain an opioid injection directly into the midbrain tegmentum or the
nucleus accumbens. The same animals do not work to obtain the opioid
if the dopaminergic neurons of the mesolimbic system are inactivated.
Apparently, then, animals engage in behaviors that increase dopamine
release.
Nor is dopamine the only rewarding compound in the brain. For
example, opioid transmitters such as encephalin and dynorphin are also
rewarding, as are benzodiazepines.
Robinson and Berridge (2008) propose that reward contains separable
psychological components corresponding roughly to wanting, which is
often called incentive, and liking, which is equivalent to an evaluation of
pleasure. This idea can be applied to discovering why we increase
contact with a stimulus such as chocolate.
Robinson and Berridge’s wanting-and-liking theory of addiction
includes a multipart reward system; see Section 6-4 .
Two independent factors are at work: our desire to eat the chocolate
(wanting) and the pleasurable effect of eating the chocolate (liking). This
distinction is important. If we maintain contact with a certain stimulus
because dopamine is released, the question becomes whether the
dopamine plays a role in the wanting or the liking aspect of the behavior.
Robinson and Berridge propose that wanting and liking processes are
mediated by separable neural systems and that dopamine is the
transmitter for the wanting. Liking, they hypothesize, entails opioid and
benzodiazepine–GABA systems.
According to Robinson and Berridge, wanting and liking are normally
two aspects of the same process, so rewards are usually wanted and liked
to the same degree. However, it is possible, under certain circumstances,
for wanting and liking to change independently.
Consider rats with lesions of the ascending dopaminergic pathway to
the forebrain. These rats do not eat. Is it simply that they do not desire to
eat (a loss of wanting), or has food become aversive to them (a loss of
liking)? To find out which factor is at work, the animals’ facial
expressions and body movements in response to food can be observed to
see how liking is affected. After all, when animals are given various
foods to taste, they produce different facial and body reactions,
depending on whether they perceive the food as pleasant or aversive.

FIGURE 12-28 Mesolimbic Dopamine System Axons

emanating from the ventral tegmentum (blue arrows) project diffusely
through the brain. Dopamine release in these mesolimbic pathways has a
role in feelings of reward and pleasure. The nucleus accumbens is a
critical structure in this reward system.
FIGURE 12-29 Human Reactions to Taste Sucrose and other
palatable tastes elicit positive (hedonic) reactions, including licking the
fingers and the lips. Quinine and other unpleasant tastes elicit negative
(aversive) reactions, including spitting, expressing distaste, and wiping the
 mouth with the back of the hand. Information from K. C. Berridge (1996). Food reward:
Brain substrates of wanting and liking. Neuroscience and Biobehavioral Reviews, 20, p. 6.

Among humans, typically when a person tastes something sweet, he

or she responds by licking the fingers or the lips, as shown at the left of
Figure 12-29 . If the taste is unpleasantly salty, say, as shown in the right
panel, the reaction is often spitting, grimacing, or wiping the mouth with
the back of the hand. Rats, too, show distinctive positive and negative
responses to pleasant and unpleasant tastes.
By watching the responses when food is squirted into the mouth of a
rat that otherwise refuses to eat, we can tell to what extent a loss of liking
is a factor in the animal’s food rejection. Interestingly, rats that do not eat
after receiving lesions to the dopamine pathway act as though they still
like food.
Now consider a rat with a self-stimulation electrode in the lateral
hypothalamus. This rat will often eat heartily while the stimulation is on.
The obvious inference is that the food must taste good—presumably
even better than usual. But what happens if we squirt food into the rat’s
mouth and observe its behavior when the stimulation is on versus when it
is off?
If the brain stimulation primes eating by evoking pleasurable
sensations, we would expect the animal to be more positive in its facial
and body reactions to foods when the stimulation is turned on. In fact,
the opposite occurs. During stimulation, rats react more aversively to
tastes such as sugar and salt than when stimulation is off. Apparently, the
stimulation increases wanting but not liking.
Such experiments show that what appears to be a single event—
reward—is actually composed of at least two independent processes. Just
as our visual system independently processes what and how information
in separate streams, our reward system appears to process wanting and
liking independently. Reward is not a single phenomenon any more than
perception or memory is.
Like the networks underlying perception and memory, the prefrontal
and limbic networks underlying reward are diffuse. Amy Janes and her
colleagues (2012) used resting-state fMRI to identify a prefrontal–
anterior cingulate network believed to support reward, illustrating the
breadth of the reward system. They then compared these networks in
nicotine addicts and nonaddicts finding greater connectivity in the
prefrontal–striatal connections in nicotine addicts. In a follow-up study
the investigators also showed that craving in nicotine addicts is related to
enhanced connectivity in this prefrontal network ( Figure 12-30 ). (Janes
et al., 2014).

Craving Increases OMPFC Network

FIGURE 12-30

Coupling Participants craving nicotine show an increase in the

coupling of the orbital and medial prefrontal cortex (OMPFC, shown in
green) with other regions including anterior cingulate cortex, other
prefrontal regions, the striatum, right hippocampal region, ventral occipital
cortex, and cerebellum (shown in shades of orange). An Increase in Tobacco
Craving Is Associated with Enhanced Medial Prefrontal Cortex Network Coupling Amy C. Janes,
Stacey Farmer, Blaise deB. Frederick, Lisa D. Nickerson, Scott E. Lukas, PLoS One. 2014 Feb
5;9(2):e88228. doi: 10.1371/journal. pone.0088228.eCollection 2014.

The general conclusions from these studies and from related studies
of gamblers are that neural reward pathways are diffuse and that the
pathways’ size and activity are related to the reward’s intensity. The hope
is that rs-fMRI can be used as a biomarker for both severity of addiction
and efficacy of treatment. But the extent of addiction-related changes
suggests that eliminating nicotine addiction is not easy—a conclusion
many nicotine addicts would agree with.
 12-6 REVIEW
Reward
Before you continue, check your understanding.
1 . Animals engage in voluntary behaviors because the behaviors are
____________.
2 . Neural circuits maintain contact with rewarding environmental
stimuli in the present or in the future through ____________ and
____________ subsystems.
3 . The neurotransmitter systems hypothesized to be basic to reward are
___________, ___________, and systems.
4 . What is intracranial self-stimulation, and why is it rewarding?
Answers appear at the back of the book.

For additional study tools, visit : Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 SUMMARY
Identifying the Causes of
12-1
Behavior
Our inner subjective feelings (emotions) and goal-directed thoughts
(motivations) influence how we behave and adapt as individuals and as a
species. Emotion and motivation are inferred states that can escape
conscious awareness or intent and make the case for free will difficult to
argue.
Biologically, reward motivates animals to engage in behavior.
Aversive circumstances prompt brain circuits to produce behaviors that
will reduce them. Such are the effects of sensory deprivation. The brain
inherently needs stimulation. In its absence, the brain will seek it out.
Sensory stimulation leads to hormone activity and to dopamine
activity in the brainstem. Neural circuits organized in the brainstem
control species-typical behaviors, such as mouse killing by cats and
singing by birds. These brainstem circuits manifest their evolutionary
advantage: they are rewarding. Rewarding behavior motivates living
beings. When animals disengage from behaviors that motivate their
species, they go extinct.

12-2 The Chemical Senses

In the olfactory and gustatory senses, chemical neuroreceptors in the
nose and tongue interact with chemosignals, leading to neural activity in
cranial nerve 1 for olfaction and cranial nerves 7, 9, and 10 for taste. The
cranial nerves enter the brainstem, and through a series of synapses, pass
into the forebrain. Smell and taste inputs merge in the orbitofrontal
cortex to produce our perception of flavor.

Evolution, Environment, and

12-3
Behavior
Behavior is controlled by its consequences as well as by its biology.
Consequences may affect a species’ evolution or an individual’s
behavior. Behaviors selected by evolution are often triggered by innate
releasing mechanisms. Behaviors selected only in an individual animal
are shaped by that animal’s environment and are learned.

Neuroanatomy of Motivated
12-4
and Emotional Behavior
The neural structures that initiate emotional and motivated behaviors are
the hypothalamus, pituitary gland, amygdala, the dopaminergic and
noradrenergic activating pathways from nuclei in the lower brainstem,
and the frontal lobes.
The experience of both emotion and motivation is controlled by
activity in the ANS, hypothalamus, and forebrain, especially the
amygdala and frontal cortex. Emotional and motivated behavior may be
unconscious responses to internal or external stimuli controlled either by
the activity of innate releasing mechanisms or by cognitive responses to
events or thoughts.

Control of Regulatory and

12-5
Nonregulatory Behavior
The two distinctly different types of motivated behaviors are (1)
regulatory (homeostatic) behaviors that maintain vital body system
balance and (2) nonregulatory behaviors, basically all nonreflexive
behaviors and behaviors not controlled by a homeostatic mechanism.
Feeding is a regulatory behavior controlled by the interaction of the
digestive and hormonal systems, the enteric nervous system, and the
hypothalamic and cortical circuits. Sexual activity is a nonregulatory
behavior motivated by the amygdala. Copulatory behavior is controlled
by the hypothalamus (ventromedial hypothalamus in females and the
preoptic area in males). Sexual orientation (a person’s attraction to the
opposite or same sex) and gender identity (a person’s feeling of being
male or female) are related to the organization of the hypothalamus.
Differences in hypothalamic organization are likely related to epigenetic
effects in early development.

12-6 Reward
Survival depends on maximizing contact with some environmental
stimuli and minimizing contact with others. The reward mechanism
controls this differential. Two independent features of reward are
wanting and liking. The wanting component is thought to be controlled
by dopaminergic activating systems, whereas the liking component is
thought to be controlled by opioid and GABA–benzodiazepine systems.
 KEY TERMS
amygdala, p. 418
androgen, p. 401
anorexia nervosa, p. 427
aphagia, p. 429
emotion, p. 399
evolutionary psychology, p. 406
gender identity, p. 435
generalized anxiety disorder, p. 424
hippocampus, p. 416
homeostatic mechanism, p. 411
hyperphagia, p. 429
hypovolemic thirst, p. 431
innate releasing mechanism (IRM), p. 406
Klüver–Bucy syndrome, p. 423
learned taste aversion, p. 409
medial forebrain bundle (MFB), p. 413
motivation, p. 399
nonregulatory behavior, p. 413
obesity, p. 427
orbitofrontal cortex (OFC), p. 403
osmotic thirst, p. 431
panic disorder, p. 424
pheromone, p. 403
phobia, p. 424
pituitary gland, p. 413
prefrontal cortex (PFC), p. 418
preparedness, p. 409
psychosurgery, p. 423
regulatory behavior, p. 411
reinforcer, p. 409
releasing hormone, p. 414
sensory deprivation, p. 401
sexual dimorphism, p. 433
sexual orientation, p. 435
somatic marker hypothesis, p. 421
transgender, p. 435

Visit Launch Pad to access the e-Book, videos, Learning

Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

13

Why Do We Sleep and

Dream?
 Katherine Streeter

CLINICAL FOCUS 13-1 DOING THE RIGHT THING AT THE

RIGHT TIME
13-1 A CLOCK FOR ALL SEASONS
ORIGINS OF BIOLOGICAL RHYTHMS
BIOLOGICAL CLOCKS
EXPERIMENT 13-1 QUESTION: IS PLANT MOVEMENT
EXOGENOUS OR ENDOGENOUS?
MEASURING BIOLOGICAL RHYTHMS
FREE-RUNNING RHYTHMS
ZEITGEBERS
CLINICAL FOCUS 13-2 SEASONAL AFFECTIVE DISORDER
13-2 NEURAL BASIS OF THE BIOLOGICAL CLOCK
SUPRACHIASMATIC RHYTHMS
KEEPING TIME
PACEMAKING CIRCADIAN RHYTHMS
RESEARCH FOCUS 13-3 SYNCHRONIZING BIORHYTHMS AT
THE MOLECULAR LEVEL
PACEMAKING CIRCANNUAL RHYTHMS
COGNITIVE AND EMOTIONAL RHYTHMS
13-3 SLEEP STAGES AND DREAMING
MEASURING HOW LONG WE SLEEP
MEASURING SLEEP IN THE LABORATORY
STAGES OF WAKING AND SLEEPING
A TYPICAL NIGHT’S SLEEP
CONTRASTING NREM SLEEP AND REM SLEEP
CLINICAL FOCUS 13-4 RESTLESS LEGS SYNDROME
DREAMING
WHAT WE DREAM ABOUT
 13-4 WHAT DOES SLEEP ACCOMPLISH?
SLEEP AS A BIOLOGICAL ADAPTATION
SLEEP AS A RESTORATIVE PROCESS
SLEEP AND MEMORY STORAGE
13-5 NEURAL BASES OF SLEEP
RETICULAR ACTIVATING SYSTEM AND SLEEP
NEURAL BASIS OF THE EEG CHANGES ASSOCIATED WITH
WAKING
NEURAL BASIS OF REM SLEEP
13-6 SLEEP DISORDERS
DISORDERS OF NREM SLEEP
CLINICAL FOCUS 13-5 SLEEP APNEA
DISORDERS OF REM SLEEP
13-7 WHAT DOES SLEEP TELL US ABOUT
CONSCIOUSNESS?
CLINICAL FOCUS 13-1

Doing the Right Thing at the Right Time

We have all heard this advice: Maintaining regular sleeping and
eating habits contributes to good health. Scientific evidence supports
this good advice.
We humans are diurnal animals (from the Latin dies, meaning
day ): we are active during daylight and we sleep when it is dark.
This circadian rhythm is the day–night rhythm found in most
animals. It evolved to maximize food acquisition during the day,
when we see best, and to minimize expending our energy stores by
sleeping during the night hours, when do not see well.
diurnal animal Organism that is active chiefly during daylight.
Today our environment allows us to intrude on our circadian
rhythm in two ways. Artificial lighting allows us to extend our
waking hours well into the night and into sleep time. Handy food
sources—often easily metabolized high-calorie foods—allow us to
eat whenever we want.
circadian rhythm Day–night rhythm.
Together these intrusions into our natural circa-dian rhythm
contribute to a combination of medical disorders known as
metabolic syndrome that collectively increase the risk of
developing sleep disorders, cardiovascular disease, and diabetes
(Lajoie et al., 2015).
metabolic syndrome Combinations of medical disorders,
including obesity and insulin abnormalities, that collectively
increase the risk of developing cardiovascular disease and
diabetes.
The roots of metabolic syndrome lie in disruptions of our
biological clock, the neural system that times behavior. One clock
controls sleep–waking. Another controls the functioning of body
organs related to feeding, such as the liver, pancreas, and gut. The
clock that controls sleep–waking responds to light, whereas the clock
 that controls feeding responds to eating. Their activity is reciprocal:
disrupting one disrupts the other.
biological clock Neural system that times behavior.
Irregular sleep and meal schedules thus change the synchrony of
biological clocks. Metabolic rate, plasma glucose, and pancreatic
insulin secretion can slow down or speed up at inappropriate times,
contributing to obesity and diabetes. Prevention and treatment for
obesity and diabetes can include doing the right thing at the right
time when it comes to sleep schedules and mealtimes.

© AntonVengo/SuperStock

Humans and other animals perform a remarkable array of behaviors to

adapt to daily and seasonal cycles. Our daily rhythms of sleeping and
waking, feeding, exercising, and social interaction are rhythmical over
days and years. Other animals share these daily activities and also
migrate, hibernate, and shed or grow feathers or fur as the seasons
change. In this chapter we answer questions related to these daily and
seasonal rhythms, including how the brain produces biological rhythms,
why sleep evolved, and what neural mechanisms regulate sleeping,
waking, and sleep-related disorders.
 13-1 A Clock for All Seasons
We first consider evidence that proved the existence of a biological
clock: how the clock keeps time and how it regulates our behavior.
Because environmental cues are not always consistent, we examine how
biological clocks help us interpret environmental cues in an adaptive
way.

Origins of Biological Rhythms

Biorhythms, the inherent timing mechanisms that control or initiate
various biological processes, are linked to the cycles of days and seasons
produced by Earth’s rotation on its axis and by its progression in orbit
around the sun ( Figure 13-1 ). Earth rotates on its axis once every 24
hours, producing a 24-hour cycle of day and night. The day–night cycle
changes across the seasons, however.
biorhythm Inherent timing mechanism that controls or initiates
biological processes.

FIGURE 13-1 Origins of Biorhythms Each point on Earth between

the Arctic and Antarctic circles faces the sun for part of its daily rotation
cycle (daytime) and faces away from the sun for the other part (nighttime).
Seasonal changes in temperature and in the amount of daylight result
from the tilt of Earth’s axis during its annual revolution around the sun.

Earth’s axis is tilted slightly, so as it orbits the sun once each year, the
North and South Poles incline slightly toward the sun for part of the year
and slightly away from it for the rest of the year. As the Southern
Hemisphere inclines toward the sun, its inhabitants experience summer:
more direct sunshine for more hours each day, and the weather is
warmer. At the same time inhabitants of the Northern Hemisphere,
inclined away from the sun, experience winter: less direct sunlight,
making the days shorter and the weather colder. Over the year the polar
inclinations reverse, as do the seasons. Tropical regions near the equator
undergo little seasonal or day length change as Earth progresses around
the sun.
Daily and seasonal changes have combined effects on organisms,
inasmuch as the onset and duration of daily change depend on the season
and latitude. Animals living in polar regions have to cope with greater
seasonal fluctuations in daily temperature, light, and food availability
than do animals living near the equator.
We humans largely evolved as equatorial animals, and our behavior is
dominated by a circadian rhythm of daylight activity and nocturnal sleep.
Nevertheless our daily cycles adapt to extreme latitudes. Not only does
human waking and sleep behavior cycle daily; so also do pulse rate,
blood pressure, body temperature, rate of cell division, blood cell count,
alertness, urine composition, metabolic rate, sexual drive, feeding
behavior, and responsiveness to medications. The activity of nearly every
cell in our bodies shares a daily rhythm.
Biorhythms are not unique to animals. Plants display rhythmic
behavior exemplified by species whose leaves or flowers open during the
day and close at night. Even unicellular algae and fungi display rhythmic
behaviors related to the passage of the day. Some animals, including
lizards and crabs, change color in a rhythmic pattern. The Florida
chameleon, for example, turns green at night, whereas its coloration
matches its environment during the day. In short, almost every living
organism and every living cell displays rhythms related to daily changes
(Bosler et al., 2015).

Biological Clocks
If animal behavior were affected only by daily changes in external cues,
the neural mechanisms that account for changes in behavior would be
simple to study. An external cue—say, sunrise—could be isolated and
the neural processes that respond to the cue identified.
 EXPERIMENT 13-1

Question: Is plant movement exogenous or endogenous?

Leaf up

Leaf down
Bryan Kolb/Ian Whishaw

Conclusion: Movement of the plant is endogenous. It is caused by an

internal clock that matches the temporal passage of a real day.

That behavior is not driven simply by external cues was first

recognized in 1729 by the French geologist Jean Jacques d’Ortous de
Mairan (see Raven et al., 1992). In an experiment similar to the one
illustrated in the Procedure section of Experiment 13-1 , de Mairan
isolated a plant from daily light, dark, and temperature cues. He noted
that the rhythmic movements of its leaves seen over a light–dark cycle
continued when it was isolated as graphed in the Results section of the
experiment.
What concerned investigators who came after de Mairan was the
possibility that some undetected external cue stimulates the plant’s
rhythmic behavior. Such cues could include changes in temperature, in
electromagnetic fields, and even in the intensity of cosmic rays from
outer space. But further experiments showed that daily fluctuations are
endogenous—they come from within the plant. Thus, the plant must have
a biological clock. The contributions of endogenous rhythms to plants is
important both to agriculture and to food storage (Bendix et al., 2015).
Similar experiments show that almost all organisms, including
humans, have biological clocks that synchronize behavior to the temporal
passage of a real day and make predictions about tomorrow. A biological
clock signals that if daylight lasts for a given time today, it will last for
about the same time tomorrow. A biological clock allows us to anticipate
events and prepare for them both physiologically and cognitively. And
unless external factors get in the way, a biological clock regulates feeding
times, sleeping times, and metabolic activity as appropriate to day–night
cycles. Biological clocks also produce epigenetic effects: they regulate
gene expression in every cell in the body (Zhang et al., 2014).

Measuring Biological Rhythms

Although the existence of endogenous biological clocks was
demonstrated nearly 300 years ago, detailed study of biorhythms had to
await the development of electrical and computer-based timing devices.
Behavioral analysis requires a method for counting behavioral events and
a method for displaying those events in a meaningful way. For example,
rodent behavior was first measured by giving the animal access to a
running wheel for exercise (Figure 13-2 A ).
A computer records each turn of the wheel and displays the result
(Figure 13-2 B). Because most rodents are nocturnal, sleeping during
light hours and becoming active during dark hours, their wheel running
takes place in the dark. If each day’s activity is plotted under the
preceding day’s activity in a column, we observe a pattern—a cycle of
activity over time. A glance at the pattern reveals when and how active
the animal is (Figure 13-2C ).
The animal’s activity cycle has a period, the time required to complete
one cycle of activity. Most animals’ activity period is about 24 hours in
an environment in which the lights go on and off regularly. Our own
sleep–wake period also is about 24 hours. The measurement of periods
and the events that control them are central to understanding circadian
rhythms.
period Time required to complete an activity cycle.
Many behaviors have periods longer or shorter than this 24-hour circa-
dian rhythm. Circannual rhythms last about a year. Many animals’
migratory and mating cycles are circannual. Other biorhythms have
monthly or seasonal periods greater than a day but less than a year. These
are infradian rhythms. The menstrual cycle and associated hormonal
changes of human females, with an average period of about 28 days, is an
infradian biorhythm linked to the cycle of the moon and thus also referred
to as a circalunar cycle (Amariei et al., 2014).
In Latin circa means about, annum means year, and dies means day.
 FIGURE 13-2 Recording the Daily Activity Cycle of a Rat
Data from C. P. Richter (1965). Biological clocks in medicine and psychiatry
(pp. 12–15). Springfield, IL: Charles C Thomas.

Ultradian rhythms have a period of less than one day. Our eating
behavior, which takes place about every 90 minutes to 2 hours, including
snacks, is one ultradian rhythm. Rodents, although active throughout the
night, display an ultradian rhythm in being most active at the beginning
and end of the dark period.
Biological rhythm Time frame Example

Circannual Yearly Migratory cycles of birds

Circadian Daily Human sleep-wake cycle

Infradian More than a day Human menstrual cycle

Ultradian Less than a day Human eating cycles

The fact that a behavior appears to be rhythmic does not mean that it is
ruled only by a biological clock. Animals may postpone migrations as
long as food supplies last. They adjust their circadian activities in
response to the availability of food, the presence of predators, and
competition from other members of their own species. We humans
obviously change our daily activities in response to seasonal changes,
work schedules, and play opportunities. Therefore, whether a rhythmic
behavior is produced by a biological clock and the extent to which it is
controlled by a clock must be demonstrated experimentally.

Free-Running Rhythms
To determine whether a rhythm is produced by a biological clock,
researchers design three types of tests in which they manipulate relevant
cues, especially light cues. A test is given (1) in continuous light, (2) in
continuous darkness, or (3) by choice of the participant. Each treatment
yields a slightly different insight into the periods of biological clocks.
Jurgen Aschoff and Rutger Weber first demonstrated that the human
sleep–waking rhythm is governed by a biological clock. They allowed
participants to select their light–dark cycle and studied them in an
underground bunker, where no cues signaled when day began or ended.
The participants selected the periods when they were active and when
they slept, and they turned the lights on and off at will. In short they
selected the length of their own day and night.
Measures of ongoing behavior and recording of sleep periods with
sensors on the beds revealed that the participants continued to show daily
sleep–activity rhythms. This finding demonstrates that humans have an
endogenous biological clock that governs sleep–waking behavior. Figure
13-3 shows, however, that the biorhythm is different when compared with
biorhythms before and after isolation. Although the period of the
participants’ sleep–wake cycles approximated 24 hours before and after
the test, during the test they lengthened to about 25 to 27 hours,
depending on the person.

FIGURE 13-3 Free-Running Rhythm in a Human The record

for days 1 through 3 shows the daily sleep period under typical day–night
conditions. The record for days 4 through 20 shows the free-running
rhythm that developed while this participant was isolated in a bunker and
allowed to control day and night lengths. The daily activity period shifts
 from 24 hours to 25.9 hours. On days 21 through 25 the period returns to
24 hours as the participant is again exposed to a natural light–dark cycle.
Data from J. A. Hobson (1989). Sleep (p. 33). New York: Scientific American Library.

The participants chose to go to bed 1 to 2 hours later every “night.”

Soon they were getting up at about the time the experimenters outside the
bunker were going to bed. Clearly. the participants were displaying their
own personal cycles. Such a free-running rhythm runs at a frequency of
the body’s own devising when environmental cues are absent. Humans’
self-selected free-running rhythm is slightly longer than 24 hours.
free-running rhythm Rhythm of the body’s own devising in the
absence of all external cues.
The period of free-running rhythms also depends on the light-related
biology of the species. When hamsters, a nocturnal species, are tested in
constant darkness, their free-running periods are a little shorter than 24
hours; when they are tested in constant light, their free-running periods
are a little longer than 24 hours. This test dependency is typical of
nocturnal animals. As Figure 13-4 shows, the opposite free-running
periods are typical of diurnal animals (Binkley, 1990). When sparrows,
diurnal birds, are tested in constant darkness, their free-running periods
are a little longer than 24 hours; when they are tested in constant light,
their free-running periods are a little shorter than 24 hours.
A rule of thumb to explain the period of free-running rhythms in light
or dark is that animals expand and contract their sleep periods as the
sleep-related period—light for hamsters and dark for sparrows—expands
or contracts. Understanding this point enables us to predict how excess
artificial lighting, which expands the light portion of our days, influences
our circadian periods. Because we are diurnal, our sleep periods contract
and we get less sleep each night.

Zeitgebers
Endogenous rhythmicity is not the only factor that contributes to
circadian periods. A mechanism exists for setting rhythms to correspond
to environmental events as well. To be useful, the biological clock must
keep to a time that predicts actual changes in the day–night cycle. If a
biological clock is like a slightly defective wristwatch, it will eventually
provide times that are inaccurate by hours and so be useless.
If we reset an errant wristwatch each day, however—say, when we
awaken—it provides useful information even though it is not perfectly
accurate. Equivalent ways of resetting a free-running biological clock
include sunrise and sunset, eating times, and many other activities that
influence the period of the circadian clock.
Aschoff and Weber called a clock-setting cue a Zeitgeber (time giver
in German). When a Zeitgeber resets a biorhythm, the rhythm is said to
be entrained. Light is the most potent entraining stimulus. Clinical Focus
13-2 , Seasonal Affective Disorder, explains its importance in entraining
circadian rhythms.
Zeitgeber Environmental event that entrains biological rhythms:
German for time giver.
entrain Determine or modify the period of a biorhythm.

FIGURE 13-4 Free-Running Rhythms of a Diurnal

Animal Data from S. Binkley (1990). The Clockwork Sparrow (p. 16). Englewood Cliffs NJ:
Prentice Hall.

The property that allows a biological clock to be entrained explains

how circadian rhythms synchronize with seasonal changes in day–night
duration. North and south of the equator the time of onset and the length
of day and night change as the seasons progress. At extreme latitudes
daylight begins very early in the morning in summer and very late in the
morning in winter. An entrained biological clock allows an animal to
synchronize its daily activity across these seasonal changes.
A biological clock that resets each day tells an animal that daylight
will begin tomorrow at approximately the same time that it began today
and that tomorrow will last approximately as long as today did. Current
research finds that light Zeitgebers are effective at both sunrise and
sunset: morning light sets the biological clock by advancing it, and
evening darkness sets the clock by retarding it (Schmal et al., 2015).
The potent entraining effect of light Zeitgebers is illustrated by
laboratory studies of Syrian hamsters, perhaps one of the most
compulsive animal timekeepers. When given access to running wheels,
hamsters exercise during the night segment of the laboratory day–night
cycle. A single brief flash of light is an effective Zeitgeber for entraining
their biological clocks.
Considering the less compulsive behavior that most of us display, we
should shudder at the way we entrain our own clocks when we stay up
late in artificial light, sleep late some days, and get up early by using an
alarm clock on other days. Light pollution, the extent to which we are
exposed to artificial lighting, disrupts circadian rhythms and accounts for
a great deal of inconsistent behavior associated with accidents, daytime
fatigue, alterations in emotional states, obesity, diabetes, and other
disorders characteristic of metabolic syndrome described in Clinical
Focus 13-1 , Doing the Right Thing at the Right time (Gerhart-Hines &
Lazar, 2015).
light pollution Exposure to artificial light that changes activity
patterns and so disrupts circadian rhythms.
Entrainment works best if the adjustment made to the biological clock
is not too large. People who work night shifts are often subject to huge
adjustments, especially when they work the graveyard shift (11:00 P.M . to
7:00 A.M .), the period when they would normally sleep. Study results
show that adapting to such a change is difficult and stressful, and it
increases susceptibility to disease by altering immune system rhythms
(Labrecque & Cermakian, 2015). Compared with people who have a
regular daytime work schedule, people who work night shifts have a
higher incidence of metabolic syndrome. Thus, shift workers benefit from
vigilance in maintaining good sleep habits and diet and in exercising to
minimize other risk factors for metabolic syndrome. Adaptations to shift
work fare better if people first work the swing shift (3:00 P.M . to 11:00
P.M .) for a time before beginning the graveyard shift.

If a hamster happens to blink during this Zeitgeber, the light will still
penetrate its closed eyelids and entrain its biological clock.
CLINICAL FOCUS 13-2

Seasonal Affective Disorder

In seasonal affective disorder (SAD), a form of depression, low
levels of sunlight in winter, do not entrain the circadian rhythm.
Consequently, a person’s biorhythm becomes a free-running rhythm.
The perception of longer nights by the circadian pacemaker
stimulates wanting more sleep. If the want is not satisfied,
cumulative sleep deprivation can result.
Because people vary in the duration of their free-running rhythms,
lack of entrainment affects individuals differently. Some are phase-
retarded, with desired sleep time coming earlier each day; some are
phase-delayed, with desired sleep time coming later each day.
The cumulative changes associated with altered circadian rhythms
can promote depression. The finding that incidence of depressive
symptoms increases as a function of the latitude at which a person
lives supports this idea.
Because a class of retinal ganglion cells that express a
photosensitive pigment called melanopsin are responsive to blue
light (see Section 13-2 ), it has been proposed that exposure to bright
white light that contains this blue frequency can reset the circadian
clock and ameliorate depression. In this treatment, called
phototherapy, the idea is to increase the short winter photoperiod by
exposing a person to artificial bright light in the morning or both
morning and evening (Mårtensson et al., 2015). Typical room
lighting is not bright enough.
A word of caution, however. Decreased exposure to sunlight in
winter can result in Vitamin D deficiency and is also suggested to
contribute to depression (Kerr et al., 2015).
 Bryan and Cherry Alexander/Science Source
During the polar night in northern Norway schoolchildren take light
treatment to combat SAD.

Long-distance air travel—say from North America to Europe or Asia

—also demands large and difficult time adjustments. For example,
travelers flying east from New York to Paris begin their first day in
Europe just when their biological clock is signaling that it is time for
sleep ( Figure 13-5 ). The difference between a person’s circadian
rhythm and the daylight cycle in a new environment can produce the
disorientation and fatigue of jet lag.
jet lag Fatigue and disorientation resulting from rapid travel through
time zones and exposure to a changed light–dark cycle.
The west-to-east traveler generally has a more difficult adjustment
than does the east-to-west traveler, who needs to stay up only a little
longer than usual. The occasional traveler may cope with jet lag quite
well, but frequent travelers such as airline personnel face a substantial
adaptive challenge. The occasional traveler can manage jet lag with sleep
on arrival or shortly after. The brain’s biological clock resets in a day and
other body organs follow after about a week. For frequent travelers and
flight crews, resetting is not so easy. Persistent asynchronous rhythms
generated by jet lag are associated with altered sleep and temperature
rhythms, fatigue, and stress, even reduced success by sports teams
traveling more than 3 hours from west to east (Weingarten and Collop,
2013).
FIGURE 13-5 Jet Lag Disruption in the entrainment of a person’s
biological clock is undoubtedly more pronounced in west-to-east jet travel
because the disruption in the person’s circadian rhythm is dramatic. On
the return journey the traveler’s biological clock has a much easier
adjustment to make.
 13-1 REVIEW
A Clock for All Seasons
Before you continue, check your understanding.
1 . Many behaviors occur in a rhythmic pattern in relation to time. These
biorhythms may display a yearly, or ___________, cycle or a daily, or
___________, cycle.
2 . Although biological clocks keep fairly good time, their ___________
rhythms may be slightly shorter or longer than 24 hours unless they
are reset each day by ___________.
3 . ___________ and ___________ can disrupt circadian rhythms.
4 . Explain why the circadian rhythm is important.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 13-2 Neural Basis of the Biological Clock
Curt Richter (1965) was the first researcher who attempted to locate
biological clocks in the brain. In the 1930s he captured wild rats and
tested them in activity wheels. He found that the animals ran, ate, and
drank when the lights were off and were relatively quiescent when the
lights were on.
By ablating brain tissue with electric current, Richter found that
animals lost their circadian rhythm after damage to the hypothalamus.
Subsequently, by making much more discrete lesions, experimenters have
shown that a region of the hypothalamus, the suprachiasmatic nucleus
(SCN), acts as the master biological clock (Webb et al., 2014). The SCN
is named for its location just above (supra- ) the optic chiasm, where the
optic tracts cross at the base of the hypothalamus.
suprachiasmatic nucleus (SCN) Master biological clock located in
the hypothalamus just above the optic chiasm.
Suprachiasmatic Nucleus in a Rat Brain
Suprachiasmatic Rhythms
Evidence for the SCN’s role in circadian rhythms now comes from
additional lines of evidence:
1. If the suprachiasmatic nuclei are selectively damaged, animals still eat,
drink, exercise, and sleep but at haphazard times.
2. If a form of glucose is tagged with a radioactive label, taken up by
metabolically active cells, and trapped in them but not used by them,
cells that are more active will subsequently emit more radioactivity.
When this tracer is injected into rodents, more is found in the SCN after
injections given in the light period of the light–dark cycle than in the
dark period. This experiment demonstrates that suprachiasmatic cells
are more active during the light period.
3. Recording electrodes placed in the SCN confirm that neurons in this
region are more active during the light period of the cycle than during
the dark period.
4. If all the pathways into and out of the suprachiasmatic nucleus are cut,
SCN neurons maintain their rhythmic electrical activity.
5. SCN cells removed from the brain and cultured in a dish retain a
periodic rhythm.
Clearly, suprachiasmatic neurons have an intrinsically rhythmic
activity pattern. Although the SCN is the master biological clock, it is not
the sole one. Two other neural structures, the intergeniculate leaflet and
the pineal gland, also display clocklike activity. Further, nearly every cell
in the body has its own clock.
After the SCN is destroyed, some behaviors retain a timed occurrence.
One is feeding. Animals without an SCN can still display anticipatory
behavior—becoming active in relation to scheduled mealtimes—and can
organize related behaviors, including memory for food locations, in
relation to mealtimes (Landgraf et al., 2015). How this anticipatory
behavior is timed is not known, but whatever the mechanism, feeding-
related activity can act as a Zeitgeber for the main SCN clock. That is, a
regular feeding schedule can entrain the SCN clock and many other body
organs, and cells and an irregular feeding schedule can be disruptive.

Keeping Time
 If SCN neurons are isolated from one another, each remains rhythmic,
but the period of some cells differs from that of other cells. Thus rhythmic
activity is a property of SCN cells, but the timing of the rhythm must be
set so that the cells can synchronize their activity in relation to each other.
In the brain, SCN cells connect one to another through inhibitory GABA
synapses, and these connections allow them to act in synchrony. Their
entrainment depends upon external inputs, however.
GABA is main inhibitory neurotransmitter in the CNS.
The SCN receives information about light through the
retinohypothalamic tract ( Figure 13-6 ). This pathway begins with
specialized retinal ganglion cells (RGCs) that contain the photosensitive
pigment melanopsin. These melanopsin-containing photosensitive RGCs
receive light-related signals from the rods and cones and send that
information to the brain’s visual centers. Melanopsin-containing pRGCs
also can be activated directly by certain wavelengths of blue light in the
absence of rods and cones.
retinohypothalamic tract Neural route formed by axons of
photosensitive retinal ganglion cells from the retina to the
suprachiasmatic nucleus; allows light to entrain the rhythmic activity
of the SCN.
Section 9-2 traces three main routes from the retina to the visual
brain. Figure 9-8 diagrams the retina’s cellular structure.
Melanopsin-containing photosensitive RGCs are distributed across the
retina, and in humans they make up between 1 percent and 3 percent of
all RGCs. Their axons project to various brain regions, including the
SCN, which they innervate bilaterally. Melanopsin-containing ganglion
cells use glutamate as their primary neurotransmitter but also contain two
cotransmitters, substance P and pituitary adenylate cyclase–activating
polypeptide (PACAP).
Glutamate is the main excitatory neurotransmitter in the CNS.
When stimulated by light, melanopsin-containing pRGCs are excited,
and in turn they excite cells in the SCN. The existence of light-sensitive
retinal ganglion cells that are involved in entraining the circadian rhythm
explains the continued presence of an entrained rhythm in people who are
blind as a result of retinal degeneration that destroys the rods and cones
(Zaidi et al., 2007). Even so, melanopsin-containing pRGCs do receive
inputs from cones and rods. Cones can influence their activity in bright
daylight, and rods can influence their activity in dim light.
As illustrated in Figure 13-6 , the SCN consists of two parts, a more
ventrally located core and a more dorsally located shell. The
retinohypothalamic tract activates the core cells. Core neurons are not
rhythmic, but they entrain the shell neurons, which are rhythmic.
In addition to retinohypothalamic input, the SCN receives projections
from other brain regions, including the intergeniculate leaflet in the
thalamus and the raphe nucleus, which is the nonspecific serotonergic-
activating system of the brainstem. The terminal regions of these inputs to
the SCN display variations, suggesting that various portions of the shell
and the core have somewhat different functions.
The SCN’s circadian rhythm is usually entrained by morning and
evening light, but it can also be entrained or disrupted by sudden changes
in lighting, by arousal, by moving about, and by feeding. These
influences differ from the light entrainment provided over the
retinohypothalamic tract.
The intergeniculate leaflet and the raphe nucleus are pathways through
which nonphotic events influence the SCN rhythm (Cain et al., 2007).
The neural structures mediating these other entraining pathways explain
why being aroused or eating during the sleep portion of the circadian
cycle disrupts the cycle (Mistlberger & Antle, 2011).
It is likely that the regional variation in SCN shell anatomy provides
the substrate for various rhythms of the circadian cycle. Findings from
studies on the genes that control rhythms in fruit flies suggest two
separate groups of circadian neurons. M cells control morning activity;
they need morning light for entrainment. E cells control evening activity;
they need onset of darkness for entrainment (Hughes et al., 2015).
Some people are early to bed and early to rise and are energetic in the
morning. Other people are late to rise and late to bed and are energetic in
the evening. Individual differences in circadian activity between these
“lark” and “owl” chronotypes are due to differences in SCN shell
neurons. The differences may be the equivalent of fruit fly M cells and E
cells, When expressed differently in people, genes may account for
differences in the amplitude of phases in the circadian period. (Pellegrino
et al, 2015). Whether students are larks or owls does affect their
performance on cognitive tasks, possibly by affecting memory for content
(Smarr, 2015).
 chronotype Individual differences in circadian activity.

FIGURE 13-6 The Retinohypothalamic Tract and the

SCN
Healthy

Suprachiasmatic lesion
 Suprachiasmatic transplant

Circadian Rhythms Restored by Neural

FIGURE 13-7

Transplantation Information from M. R. Ralph & M. N. Lehman (1991).

Transplantation: A new tool in the analysis of the mammalian hypothalamic circadian pacemaker.
Trends in Neurosciences, 14, p. 363.

In hamsters and mice, mutant gene variations produce chronotypes

with circadian periods as varied as 24, 20, or 17 hours (Monecke et al.,
2011). As genetic analysis becomes less expensive, the study of the genes
underlying human chronotypes is providing insights into individual
differences in our biological clocks (Kang et al., 2015).
Immortal Time
How do suprachiasmatic cells develop rhythmic activity? Their
endogenous rhythm is not learned. When animals are raised in constant
darkness, their behavior still becomes rhythmic. In experiments in which
animals have been maintained without entraining cues for a number of
generations, each generation continues to display rhythmic behavior.
Even if the mother has received an SCN lesion so that her behavior is not
rhythmic, her offspring’s behavior is rhythmic.
A line of evidence supporting the idea that suprachiasmatic cells are
genetically programmed for rhythmicity comes from studies performed in
Canada by Martin Ralph and his coworkers with the use of
transplantation techniques (Ralph & Lehman, 1991). Figure 13-7
illustrates the experiment.
As reflected in the top chart, hamsters are tested in constant dim light
or in constant darkness to establish their free-running rhythms. They then
receive a suprachiasmatic lesion followed by another test to show that the
lesion has abolished their rhythmicity (center chart). Finally, the hamsters
receive transplants of suprachiasmatic cells obtained from hamster
embryos. About 60 days later the hamsters again show rhythmic activity,
demonstrating that the transplanted cells have been integrated into the
host brain and have reestablished rhythmic behavior (bottom chart).
Follow-up studies show that the rhythms of many but not all body organs
also show restored rhythmic activity.
What Ticks?
Molecular research is directed toward determining what genes control the
ticking of the circadian clock. The timing device is in each SCN neuron
and in most other cells of the body as well.
The circadian rhythm involves a feedback loop in which proteins are
first made and then combine. The combined protein, called a dimer, for
two proteins, inhibits production of its component proteins. Then the
dimer degrades and the process begins anew. Research Focus 13-3 ,
Synchronizing Biorhythms at the Molecular Level, describes the main
feedback loop in mammals. Just as the back-and-forth swing of a
pendulum makes a grandfather clock tick, the increase and decrease in
protein synthesis once each day produce the cellular rhythm.
Figure 3-13 diagrams the process of protein synthesis.

Pacemaking Circadian Rhythms

The SCN itself is not directly responsible for producing behavior. After it
has been damaged, drinking and eating, sleeping and wakefulness still
occur. They no longer occur at appropriate times, however.
An explanation for how the SCN controls biological rhythms is
illustrated in Figure 13-8 . In this model, light entrains the SCN, and the
SCN in turn drives a number of slave oscillators. Each slave oscillator is
responsible for the rhythmic occurrence of one activity. In other words,
drinking, eating, body temperature, and sleeping are each produced by a
separate slave oscillator.
RESEARCH FOCUS 13-3

Synchronizing Biorhythms at the Molecular

Level
The retinohypothalamic tract carries information about light changes
from the melanopsin-containing photosensitive retinal ganglion cells
to the core of the SCN, the brain’s main biological timekeeper (see
Figure 13-6 ). Core cells synapse with SCN neurons in the shell and
entrain the SCN shell cells to the light signal’s 24-hour rhythm.
The timing mechanism in the shell cells is a pair of interlocking
feedback loops that pace the SCN’s function over a 24-hour period.
The complete clockwork in the two feedback loops involves as many
as 10 genes and their protein products. The secondary loop regulates
functions for the main clockwork loop.
The main clock mechanism is the transcription-translation-
inhibition-feedback loop. Its sequence, mapped in the illustration,
follows:
STEP 1: TRANSCRIPTION In the cell nucleus three Period genes
(Per1, * Per2, Per3 ) and two Cryptochrome genes (Cry1, Cry2 ) are
transcribed into Per1, Per2, and Per3 messenger RNA and Cry1 and
Cry2 mRNA.
* Gene and mRNA names are italicized.
STEP 2: TRANSLATION Ribosomes in the endoplasmic reticulum
translate these mRNAs into the proteins PER1, † PER2, PER3, and
CRY1, CRY2. In the intracellular fluid the proteins form various
dimers, or two-protein combinations of PERCRY.
†PROTEIN names are capitalized.
dimer Two proteins combined into one.
STEP 3: INHIBITION PERCRY dimers enter the cell nucleus,
where they bind to and inhibit the CB dimer (formed by the CLOCK
and BMAL proteins). The CB dimer turns on the Enhancer box
(Ebox), a part of the DNA that activates transcription of the Period
 and Cryptochrome genes, so that when the CB dimer is inhibited, the
Per and Cry genes are no longer expressed.
STEP 4: DECAY After they play their inhibitory role, the PERCRY
proteins decay. Then the CB dimer resumes its activity, the Per and
Cry genes resume expression, and the 24-hour cycle begins anew.
This sequence of gene turn-on followed by gene turn-off occurs in
an inexorable daily loop.
Mutations in any circadian gene can lead to circadian alterations,
including absence of a biorhythm or an altered biorhythm. For
example, alleles of Period 1 and Period 2 genes determine
chronotype—whether an individual will be early to bed and early to
rise or late to bed and late to rise. The search for therapies for clock
disorders includes looking for small molecules that can act as drugs
to reset biorhythms disrupted by jet lag, shift work, and epigenetic
and inherited gene irregularities.
Cytoplasm

Main SCN Clock Mechanism

The SCN clock entrains slave oscillators through a remarkable array

of pathways:
1. SCN neurons send axonal connections to nuclei close by in the
hypothalamus and thalamus. These nuclei in turn connect extensively
with other brain and body structures, to which they pass on the
entraining signal.
2. The SCN connects with pituitary endocrine neurons to control
hormone release. A wide range of hormones circulates through the
body to entrain many body tissues and organs.
Figure 12-14 diagrams how the pituitary gland works.

FIGURE 13-8 Circadian Timing System Organization

3. The SCN also sends indirect messages to autonomic neurons in the
spinal cord to inhibit the pineal gland from producing the hormone
melatonin, which influences daily and seasonal biorhythms.
melatonin Hormone secreted by the pineal gland during the dark
phase of the day–night cycle; influences daily and seasonal
biorhythms.
4. SCN cells themselves release hormones. Silver and colleagues (1996)
used a transplantation technique in which encapsulated SCN cells were
transplanted into hamsters that had received SCN lesions. Even though
the transplanted cells did not make axonal connections, they restored
many circadian behaviors, indicating that some SCN signals must be
hormonal and travel through the bloodstream.
An illustration of the SCN’s widespread effects is its control of two
hormones, melatonin and glucocorticoids. The SCN controls melatonin
release from the pineal gland so that melatonin circulates during the dark
phase of the circadian cycle. It also controls the release of
glucocorticoids from the adrenal glands so that they circulate during the
light phase of the circadian cycle.
Melatonin promotes sleep and influences the parasympathetic rest-
and-digest system as well as other physiological events in the body.
Glucocorticoids mobilize glucose for cellular activity to support arousal
responses in the sympathetic system. These two hormones will entrain
any body organ that has receptors for them, and most organs do. Thus
melatonin promotes rest activities, and glucocorticoids promote arousal
activities during the dark and the light portions of the circadian cycle,
respectively. Their actions explain in part why it is difficult to sleep
during the day and stay awake to work at night. The role of melatonin as
a slave oscillator in part explains its use as a drug for regulating sleep
(Claustrat & Leston, 2015).
Figure 2-30 diagrams the autonomic nervous system. Section 6-5
describes how glucocorticoids affect the body and brain.

Pacemaking Circannual Rhythms

The suprachiasmatic nucleus controls not only daily rhythms but
circannual rhythms as well. Russel Reiter (1980) first illustrated this
form of pacemaking in hamsters. Hamsters are summertime (long-day)
breeders. As the days lengthen in springtime, the gonads of male
hamsters grow and release hormones that stimulate sexual behavior. As
the days shorten in the winter, the gonads shrink, the amount of the
hormones they produce decreases, and the males lose interest in sex.
During the dark phase of the day–night cycle the pineal gland secretes
melatonin; during the light phase it does not. Figure 13-9 shows that
when a male hamster’s melatonin level is low, the gonads enlarge, and
when the level is high, the gonads shrink. The SCN thus controls the
pineal gland’s sway over the gonads. Through connections in the
autonomic nervous system the SCN drives the pineal gland as a slave
oscillator.

FIGURE 13-9 Hamster’s Circannual Pacemaker Information

from R. J. Reiter (1980). The pineal and its hormones in the control of reproduction in mammals.
Endocrinology Review, 1, p. 120.
 During the long daylight period of the circadian cycle the SCN
inhibits melatonin secretion by the pineal gland. As the days become
shorter, the melatonin inhibition period shortens and the release period
lengthens. When the daylight period is shorter than 12 hours, melatonin
release time becomes sufficient to inhibit the hamster’s gonads, and they
shrink. Melatonin also influences the testes of short-day breeders, such
as sheep and deer, that mate in the fall and early winter. Melatonin’s
effect on reproductive behavior in these species is the reverse of that in
the hamster: reproductive activities begin as melatonin release increases.
The SCN’s influence on circadian and circannual cycles is proposed
to contribute to obesity in humans (Gangwisch, 2014). The idea is that
long daylight hours involve fueling high-energy demanding activities
during summer and thus extra food consumption. If a person is exposed
to light pollution during winter, increased food consumption continues
throughout the year, leading to weight gain. Light exposure can come
from surprising sources. Some street lamps, reading lights, and e-readers
emit blue-light wavelengths that activate pRGCs and through the SCN
suppress melatonin (Chang et al., 2015). Thus, incidental light pollution
can contribute to obesity.
In his classic book Biological Clocks in Medicine and Psychiatry,
Curt Richter (1965) hypothesized that many physical and behavioral
disorders might be caused by shocks, either physical or environmental,
that upset the timing of biological clocks. For example, the record of
psychotic episodes of the English writer Mary Lamb illustrated in Figure
13-10 is one of many rhythmic records that Richter thought represented
the action of an abnormally functioning biological clock.

FIGURE 13-10Dysfunctional Clock? Attacks of mental illness

displayed by the English writer Mary Lamb through her adult life appear to
have had a cyclical component. Such observations would be difficult to
obtain today because the drugs used to treat psychiatric disorders can
mask disordered biorhythms. Information from C. P. Richter (1965). Biological clocks in
medicine and psychiatry (p. 92). Springfield IL: Charles C Thomas.

Cognitive and Emotional Rhythms

Circadian rhythms are synchronized in many parts of the body. In a
phasic manner they influence cognitive and emotional functions,
including emotional experience, learning and retention, decision making,
and motivation. The extent to which a process depends on the
expenditure of metabolic energy dictates optimal times for its activity
during the circadian cycle: time of day can serve as a good index for the
time and place at which things should happen. Studies suggest that as
much as 10 percent of the genome is under the epigenetic control of
circadian rhythms.
Many cognitive events require changes in gene expression. Animals
remember previous events better if they are tested at the time of the
circadian period when the initial event occurred. Donald Cain and his
colleagues (2008) used a conditional place response to test rats’
memories for a location at which they had previously received a small
foot shock. The rats receive the noxious stimulation in a test box, then
are returned to their home cage.
The following day groups of rats are tested at the time of training or a
different time. Rats trained at time 1 and tested at time 1 show better
retention as measured by the time they spent immobile (freezing) than
rats trained at time 1 and tested at time 2, six hours later in the day.
Similarly, rats trained at time 2 and tested at time 2 show better retention
than rats trained at time 2 and tested at time 1, six hours earlier in the
day. The results show that the circadian cycle puts a time stamp on the
memory that allows it to be better recalled at the same time of the period
that the initial event occurred.
Cognitive behaviors also synchronize with circadian periods. Animals
have a variety of needs for food, water, and sleep, and it is adaptive for
them to know when these resources become available. If food is
available on a schedule, animals display anticipatory behaviors,
becoming active as the feeding time arrives, for example. Other
anticipatory events include salivation, intestinal activity, and sensations
of hunger. Anticipatory activity might also include recalling events
related to the timing of feeding and food location. Many cognitive
activities can occur in the absence of the SCN, but it is adaptive for them
to occur at the right time and place. SCN activity enables this. As
animals age, their ability to associate appropriate activity with
appropriate time declines, impairing their daily schedule, an effect that
might in part account for poor scheduling and sleep in some older
humans (Mulder et al., 2015).
Studies also find that the circadian period influences emotional
behavior. A time of day effect may account for some of our emotional
responses to daily events independent of the events themselves (Li et al.,
2015). Nighttime fear is common, but is it the dark or the nighttime
circadian rhythm that accounts for heightened emotion? By
independently varying lighting conditions and test times during the
circadian cycle, Li and colleagues found heightened emotional responses
to stimuli at night independent of ambient lighting. Thus the cycle, not
just darkness, contributes to emotional responding. Apparently at least
two factors explain why horror movies watched at night are scarier: the
movie’s content and the time of day effect.
 13-2 REVIEW
Neural Basis of the Biological Clock
Before you continue, check your understanding.
1 . Biological rhythms are timed by internal biological clocks. The
master clock is the ___________.
2 . Light cues entrain the suprachiasmatic nucleus to control daily
rhythms via the ___________ tract, which receives information via
___________ cells.
3 . Pacemaking produced by the SCN is a product of its ___________
cells, which activate slave oscillators via both ___________ signals
and ___________ connections.
4 . Why should studying for an exam and taking the exam occur at the
same time of day?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 13-3 Sleep Stages and Dreaming
Waking behavior encompasses periods when we are physically active or
inactive, and so does sleep. Our sleeping behavior consists of periods of
rest, napping, long bouts of sleep, and sleep-related events, including
snoring, dreaming, thrashing about, even sleepwalking. In this section we
describe some sleeping and dreaming behaviors and the neural processes
underlying them.
Recommended Sleep Duration by Age
Age Sleep time

Newborn up to 3 months 14-17

Infant under 1 year 12-15

Toddler up to 3 years 11-14

Preschool 10-13

Elementary-school age 9-11

Adolescent 8-10

Adult 7-9

Adult 65 years and older 7-8

Source: Information from National Sleep Foundation

Measuring How Long We Sleep

A crude measure of sleeping and waking behavior is the self-report :
people record in a diary when they wake and when they retire to sleep.
The diaries show both optimal average sleep durations and considerable
variation in sleep–waking behavior. An optimal sleep time of 7 to 8 hours
per night is a popular adage, but many exceptions exist. People sleep
more when they are young, after engaging in physical activity, or when
pregnant. Some people are long sleepers; some are short sleepers.
Numerous genetic mutations have been identified in people displaying
very short sleep durations—as short as 1 hour.
Some people nap for a brief period in the daytime; others never nap.
Benjamin Franklin is credited with the aphorism “early to bed and early
to rise makes a man healthy wealthy and wise,” but measures of sleep
behavior indicate that the correlation Franklin proposed does not actually
exist. Variations in sleeping times are normal, and napping normally is
good.

FIGURE 13-11 Sleep Laboratory Setup Electronic equipment

records readouts from electrodes attached to the sleeper. (A) EEG made
from a point on the skull relative to a neutral point on the ear. (B) EMG
made between two muscles, such as those on the chin and throat. (C)
EOG made between the eye and a neutral point on the ear.

(A) Electroencephalogram (EEG)

(B) Electromyogram (EMG)

 (C) Electrooculogram (EOG)

Measuring Sleep in the Laboratory

Laboratory sleep studies allow researchers to measure sleep accurately
and to record physiological changes associated with sleep. Miniaturized
sleep-measuring technology and data compression now allow laboratory
methods to be extended into the home (Lan et al., 2015). Measuring sleep
requires recording at least three electrical body signals; the brain activity,
muscle activity, and the eye movement. Figure 13-11 illustrates a typical
polygraph setup in a sleep laboratory and these commonly used measures
that define sleep.
Electrodes pasted onto standard locations on the skull’s surface yield
an electroencephalogram (EEG), a record of brain wave activity.
Electrodes placed on neck muscles provide an electromyogram (EMG), a
record of muscle activity. Electrodes located near the eyes provide an
electrooculogram (EOG), a record of eye movements. Body temperature,
circulating hormones, and blood glucose levels provide additional
measures of sleep.

Stages of Waking and Sleeping

Biological measurements show that sleep, like waking, is not a unitary
state but encompasses several stages. For example, the EEG recording
shows distinct patterns of brain wave activity as the neocortex generates
distinct rhythmic patterns for states categorized as awake, relaxed,
drowsy, sleep, deep sleep, and dreaming.
Waking State
When a person is awake, the EEG pattern consists of small-amplitude
(height) waves with a fast frequency (repetition period). This pattern, the
beta (β) rhythm, is defined by a frequency of 15 to 30 Hz (times per
second). The pattern is also called fast-wave activity-activated EEG, or
waking EEG. Also associated with waking, the EMG is active and the
EOG indicates that the eyes move.
beta ( β ) rhythm Fast brain wave activity pattern associated with a
waking EEG.
Figure 7-9 diagrams EEG patterns that reflect a range of conscious
states in humans.
Excited

Relaxed, eyes closed

Deep sleep
Relaxed State
When participants relax and close their eyes, they may produce the alpha
( a) rhythm —large, extremely regular brain waves with a frequency
ranging from 7 to 11 Hz. Humans generate alpha rhythms in the region of
the visual cortex at the back of the brain, and the rhythms abruptly stop if
a relaxed person is disturbed or opens his or her eyes. Not everyone
displays alpha rhythms, and some people display them much better than
others.
Drowsy State
When a person grows drowsy, the EEG indicates that beta wave activity
in the neocortex gives way to slower EEG wave activity. The amplitude
of the EEG waves increases and their frequency becomes a slower theta (
θ) rhythm of 4- to 7-Hz waves. Concurrently the EMG remains active, as
the muscles have tone, and the EOG indicates that the eyes are not
moving.
Sleeping State
As participants enter deeper sleep, they produce yet slower, larger EEG
waves called delta (δ) rhythms. Delta rhythm has a frequency of 1 to 3
Hz and is associated with the loss of consciousness that characterizes
sleep. This stage is sometimes called slow-wave sleep. Still, the EMG
indicates muscle activity, signifying that the muscles retain tone, although
the EOG indicates that the eyes do not move.
delta ( δ ) rhythm Slow brain wave activity pattern associated with
deep sleep.
 slow-wave sleep NREM sleep.
REM and NREM Sleep Phases
Sleep consists of periods when a sleeper is relatively still and periods
when the mouth, fingers, and toes twitch. This behavior is readily
observed in household pets and bed partners. In 1955 Eugene Aserinsky
and Nathaniel Kleitman (Lamberg, 2003), working at the University of
Chicago, observed that the twitching is periodic and is also associated
with rapid eye movements (REM). Other than twitches and eye
movements, the EMG indicates that muscles are inactive, a condition
termed atonia (Greek via Latin, “without tone”).
atonia Lacking tone; condition of complete muscle inactivity
produced by motor neuron inhibition.
By accumulating and analyzing REM recorded on EEGs, the Chicago
investigators were the first to identify REM sleep, a fast-wave sleep
period whose pattern is reminiscent of a waking EEG (see Dement,
1972). This discovery led to the contemporary naming of two sleep states,
REM and NREM. The delta rhythm sleep period, during which the EEG
pattern is slow and large and the EOG is inactive, is called NREM (for
non-REM) sleep to distinguish it from REM sleep.
REM sleep Fast brain wave pattern displayed by the neocortical
EEG record during sleep.
Other Sleep- and Waking-Related Activities
Although electrophysiological measures define the sleep stages, many
other bodily and physiological events are associated with waking and
sleep stages. Measures of metabolic activity, such as body temperature,
generally decline during sleep. Breathing and heart rate provide further
insights into waking and sleeping. The sleeper’s behavior—tossing and
turning, moaning and laughing—also occur during specific sleep stages.
Taken together, these measures yield insights into the many causes and
symptoms of normal sleep and disturbed sleep.
NREM (non-REM) sleep Slow-wave sleep associated with delta
rhythms.

A Typical Night’s Sleep

Figure 13-12 A displays the EEG patterns associated with waking,
NREM sleep, and REM sleep from a typical night’s sleep. NREM sleep is
divided into four stages on the basis of EEG recordings. The main change
in the progression from stage 1 sleep through stage 4 sleep is the
increased size and slowing speed of brain waves.
The designation of these stages assumes that the sleeper moves from
relatively shallow sleep in stage 1 to deep sleep in stage 4. Self-reports
from participants who are awakened from sleep at different times suggest
that stage 4 is the deepest sleep: participants act groggy when awakened
from it. As described earlier, REM sleep is distinctive because although a
participant is asleep, EEG activity shows a waking pattern.
(A) EEG

(B) Sleep
 FIGURE 13-12 Sleep Recording and Revelations (A) EEG
patterns associated with waking with the four NREM sleep stages and with
REM sleep. (B) Over a typical night’s sleep, a person undergoes several
sleep state changes in roughly 90-minute periods. NREM sleep dominates
the early sleep periods, and REM sleep dominates later sleep. The
duration of each sleep stage is reflected in the thickness of each bar, which
is color-coded to the corresponding stage in part A. The depth of each
stage is graphed as the relative length of the bar. Information from D. D. Kelley
(1991). Sleep and Dreaming (p. 794). In E. R. Kandel, J. H. Schwartz, & T. M. Jessell (Eds.).
Principles of Neuroscience. New York: Elsevier.

Figure 13-12 B graphs one participant cycling through these stages in

the course of a night’s sleep. Notice that the depth of sleep changes
several times through the four stages of NREM sleep, then entry into
REM sleep. This NREM–REM sequence lasts approximately 90 minutes
and occurs five times in the course of the participant’s sleep period.
The labels indicating REM sleep in Figure 13-12 B tell us that the
sleep stage durations roughly divide sleep into two parts, the first
dominated by NREM sleep, the second dominated by REM sleep.
Separate measures of body temperature record that it is lowest (about
1.5°C below a normal temperature of 37.7°C) during the earlier NREM-
dominated part of the sleep period and rises during the later REM-
dominated part.
Findings from sleep laboratory studies confirm that individuals tend to
conform to this sleep pattern with some variability. Studies also confirm
that REM sleep takes up substantial time: adults who typically sleep
about 8 hours spend about 2 of those hours in REM. A person’s duration
of REM sleep varies at different times of life and changes dramatically
over the life span. Periods of REM sleep are high in infancy; they
increase during growth spurts, in conjunction with physical exertion, and
during pregnancy. Figure 13-13 shows that most people sleep less as they
grow older. In the first 2 years of life REM sleep makes up nearly half of
sleep time, but it declines proportionately until in middle age it
constitutes little more than 10 percent of sleep time.

FIGURE 13-13 Sleeping and Waking over the Life Span

The amount of time humans spend sleeping decreases with age. The
proportion of REM sleep is especially high in the first few years of life.
Information from H. P. Roffward, J. Muzio, & W. C. Dement (1966). Ontogenetic development of
the human sleep–dream cycle. Science, 152, 604–619.

Contrasting NREM Sleep and REM Sleep

Although it seems an inactive period, a remarkable range of activity takes
place during sleep. Events associated with NREM sleep and REM sleep,
for example, are dramatically different, not only in physiological
measures but also in such behavioral events as cognition, memory
storage, and sleep disorders.
During NREM sleep body temperature declines, heart rate and blood
flow decrease, body weight decreases from water loss in perspiration, and
growth hormone levels increase. NREM sleep is also the time when we
toss and turn in bed, pull on the covers, and engage in other movements.
(For an extreme example see Clinical Focus 13-4 , Restless Legs
Syndrome.) If we talk in our sleep or grind our teeth, we do so during
NREM sleep. If we flail, banging an arm or kicking a foot, we usually do
so in NREM sleep. Some people even get up and walk around, and this
sleepwalking takes place during NREM sleep. All this activity during our
so-called resting state is remarkable! We maintain muscle tone during
NREM sleep and can sleep in a variety of postures, including standing up,
sitting (as might occur in a lecture), or in any of several reclining
positions.
CLINICAL FOCUS 13-4

Restless Legs Syndrome

I’ve always been a fairly untalented sleeper. Even as a child, it would
take me some time to fall asleep, and I would often roll around
searching for a comfortable position before going under. But my real
difficulties with sleeping did not manifest themselves until early
adulthood.…
Initially, my symptoms consisted of a mild tingling in my legs. It
caused me to be fidgety and made it hard to fall asleep. Eventually, I
went through a number of days without much sleep and reached a point
where I simply could not function. I went to a doctor who prescribed a
small course of sleeping medication (a benzodiazepine). I was able to
get good sleep and my sleep cycle seemed to get back on track. Over
the next decade I had periodic bouts of tingling in my legs which
caused me to be fidgety and interfered with sleep. As time passed, the
bouts occurred with increasing frequency and the symptoms became
more noticeable and uncomfortable. I would simply suffer through
these bouts, sleeping poorly and paying the consequences.…
Being a student, I did not have a regular doctor. Unfortunately, most
physicians I met did not know about restless legs syndrome, or RLS,
and thought I was “drug seeking” or merely stressed out. I received a
variety of patronizing responses and found these experiences insulting
and demeaning.…
When I took my current position, I started seeing a doctor on a
regular basis, and experimented with better medications. By this time,
my sleep was being seriously affected by RLS. The sensations in my
legs were something like a combination of an ache in my muscles
(much like one gets after exercising) and an electrical, tingling
sensation. They would be briefly relieved with movement, such as
stretching, rubbing, contracting my muscles, or changing position, but
would return within seconds. In fact, my wife says my cycle is about 13
to 15 seconds between movements. I do this either when awake or
during sleep. Trying not to move greatly increases the discomfort—
much like trying to not scratch a very bad itch. The symptoms get
worse in the evening and at night. Most nights, I have trouble falling
asleep. Other nights, I wake up after an hour or so and then have
trouble going back under.…
 I am very up front about the fact that I have RLS. In fact, whenever I
teach the topic of sleep and sleep disorders in my brain and behavior
classes, I always make some time to talk about my experiences with
RLS. Occasionally, students approach me with their own difficulties,
and I try to provide them with information and resources. (Stuart Hall,
Ph.D., University of Montana)
People with the sleep disorder restless legs syndrome (RLS)
experience unpleasant sensations in the legs—usually in the calf area
but anywhere from thigh to ankle—described as creeping, crawling,
tingling, pulling, or pain. One or both legs may be affected; some
people also feel the sensations in their arms.
B. W. Hoffmann, U of WI Hospital, Sleep Study Program, Madison, WI/Envision
 Many people who display RLS have a related sleep disorder,
periodic limb movement in sleep (PLMS), characterized by involuntary
jerking or bending leg movements that typically occur every 10 to 60
seconds during sleep. Some people make hundreds of such movements
per night; they disturb their sleep, can wake themselves, and assuredly
annoy bed partners.
RLS may affect as much as 10 percent of the population, more
commonly women than men. In mild cases massage, exercise,
stretching, and hot baths may be helpful. For more severe cases,
patients can restrict their intake of caffeine and take benzodiazepines to
help them get to sleep.
RLS is difficult to treat (Wijemanne & Jankovic, 2015). L -Dopa, a
drug used to treat Parkinson disease, is a frequent treatment, but no
evidence confirms that RLS occurs more frequently in Parkinson
patients, whose condition is related to low dopamine function. RLS has
been associated with poor iron uptake, especially in the substantia
nigra, and some people have been helped by iron supplements. One
focus of research into RLS is to improve iron absorption by the brain.

REM sleep is no less eventful than NREM sleep. During REM sleep our
eyes move; our toes, fingers, and mouths twitch; and males have penile
erections. Still, we are paralyzed, as indicated by atonia. This absence of
muscle tone stems from motor neuron inhibition by sleep regions of our
brainstem. In the sleep lab atonia is recorded on an electromyogram as the
absence of muscle activity (see Figure 13-11 B).
Posture is not completely lost during NREM sleep. You can get an idea
of NREM sleep posture by observing a cat or dog sleeping. During NREM
they may be lying down but still have some posture, with the head partly
supported in a partially upright position. At the onset of REM sleep the
animal usually subsides into a sprawled position as muscle paralysis sets in.
Figure 13-14 illustrates the sleep postures of a horse. Horses can sleep
while standing up by locking their knee joints, and they can sleep while
lying down with their head held slightly up. At these times they are in
NREM sleep. When they are completely sprawled out, they are in REM
sleep.
During REM sleep mammals’ limbs twitch visibly, and if you look
carefully at the face of a dog or cat, you will also see the skin of the snout
twitch and the eyes move behind the eyelids. It might seem strange that an
animal that is paralyzed can make small twitching movements, but the
neural pathways that mediate these twitches obviously are spared the
paralysis.
One explanation for the twitching of eyes, face, and distal parts of the
limbs is that such movements help to maintain blood flow in those parts of
the body. Another explanation is that the brain is developing coordinated
movements and tuning the neural circuits that support those movements—
an activity especially important to infants, who have not yet developed full
motor control (Blumberg, 2015).
An additional change resulting from atonia during REM sleep is that
mechanisms that regulate body temperature stop working and body
temperature moves toward room temperature. You may wake up from REM
sleep feeling cold or hot (or because you are cold or hot), depending on the
temperature of the room, because your body has drifted toward room
temperature during a REM period.

Courtesy of Ian Whishaw

 Courtesy of Ian Whishaw

FIGURE 13-14 Nap Time Horses usually seek open, sunny areas for a brief
sleep. I. Q. W.’s horse Lady Jones illustrates three sleep postures. Top:
NREM sleep, standing with legs locked and head down. Center: NREM
sleep, lying down with head up. Bottom: REM sleep, in which all postural and
muscle tone is lost.

Dreaming
The most remarkable aspect of REM sleep—dreaming—was discovered by
William Dement and Nathaniel Kleitman in 1957 (Dement, 1972). When
participants were awakened from REM sleep, they reported that they had
been having vivid dreams. In contrast, participants aroused from NREM
sleep were much less likely to report that they had been dreaming, and the
dreams they did report were much less vivid. The technique of electrical
recording from a sleeping participant in a sleep laboratory made it possible
to subject dreams and dreaming to experimental analysis. Such studies
provided objective answers to interesting questions concerning dreaming.
They also raised many more questions, because the electrical events of
sleep are complex and difficult to associate with the content of specific
dreams (Nir & Tononi, 2010).
How often do we dream? Reports by people on their dreaming behavior
once suggested that dreaming was quite variable: some reported that they
dreamed frequently and others that they never dreamed. Waking
participants up during REM periods showed that everyone dreams, that they
dream several times each night, and that dreams last longer as a sleep
session progresses. Those who claimed not to dream presumably forgot
their dreams. Perhaps people forget their dreams because they do not wake
up during a dream or immediately afterward, which allows subsequent
NREM sleep activity to erase the memory of the dream. Perhaps, too, the
neural systems that store our daily memories are inactive during NREM
sleep.
How long do dreams last? Common wisdom once suggested that dreams
last but an instant. By waking people up at different intervals after the onset
of REM sleep and matching the reported dream content to the previous
duration of REM sleep, however, researchers demonstrated that dreams
appear to take place in real time. An action that a person performs in a
dream lasts about as long as it would take to perform while awake. It is
likely that time shrinking is a product of remembering a dream, just as time
shrinking is a feature of our recall of other memories.

What We Dream About

Studying dreaming in a sleep laboratory allows researchers to study other
questions that have always intrigued people: Why do we dream? What do
we dream about? What do dreams mean?
Past explanations of dreaming have ranged from messages from the gods
to indigestion. The first modern treatment of dreams was described by the
founder of psychoanalysis, Sigmund Freud, in The Interpretation of
Dreams, published in 1900. Freud reviewed the early literature on dreams,
described a methodology for studying them, and provided a theory to
explain their meaning. We briefly consider Freud’s theory because it
remains popular in psychoanalysis and in the arts and is representative of
other psychoanalytical theories of dreams.
Figure 16-1 presents a contemporary take on Freud’s model of the
mind.
Freud suggested that the function of dreams is the symbolic fulfillment
of unconscious wishes. His theory of personality is that people have both a
conscious and an unconscious. Freud proposed that the unconscious
contains unacknowledged desires and wishes that are sexual. He further
proposed that dreams have two levels of meaning. The manifest content of a
dream is a series of often-bizarre, loosely connected images and actions.
The latent content of the dream contains its true meaning. Freud’s images
called phallic symbols reflect sexual events. As interpreted by a
psychoanalyst, the symbolic events of a dream provide a coherent account
of the dreamer’s unconscious wishes—for Freud, the wishes were related to
sex.
Freud provided a method for interpreting manifest symbols and
reconstructing the latent content of dreams. For example, he pointed out
that a dream usually begins with an incident from the previous day,
incorporates childhood experiences, and includes ongoing unfulfilled
wishes. He also identified several types of dreams, such as those that deal
with childhood events, anxiety, and wish fulfillment. The latent content of
the dream was important to Freud and other psychoanalysts in clinical
practice because interpretation of dreams was proposed to offer insight into
a patient’s problems.
Other psychoanalysts, unhappy with Freud’s emphasis on sex, developed
their own methods of interpretation. The psychoanalyst Carl Jung, a
contemporary of Freud, proposed that dream symbolism signifies distant
human memories encoded in the brain but long since lost to conscious
awareness. Jung proposed that dreams allow the dreamer to relive the
history of the human race—our “collective unconscious.” As more theories
of dream interpretation developed, their central weakness became apparent:
it was impossible to know which interpretation was correct.
The dream research of Freud and his contemporaries was also impeded
by their reliance on a subject’s memory of a dream and by the fact that
many subjects were patients. This situation unquestionably resulted in the
selection of the unusual by both the patient and the analyst. Now
researchers study dreams more objectively by waking participants and
questioning them.
Experimental analysis indicates that most dreams are related to events
that happened quite recently and concern ongoing problems. Colors of
objects, symbols, and emotional content most often relate to events taking
place in a person’s recent waking period. Calvin Hall and his colleagues
(1982) documented more than 10,000 dreams of healthy people and found
that more than 64 percent are associated with sadness, anxiety, or anger.
Only about 18 percent are happy. Hostile acts against the dreamer
outnumber friendly acts by more than two to one. Surprisingly, in regard to
Freud’s theory, only about 1 percent of dreams include sexual feelings or
acts.
Contemporary researchers continue to attempt to interpret dream
content. The two approaches that follow are polar: one sees no meaning in
dreams, and the other sees the content of dreams as reflecting biologically
adaptive coping mechanisms. The first approach is bottom-up: the person
has a dream, and then either the dreamer or a dream interpreter analyzes it.
The second approach is top-down: the dreamer creates the dream (Foulkes
& Domhoff, 2014).
Dreams as Meaningless Brain Activity
In his bottom-up approach, J. Allan Hobson (2004) proposed the
activation–synthesis hypothesis. During a dream the cortex is bombarded by
signals from the brainstem, and these signals produce the pattern of waking
(or activated) EEG. The cortex in response to this excitation generates
images, actions, and emotion from personal memory stores. In the absence
of external verification these dream events are fragmented and bizarre and
reveal nothing more than that the cortex has been activated.
Furthermore, Hobson proposes, on the basis of PET imaging, that part of
the frontal cortex is less active in dreaming than in waking. The frontal
cortex controls working memory for recent events and attention. The
dreamer thus cannot remember and link dream events as they take place,
because monitoring by the frontal cortex is required for these functions. On
waking, the dreamer may attempt to come up with a story line for these
fragmented meaningless images.
Chapter 14 describes the extent of frontal cortex involvement in
memory. Attention is the topic of Section 15-2 .
In Hobson’s hypothesis dreams are personal in that memories and
experiences are activated but have no meaning. So the following dream, for
example, with its bizarre delusional and fragmented elements, represents
images synthesized to accompany brain activation. Any apparent meaning
is invented after the fact, in this case by the middle-aged dreamer
recounting it.
I found myself walking in a jungle. Everything was green and fresh and I felt refreshed and
content. After some time I encountered a girl whom I did not know. The most remarkable thing
about her was her eyes, which had an almost gold color. I was really struck by her eyes not only
because of their unique color but also because of their expression. I tried to make out other
details of her face and body but her eyes were so dominating that was all I could see. Eventually,
however, I noticed that she was dressed in a white robe and was standing very still with her hands
at her side. I then noticed that she was in a compound with wire around it. I became concerned
that she was a prisoner. Soon, I noticed other people dressed in white robes and they were also
standing still or walking slowly without swinging their arms. It was really apparent that they
were all prisoners. At this time I was standing by the fence that enclosed them, and I was starting
to feel more concerned. Suddenly it dawned on me that I was in the compound and when I
looked down at myself I found that I was dressed in a white robe as well. I remember that I
suddenly became quite frightened and woke up when I realized that I was exactly like everyone
else. The reason that I remembered this dream is the very striking way in which my emotions
seemed to be going from contentment, to concern, to fear as the dream progressed. I think that
this dream reflected my desire in the 1970s to maintain my individuality. (Recounted by A. W.)

Dreams as a Coping Strategy

Anttio Revonsuo of Finland uses content analysis to argue that dreams are
biologically adaptive in that they lead to enhanced coping strategies for
threatening life events (Valli & Revonsuo, 2009). The evolutionary aspect
of this top-down approach, or coping hypothesis, is that enhanced
performance is especially important for people whose environment
typically includes dangerous events that constitute extreme threats to
reproductive success. Revonsuo notes that dreams are highly organized and
significantly biased toward threatening images, as was A. W.’s dream.
People seldom dream about reading, writing, and calculating even if these
behaviors occupy much of their day.
Dream threats are the same events that are threatening in waking life (
Figure 13-15 ). For example, animals and strange men who could be
characterized as enemies figure prominently in dreams. Dream content
incorporates the current emotional problems of the dreamer and leads to
improvements in and adjustments to life problems.
 FIGURE 13-15Dream Content Terrifying visions that may persist even
after awakening from a frightening dream as represented in The Night, by
Swiss painter Ferdinand Hodler. The Night, by Ferdinand Hodler (1853–1918). Oil on
canvas 116 × 299 cm. Kunstmuseum, Bern, Switzerland.

In contrast with the threat interpretation of dreams and from their own
analysis of dream content, Malcolm-Smith and her coworkers (2012) report
that approach behavior occurs more frequently in dreams than does
avoidance behavior. They therefore suggest that reward-seeking behavior is
as likely to represent a dream’s latent content as avoidance behavior is.
An extension of the top-down approach to dream interpretation contends
that people are problem solvers when awake, and problem solving
continues during sleep (Edwards et al., 2013). Have you ever been advised
to sleep on it? Did that prove to be good advice?
Part of the challenge in studying dreams is that they occur throughout
our sleep–waking behavior. Dreams occur during NREM sleep but not as
vividly as in REM sleep. We can have dreamlike experiences just as we
drop off to sleep, as our ongoing thoughts seem to disintegrate into
hallucinations. Sometimes we are aware of our dreams as we dream, a
phenomenon called lucid dreaming. People who have vivid dreamlike
experiences when awake are said to be hallucinating. And of course we
daydream when awake. Eric Klinger (1990) suggests that daydreams are
ordinary and often fun, with little of the turmoil of REM dreams, and so
seem the true opposite of night dreams.
Much about dreams is not understood. Very young children spend a lot
of time in REM sleep yet do not report complex dreams filled with emotion
and conflict. Children may experience brief frightening dreams called night
terrors during NREM sleep. Night terrors can be so vivid that the child
continues to experience the dream and the fear after awaking. A 4-year-old
child suddenly woke up screaming that she was covered in ants. It took
hours for her father to convince her that her experience was not real and
that she could go back to bed. Only reassurance from a sleep expert later
convinced the father that nothing was amiss with his daughter and that night
terrors are common among young children (Carter et al., 2014).
 13-3 REVIEW
Sleep Stages and Dreaming
Before you continue, check your understanding.
1 . Sleep consists of two phases: ___________, which stands for
___________, and ___________, which stands for ___________.
2 . REM sleep is characterized by eye movement, as recorded by the
___________; atonia, recorded by the ___________; and waking
activity, recorded by the.
3 . Sleepers experience about ___________ REM sleep periods each
night, with each period ___________ as sleep progresses.
4 . Evidence from sleep lab analysis suggests that ___________ dreams
and that dreams take place in ___________.
5 . What major factor makes interpreting dreams difficult?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 13-4 What Does Sleep Accomplish?
Sleep is not a passive process that results from a decrease in sensory
stimulation. Findings from sensory deprivation research reveal that when
participants are isolated in quiet bedrooms, they spend less time asleep,
not more. These results do not support the idea that sleep sets in for lack
of anything else to do. Here we consider three contemporary explanations
for sleep: as adaptive, as restorative, and as supportive of memory.

Sleep As a Biological Adaptation

Many lines of evidence argue that sleep is a biologically adaptive
behavior influenced by the ways a species has evolved to interact with its
environment:
• Sleep serves as an energy-conserving strategy for coping with times
when food is scarce. Each animal species gathers food at optimal times
and conserves energy the rest of the time. If the food that a species eats
has a high nutrient value, the species can spend less time foraging and
more time sleeping.
• Whether a species is predator or prey influences its sleep behavior. A
predator can sleep at its ease; the prey’s sleep time is reduced because it
must remain alert and ready to fight or flee at unpredictable times (
Figure 13-16 ).
• Strictly nocturnal or diurnal animals are likely to sleep when they cannot
travel easily. Dement proposed this colloquially: “We sleep to keep from
bumping into things in the dark.”
Much about animals’ sleep patterns are consistent with the adaptive
explanation. Figure 13-17 charts the average sleep time of some common
mammals. Herbivores, including donkeys, horses, and cows, spend a long
time collecting enough food to sustain themselves. Relatively short sleep
time for them is adaptive. Because they are also prey, not sleeping much
is adaptive, as they watch for predators. Carnivores, including domestic
cats and dogs, eat nutrient-rich foods and usually consume most of a
day’s or even a week’s food at a single meal. Because they do not need to
eat constantly and because by resting they can conserve energy, and
because they are not at great risk of predation, a great deal of sleep is
adaptive.
 The behavior of some animals does appear odd, so understanding any
animal’s sleep behavior requires understanding its natural history.
Opossums, which spend much of their time asleep, may have specialized
in energy conservation as a survival strategy. We humans are average
among species in our sleep time. As we are omnivores, not subject to
overwhelming predation, our sleep is intermediate between that of
herbivores and carnivores.
Sleep can contribute to energy conservation. During sleep, energy is
not being expended in moving the body or supporting its posture. The
brain is a major energy user, so switching off the brain during sleep,
especially NREM sleep, conserves energy. The decline in body
temperature during sleep is an adaptive energy-conserving mechanism: it
decreases the body’s metabolism, as exemplified by animals that display
extreme decreases in body temperature characteristic of hibernation.
A good explanation of sleep must account not only for sleep but also
for NREM and REM sleep. Before the discovery of REM sleep, Kleitman
suggested that animals have a basic rest–activity cycle (BRAC) that for
humans lasts about 90 minutes (see Dement, 1972). Kleitman based his
hypothesis on the observation that human infants have frequent feeding
periods between which they sleep.
basic rest–activity cycle (BRAC) Recurring cycle of temporal
packets, about 90-minute periods in humans, during which an
animal’s level of arousal waxes and wanes.
As illustrated in Figure 13-18 , the behavior of adult humans does
suggest that activity and rest are organized into 90-minute temporal
packets. School classes, work periods, exercise sessions, mealtimes,
coffee breaks, and snack times appear to be divided into intervals of 90
minutes or so. The later discovery that REM sleep occurs at intervals of
about 90 minutes suggests that it too can be considered a continuation
into sleep of the 90-minute BRAC cycle. This hypothesis assumes that
periods of eating are periods of high brain activity, just as are periods of
REM.
Kleitman proposed that the BRAC rhythm is so fundamental that it
cannot be turned off. Accordingly, for a night’s sleep to be uninterrupted
by periodic waking (and perhaps snacking), the body is paralyzed and
only the brain is active. An analogy: rather than turning off your car’s
engine when you’re stopped at a red light, you apply the brakes to keep
the idling car from moving. For REM sleep the atonia that paralyzes
movement is the brake.
FIGURE 13-16 Do Not Disturb Biological theories of sleep suggest that it is an
energy-conserving strategy that serves other functions as well, such as staying safe
through the night.

FIGURE 13-17 Average Sleep Time Sleep time is affected both by

the amount of time species require to obtain food and by the risk of
predation.

FIGURE 13-18Behavioral Rhythms Our behavior is dominated by a

basic rest–activity cycle (red) through which our activity levels change in
 the course of the day and by an NREM–REM sleep cycle (purple) during
the night.

Sleep as a Restorative Process

In Macbeth’s description of sleep Shakespeare illustrates in words the
idea that sleep has restorative properties:
Sleep that knits up the ravell’d sleave of care,
The death of each day’s life, sore labour’s bath,
Balm of hurt minds, great nature’s second course,
Chief nourisher in life’s feast. —Act II, scene 2
Sleep Deprivation Studies
We can understand the idea of sleep as a restorative from our personal
perspective. Toward the end of the day we grow tired, and when we
awaken from sleep, we are refreshed. If we do not get enough sleep, we
become irritable. One hypothesis of sleep as restorative proposes that the
chemical events that provide energy to cells are reduced during waking
and replenished during sleep.
Even so, fatigue and alertness may simply be aspects of the circadian
rhythm and have nothing at all to do with wear and tear on the body or
depletion of its essential resources. To evaluate whether sleep is essential
for bodily processes, investigators have conducted sleep deprivation
studies. These studies have not clearly identified any essential function
for sleep but rather point to multiple physiological and cognitive
functions altered by various degrees of sleep deprivation (Elliott et al.,
2014).
Dement participated as an observer in one case study on sleep
deprivation that illustrates this point. In 1965, as part of a science fair
project, a high school student named Randy Gardner planned to break the
world record of 260 hours (almost 11 days) of consecutive wakefulness
with the help of two classmates who would keep him awake. Gardner did
break the record, then slept for 14 hours and reported no ill effects. Given
concerns about the deleterious effects that sleep deprivation has on health,
Guinness World Records no longer records wakefulness records.
Dement reported that Gardner hallucinated and had cognitive and
memory lapses during his period of sleep deprivation. These negative
effects did not last. Reviews of sleep deprivation research are consistent
in concluding that at least limited periods of sleep deprivation produce no
marked physiological alterations.
Sleep deprivation does not seem to have adverse physiological
consequences, but it is associated with poor cognitive performance.
Performance on tasks that require attention declines as a function of hours
of sleep deprivation. Irregular sleep can contribute to metabolic
syndrome, described in Clinical Focus 13-1 . Finally, sleep deprivation
figures in accidents at work and on the road. The sleep deprivation deficit
does not manifest itself in an inability to do a task, because sleep-
deprived participants can perform even very complex tasks; rather the
deficit is in maintaining sustained attention.
A confounding factor in evaluating sleep-deprived participants is that
they take microsleeps, brief sleep periods lasting up to a few seconds.
During microsleep, participants may remain sitting or standing, but their
eyelids droop briefly and they become less responsive to external stimuli.
If you have driven a car while tired, you may have had a microsleep and
awakened just in time to prevent yourself from driving off the road—or
worse.
microsleep Brief sleep period lasting a second or so.
REM Sleep Deprivation
Some studies have focused on the selective benefits of REM sleep. To
deprive a participant of REM sleep, researchers allow participants to
sleep but awaken them as REM sleep begins. REM-sleep deprivation has
two effects:
1. Participants show an increased tendency to enter REM sleep in
subsequent sleep sessions, so awakenings must become more and more
frequent.
2. After REM deprivation, participants experience REM rebound,
showing more than the usual amount of REM sleep in the first available
sleep session.
Because most sleep studies are of relatively brief duration, capturing
potential long-term physiological changes that may take place during or
after sleep deprivation remains elusive. The consequences of sleep
deprivation may become apparent only some time after an experimental
manipulation has taken place. Furthermore, gross assessment of behavior
may be less adequate for documenting sleep deprivation’s effects than
more focal physiological and behavioral assessments. For example, some
evidence suggests that REM sleep deprivation weakens the immune
system, decreasing resistance to infections and other disease (Lungato et
al., 2015). Other evidence suggests that REM sleep deprivation reduces
neurogenesis, especially in the hippocampus, thus impairing memory
processes and weakening resistance to stress (Kreutzmann et al., 2015).
Two kinds of observations, however, argue against effects of
prolonged or even complete REM sleep deprivation. Virtually all
antidepressant drugs, including MAO inhibitors, tricyclic antidepressants,
and SSRIs, suppress REM sleep either partly or completely. The clinical
effectiveness of these drugs may in fact derive from their REM-
suppressant effects (Wilson & Argyropoulos, 2005). Nevertheless, about
6 percent of people on antidepressants display REM sleep behavioral
disorder, characterized by agitated movements, as if the sleeper were
acting out dreams (see Section 13-6 ). This disorder argues against the
idea that REM suppression by antidepressant drugs is complete (Postuma
et al., 2013).
Section 6-2 reviews the full spectrum of antidepressant drugs.
In several reported cases lower-brainstem damage has resulted in a
complete loss of REM sleep. For example, patients with brainstem lesions
reportedly remained ambulatory and verbally communicative, but their
REM was abolished. They were reported to live quite satisfactorily
without REM sleep (Osorio & Daroff, 1980).

Sleep and Memory Storage

The suggestion that sleep plays a role in memory dates back over a
century, and in the interval a lot has changed with respect to our
understanding of memory and of sleep. Investigators now know of two
general categories of memory. Episodic memory includes conscious
information such as our autobiographical memories and knowledge of
facts. Implicit memory includes unconscious processes such as motor
skills learning. Within these categories specific types of memory include
spatial, emotional, verbal, even immune system memory. Investigators
also know that during the various stages of sleep many EEG and neuronal
events, biochemical events, and genetic events take place. Thus the
central challenge for sleep-related memory research lies in associating the
complexity of memory with the complexity of brain metabolic and
genetic events (Rasch and Born, 2013).
 Section 14-1 expands on the workings of explicit and implicit
memory systems.
Investigators also know that storing memories takes time. Memory is
proposed to have at least three phases: labile, consolidation (storage), and
recall. During the initial labile phase, as a memory is encoded, it is fragile
and must compete with existing memories and the addition of new
memories. The consolidation phase forges a relatively permanent
representation of the memory; it depends upon biochemical and genetic
activity that underlie structural changes in the nervous system. The recall
phase puts the memory to work at some future time and also integrates it
into existing memory stores.
Research on the role of sleep in memory focuses on the latter two
processes, consolidation and recall, and is conducted within the
framework of three theories: multiple process, sequential process, and
storage process. Multiple process theories propose that different kinds of
memory are stored during different sleep states. Sequential process
theories propose that memory is manipulated in different ways during
different sleep states. For example, one sleep state erases older competing
memories, while another sleep state stores the new memories. Storage
process theories propose that brain regions that handle different kinds of
memory during waking continue to do so during sleep. The advantage is
that sleep offers a state relatively free from the competition of new
waking experiences.
Each theory of memory and sleep has generated volumes, but the
remainder of this section focuses on experimental demonstrations of
sleep’s role in the general memory categories of explicit and implicit
memory storage during sleep.
NREM Sleep and Explicit Memory
Gerrard and colleagues (2008) used a method which had found that many
hippocampal cells fire when a rat is in a certain location in an
environment. These place cells are relatively inactive until the rat passes
through that place again. Recordings from as many as 100 cells at the
same time in three conditions—during NREM sleep, during a food search
task, and during NREM sleep after a food search—show that during the
food search the activity of some place cells correlates. During the rats’
subsequent periods of NREM sleep the correlations recur ( Figure 13-19
).
 place cell Hippocampal neuron maximally responsive to specific
locations in the world.
Figure 7-8 shows the classes of place cells and their directional
selectivity.
This result suggests that the memory of the previous food-searching
experience is being replayed and thus stored during NREM sleep. In
pursuing the idea that memory for places is stored during sleep, one
research group identified neuronal firing of hippocampal cells in awake
animals in relation to a specific location in a maze. Then during sleep
they provided rewarding brain stimulation whenever that neuronal firing
pattern occurred. In a subsequent test in the maze, the reinforced animals
showed a preference for the target location. The experiments had
produced an episodic memory for that place as the animals slept (de
Lavilléon et al., 2015).
REM Sleep and Implicit Memory
To determine whether humans’ dreams are related to memory, Pierre
Maquet and his coworkers in Belgium (2000) trained participants on a
serial reaction task. The investigators observed regional blood flow in the
brain with PET scans during training and during REM sleep on the
subsequent night. The participants faced a computer screen displaying six
positional markers and were instructed to push one of six keys when a
corresponding positional marker was illuminated. They did not know that
the illumination sequence was predetermined. This exemplifies an
implicit memory task in which a motor skill is mastered.
Consequently, as training progressed, the participants indicated that
they were learning by the fact that their reaction time improved during
trials in which one positional marker was correlated with a preceding
marker. On PET scan measures of brain activation, a similar pattern of
neocortical activation appeared during task acquisition and during REM
sleep ( Figure 13-20 ). On the basis of this result Maquet and coworkers
suggest first that the participants were dreaming about their learning
experience and second that replay during REM strengthened the task
memory. Research in which participants are given a language task that
contains hidden rules finds that sleep also strengthens this implicit rule
learning (Batterink et al., 2014). Thus, much rule learning in both motor
and cognitive domains likely is strengthened during sleep, including REM
sleep.
 FIGURE 13-19 Neural Replay? Hippocampal cell activity suggests that
rats dream about their experiences. Dots on the periphery of the circles
represent the activity of 42 hippocampal cells recorded at the same time
during (left) NREM sleep before a food-searching task, (center) the food-
searching task, and (right) NREM sleep after the task. No strong
correlations among cells emerged during the NREM sleep that preceded
the food search, but correlations were strong among cells during the food
search and during the subsequent slow-wave sleep. Information from M. A.
Wilson & B. L. McNaughton (1994). Reactivation of hippocampal ensemble memories during
sleep. Science, 165, p. 678.

Reaction-time task

REM sleep that night

 Do We Store Implicit Memories During
FIGURE 13-20

REM Sleep? Information from P. Maquet, S. Laureys, P. Peigneux, S. Fuchs, C.

Petiau, et al. (2000). Experience-dependent changes in cerebral activation during human REM
sleep. Nature Neuroscience, 3, p. 832.

Storing Memories During Sleep

Although evidence shows that memory strengthens during sleep, less
clear is whether the neural and molecular changes that support sleep
memory storage are similar or different from those that store memory
during wakefulness. Researchers are addressing this question in
innovative animal models of sleep. Nelini and coworkers (2012) studied
spatial memory formation in chicks, a species in which such memories
are stored mainly in the right hemisphere. Chickens, like many bird
species, alternate sleep in each hemisphere, and the researchers showed
that after a learning experience, the right hemisphere displayed more
sleep than did the left hemisphere. Birds’ selectivity in hemispheric sleep
opens up the possibility of comparing plastic changes between the
hemispheres as a way of understanding genetic, biochemical, and plastic
changes associated with memory formation.
The fruit fly Drosophila also offers insights into the effects of sleep on
memory and on plasticity (Dissel et al., 2015). These researchers
identified a variety of mutations that disrupt memory formation and
plasticity and found that the memory disruptions decrease after sleep.
Slight increases in ambient temperature put one mutant strain of fly to
sleep, which greatly aided the research. For this strain a learning task can
be followed by various sleep doses induced by manipulating room
temperature. A finding of this research is that the same group of neurons
that enhance memory are those that induce sleep. This finding suggests a
causal link between memory and sleep: Drosophila sleeps to remember!
Generalizing this finding to us humans suggests that learning will make
us tired.
 13-4 REVIEW

What Does Sleep Accomplish?

Before you continue, check your understanding.
1 . Sleep is proposed to occur as a(n) ___________ adaption, as a(n)
___________ process, or as an aid in storing ___________.
2 . ___________ memory is associated with NREM sleep, and
___________ memory is associated with REM sleep.
3 . In rats performing a spatial task, correlations develop between firing
in the hippocampus that is then replayed in ___________ sleep.
4 . When you are sleep-deprived, you are more likely to slip into a
___________ for a few seconds.
5 . Describe a difficulty in relating memory formation to sleep.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 13-5 Neural Bases of Sleep
The idea that the brain contains a sleep-inducing substance has long been
popular and is reinforced by the fact that a variety of chemical agents
induce sleep. Such substances include sedative-hypnotics and morphine.
Our understanding of circadian rhythms suggests, however, that changes
in many neurochemicals and hormones and the metabolic activity of
most of the body’s cells produce our sleep–waking cycles.
The hormone melatonin, secreted from the pineal gland during the
dark phase of the light–dark cycle, causes sleepiness. A synthetic form
can be taken as a sleep aid, so melatonin might be thought to be the
sleep-producing substance. But sleep survives the removal of the pineal
gland. Thus melatonin and many other chemical substances may only
contribute to sleep, not cause it (see Research Focus 13-3 ).
Some observations suggest that it is not a circulating bloodstream
compound that produces sleep. In dolphins and birds only one brain
hemisphere sleeps at a time. This ability presumably allows an animal’s
other hemisphere to remain behaviorally alert. More important, it
suggests that sleep is produced by the action of some brain region, and in
these species, within each hemisphere.
In this section we consider the neural mechanisms that regulate sleep.
First we examine evidence that the activity of a slave oscillator of the
suprachiasmatic nucleus produces sleep (see Figure 13-8 ). Second we
look at evidence that a number of brainstem nuclei control the various
events associated with sleep, including those associated with REM and
NREM sleep.

Reticular Activating System and Sleep

A pioneering experiment by Giuseppe Moruzzi and Horace Magoun
(1949) began to answer the question of which brain areas regulate sleep.
The experimenters were recording the cortical EEG from anesthetized
cats while electrically stimulating the cats’ brainstem. They were
surprised to find that, in response to the electrical stimulation the large,
slow delta EEG typical of anesthesia is replaced by the low-voltage fast-
wave beta EEG typical of waking.
The beta EEG activity outlasted the stimulation period, demonstrating
that the effect was not simply due to the online activity of neurons in the
region of the stimulating electrode but could be maintained by these
neurons independent of the stimulation. During the “waking period” the
anesthetized cat did not become behaviorally aroused, but its cortical
EEG appeared to indicate that it was awake. In a sleeping cat the same
stimulation did lead to waking.
Subsequent experiments show that a waking EEG and waking
behavior can be induced from a large neural area running through the
center of the brainstem. Anatomically this area is composed of a mixture
of cell nuclei and nerve fibers that form a reticulum. Moruzzi and
Magoun named this brainstem area the reticular activating system
(RAS) and proposed that it is responsible for sleep–waking behavior.
Figure 13-21 diagrams the location of the RAS.
reticular activating system (RAS) Large reticulum (mixture of cell
nuclei and nerve fibers) that runs through the center of the
brainstem; associated with sleep–wake behavior and behavioral
arousal; also called the reticular formation.
If someone disturbs you when you are asleep, you usually wake up.
To explain that their experimentally induced effect did not result simply
from sensory stimulation, Moruzzi and Magoun cut the brainstem just
behind the RAS, severing its incoming sensory pathways. RAS
stimulation still produced a desynchronized EEG. Thus, the RAS is the
source of waking, and sensory stimulation produces waking because it
activates RAS neurons.
The idea that the brainstem participates in waking behavior helps to
explain why brainstem damage can result in coma, a prolonged state of
deep unconsciousness resembling sleep. In one well-publicized case,
after taking a minor tranquilizer and having a few drinks at a birthday
party, a 21-year-old woman named Karen Ann Quinlan sustained RAS
damage that left her comatose (Quinlan & Quinlan, 1977). She was
hospitalized, placed on a respirator to support breathing, and fed by
tubes. Her family fought a protracted legal battle to have her removed
from life support, a battle they finally won before the Supreme Court of
New Jersey. Even after she was removed from life support, however,
Karen Ann lived for 10 more years in a perpetual coma.
coma Prolonged state of deep unconsciousness resembling sleep.
 FIGURE 13-21 Sleep–Wake Controller The reticular activating
system, a region at the center of the brainstem, contains a mixture of cell
bodies and fiber pathways. RAS stimulation produces a waking EEG,
whereas damaging it produces a slow-wave sleeplike EEG.

Neural Basis of EEG Changes Associated

with Waking
Research built on those pioneering studies of the RAS has since revealed
that many neural systems in the brainstem play a role in sleeping and
waking behavior. Case Vanderwolf and his coworkers (Vanderwolf,
2002) showed that at least two brainstem systems influence waking
EEG. Figure 13-22 illustrates their locations in the rat brain.
Figure 5-17 summarizes the major neural activating systems and
their functions.
The basal forebrain contains large cholinergic cells. These neurons
secrete acetylcholine (ACh) from their terminals onto cortical neurons to
stimulate a waking EEG (beta rhythm). The midbrain structure the
median raphe contains serotonin (5-HT) neurons whose axons also
project diffusely to the cortex, where they also stimulate cortical cells to
produce a waking EEG.
Although the two pathways produce similar patterns of waking EEG
activity, their relations to behavior differ. If the activity of the cholinergic
projection is blocked by drugs or by lesions to the cells of the basal
forebrain, the waking EEG normally recorded from an immobile rat is
replaced by EEG activity resembling that of NREM sleep. Only if the rat
walks or is otherwise active is a waking EEG obtained from the cortex.
These findings, graphed in Figure 13-22 , suggest that the cholinergic
EEG is responsible for waking associated with being alert yet still,
whereas the serotonergic activation is responsible for the waking EEG
associated with movement.
Neither the basal forebrain system nor the median raphe system is
responsible for behavior. In fact, if both structures are pharmacologically
or surgically destroyed, a rat can still stand and walk around. Its EEG,
however, permanently resembles that of a sleeping animal.
As long as one activating system is producing a waking EEG, rats can
learn simple tasks. If both systems are destroyed, an animal, although
still able to walk around, is no longer able to learn or display intelligent
behavior. In a sense the cortex is like a house in which the lights are
powered by two separate sources: both must fail for the house to be left
in darkness, but if at least one source is operating, the lights stay on.
These experimental results suggest that the RAS produces its arousal
effects by influencing activity in these two pathways, which then
produce EEG events associated with waking. In humans the basal
forebrain and median raphe likely produce the same two desynchronized
EEG patterns that they produce in rats. Consequently, when we are alert
and still, cholinergic neurons are active; when we move, serotonin
neurons also are active.
Perhaps when you have felt sleepy, say in a class or behind the wheel
of a car, you may have been able to wake yourself up by moving—
shaking your head or stretching. Presumably, while sitting still, your
arousal level decreased as your cholinergic neurons became inactive.
When you moved, activating your serotonergic neurons restored your
arousal level. When we enter sleep, both cholinergic and serotonergic
neurons become less active, allowing slow waves to emanate from the
cortex.
 FIGURE 13-22Brain Activators Basal forebrain ACh neurons produce
an activated EEG pattern when a rat is alert but immobile. The 5-HT raphe
neurons of the midbrain produce an activated EEG pattern when the rat
moves.

Neural Basis of REM Sleep

Barbara Jones (1993) and her colleagues described a group of
cholinergic neurons known as the peribrachial area that contributes to
REM sleep. This area is located in the dorsal brainstem just anterior to
the cerebellum ( Figure 13-23 ). Jones selectively destroyed peribrachial
cells by spraying them with the neurotoxin kainic acid. She found that
REM sleep was drastically reduced. This result suggests that the
peribrachial area contributes to REM sleep and REM-related behaviors.
peribrachial area Cholinergic nucleus in the dorsal brainstem
having a role in REM sleep behaviors; projects to medial pontine
reticular formation.
The peribrachial area extends into a more ventrally located nucleus
called the medial pontine reticular formation (MPRF), shown in
Figure 13-23 . Lesions of the MPRF also abolish REM sleep, and
injections of cholinergic agonists (drugs that act like ACh) into this
region induce REM sleep. If both the peribrachial area and the MPRF
take part in producing REM sleep, how do other events related to REM
sleep, including a waking EEG, rapid eye movements (REM), and
atonia, take place in the absence of muscle tone? Figure 13-24 charts an
explanation showing how other REM-related activities are induced:
 medial pontine reticular formation (MPRF) Nucleus in the pons
participating in REM sleep.

FIGURE 13-23 Brainstem Nuclei Responsible for REM

Sleep Damage to either the peribrachial area or the medial pontine
formation reduces or abolishes REM sleep.

• The peribrachial area initiates REM sleep by activating the medial

pontine reticular formation.
• The MPRF sends projections to excite basal forebrain cholinergic
neurons, resulting in an activated EEG recorded from the cortex.
• The MPRF also excites brainstem motor nuclei to produce rapid eye
movements and other twitches.
• The atonia of REM sleep is produced by the MPRF through a pathway
that sends input to the subcoerulear nucleus located just behind it.
• The subcoerulear nucleus excites the magnocellular nucleus of the
medulla, which sends projections to the spinal motor neurons to inhibit
them so that paralysis is achieved during the REM sleep period.
 In support of such a neural arrangement French researcher Michel
Jouvet (1972) observed that cats with lesions in the subcoerulear nucleus
display a remarkable behavior when they enter REM sleep. Rather than
stretching out in the atonia that typically accompanies REM sleep, the
cats he was studying stood up, looked around, and made movements of
catching an imaginary mouse or running from an imaginary threat.
Apparently if cats with damage to this brain region dream about catching
mice or escaping from a threat, they are now acting out their dreams. We
revisit Jouvet’s phenomenon in the next section, describing sleep
disorders.
Figure 6-5 shows agonist action at the ACh synapse.

FIGURE 13-24 Neural Control of REM Sleep

 13-5 REVIEW

Neural Bases of Sleep

Before you continue, check your understanding.
1 . The ___________ in the central region of the brainstem is responsible
for producing ___________ sleep.
2 . Loss of the RAS produces ___________.
3 . The peribrachial area and the MPRF, through activating pathways to
the neocortex and spinal cord, are responsible for producing events
associated with ___________.
4 . Cats with lesions to the ___________ nucleus act out their dreams.
5 . If you nod off to sleep at an inconvenient time, why does moving
awaken you?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 13-6 Sleep Disorders
Occasional sleep disturbances are annoying and may impair performance
the following day. About 15 percent of people complain of ongoing sleep
problems; an additional 20 percent complain of occasional sleep
problems. As people age, the incidence of complaints increases.
In the extreme, a rare genetic condition, fatal familial insomnia,
causes individuals to stop sleeping altogether. Their insomnia contributes
to death after a number of months without sleep. Prions (misfolded
proteins) are proposed to cause the condition. A proposed treatment is
doxycycline, an antibiotic with antiprion activity (Forloni et al., 2015). In
this section we consider more common dysfunctions of NREM sleep and
REM sleep (for more about prion disorders, see Chapter 16 ).

Disorders of NREM Sleep

The two most common sleep disorders occur during NREM sleep are
insomnia, prolonged inability to sleep, and narcolepsy, uncontrollably
falling asleep at inappropriate times. Insomnia and narcolepsy are
related, as anyone who has stayed up late at night can confirm: a night
without sleep is often accompanied by a tendency to fall asleep at
inconvenient times the next day.
insomnia Disorder of slow-wave sleep resulting in prolonged
inability to sleep.
narcolepsy Slow-wave sleep disorder in which a person
uncontrollably falls asleep at inappropriate times.
Narcolepsy derives from the Greek words for numbness and to be
seized.
Insomnia
Our understanding of insomnia is complicated by the wide variation
among people in how much time they spend asleep. Some short sleepers
may think they should sleep more, and some long sleepers may think
they should sleep less. Yet the sleeping pattern may be appropriate for
each.
People’s sleep is disrupted by lifestyle choices such as those described
in Clinical Focus 13-1 . Staying up late, for example, may set a person’s
circadian rhythm forward, encouraging a cascade of late sleep followed
by staying up still later. Indoor and outdoor light pollution contributes to
sleep disorders by disrupting circadian rhythms. Some sleep problems
are brought on by shift work or by jet lag, as described in Section 13-1 .
Other common causes of sleep disorders are stress, long work hours, and
an irregular lifestyle. Just worrying about insomnia is estimated to play a
major role in 15 percent of cases.
Depressed people may sleep too much or too little. Anxiety and
depression account for about 35 percent of insomnias. Quantitative
differences also exist in depressed patients’ sleep because they enter
REM sleep very quickly, as do people who are sleep-deprived.
Insomnia is brought on by sedative-hypnotic drugs, including
Seconal, sodium amytal, and many minor tranquilizers. These sleeping
pills do help people get to sleep, but the person is likely to feel groggy
and tired the next day, which defeats the purpose of taking the drug.
Although sleeping pills promote NREM sleep, they deprive the user of
REM sleep. In addition, people develop tolerance to these medications,
become dependent on them, and display rebound insomnia when they
stop taking them. A person then may increase the dose each time the
drug fails to produce the desired effect. The syndrome in which patients
unsuccessfully attempt to sleep by increasing their drug dosage is called
drug dependence insomnia.
drug dependence insomnia Condition resulting from continuous
use of sleeping pills; drug tolerance also results in deprivation of
either REM or NREM sleep, leading the user to increase the drug
dosage.
Section 6-4 presents theories of drug tolerance and dependence.
Narcolepsy
Like many people, you may suddenly have been overcome by an urge to
sleep at an inconvenient time, perhaps while attending a lecture. For
some people such experiences with narcolepsy are common and
disruptive. J. S., a junior in college, sat in the front row for his course on
the brain. Within a few minutes after each class began, he dropped off to
sleep. The instructor became concerned and asked J. S. to stay after class
to discuss his sleeping behavior.
J. S. reported that sleeping in classes was a chronic problem. Not only
did he sleep in class, he fell asleep whenever he tried to study. He even
fell asleep at the dinner table and in other inappropriate locations. His
sleeping problem had made getting through high school a challenge and
was making it difficult for J. S. to pass his college courses.
About 1 percent of people have narcolepsy, which takes surprisingly
varied forms. J. S. fell asleep while sitting still, and his sleeping bouts
consisted of brief spurts of NREM sleep lasting 5 to 10 minutes. This
pattern is similar to napping and to dropping off to sleep in class after a
late night but is distinguishable as narcolepsy by its frequency and
disruptive effect. J. S. eventually discussed his problem with his
physician and received a prescription for Ritalin, an amphetaminelike
drug that stimulates dopamine transmission. The treatment proved
helpful.
Focus 6-1 explores amphetamine use for cognitive enhancement.
Focus 7-4 describes how Ritalin mitigates symptoms of ADHD.
Studies of narcoleptic people in sleep clinics resulted in a surprising
discovery concerning one cause of narcolepsy: sleep apnea, an inability
to breathe during sleep. Clinical Focus 13-5 , Sleep Apnea, describes a
person who spent all night every night waking up to breathe. This
nighttime behavior left him extremely tired and caused him to nod off in
the daytime. Being overweight contributes to sleep apnea as well as to
metabolic syndrome. Clearly the relationship between sleep and health is
both complex and interconnected.
sleep apnea Inability to breathe during sleep, causing a sleeper to
wake up to breathe.
Apnea from Latin a, not, and pnea, breathing.
CLINICAL FOCUS 13-5

Sleep Apnea
The first time I went to a doctor for my insomnia, I was twenty-
five—that was about thirty years ago. I explained to the doctor
that I couldn’t sleep; I had trouble falling asleep, I woke up many,
many times during the night, and I was tired and sleepy all day
long. As I explained my problem to him, he smiled and nodded.
Inwardly, this attitude infuriated me—he couldn’t possibly
understand what I was going through. He asked me one or two
questions: Had any close friend or relative died recently? Was I
having any trouble in my job or at home? When I answered no, he
shrugged his shoulders and reached for his prescription pad. Since
that first occasion I have seen I don’t know how many doctors,
but none could help me. I’ve been given hundreds of different
pills—to put me to sleep at night, to keep me awake in the
daytime, to calm me down, to pep me up—have even been
psychoanalyzed. But still I cannot sleep at night. (In Dement,
1972, p. 73)
When this patient entered the Stanford University Sleep Disorders
Clinic in 1972, recording electrodes monitored his brain, muscle,
eye, and breathing activity while he slept (see Figure 13-11 ). The
attending researchers were amazed to find that he had to wake up to
breathe. They observed that he would go more than a minute without
breathing before he woke up, gasped for breath, and returned to
sleep. Then the sequence began again.
Sleep apnea may be produced by a CNS problem, such as weak
neural command to the respiratory muscles, or it may be obstructive,
caused by collapse of the upper airway. When people with sleep
apnea stop breathing, they either wake up completely and have
difficulty getting back to sleep or they partially awaken repeatedly
throughout the night to gasp for breath.
Sleep apnea affects people of all ages and both sexes, and 30
percent of those older than 65 may have some form of it. Sleep apnea
can even occur in children; it may be related to some cases of sudden
infant death syndrome (SIDS), or crib death, in which otherwise
 healthy infants inexplicably die in their sleep. Sleep apnea is thought
to be more common among overweight people and those who snore,
two conditions in which airflow is restricted.

Breathing rate and blood oxygen level recorded during REM sleep
from a person with sleep apnea. Blood oxygen increased after each
breath, then continued to fall until another breath was taken. This
person inhaled only 4 times in the 6-minute period; a healthy sleeper
would breathe more than 60 times in the same interval.

Treatments for sleep apnea include surgery or an appliance to

expand the upper airway, weight loss, and a face mask to deliver
negative pressure to open the airway. Untreated sleep apnea can
cause high blood pressure and other cardiovascular disease, memory
problems, weight gain, impotence, headaches, and brain damage due
to oxygen insufficiency (Corrêa Cde et al., 2015).

Disorders of REM Sleep

Several sleep disorders are associated with the unexpected onset of
atonia and dreams, two main features of REM sleep. We describe three:
sleep paralysis, cataplexy, and REM sleep behavioral disorder.
Sleep Paralysis
In sleep paralysis both atonia and dreaming can occur when a person is
awake, usually just falling asleep or waking up. L. M., a college senior,
recounted the following experience.
sleep paralysis Atonia and dreaming occurring when a person is
awake, usually just falling asleep or waking up.
She had just gone to sleep when her roommate came into their room.
L. M. woke up and intended to ask her roommate if she wanted to go
skating the next morning but found herself unable to speak. She tried to
turn her head to follow her roommate’s movements across the room but
found that she was paralyzed. She had the terrifying feeling that some
creature was hiding in the bathroom waiting for her roommate. She tried
to cry out but produced only harsh gurgling noises. In response to these
peculiar noises the roommate knocked her out of her paralysis by hitting
her with a pillow.
Sleep paralysis is common. In informal class surveys almost a third of
students report having had such an experience, as do some war veterans
during group therapy sessions. The atonia is typically accompanied by
dread or fear. It seems likely that in sleep paralysis a person has entered
REM sleep partially. He or she is dreaming, atonia has occurred, but the
sleeper remains “awake.” When sleep paralysis occurs as a person wakes
up, the paralysis and dreaming characteristic of a REM episode continue.
Cataplexy
The atonia of REM sleep can also occur while a person is awake and
active, a condition called cataplexy. The person loses muscle tone and
gradually or even quickly falls to the floor, atonic. The collapse can be so
sudden that injury is a real risk. Cataplexy can be triggered by
excitement or laughing. While in an atonic condition, the person sees
imaginary creatures or hears imaginary voices. People who fall into a
state of cataplexy with these hypnogogic hallucinations give every
appearance of having fallen into REM sleep while remaining “awake.”
cataplexy State of atonia, as in REM sleep, occurring while a
person is awake and active; linked to strong emotional stimulation.
hypnogogic hallucination Dreamlike event as sleep begins or while
a person is in a state of cataplexy.
The word cataplexy comes from the Greek word kataplessein,
meaning to strike down. Hypnogogic comes from the Greek hypnos,
sleep and agogos, leading into.
Cataplexy can have a genetic basis. In 1970 William Dement was
given a litter of Doberman pinscher dogs and later a litter of Labrador
retrievers. These dogs displayed cataplexy. The disease is transmitted as
a recessive trait: to develop it, a dog must inherit the gene from both its
mother and its father. The descendants of those dogs continue to provide
animal models for investigating the neural basis of the disease as well as
its treatment.
 Figure 3-21 explains inheritance patterns for genetic disorders.
Jerome Siegel (2004) investigated the cause of narcolepsy in dogs. He
found that neurons in the subcoerulear nucleus become inactive and
neurons in the magnocellular nucleus of the medulla become active
during attacks of cataplexy, just as they do during REM sleep. On the
basis of anatomical examinations of the brains of narcoleptic dogs,
Siegel suggested that the death of neurons in the amygdala and adjacent
forebrain areas is a one-time event that occurs just before the onset of the
disease early in life.
View a researcher working with narcoleptic dogs at
https://www.youtube.com/watch?v=R6_hwbp97eU .
A remarkable discovery that came from this line of investigation is
that a subset of these affected neurons produces a peptide called orexin
(also called hypocretin ) that serves as a signaling molecule to maintain
wakefulness. Orexin cells, which are located in the hypothalamus, send
projections to many other brain regions, as do the nonspecific activating
systems using acetylcholine and serotonin. This suggests that orexin
plays a role in maintaining activity during waking.
To test the idea that orexin loss is related to cataplexy, investigators
have bred knockout mice that lack orexin. When these mice become
active, such as at feeding time, they collapse into cataplexy, supporting
the idea that an orexin system contributes to healthy waking behavior.
Research with mice also suggests that lifestyle may contribute to orexin
cell loss. Mice fed a high-fat diet display a reduction in orexin cells and
symptoms of cataplexy (Nobunaga et al., 2014). Another proposed cause
of narcolepsy in humans is an autoimmune reaction: the immune system
attacks and kills orexin cells.
Section 3-3 investigates knockout technology and other genetic
engineering techniques.
View a dancer experiencing narcolepsy with cataplexy at
https://www.youtube.com/watch?v=1PuvXpv0yDM .
REM Sleep Behavioral Disorder
In Section 13-4 we described REM sleep behavioral disorder (REM
without atonia), a symptom displayed by some people who take
antidepressant drugs. They wake up seemingly acting out dream activity.
In Section 13-5 we described Jouvet’s experiment: he reported that cats
with lesions to the subcoerulear region of the brainstem entered REM
sleep without accompanying atonia and so apparently acted out their
dreams.
A similar condition reported in people may have either a genetic basis
or a neurological cause associated with aging. People who display REM
sleep behavioral disorder behave as though they are acting out their
dreams (Mahowald & Schenck, 2015). Following is the account of a 67-
year-old patient (Schenck et al., 1986):
I had a dream where someone was shooting at me with a rifle and it
was in a field that had ridges in it, so I decided to crawl behind a ridge
—and I then had a gun too—and I look over the ridge so when he
showed up I would shoot back at him and when I came to [i.e.,
awakened] I was kneeling alongside the bed with my arms extended
like I was holding the rifle up and ready to shoot.
In the dream the patient saw vivid images but heard nothing and felt
afraid. Although many patients have described such experiences, most
are elderly and suffer from brain injury or other brain-related disorders.
REM sleep behavioral disorder can be treated with benzodiazepines,
antianxiety drugs that block REM sleep.
 13-6 REVIEW

Sleep Disorders
Before you continue, check your understanding.
1 . Disorders of NREM sleep include ___________, in which a person
has difficulty falling asleep at night, and ___________, in which a
person falls asleep involuntarily in the daytime.
2 . Treating insomnia with sleeping pills, usually sedative-hypnotics,
may cause ___________: progressively higher doses must be taken to
achieve sleep.
3 . Disorders of REM sleep include ___________, in which a person
awakens but cannot move and is afraid, and ___________, in which a
person may lose all muscle tone and collapse while awake.
4 . The people who act out their dreams, a condition termed
___________, may have damage to the ___________ nucleus.
5 . Is orexin the substance that produces waking?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 What Does Sleep Tell Us about
13-7

Consciousness?
René Descartes conceived his idea of a mind through a lucid dream. He
dreamed that he was interpreting the dream as it occurred. Later, when
awake, he reasoned that if he could think and analyze a dream while
asleep, his mind must function during both waking and sleeping. He
proposed therefore that the mind must be independent of the body that
undergoes sleeping and waking transitions. Contemporary fMRI studies
suggest that lucid dreaming is especially common in people who display
high levels of prefrontal cortex activity in Brodmann’s areas 9 and 10
(Filevich et al., 2015).
Section 1-2 recounts how Descartes chose the pineal gland as the
seat of the mind.
As described in preceding sections, what we colloquially refer to as
waking comprises at least three states. First, alert consciousness without
accompanying movement is associated with cholinergic system activity.
Second, consciousness with movement is associated with serotonergic
system activity. Third, the peptide orexin also plays a role in maintaining
waking activity.
Similarly, sleep consists of NREM and REM phases. NREM sleep
consists of the four stages indicated by the EEG (see Figure 13-12 A).
REM sleep periods consist of at least two stages, one in which small
twitching movements occur and one in which such motion twitching is
absent.
REM neurobehavioral events can occur relatively independently.
Sleepers may awake to find themselves in a condition of sleep paralysis,
during which they experience the hallucinations and fear common in
dreams. People who are awake may fall into a state of cataplexy: they are
conscious of being awake during the atonia and visual and emotional
features of dreams.
Sleep researcher J. Allan Hobson reported his peculiar symptoms
after a brainstem stroke (Hobson, 2002). For the first 10 days after the
lesion, he had complete insomnia, neither REM nor NREM sleep.
Whenever he closed his eyes, however, he did have visual hallucinations
that had a dreamlike quality. This experience suggested that eye closure
is sufficient to produce the visual components of REM sleep but with
neither loss of consciousness nor atonia. Hobson eventually recovered
typical sleeping patterns, and the hallucinations stopped.
Beyond teaching us that the neural basis of consciousness is
extremely complex, the study of sleep states and dreaming may help to
explain some psychiatric and drug-induced conditions. For example
visual and auditory hallucinations are among the symptoms of
schizophrenia. Are these hallucinations dream events that occur
unexpectedly during waking? Many people who take hallucinogenic
drugs such as LSD report visual hallucinations. Does the drug initiate the
visual features of dreams? People who have panic attacks suffer from
very real fright that has no obvious cause. Are they experiencing the fear
attacks that commonly occur during sleep paralysis and cataplexy?
What the study of sleep tells us about consciousness is that a
remarkable number of variations of conscious states exist. Some are
associated with waking and some with sleeping, and the two can mix
together to produce a variety of odd conditions. When it comes to
consciousness, there is far more to sleeping and waking than just
sleeping and waking.
Section 15-7 explores the neural basis of consciousness and ideas
about why humans are conscious.
SUMMARY
13-1 A Clock for All Seasons
Biorhythms are cyclic behavior patterns of varying length displayed by
animals, plants, even single-celled organisms. Biorhythms displayed by
mammals include, among others, circadian (daily) rhythms and
circannual (yearly) rhythms. In the absence of environmental cues
circadian rhythms are free-running, lasting a little more or a little less
than their usual period of about 24 hours depending on the individual
organism or the environmental conditions. Cues called Zeitgebers reset
biological clocks to a 24-hour rhythm. Circadian rhythms allow us to
synchronize our behavior with our body’s metabolic processes—so that
we are hungry, and at optimal times. Environmental intrusions into our
natural circadian rhythm, from artificial lighting to jet lag, contribute to
metabolic syndrome. Biological clocks produce epigenetic effects: they
regulate gene expression in every cell in the body.
 13-2 Neural Basis of the Biological Clock
A biological clock is a neural structure responsible for producing
rhythmic behavior. Our master biological clock is the suprachiasmatic
nucleus. The SCN is responsible for circadian rhythms; it has its own
free-running rhythm with a period of a little more or a little less than 24
hours. Stimuli from the environment, such as sunrise and sunset, meals,
or exercise, entrain the free-running rhythm so that its period
approximates 24 hours.
SCN neurons are active in the daytime and inactive at night. These
neurons retain their rhythmicity when disconnected from other brain
structures, when removed from the brain and cultured in a dish, and after
culture in a dish for many generations. When reimplanted in a brain
without an SCN, they restore the animal’s circadian rhythms. Aspects of
neuronal circadian rhythms, including their period, are under genetic and
epigenetic control.
 13-3 Sleep Stages and Dreaming
Sleep events are measured by recording the brain’s activity to produce an
electroencephalogram (EEG), muscular activity to produce an
electromyogram (EMG), and eye movements to produce an
electrooculogram (EOG).
A typical night’s sleep, as indicated by physiological measures,
consists of stages that take place in cycles over the course of the night.
During REM sleep the EEG displays a waking pattern and the sleeper
displays rapid eye movements. Sleep stages in which the EEG has a
slower rhythm are called non-REM (NREM) sleep.
Intervals of NREM sleep and REM sleep alternate four or five times
each night. The duration of NREM sleep periods is longer earlier in
sleep, whereas the duration of REM sleep periods is longer in the later
part of sleep. These intervals also vary with age.
A sleeper in NREM has muscle tone, may toss and turn, and has
dreams that are not especially vivid. A sleeper in REM sleep has vivid
dreams in real time but has no muscle tone and so is paralyzed. Dream
duration coincides with the duration of the REM period.
The activation–synthesis hypothesis proposes that dreams are not
meaningful, merely a by-product of the brain’s state of excitation during
REM. The coping hypothesis suggests that dreaming evolved as a
mechanism to deal with challenges and fears posed by life.
 13-4 What Does Sleep Accomplish?
Several theories of sleep have been advanced, but the main proposition is
that sleep is a biological adaptation that conserves energy. Sleep is
suggested as a restorative process that fixes wear and tear in the brain
and body. Sleep also organizes and stores memories.
 13-5 Neural Bases of Sleep
Separate neural regions are responsible for NREM and REM sleep. The
reticular activating system, located in the central brainstem, is
responsible for NREM sleep. If the RAS is stimulated, a sleeper awakes;
if it is damaged, a person may enter a coma.
The peribrachial area and the medial pontine reticular formation in the
brainstem are responsible for REM sleep. If these areas are damaged,
REM sleep may no longer occur. Pathways projecting from these areas to
the cortex produce the cortical activation of REM, and those projecting
to the brainstem produce the muscular paralysis of REM.
 13-6 Sleep Disorders
Disorders of NREM sleep include insomnia, the inability to sleep at
night, and narcolepsy, inconveniently falling asleep in the daytime.
Sedative-hypnotics used to induce sleep may induce drug dependence
insomnia, a sleep disorder in which progressively larger doses are
required to produce sleep.
Disorders of REM sleep include sleep paralysis, in which a person
awakens but remains unable to move and sometimes feels fear and dread.
In cataplexy, caused by a loss of orexin cells in the brain, a person
collapses into a state of paralysis while awake. At the same time the
person may have hypnogogic hallucinations similar to dreaming. In
REM sleep behavioral disorder a sleeping person acts out dreams.
 13-7 What Does Sleep Tell Us about
Consciousness?
Sleep research provides insight into consciousness by revealing many
kinds of waking and sleeping. Just as the events of wakefulness intrude
into sleep, the events of sleep can intrude into wakefulness. The array of
conditions thus produced demonstrates that consciousness is not a
unitary state.
KEY TERMS
atonia, p. 458
basic rest–activity cycle (BRAC), p. 464
beta (β) rhythm, p. 457
biological clock, p. 443
biorhythm, p. 443
cataplexy, p. 474
chronotype, p. 450
circadian rhythm, p. 443
coma, p. 470
delta (δ) rhythm, p. 458
dimer, p. 452
diurnal animal, p. 443
drug dependence insomnia, p. 473
entrain, p. 446
free-running rhythm, p. 446
hypnogogic hallucination, p. 474
insomnia, p. 473
jet lag, p. 448
light pollution, p. 446
medial pontine reticular formation (MPRF), p. 470
melatonin, p. 454
metabolic syndrome, p. 443
microsleep, p. 466
narcolepsy, p. 473
NREM (non-REM) sleep, p. 458
peribrachial area, p. 470
period, p. 445
place cell, p. 468
REM sleep, p. 458
reticular activating system (RAS), p. 470
retinohypothalamic tract, p. 450
sleep apnea, p. 473
sleep paralysis, p. 474
slow-wave sleep, p. 458
suprachiasmatic nucleus (SCN), p. 450
Zeitgeber, p. 446

Visit Launch Pad to access the e-Book, videos,

Learning Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

14

How Do We Learn and

Remember?
 Katherine Streeter

CLINICAL FOCUS 14-1 REMEDIATING DYSLEXIA

14-1 CONNECTING LEARNING AND MEMORY
STUDYING LEARNING AND MEMORY IN THE LABORATORY
EXPERIMENT 14-1 QUESTION: DOES AN ANIMAL LEARN THE
ASSOCIATION BETWEEN EMOTIONAL EXPERIENCE AND
ENVIRONMENTAL STIMULI?
TWO CATEGORIES OF MEMORY
WHAT MAKES EXPLICIT AND IMPLICIT MEMORY DIFFERENT?
WHAT IS SPECIAL ABOUT PERSONAL MEMORIES?
14-2 DISSOCIATING MEMORY CIRCUITS
DISCONNECTING EXPLICIT MEMORY
DISCONNECTING IMPLICIT MEMORY
CLINICAL FOCUS 14-2 PATIENT BOSWELL’S AMNESIA
14-3 NEURAL SYSTEMS UNDERLYING EXPLICIT AND
IMPLICIT MEMORIES
NEURAL CIRCUIT FOR EXPLICIT MEMORIES
CLINICAL FOCUS 14-3 ALZHEIMER DISEASE
CLINICAL FOCUS 14-4 KORSAKOFF SYNDROME
CONSOLIDATION OF EXPLICIT MEMORIES
NEURAL CIRCUIT FOR IMPLICIT MEMORIES
NEURAL CIRCUIT FOR EMOTIONAL MEMORIES
14-4 STRUCTURAL BASIS OF BRAIN PLASTICITY
LONG-TERM POTENTIATION
MEASURING SYNAPTIC CHANGE
ENRICHED EXPERIENCE AND PLASTICITY
SENSORY OR MOTOR TRAINING AND PLASTICITY
EXPERIMENT 14-2 QUESTION: DOES THE LEARNING OF A
FINE MOTOR SKILL ALTER THE CORTICAL MOTOR MAP?
 RESEARCH FOCUS 14-5 MOVEMENT, LEARNING, AND
NEUROPLASTICITY
EXPERIENCE-DEPENDENT CHANGE IN THE HUMAN BRAIN
EPIGENETICS OF MEMORY
PLASTICITY, HORMONES, TROPHIC FACTORS, AND DRUGS
EXPERIMENT 14-3 QUESTION: WHAT EFFECT DO REPEATED
DOSES OF AMPHETAMINE, A PSYCHOMOTOR STIMULANT,
HAVE ON NEURONS?
SOME GUIDING PRINCIPLES OF BRAIN PLASTICITY
14-5 RECOVERY FROM BRAIN INJURY
DONNA’S EXPERIENCE WITH TRAUMATIC BRAIN INJURY
THREE-LEGGED CAT SOLUTION
NEW-CIRCUIT SOLUTION
EXPERIMENT 14-4 QUESTION: DOES NERVE GROWTH
FACTOR STIMULATE RECOVERY FROM STROKE, INFLUENCE
NEURAL STRUCTURE, OR BOTH?
LOST NEURON REPLACEMENT SOLUTION
CLINICAL FOCUS 14-1

Remediating Dyslexia
As children absorb their society’s culture, acquiring language skills
seems virtually automatic. Yet some people face lifelong challenges
in mastering language-related tasks. Educators classify these
difficulties under the umbrella of learning disabilities.
Dyslexia, impairment in learning to read, may be the most
common learning disability. Children with dyslexia (from Greek
words suggesting bad and reading ) have difficulty learning to write
as well as to read.
dyslexia Impairment in learning to read and write; probably the
most common learning disability.
In 1895, James Hinshelwood, an eye surgeon, examined some
schoolchildren who were having reading problems, but he could find
nothing wrong with their vision. Hinshelwood was the first to
suggest that children with reading problems were impaired in brain
areas associated with language use. Norman Geshwind and Albert
Galaburda (1985) proposed how such impairment might come about.
Struck by the finding that dyslexia is far more common in boys
than in girls, they reasoned that hormones influence early brain
development. They examined postmortem the brains of a small
sample of people who had dyslexia and found abnormal collections
of neurons, or warts, in and around the brain’s language areas.
This relation between structural abnormalities in the brain and
learning disabilities is further evidence that an intact brain is
necessary for healthy human functioning. Gesh-wind and Galaburda
also found abnormalities in the auditory thalamus, suggesting a
deficit in auditory processing. More recently, brain imaging has
determined that, relative to the brains of healthy participants, activity
is reduced in the left temporoparietal cortex of people with dyslexia.
Michael Merzenich and his colleagues designed a remedial
treatment program based on the assumption that the fundamental
problem in learning disabilities lies in auditory processing,
specifically of language sounds (e.g., Temple et al., 2003).
Remediation involves learning to make increasingly difficult sound
discriminations, for example, discriminating ba and da.
When the sounds are spoken slowly, discriminating between them
is easy, but as they grow briefer and occur faster, discrimination
becomes more difficult. Previous studies using rats and monkeys
showed that discrimination training stimulates neural plasticity in the
auditory system, making it capable of discrimination of sounds that
previously was not possible.
The representative fMRIs shown here reveal decreased activation
in many brain regions in untreated dyslexic children compared with
typical children. With training, dyslexic readers can normalize their
brain activity and presumably its connectivity.
The extent of increased brain activation in the language-related
regions (circled in the images) correlates to the amount of increased
brain activation overall. The results suggest that the remedial
treatment both improves brain function in regions associated with
phonological processing and produces compensatory activation in
related brain regions.

Typical-reading children while rhyming

 Dyslexic-reading children while rhyming (before remediation)
Regions of the frontal and temporoparietal cortex that showed
decreased activation in children with untreated dyslexia. “Neural Deficits
in Children with Dyslexia Ameliorated by Behavioral Remediation: Evidence from
Functional MRI,” by E. Temple, G. K. Deutsch, R. A. Poldrack, S. L. Miller, P. Tallal, M. M.
Merzenich, and J. D. E. Gabrieli, 2003, Proceedings of the National Academy of
Sciences (USA) 100, pp. 2860–2865.

Neuroplasticity is the nervous system’s potential for physical or

chemical change that enhances adaptability.

The brain is plastic. It changes throughout life, allowing us to

modify our behavior, to adapt and learn, and to remember. If we reflect
on our own lives, we can easily compile a list of experiences that must
change the brain:
• Profound changes during development
• Acquisition of culture
• Preferences among foods and beverages, art and music, and other
activities and experiences
• Ability to cope with the neurodegeneration of aging and to
accommodate neurological injury or disease at any age
 Learning is common to all these experiences. Understanding how the
brain supports learning is fundamental in neuroscience. At the level of
the neuron, synapses change with experience—learning new
information, for example. Such changes can take place anywhere in the
brain.
We can investigate neuronal changes that support learning specific
types of information by describing changes in cells exposed to specific
sensory experiences. Or we can look at the neural changes that mediate
brain plasticity—recovery from brain injury, addiction to drugs, or
conquering a learning disability. This chapter’s goal is to move beyond
the general concept of neuroplasticity toward understanding what
stimulates plastic change in the brain. We inspect changes related to
environment and experience, learning and memory, electrical
stimulation, chemical influences, and brain injury.
 14-1 Connecting Learning and Memory
Learning is a relatively permanent change in an organism’s behavior as
a result of experience. Memory is the ability to recall or recognize
previous experience. Memory thus implies a mental representation of a
previous experience, sometimes termed a memory trace. Neuro-scientists
presume that this hypothetical memory trace corresponds to a physical
change in the brain, most likely involving synapses.
learning Relatively permanent change in an organism’s behavior as
a result of experience.
memory Ability to recall or recognize previous experience.
The memory trace is a psychological construct, an abstract mental
process inferred only from behavior (see Section 15-1 ). Others
include learning, language, emotion, motivation, and thinking.
At the macro level, we infer what we know about learning and
memory formation from behavioral changes, not by observing the brain
directly. Studying learning and memory therefore requires behavioral
measures that evaluate how these changes come about. We begin here by
reviewing how learning and memory researchers study animals in the
laboratory. The results suggest, in a general way, how the brain organizes
its learning and memory systems.

Studying Learning and Memory in the

Laboratory
A challenge for psychologists studying memory in laboratory animals (or
people) is to get subjects to reveal what they remember. Because
laboratory animals do not speak, investigators must devise ways for a
subject to show its knowledge. Different species “talk” to us in different
ways, so the test choice must match each species’ capabilities.
Mazes or swimming pools are typically used to study rats because rats
live in tunnels and near water. Monkey studies take advantage of their
sharp vision and avid curiosity by requiring them to look under objects
for food or watch television monitors. With birds, natural behaviors such
as singing are used. And for humans, investigators tend to use paper-and-
pencil tests.
 Figure 7-4 samples swimming pool tests for rats, Experiment 15-1 ,
monkeys’ perceptual threshold, and Focus 15-4, the effects of brain
injuries on humans’ cognitive performance.
Psychologists have devised hundreds of tests over the past century,
and the test results reveal many types of learning and memory. Each
appears to have its own neural circuitry. Two classic traditions for
training animals to talk to investigators emerged a century ago. These
diverse approaches are based on the work of Edward Thorndike (1898)
in the United States and on experiments conducted by Ivan Pavlov in
Russia.
Pavlovian Conditioning
Early in the twentieth century, Ivan Pavlov, a Russian physiologist,
discovered that when a food reward accompanies some stimulus, such as
a tone, dogs learn to associate the stimulus with the food. Then whenever
they hear the tone, they salivate even though no food is present. This
type of learning has many names, including Pavlovian conditioning,
respondent conditioning, and classical conditioning, and many studies
document its characteristics.
Pavlovian conditioning Learning achieved when neutral stimulus
(such as a tone) comes to elicit a response after its repeated pairing
with some event (such as delivery of food); also called classical
conditioning or respondent conditioning.
A key feature of Pavlovian conditioning is that animals learn to
associate two stimuli (the presentation of the food and the tone) and to
communicate to us that they have learned it by giving the same response
(salivation) to both stimuli. Pet owners know that to a cat or dog, the
sound of a can being opened is a clear stimulus for food. Two forms of
Pavlovian conditioning are common in experiments today: eyeblink
conditioning and fear conditioning. Each is associated with neural
circuits in discrete brain regions; thus both are especially useful.
 FIGURE 14-1 Eyeblink Conditioning Neural circuits in the cerebellum
mediate this form of stimulus–response learning.

Eyeblink conditioning has been used to study Pavlovian learning in

rabbits and people ( Figure 14-1 ). In these studies, a tone (or some other
stimulus) is associated with a painless puff of air to the participant’s eye.
The tone is the conditioned stimulus (CS) that comes to elicit a blink
produced initially by the air puff. The air puff is the unconditioned
stimulus (UCS), because blinking is the normal reaction—the
unconditioned response (UCR)—to a puff of air. The participant
communicates having learned that the signal stimulus predicts the puff
by blinking in response to the signal (the CS) alone—a conditioned
response (CR). The circuits in the cerebellum that mediate such
Pavlovian learning are designed to pair motor responses with
environmental events. Eyeblink conditioning experiments take advantage
of this biological predisposition.
eyeblink conditioning Experimental technique in which subjects
learn to pair a formerly neutral stimulus with a defensive blinking
 response.
conditioned stimulus (CS) In Pavlovian conditioning, an originally
neutral stimulus that after association with an unconditioned
stimulus (UCS) triggers a conditioned response (CR).
unconditioned stimulus (UCS) A stimulus that naturally and
automatically (unconditionally) triggers an unconditioned response
(UCR).
unconditioned response (UCR) Unlearned, naturally occurring
response to the unconditioned stimulus (UCS), such as salivation
when food is in the mouth.
conditioned response (CR) In Pavlovian conditioning, the learned
response to a formerly neutral conditioned stimulus (CS).
In the cerebellum, the flocculus controls eye movements; see Figure
11-14 .
In fear conditioning, an unpleasant but harmless stimulus is used to
elicit an emotional response: fear. A rat or other animal is placed in a
box. A mild but unpleasant electric current can be passed through the
grid floor. As shown in Experiment 14-1 , a tone (the CS) is presented
just before a brief, unexpected mild electric shock. When the tone is
presented later without the shock, the animal acts afraid, becoming
motionless and perhaps urinating in anticipation of the shock. A novel
stimulus, say, a light, presented in the same environment has little effect.
Thus, the animal communicates that it has learned the association
between the tone and the shock.
fear conditioning Conditioned emotional response between a
neutral stimulus and an unpleasant event, such as a shock, that
results in a learned association.
The shock approximates a spark of static electricity.
Because the CR is emotional, circuits of the amygdala rather than the
cerebellum mediate fear conditioning. Although both eyeblink and fear
conditioning are Pavlovian, different brain areas mediate the learning.
Operant Conditioning
In the United States, Edward Thorndike (1898) began a second tradition
for studying learning and memory. Thorndike was interested in how
animals solve problems. In one series of experiments, he placed cats in a
box with a plate of fish outside it ( Figure 14-2 ). The only way for a
hungry cat to get to the fish was to figure out how to get out of the box.
The solution was to press on a lever to activate a system of pulleys
that opened the box door. The cat gradually learned that its actions had
consequences: on the initial trial, the cat touched the releasing
mechanism only by chance as it restlessly paced inside the box. The cat
apparently learned that something it had done opened the door, and it
tended to repeat its behaviors from just before the door opened. After a
few trials, the cat took just seconds to get the door open to devour the
fish.
 EXPERIMENT 14-1

Question: Does an animal learn the association between

emotional experience and environmental stimuli?
Procedure and results

Conclusion: The rat has learned an association between the tone and the
shock, which produces a fear response. Circuits that include the amygdala
take part in this learning process.

FIGURE 14-2 Thorndike’s Puzzle Box

Later studies by B. F. Skinner (e.g., 1938) used a similar strategy of
reinforcement to train rats to press bars or pigeons to peck keys to obtain
food. Just as Thorndike’s cats learned to escape his puzzle boxes, many
animals learn to press the bar or peck the key simply if they are placed in
the apparatus and allowed to discover the response that obtains the
reward. This type of learning is operant conditioning, or instrumental
conditioning, as Thorndike called it. The animal demonstrates that it has
learned the association between its actions and the consequences by
performing the task faster.
 operant conditioning Learning procedure in which the
consequences (such as obtaining a reward) of a particular behavior
(such as pressing a bar) increase or decrease the probability of the
behavior occurring again; also called instrumental conditioning.
The variety of operant associations is staggering: we learn constantly
to associate our behavior with its consequences. No surprise, then, that
operant learning is not localized to any particular brain circuit. The
circuits needed vary with the task requirements. For example, olfactory
tasks involve olfactory-related structures like the orbitofrontal cortex and
amygdala, spatial tasks recruit the hippocampus, and motor tasks require
the basal ganglia.

Two Categories of Memory

Humans present a distinct challenge to researchers studying memory
because so much of our learning is verbal. Psychologists have studied
human memory since the mid-1800s. More recently, cognitive
psychologists have developed sophisticated measures of learning and
memory for neuropsychological investigations. Two such measures help
to distinguish between two categories of memory in humans.
In one kind of task, a group of participants reads a list of words, such
as spring, winter, car, and boat. Another group reads a list consisting of
trip, tumble, run, and sun. All the participants are then asked to define a
series of words. One is fall.
The word fall has multiple meanings, including the season and a
tumble. People who have just read the word list containing names of
seasons are likely to give the meaning as autumn ; those who have read
the second list, containing action words, typically give the meaning as
tumble. Some form of unconscious (and unintentional) learning takes
place as the participants read the word lists.
This task measures implicit memory: participants demonstrate
knowledge—a skill, conditioned response, or recall of events on
prompting—but cannot explicitly retrieve the information. People with
amnesia, a partial or total loss of memory, perform at normal on tests of
implicit memory. The amnesic person has no recollection of having read
the word list yet acts as though some neural circuit has been influenced
by it. In amnesia, a dissociation —a disconnect—occurs between the
memory of the unconscious (or implicit) learning and explicit memory,
conscious recollection of training. Nonamnesic people can retrieve an
explicit memory and indicate that they know the retrieved item is correct.
implicit memory Unconscious memory: subjects can demonstrate
knowledge, such as a skill, conditioned response, or recall of events
on prompting but cannot explicitly retrieve the information.
amnesia Partial or total loss of memory.
explicit memory Conscious memory: subjects can retrieve an item
and indicate that they know the retrieved item is the correct one.
This implicit–explicit distinction is not restricted to verbal learning; it
is true of visual learning and motor learning as well. For example, when
people are shown the top panel of the Gollin figure test in Figure 14-3
and asked what it shows, they are unlikely to identify an image. They are
then presented with a succession of more nearly complete sketches until
they can identify the picture. When control participants and amnesics are
later shown the same sketch, both groups identify the figure sooner than
they could the first time. Even though the amnesic subjects may not recall
seeing the sketches before, they behave as though they had.
To measure implicit motor skills learning, a person learns a skill, such
as the pursuit rotor task shown in Figure 14-4 . A small metal disc moves
in a circular pattern on a turntable that also is moving. The task is to hold
a stylus on the small disc as it spins. This task is not as easy as it looks,
especially when the turntable is moving quickly. Nonetheless, with an
hour’s practice most people become reasonably proficient. Presented with
the same task a week later, both controls and amnesics take less time to
perform it. Here, too, the amnesics fail to recall performing the task
before.
The distinction between tests of implicit and explicit memory is
consistent and therefore must offer a key to how the brain stores
information. Some theorists make subtle distinctions between the
implicit–explicit dichotomy we use and other terminologies for
categorizing unconscious and conscious memory. Many researchers
prefer to distinguish between declarative memory, the specific contents
of specific experiences that can be verbally recalled (times, places, or
circumstances), and procedural memory, the ability to perform a task.
As applied to humans there is little practical difference.
declarative memory Ability to recount what one knows, to detail the
time, place, and circumstances of events; often lost in amnesia.
procedural memory Ability to recall a movement sequence or how
to perform some act or behavior.
FIGURE 14-3 Gollin Figure Test Participants are shown a series of drawings in
sequence, from least to most clear, and asked to identify the image. Most people must
see several panels before they can identify it. On a retention test some time later,
however, participants identify the image sooner than they did on the first test, indicating
some form of memory for the image. Amnesic subjects also show improvement on this
test, even though they do not recall taking it.

Table 14-1 lists commonly used dichotomies, the general distinction

being that one memory category requires recalling specific information,
whereas the other refers to knowledge of which we are not consciously
aware. We can include Pavlovian conditioning and Thorndike’s and
Skinner’s operant learning in this analysis too: all are forms of implicit
learning.
Nonspeaking animals can display explicit memory. One of us owned a
cat that loved to play with a little ball. One day, as the cat watched, the
ball was temporarily put on a high shelf to keep it away from an
inquisitive toddler. For weeks afterward, the cat sat and stared at the shelf
where the ball had been placed, even though the ball was not visible—an
example of explicit memory.
Animals also display explicit memory when they learn psychological
tasks. Rats can be trained to find highly palatable food in a new location
in a large compound each day. The task is to go to the most recent
location. This piece of information is explicit and demonstrably can be
forgotten.
 FIGURE 14-4 Pursuit-Rotor Task The participant must keep the stylus in
contact with a metal disc moving in a circular pattern on a turntable while
also rotating in a circular pattern. Although the task is difficult, most people
show significant improvement after brief training. Given a second test at
some later time, both participants and amnesics show task retention, but
typically the amnesics do not recall learning it before.

Suppose a rat trained to find food in a particular location in a small

arena is given several trials with the food at a new location and then
retested an hour, a day, 3 days, or a week later. The rat has no difficulty
with an hour’s delay or perhaps even a day’s. Some rats are flawless at 3
days, but most have forgotten the location by the time a week has elapsed.
Instead, they wander around looking for the food. This behavior
illustrates their implicit memory of the learning set, the rules of the game
—an implicit understanding of how a problem can be solved with a rule
that can be applied in many situations—namely, here, that a desired food
can be found with a certain search strategy.
learning set Rules of the game; implicit understanding of how a
problem can be solved with a rule that can be applied in many
different situations.
TABLE 14-1 Differentiating Two Memory Categories
Terms that describe conscious memory Terms that describe unconscious memory

Explicit Implicit

Declarative Nondeclarative

Fact Skill

Memory Habit

Knowing that Knowing how

Locale Taxon

Conscious recollection Skills

Elaboration Integration

Memory with record Memory without record

Autobiographical Perceptual

Representational Dispositional

Episodic Procedural

Semantic Nonassociative
Working Reference

Note: This paired list of terms differentiates conscious from unconscious forms of
memory. It will help you relate other memory discussions to the one in this book, which
favors the explicit–implicit distinction.

What Makes Explicit and Implicit Memory

Different?
One reason explicit and implicit memories differ is that the set of neural
structures that houses each is different. Another reason they differ is that
the brain processes explicit and implicit information differently.
Encoding Memories
Implicit information is encoded in much the same way it is perceived: it
can be described as data-driven, or bottom-up, processing. The idea is that
information enters the brain through sensory receptors, then is processed
in a series of subcortical and cortical regions. For example, visual
information about an object moves from the photoreceptors (the bottom)
to the thalamus, occipital cortex, then through the ventral stream to the
temporal lobe (the top), where the object is recognized.
Explicit memory, in contrast, depends on conceptually driven, or top-
down, processing: the person reorganizes the data. If you were searching
for a particular object, your keys, for example, you would ignore other
objects. This process is top-down because circuits in the temporal lobe
(the top) form an image (keys) that influences how incoming visual
information (the bottom) is processed and in turn greatly influences
information recall later.
Because a person has a relatively passive role in encoding implicit
memory, he or she has difficulty recalling the memory spontaneously but
recalls it more easily with priming by the original stimulus or some
feature of it. Because a person plays an active role in processing
information explicitly, internal cues used in processing can also be used to
initiate spontaneous recall.
priming Using a stimulus to sensitize the nervous system to a later
presentation of the same or a similar stimulus.
Findings from studies of eyewitness testimony demonstrate the active
nature of explicit memory recall—and its fallibility (e.g., Loftus, 1997).
In a typical experiment, participants view a video clip of an accident in
which a car collides with another car stopped at an intersection. One
group is asked to estimate how fast the moving car was going when it
“smashed” into the other car. A second group is asked how fast the car
was going when it “bumped” into the other car.
Later questioning indicates that the memory of how fast the moving
car was going is biased by the instruction: participants looking at
“smashing” cars estimate faster speeds than those estimated by
participants looking at “bumping” cars. The instruction actually causes
the information to be processed differently. In both cases, participants
were certain their memories were accurate.
Other experiments show that implicit memory also is fallible. For
example, participants are read the following list of words: sweet,
chocolate, shoe, table, candy, horse, car, cake, coffee, wall, book, cookie,
hat. After a few minutes’ delay, they hear another list of words that
includes some from the first list and some that are new. Participants are
asked to identify which words were present on the first list and to indicate
how certain they are of the identification.
One of the words on the second list is sugar. Most participants indicate
not just that sugar was on the first list but that they are certain it was.
Although other sweet things were, sugar was not. This demonstration is
intriguing, because it shows how easily we can form false memories and
defend their veracity with certainty.
Processing Memories
Although we can distinguish memories generally as implicit or explicit,
the brain does not process all implicit or all explicit memories in the same
way. Memories can be divided according to categories that differ from
those listed in Table 14-1 . For example, we can make a distinction
between memories for different types of sensory information.
Different neural areas process visual and auditory information, so it is
reasonable to assume that auditory memories are stored in brain regions
different from the regions that store visual memories. We can also make a
distinction between information stored in so-called short-term memory
and information held in long-term memory. In short-term memory,
information—the final score of a playoff game or the combination of your
friend’s bike lock, for instance—is held in memory only briefly, for a few
minutes at most, and then discarded. In long-term memory, information—
such as a close friend’s name—is held in memory indefinitely, perhaps for
a lifetime.
 The frontal lobes are central in short-term memory, whereas the
temporal lobe is central in long-term storage of verbal information. The
crucial point is that no single place in the nervous system can be
identified as the location for memory or learning. Virtually the entire
nervous system can be changed by experience, but different parts of an
experience change different parts of the nervous system. One challenge
for the experimenter is to devise ways of manipulating experience to
demonstrate change in different parts of the brain.
Storing Memories
Understanding that every part of the brain can learn influences how we
view the neural circuits that mediate memory. We could expect areas that
process information to also house the memory of that information. Areas
that process visual information, for example, probably house visual
memory. Since the temporal lobe has specialized regions for processing
color, shape, and other visual characteristics, we can predict that the
memory for various visual attributes of objects is stored separately.
A series of PET studies by Alex Martin and colleagues (1995) at the
U.S. National Institute of Mental Health confirmed this prediction. In one
study, participants were shown black-and-white line drawings of objects
and asked to generate words denoting either their colors or actions. The
idea is that processing color and motion are carried out in different
temporal lobe locations, and thus the activity linked with the memories of
color and motion also might be dissociated.
Just such dissociation was demonstrated. Figure 14-5 shows that color
recall activates a region in the ventral temporal lobe, just anterior to the
area controlling color perception, whereas recall of action words activates
a region in the middle temporal gyrus, just anterior to the area controlling
motion perception. This distribution of neural activation shows not only
that object memory is at least partly located in the temporal lobes but also
that it is found in regions associated with the original perception of the
objects.
KEY

Color words
Action words
Overlap
 FIGURE 14-5 Memory Distribution Blood flow in left-hemisphere
regions increases when participants generate color words (red) and action
words (blue) to describe static black-and-white drawings of objects. Purple
areas indicate overlap. The red region extends into the ventral temporal
lobe, suggesting that object memory is organized as a distributed system.
Objects’ attributes are stored close to the cortical regions that mediate their
perceptions. Parietal lobe activation likely is related to movements
associated with action words, and frontal lobe activation, to the
spontaneously generated behavior. Information from A. Martin, J. V. Haxby,
F. M. Lalonde, C. L. Wiggs, & L. G. Ungerleider (1995). Discrete cortical
regions associated with knowledge of color and knowledge of action.
Science, 270, p. 104.

What Is Special about Personal Memories?

One aspect of memory unique to each of us is our personal, or
autobiographical, memory. This episodic memory includes not only a
record of events (episodes) that took place but also a record of our
presence and role in the events. Our personal experiences form the basis
of who we are and the rules by which we live. That is, we have memories
not only for events but also for their context at a particular time in a
particular place. We thus gain a concept of time and a sense of our
personal role in a changing world.
episodic memory Autobiographical memory for events pegged to
specific place and time contexts.
 Imagine what would happen if we lost our personal memories. We
would still recall events but we would be unable to see our role in them.
People with frontal lobe injuries sometimes exhibit such symptoms, as
illustrated in a case described by Endel Tulving (2002).
K. C. suffered a serious traumatic brain injury in a motorcycle accident
that produced multiple cortical and subcortical lesions. Remarkably, K.
C.’s cognitive abilities were intact and indistinguishable from those of
most typical healthy adults. He played chess and the organ, and his short-
term memory was intact. He knew who he was and when his birthday
was, the names of schools he had attended, and the location of the family
cottage. Recalling facts, figures, dates and times posed no difficulty for K.
C.
What K. C. could not do was to recall any personally experienced
events. This episodic amnesia covered his entire life, from birth. He knew
facts about himself but had no memory for events that included him
personally. For example, K. C. could not describe an event that took place
in school that specifically included him, while at the same time recalling
going to school and the knowledge he had gained there.
Findings from neuroimaging studies of people with episodic amnesia
suggest that they consistently have frontal lobe injuries (Lepage et al.,
2001), but exactly why these lesions produce episodic amnesia remains
unclear. Nonetheless, Tulving made the interesting proposal that episodic
memory is a marvel of nature: it transforms the brain into a kind of time
machine that allows us to dwell on the past and make plans for the future.
He goes further, suggesting that this ability may be unique to humans and
is presumably due to some novel evolutionary development of the frontal
lobe.
Not all people with episodic amnesia have brain injury, however.
Many case reports describe patients with massive memory disturbances
resulting from some “psychiatric” or “psychogenic” disorder. Such cases
have been fodder for numerous movie plots. Hans Markowitsch (2003)
noted that the amnesia reported in some of these cases is remarkably
similar to episodic amnesia seen in neurological patients. Neuroimaging
of patients with psychogenic amnesia shows a massive reduction in brain
activity in frontal regions, a reduction remarkably similar to that seen in
neurological patients with episodic amnesia ( Figure 14-6 ). Therefore,
we can assume that patients with psychogenic amnesias have a
dysfunction of frontal brain activity that blocks the retrieval of
autobiographical memory.
 Just as some people exhibit poor autobiographical memory, a rare
group displays highly superior autobiographical memory (HSAM)
(LePort et al., 2012). These people display virtually complete recall for
events in their lives, usually beginning around age 10, and can often
describe any episode, including the day of the week that it occurred and
the date. They can even recall the weather that day, as well as social and
public events. Brain imaging of those who display HSAM shows
increased gray matter in the temporal and parietal lobes and increased
size in the fiber projection between the temporal and frontal lobes.
Lawrence Pathihis and colleagues (2013) wondered if HSAM
individuals might also be immune to memory distortion, such as the false
memories described earlier. The investigators found that HSAM
individuals are as likely to develop false memories as are other
participants. Whatever the source of their extraordinary autobiographical
memory, it does not prevent the sort of memory distortions the rest of us
experience. Possibly that is because the research paradigms employed are
not strictly autobiographical.

FIGURE 14-6 Lost Episodes Left to right: Horizontal, frontal, and sagittal
sections imaged in a patient with impaired autobiographical memory. White
arrows point to areas of reduced glucose metabolism in frontal and
temporal regions as she attempts to retrieve remote personal memories.
Her MRI scan was normal. Republished with permission of Elsevier Science and
Technology Journals from “The impairment of recollection in functional amnesic states” Hans J.
Markowitsch and Angelica Staniloiu, Cortex 49 (2013) 1494–1510. Permission conveyed through
Copyright Clearance Center, Inc.
 14-1 REVIEW
Connecting Learning and Memory
Before you continue, check your understanding.
1 . An organism learns that some stimulus is paired with a reward. This
is ___________ conditioning.
2 . After learning that consequences follow its behavior, an organism
modifies its behavior. This is ___________ conditioning.
3 . Information that is unconsciously learned forms ___________
memory, whereas specific factual information forms ___________
memory.
4 . ___________ memory is autobiographical and unique to each person.
5 . Where is memory stored in the brain?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 14-2 Dissociating Memory Circuits
Beginning in the 1920s and continuing until the early 1950s, American
psychologist Karl Lashley searched in vain for the neural circuits
underlying memories. Lashley’s working hypothesis was that memories
must be represented in the perceptual and motor circuitry used to learn to
solve problems. To find that circuitry, he investigated the ways
laboratory rats and monkeys learn specific tasks for food reward. He
believed that if he removed bits of this circuitry or disconnected it,
amnesia should result.
In fact, neither ablation procedure produced amnesia. Lashley found
instead that the severity of memory disturbance was related to the size of
the lesion rather than to its location. After searching for 30 years,
Lashley concluded that he had failed to find the location of a memory
trace, although he believed that he knew where it was not located
(Lashley, 1960).
Brain lesions are an ablation technique—the first and simplest brain
manipulation; see Section 7-1 .
Just two years later, neurosurgeon William Scoville discovered
serendipitously what Lashley’s studies had not predicted. Scoville was
attempting to rid people of seizures by removing the abnormal brain
tissue that caused them. In August 1953, Scoville performed a bilateral
medial temporal lobe resection on a young man, Henry Molaison (H.
M.), whose severe epilepsy was not controlled by medication. H. M.’s
seizures originated in the medial temporal lobe region, so Scoville
bilaterally removed much of the hippocampal formation, along with
some of the amygdala and adjacent neo-cortical structures. The
procedure left the more lateral temporal lobe tissue intact. As shown in
Figure 14-7 , removal specifically included the anterior part of the
hippocampus, the amygdala, and adjacent cortex.
 FIGURE 14-7 Extent of H. M.’s Surgery H. M.’s right-hemisphere
lesion is highlighted in the brain viewed ventrally. The lesion runs along the
wall of the medial temporal lobe. The left side of the brain has been left
intact to show the relative location of the medial temporal structures. Parts
A, B, and C, based on MRI scans, depict a series of coronal sections of H.
M.’s brain. Research from S. Corkin, D. G. Amaral, R. G. Gonzalez, K. A. Johnson, & B. T.
Hyman (1997). H. M.’s medial temporal lobe lesion: findings from magnetic resonance imaging.
by Journal of Neuroscience, 17, p. 3966.

Disconnecting Explicit Memory

The behavioral symptoms Scoville noted after the surgery were
completely unexpected. He invited Brenda Milner (Milner et al., 1968)
to study H. M. Milner had been studying memory difficulties in patients
with unilateral temporal lobe removals for the treatment of epilepsy. She
and her colleagues worked with H. M. for more than 50 years, making
his the most studied case in neuroscience (e.g., Corkin, 2002). H. M.
died in 2008.
 His most remarkable symptom was severe amnesia: he was unable to
recall anything that had happened since his surgery in 1953. H. M.
retained an above-average I.Q. score (118 on the Wechsler Adult
Intelligence Scale; 100 is average), and he performed at normal on
perceptual tests. His recall of events from his childhood and school days
was intact. Socially, H. M. was well mannered, and he engaged in
sophisticated conversations. However, he had no recall for recent events.
H. M. lacked any explicit memory.
In one study by Suzanne Corkin (2002), H. M. was given a tray of
hospital food, which he ate. A few minutes later, he was given another
tray. He did not recall having eaten the first meal and proceeded to eat
another. A third tray was brought, and this time he ate only the dessert,
explaining that he did not seem to be very hungry.
To understand the implications and severity of H. M.’s condition, one
need only consider a few events in his postsurgical life. His father died,
but H. M. continued to ask where his father was, only to experience
anew the grief of learning that his father had passed away. (Eventually H.
M. stopped asking about his father, suggesting that some type of learning
had taken place.)
Similarly, in the hospital, he typically asked the nurses, with many
apologies, to tell him where he was and how he came to be there. He
remarked on one occasion, “Every day is alone in itself, whatever
enjoyment I’ve had and whatever sorrow I’ve had.” He perceived his
surroundings but could not comprehend his situation because he did not
remember what had gone before.
Formal tests of H. M.’s memory showed, as you would expect, no
recall for specific information just presented. In contrast, his implicit
memory performance was nearly intact. He performed at normal on tests
such as the incomplete figure and pursuit rotor tasks, illustrated in
Figures 14-3 and 14-4 , respectively. So while his implicit memory
system must have been intact, the systems crucial to explicit memory
were missing or dysfunctional. Yet H. M. recognized faces, including his
own, and he recognized that he aged. Face recognition depends on the
parahippocampal gyrus, which was partly intact on H. M.’s right side.
Clinical Focus 14-2 , Patient Boswell’s Amnesia, describes a case similar
to H. M.’s.
Prosopagnosia, an inability to recognize faces, and other visual form
agnosias are topics in Chapter 9 .
Disconnecting Implicit Memory
Among the reasons Lashley’s research did not find a syndrome like that
shown by H. M., the two most important are that Lashley did not damage
the medial temporal regions. Nor did he use tests of explicit memory, so
his animal subjects would not have shown H. M.’s deficits. Rather,
Lashley’s tests were mostly measures of implicit memory, with which H.
M. had no problems.
The following case illustrates that Lashley probably should have been
looking in the basal ganglia for the deficits that his implicit memory tests
revealed. The basal ganglia play a central role in motor control. Among
the compelling examples of implicit memory is motor learning—driving
and playing musical instruments or online games, to name a few.
J. K. was above average in intelligence and worked as a petroleum
engineer for 45 years. In his mid-70s, he began to show symptoms of
Parkinson disease, in which the projections from the dopaminergic cells
of the brainstem to the basal ganglia die. At about age 78, J. K.’s
memory difficulties started.
Focus features 5-2, 5-3, and 5-4 and Section 7-1 detail aspects of
Parkinson disease. Section 16-3 reviews treatments.
Curiously, his memory disturbance was related to tasks J. K. had
performed his whole life. On one occasion, he stood at his bedroom door,
frustrated by his inability to recall how to turn on the lights. “I must be
crazy,” he remarked. “I’ve done this all my life and now I can’t
remember how to do it!” On another occasion, he was seen trying to turn
the radio off with the television remote control. This time he explained,
“I don’t recall how to turn off the radio so I thought I would try this
thing!”
CLINICAL FOCUS 14-2

Patient Boswell’s Amnesia

At the age of 48, Boswell developed herpes simplex encephalitis, a
brain infection. He had completed 13 years of schooling and had
worked for nearly 30 years in newspaper advertising. By all accounts
a normal, well-adjusted person, Boswell was successful in his
profession.
Boswell recovered from the acute symptoms, including seizures
and a 3-day coma. His intelligence post disease was low average,
probably owing to neurological damage caused by the infection.
Nonetheless, his speech and language remained typical in every
respect, and he showed no perceptual or movement deficits.
But Boswell was left with a severe amnesic syndrome. If he hears
a short paragraph and is asked to describe its main points, he
routinely scores zero. He can only guess the day’s date and is unable
even to guess the year. When asked what city he is in, he simply
guesses.
Boswell does know his place of birth and can correctly recall his
birth date about half the time. In sum, Boswell has severe amnesia
for events both before and since his encephalitis. Like H. M., he does
show implicit memory on tests such as the pursuit rotor task.
Antonio Damasio and his colleagues (1989) have investigated
Boswell’s amnesia extensively, and his brain pathology is now well
documented. The critical damage, diagrammed in the adjoining
illustration, is bilateral destruction of the medial temporal regions
and a loss of the basal forebrain and the posterior part of the
orbitofrontal cortex. In addition, Boswell has lost the insular cortex
from the lateral fissure (not visible in the illustration).
Boswell’s sensory and motor cortices are intact, as are his basal
ganglia, but his injury is more extensive than H. M.’s. Like H. M., he
has no new memories. Unlike H. M., he also has a severe loss of
access to old information, probably owing to his insular and
prefrontal injuries. Nonetheless, again like H. M.’s, Boswell’s
 procedural memory is intact, illustrating the dissociation between
neural circuits underlying explicit and implicit forms of memory.

After recovering from a herpes simplex encephalitis infection,

patient Boswell has great difficulty remembering events before
and after his illness. Areas of damage in the medial temporal
region, basal forebrain, and posterior orbitofrontal cortex are
highlighted in red. Compare Figure 14-6 .

J. K.’s clear implicit memory deficit contrasts sharply with his

awareness of daily events. He recalled explicit events as well as most
men his age and spoke intelligently on issues of the day that he had just
read about. Once when two of us visited him, one of us entered the room
first and he immediately asked where the other was, even though it had
been 2 weeks since we told him that we would be coming to visit.
This intact long-term memory is vastly different from H. M.’s
situation: he would not have remembered that anybody was coming even
5 minutes after being told. Because Parkinson disease primarily affects
the basal ganglia, J. K.’s deficit in implicit memory was probably related
to his basal ganglia dysfunction.
 14-2 REVIEW
Dissociating Memory Circuits
Before you continue, check your understanding.
1 . Based on the case of H. M., we can conclude that the structures
involved in explicit memory include the ___________, the
___________, and adjacent cortex.
2 . Implicit memory deficits in patients with Parkinson disease
demonstrate that a major structure in implicit memory is the
___________.
3 . What is the main difference between the Lashley and Milner studies?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 Neural Systems Underlying Explicit
14-3

and Implicit Memories

Findings from laboratory studies, largely on rats and monkeys, have
reproduced the symptoms of patients such as H. M. and J. K. by injuring
the animals’ medial temporal regions and basal ganglia, respectively.
Other structures, most notably in the frontal and temporal lobes, also
participate in certain types of explicit memory. We now consider the
systems for explicit and implicit memory separately.

Neural Circuit for Explicit Memories

The dramatic amnesic syndrome discovered in H. M. in the 1950s led
investigators to focus on the hippocampus, at the time regarded as a large
brain structure in search of a function. But H. M. had other damaged
structures, too, and the initial focus on the hippocampus as the location
of explicit memory processing turned out to be misguided.
Turns out, the hippocampus participates in species-specific
behaviors, spatial navigation, and memory, and it is vulnerable to
stress.
After decades of anatomical and behavioral studies sorted out the
complexities, consensus on the anatomy of explicit memory had
coalesced by the mid-1990s. The primary structures for explicit memory
include the medial temporal region, the frontal cortex, and structures
closely related to them.
Consult sources published before 1995, and you may find
explanations for memory far different from this chapter’s (see
Gazzaniga, 2000).
Before considering the model, we first revisit medial temporal
anatomy. Review Figure 14-5 ’s summary of findings, which show that
memories for objects’ colors and motion characteristics reside in
separate temporal lobe locations. Thus the medial temporal region
receives multiple sensory inputs.
The macaque monkey’s medial temporal region shares many
anatomical similarities with the region in the human brain. In addition to
the hippocampus and amygdala, three medial temporal areas illustrated
in Figure 14-8 take part in explicit memory: lying adjacent to the
hippocampus are the entorhinal cortex, the parahippocampal cortex,
and the perirhinal cortex. A sequential arrangement of two-way
connections, charted in Figure 14-9 , projects from the major cortical
regions into the perirhinal and parahippocampal cortices, which in turn
project to the entorhinal cortex, then to the hippocampus.
entorhinal cortex Located on the medial temporal lobe surface;
provides a major route for neocortical input to the hippocampal
formation; often degenerates in Alzheimer disease.
parahippocampal cortex Cortex located along the dorsal medial
temporal lobe surface.
perirhinal cortex Cortex lying next to the rhinal fissure on the
ventral surface of the brain.
In Greek, para means beside; rhino means nose. The perirhinal
cortex lies beside the rhinal sulcus on the bottom of the brain.
The prominent cortical input to the perirhinal region is from the visual
ventral stream coursing through the temporal lobe. The perirhinal region
is thus a prime candidate location for visual object memory. Similarly,
the parahippocampal cortex receives strong input from parietal regions
believed to take part in visuospatial processing and likely participates in
visuospatial memory —using visual information to recall an object’s
location in space.
visuospatial memory Use of visual information to recall an object’s
location in space.
Section 9-2 traces visual pathways in detail.
FIGURE 14-8 Medial Temporal Structures Ventral view of the rhesus macaque
monkey brain. Left side: The medial temporal regions. Each plays a distinct role in
processing sensory information for memory storage. Right side: The hippocampus and
amygdala are not directly visible from the brain surface; they lie within the cortical
regions illustrated on the left. All these structures are present on both sides of the brain.
 Reciprocal Medial Temporal Connections Flow of input from
FIGURE 14-9

the sensory cortices: first to the parahippocampal and perirhinal regions, then to the
entorhinal cortex, and finally to the hippocampus. The hippocampus feeds back to the
medial temporal regions and then to the neocortical sensory regions.
CLINICAL FOCUS 14-3

Alzheimer Disease
In the 1880s it was noted that the brain may undergo atrophy with
aging, but the reason was not really understood until the German
physician Alois Alzheimer published a landmark study in 1906.
Alzheimer described a set of behavioral symptoms and associated
neuropathology in a 51-year-old woman who was demented. The
cellular structure of her neocortex and allocortex showed various
abnormalities.
An estimated 5.4 million people in the United States have
Alzheimer disease, although the only certain diagnostic test remains
postmortem examination of cerebral tissue. The disease progresses
slowly, and many people with Alzheimer disease probably die of
other causes before the cognitive symptoms incapacitate them.
We knew of a physics professor who continued to work until,
when he was nearly 80, he died of a heart attack. Postmortem
examination of his brain revealed significant Alzheimer pathology.
His colleagues had attributed the professor’s slipping memory to the
old-timer’s disease.
The cause of Alzheimer disease remains unknown, although it has
been variously attributed to genetic predisposition, abnormal levels
of trace elements (e.g., aluminum), immune reactions, slow viruses,
and prions (abnormal, infectious forms of proteins). Two principal
neuronal changes take place in Alzheimer disease:
1. Loss of cholinergic cells in the basal forebrain. One treatment for
Alzheimer disease, therefore, is medication that increases
acetylcholine levels in the forebrain. An example is Exelon, which
is the trade name for rivastigmine, a cholinergic agonist that
appears to provide temporary relief from the progression of the
disease and is available both orally and as a skin patch.
2. Development of neuritic plaques in the cerebral cortex. A
neuritic plaque consists of a central core of homogeneous protein
material ( amyloid ) surrounded by degenerative cellular
fragments. The plaques are not distributed evenly throughout the
 cortex but are concentrated especially in temporal lobe areas
related to memory. Neuritic plaques are often associated with
another abnormality, neurofibrillary tangles, paired helical
filaments found in both the cerebral cortex and the hippocampus.
The prion paradigm holds that misfolded tau proteins, illustrated
here, which have the ability to self-propagate, cause many age-
related neurodegenerative diseases (Walker & Jucker, 2015).
Researchers are conducting clinical trials on new drugs that act
either to find and neutralize misfolded proteins or as immunizing
agents, to prevent protein misfolding (Wisniewski & Goni, 2015).
neuritic plaque Area of incomplete necrosis (dead tissue)
consisting of a central protein core (amyloid) surrounded by
degenerative cellular fragments; often seen in the cortex of
people with dementias such as Alzheimer disease.
Cortical neurons begin to deteriorate as the cholinergic loss,
plaques, and tangles develop. The first cells to die are in the
entorhinal cortex (see Figure 14-8 ). Significant memory disturbance
ensues.
A controversial idea emerging from stroke neurologists is that
dementia may reflect a chronic cerebrovascular condition, marginal
high blood pressure. Marginal elevations in blood pressure can lead
to cerebral microbleeds, especially in white matter. The cumulative
effect of years or even decades of tiny bleeds would eventually lead
to increasingly disturbed cognition. This may first appear as mild
cognitive impairment (MCI) that slowly progresses with cumulative
microbleeds.
 Thomas Deerinck, MCMIR/Science Source
The red area near the cell nucleus in this false-color brain cell
from a person with Alzheimer disease represents a
neurofibrillary tangle of misfolded tau proteins.

Because both the perirhinal and the parahippocampal regions project

to the entorhinal cortex, this region probably participates in more
integrative memory functions. The entorhinal cortex is in fact the first
area to show cell death in Alzheimer disease, a dementia characterized
by severe deficits in explicit memory (see Clinical Focus 14-3 ,
Alzheimer Disease).
Section 16-3 elaborates on Alzheimer and other dementias and on
prion theory.
The Hippocampus and Spatial Memory
We are left with a conundrum. If the hippocampus is not the key
structure in explicit memory even as it receives the entorhinal
connections, what does it do? John O’Keefe and Lynn Nadel were the
first to advance the idea, in 1978, that the hippocampus is probably
engaged in visuospatial memory processes required for places, such as
recalling an object’s location.
Certainly both laboratory animals and human patients with selective
hippocampal injury have severe deficits in various forms of spatial
memory. Similarly, monkeys with hippocampal lesions have difficulty
learning the location of objects (visuospatial learning ), as can be
demonstrated in tasks such as the ones illustrated in Figure 14-10 .
Monkeys are trained to displace objects to obtain a food reward
(Figure 14-10 A), then given one of two tasks. In the visual recognition
task (Figure 14-10 B), the animal displaces a sample object for the food
reward. After a short delay, the animal is presented with two objects.
One is novel. The task is to learn to displace the novel object for the food
reward. This task tests explicit visual object memory. Monkeys with
perirhinal lesions are impaired at the task.
In the object position task in Figure 14-10C , the monkey is shown
one object to be displaced for a food reward. Then the monkey is shown
the same object along with a second identical one. The task is to learn to
displace the object that is in the same position as it was in the initial
presentation. Monkeys with hippocampal lesions are selectively impaired
at this task.
From these results, we would predict that a species with an especially
good spatial memory should have bigger hippocampi than do species
with a poorer spatial memory. David Sherry and his colleagues (1992)
tested this hypothesis in birds.
Section 1-4 explains the encephalization quotient, an index of ratios
of brain to body size. EQs allow comparisons of the relative brain
sizes of different species.
Many birds are cachers: they harvest sunflower seeds and other
favored foods and hide (cache) them to eat later. Some birds can find
hundreds of items they have cached. To evaluate whether the
hippocampus plays a role in this activity, Sherry and his coworkers
measured hippocampal size in closely related bird species, only one of
which is a food cacher. As shown in Figure 14-11 , the hippocampal
formation is larger in birds that cache food than in birds that do not. In
fact, the hippocampi of food-storing birds are more than twice as large as
expected for birds of their brain size and body weight.
Sherry found a similar relation when he compared different species of
food-storing rodents. Merriam’s kangaroo rats, rodents that store food
throughout their territory, have larger hippocampi than bannertail
kangaroo rats, which store food only in their burrow. Hippocampal size,
both in birds and in mammals, appears to be related to the cognitive
demands of two highly spatial activities, foraging for and storing food.
(A) Basic training

(B) Visual-recognition task

(C) Object-position task

 FIGURE 14-10 Two Memory Tasks for Monkeys (A) In “basic
training,” a monkey learns to displace an object to obtain a food reward. In
(B) and (c) the plus and minus signs indicate whether the object (1) is or
(2) is not associated with food.

One prediction we might make based on the Sherry experiments is

that people who have a job with high spatial demands have large
hippocampi. Taxi drivers in London fit this category. Successful
candidates for a cab driver’s license in London must demonstrate that
they know the location of every street in that huge and ancient city.
Using MRI, Eleanor Maguire and her colleagues (2000) found the
posterior region of the hippocampus in London taxi drivers to be
significantly larger than the same region in the control participants. This
finding presumably explains why a select few pass a spatial memory test
that most of us would fail miserably.
 FIGURE 14-11 Inferring Spatial Memory This graph relates
hippocampal volume to forebrain volume in food-storing (left) and non-
food-storing (right) families of songbirds. Birds that cache food, such as
the black-capped chickadee, have hippocampi about twice as large as
those of birds, such as the sparrow, that are not cachers. Data from D. F.
Sherry, L. F. Jacobs, & S. J. C. Gaulin (1992). Spatial memory and
adaptive specialization of the hippocampus. Trends in Neuroscience, 15,
pp. 298–303.

Spatial Cells in the Hippocampal Formation

Given the role of the hippocampus in spatial behavior, we might predict
that individual cells would code spatial information. They do. Three
classes of spatially related cells have been identified in the rat and mouse
hippocampus (Figure 14-12 ). Together they form an internal GPS, a
neural global positioning system. That is, neurons vigorously fire when
an animal is in a specific place in the environment. In 2014, John
O’Keefe, Edvard Moser, and May-Britt Moser were awarded the Nobel
Prize in Physiology or Medicine for this discovery.
Place cells, shown in Figure 14-12 A and B, discharge when rats are
in a spatial location, irrespective of its orientation. Head direction cells
(Figure 14-12C ) discharge whenever a rat’s head points in a particular
direction. Grid cells (Figure 14-12 D) discharge at many locations,
forming a virtual grid invariant to changes in the rat’s direction,
movement, or speed.
These cells are not localized to the hippocampus but are found within
a network that includes the hippocampus as its central structure. Place
cells and head direction cells are located in the hippocampus and closely
related structures. Grid cells are found in the entorhinal cortex, a major
afferent route into the hippocampus (see Figure 14-9 ). Taken together,
we can envision the place cell system as indicating where things are in
the world, the grid system indicating how big our present navigating
environment is, and the head direction and grid systems telling us where
we ourselves are in the environment.
Reciprocal Connections for Explicit Memory
Explicit memory’s temporal pathway is reciprocal: connections from the
neocortex run to the entorhinal cortex, then back to the neocortex (see
Figure 14-9 ). Reciprocal connections have two benefits:
1. Signals from the medial temporal regions back to the cortical sensory
regions keep the sensory experience alive in the brain: the neural
record of an experience outlasts the actual experience.
(A) Place cell

(B) Place-by-direction cell

(C) Head direction cell

(D) Grid cell

Courtesy of John O’Keefe.

Classes of Spatially Related Cells in the

FIGURE 14-12

Hippocampal Formation At right in each part, X–Y coordinates

indicate the directional selectivity of the cell recorded at left. (A and B)
Place cells discharge when a rat is at a spatial location, irrespective of its
orientation. (C) Head direction cells discharge when the rat’s head points
in a given direction, irrespective of its location. (D) Grid cells discharge at
 many locations, forming a virtual grid that is invariant in the face of
changes in the rat’s direction, movement, or speed. Research from
O’Keefe, 2006, Fig. 11-21.

2. The pathway back to the neocortex keeps it appraised of information

being processed in the medial temporal regions.
The basal ganglia systems that take part in implicit memory do not
feed back to the cortex, which helps explain its unconscious nature.
Although we have focused on the medial temporal regions, other
structures also are important in explicit memory. People with frontal lobe
injuries are not amnesic like H. M. or J. K., but they do have difficulties
with memory for the temporal (time) order of events. Imagine being
shown a series of photographs and asked to remember them. A few
minutes later, you are asked whether you recognize two photographs and
if so, to indicate which one you saw first.
H. M. would not remember the photographs. People with frontal lobe
injuries would recall seeing the photographs but would have difficulty
recalling which one they had seen more recently. The frontal lobe’s role
in explicit memory clearly is subtler than that of the medial temporal
lobe.
 FIGURE 14-13 Testing Short-Term Memory A monkey performing a
short-term memory task responds by pressing the disc to get a fruit juice
reward (top). The correct disc varies, depending on the task requirements
(bottom). (For each task, an arrowhead shows the correct choice.)
Information from J. Fuster (1995). Memory in the cerebral cortex (p. 178).
Cambridge, MA: MIT Press.

THE FRONTAL LOBE AND SHORT-TERM MEMORY All sensory systems in the
brain send information to the frontal lobe, as do the medial temporal
regions. This information is not used for direct sensory analysis, so it
must have another purpose. In general, the frontal lobe appears to
participate in many forms of short-term memory.
Joaquin Fuster (e.g., Fuster, Bodner, & Kroger, 2000) studied single-
cell activity in the frontal lobe during short-term memory tasks. For
example, if monkeys are shown an object that they must remember for a
short time before being allowed to make a response, neurons in the
prefrontal cortex show sustained firing during the delay. Consider the
tests illustrated in Figure 14-13 :
• In the general design for each test, a monkey is shown a light (the cue),
and after a delay it must make a response to get a reward.
• In the delayed-response task, the monkey is shown two lights in the
choice test and must choose the one that is in the same location as the
cue.
• In the delayed-alternation task, the monkey is again shown two lights
in the choice tests but now must choose the light that is not in the same
location as the cue.
• In the delayed matching-to-sample task, the monkey is shown, say, a
red light, then, after a delay, a red and a green light. The task is to
choose the red light regardless of its new location.
Fuster found that in each task certain cells in the prefrontal cortex fire
throughout the delay. Animals that have not learned the task show no
such cell activity. Curiously, if a trained animal makes an error, its
cellular activity corresponds: the cells stop responding before the error
occurs. They have “forgotten” the cue.
TRACING THE EXPLICIT MEMORY CIRCUIT People who have chronically
abused alcohol can develop an explicit memory disturbance known as
Korsakoff syndrome. In some cases, severe deficits in explicit memory
extend to implicit memory as well. Korsakoff syndrome is caused by a
thiamine (vitamin B1 ) deficiency that kills cells in the medial part of the
diencephalon—the between brain at the top of the brainstem—including
the medial thalamus and mammillary bodies in the hypothalamus. In 80
percent of Korsakoff patients, the frontal lobes show atrophy (loss of
cells). The memory disturbance is probably so severe because the
damage includes not only forebrain but also brainstem structures (see
Clinical Focus 14-4 , Korsakoff Syndrome).
Korsakoff syndrome Permanent loss of the ability to learn new
information (anterograde amnesia) and to retrieve old information
(retrograde amnesia) caused by diencephalic damage resulting from
chronic alcoholism or malnutrition that produces a vitamin B1
deficiency.
Mortimer Mishkin and his colleagues (Mishkin, 1982; Murray, 2000)
proposed a neural circuit for explicit memory that incorporates the
evidence from both humans and laboratory animals with injuries to the
temporal and frontal lobes. Figure 14-14 presents a modified version of
the Mishkin model. Anatomically (Figure 14-4 A), it includes not only
the frontal and temporal lobes but also the medial thalamus, implicated
in Korsakoff syndrome, and the basal forebrain–activating systems
implicated in Alzheimer disease. Figure 14-4 B charts the information
flow:
CLINICAL FOCUS 14-4

Korsakoff Syndrome
Over the long term, alcoholism, especially when accompanied by
malnutrition, obliterates memory. When 62-year-old Joe R. was
hospitalized, his family complained that his memory had become
abysmal. His intelligence was in the average range, and he had no
obvious sensory or motor difficulties. Nevertheless, he could not say
why he was in the hospital and usually stated that he was actually in
a hotel.
When asked what he had done the previous night, Joe R. typically
said that he “went to the Legion for a few beers with the boys.”
Although he had, in fact, been in the hospital, it was a sensible
response because going to the Legion is what he had done on most
nights in the preceding 30 years.
Joe R. was not certain what he had done for a living but believed
he had been a butcher. In fact, he had been a truck driver for a local
delivery firm. His son was a butcher, however, so once again his
story related to something in his life.
Joe’s memory for immediate events was little better. On one
occasion, we asked him to remember having met us; then we left the
room. On our return 2 or 3 minutes later, he had no recollection of
ever having met us or of having taken psychological tests that we
had administered.
Joe R. had Korsakoff syndrome. Sergei Korsakoff was a Russian
physician who in the 1880s first called attention to a syndrome that
accompanies chronic alcoholism. The most obvious symptom is
severe memory loss, including amnesia for both information learned
in the past ( retrograde amnesia ) and information learned since the
onset of the memory disturbance ( anterograde amnesia ).
retrograde amnesia Inability to remember events that took
place before the onset of amnesia.
anterograde amnesia Inability to remember events subsequent
to a disturbance of the brain such as head trauma,
electroconvulsive shock, or neurodegenerative disease.
 One unique characteristic of the amnesic syndrome in Korsakoff
patients is that they tend to make up stories about past events rather
than admit that they do not remember. These stories are generally
plausible, like those Joe R. told, because they are based on actual
experiences.
Curiously, Korsakoff patients have little insight into their memory
disturbance and are generally indifferent to suggestions that they
have a memory problem. Such patients are generally apathetic to
what’s going on around them too. Joe R. was often seen watching
television when the set was turned off.
The cause of Korsakoff syndrome is a thiamine (vitamin B1 )
deficiency resulting from poor diet and prolonged intake of large
quantities of alcohol. (In addition to a “few beers with the boys,” Joe
R. had a long history of drinking a 26-ounce bottle of rum every
day.) The thiamine deficiency results in the death of cells in the
midline diencephalon, including especially the medial regions of the
thalamus and the mammillary bodies of the hypothalamus.
Most Korsakoff patients also show cortical atrophy, especially in
the frontal lobe. With the appearance of Korsakoff symptoms, which
can happen suddenly, prognosis is poor. Only about 20 percent of
patients show much recovery after a year on a vitamin B1 –enriched
diet. Joe R. has shown no recovery after several years and will spend
the rest of his life in a hospital setting.
 Dr. Peter R. Martin from Alcohol Health & Research World, 9 (Spring
1985), cover
PET scans from a healthy patient (larger image) and a Korsakoff
patient (inset) reveal reduced activity in the frontal lobes of the
diseased brain. (The frontal lobes are at the bottom center of
each scan.) Red and yellow represent areas of high metabolic
activity; activity is lower in the darker areas.

• Sensory and motor neocortical areas send their connections to the

medial temporal regions, which are in turn connected to the medial
thalamus and prefrontal cortex.
• Basal forebrain structures are hypothesized to play a role in
maintaining appropriate activity levels in other forebrain structures so
that they can process information.
• The temporal lobe structures are hypothesized to be central to long-
term explicit memory formation.
• The prefrontal cortex is central to maintaining temporary (short-term)
explicit memories as well as memory for the recency (chronological
order) of explicit events.
(A)

(B)

Reciprocal Neural Circuit Proposed for

FIGURE 14-14

Explicit Memory (A) General neuroanatomical areas controlling

explicit memory. (B) The information flow begins on the right with inputs
from the sensory and motor systems, which are not considered part of the
explicit memory circuit.

Consolidation of Explicit Memories

Amnesia often appears to be time-dependent. H. M. could not form new
explicit memories but appeared to have good recall of facts and events
from periods long before his surgery, including his childhood. Such
findings led to the idea that the medial temporal region could not be the
ultimate storage site for long-term memories; more likely that site was
the neocortex (for a review, see Squire et al., 2015).
This idea led to the hypothesis that the hippocampus consolidates new
memories, a process that makes them permanent. In consolidation, or
stabilizing a memory trace after learning, memories move from the
hippocampus to diffuse neocortical regions. Once they move,
hippocampal involvement is no longer needed.
consolidation Process of stabilizing a memory trace after learning.
It is not clear how memories are moved, however, or how long it
takes. Robert Sutherland and his colleagues (2010) propose a model of
consolidation, the distributed reinstatement theory. In their model, a
learning episode rapidly produces a stored memory representation that is
strong in the hippocampus but weak elsewhere. The memory is replayed
on the time scale of hours or days after the learning, leading to enhanced
representations outside the hippocampus. Each repetition of the learning
—that is, each practice—progressively enhances the nonhippocampal
memory representation. Then if the hippocampus is extensively
damaged, the memory remains.
Memory is not constant over time. When people get misleading
information about events they have experienced, for example, their later
recall of those events often is modified. Indeed, this contributes to the
notorious unreliability of eyewitness testimony. (Do you remember the
“smashing” and “bumping” car collisions from Section 14-1 ?) The fact
that memories appear changeable seems to fly in the face of the
consolidation concept, which presumes that once consolidated, memories
are fixed.
One solution to this conundrum suggests that whenever a memory is
replayed in the mind, it is open to further consolidation, or
reconsolidation, the process of restabilizing a memory trace after the
memory is revisited. Interest in this idea has been intense, and although
the final story is yet to be written, it appears that reconsolidation does
occur, at least for some types of memories.
 reconsolidation Process of restabilizing a memory trace after the
memory is revisited.
One way to think of the process is to see memory consolidation as
never-ending: new information is constantly being integrated into
existing memory networks (for a review, see McKenzie and
Eichenbaum, 2011). After all, we frequently recall memories, rehash
them, and integrate them with new events. Our memories are not laid on
a tabula rasa but must be interwoven into a lifetime of memories.
One implication of reconsolidation is that it ought to be possible to
erase negative memories by using amnesic agents when the memory is
revisited. This idea has important implications for reducing or
eliminating the effects of strong emotional experiences, such as those
seen in posttraumatic stress disorder (PTSD). One promising agent is the
inert gas xenon, which has been used in humans as a fast-acting
anesthetic and has been shown to erase memories during reconsolidation
in a rat model of PTSD (Meloni et al., 2014).
Section 5-4 links sensitization to PTSD. Sections 6-5 and 12-4
document how stress fosters and prolongs its effects, and Focus 16-1
covers treatments.

Neural Circuit for Implicit Memories

Hypothesizing that the basal ganglia are central to implicit memory,
Mishkin and his colleagues proposed a neural circuit for implicit
memories (Mishkin, 1982; Mishkin et al., 1997). As Figure 14-15
shows, the basal ganglia receive input from the entire neocortex and send
projections first to the ventral thalamus and then to the premotor cortex.
The basal ganglia also receive widely and densely distributed projections
from dopamine-producing cells in the substantia nigra. Dopamine
appears necessary for basal ganglia circuits to function and may
indirectly participate in implicit memory formation.
The connection from the cortex to the basal ganglia in the implicit
memory system flows only in one direction. Most of the neocortex
receives no direct information regarding activities in the basal ganglia.
Mishkin believes that this unidirectional flow accounts for the
unconscious nature of implicit memories. For memories to be conscious,
the neocortical regions involved must receive feedback, as they do in the
explicit memory system Mishkin and colleagues proposed (see Figure
14-14 ).
 Mishkin’s models show why people with basal ganglia dysfunction,
as occurs in Parkinson disease, have implicit memory deficits. People
with frontal or temporal lobe injuries, by contrast, have relatively good
implicit memories even as they may have profound explicit memory
disturbances. Some people with Alzheimer disease can play games
expertly, even with no recollection of having played them before. Daniel
Schacter (1983) wrote of a golfer with Alzheimer disease whose medial
temporal system was severely compromised by the disease, but his basal
ganglia were unaffected. Despite his explicit knowledge impairment, as
indexed by his inability to find balls he had shot or to remember how
many strokes he made on each hole, the man retained his ability to play
the game.
(A)

(B)
 Unidirectional Neural Circuit Proposed for
FIGURE 14-15

Implicit Memory (A) Anatomical areas controlling implicit memory.

(B) Circuit diagram showing the one-way flow of implicit information,
beginning with inputs from the sensory and motor systems not considered
part of the memory circuit.

Neural Circuit for Emotional Memories

Whether emotional memory for the affective properties of stimuli or
events is implicit or explicit is not altogether clear. It could be both.
Certainly people can react with fear to specific stimuli they can identify,
and we have seen that they can also fear situations for which they do not
seem to have specific memories. Panic disorder is a common pathology
of emotional memory. People show marked anxiety but cannot identify a
specific cause. Emotional memory has a unique anatomical component
—the amygdala, which mediates fear conditioning (see Experiment 14-1
) and seems to evoke our feelings of anxiety toward stimuli that by
themselves would not typically produce fear.
Section 12-4 details the amygdala’s influence on emotional
behavior. Focus 12-3 describes panic and other anxiety disorders.
emotional memory Memory for the affective properties of stimuli
or events.
Emotional memory has been studied most thoroughly in fear
conditioning by pairing unpleasant stimuli, such as foot shock, with a
tone. Michael Davis (1992) and Joseph LeDoux (1995) used fear
conditioning to demonstrate that the amygdala is critical to emotional
memory. Damage to the amygdala abolishes emotional memory but has
little effect on implicit or explicit memory.
 The amygdala has close connections with medial temporal cortical
structures as well as with the rest of the cortex. It also sends projections
to brainstem structures that control autonomic responses such as blood
pressure and heart rate; to the hypothalamus, which controls hormonal
systems; to the periaqueductal gray matter (PAG), which affects pain
perception; and to the enteric nervous system. The amygdala hooks in to
the implicit memory system through its connections with the basal
ganglia ( Figure 14-16 ).
(A)

(B)
 Neural Circuit Proposed for Emotional
FIGURE 14-16

Memory (A) The amygdala is the key structure in emotional memory.

(B) Circuit diagram showing information flow in emotional memory.

The ANS monitors and controls life support functions (Figure 2-30
); the ENS controls the gut (Figure 2-31 ). Section 11-4 reviews the
PAG’s role in pain perception.
Fear is not the only aspect of emotional memory the amygdala codes,
as a study of severely demented patients by Bob Sainsbury and Marjorie
Coristine (1986) nicely illustrates. The patients were believed to have
severe cortical abnormalities but intact amygdalar functioning. The
researchers first established that the patients’ ability to recognize
photographs of close relatives was severely impaired.
The patients were then shown four photographs, one depicting a
relative (either a sibling or a child) who had visited in the past 2 weeks.
The task was to identify the person whom they liked better than the other
three. Although the subjects were unaware they knew anyone depicted in
the photographs, they consistently preferred pictures of their relatives.
This result suggests that although the explicit, and probably the implicit,
memory of the relative was gone, each patient‘s emotional memory
guided his or her preference.
We tend to remember emotionally arousing experiences vividly, a fact
confirmed by findings from both animal and human studies. James
McGaugh (2004) concluded that emotionally significant experiences,
pleasant and unpleasant, must activate hormonal and brain systems that
act to stamp in these vivid memories.
McGaugh noted that many neural systems probably take part, but the
basolateral part of the amygdala is critical. The general idea is that
emotionally driven hormonal and neuro-chemical activating systems
(probably cholinergic and noradrenergic) stimulate the amygdala. The
amygdala in turn modulates the laying down of emotional memory
circuits in the rest of the brain, especially in the medial temporal and
prefrontal regions and in the basal ganglia. We would not expect people
with amygdala damage to have enhanced memory for emotionladen
events, and they do not (Cahill et al., 1995).
Figure 5-17 traces neural activating system connections. Section 6-5
explains how hormones work.
 14-3 REVIEW
Neural Systems Underlying Explicit and Implicit Memories
Before you continue, check your understanding.
1 . The two key structures for explicit memory are ___________ and
___________.
2 . A system consisting of the basal ganglia and neocortex forms the
neural basis of the ___________ memory system.
3 . The ___________ and associated structures form the neural basis for
emotional memory.
4 . The progressive stabilization of memories is known as ___________.
5 . Why do we remember emotionally arousing experiences so vividly?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 14-4 Structural Basis of Brain Plasticity
We have encountered three categories of memory—explicit, implicit, and
emotional—and their underlying brain circuits. Next we consider how
the neurons in these circuits change to allow us to consolidate and store
memories. The consensus among neuroscientists is that the changes take
place at the synapse, in part simply because that is where neurons
influence one another. This idea dates to 1928, when the Spanish
anatomist Santiago Ramón y Cajal suggested that learning might
produce prolonged morphological (structural) changes in the efficiency
of synapses activated in the learning process. Cajal’s idea turned out to
be easier to propose than to study.
Researchers still encounter a major challenge as they investigate
Cajal’s suggestion because where in the brain to look for synaptic
changes that might correlate with memory for a specific stimulus is
unclear. The task is formidable. Imagine trying to find the exact location
of the neurons responsible for storing your grandmother’s name. You
would face a similar challenge in trying to pinpoint the neurons
responsible for the memory of an object in a monkey’s brain as the
monkey performs the visual recognition task illustrated in Figure 14-10
B.
Cajal’s neuron theory—that it is the nervous system’s functional unit
—is now universally accepted, including the idea that these discrete
cells’ interactions enable behavior.
One approach to finding memory’s neuronal correlates aims first to
determine that synaptic changes do correlate with memory in the
mammalian brain; second, to localize the synaptic changes to specific
neural pathways; and third, to analyze the synaptic changes themselves.
This section reviews studies that begin to show how experience
correlates with synaptic changes related to memory. We first consider a
strategy based on neuronal physiology and experience. We then look at
gross neural changes that correlate with select experiences. These range
from potentially good—living in enriched environments and learning
specific tasks—to probably bad—chronic administration of trophic
factors, hormones, and addictive drugs. Each diverse experience
modifies the brain’s general synaptic organization in a strikingly similar
manner.
Long-Term Potentiation
Findings from studies of behavioral habituation (a weakened response to
a stimulus) and sensitization (a strengthened response) in the sea slug
Aplysia show that physical changes in synapses do underlie learning.
Adaptive synapses in the mammalian brain participate in associative
learning, a response elicited by linking unrelated stimuli together—by
learning that A goes with B.
Experiment 5-2 explains habituation at the neuronal level,
Experiment 5-3 , sensitization.
associative learning Linkage of two or more unrelated stimuli to
elicit a behavioral response.
Learned associations are a common type of explicit memory.
Associating a face with a person, an odor with a food, a sound with a
musical instrument are everyday examples. Learning that learning takes
place at synapses is another. The phenomenon underlying associative
learning entails an enduring neural change in a postsynaptic cell after an
excitatory signal, or EPSP, from the presynaptic cell crosses the synaptic
gap.
Both the relatively simple circuitry of the hippocampus and the ease
of recording post-synaptic potentials there make it ideal for studying the
neural basis of associative learning. In 1973, Timothy Bliss and Terje
Lømø demonstrated that repeated electrical stimulation of the pathway
entering the hippocampus progressively increases EPSP size as recorded
from hippocampal cells. The enhancement in the size of these graded
field potentials lasts several hours to weeks or even longer. Bliss and
Lømø called it long-term potentiation (LTP), a long-lasting increase in
synaptic effectiveness after high-frequency stimulation.
Postsynaptic potentials increase (excitatory/EPSP) or decrease
(inhibitory/IPSP) the probability that an action potential will occur.
See Experiment 4-1 .
long-term potentiation (LTP) Long-lasting increase in synaptic
effectiveness after high-frequency stimulation.
Figure 14-17 A illustrates the experimental procedure for obtaining
LTP. The presynaptic neuron is stimulated electrically while the
electrical activity the stimulation produces is recorded from the
postsynaptic neuron. The readout in Figure 14-17 A shows the EPSP
produced by a single pulse of electrical stimulation. In a typical
experiment, many test stimuli are given to estimate the size of the
induced EPSP. Then a strong burst of stimulation, consisting of a few
hundred pulses of electrical current per second, is administered (Figure
14-17 B). The test pulse is then given again. The increased amplitude of
the EPSP endures for as long as 90 minutes after the high-frequency
burst: LTP has taken place. For the EPSP to increase in size, more
neurotransmitter must be released from the presynaptic membrane, or the
postsynaptic membrane must become more sensitive to the same amount
of transmitter, or both changes must take place.
(A

(B)

FIGURE 14-17 Recording Long-Term Potentiation (A)

Experimenters stimulate the presynaptic neuron with a test pulse and
record the EPSP from the postsynaptic neuron. (B) After an intense
 stimulation period, the amplitude of the EPSP produced by the test pulse
increases: LTP has taken place.

Deep brain stimulation used for severely depressed subjects induces

a change, similar to LTP, which appears to increase brain plasticity;
see Section 16-1 .
The discovery of LTP led to a revolution in thinking about how
memories are stored. As investigators varied the stimulation that
produced LTP, they discovered its opposite. Instead of using high-
frequency stimulation (e.g., 100 Hz), they used low-frequency
stimulation (e.g., 5 Hz) and recorded a decrease in EPSP size, termed
long-term depression (LTD). If LTP is a mechanism for creating
memories, perhaps LTD is a mechanism for clearing out old memories.
long-term depression (LtD) Long-lasting decrease in synaptic
effectiveness after low-frequency electrical stimulation.
If LTP and LTD form a basis for understanding synaptic changes
underlying memory, two predictions follow. First, when animals learn
problems, we should see enhanced LTP in the recruited pathways.
Second, LTP should produce enduring changes in synaptic morphology
that resemble those seen in memory. Both predictions appear to be true.
The original studies of LTP concentrated on excitatory glutamate
synapses. Glutamate is released from the presynaptic neuron and acts on
two different types of receptors on the postsynaptic membrane, the
NMDA and AMPA receptors, as shown in Figure 14-18 A . AMPA
receptors ordinarily mediate responses produced when glutamate is
released from a presynaptic membrane. They allow sodium ions (Na+ )
to enter, depolarizing and thus exciting the postsynaptic membrane. The
initial amplitude of the EPSP in Figure 14-17 A is produced by this
AMPA receptor action.
 FIGURE 14-18 Lasting Effects of Glutamate Enhanced glutamate
prompts a neurochemical cascade that underlies synaptic change and
LTP.

NMDA is shorthand for N -methyl-D -aspartate; AMPA stands for

alpha-amino-3-hydroxy-5-methylisoazole-4-proprionic acid.
NMDA receptors do not usually respond to glutamate, because their
pores are blocked by magnesium ions (Mg2+ ). NMDA receptors are
doubly gated ion channels that can open to allow the passage of calcium
ions if two events take place at approximately the same time:
1. The postsynaptic membrane is depolarized, displacing the magnesium
ion from the NMDA pore ( Figure 14-18 B). The strong electrical
stimulation delivered by the experimenter serves as a way of
displacing magnesium.
2. NMDA receptors are activated by glutamate from the presynaptic
membrane ( Figure 14-18C ).
With the doubly gated NMDA channels open, calcium ions enter the
postsynaptic neuron and act through second messengers to initiate the
cascade of events associated with LTP. These events include increased
responsiveness of AMPA receptors to glutamate, formation of new
AMPA receptors, and even retrograde messages to the presynaptic
terminal to enhance glutamate release. One or more of these actions
produce the final EPSP amplitude in Figure 14-17 B.
Although the studies generated by the Bliss and Lømø discoveries
have focused on excitatory synapses, experiments on inhibitory GABA
interneurons demonstrate phenomena similar to LTP and LTD, labeled
LTPi and LTDi. This discovery was a surprise. At the time it was
generally believed that inhibitory neurons were not plastic, but they
definitely are. It appears that plasticity of GABAergic (inhibitory)
synapses plays some fundamental role in modulating networks of
excitatory neurons.
Studying LTP mechanisms highlights neuroscientists’ uncertainty
over where plastic changes are located. Our discussion emphasizes
postsynaptic changes, but a strong case can be made that key presynaptic
changes are at work too (e.g,, MacDougall & Fine, 2014). In general,
plasticity likely requires change on both sides of the synapse. The
presynaptic side, by virtue of being activated first, may prove key in the
early phases of synaptic changes.
Measuring Synaptic Change
In principle, experience could change the brain in either of two ways: by
modifying existing circuitry or by creating novel circuitry. In actuality,
the plastic brain uses both strategies.
Modifying Existing Circuits
The simplest way to find synaptic change is to look for gross changes in
the morphology of dendrites. Essentially, dendritic spines are extensions
of the neuron membrane that allow more space for synapses. Cells that
have few or no dendrites have limited space for inputs, whereas cells
with complex dendritic protrusions may have space for tens of thousands
of inputs.
So more dendrites mean more connections. Change in dendritic
structure, therefore, implies change in synaptic organization. In complex
neurons, such as pyramidal cells, 95 percent of synapses are on the
dendrites. Measuring the extent of dendritic changes allows us to infer
synaptic change.
Figure 3-5 shows how dendrites branch from three types of neurons.
Dendritic shape is highly changeable. Dale Purves and his colleagues
(Purves & Voyvodic, 1987) labeled cells in the dorsal root ganglia of
living mice with a dye that allowed them to visualize the cells’ dendrites.
When they examined the same cells at intervals ranging from a few days
to weeks, they identified obvious qualitative changes in dendritic extent
(Figure 14-19 ). We can assume that new dendritic branches have new
synapses and that lost branches mean lost synapses.
An obvious lesson from the Purves studies is that neuronal
morphology is not static: neurons change their structure in response to
changing experiences. As they search for neural correlates of memory,
researchers can take advantage of this changeability by studying
variations in dendritic morphology that are correlated with specific
experiences, such as learning some task.
What do changes in dendritic morphology reveal? Let us consider a
given neuron that generates more synaptic space. The new synapses can
provide either additional contacts between neurons that were already
connected with that neuron or contacts between neurons not formerly
connected. Figure 14-20 illustrates examples of these distinct synapse
types.
 Focus 5-5 diagrams how dendritic spines form and explains why
they provide the structural basis for behavior.
New synapses can result either from the growth of new axon
terminals or from the formation of synapses along axons as they pass by
dendrites (Figure 14-20 A and B). In both cases, new synapses
correspond to changes in local or regional circuitry rather than to the
development of new connections between distant parts of the brain.
Forming new connections between widely separated brain regions would
be difficult in a fully grown brain: the dense plexus of cells, fibers, and
blood vessels blocks the way.
Thus, the growth of new synapses indicates modifications to basic
circuits already in the brain. This strategy has an important implication
for the location of synaptic changes underlying memory. During
development, the brain forms circuits to process sensory information and
to produce movement (behavior). These are the circuits most likely to be
modified to form memories (see Figure 14-5 ).
 FIGURE 14-19 Dendritic Plasticity Reconstructions of parts of the
dendrites from three mouse spinal ganglion cells after 3 months evince
changes in both the extension and the retraction of particular dendritic
branches. Information from D. Purves & J. T. Voyvodic (1987). Imaging
mammalian nerve cells and their connections over time in living animals.
Trends in Neuroscience, 10, p. 400.

Creating Novel Circuits

Only 25 years ago, the general assumption was that the mammalian brain
did not generate new neurons in adulthood. The unexpected discovery in
the 1970s that the brains of songbirds such as canaries grow new neurons
to produce songs in the mating season led researchers to reconsider this
assumption. They found that the adult mammalian brain, too, is capable
of generating new neurons.
This discovery emerged from directly injecting animals with a
compound—bromodeoxyuridine (BrdU)—taken up by cells when they
divide to produce new cells, including neurons. When the compound is
injected into adult rats, dividing cells incorporate it into their DNA. In
later analysis, a specific stain can identify the new neurons.
The BrdU technique yielded considerable evidence that the
mammalian brain, including the primate brain, can generate neurons
destined for the olfactory bulb, the hippocampal formation, and possibly
even the frontal and temporal lobe neocortex (Eriksson et al., 1998;
Gould et al., 1999). The reason is not yet clear, but adult neurogenesis
may enhance brain plasticity, particularly in processes underlying
learning and memory. Elizabeth Gould and her colleagues (1999)
showed, for example, that generation of new neurons in the hippocampus
is enhanced when animals learn explicit memory tasks.
Experiment 7-1 confirms the hypothesis that hippocampal neurons
contribute to memory formation.
Experience appears to increase the generation of these new neurons.
A fascinating demonstration of experience driving neurogenesis comes
from a study by Katherine Woollett and Eleanor Maguire (2011). We
noted in Section 14-3 that London taxi drivers, who must learn the
locations of and pass an exam on central London’s roughly 25,000
irregular streets, have larger-than-normal volume in their hippocampal
posterior region. The investigators asked whether the increase resulted
from taking a 4-year course to pass the exam or was already present
when the candidate drivers started the course.
(A) Before experience

(B) After experience

 (C) Various observed shapes of new dendritic spines

FIGURE 14-20 Effects of Experience on Dendrites (A) Three

inputs to a pyramidal cell dendrite. Each axon forms a synapse with a
different dendritic spine. (B) In forming multiple spine heads, either the
original axons can divide and innervate two spine heads or new axons or
axon collaterals (dotted outlines) can innervate the new spine heads. (C)
Single dendritic spines may sprout multiple synapses.

Woollett and Maguire recorded structural MRIs from the would-be

taxi drivers before and after training, then compared the trainees who
qualified (n = 39) to those who failed (n = 20). The images in Figure 14-
21 show that hippocampal volume increased in the qualifiers. Those who
failed showed no changes. The trainees’ average age was about 40 years,
leading Woollett and Maguire to conclude that the capacity for memory
improvement and correlated structural changes in the hippocampus
extends well into adulthood.
 FIGURE 14-21 Learning Effects on Hippocampal Volume
After a 4-year course devoted to learning London’s street layout, trainees
who qualified as licensed taxi drivers show increased gray matter volume
in the most posterior part of the hippocampus (orange and yellow areas).
Republished with permission of Elsevier Science and Technology Journals, from Woollett, K.
and Maguire, E.A. (2011) Acquiring “the knowledge” of London’s layout
drives structural brain changes. Current Biology, 21, 2109–2114.
Permission conveyed through Copyright Clearance Center, Inc.

Enriched Experience and Plasticity

One way to stimulate animals’ brains is to house the animals in
environments that provide sensory or motor experience. Donald Hebb
(1947) took laboratory rats home and gave them the run of his kitchen.
After an interval, Hebb compared these “enriched” rats with a group that
had remained caged in his laboratory at McGill University: he trained
both groups to solve various mazes. The enriched animals performed
better, and Hebb concluded that one effect of the enriched experience is
to enhance later learning. This important conclusion laid the foundation
for the U.S. Head Start programs, which provide academic experience
for preschool-aged children living in under-resourced environments.
Section 8-4 details Hebb’s first enrichment exercise—and his wife’s
reaction.
Subsequent investigators have opted for a more constrained enriched
enclosure. For example, in our own studies, we place groups of about six
rats in enclosures. The enclosures give animals a rich social experience
as well as extensive sensory and motor experience. The most obvious
consequence is increased brain weight—on the order of 10 percent
relative to cage-reared animals—even though the “enriched” rats
typically weigh less, in part because they get more exercise.
The key question is: What is responsible for the increased brain
weight? A comprehensive series of studies by Anita Sirevaag and
William Greenough (1988) used light- and electron-microscopic
techniques to analyze 36 aspects of cortical synaptic, cellular, and
vascular morphology in rats raised either in a cage or in a complex
environment. The simple conclusion: in response to differential
experiences a coordinated change occurs not only in dendritic extent but
also in glial, vascular, and metabolic processes ( Figure 14-22 ).
Enriched Enclosure for Rats
 Animals with enriched experience have more synapses per neuron and
also more astrocytes, more blood capillaries, and higher mitochondrial
volumes. Clearly, when the brain changes in response to experience, the
expected neural changes take place, and adjustments in the metabolic
requirements of the now larger neurons take place as well.
Gerd Kempermann and his colleagues (1998) sought to determine
whether experience actually alters the number of neurons in the brain. To
test this idea, they compared neuronal generation in the hippocampi of
mice housed in a complex environment with that of mice reared in a
laboratory cage. They located the number of new neurons by injecting
the animals with BrdU several times while they were living in complex
housing.
Mitochondria power the cell. Figure 3-10 diagrams these organelles
in the context of the neuron’s other internal components.
The new neurons generated in the brain during the experiment
incorporated the BrdU. When the researchers later looked at the
hippocampi, they found more new neurons in the complex-housed rats
than in the caged rats. Although the investigators did not look in other
parts of the brain, such as the olfactory bulb, we can reasonably expect
that similar changes took place in other neural structures. This result is
exciting because it implies that experience not only can alter existing
circuitry but also can influence neurogenesis and thus new circuitry.
 FIGURE 14-22 Consequences of Enrichment Cortical changes
that occur in response to experience are found not only in neurons but
also in astrocytes and vasculature. Data from A. Turner & W. T.
Greenough (1985). Differential rearing effects on rat visual cortex
synapses. I. Synaptic and neuronal density and synapses per neuron.
Brain Research, 329, pp. 195–203 No ref.3; A. M. Sirevaag & W. T.
Greenough (1987). Differential rearing effects on rat visual cortex
synapses. III. Neuronal and glial nuclei. Brain Research, 424, pp. 320–
332; and B. Kolb, R. Gibb, & G. Gorny (2003). Experience-dependent
changes in dendritic arbor and spine density in neocortex vary with age
and sex Neurobiology of Learning and Memory, 79, pp. 1–10.

Sensory or Motor Training and Plasticity

Studies showing neuronal change in animals housed in a complex
environment demonstrate that large areas of the brain can change with
such experience. This finding leads us to ask whether specific
experiences produce synaptic changes in localized cerebral regions. One
way to approach this question is to give animals specific experiences,
then see how their brain has changed. Another way is to look at the brain
of people who have had a lifetime of some particular experience. We
consider each research strategy separately.
Manipulating Experience Experimentally
Fen-Lei Chang and William Greenough (1982) conducted perhaps the
most convincing manipulated-experience study. They took advantage of
the fact that the laboratory rat’s visual pathways are about 90 percent
crossed. That is, about 90 percent of connections from the left eye to the
cortex project through the right thalamus to the right hemisphere and
vice versa for the right eye.
In humans, only about half the optic fibers cross. Figure 9-10
diagrams the pathways.
Chang and Greenough placed a patch over one eye of each rat, then
trained the animals in a maze. The visual cortex of only one eye received
input about the maze, but their two hemispheres’ auditory, olfactory,
tactile, and motor regions were equally active as the animals explored. A
comparison of the neurons in each hemisphere revealed that those in the
visual cortex of the trained hemisphere had more extensive dendrites.
Because the hemispheres did not differ in other respects, the researchers
concluded that some feature associated with encoding, processing, or
storage of visual input from training was responsible for forming new
synapses.
 Randy Nudo and his colleagues (1997) conducted complementary
studies, mapping the motor cortex of monkeys. They noted striking
individual differences in topography. The investigators speculated that
individual variability might be due to each monkey’s experiences up to
the time at which the cortical map was derived. To test this idea directly,
Nudo and colleagues trained two groups of squirrel monkeys to retrieve
banana-flavored food pellets from either a small or a large food well. A
monkey was able to insert its entire hand into the large well but only one
or two fingers into the small well, as illustrated in the Procedures section
of Experiment 14-2 .
Monkeys in the two groups were matched for number of finger
flexions, which totaled about 12,000 for the entire study. The monkeys
trained on the small well improved with practice, making fewer finger
flexions per food retrieval as training proceeded. Maps of forelimb
movements, shown in the Results section, were produced by
microelectrode stimulation of the cortex. The maps show systematic
changes in the animals trained on the small but not on the large well.
Presumably, these changes result from the more demanding motor
requirements of the small-well condition. The results demonstrate that
learning new motor skills, not simply repetitive motor use, shapes the
functional topography of the motor cortex.
Most studies demonstrating plasticity in the motor cortex have been
performed with laboratory animals whose cortex was mapped by
microelectrode stimulation. Today, imaging techniques such as
transcranial magnetic stimulation (TMS) and functional magnetic
resonance imaging (fMRI) make it possible to show parallel results in
humans who have special motor skills. For example, right-handed
musicians who play stringed instruments show an increased cortical
representation of the fingers of the left hand and Braille readers an
increased cortical representation of the reading finger.
Thus, the functional organization of the motor cortex is altered by
skilled use in humans. It can also be altered by chronic injury in humans
and laboratory animals. Jon Kaas (2000) showed that when the sensory
nerves in one limb are severed in monkeys, large-scale changes in
somatosensory maps ensue. In particular, in the absence of input, the
relevant part of the cortex no longer responds to limb stimulation, which
is not surprising. But this cortex does not remain inactive. Rather, the
deafferented cortex begins to respond to input from other body parts. The
region that formerly responded to hand stimulation now responds to
stimulation on the face, a cortical area normally adjacent to the hand
area.
Similar results can be found in the cortical maps of people whose
limb has been amputated. For example, Vilayanur Ramachandran (1993)
found that when a hand amputee’s face is brushed lightly with a cotton
swab, the person has a sensation of the amputated hand being touched.
Figure 14-23 illustrates the rough map of the hand that Ramachandran
was actually able to chart on the face. The likely explanation is that the
face area in the motor cortex has expanded to occupy the deafferented
limb cortex, but the brain circuitry still responds to the cortical activity
as representing input from the limb. This response may explain the
phantom limb pain often experienced by amputees.
 EXPERIMENT 14-2

Question: Does the learning of a fine motor skill alter the

cortical motor map?
Procedures
Difficult task

Simple task
Both groups were allowed 12,000 finger flexions.
The small-well task was more difficult and required
the learning of a fine motor skill in order to match
performance of the simpler task.
Results
The motor representation of digit, wrist, and arm
was mapped.
Conclusion: The digit representation in the brain of the animal with the
more difficult task is larger, corresponding to the neuronal changes
necessary for the acquired skill.
Information from R. J. Nudo, E. J. Plautz, & G. W. Miliken (1997).
Adaptive plasticity in primate motor cortex as a consequence of
 behavioral experience and neuronal injury. Seminars in Neuroscience, 9,
p. 20.

(A)

(B)
FIGURE 14-23 Cortical Reorganization When a hand amputee’s face is stroked
lightly with a cotton swab (A), the person experiences the stroke as a light touch on the
missing hand (B) as well as a touch to the face. The deafferented cortex forms a
representation of the amputated hand on the face. As in the normal somatosensory
homunculus, the thumb is disproportionately large. Information from V. S.
Ramachandran (1993). Behavioral and magnetoencephalographic correlates of
plasticity in the adult human brain. Proceedings of the National Academy of Sciences
USA, 90, p. 10418.

The idea that experience can alter cortical maps can be demonstrated
with other experiences. For example, if animals are trained to make
certain digit movements over and over again, the cortical representation
of those digits expands at the expense of the remaining motor areas.
Similarly, if animals are trained extensively to discriminate among
different sensory stimuli such as tones, the auditory cortical areas
responding to those stimuli increase in size.
Focus 11-5 recounts Ramachandran’s therapy for minimizing
phantom limb pain.
As described in Research Focus 14-5 , Movement, Learning, and
Neuroplasticity, one effect of musical training is to alter the motor
representations of the digits used to play different instruments. We can
speculate that musical training probably alters the auditory
representations of specific sound frequencies as well. Both changes are
essentially forms of memory, and the underlying synaptic changes likely
take place on the appropriate sensory or motor cortical maps.
Sections 10-4 and 15-4 discuss music’s benefits for the brain.
RESEARCH 14-5

Movement, Learning, and Neuroplasticity

Many lines of research show that practicing a motor skill—playing a
musical instrument, for instance—induces changes in the cortical
somatosensory and motor maps. The mental maps generally become
larger, at least the finger and hand representations.
Presumably, musical skill improves with practice, but are other
abilities enhanced too? Patrick Ragert and colleagues (2003) showed
that professional pianists not only have better motor skills in their
fingers but enhanced somatosensory perception as well.
When the researchers measured the ability to detect subtle sensory
stimulation of the fingertips, they found that the pianists were more
sensitive than controls. They also found that the enhanced tactile
sensitivity was related to the hours per day that the musicians spent
practicing.
The investigators then asked whether the enhanced perceptual ability
precluded further improvement in the musicians. Surprisingly, when
both the musicians and controls were given a 3-hour training session
designed to improve tactile sensitivity, the musicians showed more
improvement than did the controls. Again the extent of improvement
correlated with daily practice time.
This result implies that well-practiced musicians not only learn to
play music but also develop a greater capacity for learning. Rather than
using up all the available synapses, they gain the capacity to make even
more.
Not all motor learning is good, however. Many musicians develop
focal hand dystonia— abnormal finger and hand positions, cramps, and
difficulty in coordinating hand and finger movements. Dystonia can be
so disabling that some musicians must give up their occupation.
Typically, dystonia afflicts musicians who practice trying to make
perfect finger movements on their instruments. Musicians at high risk
include string players, who receive vibratory stimulation at their
fingertips. The constant practice has been suggested to lead not only to
improved musical ability but also to distorted or disordered cortical
motor maps. Synchronous activation of the digits by the vibration leads
to this unwanted side effect.
Victor Candia and colleagues (2003) reasoned that musicians’
dystonia was probably an example of disordered learning and could be
treated by retuning the motor map. The investigators used
magnetoencephalography (MEG) to measure changes in sensory-
evoked magnetic fields in the cortex.
At the beginning of the study, the musicians with dystonia had a
disordered motor map: the finger areas overlapped one another. In
training, each subject used a hand splint tailored to his or her hand. The
splint allowed for immobilizing different fingers while the subjects
independently moved the others.
After 8 days of training for about 2 hours per day, the subjects
showed marked alleviation in the dystonic symptoms, and the neuro-
imaging showed a normalization of the cortical map, with distinct
finger areas. Thus, training reversed the learned changes in the motor
map and treated the dystonia. The musicians had actually learned a
disorder, and they were able to unlearn it.
© Michel Garnier/Lebrecht Music & Arts/Corbis
Experience-Dependent Change in the Human
Brain
According to Ramachandran’s amputee study, the human brain appears to
change with altered experience. But this study did not examine neuronal
change directly; it inferred neuronal change from behavior. The only way to
examine synaptic change directly is to look directly at brain tissue. In living
humans, this is not an option, but the brain of people who died of something
other than neurological causes can be examined and the structure of their
cortical neurons related to their experiences.
One way to approach this idea is to look for a relation between neuronal
structure and education. Arnold Scheibel and his colleagues conducted
many such studies in the 1990s (e.g., Jacobs and Scheibel, 1993; Jacobs,
Scholl, and Scheibel, 1993). In one, they found a relation between dendrite
size in Wernicke’s area and level of education. In the brain of deceased
people with a college education, the cortical neurons from this language
area had more dendritic branches than did those from people with a high-
school education, which in turn, had more dendritic material than did those
from people with less education. People who have more dendrites may be
more likely to go to college, but that hypothesis is not easy to test.
Wernicke’s area contributes to speech and to language comprehension;
see Figure 10-18 .
Another way to look at the relation between neurons in Wernicke’s area
and behavior is to take advantage of the now well-documented observation
that on average females’ verbal abilities are superior to those of males.
When Scheibel and his colleagues examined the structure of neurons in
Wernicke’s area, they found that females do have more extensive dendritic
branching there than males do.
Figure 15-16 diagrams tasks that consistently show, on average, that
females’ verbal fluency surpasses males’ and that males outperform
females on spatial reasoning tasks.
Finally, these investigators took a slightly different approach to the link
between experience and neuronal morphology. They began with two
hypotheses. First, they suggested a relation between the complexity of
dendritic branching and the nature of the computational tasks performed by
a brain area.
 To test this hypothesis, they examined the dendritic structure of neurons
in different cortical regions that handle different computational tasks. For
example, when they compared the structure of neurons corresponding to the
somatosensory representation of the trunk with those for the fingers, they
found the latter to have more complex cells ( Figure 14-24 ). They reasoned
that the somatosensory inputs from receptive fields on the chest wall would
constitute less of a computational challenge to cortical neurons than would
those from the fingers and that the neurons representing the chest would
therefore be less complex.
The group’s second hypothesis was that dendritic branching in all
regions is subject to experience-dependent change. The researchers
hypothesized that predominant life experience (e.g., occupation) should, as
a result, alter dendritic structure. Although they did not test this hypothesis
directly, they did make an interesting observation. In their study comparing
cells in the trunk area, in the finger area, and in the supramarginal gyrus—a
parietal lobe region associated with higher cognitive processes (thinking)—
they found curious individual differences.
For example, especially large differences in trunk and finger neurons
appeared in the brain of people who had a high level of finger dexterity
maintained over long periods (say, career word processors). In contrast, no
difference between trunk and finger neurons was found in sales
representatives. Remember, Scheibel and colleagues conducted their
research before portable electronic devices entered the workplace. We
would not expect a good deal of specialized finger use among sales reps of
that time and thus less complex demands on their finger neurons.
In summary, although the studies showing a relation between experience
and neuronal structure in humans depend on correlations rather than actual
experiments, the findings are consistent with those observed in
experimental studies of other species. We are thus led to the general
conclusion that specific experiences can produce localized changes in the
synaptic organization of the brain and that such changes form the structural
basis of memory.
FIGURE 14-24 Experience and Neuronal Complexity Confirmation of Scheibel’s
hypothesis that cell complexity is related to the computational demands required of the cell.
Neurons that represent the body’s trunk area have relatively less computational demand
than do cells representing the finger region. In turn, cells engaged in higher cognitive
functions (such as language, as in Wernicke’s area) have greater computational demand
than do those engaged in finger functions.

Epigenetics of Memory
An enigma in the search for neural mechanisms underlying memory is the
fact that whereas memories remain stable over time, all cells are constantly
undergoing molecular turnover. The simplest explanation for this is
epigenetic: specific sites in the DNA of neurons involved in specific
memories might exist in either a methylated or a nonmethylated state.
Courtney Miller and colleagues (2010) tested this idea directly by
measuring methylation in the hippocampi of rats that underwent contextual
fear conditioning (see Experiment 14-1 ). They showed that fear
conditioning is associated with rapid methylation, but if they blocked
methylation, there was no memory. The investigators conclude that
epigenetic mechanisms mediate synaptic plasticity broadly, but especially in
learning and memory. One implication of these results is that cognitive
disorders, including memory defects, could result from aberrant epigenetic
modifications (for a review, see Day et al., 2015).
Figure 3-25 illustrates two aspects of methylation: histone and DNA
modification.

Plasticity, Hormones, Trophic Factors, and

Drugs
The news media often report that psychoactive drugs can damage your
brain. Some drugs certainly do act as toxins and can selectively kill brain
regions, but a more realistic mode of drug action is to change the brain.
Although not many studies have looked at drug-induced morphological
changes, evidence reveals that some compounds can greatly change the
brain’s synaptic organization. These compounds include hormones,
neurotrophic factors, and psychoactive drugs. We briefly consider each
category.
Hormones and Plasticity
Levels of circulating hormones are critical both in determining brain
structure and in eliciting certain behaviors in adulthood. Although the
structural effects of hormones were once believed to be expressed only in
the course of development, current belief is that adult neurons also can
respond to hormonal manipulations with dramatic structural changes. We
consider the actions of gonadal hormones and stress hormones here.
Section 6-5 explains the classes, functions, and control that hormones
exert; Section 8-4 , their organizing effects during development;
Section 12-5 , their activating effects in adulthood.
Research findings have established that structural differences in cortical
neurons of male and female rats depend on gonadal hormones. More
surprising, perhaps, is that gonadal hormones continue to influence cell
structure and behavior in adulthood. Elizabeth Hampson and Doreen
Kimura (1988) showed that women’s performance on various cognitive
tasks changes throughout the menstrual cycle as their estrogen levels
fluctuate.
Changes in estrogen level appear to alter the structure of neurons and
astrocytes in the neocortex and hippocampus, which probably accounts for
at least part of the performance fluctuation. Figure 14-25 illustrates
changes in dendritic spines in the hippocampal cells of female rats at
different phases of their 4-day estrous cycle. As the estrogen level rises, the
number of synapses rises; as the estrogen level drops, the number of
synapses declines.
Curiously, estrogen’s influence on cell structure may differ in the
hippocampus and neocortex. Jane Stewart found, for example, that when
the ovaries of middle-aged female rats are removed, estrogen levels drop
sharply, producing increased numbers of spines on pyramidal cells
throughout the neocortex but decreased spine density in the hippocampus
(Stewart & Kolb, 1994). How these synaptic changes might influence
processes such as memory is not immediately obvious, but the question is
reasonable, especially because menopausal women also experience sharp
drops in estrogen levels and a corresponding decline in verbal memory
ability.
This question is also relevant to middle-aged men, who show a slow
decline in testosterone levels that correlates with a drop in spatial ability.
Rats that are gonadectomized in adulthood show increased cortical spine
density, much like the ovariectomized females. Although we do not know
how this change relates to spatial behavior, a reasonable supposition is that
testosterone levels might influence spatial memory throughout life.
 FIGURE 14-25 Hormones and Neuroplasticity Sections of dendrites
from hippocampal cells during times of high and low estrogen levels during
the rat’s 4-day estrous cycle reveal many more dendritic spines when
estrogen levels are high. Information from C. S. Woolley, E. Gould, M.
Frankfurt, & B. S. McEwen (1990). Naturally occurring fluctuation in dendritic
spine density on adult hippocampal pyramidal neurons. Journal of
Neuroscience, 10, p. 4038.

When the body is stressed, the pituitary gland produces

adrenocorticotrophic hormone (ACTH), which stimulates the adrenal cortex
to produce steroid hormones, the glucocorticoids. Important in protein and
carbohydrate metabolism, controlling sugar levels in the blood, and the
absorption of sugar by cells, glucocorticoids have many actions on the
body, including the brain. Robert Sapolsky (1992) proposed that
glucocorticoids can sometimes be neurotoxic.
In particular, he found that with prolonged stress, glucocorticoids appear
to kill hippo-campal cells. Elizabeth Gould and her colleagues (1998)
showed that even brief periods of stress can reduce the number of new
granule cells produced in the hippocampi of monkeys, presumably through
the actions of stress hormones. Evidence of neuron death and reduced
neuron generation in the hippocampus has obvious implications for animal
behavior, especially for processes such as spatial memory. Finally, Richelle
Mychasiuk and her colleagues (2015) showed that stress has contrasting
epigenetic effects in the hippocampus and prefrontal cortex, with virtually
no overlap between males and females.
Figure 6-23 illustrates the body’s stress response.
In sum, hormones can alter the brain’s synaptic organization and even
the number of neurons in the brain. Little is known today about the
behavioral consequences of such changes. It is likely that hormones can
alter the course of plastic changes in the brain, possibly through epigenetic
mechanisms.
Neurotrophic Factors and Plasticity
Neurotrophic factors, chemical compounds listed in Table 14-2 that signal
stem cells to develop into neurons or glia, also act to reorganize neural
circuits. The first, nerve growth factor (NGF), was discovered in the
peripheral nervous system more than a generation ago. NGF is trophic
(nourishing) in the sense that it stimulates neurons to grow dendrites and
synapses and in some cases promotes neuronal survival.
nerve growth factor (nGF) Neurotrophic factor that stimulates
neurons to grow dendrites and synapses and in some cases promotes
the survival of neurons.
Section 8-2 explains how neurotrophic factors send these signals.
Trophic factors produced in the brain by neurons and glia can affect
neurons both through cell membrane receptors and by actually entering the
neuron to act internally on its operation. Trophic factors may be released
postsynaptically, for example, to act as signals that can influence the
presynaptic cell. Experience stimulates their production, so neurotrophic
factors have been proposed as agents of synaptic change. For example,
brain-derived neurotrophic factor (BDNF) increases when animals solve
specific problems such as mazes. This finding has led to speculation that
BDNF release may enhance such plastic changes as the growth of dendrites
and synapses.
A Hebb synapse—one that changes with use so that learning takes
place—hypothetically employs just such a mechanism; see Section 5-4
.
Although many researchers would like to conclude that BDNF has a role
in learning, this conclusion does not necessarily follow. When animals
solve mazes, their behavior differs from their behavior when they remain in
cages. So we must first demonstrate that changes in BDNF, NGF, or any
trophic factor are actually related to forming new synapses. Nevertheless, if
we assume that trophic factors do act as synaptic change agents, then we
should be able to use increased trophic factor activity during learning as a
marker for where to look for changed synapses associated with learning and
memory.
TABLE 14-2 Molecules Exhibiting Neurotrophic Activities
Proteins initially characterized as neurotrophic factors

Nerve growth factor (NGF)

Brain-derived neurotrophic factor (BDNF)

Neurotrophin 3 (NT-3)
 Ciliary neurotrophic factor (CNTF)

Growth factors with neurotrophic activity

Fibroblast growth factor, acidic (aFGF or FGF-1)

Fibroblast growth factor, basic (bFGF or FGF-2)

Epidermal growth factor (EGF)

Insulinlike growth factor (ILGF)

Transforming growth factor (TGF)

Lymphokines (interleukin 1, 3, 6 or IL-1, IL-3, IL-6)

Protease nexin I, II

Cholinergic neuronal differentiation factor

Psychoactive Drugs and Plasticity

Many people regularly use the stimulant caffeine, and some use more
stimulating psychoactive drugs such as nicotine, amphetamine, or cocaine.
The long-term consequences of abusing psychoactive drugs are now well
documented, but the question of why these drugs cause problems remains to
be answered. One explanation for the behavioral changes associated with
chronic psychoactive drug abuse is that the drugs change the brain.
One experimental demonstration of these changes is drug-induced
behavioral sensitization, often referred to simply as behavioral
sensitization, the progressive increase in behavioral actions in response to
repeated administration of a drug. Behaviors increase even when the
amount given in each dose does not change. Behavioral sensitization occurs
with most psychoactive drugs, including amphetamine, cocaine, morphine,
and nicotine.
behavioral sensitization Escalating behavioral response to the
repeated administration of a psychomotor stimulant such as
amphetamine, cocaine, or nicotine; also called drug-induced
behavioral sensitization.
The sea slug Aplysia becomes more sensitive to a stimulus after repeated
exposure. Psychoactive drugs appear to have a parallel action: they lead to
increased behavioral sensitivity to their actions. For example, a rat given a
small dose of amphetamine may show increased activity. When the rat is
given the same dose of amphetamine on subsequent occasions, the increase
in activity is progressively larger. If no drug is given for weeks or even
months and then amphetamine is given in the same dose as before,
behavioral sensitization picks up where it left off and continues to progress.
Some long-lasting change must have taken place in the brain in response to
the drug. Drug-induced behavioral sensitization can therefore be viewed as
a memory for a particular drug.
The parallel between drug-induced behavioral sensitization and other
forms of memory leads us to ask if the changes in the brain after behavioral
sensitization are similar to those found after other forms of learning. They
are. For example, there is evidence of increased numbers of receptors at
synapses and of more synapses in sensitized animals.
In a series of studies, Terry Robinson and his colleagues found dramatic
increases in dendritic growth and spine density in rats sensitized to
amphetamine, cocaine, or nicotine relative to rats that received injections of
a saline solution (Robinson & Kolb, 2004). Experiment 14-3 compares the
effects of amphetamine and saline treatments on cells in the nucleus
accumbens in the basal ganglia. Neurons in amphetamine-treated brains
have more dendritic branches and increased spine density. Repeated
exposure to psychoactive stimulants thus alters the structure of brain cells.
These changes in turn may be related to learned addictions.
These plastic changes were not found throughout the brain. Rather, they
were localized to regions such as the prefrontal cortex and nucleus
accumbens that receive a large dopamine projection. Dopa-mine is believed
to factor significantly in the rewarding properties of drugs (Wise, 2004).
Other psychoactive drugs also appear to alter neuronal structure. Marijuana,
morphine, and certain antidepressants change dendritic length and spine
density, although in ways different from those of stimulants. Morphine, for
example, reduces dendritic length and spine density in the nucleus
accumbens and prefrontal cortex (Robinson & Kolb, 2004).
What do drug-induced changes in synaptic organization mean for later
experience-dependent plasticity? If rats are given amphetamine, cocaine, or
nicotine for 2 weeks before being placed in a complex environment, the
expected increases in dendritic length and spine density in the cortex do not
happen (Kolb et al., 2003). This is not because the brain can no longer
change: giving the animals additional drug doses can still produce change.
Rather, something about prior drug exposure alters the way in which the
brain later responds to experience.
Why prior drug exposure has this effect is as yet unknown, but obviously
drug taking can have long-term effects on brain plasticity. One possible
explanation is epigenetic. Giving animals repeated doses of amphetamine or
nicotine decreases methylation in both the prefrontal cortex and the nucleus
accumbens, and decreased methylation is related to drug-and region-
specific increases in gene expression (Mychasiuk et al., 2013). These
epigenetic changes may render the synapses less able to change in response
to later experiences.
Figure 12-30 shows enhanced connectivity in prefrontal and limbic
circuits in nicotine-dependent smokers.
 EXPERIMENT 14-3

Question: What effect do repeated doses of amphetamine, a

psychomotor stimulant, have on neurons?

Conclusion: The sensitization induced by repeated exposure to

amphetamine changes the structure of neurons in certain brain areas.
Information from T. E. Robinson & B. Kolb (1997). Persistent structural
adaptations in nucleus accumbens and prefrontal cortex neurons
produced by prior experience with amphetamine. Journal of
Neuroscience, 17, p. 8496.

Some Guiding Principles of Brain Plasticity

Brain plasticity will continue as a fundamental concept underlying
research into brain–behavior relationships through the coming decades.
Some basic rules have emerged to guide this research (see Kolb and
Gibb, 2014, for more details). Here we list seven.
1. Behavioral Change Reflects Brain Change
The brain’s primary function is to produce behavior, but behavior is not
static. We learn and remember, we think new thoughts or visualize new
images, and we change throughout life. All these processes require
changes in neural networks. Whenever neural networks change,
behavior, including mental behavior, also changes. A corollary is
especially important as neuroscientists search for treatments for brain
injuries or behavioral disorders: To change behavior, we must change the
brain.
2. All Nervous Systems Are Plastic in the Same General Way
Even the simplest animals, such as the roundworm C. elegans, can show
simple learning that correlates with neuronal plasticity. The molecular
details may differ between simple and complex systems, but the
principles of neuroplasticity appear to be conserved across both simple
and complex animals. This conservation allows more studies of neural
plasticity among a wider range of animal species than in most areas of
neuroscience.
Investigators study neuroplasticity in species ranging from worms
and insects to fish, birds, and mammals.
3. Plastic Changes Are Age-Specific
The brain responds to the same experiences differently at different ages
—and especially during development. The prefrontal cortex is late to
mature, for example, so the same experience affects this region
differently in infancy than it does in adolescence and on throughout life.
Section 8-4 traces how brain organization details change rapidly—
and sometimes critically—during development.
4. Prenatal Events Can Influence Brain Plasticity Throughout
Life
Prenatal experiences can alter brain organization. Potentially negative
experiences, such as prenatal exposure to recreational or prescription
drugs, and positive experiences, such as tactile stimulation of the
mother’s skin, may alter gene expression or induce other epigenetic
effects that produce enduring effects on brain organization. Even paternal
or maternal experiences before conception can alter later offsprings’
brain development and organization.
Section 8-4 recounts benefits of tactile stimulation; Focus 8-2,
epigenetic factors in the autism spectrum; Focus 6-2, the tragedy of
fetal alcohol spectrum disorder.
5. Plastic Changes Are Brain Region Dependent
Although we are tempted to expect plastic changes in neuronal networks
to be fairly general, it is becoming clear that many experience-dependent
changes are highly specific. We saw this specificity in the effects of
psychoactive drugs on the prefrontal cortex but not on other cortical
regions. Not only do drugs selectively change the prefrontal cortex but
the dorsolateral and orbital prefrontal areas also show opposite changes
—the precise changes varying with the particular drug. For example,
stimulants such as amphetamine increase spine density in the
dorsolateral region but decrease it in the orbital region.
Figure 12-19 diagrams these prefrontal regions.
6. Experience-Dependent Changes Interact
Metaplasticity is a property of a lifetime’s interaction among different
plastic changes in the brain. As an animal travels through life, infinite
experiences can alter its brain organization. A lifetime’s experiences
might interact. Housing animals in complex environments produces
profound changes in their neural network organization, but prior
exposure to psychoactive drugs completely blocks the enrichment effect.
Conversely, although complex housing does not block drug effects,
enrichment markedly attenuates them. Prenatal events can affect later
drug effects: prenatal tactile stimulation of the mother, for example,
reduces the later effects of psychoactive drugs on the child.
metaplasticity Interaction among different plastic changes in the
brain.
7. Plasticity Has Pros and Cons
We have mainly emphasized the neuroplastic changes that can support
improved motor and cognitive function. But as noted for the effects of
psychoactive drugs, plastic changes in neural networks can also interfere
with behavior. Drug addicts whose prefrontal cortex has been altered are
prone to poor judgment in their personal life. People who have
posttraumatic stress disorder show altered blood flow in the amygdala
and cingulate cortex. That’s the bad news.
Encouraging plastic changes that reverse these prefrontal alterations is
the good news, and it is associated with a loss of the prefrontal disorder.
Age-related dementia is related to synaptic loss that various forms of
cognitive therapy can reverse (e.g., Mahncke, Bronstone, & Merzenich,
2006).
 14-4 REVIEW
Structural Basis of Brain Plasticity
Before you continue, check your understanding.
1 . Repeated high-frequency stimulation of excitatory neurons leads to
the phenomenon of ___________, whereas repeated low-frequency
stimulation leads to ___________.
2 . LTPi and LTDi are found in ___________ neurons.
3 . Structural changes underlying memory include changes in both
___________ and ___________.
4 . Learning complex spatial information has been linked to increased
gray matter in the ___________.
5 . The progressive increase in behavioral actions in response to repeated
administration of a drug is called ___________.
6 . How can plastic changes in the brain produce adverse effects?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 14-5 Recovery from Brain Injury
The nervous system appears conservative in its use of mechanisms
related to behavioral change. If neuroscientists wish to change the brain,
as after injury or disease, then they should look for treatments that will
produce plastic changes related to learning, memory, and other
behaviors.
Recall that H. M. failed to recover his lost memory capacities, even
after 55 years of practice in trying to remember information. Relearning
simply was not possible for H. M. He had lost the requisite neural
structures. But other people do show some recovery.
An average person would probably say that the recovery process after
brain trauma requires the injured person to relearn lost skills, whether
walking, talking, or using the fingers. But what exactly does recovery
entail? Partial recovery of function is common after brain injury, but a
person with brain trauma or brain disease has lost neurons. The brain
may be missing structures critical for relearning or remembering.

Donna’s Experience with Traumatic Brain

Injury
Donna started dancing when she was 4 years old, and she was a natural.
By the time she finished high school, she had the training and skill
necessary to apprentice with and later join a major dance company.
Donna remembers vividly the day she was chosen to dance a leading role
in The Nutcracker. She had marveled at the costumes as she watched the
popular Christmas ballet as a child, and now she would dance in those
costumes!
The births of two children interrupted her career as a dancer, but
Donna never lost the interest. In 1968, when both her children were in
school, she began dancing again with a local company. To her
amazement, she could still perform most of the movements, although she
was rusty on the choreography of the classical dances that she had once
memorized so meticulously. Nonetheless, she quickly relearned. In
retrospect, she should not have been so surprised, because she had
always had an excellent memory.
 One evening in 1990, while on a bicycle ride, a drunk driver struck
Donna. She was wearing a helmet but received a brain-damaging blow to
the head—a traumatic brain injury, or TBI. She was comatose for
several weeks. As she regained consciousness, she was confused and had
difficulty talking to and understanding others. Her memory was very
poor; spatial disorientation meant she often got lost; she endured various
motor disturbances; and she had difficulty recognizing anyone but her
family and closest friends.
traumatic brain injury (TBI) Damage to the brain that results
from a blow to the head.
Focus 1-1 and Section 1-2 introduce consequences of and treatments
for TBI, which we elaborate here and in Section 16-3 .
Over the ensuing 10 months, Donna regained most of her motor
abilities and language skills, and her spatial abilities improved
significantly. Nonetheless, she was short-tempered and easily frustrated
by the slowness of her recovery, symptoms typical of people with brain
trauma. She had periods of depression.
Donna also found herself prone to inexplicable surges of panic when
doing simple things. On one occasion early in her rehabilitation, she was
shopping in a large supermarket and became overwhelmed by the
number of salad dressing choices. She ran from the store, and only after
she sat outside and calmed herself could she go back inside to continue
shopping.
Two years later, Donna was dancing once again, but now she found
learning and remembering new steps difficult. Her emotions were still
unstable, which put a strain on her family, but her episodes of frustration
and temper outbursts grew far less frequent. A year later, they were gone,
and her life was not obviously different from that of other middle-aged
women.
Even so, some cognitive changes persisted. Donna seemed unable to
remember the names or faces of new people she met. She lost
concentration if background distractions such as a television or a radio
playing intruded. She could not dance as she had before her injury, but
she did work at it diligently. Her balance on sudden turns gave her the
most difficulty. Rather than risk falling, she retired from her life’s first
love.
 Donna’s case demonstrates the human brain’s capacity for
continuously changing its structure and ultimately its function
throughout a lifetime. From what we have learned in this chapter, we can
identify three ways in which Donna could recover from her brain injury:
she could learn new ways to solve problems, she could reorganize the
brain to do more with less, and she could generate new neurons to
produce new neural circuits. We briefly examine each possibility.

Dean Berry/Getty Images

The brain changes in response to these dancers’ new experiences and
new abilities. After her accident, Donna’s brain had to change to allow her
to regain her lost abilities, but she never recovered the ability these young
women have to learn new dances.

Three-Legged Cat Solution

Cats that lose a leg quickly learn to compensate for the missing limb and
once again become mobile. They show recovery of function: the limb is
gone, but behavior has changed to compensate. This simplest solution to
recovery from brain injury we call the three-legged cat solution.
A similar explanation can account for many instances of apparent
recovery of function after TBI. Imagine that a right-handed person has a
stroke that costs her the use of her right hand and arm. Unable to write
with the affected limb, she switches to her left hand. Such behavioral
compensation presupposes that some nervous system changes underlie
this new skill.
New-Circuit Solution
A second way to recover from brain damage is for the brain to form new
connections that allow it to do more with less. This change is most easily
accomplished by processes similar to those we considered for other
forms of plasticity. The brain changes its neural connections to overcome
the loss.
Without some intervention, recovery from most brain injuries is
relatively modest. Recovery can increase significantly if the person
engages in behavioral, pharmacological, or brain-stimulation therapy that
encourages the brain to make new connections.
 EXPERIMENT 14-4

Question: Does nerve growth factor stimulate recovery from

stroke, influence neural structure, or both?
Procedure Results

Results
 Conclusion: Nerve growth factor stimulates dendritic growth and
increased spine density in both healthy and injured brains. These
neuronal changes correlate with improved motor function after stroke.
Information from B. Kolb, S. Cote, A. Ribeiro-da-Silva, & A. C. Cuello
(1997). Nerve growth factor treatment prevents dendritic atrophy and
promotes recovery of function after cortical injury. Neuroscience, 76, p.
1146.

Behavioral therapy—speech therapy, physiotherapy, and music

therapy are examples—presumably increases brain activity, which
facilitates neural changes. In a pharmacological intervention, the patient
takes a drug, such as nerve growth factor, known to influence brain
plasticity. When NGF is given to animals with strokes that damaged the
motor cortex, their motor functions improve ( Experiment 14-4 ). The
behavioral changes correlate with a dramatic increase in dendritic
branching and spine density in the remaining intact motor regions. The
morphological changes correlate with improved motor functions, such as
reaching with the forelimb to obtain food, as illustrated in Experiment
14-2 (Kolb, Cote, et al., 1997). But because brain tissue is still missing,
recovery is by no means complete.
In principle, we might expect that any drug that stimulates the growth
of new connections would help people recover from brain injury.
However, that neural growth must occur in brain regions that can
influence a lost function. A drug that stimulates synaptic growth on cells
in the visual cortex, for example, would not enhance recovery of hand
use. The visual neurons play no direct role in moving the hand.
A third strategy to generate new neural circuits uses either deep brain
stimulation (DBS) or direct electrical stimulation of perilesional regions.
The goal of electrical stimulation is to directly increase activity in
remaining parts of specific damaged neural networks. In DBS, it is to put
the brain into a more plastic (trainable) state so that rehabilitation
therapies work better. Both strategies are in preliminary clinical trials.

Lost Neuron Replacement Solution

The third strategy a patient like Donna could pursue is to generate new
neurons to produce new neural circuits. The idea that brain tissue could
be transplanted from one animal to another goes back a century. The
evidence is good that tissue transplanted from fetal brains will grow and
form some connections in the new brain.
 Focus 5-4 recounts a successful case of fetal stem cell
transplantation. Section 13-2 describes SCN cell replacement.
Unfortunately, in contrast with transplanted hearts or livers,
transplanted brain tissue functions poorly. The procedure seems most
suited to conditions in which a small number of functional cells are
required, as in the replacement of dopamine-producing cells in Parkinson
disease or in the replacement of suprachiasmatic cells to restore circadian
rhythms.
By 2004, dopamine-producing cells had been surgically transplanted
into the striata of many Parkinson patients. Although the disease has not
been reversed, some patients, especially the younger ones, have shown
functional gains that justify the procedure. Nonetheless, ethical issues
will remain as long as the tissue is taken from aborted human fetuses.
The striatum, a region in the basal ganglia, includes the caudate
nucleus and putamen.
Adult stem cells offer a second way to replace lost neurons.
Investigators know that the brain is capable of making neurons in
adulthood. The challenge is to get the brain to do so after an injury. Brent
Reynolds and Sam Weiss (1992) made the first breakthrough in this
research.
Even in adults, neural stem cells line the subventricular zone,
diagrammed in Figure 8-10 A.
Cells lining the ventricles of adult mice were removed and placed in a
culture medium. The researchers demonstrated that if the correct trophic
factors are added, the cells begin to divide and can produce new neurons
and glia. Furthermore, if the trophic factors—particularly epidermal
growth factor (EGF)—are infused into the ventricle of a living animal,
the subventricular zone generates cells that migrate into the striatum and
eventually differentiate into neurons and glia.
epidermal growth factor (EGF) Neurotrophic factor; stimulates
the subventricular zone to generate cells that migrate into the
striatum and eventually differentiate into neurons and glia.
In principle, it ought to be possible to use trophic factors to stimulate
the subventricular zone to generate new cells in the injured brain. If these
new cells were to migrate to the site of injury and essentially regenerate
the lost area, as shown in Figure 14-26 , then it might be possible to
restore at least some lost function. Not all lost behaviors could be
restored, however, because the new neurons would have to establish the
same connections with the rest of the brain that the lost neurons once
had.
This task would be daunting: connections would have to be formed in
an adult brain that already has billions of connections. Nonetheless, such
a treatment might someday be feasible. Cocktails of trophic factors are
effective in stimulating neurogenesis in the subventricular zone after
brain injury. For example, in Figure 14-26 at left, animals first received
ischemic injuries (strokes), then received intraventricular infusions of
trophic factors for 14 days. New cells migrated to the site of injury, as
shown at right in Figure 14-26 , and many differentiated into immature
neurons.
 Bryan Kolb

FIGURE 14-26 Stem Cells Do the Trick Left: After cortical stroke—
damage is visible at upper right—infusion of epidermal growth factor into a
rat’s lateral ventricle induced neurogenesis in the subventricular zone.
Right: The stem cells migrated to the site of injury and filled in the
damaged area. But the cytological organization is abnormal.

Although they did not integrate well into the existing brain, the new
cells influenced behavior and led to functional improvement (Kolb et al.,
2007). The mechanism of influence is poorly understood. The new
neurons apparently had some trophic influence on the surrounding
uninjured cortex. Preliminary clinical trials with humans are under way
and so far show no ill effects in volunteers.
 14-5 REVIEW
Recovery from Brain Injury
Before you continue, check your understanding.
1 . Three ways to compensate for the loss of neurons are (1)
___________, (2) ___________, and (3) ___________.
2 . Two ways of using electrical stimulation to enhance postinjury
recovery are ___________ and ___________.
3 . Endogenous stem cells can be recruited to enhance functional
improvement by using ___________ factors.
4 . What is the lesson of the three-legged cat?
Answers appear at the back of the book.

For additional study tools, visit Launch Pad :

www.macmillanhighered.com/launchpad/kolb5e
 SUMMARY
14-1 Connecting Learning and Memory
Learning is a change in an organism’s behavior as a result of experience.
Memory is the ability to recall or recognize previous experience. For
more than a century, laboratory studies using animals have uncovered
two diverse types of learning: Pavlovian (or classical) and operant (or
instrumental).
The two basic types of memory are implicit (unconscious) and
explicit (conscious). Episodic memory includes not only a record of
events (episodes) that occurred but also our presence there and our role
in the events. The frontal lobe likely plays a unique role in this
autobiographical memory.
14-2 Dissociating Memory Circuits
Multiple subsystems control different aspects of memory within the
explicit and implicit systems. People with damaged explicit memory
circuits have impaired recall for facts and events. People with damaged
implicit memory circuits are impaired in their recall and/or performance
of skills and habits.
14-3 Neural Systems Underlying Explicit and Implicit
Memories
The neural circuits underlying implicit and explicit memory are
distinctly different: the reciprocal system for explicit memory includes
medial temporal structures; the unidirectional system for implicit
memory includes the basal ganglia. Emotional memory has
characteristics of both implicit and explicit memory. Neural circuits for
emotional memory also are unique in that they include the amygdala.
The chart summarizes broad categories within these multiple memory
systems.
For memories to become established in the brain—the process of
consolidation—experiences must change neural connections, and these
changes must become relatively permanent. When memories are
revisited, neural connectivity can become less fixed, allowing for the
neural networks and thus the memory to be modified, a process called
reconsolidation.
 Multiple Memory Systems
14-4 Structural Basis of Brain Plasticity
The brain has the capacity for structural change, and structural change
presumably underlies functional change. The brain changes structure in
two fundamental ways in response to experience.
Some Guiding Principles of Brain Plasticity
1. Behavioral change reflects brain change.

2. All nervous systems are plastic in the same general way.

3. Plastic changes are age-specific.

4. Prenatal events can influence brain plasticity throughout life.

5. Plastic changes are brain region dependent.

6. Experience-dependent changes interact.

7. Plasticity has pros and cons.

First, existing neural circuits change largely by modifying synaptic

connections. One proposed mechanism of synaptic change is long-term
potentiation (LTP), reflected in modification of EPSPs following
learning.
Second, novel neural circuits form both by forging new connections
among existing neurons and by generating new neurons. Generating new
neurons in the hippocampus is one mechanism for establishing novel
circuits. A likely mechanism for maintaining synaptic changes is
epigenetic: specific sites in the neuronal DNA in modified circuits can
exist in either methylated or unmethylated states.
Neuronal activity is key to brain plasticity: through it, synapses form
and change. Neuronal activity can be induced by general or specific
experience as well as by electrical or chemical stimulation. Chemical
stimulation may range from hormones and neurotrophic compounds to
psychoactive drugs.
Much of the brain is capable of plastic change with experience.
Different experiences lead to changes in different neural systems. The
table summarizes seven principles that guide research about brain
plasticity and behavior.
14-5 Recovery from Brain Injury
Plastic changes after brain injury parallel those seen when the brain
changes with experience. Changes related to recovery do not always
occur spontaneously, however, but must be stimulated by behavioral
training, by the effects of psychoactive drugs or neurotrophic factors, or
by electrical brain stimulation. The key to stimulating recovery from
brain injury is to increase the plastic changes underlying the recovery.
 KEY TERMS
amnesia, p. 483
anterograde amnesia, p. 497
associative learning, p. 500
behavioral sensitization, p. 511
conditioned response (CR), p. 483
conditioned stimulus (CS), p. 483
consolidation, p. 497
declarative memory, p. 485
dyslexia, p. 481
emotional memory, p. 498
entorhinal cortex, p. 491
epidermal growth factor (EGF), p. 516
episodic memory, p. 487
explicit memory, p. 485
eyeblink conditioning, p. 483
fear conditioning, p. 483
implicit memory, p. 483
Korsakoff syndrome, p. 495
learning, p. 481
learning set, p. 485
long-term depression (LTD), p. 500
long-term potentiation (LTP), p. 500
memory, p. 481
metaplasticity, p. 512
nerve growth factor (NGF), p. 511
neuritic plaque, p. 493
operant conditioning, p. 483
parahippocampal cortex, p. 491
Pavlovian conditioning, p. 481
perirhinal cortex, p. 491
priming, p. 485
procedural memory, p. 485
reconsolidation, p. 497
retrograde amnesia, p. 497
traumatic brain injury (TBI), p. 514
unconditioned response (UCR), p. 483
unconditioned stimulus (UCS), p. 483
visuospatial memory, p. 493

Visit Launch Pad : to access the e-Book, videos,

Learning Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

15

How Does the Brain

Think?
 Katherine Streeter

RESEARCH FOCUS 15-1 SPLIT BRAIN

15-1 THE NATURE OF THOUGHT
CHARACTERISTICS OF HUMAN THOUGHT
NEURAL UNIT OF THOUGHT
COMPARATIVE FOCUS 15-2 ANIMAL INTELLIGENCE
EXPERIMENT 15-1 QUESTION: HOW DO INDIVIDUAL
NEURONS MEDIATE COGNITIVE ACTIVITY?
15-2 COGNITION AND THE ASSOCIATION CORTEX
KNOWLEDGE ABOUT OBJECTS
MULTISENSORY INTEGRATION
SPATIAL COGNITION
ATTENTION
EXPERIMENT 15-2 QUESTION: CAN NEURONS LEARN TO
RESPOND SELECTIVELY TO STIMULI?
PLANNING
IMITATION AND UNDERSTANDING
RESEARCH FOCUS 15-3 THE RISE AND FALL OF MIRROR
NEURONS
15-3 EXPANDING FRONT IERS OF COGNITIVE
NEUROSCIENCE
CLINICAL FOCUS 15-4 NEUROPSYCHOLOGICAL
ASSESSMENT
MAPPING THE BRAIN
COGNITION AND THE CEREBELLUM
SOCIAL NEUROSCIENCE
NEUROECONOMICS
15-4 CEREBRAL ASYMMETR Y IN THINKING
ANATOMICAL ASYMMETRY
 FUNCTIONAL ASYMMETRY IN NEUROLOGICAL PATIENTS
FUNCTIONAL ASYMMETRY IN THE HEALTHY BRAIN
FUNCTIONAL ASYMMETRY IN THE SPLIT BRAIN
EXPERIMENT 15-3 QUESTION: WILL SEVERING THE CORPUS
CALLOSUM AFFECT THE WAY IN WHICH THE BRAIN
RESPONDS?
EXPLAINING CEREBRAL ASYMMETRY
EXPERIMENT 15-4 (A) QUESTION: HOW CAN THE RIGHT
HEMISPHERE OF A SPLIT-BRAIN SUBJECT SHOW THAT IT
KNOWS INFORMATION? (B) QUESTION: WHAT HAPPENS IF
BOTH HEMISPHERES ARE ASKED TO RESPOND TO
COMPETING INFORMATION?
LEFT HEMISPHERE, LANGUAGE, AND THOUGHT
15-5 VARIATIONS IN COGNITIVE ORGANIZATION
SEX DIFFERENCES IN COGNITIVE ORGANIZATION
HANDEDNESS AND COGNITIVE ORGANIZATION
CLINICAL FOCUS 15-5 SODIUM AMOBARBITAL TEST
SYNESTHESIA
CLINICAL FOCUS 15-6 A CASE OF SYNESTHESIA
15-6 INTELLIGENCE
CONCEPT OF GENERAL INTELLIGENCE
MULTIPLE INTELLIGENCES
DIVERGENT AND CONVERGENT INTELLIGENCE
INTELLIGENCE, HEREDITY, EPIGENETICS, AND THE SYNAPSE
15-7 CONSCIOUSNESS
WHY ARE WE CONSCIOUS?
EXPERIMENT 15-5 QUESTION: CAN PEOPLE ALTER THEIR
MOVEMENTS WITHOUT CONSCIOUS AWARENESS?
WHAT IS THE NEURAL BASIS OF CONSCIOUSNESS?
RESEARCH FOCUS 15-1

Split Brain
Epileptic seizures may begin in a restricted region of one brain
hemisphere and spread through the fibers of the corpus callosum to
the corresponding location in the opposite hemisphere. To prevent
the spread of seizures that cannot be controlled through medication,
neurosurgeons sometimes sever the 200 million nerve fibers of the
corpus callosum.
The procedure is medically beneficial for many people with
epilepsy, leaving them virtually seizure free, with only minimal
effects on their everyday behavior. In special circumstances,
however, the aftereffects of a severed corpus callosum become more
readily apparent, as extensive psychological testing by Roger Sperry,
Michael Gazzaniga, and their colleagues (Sperry, 1968; Gazzaniga,
1970) has demonstrated.
On close inspection, such split-brain patients reveal a unique
behavioral syndrome that offers insight into the nature of cerebral
asymmetry. Cortical asymmetry is essential for such integrative tasks
as language and body control.
split brain Surgical disconnection of the hemispheres by
severing the corpus callosum.
One split-brain subject was presented with several blocks. Each
block had two red sides, two white sides, and two half-red and half-
white sides, as illustrated. The task was to arrange the blocks to form
patterns identical with those shown on cards.
When the subject used his right hand to perform the task, he had
great difficulty. His movements were slow and hesitant. In contrast,
when he performed the task with his left hand, his solutions were not
only accurate but also quick and decisive.
Findings from studies of other split-brain patients have shown
that, as tasks of this sort become more difficult, left-hand superiority
increases. Participants whose brain is intact perform equally well
with either hand, indicating the intact connection between the two
hemispheres. But in split-brain subjects, each hemisphere works on
its own.
Apparently, the right hemisphere, which controls the left hand,
has visuospatial capabilities that the left hemisphere does not.
 In this experiment, a split-brain patient’s task is to arrange a set
of blocks to match the pattern shown on a card. Information from M. S.
Gazzaniga, R. B. Ivry, and G. R. Mangun (1999). Cognitive Science: The Biology of the
Mind (p. 323). New York: Norton.

Studies of split-brain patients reveal that the left and right cerebral
hemispheres engage in fundamentally different types of thinking. Yet
typically we are unaware of these brain asymmetries. In this chapter we
examine the neural systems and subsystems that control thinking. In the
mammalian brain these systems are in the cortex.
Our first task is to define the mental processes we wish to study—to
ask, what is the nature of thought? Then we consider the cortical regions
—for vision, audition, movement, and associative function—that play
major roles in thinking. We examine how these cortical connections are
organized into such systems and subsystems as the dorsal and ventral
visual streams and how neuroscientists study them.
Next we explore the brain’s asymmetrical organization and delve
deeper into split-brain phenomena. Another distinguishing feature of
human thought is the different ways that individual people think. We
consider several sources of these differences, including those related to
gender and to what we call intelligence. Finally, we address
consciousness and how it may relate to the neural control of thought.
 15-1 The Nature of Thought
Studying abstract mental processes such as thought, language, memory,
emotion, and motivation is tricky. They cannot be seen but can only be
inferred from behavior and are best thought of as psychological
constructs, ideas that result from a set of impressions. The mind
constructs the idea as being real, even though it is not tangible.
psychological construct Idea or set of impressions that some
mental ability exists as an entity; memory, language, and emotion
are examples.
We run into trouble when we try to locate constructs such as thought
or memory in the brain. That we have words for these constructs does
not mean that the brain is organized around them. Indeed, it is not. For
instance, although people talk about memory as a unitary thing, the brain
neither treats memory as unitary nor localizes it in one particular place.
The many forms of memory are each treated differently by widely
distributed brain circuits. The psychological construct of memory that we
think of as being a single thing turns out not to be unitary at all.
Assuming a neurological basis for psychological constructs such as
memory and thought is risky, but we certainly should not give up
searching for where and how the brain produces them. After all, thought,
memory, emotion, motivation, and other such constructs are the most
interesting activities the brain performs.
Psychologists typically use the term cognition (knowing) to describe
thought processes, that is, how we come to know about the world. For
behavioral neuroscientists, cognition usually entails the ability to pay
attention to stimuli, whether external or internal, to identify stimuli, and
to plan meaningful responses to them. External stimuli cue neural
activity in our sensory receptors. Internal stimuli can spring from the
autonomic nervous system (ANS) as well as from neural processes—
from constructs such as memory and motivation.
cognition Act or process of knowing or coming to know; in
psychology, refers to thought processes.
Section 14-1 details types of memory, Section 14-4 how
neuroplasticity contributes to memory processing and storage.

Characteristics of Human Thought

Human cognition is widely believed to have unique characteristics. One
is that human thought is verbal, whereas the thought of other animals is
nonverbal. Language is presumed to give humans an edge in thinking,
and in some ways it does:
The appearance of human language correlates with a dramatic brain
size increase; see Section 2-3 . Section 10-4 explains foundations
underlying all languages.
• Language provides the brain a means of categorizing information. It
allows us easily to group together objects, actions, and events that have
common factors.
• Language provides a means of organizing time, especially future time.
It enables us to plan our behavior around time (say, Monday at 3:00
P.M. ) in ways that nonverbal animals cannot.

• Perhaps most important, human language has syntax —sets of rules for
putting words together to create meaningful utterances.
syntax Ways in which words are put together; proposed to be
unique to human language.
Linguists argue that although other animals, such as chimpanzees, can
use and recognize vocalizations (about three dozen for chimps), they do
not rearrange these sounds to produce new meanings. This lack of
syntax, linguists maintain, makes chimpanzee language literal and
inflexible. Human language, in contrast, has enormous flexibility that
enables us to talk about virtually any topic, even highly abstract ones like
psychological constructs. In this way, our thinking is carried beyond a
rigid here and now.
Before you accept the linguists’ position, review Focus 1-2,
featuring the chimp Kanzi.
Neurologist Oliver Sacks illustrated the importance of syntax to
human thinking in his description of Joseph, an 11-year-old deaf boy
who was raised without sign language for his first 10 years and so was
never exposed to syntax. According to Sacks:
Joseph saw, distinguished, used; he had no problems with perceptual
categorization or generalization, but he could not, it seemed, go much
beyond this, hold abstract ideas in mind, reflect, play, plan. He seemed
completely literal—unable to juggle images or hypotheses or
possibilities, unable to enter an imaginative or figurative realm…. He
 seemed, like an animal, or an infant, to be stuck in the present, to be
confined to literal and immediate perception. (Sacks, 1989, p. 40)
Language, including syntax, develops innately in children because the
human brain is programmed to use words in a form of universal
grammar. But in the absence of words—either spoken or signed—no
grammar can develop. Without the linguistic flexibility that grammar
allows, no “higher-level” thought can emerge. Without syntactical
language, thought is stuck in the world of concrete, here-and-now
perceptions. Syntax, in other words, influences the very nature of our
thinking.
In addition to arranging words in syntactical patterns, the human brain
has a passion for stringing together events, movements, and thoughts.
We combine musical notes into melodies, movements into dance, images
into videos. We design elaborate rules for games and governments. To
conclude that the human brain is organized to chain together events,
movements, and thoughts seems reasonable. Syntax is merely one
example of this innate human way of thinking about the world.
We do not know how this propensity to string things together evolved,
but one possibility is natural selection: stringing movements together
into sequences is highly adaptive. It would allow for building houses or
weaving threads into cloth, for instance.
William Calvin (1996) proposed that the motor sequences most
important to ancient humans were those used in hunting. Throwing a
rock or a spear at a moving target is a complex act that requires much
planning. Sudden ballistic movements, such as throwing, last less than an
eighth of a second and cannot be corrected by feedback. The brain has to
plan every detail and then spit them out as a smooth-flowing sequence.
Figure 11-2 diagrams the frontal lobe hierarchy that initiates motor
sequences.
Today, a football quarterback does just this when he throws a football
to a receiver running a zigzag pattern to elude a defender. A skilled
quarterback can hit the target on virtually every throw, stringing
movements together rapidly in a continuous sequence with no pauses or
gaps. This skill is uniquely human. Chimpanzees can throw, but their
throws are inaccurate. No chimpanzee could learn to throw a ball to hit a
moving target.
 The human predisposition to sequence movements may have
encouraged language development. Spoken language, after all, is a
sequence of movements involving the throat, tongue, and mouth
muscles. Viewed in this way, language is the by-product of a brain that
was already predisposed to operate by stringing movements, events, or
even ideas, together.
A critical characteristic of human motor sequencing is our ability to
create novel sequences with ease. We constantly produce new sentences.
Composers and choreographers earn their living making new music and
dance sequences. Novel movement or thought sequences are a product of
the frontal lobe.
People with frontal lobe damage have difficulty generating novel
solutions to problems. They are described as lacking imagination. The
frontal lobes are critical not only for organizing behavior but also for
organizing thinking. One major difference between the human brain and
other primates’ brains is the size of the frontal lobes.

Parrot
 Human

Neural Unit of Thought

What exactly goes on within the brain to produce what we call thinking?
Is thought an attribute exclusive to humans? Before you answer, consider
the mental feats of Alex the parrot, profiled in Comparative Focus 15-2,
Animal Intelligence.
Alex’s cognitive abilities are unexpected in a bird. In the past 40
years, the intellectual capacities of chimpanzees and dolphins have
provoked great interest, but Alex’s mental life appears to have been just
as rich as the mental life of those two large-brained mammals.
The fact that birds are capable of thought is a clue to the neural basis
of thought. A logical presumption may be that thinking, which humans
are so good at, must be due to some special property of the massive
human neocortex. But birds do not possess a neocortex. Rather, they
evolved specific brain nuclei that function much as the layers of the
human cortex do. This organizational difference in the forebrain of birds
and mammals implies that thinking must be an activity of complex
neural circuits, not of some particular brain region.
 The idea of neural circuits is the essence of Donald Hebb’s (1949)
concept that cell assemblies (networks of neurons) represent objects or
ideas, and the interplay among the networks results in complex mental
activity such as cognition. Connections among neurons are not random
but rather are organized into systems and subsystems. Thinking must
result from the activity of these complex neural circuits. One way to
identify their role is to consider how individual neurons respond during
cognitive activity.
cell assembly Hypothetical group of neurons that become
functionally connected via common sensory inputs; proposed by
Hebb as the basis of perception, memory, and thought.
William Newsome and his colleagues (1995) took this approach in
training monkeys to identify apparent motion in a set of moving dots on
a television screen. The Procedure section of Experiment 15-1 on page
524 shows how the researchers varied the difficulty of the task by
manipulating the number of dots that moved in the same direction. If all
the dots move in the same direction, perceiving the whole array as
moving is very easy. If only a small percentage of the dots move in the
same direction, however, perceiving apparent motion in that direction is
much more difficult.
COMPARATIVE FOCUS 15-2

Animal Intelligence
Intelligent animals think. We all know that parrots can talk, but most
of us assume that no real thought lies behind their words. An African
grey parrot named Alex proved otherwise. Irene Pepperberg,
pictured here with Alex, studied his ability to think and use language
for more than three decades (Pepperberg, 1990, 1999, 2006).
A typical session with Alex and Pepperberg proceeded roughly as
follows (Mukerjee, 1996): Pepperberg would show Alex a tray with
four corks. “How many?” she would ask. “Four,” Alex would reply.
She then might show him a metal key and a green plastic one.
“What toy?”
“Key.”
“How many?”
“Two.”
“What’s different?”
“Color.”
Alex did not just have a vocabulary: words had meaning to him.
He correctly applied English labels to numerous colors (red, green,
blue, yellow, gray, purple, orange), shapes (two-, three-, four-, five-,
six- cornered), and materials (cork, wood, rawhide, rock, paper,
chalk, wool). He also labeled various items made of metal (chain,
key, grate, tray, toy truck), wood (clothespin, block), and plastic or
paper (cup, box).
Most surprisingly, Alex used words to identify, request, and
refuse items. He responded to questions about abstract ideas, such as
the color, shape, material, relative size, and quantity of more than
100 objects.
Alex’s thinking was often quite complex. Presented with a tray
that contained seven items—a circular rose-colored piece of rawhide,
a piece of purple wool, a three-cornered purple key, a four-cornered
yellow piece of rawhide, a five-cornered orange piece of rawhide, a
six-cornered purple piece of rawhide, and a purple metal box—and
then asked, “What shape is the purple hide?” Alex would answer
correctly, “Six-corner.”
To come up with this answer, Alex had to comprehend the
question, locate the correct object of the correct color, determine the
answer to the question about the object’s shape, and encode his
answer into an appropriate verbal response. This task was not easy.
After all, four objects were pieces of rawhide and three objects were
purple.
Alex could not respond just to one attribute. Rather, he had to
combine the concepts of rawhide and purple and find the object that
possessed them both. Then he had to figure out the object’s shape.
Clearly, considerable mental processing was required, but Alex
succeeded at such tasks time and again.
Alex also demonstrated that he understood what he said. If he
requested one object and was presented with another, he was likely
to say no and repeat his original request. In fact, when given
incorrect objects on numerous occasions in formal testing, he said no
and repeated his request 72 percent of the time, said no without
repeating his request 18 percent of the time, and made a new request
the other 10 percent of the time.
These responses suggest that Alex’s requests led to an expectation
in his mind. He knew what he was asking for, and he expected to get
it.
 Wm. Munoz
The African grey parrot Alex, shown here with Irene Pepperberg
and a sampling of the items he could count, describe, and
answer questions about. Alex died in 2007 at the age of 31.

In fact, a threshold number of dots moving together is required to

make directional motion apparent. If too few dots are moving in the
same direction, the viewer gets an impression of random movement.
Apparently, on the basis of the proportion of dots moving in the same
direction, the brain decides whether dots are moving in a consistent
direction.
After the monkeys were trained in the task, the investigators recorded
from single neurons in visual area V5. V5 contains cells sensitive to
movement in a preferred direction. When vertical movement crosses its
receptive field, a neuron that is sensitive to vertical motion responds with
a vigorous burst of action potentials. But just as the observer has a
threshold for perceiving coherent motion in one direction, so too does the
neuron. If at some point the random activity of the dots increases to a
level that obscures movement in a neuron’s preferred direction, the
neuron will stop responding because it does not detect any consistent
pattern.
Figure 9-16 locates visual regions V1 through V5 in the occipital
lobe.
 EXPERIMENT 15-1

Question: How do individual neurons mediate cognitive

activity?
Procedure

Monkeys were trained to identify apparent motion in a set of

moving dots on a TV screen.

1. Random dot movement - dots move randomly. No

apparent motion is perceived.
2. Semirandom dot movement - 3 dots move in one
direction; others are random. Still no apparent motion is
perceived.
3. Semicoordinated dot movement - about half the dots
move in the same direction; others are random. Threshold
level is needed to perceive apparent motion.
4. Coordinated dot movement - all dots move in the same
direction. Apparent motion is strongly perceived.
Results

After the monkeys were trained in the task, investigators

recorded from single neurons in visual area V5, which contains
cells that are sensitive to motion in a preferred direction. The
neural responses to the four different patterns of movement are
shown below.
 1. Random dot movement: baseline response of no increased
activity.
2. Semirandom dot movement: baseline response of no
increased activity.
3. Semicoordinated dot movement: moderate response;
activity spikes occur more frequently.
4. Coordinated dot movement: strong response; activity
spikes occur with high frequency.
Conclusion: The increase in neuronal firing rate correlates with the
monkey’s perception of motion, suggesting that individual neurons, not
the summed activity of many neurons, influence perception.

So how does the activity of any given neuron correlate with the
perceptual threshold for apparent motion? On the one hand, if our
perception of apparent motion results from the summed activity of many
dozens or even thousands of neurons, little correlation would exist
between the activity of any one neuron and the perception. On the other
hand, if individual neurons influence our perception of apparent motion,
then a strong correlation would exist between the activity of a single cell
and the perception.
The results of Experiment 15-1 are unequivocal: the sensitivity of
individual neurons is very similar to the perceptual sensitivity of the
monkeys to apparent motion. As shown in the Results section, if
individual neurons failed to respond to the stimulus, the monkeys
behaved as if they did not perceive any apparent motion.
This finding is curious. Given the large number of V5 neurons, it
seems logical that perceptual decisions are based on the responses of a
large pool of neurons. But Newsome’s results show that the activity of
individual cortical neurons is correlated with perception rather than
perception being the property of a particular brain region.
Still, Hebb’s idea of a cell assembly—an ensemble of neurons that
represents a complex concept—suggests some way of converging the
inputs of individual neurons to arrive at a consensus. Here, the neuronal
ensemble represents a sensory event (apparent motion) that the activity
of the ensemble detects. Cell assemblies could be distributed over fairly
large regions of the brain, or they could be confined to smaller areas,
such as cortical columns.
 Figures 9-33 to 9-35 diagram functional columns in occipital and
temporal cortices.

Hebb’s Cell Assembly “Cells that fire together wire together.” Image from D.
O. Hebb (1949). The Organization of Behavior (Figure 9, p. 71). New York: McGraw-Hill.

Via computer modeling, cognitive scientists have demonstrated the

capacity of cell assembly circuits to perform sophisticated statistical
computations. Other complex tasks, such as Alex the parrot’s detecting
an object’s color, also are believed to entail neuronal ensembles. Cell
assemblies provide the basis for cognition. Different ensembles come
together, much like words in language, to produce coherent thoughts.
What do individual neurons contribute to a cell assembly? Each acts
as a computational unit. As Experiment 15-1 shows, even one solitary
neuron can decide on its own when to fire if its summed inputs indicate
that movement is taking place. Neurons are the only elements in the
brain that combine evidence and make decisions. Neurons are the
foundation of cognitive processes and of thought. The combination of
individual neurons into novel neural networks produces complex mental
representations—ideas, for instance.
 15-1 REVIEW

The Nature of Thought

Before you continue, check your understanding.
1 . Cognition, or thought, entails the abilities of
___________,___________, and ___________ stimuli.
2 . Unlike thought in other animals, humans have the added advantage of
___________, which adds ___________ to thought.
3 . The ___________ is the basic unit of thought production.
4 . Describe the most important way in which human thought differs
from thinking in other animals.
Answers appear at the back of the book.

For additional study tools, visit LaunchPad Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 15-2 Cognition and the Association Cortex
Altogether, the primary sensory and motor cortical regions occupy about
a third of the neocortex (Figure 15-1 ). The remaining two-thirds,
located in the frontal, temporal, parietal, and occipital lobes, is referred
to generally as the association cortex. It functions to produce cognition.
association cortex Neocortex outside primary sensory and motor
cortices; functions to produce cognition.
A fundamental difference between association cortex and primary
sensory and motor areas is that the association cortex has a distinctive
pattern of connections. A major source of input to all cortical areas is the
thalamus, which rests atop the brainstem. The primary sensory cortex
receives inputs from thalamic nuclei that receive information from the
body’s sense organs. But inputs to the association cortex come from
thalamic areas that receive their inputs from other cortical regions. As a
result, inputs to the association cortex are already highly processed. So
this information must be fundamentally different from the raw
information reaching the primary sensory and motor cortex. The
association regions contain knowledge either about our external or
internal world or about movements.
Owing to its close relationship to the visual and auditory sensory
regions, the temporal association regions tend to produce cognition
related to visual and auditory processing. Similarly, the parietal cortex is
closely related to somatosensation and movement control. In contrast,
the frontal cortex coordinates information coming from the parietal and
temporal association regions with information coming from subcortical
regions.
KEY (cortical areas)

Primary motor
Primary sensory
Primary visual
Primary auditory
Primary olfactory and taste
 FIGURE 15-1Cortical Functions Lateral view of the left hemisphere
and medial view of the right hemisphere, showing the primary motor and
sensory areas. All remaining cortical areas are collectively referred to as
the association cortex, which functions in thinking.

(A) Lateral view

(B) Medial view

 FIGURE 15-2 Prefrontal Association Cortex Lateral view of the
brain’s left hemisphere (A) and medial view of the right hemisphere (B)
represent regions of the prefrontal cortex (PFC) in relation to the
associated anterior cingulate allocortex, shown in (B). Figure 12-19
illustrates how these areas function in producing emotional behavior.

As diagrammed in Figure 15-2 , the multiple subdivisions of the

prefrontal cortex (PFC) encompass its dorsal, lateral, orbital, and medial
regions. Activity in each prefrontal region is associated with the types of
cognitive processing that we describe throughout this chapter. An
additional frontal lobe region shown in Figure 15-2 is the anterior
cingulate cortex (ACC). Although the ACC was once believed only to
play a role in emotion, it is becoming clear that it functions as an
interface between emotion and cognition.
To understand the types of knowledge that the association areas
contain, we next consider discrete cognitive behaviors, then trace these
behaviors to different parts of the association cortex.

Knowledge about Objects

Visualize a milk carton sitting on a counter directly in front of you. What
do you see? Now imagine moving the carton a few inches off to one side
as you continue to stare directly ahead. What do you see now? Next,
imagine that you tilt the carton toward you at a 45° angle. Again, what
do you see? Probably you answered that you saw the same thing in each
situation: a rectangular box with lettering on it.
Intuitively, you feel that the brain must see the object much as you
have perceived it. The brain’s seeing, however, is more
compartmentalized than are your perceptions. Compartmentalization is
revealed in people with damage to various regions of the occipital cortex,
many of whom lose one particular aspect of visual perception. For
instance, those with damage to visual area V4 can no longer perceive
color, whereas those with damage to area V5 can no longer see
movement (when the milk carton moves, it becomes invisible to them).
Moreover, your perception of the milk carton’s consistently
rectangular shape does not always match the forms your visual system is
processing. When you tip the carton toward you, you still perceive it as
rectangular, even though it is no longer presenting a rectangular shape to
your eyes. Your brain has somehow ignored the change in information
about shape that your retinas have sent it and concluded that this object,
no matter its apparent shape, remains the same milk carton.
There is more to your conception of the milk carton than merely
perceiving and processing its physical characteristics. You also know
what a milk carton is, what it contains, and where you can get one. The
knowledge about milk cartons that you have acquired is represented in
the temporal association cortex, which forms the ventral stream of visual
processing. If the temporal association regions are destroyed, a person
loses visual knowledge not only about milk cartons but also about all
other objects. The person becomes agnosic (unknowing).
Section 9-4 recounts cases illustrative of various visual-form
agnosias.
Knowledge about objects includes even more than how they look and
what they are used for. It depends on what will be done with the
information—how to pick up the milk carton, for example. Knowledge
of what things are is temporal; knowledge of how to grasp the object is
parietal ( Figure 15-3 ).
 FIGURE 15-3 Streaming Visual Information The dorsal visual
stream mediates vision for action. The ventral stream mediates vision for
object recognition.

Multisensory Integration
Our knowledge about the world comes through multisensory channels.
When we see and hear a barking dog, the visual information and auditory
information fit together seamlessly. How do all our neural systems and
functional levels combine to afford us a unified conscious experience?
Philosophers, impressed with this integrative capacity, identified the
binding problem, which asks how the brain ties its single and varied
sensory and motor events together into a unified perception or behavior.
It is gradually becoming clear how the brain binds up our perceptions
and how this ability is gradually acquired in postnatal life (see the review
by Stein & Rowland, 2011).
binding problem Philosophical question focused on how the brain
ties single and varied sensory and motor events together into a
unified perception or behavior.
One solution to the sensory integration aspect of the binding problem
lies in multimodal regions of the association cortex, that is, regions
populated by neurons that respond to information from more than one
sensory modality, as illustrated in Figure 15-4 . Investigators presume
that multimodal regions combine characteristics of stimuli across
different senses when we encounter them separately or together. For
example, the fact that we can visually identify objects that we have only
touched implies a common perceptual system linking the visual and
somatic circuits. In Section 15-5 , Clinical Focus 15-6 profiles a man in
whom stimulation from one sensory modality (taste) concurrently
induces the experience of a different modality (touch).
The senses of smell and taste combine to produce the experience of
flavor; see Section 12-2 .
KEY (multimodal cortex)

Auditory, visual, and somatosensory

Auditory and visual
Auditory and somatosensory

FIGURE 15-4 Multisensory Areas in the Monkey Cortex

Color-coded areas represent regions where anatomical data and/or
electrical stimulation demonstrate multisensory interactions. Dashed lines
represent multimodal areas revealed when sulci are opened. Information from
A. A. Ghanzanfar & C. E. Schroeder (2006). Is neocortex essentially multisensory? Trends in
Cognitive Science, 10, pp. 278-285.

Spatial Cognition
The location of objects is just one aspect of what we know about space.
Spatial cognition encompasses a whole range of mental functions that
vary from navigational ability (getting from point A to point B) to
mentally manipulating complex visual arrays like those shown in Figure
15-5 .
Imagine going for a walk in an unfamiliar park. You do not go around
and around in circles. Rather, you proceed in an organized, systematic
way. You also need to find your way back. These abilities require a
representation of the physical environment in your mind’s eye.
At some time during the walk, let’s assume you are uncertain where
you are—a common problem. One solution is to make a mental image of
your route, complete with various landmarks and turns. It is a small step
from mentally manipulating these kinds of navigational landmarks and
movements to manipulating other kinds of images in your mind. Thus
the ability to mentally manipulate visual images seems likely to have
arisen in parallel with the ability to navigate in space.

FIGURE 15-5 Spatial Cognition These two figures are the same but
are oriented differently in space. Researchers test spatial cognition by
giving subjects pairs of stimuli like this and asking if the shapes are the
same or different.

The evolution of skill in mental manipulation is also closely tied to

the evolution of physical movements. It is likely that animals first moved
using whole-body movements (the swimming motion of a fish), then
developed coordinated limb movements (quadrupedal walking), and
finally mastered discrete limb movements, such as a human arm reaching
out. As the guidance strategies for controlling movements became more
sophisticated, cognitive abilities evolved to support the guidance
systems.
 The Basics, Section 1-3 , traces nervous system evolution across the
animal kingdom.
It seems unlikely that more sophisticated cognitive abilities evolved
on their own. Why would a fish, say, be able to manipulate an object in
its mind that it could not manipulate in the real world? But a human, who
can manipulate objects by hand, should be able to imagine such
manipulations. After all, we are constantly observing our hands or feet
manipulating things: we must have many mental representations of such
activities.
Alex the parrot manipulated objects with his beak.
Once the brain can manipulate objects that are physically present, it
seems a small step to manipulating imagined objects—to solve problems
like the one depicted in Figure 15-6 . The ability to manipulate an object
in the mind’s eye probably flows from the ability to manipulate tangible
objects with the hands.
Research findings provide clues to the brain regions participating in
various aspects of spatial cognition. For instance, the dorsal stream in the
parietal lobes is central in controlling vision for action. Humans make
discrete limb movements to points in space, so a reasonable supposition
is that the dorsal stream’s evolutionary development provided a neural
basis for such spatial cognitive skills as mentally rotating objects. In fact,
people with damaged parietal association regions, especially in the right
hemisphere, have deficits in processing complex spatial information,
both in the real world and in their imagination.
By tracing the evolutionary development of the human brain, we find
that the parietal association regions expanded considerably more in
humans than in other primates. This expanded brain region functions in
part to perform the complex spatial operations just discussed. Humans
have a capacity for building that far exceeds that of our nearest relative,
the chimpanzee. You may consider it a long leap of logic, but perhaps
our increased capacity for building and manipulating objects played
heavily into our developing cognitive spatial abilities.
 FIGURE 15-6 Mental Manipulation Try this sample test item used to
measure spatial orientation. Compare the three cubes on the right with the
one on the left. No letter appears on more than one face of a given cube.
Which cube—a, b, or c—could be a different view of the cube on the left?
The correct answer is at the bottom of the page.

Attention
Imagine you’re meeting some friends at a football game. You search for
them as you meander through the crowd in the stadium. Suddenly you
hear one friend’s distinctive laugh and turn to scan in that direction. You
see your group and rush to join them.
This everyday experience demonstrates the nature of attention,
selective narrowing or focusing of awareness to part of the sensory
environment or to a class of stimuli. Even as sounds, smells, feelings,
and sights bombard you, you still can detect a familiar laugh or spot a
familiar face: you can direct your attention.
attention Narrowing or focusing awareness to a part of the sensory
environment or to a class of stimuli.
More than 100 years ago, William James (1890) defined attention: “It
is the taking possession by the mind in clear and vivid form of one out of
what seem several simultaneous objects or trains of thought.” James’s
definition goes beyond our example of locating friends in a crowd,
inasmuch as he notes that we can attend selectively to thoughts as well as
to sensory stimuli. Who hasn’t at some time been so preoccupied with a
thought as to exclude all else from mind? So attention can be directed
inward as well as outward.
Selective Attention
As with many other inferred mental processes, studying the neural basis
of attention is challenging. Research with monkeys trained to attend to
particular locations or visual stimuli, however, has identified neurons in
the cortex and midbrain that show enhanced firing rates to particular
locations or visual stimuli. Significantly, the same stimulus can activate a
neuron at one time but not at another, depending on the monkey’s
learned focus of attention.
The answer to the mental manipulation in Figure 15-6 is a.
 EXPERIMENT 15-2

Question: Can neurons learn to respond selectively to

stimuli?
Procedure

Monkeys were trained to release a bar when a certain stimulus

was presented in a certain location. The monkeys learned to
ignore stimuli in all other locations.

Results
 During performance of this task, researchers recorded the
firing of neurons in visual area V4, which are sensitive to color
and form. Stimuli were presented in either rewarded or
unrewarded locations.

Pretraining recordings:

Pretraining recordings:

Conclusion: Neurons can learn to respond selectively to information in

their receptive field.

In the study shown in Experiment 15-2 , James Moran and Robert

Desimone (1985) trained monkeys to hold a bar while gazing at a
fixation point on a screen. A sample stimulus (e.g., a vertical red bar)
appeared briefly at one location in the visual field, followed about 500
milliseconds later by a test stimulus at the same location. When the test
stimulus was identical with the initial sample stimulus, an animal was
rewarded if it immediately released the bar.
Each animal was trained to attend to stimuli presented in one
particular area of the visual field and to ignore stimuli in any other area.
In this way, the same visual stimulus could be presented to different
regions of a neuron’s receptive field to test whether the cell’s response
varied with stimulus location.
 As the animals performed the task, the researchers recorded neurons
firing in visual area V4. Neurons in V4 are sensitive to color and form,
and different neurons respond to different combinations of the two
variables (e.g,, a red vertical bar or a green horizontal bar). Visual stimuli
were presented either in the correct location for a reward or in an
incorrect location for no reward.
As diagrammed in the Results section of Experiment 15-2 , neurons
responded only when a visual stimulus was in the reward location, even
though the same stimulus was presented in a no-reward location. Before
training, the neurons responded to all stimuli in both locations. This
finding tells us that attending to specific parts of the sensory world is a
property of single neurons: more evidence that the neuron is the
computational unit of cognition.
Deficits of Attention
Attention is probably a property of neurons throughout the brain, with
some regions playing more prominent roles than others. The frontal
lobes, for instance, are central in attention. People with frontal lobe
injuries tend to become overly focused on environmental stimuli. They
seem to selectively direct attention to an excessive degree or to have
difficulty shifting attention. Studies of these people suggest that the
frontal association cortex controls the ability to direct attention flexibly
to where it is needed. Indeed, planning, a key frontal lobe function,
requires this ability.
That the parietal association cortex is key in other aspects of attention
is perhaps best illustrated by the attention deficit referred to as neglect.
Neglect occurs when a brain-injured person ignores sensory information
that should be considered important. Usually the condition affects only
one side of the body and is called contralateral neglect. We observed a
dog that had developed a right-hemisphere tumor and ate only the food
on the right side of its dish, ignoring the food on the left side. Neglect is
a fascinating symptom because often no damage to sensory pathways
accompanies it. Rather, neglect is a failure of attention.
contralateral neglect Ignoring a part of the body or world on the
side opposite (contralateral to) that of a brain injury.
People with damage to the parietal association cortex of the right
hemisphere may have particularly severe neglect of objects or events in
the left side of their world. For example, one man dressed only the right
side of his body, shaved only the right side of his face, and read only the
right side of a page (if you can call that reading). He could move his left
limbs spontaneously, but when asked to raise both arms, he would raise
only the right. When pressed, he could be induced to raise the left arm,
but he quickly dropped it to his side again.
As people with contralateral neglect begin to recover, they show
another interesting symptom. They neglect information on one side of
the body when it is simultaneously presented with similar information on
the other side of the body. Figure 15-7 shows a common clinical test for
this symptom, called extinction.
extinction In neurology, neglect of information on one side of the
body when presented simultaneously with similar information on
the other side of the body.

When shown two identical objects

 When shown two different objects

When shown two kinds of an object

FIGURE 15-7 Testing for Extinction A stroke patient who shows

neglect for information presented to his left responds differently depending
on whether objects in the left and right visual fields are similar or different.

In an extinction test, the patient is asked to keep his or her eyes fixed
on the examiner’s face and to report objects presented in one or both
sides of the visual field. When presented with a single object (a fork) to
one side or the other, the patient orients himself or herself toward the
appropriate side of the visual field, so we know that he or she cannot be
blind on either side. But now suppose that two forks are presented, one
on the left and one on the right. The patient ignores the fork on the left
and reports the one on the right. When asked about the left side, the
patient is quite certain that nothing appeared there and that only one fork
was presented, on the right.
Perhaps the most curious aspect of neglect is that people who have it
fail to pay attention not only to one side of the physical world around
them but also to one side of the world represented in their mind. We
studied one woman who had complete neglect for everything on her left
side. She complained that she could not use her kitchen because she
could never remember the location of anything on her left.
We asked her to imagine standing at the kitchen door and to describe
what was in the various drawers on her right and left. She could not
recall anything on her left. We then asked her to imagine walking to the
end of the kitchen and turning around. We again asked her what was on
her right, the side of the kitchen that had previously been on her left. She
broke into a big smile and tears ran down her face as she realized that
she now knew what was on that side of the room. All she had to do was
reorient her body in her mind’s eye. She later wrote and thanked us for
changing her life, because she was now able to cook again. Clearly,
neglect can exist in the mind as well as in the physical world.
Although complete contralateral neglect is usually associated with
parietal lobe injury, specific forms of neglect can arise from other
injuries. Ralph Adolphs and his colleagues (2005) describe the case of S.
M., a woman with bilateral amygdala damage who could not recognize
fear in faces. On further study, the reason was discovered: S. M. failed to
look at the eyes when she looked at faces; instead, she looked at other
facial features such as the nose. Because fear is most clearly identified in
the eyes, not the nose, she did not identify the emotion. When she was
specifically instructed to look at the eyes, her recognition of fear became
entirely normal. Thus, the amygdala plays a role in directing attention to
the eyes to identify facial expressions.

Planning
At noon on a Friday, a friend proposes that she and you go to a nearby
city for the weekend to attend a concert. She will pick you up at 6:00 P.M
. and you will drive there together.
 Because you are completely unprepared for this invitation and
because you are going to be busy until 4:00, you must rush home and get
organized. En route you stop at a fast food restaurant so that you won’t
be hungry on the 2-hour drive. You also need cash, so you head to the
nearest ATM. When you get home, you grab various pieces of clothing
appropriate for the concert and the trip. You also pack your toiletries.
You somehow manage to get ready by 6:00, when your friend arrives.
Although the task of getting ready in a hurry may make us a bit
harried, most of us can manage it. People with frontal lobe injury cannot.
To learn why, let’s consider what the task requires.
1. To plan your behavior, you must select from many options. What do
you need to take with you? Cash? Then which ATM is closest, and
what is the quickest route to it? Are you hungry? Then what is the
fastest way to get food on a Friday afternoon?
2. In view of your time constraint, you have to ignore irrelevant stimuli.
If you pass a sign advertising a sale in your favorite store, for instance,
you have to ignore it and persist with the task at hand.
3. You have to keep track of what you have done already, a requirement
especially important while you are packing. You do not want to forget
anything or pack duplicates. You do not want to take four pairs of
shoes but no toothbrush.
• Group 1: Single black dot, two red dots, three blue dots, four green
dots.
• Group 2: Single blue square, two green squares, three red squares, four
black squares.
• Group 3: Single green star, two blue stars, three black stars, four red
stars.
• Group 4: Single red diamond, two black diamonds, three green
diamonds, four blue diamonds
FIGURE 15-8 Wisconsin Card Sorting Test The subject receives a deck of
cards containing multiple copies of those represented here and is presented with a row
of four cards selected from among them. The task is to place each card in the pile under
the appropriate card in the row, sorting by one of three possible categories. Subjects are
never explicitly told what the correct sorting category is—color, number, or form; they are
told only whether their responses are correct or incorrect. After subjects have begun
sorting by one category, the tester unexpectedly changes to another category.

The task’s general requirements can be described as the temporal

(time) organization of behavior. You are planning what you need to do
and when you need to do it. Temporal planning is the general function of
the frontal lobes, especially the prefrontal cortex.
 But to plan, you also need to recognize objects (an occipital and
temporal lobe function) and to make appropriate movements with respect
to them (a parietal lobe function). You can therefore think of the frontal
lobes as acting like an orchestra conductor. The frontal lobes make and
read a motor plan to organize behavior in space and time—a kind of
score, analogous to the musical score a conductor uses. People with
frontal lobe injuries are simply unable to organize their behavior.
Performance on the Wisconsin Card Sorting Test exemplifies the
deficits frontal lobe injury causes. Figure 15-8 shows the testing
materials. The subject is presented with four stimulus cards bearing
designs that differ in color, form, and number of elements, thus setting
up three possible sorting categories. The subject must sort a deck of
cards into piles in front of the various stimulus cards, depending on the
sorting category called for. But the correct sorting category is never
stated. The subject is simply told after placing each card whether the
choice is correct or incorrect.
In one trial, for example, the first correct sorting category is color.
After the subject has sorted a number of cards by color, the correct
solution switches, without warning, to form. When the subject has
started to sort by form, the correct solution again changes unexpectedly,
this time to the number of items on each card. The sorting rule later
becomes color again, and so on, with each change in rule coming
unannounced.
Shifting response strategies is particularly difficult for people with
frontal lobe lesions: they may continue responding to the original
stimulus (color) for as many as 100 cards until the test ends. This pattern,
known as perseveration, is the tendency to emit repeatedly the same
verbal or motor response to varied stimuli.
perseveration Tendency to emit repeatedly the same verbal or
motor response to varied stimuli.
Frontal lobe subjects may even comment that they know that color is
no longer the correct category, but they continue to sort by color. One
stated: “Form is probably the correct solution now so this [sorting by
color] will be wrong, and this will be wrong, and wrong again.” Despite
knowing the correct sorting category, the frontal lobe patient cannot shift
behavior in response to the new external information.

Imitation and Understanding

In all communication—verbal and nonverbal—the sender and receiver
must share an understanding of what counts. If a person speaks a word or
makes a gesture, another person will understand only if he or she
interprets it correctly. To accomplish this coordination in
communication, the processes of producing and perceiving a message
must share a common representation in the sender’s and the receiver’s
brains.
How do both sender and receiver of a potentially ambiguous gesture,
such as a raised hand or a faint smile, achieve a common understanding?
Giacomo Rizzolatti and his colleagues (Rizzolatti, 2007; Rizzolatti &
Craighero, 2004) proposed an answer. In monkeys’ frontal lobes they
identified neurons that discharge during active movements of the hand or
mouth or both. These neural discharges do not precede the movements
but instead occur in synchrony with them. But it takes time for a neural
message to go from a frontal lobe to a hand, so we would predict that, if
these cells are controlling the movements, they will discharge before the
movements take place. The cells must therefore be recording a
movement that is taking place.
In the course of his studies, Rizzolatti also found that many
“movement” neurons located in the inferior frontal and posterior parietal
cortex discharge when a monkey sees other monkeys make the same
movements. They also discharge when the monkey sees the experimenter
make the movements. Rizzolatti called them mirror neurons. The
researchers proposed that mirror neurons represent actions, one’s own or
those of others. Such neural representations could be used both for
imitating others’ actions and for understanding their meanings, thus
enabling appropriate responses. Mirror neurons therefore could provide
the link between the sender and the receiver of a communication.
mirror neuron Cell in the primate premotor and parietal cortex that
fires when an individual observes an action taken by another
individual.
Rizzolatti and his colleagues used PET to look for these same neuron
populations in humans. Participants were asked to watch a movement, to
make the same movement, or to imagine the movement. Each condition
activated a region of the lateral frontal lobe in the left hemisphere,
including Broca’s area. Taken together with the results of the monkey
studies, this finding suggests that primates have a fundamental
mechanism for recognizing action. People apparently recognize others’
actions, because the neural patterns produced when they observe those
actions are similar to those produced when they themselves make those
same actions. Research Focus 15-3 , The Rise and Fall of Mirror
Neurons, frames the debate on mirror neuron function.
RESEARCH FOCUS 15-3

The Rise and Fall of Mirror Neurons

Rizzolatti and colleagues’ discovery of mirror neurons in the 1990s
was serendipitous (e.g., Rizzolatti, 2007). The group was
investigating how neurons in the premotor cortex of macaque
monkeys control grasping actions. The monkeys were trained to
make different grasping movements to retrieve bits of food. When
the animals reached for the food, cells in the premotor cortex were
highly active, revealing their role in movement control.
Between reaching trials the monkeys could observe an
investigator making reaching movements similar to those the
monkey had made. Unexpectedly, many of the same neurons fired in
response to the monkeys observing the experimenter’s reaching: the
cells appeared to mirror others’ behavior. The name mirror neurons
stuck. Studies using noninvasive imaging demonstrated similar
neuronal populations, although apparently more widespread, in
humans.
Over the ensuing decade, mirror neurons were hypothesized to be
the basis of understanding actions rather than merely recognizing
them. This possibility had profound implications and led to
propositions that mirror neurons were the basis of speech and
language, empathy, social cognition, theory of mind—even
civilization! Dysfunction of the mirror neuron system was proposed
as a basis for disorders such as the broken mirror hypothesis of
autism (Ramachandran & Oberman, 2006).
The lure of mirror neurons spread well beyond neuroscience and
into the popular media. All the hype resulted in mirror neurons being
widely perceived as among the most important discoveries in
neuroscience in the past generation.
But by the early 2000s, cracks began to show in the mirror.
Gregory Hickok (2014) has argued that mirror neurons do not make
actions understandable, but they do refine movement control. Hickok
and others suggest that mirror neurons do not “understand” action,
but rather their function arises from an association between
executing an action and the self-observation of the action.
 Thus, the neurons learn to mirror. But why? What is the benefit?
One possibility is that because the actions of others are relevant to
one’s own actions, having a system to link others’ perceived actions
with one’s own appropriate actions is adaptive. An extension of this
idea is that mirror neurons are activated after an action is understood
by other brain regions as a way to make predictions about future
actions (Hickok, 2013). In this view, mirror neurons simply reflect
the fact that the brain understands actions (Csibra, 2007). The
advantage of this type of mirror system is that with this knowledge
we can make movements faster and more accurately.
The lessons from the rise and fall of mirror neurons: First,
although the mirror neuron theory of functioning to understand
action may be wrong, it has served the field well by stimulating new
research. That research has led to better understanding of how the
brain thinks. A second lesson is vigilance: some scientists and media
can push scientific theories well beyond the data.
 15-2 REVIEW

Cognition and the Association

Cortex
Before you continue, check your understanding.
1 . The association cortex contains ___________ and functions to
produce ___________
2 . As a general rule, the ___________ lobes generate knowledge about
objects, whereas the ___________ lobes produce various forms of
spatial cognition.
3 . The frontal lobes function not only to make movements but also to
___________ and to ___________
4 . ___________ neurons in the frontal and parietal lobes represent
actions, one’s own or those of others.
5 . Describe the function of multimodal cortex.
Answers appear at the back of the book.

For additional study tools, visit LaunchPad Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Expanding Frontiers of Cognitive
15-3

Neuroscience
Sophisticated noninvasive stimulation and recording techniques for
measuring the brain’s electrical activity and noninvasive brain imaging
methods led to a major shift in studying brain and behavior: cognitive
neuroscience, the field that studies the neural bases of cognition.
Cognitive neuroscience focuses on high-tech research methods but
continues to rely on the decidedly low-tech tools of neuropsychological
assessment—behavioral tests that compare the effects of brain injuries
on performing particular tasks. Clinical Focus 15-4 , Neuropsychological
Assessment, illustrates its benefits.
cognitive neuroscience Study of the neural bases of cognition.
CLINICAL FOCUS 15-4

Neuropsychological Assessment
In this high-tech age of PET, fMRI, and ERP, low-tech behavioral
assessment endures as among the best, simplest, most economical
ways to measure cognitive function.
To illustrate the nature and power of neuropsychological
assessment, we compare three patients’ test performance on an array of
tests selected from among those used in a complete
neuropsychological assessment. The five tests presented here measure
verbal and visual memory, verbal fluency, abstract reasoning, and
reading. Performance was compared with that of a healthy control
participant.
In the delayed memory tests—one verbal, the other visual—the
patients and the control were read a list of words and two short stories.
They were also shown a series of simple drawings. Their task: repeat
the words and stories immediately after hearing them and draw the
simple figures.
Half an hour later, without warning, they were asked to perform the
tasks again. Their performance on these tests yielded the delayed
verbal and visual memory scores listed in the table.
In the delayed verbal fluency test, patients and control had 5
minutes to write down as many words as they could think of that start
with the letter s, excluding numbers and people’s names. Then came
the Wisconsin Card Sorting Test, which assesses abstract reasoning
(see Figure 15-8 ). Finally, all were given a reading test.
Subjects’ Scores
Test Control J. N. E. B. J. w.

Delayed verbal memory 17 9* 16 16

Delayed visual memory 12 14 8* 12

Verbal fluency 62 62 66 35*

Card-sorting errors 9 10 12 56*

Reading 15 21 22 17
 * Atypically poor score.

The first patient, J. N., was a 28-year-old man who had developed a
tumor in the anterior and medial left temporal lobe. His preoperative
psychological tests showed superior intelligence scores. His only
significant deficits appeared on tests of verbal memory.
When we saw J. N. a year after surgery that successfully removed
the tumor, he had returned to his job as a personnel manager. His
intelligence was still superior, but as the score summary shows, he was
impaired on the delayed verbal memory test, recalling only about 50
percent as much as the control and other subjects.
The second patient, E. B., was a college senior majoring in
psychology. An aneurysm in her right temporal lobe had burst due to a
bulge in the artery. The anterior part of that lobe had been removed. E.
B. was of above-average intelligence and completed her undergraduate
degree with good grades. Her score on the delayed visual memory test,
just over half the scores of the other test-takers, clearly showed her
residual deficit.
The third patient, also of above-average intelligence, was J. W., a
42-year-old police detective who had a college degree. A benign tumor
had been removed from his left frontal lobe.
We saw J. W. 10 years after his surgery. He was still on the police
force but working a desk job. His verbal fluency was markedly
reduced, as was his ability to solve the card-sorting task. His reading
skill, however, was unimpaired. This was also true of the other
patients.
Two principles emerge from the results of these three neuropsycho-
logical assessments:
1. Brain functions are localized. Damage to different brain regions
produces different symptoms.
2. Brain organization is asymmetrical. Left-hemisphere damage
preferentially affects verbal functions; right-hemisphere damage
preferentially affects nonverbal functions.

Sophisticated imaging techniques are helping cognitive neuroscientists

map the human brain. Its methods assist social psychologists in
discovering how the brain mediates social interactions and economists in
discovering how the brain makes decisions.
Mapping the Brain
Among the great scientific challenges of the twenty-first century, mapping
the human brain connectome may be the most intriguing. Toward this
end, the U.S. National Institutes of Health (NIH) awarded grants totaling
$40 million to map the complete structural and functional fiber pathway
connections of the human brain in vivo. Researchers participating in the
Human Connectome Project (HCP) are combining diffusion tensor
imaging (DTI) and functional connectivity magnetic resonance imaging
(fcMRI) to plot these connections in the living human brain. By the end of
2015 HCP investigators had completed scanning 1200 healthy adults’
brains, including 300 twin pairs.
brain connectome Map of the complete structural and functional
fiber pathways of the human brain in vivo.
The HCP’s goal is to provide a reference atlas for those seeking to
understand human brain function and dysfunction. It has attracted
considerable public interest, and an explosion of studies outside the HCP
also seeks to map the human brain. For example, in a review, Roser Sala-
Llonch and colleagues (2015) report that as people age, they show reduced
functional connectivity compared to young adults. The investigators
hypothesize that this finding could explain age-related cognitive changes.
For more on the HCP, including connectome images, go to
www.humanconnectomeproject.org . National Geographic published
an accessible article in February 2014.
Using fMRI in Brain Mapping
The fcMRI technique uses resting-state fMRI (rs-fMRI) to measure
functional correlations between brain regions. Pooling rs-fMRI data across
thousands of healthy young adults makes it possible to identify consistent
patterns of connectivity, or nerve tracts, in the brain. Utilizing rs-fMRI data
from 1000 participants, Thomas Yeo and colleagues (2011) parcellated the
human cerebral cortex into the 17 networks illustrated in Figure 15-9 .
The cerebral cortex is made up of primary sensory and motor networks
as well as the multiple, large-scale networks that form the association
cortex. The sensory and motor networks are largely local: adjacent areas
tend to show strong functional coupling with one another. In Figure 15-9 ,
the turquoise and blue/gray regions in somatosensory and motor cortex and
the purple region in visual cortex illustrate these couplings.
 In contrast, the association networks include areas distributed
throughout the prefrontal, parietal, anterior temporal, and midline regions.
In Figure 15-9 , the distributed yellow regions show prefrontal–posterior
parietal connectivity. Some distributed networks, shown in light red,
include temporal, posterior parietal, and prefrontal regions.
Unlike DTI, fcMRI does not measure static anatomical connectivity but
rather uses temporal (time-based) correlations between neurophysiological
activities in different regions to infer functional connectivity. One obvious
direction of investigations based on fcMRI is searching for individual
phenotypic variations. Such mapping will allow examination of specific
traits (e.g., musical ability) or psychiatric diagnoses (see the review by
Kelly and colleagues, 2012).

Left hemisphere, lateral view Left hemisphere

 Left hemisphere, Medial view
FIGURE 15-9 Parcellation of Cerebral Cortical Networks
An estimate of 17 cortical networks based on fcMRI data from 1000
participants. Each color represents a network. Some, such as the blue
auditory areas in temporal lobe, are localized; others are widely distributed,
such as the yellow regions, which reveal prefrontal–posterior parietal
connectivity. Republished with permission of the American Physiological Society from B. T. T.
Yeo, F. M. Fienen, J. Sepulcre, M. R. Sabuncu, D. Lashkari, et al., “The Organization of the Human
Cerebral Cortex Estimated by Intrinsic Functional Connectivity,” 2011, Journal of Neurophysiology,
106, pp. 1125–1165. Permission conveyed through Copyright Clearance Center, Inc.

Tractography Using Diffusion Tensor Imaging

DTI studies provide results, often called tractography, that complement the
networks mapped by fcMRI. Tractography measures actual
neuroanatomical pathways that can be related to specific traits. Traditional
postmortem tract tracing was performed on single brains. Today,
tractography can be performed quickly on many living brains, and
measurements can be made simultaneously in the entire brain. This
advance allows researchers to correlate specific behavioral traits with
specific patterns of connectivity.
Psyche Loui and her colleagues (2011) were interested in the neural
basis of perfect (or absolute) pitch, the ability not only to discriminate
among musical notes but also to name any note heard. Perfect pitch is rare
among humans but shared by people with remarkable musical talents.
Think Mozart. Development of perfect pitch is sensitive to early
experiences, including musical training and exposure to tonal languages
such as Japanese.
 Loui’s team studied musicians, with and without absolute pitch, who
were matched in gender, age, handedness, ethnicity, IQ score, and years of
musical training. Participants were given a test of pitch-labeling that
allowed the researchers to place the musicians with absolute pitch into two
categories: more accurate and less accurate. The less accurate group was
superior to participants without absolute pitch, who could not accurately
identify the note.
The investigators hypothesized that absolute pitch could be related to
increased connectivity in brain regions that process sounds. They used DTI
to reconstruct white-matter tracts connecting two temporal cortex regions
involved in auditory processing, the superior and middle temporal gyri,
and regions not involved in auditory processing (corticospinal tract). The
results, reproduced in Figure 15-10 , show that people with absolute pitch
have greater connectivity in temporal lobe regions responsible for pitch
perception than do people without it. The effect is largest in people in the
more accurate group.
Although enhanced connectivity appears in both hemispheres of the
musicians, when the investigators correlated performance on a test of
absolute pitch with tract volume, only left-hemisphere tract volume
predicted performance. It appears that having more local connections, or
hyperconnectivity, in the left hemisphere is responsible for absolute pitch.
hyperconnectivity Increased local connections between two related
brain regions.
It is tempting to speculate that other exceptional talents, such as
creativity, might be related to hyperconnectivity in cerebral regions.
Conversely, we can speculate that reduced structural and functional
connectivity is related to cognitive impairments after acquired brain
injuries and/or neurodevelopmental and psychiatric disorders.

Cognition and the Cerebellum

So far we have emphasized the role of the neocortex in cognitive
functions, in part because of its marked expansion in size and neuron
numbers in primate brains. Yet the human cerebellum accounts for 80
percent of the brain’s neurons. The cerebellum has long been known to
play a central role in motor control and motor learning, but the concurrent
evolution of neocortex, cerebellum, and cognitive complexity in primates
suggests that the cerebellum may play a larger role in cognitive processes
than investigators have appreciated (e.g., Barton, 2012).
 Research Focus 2-1 describes the effects of cerebellar agenesis.
(A) More accurate perfect pitch

(B) Less accurate perfect pitch

(C) Lacking perfect pitch
 FIGURE 15-10 Tractography of Temporal Lobe Auditory
Circuits Color overlaid on DTI images demonstrates tracts between the
superior temporal gyrus and middle temporal gyrus in three individuals.
Participants A and B had more accurate and less accurate perfect pitch,
respectively; Case C did not. The tracts that connect the regions in the left
hemisphere (orange) are larger in participants A and B than in C. Tracts
colored purple connect the regions in the right hemisphere. Copyright © 2011,
Massachusetts Institute of Technology. Loui, P., Li, H. C., Hohmann, A., & Schlaug, G. (2011).
Enhanced Connectivity in Absolute Pitch Musicians: A Model of Hyperconnectivity. Journal of
Cognitive Neuroscience 23 (4), 1015-1026. Permission conveyed through Copyright Clearance
Center, Inc.

The extensive neocortex–cerebellum interconnections include prefrontal

cortex, Broca’s area, and neocortical regions that have sensory or
perceptual functions. Thus, the cerebellum appears to be critical in
producing fine movements and perception, but some executive function
also may be associated with working memory, attention, language, music,
and decision-making processes (Bauman et al., 2015). No single coherent
model of cerebellar activity in cognition has emerged, partly because
researchers interested in cognitive functions have neglected the cerebellum
for decades. Undoubtedly, the coming decade will deliver an abundance of
new information, allowing for a better- informed model of cerebellar
functions in cognition.

Social Neuroscience
By combining cognitive neuroscience tools, especially functional
neuroimaging, with abstract constructs from social psychology, social
neuroscience seeks to understand how the brain mediates social
interactions. Matthew Lieberman (2007) identified broad themes that
attempt to encompass all cognitive processes involved in understanding
and interacting with others and in understanding ourselves.
social neuroscience Interdisciplinary field that seeks to understand
how the brain mediates social interactions.
Understanding Others
Animals’ mind and experiences are not open to direct inspection. We
infer animals’ mind in part by observing their behaviors and peoples’ mind
by listening to their words. In doing so, we may develop a theory of mind,
the attribution of mental states to others. Theory of mind includes an
understanding that others may have feelings and beliefs different from our
own. This broader understanding has led some investigators to conclude
that theory of mind may be uniquely human. But many researchers who
study apes strongly believe that other apes, too, possess a theory of mind.
theory of mind Ability to attribute mental states to others.
Many fMRI studies over the past decade suggest that the brain region
believed most closely associated with theory of mind is the dorsolateral
prefrontal cortex (see Figure 15-2 ).
Human prefrontal regions are disproportionately large as corrected for
brain size, but other apes also have large prefrontal regions. The anatomy
supports the likelihood that they also possess a theory of mind.
The capacity to understand others can also be inferred from the
presence of empathy. For example, when participants watch videos of
others smelling disgusting odors, they report a feeling of disgust.
Lieberman and his colleagues (Rameson et al., 2012) used fMRI to assess
the neural correlates of empathy by asking participants to empathize with
sad images. Empathy correlated with increased activity in the medial
prefrontal region, suggesting that the area is critical for empathic
experience.
 The Povinelli Group LLC
Looking at its reflection and pointing to a dot placed on its forehead,
this chimpanzee displays self-recognition, a cognitive ability
possessed by higher primates.

Understanding Oneself
Not only are we humans aware of others’ intentions, we also have a sense
of self. Humans and apes have the ability to recognize themselves in a
mirror, an ability that human infants demonstrate by about 21 months of
age. Studies using fMRI show that when we recognize our own face versus
the face of familiar others, brain activity increases in the right lateral
prefrontal cortex and in the lateral parietal cortex. The parietal cortex
activation is thought to reflect the body’s recognition of what itself feels
like.
But self-recognition is only the beginning of understanding oneself.
People also have a self-concept that includes beliefs about their own
personal traits (e.g., kind, intelligent). When participants are asked to
determine whether trait words or sentences are self-descriptive, brain
activity in medial prefrontal regions increases.
Self-Regulation
Self-regulation is the ability to control emotions and impulses as a means
of achieving long-term goals. We may wish to yell at the professor because
an exam was unfair, but most of us recognize that this course will not be
productive. Dynamic imaging studies again reveal that prefrontal regions
are critical in social cognition, in this case in self-regulation.
Children are often poor self-regulators, which probably reflects slow
development of the prefrontal regions responsible for impulse control. A
uniquely human ability to self-regulate is by putting feelings into words, a
strategy that allows us to control emotional outbursts. Curiously, such
verbal labeling is associated with increased activity in the right lateral pre-
frontal regions but not in the left.
Section 8-2 describes unique aspects of frontal lobe development that
extend beyond childhood—up to age 30.
Not only can humans control their emotions; they also have
expectations about how a stimulus might feel (e.g., an injection by
syringe). Our expectations can alter the actual feeling of an event. It is
common for people to say ouch when they do something like stub a toe,
even if they actually feel no pain. Nobukatsu Sawamoto and colleagues
(2000) found that when participants expect pain, activity increases in the
anterior cingulate cortex (see Figure 15-2 B), a region associated with pain
perception, even if the stimulus turns out not to be painful.
Feeling and treating physical pain is a topic in Section 11-4 . Focus
12-1 reports on emotional pain.
Living in a Social World
We spend much of our waking time interacting with others socially. In a
sense, our understanding of our self and our social interactions link
together into a single mental action. One important aspect of this behavior
includes forming attitudes and beliefs about ourselves and about others.
When we express attitudes (including prejudices) toward ideas or human
groups, brain imaging shows activation in prefrontal, anterior cingulate,
and lateral parietal regions.
Samuel McLure and colleagues (2004) took advantage of the fact that
many people have strong attitudes toward cola-flavored sodas. Coca-Cola
and Pepsi Cola are nearly identical in chemical composition, yet
subjectively, people routinely prefer one to the other. The researchers ran
blind taste tests among people who stated a cola brand preference.
As a group, participants failed to discriminate the drinks accurately
when they were presented in a blind taste test. Brain activity was also
equivalent for each cola in the blind condition. However, when participants
believed that they were drinking Coca-Cola, significant changes in brain
activity were recorded in many regions, including the hippocampus and
dorsolateral prefrontal cortex. The investigators concluded that cultural
information biases brain systems, which in turn biases attitudes.
Social Cognition and Brain Activity
Social cognitions running the gamut from understanding ourselves to
understanding others clearly are associated with activation of specific brain
regions, especially prefrontal regions. The obvious conclusion is that
prefrontal activity produces our social cognitions, just as activity in visual
regions produces our visual perceptions. But this conclusion has proved
controversial. Ed Vul and colleagues (2009, 2012) go so far as to suggest
that “correlations in social neuroscience are voodoo.” Their assertion has
led to strong disputations (e.g., Lieberman et al., 2012). The arguments are
complex, focus on the nature of the analysis of fMRI data, and will
certainly continue. In our view, the debate does not impugn the general
conclusion that brain states produce behavioral states.

Neuroeconomics
Historically, economics was a discipline based on the “rational actor,” the
belief that people make rational decisions. In the real world, people often
make decisions based on assumption or intuition, as is common in
gambling. Why don’t people always make rational decisions?
Leonard Mlodinow’s wonderful 2009 book, The Drunkard’s Walk:
How Randomness Rules Our Lives, offers many everyday examples.
The cerebral processes underlying human decision making are not
easily inferred from behavioral studies. But investigators in the field of
neuroeconomics, which combines ideas from economics, psychology, and
neuroscience, attempt to explain those processes by studying patterns of
brain activity as people make decisions in real time. The general
assumption among neuroeconomists is that two neural decision pathways
influence our choices. One is deliberate, slow, rule-driven, and emotionally
neutral; it acts as a reflective system. The other pathway—fast, automatic,
emotionally biased—forms a reflexive system.
neuroeconomics Interdisciplinary field that seeks to understand how
the brain makes decisions.
If people must make quick decisions they believe will provide
immediate gain, widespread activity appears in the dopaminergic reward
system. This includes the ventromedial prefrontal cortex and ventral
striatum (nucleus accumbens): the reflexive pathway. If slower,
deliberative decisions are possible, activity is greater in the lateral
prefrontal, medial temporal, and posterior parietal cortex, the areas that
form the reflective pathway.
Figure 6-17 maps the dopaminergic pathways associated with reward.
Neuroeconomists are looking to identify patterns of neural activity in
everyday decision making, patterns that may help account for how people
make decisions about their finances, social relations, and other personal
choices. Although most neuroeconomic studies to date have used fMRI, in
principle these studies could also use other noninvasive imaging
technologies. Epigenetic factors probably contribute to developing the
balance between the reflective and reflexive systems in individuals.
Epigenetic studies therefore may help explain why many people make
decisions that are not in their long-term best interest.
Because of predictions that all mammals will have similar reflective and
reflexive decision systems and because all animals make decisions, the
neural bases of decision processes in nonhumans undoubtedly will receive
more study in the future.
 15-3 REVIEW
Expanding Frontiers of Cognitive Neuroscience
Before you continue, check your understanding.
1 . Noninvasive imaging techniques enable cognitive psychologists to
investigate the neural bases of thought in the “normal” brain, leading
to the field called ___________.
2 . Imaging methods such as DTI and fcMRI are allowing researchers to
develop a ___________, a map of the complete structural and
functional fiber pathway connections in the living human brain.
3 . The role of the ___________ in cognition, formerly unappreciated, is
now attracting researchers’ attention.
4 . Social neuroscience is an interdisciplinary field that seeks to
understand how the brain mediates ___________.
5 . Our attribution of mental states to others is known as ___________.
6 . Neuroeconomics seeks to understand the neural bases of
___________.
7 . List four general themes of social neuroscience research.
Answers appear at the back of the book.

For additional study tools, visit LaunchPad: Launch Pad

www.macmillanhighered.com/launchpad/kolb5e
 15-4 Cerebral Asymmetry in Thinking
Fundamental to behavioral neuroscience was the finding by Paul Broca
and his contemporaries in the mid-1800s that language is lateralized to
the brain’s left hemisphere. But the implications of lateralized brain
functions were not really understood until the 1960s, when Roger Sperry
(1968) and his colleagues began to study people who, as described in
Research Focus 15-1 , had undergone surgical separation of the two
hemispheres as a treatment for intractable epilepsy. It soon became
apparent that the cerebral hemispheres are more functionally specialized
than researchers had previously realized. Before considering how the
brain’s two sides cooperate in generating cognitive activity, we look at the
anatomical differences between the left and right hemispheres.
Seizing on Sperry’s findings, the 1980s saw an avalanche of self-help
books about “left-brained” and “right-brained” people. The novelty
wore off, but cerebral asymmetry remains important to understanding
how the human brain thinks.

Anatomical Asymmetry
Building on Broca’s findings, investigators have learned how the
language- and music-related areas of the left and right temporal lobes
differ anatomically. In particular, the primary auditory area is larger on
the right, whereas the secondary auditory areas are larger on the left in
most people. Other brain regions also are asymmetrical.
Figure 15-11 shows that the lateral fissure, which partly separates the
temporal and parietal lobes, has a sharper upward course in the right
hemisphere relative to the left. As a result, the posterior right temporal
lobe is larger than the same region on the left, as is the left parietal lobe
relative to the right.
Among the anatomical asymmetries in the frontal lobes, the region of
sensorimotor cortex representing the face is larger in the left hemisphere
than in the right, a difference that presumably corresponds to the left
hemisphere’s special role in talking. Broca’s area is organized differently
on the left and the right. The area visible on the brain’s surface is about
one-third larger on the right than on the left, whereas the cortical area
buried in the sulci of Broca’s area is greater on the left than on the right.
 Not only do these gross anatomical differences exist but so too do
hemispheric differences in the details of their cellular and neurochemical
structures. For example, neurons in Broca’s area on the left have larger
dendritic fields than do corresponding neurons on the right. The discovery
of structural asymmetries told us little about the reasons for such
differences, but ongoing research is revealing that they result from
underlying differences in cognitive processing by the brain’s two sides.
Although many anatomical asymmetries in the human brain are related
to language, brain asymmetries are not unique to humans. Most if not all
mammals have asymmetries, as do many bird species. The functions of
cerebral asymmetry therefore cannot be limited to language processing.
Rather, human language likely evolved after the brain became
asymmetrical. Language simply took advantage of processes, including
the development of mirror neurons, that had already been lateralized by
natural selection in earlier members of the human lineage.

FIGURE 15-11 Cerebral Asymmetry The lateral fissure takes a

flatter course in the left hemisphere than in the right. As a result, the
posterior right temporal lobe is larger than the same region on the left side,
and the inferior parietal region is larger on the left than on the right.

Functional Asymmetry in Neurological

Patients
The specialized functions of the cerebral hemispheres become obvious in
people with damage to the left or right side of the brain. To see these
functional differences clearly, compare the cases of G. H. and M. M.
Right Parietal Damage
When G. H. was 5 years old, as he was hiking with his family, a large
rock rolled off an embankment and hit him on the head. He was
unconscious for a few minutes and had a severe headache for a few days
but quickly recovered. Around age 18, however, he started having
seizures. Neurosurgical investigation revealed that G. H. had had a right
posterior parietal injury from the rock accident. Figure 15-12 A shows
the area affected. After surgery to remove this area, G. H. had weakness
on the left side of his body and showed contralateral neglect. But these
symptoms lessened fairly quickly, and a month after the surgery, they had
completely cleared.
Nevertheless, G. H. had chronic difficulties in copying drawings; 4
years later, he still performed this task at about the level of a 6-year-old.
He also had trouble assembling puzzles, a pastime he enjoyed before his
surgery. When asked to perform mental manipulations like the one in
Figure 15-6 , he became very frustrated and refused to continue. G. H.
also had difficulty finding his way around familiar places. The landmarks
he had used to guide his travels before the surgery no longer worked for
him. G. H. now has to learn street names and use a verbal strategy to go
from one place to another.
 FIGURE 15-12 Contrasting Parietal Lobe Injuries
Left Parietal Damage
M. M.’s difficulties were quite different. A meningioma had placed
considerable pressure on the left parietal region. The tumor was surgically
removed when M. M. was 16 years old. It had damaged the area shown in
Figure 15-12 B.
Meningioma is imaged in Focus 3-3.
After the surgery, M. M. had various problems, including aphasia,
impaired language use. The condition lessened over time: a year after the
surgery, M. M. spoke fluently. Unfortunately, other difficulties persisted.
In solving arithmetic problems, in reading, and even in simply calling
objects or animals by name, M. M. performed at about a 6-year-old level.
She had no difficulty making movements spontaneously, but when asked
to copy a series of arm movements, such as those diagrammed in Figure
15-13 , she had great difficulty. She could not figure out how to make her
arm move to match the example. A general impairment in making
voluntary movements in the absence of paralysis or a muscular disorder is
a symptom of apraxia, the inability to complete a plan of action
accurately.
Section 10-4 describes how left-hemisphere damage causes aphasias.
Section 11-5 explains how somatosensory cortex damage contributes
to apraxia.

Series 1
Series 2
 FIGURE 15-13 Two Arm Movement Series Subjects observe the
tester perform each sequence, then copy it as accurately as they can.
People with left-hemisphere injury, especially in the posterior parietal
region, are impaired at copying such movements.

Lessons from Patients G. H. and M. M.

What can we learn about brain function by comparing G. H. and M. M.?
Their lesions were in approximately the same location but in opposite
hemispheres, and their symptoms were very different.
Judging from G. H.’s difficulties, the right hemisphere contributes to
controlling spatial skills, such as drawing, assembling puzzles, and
navigating in space. In contrast, M. M.’s condition reveals that the left
hemisphere seems to contribute to controlling language functions and
cognitive tasks related to schoolwork—namely, reading and arithmetic. In
addition, the left hemisphere’s role in controlling voluntary movement
sequences differs from the right hemisphere’s role.
To some extent, then, the left and right hemispheres think about
different types of information. The question is whether these functional
differences can be observed in a healthy brain.

Functional Asymmetry in the Healthy Brain

In the course of studying the auditory capacity of people with a temporal
lobe lesion, Doreen Kimura (1967) found something unexpected. She
presented her control participants with two strings of digits, one played
into each ear, a procedure known as dichotic listening. The task was to
recall as many digits as possible.
dichotic listening Experimental procedure for simultaneously
presenting a different auditory input to each ear through stereophonic
earphones.
Kimura found that the controls recalled more digits presented to the
right ear than to the left. This result is surprising because the auditory
system crosses repeatedly, beginning in the midbrain. Nonetheless,
information coming from the right ear seems to have preferential access
to the left (speaking) hemisphere.
In a later study, Kimura (1973) played two pieces of music for
participants, one to each ear. She then gave the participants a multiple-
choice test, playing four bits from musical selections and asking the
participants to pick out the bits they had heard before. In this test, she
found that participants were more likely to recall the music played to the
left ear than to the right. This result implies that the left ear has
preferential access to the right (musical) hemisphere.
The demonstration of this functional asymmetry in the healthy brain
provoked much interest in the 1970s, leading to demonstrations of
functional asymmetries in the visual and tactile systems as well. Consider
the visual system. If we fixate on a target, such as a dot positioned
straight ahead, all the information to the left of the dot goes to the right
hemisphere and all the information to the right of the dot goes to the left
hemisphere, as shown in Figure 15-14 .
If information is presented for a relatively long time—say, 1 second—
we can easily report what was in each visual field. If, however, the
presentation is brief—say, only 40 milliseconds—then the task is
considerably harder. This situation reveals a brain asymmetry.
Words presented briefly to the right visual field and hence sent to the
left hemisphere are more easily reported than are words presented briefly
to the left visual field. Similarly, if complex geometric patterns or faces
are shown briefly, those presented to the left visual field and hence sent to
the right hemisphere are more accurately reported than are those
presented to the right visual field.
Apparently, the hemispheres not only think about different types of
information, they also process information differently. The left
hemisphere seems biased toward processing language-related
information, whereas the right hemisphere seems biased toward
processing nonverbal, and especially spatial, information.
A word of caution: Although asymmetry studies are fascinating, what
they tell us about the differences between the hemispheres is not entirely
clear. They tell us something is different, but it is a broad leap to conclude
that the hemispheres house entirely different skill sets.
Those popular left brain–right brain accounts of the 1980s ignored
the many functions the hemispheres have in common.
The hemispheres have many common functions, such as controlling
movement in the contralateral hand and processing sensory information
through the thalamus. Still, differences in the hemispheres’ cognitive
operations do exist. We can better understand these differences by
studying split-brain patients, whose cerebral hemispheres have been
surgically separated for medical treatment.
FIGURE 15-14 Visual Pathways to the Hemispheres When fixating at a
point, each eye sees both visual fields but sends information about the right visual field
only to the left hemisphere. Information about the left visual field proceeds only to the
right hemisphere. In healthy participants given short exposures to stimuli (well under 1
second), the left hemisphere is more accurate at perceiving words, whereas the right
hemisphere is more accurate at perceiving objects, including faces.

Functional Asymmetry in the Split Brain

Before considering the details of split-brain studies, let us review what we
already know about cerebral asymmetry. First, the left hemisphere has
speech; the right hemisphere does not. Second, as demonstrated in
Research Focus 15-1 , on page 520 , the right hemisphere performs better
than the left on certain nonverbal tasks, especially those that engage
visuo-spatial skills.
But how does a severed corpus callosum affect how the brain thinks?
After the corpus callosum has been cut, the hemispheres have no way of
communicating with one another. The left and right hemispheres are
therefore free to think about different things. In a sense, a split-brain
patient has two brains.
One way to test the hemispheres’ cognitive functions in a split-brain
patient takes advantage of the fact that information in the left visual field
goes to the right hemisphere and information in the right field goes to the
left hemisphere (see Figure 15-14 ). With the corpus callosum cut,
however, information presented to one side of the brain has no way of
traveling to the other side. It can be processed only in the hemisphere that
receives it.
Experiments 15-3 and 15-4 show some basic testing procedures based
on this dichotomy. The split-brain subject fixates on the dot in the center
of the screen while information is presented to the left or right visual
field. The person must respond with the left hand (controlled by the right
hemisphere), with the right hand (controlled by the left hemisphere), or
verbally (also a left-hemisphere function). In this way, researchers can
observe what each hemisphere knows and what it is capable of doing.
As illustrated in Experiment 15-3 , for instance, a picture—say, of a
spoon—might be flashed and the subject asked to state what he or she
sees. If the picture is presented to the right visual field, the person will
answer, “Spoon.” If the picture is presented to the left visual field,
however, the person will say, “I see nothing.” The subject responds in this
way for two reasons:
1. The right hemisphere (which receives the visual input) does not talk, so
it cannot respond verbally, even though it sees the spoon in the left
visual field.
2. The left hemisphere does talk, but it does not see the spoon, so it
answers—quite correctly, from its own perspective—that nothing was
presented.
 EXPERIMENT 15-3

Question: Will severing the corpus callosum affect the way

in which the brain responds?
Procedure

The split-brain subject fixates on the dot in the center of the

screen while an image is projected to the left or right visual
field. He is asked to identify verbally what he sees.

Results

If the spoon is presented to the right visual field, the subject

answers, “Spoon.”

If the spoon is presented to the left visual field, the subject

answers, “I see nothing.”
Conclusion: When the left hemisphere, which can speak, sees the
spoon in the right visual field, the subject responds correctly. When the
right hemisphere, which cannot speak, sees the spoon in the left visual
field, the subject does not respond.
 Braille

Now suppose the task changes. In Experiment 15-4 A, the picture of a

spoon is still presented to the left visual field, but the subject is asked to
use the left hand to pick out the object shown on the screen. In this case,
the left hand, controlled by the right hemisphere, which sees the spoon,
readily picks out the correct object. Can the right hand also choose
correctly? No, because it is controlled by the left hemisphere, which
cannot see the spoon. If the person in this situation is forced to select an
object with the right hand, the left hemisphere does so at random.
Now let’s consider an interesting twist. In the Procedure for
Experiment 15-4 B, each hemisphere is shown a different object—say, a
spoon to the right hemisphere and a pencil to the left. The subject is
asked to use both hands to pick out “the object.” The problem here is that
the right and left hands do not agree. While the left hand tries to pick up
the spoon, the right hand tries to pick up the pencil or tries to prevent the
left hand from picking up the spoon.
This conflict between the hemispheres can be seen in the everyday
behavior of some split-brain subjects. One woman, P. O. V., reported
frequent interhemispheric competition for at least 3 years after her
surgery. “I open the closet door. I know what I want to wear. But as I
reach for something with my right hand, my left comes up and takes
something different. I can’t put it down if it’s in my left hand. I have to
call my daughter.”
We know from Experiment 15-3 that the left hemisphere is capable of
using language, and Research Focus 15-1 reveals that the right
hemisphere has visuospatial capabilities that the left hemisphere does
not. Although findings from half a century of studying split-brain
patients show that the hemispheres process information differently,
another word of caution is needed. There is more functional overlap
between the hemispheres than was at first suspected. The right
hemisphere, for instance, does have some language functions, and the
left hemisphere does have some spatial abilities. Nonetheless, the two
undoubtedly are different.

Explaining Cerebral Asymmetry

Various hypotheses propose to explain hemispheric differences. One
idea, that the left hemisphere is important in controlling fine movements,
dates back a century. Recall M. M., the meningioma patient with left
parietal lobe damage and apraxia (see Figure 15-12 B). Although the
apraxia subsided, she was left with chronic trouble in copying
movements.
Perhaps one reason that the left hemisphere has a role in language is
that speaking requires fine motor movements of the mouth and tongue.
Significantly, damage to the language-related areas of the left
hemisphere almost always interferes with both language and movement,
whether the person speaks or signs. Reading Braille, however, may not
be so affected by left-hemisphere lesions. Most people prefer to use the
left hand to read Braille, which essentially consists of spatial patterns, so
processes related to reading Braille may reside in the right hemisphere.
That said, another clue that the left hemisphere’s specialization for
language may be related to its special role in controlling fine movements
comes from investigating where the brain processes certain parts of
speech. Recall that cognitive systems for representing abstract concepts
likely are related to systems that produce more concrete behaviors.
Consequently, we might expect that the left hemisphere would
participate in forming concepts related to fine movements.
 EXPERIMENT 15-4

(A) Question: How can the right hemisphere of a split-brain

subject show that it knows information?
Procedure

The split-brain participant is asked to use his left hand to pick

out the object shown on the screen to the left visual field (right
hemisphere).

Results

The participant chooses the spoon with his left hand because
the right hemisphere sees the spoon and controls the left hand.
If the right hand is forced to choose, it will do so by chance
because no stimulus is shown to the left hemisphere.
(B) Question: What happens if both hemispheres are asked
to respond to competing information?
Procedure

Each visual field is shown a different object—a spoon to the left

and a pencil to the right. The split-brain participant is asked to
use both hands to pick up the object seen.

Results

In this case, the right and left hands do not agree. They may
each pick up a different object, or the right hand may prevent
the left hand from performing the task.
 Conclusion: Each hemisphere is capable of responding independently.
The left hemisphere may dominate in a competition, even if the
response is not verbal.

Concepts that describe movements are the parts of speech we call

verbs. A fundamental difference between left- and right-hemisphere
language abilities is that verbs seem to be processed only in the left
hemisphere, whereas nouns are processed in both hemispheres. In other
words, not only does the left hemisphere specialize in producing actions,
it also produces mental representations of actions in the form of words.
If the left hemisphere excels at language because it is better at
controlling fine movements, what is the basis of the right hemisphere’s
abilities? One idea is that the right hemisphere specializes in controlling
movements in space. In a sense, this role elaborates the functions of the
dorsal visual stream (diagrammed in Figure 15-3 ).
Once again, we can propose a link between movement at a concrete
level and movement at a more abstract level. If the right hemisphere is
producing movements in space, then it is also likely to produce mental
images of such movements. We would therefore predict impairment of
right-hemisphere patients’ ability both to think about and to make
spatially guided movements. And they are thus impaired.
Bear in mind that theories about the reasons for hemispheric
asymmetry are highly speculative. The brain has evolved to produce
movement and to construct a sensory reality, so the observed asymmetry
must somehow relate to these overriding functions. That is, more
recently evolved functions, such as language, likely are extensions of
preexisting functions. So the fact that language is represented
asymmetrically does not mean that the brain is asymmetrical because of
language. After all, other species that do not talk have an asymmetrical
brain.
The nervous system produces movement within a perceptual world
the brain constructs.

Left Hemisphere, Language, and Thought

As we end our examination of brain asymmetry, consider one more
provocative idea. Michael Gazzaniga (1992) proposed that the left
hemisphere’s superior language skills are important for understanding
the differences between humans’ and other animals’ thinking. He called
the speaking hemisphere the interpreter. The following experiment, using
split-brain patients as subjects, illustrates what Gazzaniga meant.
Each hemisphere is shown a picture of a match followed by a picture
of a piece of wood, for example. Another set of pictures is then shown.
The task is to pick from this set a third picture that has an inferred
relation to the first two. In this example, the third related picture might
be a bonfire. The right hemisphere is incapable of making the inference
that a match struck and held to a piece of wood could start a bonfire,
whereas the left hemisphere easily arrives at this interpretation.
An analogous task uses words. One or the other hemisphere might be
shown the words pin and finger then be asked to pick out a third word
related to the other two. In this case, the correct answer might be bleed.
The right hemisphere cannot make this connection. Although it has
enough language ability to pick out close synonyms for pin and finger
(needle and thumb, respectively), it cannot make the inference that
pricking a finger with a pin will result in bleeding.
Again, the left hemisphere has no difficulty with this task. Apparently,
the left hemisphere’s language capability gives it a capacity for
interpretation that the right hemisphere lacks. One reason may be that
language serves to label and express the computations of other cognitive
systems.
Gazzaniga goes even further. He suggests that the evolution of left-
hemisphere language abilities makes humans a “believing” species:
humans can make inferences and have beliefs about sensory events. By
contrast, Alex, the African grey parrot profiled in Comparative Focus 15-
2, would not have been able to make inferences or hold beliefs because
he did not have a system analogous to our left-hemisphere language
system. Alex could use language but could not make inferences about
sensory events with language.
Gazzaniga’s idea is intriguing. It implies a fundamental difference in
the nature of cerebral asymmetry—and therefore in the nature of
cognition—that exists between humans and other animals because of the
nature of human language. We return to this idea in Section 15-7 .
 15-4 REVIEW
Cerebral Asymmetry in Thinking
Before you continue, check your understanding.
1 . The right hemisphere plays a role in ___________ and ___________.
2 . The left hemisphere plays a role in ___________ and ___________.
3 . The split brain results from cutting apart the ___________.
4 . Why does it matter that the two cerebral hemispheres process
information differently?
Answers appear at the back of the book.

For additional study tools, visit LaunchPad: Launch Pad

www.macmillanhighered.com/launchpad/kolb5e
 15-5 Variations in Cognitive Organization
No two brains are identical. Some differences are genetically
determined; others result from plastic changes caused, for example, by
experience and learning or epigenetic factors. Some brain differences are
idiosyncratic (unique to a particular person); many others are systematic
and common to whole categories of people. In this section, we consider
two systematic variations in brain organization, those related to sex and
handedness, and one idiosyncratic variation, the fascinating sensory
phenomenon synesthesia.

Sex Differences in Cognitive Organization

The idea that men and women think differently probably originated with
the first men and women. Science backs it up. Books, including one by
Doreen Kimura (1999), present persuasive evidence for marked
differences between men’s and women’s performance on many cognitive
tests. As illustrated in Figure 15-15 , paper-and-pencil tests consistently
show that on average females have better verbal fluency than males do,
whereas males do better on tests of spatial reasoning. Our focus here is
on how such differences relate to the brain.
Neural Bases of Sex Differences
Considerable evidence points to sex differences, both in the brain’s gross
cerebral structure and at a neuronal level. Jill Goldstein and her
colleagues (2001) conducted a large MRI study of sexual dimorphism in
the human brain. They found that women have larger volumes of dorsal
prefrontal and associated paralimbic regions, whereas men have larger
volumes of more ventral prefrontal regions (Figure 15-16 ). (Brain size
is related to body size, and on average, male brains are bigger than
female brains, so the investigators corrected for size.)
Another way to measure sex differences is cortical thickness
independent of volume. Figure 15-17 shows that relative to men, women
have increased cortical gray matter concentration in many cortical
regions. Men’s gray matter concentration, by contrast, is more uniform
across the cortex. The MRI studies represented in Figures 15-16 and 15-
17 thus point to differences between men’s and women’s cortical
organization.
 Sex differences in neuronal structure also exist. Gonadal hormones
influence the structure of neurons in the prefrontal cortices of rats (Kolb
& Stewart, 1991). The cells in one pre-frontal region, located along the
midline, have larger dendritic fields (and presumably more synapses) in
males than in females, as shown in the top row of Figure 15-18 on page
548 . In contrast, the cells in the orbitofrontal region have larger
dendritic fields (and presumably more synapses) in females than in
males, as shown in the bottom row. These sex differences are not found
in rats that have had their testes or ovaries removed at birth. Presumably,
sex hormones somehow change the brain’s organization and ultimately
its cognitive processing.

Participants were asked to draw a line to indicate waterline in

tipped glass.

(A) Spatial relation–type task

(B) Mental rotation–type task

Participants were asked to choose the block that could be made

from a plan.
 Males are generally more accurate than females at this task.

(C) Short-term-memory–type task

Participants were asked to fill in the empty boxes with the

appropriate symbols from the top row.

When given a larger number of boxes to fill in and a time limit,

females complete from 10 to 20 percent more items than males
do.

(D) Verbal fluency–type task

 Participants were asked to fill in each blank to form words that
make a sentence.

1. F ________ M ________ A ________ J ________

2. C ________ B ________ E ________ S ________
3. D ________ I ________ J ________ K ________

Females are generally faster at this type of test than males are.

Lateral view

FIGURE 15-15 Tasks

That Reliably Show Sex-Related
Cognitive Differences
Medial view
 FIGURE 15-16 Sex Differences in Brain Volume Women’s
brain volume in prefrontal and medial paralimbic regions (orange) is
significantly higher than men’s. Men have larger relative volumes in the
medial and orbitofrontal cortex and the angular gyrus (green). Orange
areas correspond to regions that have high levels of estrogen receptors
during development, green to regions high in androgen receptors during
development. Information from J. M. Goldstein, L. J. Seidman, N. J. Horton, N. Makris, D. N.
Kennedy, et al. (2001). Normal sexual dimorphism of the adult human brain assessed by in vivo
magnetic resonance imaging. Cerebral Cortex 11, pp. 490–497.

Stewart and Kolb (1994) found that the presence or absence of

gonadal hormones affects the brain in adulthood as well as in early
development. In this study, which focused on how hormones affect
recovery from brain damage, middle-aged female rats’ ovaries were
removed. On examining the brains of these rats and those of control rats
some months later, researchers observed that the cortical neurons of the
rats whose ovaries had been removed—especially the prefrontal neurons
—had undergone structural changes. The cells had grown 30 percent
more dendrites, and their spine density increased compared with the
control rats’ cells. Clearly, gonadal hormones can affect the brain’s
neuronal structure at any point in an animal’s life.
An additional way to consider the neural basis of sex differences is to
look at the effects of cortical injury in men and women. If sex
differences exist in the neural organization of cognitive processing,
differences in the effects of cortical injury in the two sexes should
appear. Doreen Kimura (1999) conducted this kind of study and showed
that the pattern of cerebral organization within each hemisphere may in
fact differ between the sexes.

Courtesy Dr. Arthur Toga, Laboratory of Neuro Imaging at USC

Left hemisphere
FIGURE 15-17 Sex Differences in Gray Matter
Concentration Women show increased gray matter concentration in
the cortical regions, shown in color on this MRI. Gray-shaded regions are
not statistically different in males and females.

Investigating people who had a cortical stroke in adulthood, Kimura

tried to match the location and extent of injury in her male and female
subjects. She found that men and women were almost equally likely to
be aphasic subsequent to left-hemisphere lesions of some kind. But men
were more likely to be aphasic and apraxic after damage to the left
posterior cortex, whereas women were far more likely to be aphasic and
apraxic after lesions to the left frontal cortex. These results, summarized
in Figure 15-19 , suggest a sex difference in intrahemispheric
organization, a conclusion supported by a later study (Figure 15-20 )
using diffusion tensor analysis of brain networks in over 900
participants. The population, comprising nearly equal numbers of each
sex, showed that females have greater inter hemispheric connectivity,
whereas males’ intra hemispheric connectivity is greater (Ingalhalikar et
al., 2013).
Evidence strongly favors a neural basis for gender identity, including
transgender identity. Georg Krantz and colleagues (2014) used diffusion
tensor analysis to compare brain networks of female-to-male and male-
to-female transsexuals with those of gender-typical females and males.
The imaging replicated the distinctly different pattern of hemispheric
connectivity in gender-typical females and males. The pattern of
connectivity in transsexuals, however, falls halfway between those of
females and males.
Section 12-5 describes the gender identity spectrum.
That is, DTIs of the white matter microstructure of transgender
females and males falls halfway between that of gender-typical females
and males. The investigators take these patterns as evidence that neural
white matter microstructure is influenced by the hormonal environment
during late prenatal and early postnatal brain development. This is the
time, they hypothesize, that determines gender identity. But genital
differentiation is determined earlier in development. The timing
difference thus makes a genital–gender mismatch possible.
Evolution of Sex-Related Cognitive Differences
Although gonadal hormones have taken center stage in explaining sex
differences in cognitive function, we are still left to question how these
differences arose. To answer this question, we must look back at human
evolution. Mothers pass their genes to both sons and daughters, and
fathers do the same. Ultimately then, males and females of a species
have virtually all their genes in common.
The only way a gene can affect one sex preferentially is for the
animal’s gonadal hormones to influence the gene’s activities. Gonadal
hormones are in turn determined by the presence or absence of the Y
chromosome, which carries a gene called the testes-determining factor.
TDF stimulates the body to produce testes, which then manufacture
androgens, which in turn influence other genes’ activities.
Like other body organs, the brain is a potential target of natural
selection. We should therefore expect to find sex-related differences in
the brain whenever the sexes differ in the adaptive problems they have
faced in their species’ evolution. Aggressive behavior is a good example.
Males in most mammalian species typically are more physically
aggressive than females. This trait presumably improved males’
reproductive success by selecting against individuals with lesser
aggressiveness. Producing higher levels of aggression entails male
hormones. We know from studies of nonhuman species that aggression is
related directly to the presence of androgens and to their effects on gene
expression, both during brain development and later in life. In this case,
therefore, natural selection has worked on gonadal hormone levels to
favor aggressiveness in males.
Cells from medial frontal cortex
 Cells from orbitofrontal region
FIGURE 15-18 Sex Differences in Neuronal
Architecture In the frontal cortices of male and female rats, cells in
the midline frontal region (top two drawings) are more complex in males
than in females, whereas the opposite is true of the orbitofrontal region
(bottom two drawings).

Apraxia
Aphasia
KEY

Females
Males
 FIGURE 15-19 Evidence
for Sex Differences in
Cortical Organization Apraxia and aphasia are associated with
frontal damage to the left hemisphere in women and with posterior
damage in men. Information from D. Kimura (1999). Sex and Cognition,
Cambridge, MA: MIT Press.

Explaining sex-related differences in cognitive processes, such as

language or spatial skills, is more speculative than explaining sex-related
differences in aggressive behavior. Nevertheless, some hypotheses come
to mind. We can imagine, for instance, that in the history of mammalian
evolution, males have tended to range over larger territories than have
females. This behavior requires spatial abilities, so evolution would have
favored these skills in males.
Support for this hypothesis comes from comparing spatial problem
solving in males of closely related mammalian species—species in
which the males range over large territories versus species in which the
males’ range is not extensive. Pine voles, for example, have a restricted
range and no sex-related difference in range, whereas meadow voles
have a range about 20 times as large as pine voles’, and male meadow
voles range more widely than the females.
 Meadow voles display far superior spatial skills to those of pine voles.
A sex difference in spatial ability among meadow voles favors males, but
pine voles have no such sex difference. The hippocampus is implicated
in spatial navigation skills. Significantly, the hippocampus is larger in
meadow voles than in pine voles, and it is larger in male meadow voles
than in females (Gaulin, 1992). A similar logic could help explain sex-
related differences in spatial abilities between human males and females
(see Figure 15-15 ).
Explaining sex-related differences in language skills also is
speculative. One hypothesis holds that if males were hunters and often
away from home, home-based females formed social groups selectively
favored to develop tools, one of which is language, for social
interactions. We might also argue that females with superior fine motor
skills (such as foraging for food and making clothing and baskets) had a
selective advantage. The relation between language and fine motor skills
may have favored enhanced language capacities in females.
Although such speculations are interesting, they are not testable. We
will probably never know with certainty why sex-related differences in
brain organization developed.
(A) Male brain
(B) Female brain
 FIGURE 15-20Sex Differences in the Connectome DTI analysis of brain
networks in these dorsal views reveals greater intrahemispheric
connections in males (A) and greater interhemispheric connections in
females (B). Image from M. Ingalhalikar, A. Smith, D. Parker, P. D. Satterthwaite, M. A.
Elliott, K. Ruparel, et al. (2013). Sex differences in the structural connectome of the human
brain. Proceedings of the National Academy of Sciences U S A, 111, 823–828, Fig. 2.

Handedness and Cognitive Organization

Nearly everyone prefers one hand to the other for writing or throwing a
ball. Most people prefer the right hand. In fact, left-handedness has
historically been viewed as odd. But it is not rare. An estimated 10
percent of the human population worldwide is left-handed. This
proportion represents only the number of people who write with the left
hand. When broader criteria are used to determine left-handedness,
estimates range from 10 percent to 30 percent of the population.
CLINICAL FOCUS 15-5

Sodium Amobarbital Test

Guy, a 32-year-old lawyer, had a vascular malformation over the region
corresponding to the posterior speech zone. The malformation was
beginning to cause neurological symptoms, including seizures. The
ideal surgical treatment was removal of the abnormal vessels.
The complication with this surgery is that removing vessels sitting
over the posterior speech zone poses a serious risk of permanent
aphasia. Because Guy was left-handed, his speech areas could be in the
right hemisphere. If so, the surgical risk would be much lower.
To achieve certainty in such doubtful cases, Jun Wada and Ted
Rasmussen (1960) pioneered the technique of injecting sodium
amobarbital, a barbiturate, into the carotid artery to briefly anesthetize
the ipsilateral hemisphere. (Injections are now usually made through a
catheter inserted into the femoral artery.) The procedure enables an
unequivocal localization of speech because injection into the speech
hemisphere results in speech arrest lasting as long as several minutes.
As speech returns, it is characterized by aphasic errors.
Injection into the nonspeaking hemisphere may produce no or only
brief speech arrest. The amobarbital procedure has the advantage of
allowing each hemisphere to be studied separately in the functional
absence of the other (anesthetized) hemisphere. Because the period of
anesthesia lasts several minutes, a variety of functions, including
memory and movement, can be studied to determine a hemisphere’s
capabilities.
The sodium amobarbital test is always performed bilaterally, with
the second cerebral hemisphere being injected several days after the
first one to make sure that no residual drug effect lingers. In the brief
period of drug action, the patient is given a series of simple tasks
requiring the use of language, memory, and object recognition. To test
speech, the patient is asked to name some common objects presented in
quick succession, to count, to recite the days of the week forward and
backward, and to spell simple words.
If the injected hemisphere is nondominant for speech, the patient
may continue to carry out the verbal tasks, although there is often a
period as long as 30 seconds during which he or she appears confused
and is silent but can resume speech with urging. When the injected
hemisphere is dominant for speech, the patient typically stops talking
and remains completely aphasic until recovery from the anesthesia is
well along, somewhere in the range of 4 to 10 minutes.
Guy was found to have speech in the left hemisphere. During the test
of his left hemisphere, he could not talk. Later, he said that when he
was asked about a particular object, he wondered just what the question
meant. When he finally had some vague idea, he had no idea of what
the answer was or how to say anything. By then he realized that he had
been asked all sorts of other questions to which he had also not
responded.
When asked which objects he had been shown, he said he had no
idea. However, when given an array of objects and asked to choose
with his left hand, he identified the objects by pointing because his
nonspeaking right hemisphere controlled that hand. In contrast, his
speaking left hemisphere had no memory of the objects: it had been
asleep.
 To avoid damaging speech zones in patients about to undergo brain surgery,
surgeons inject sodium amobarbital into the carotid artery. The drug
anesthetizes the hemisphere where it is injected (here, the left), allowing the
surgeon to determine whether that hemisphere is dominant for speech.

Because the left hemisphere controls the right hand, the general
assumption is that right-handedness is somehow related to the presence of
speech in the left hemisphere. If this were so, language would be located in
the right hemisphere of left-handed people. This hypothesis is easily tested,
and it turns out to be false.
In the course of preparing patients with epilepsy for surgery to remove
the abnormal tissue causing their seizures, Ted Rasmussen and Brenda
Milner (1977) injected the left or right hemisphere with sodium
amobarbital. This drug produces a short-acting anesthesia of the entire
hemisphere, making it possible to determine where speech originates. As
described in Clinical Focus 15-5 , Sodium Amobarbital Test, if a person
becomes aphasic when the drug is injected into the left hemisphere but not
when the drug is injected into the right, then speech must reside in that
person’s left hemisphere.
Rasmussen and Milner found that in virtually all right-handed people,
speech was localized in the left hemisphere, but the reverse was not true for
left-handed people. About 70 percent of left-handers also had speech in the
left hemisphere. Of the remaining 30 percent, about half had speech in the
right hemisphere and half had speech in both hemispheres. Findings from
neuroanatomical studies have subsequently shown that left-handers with
speech in the left hemisphere have asymmetries similar to those of right-
handers. By contrast, in left-handers with speech originating in the right
hemisphere or in both hemispheres—known as anomalous speech
representation —the anatomical symmetry is reversed or absent.
anomalous speech representation Condition in which a person’s
speech zones are located in the right hemisphere or in both
hemispheres.
Findings from neuroanatomical studies have subsequently shown that
left-handers with speech in the left hemisphere have asymmetries similar to
those of right-handers. By contrast, in left-handers with speech originating
in the right hemisphere or in both hemispheres—known as anomalous
speech representation —the anatomical symmetry is reversed or absent.
Findings from neuroanatomical studies have subsequently shown that
left-handers with speech in the left hemisphere have asymmetries similar to
those of right-handers. By contrast, in left-handers with speech originating
in the right hemisphere or in both hemispheres—known as anomalous
speech representation —the anatomical symmetry is reversed or absent.
Findings from neuroanatomical studies have subsequently shown that left-
handers with speech in the left hemisphere have asymmetries similar to
those of right-handers. By contrast, in left-handers with speech originating
in the right hemisphere or in both hemispheres—known as anomalous
speech representation —the anatomical symmetry is reversed or absent.
Sandra Witelson and Charlie Goldsmith (1991) asked whether any other
gross differences in the brain structure of right- and left-handers might
exist. One possibility is that the connectivity of the cerebral hemispheres
may differ. To test this idea, the investigators studied the hand preference of
terminally ill subjects on a variety of one-handed tasks. They later
performed postmortem studies of these patients’ brains, paying particular
attention to the size of the corpus callosum. They found that the callosal
cross-sectional area was 11 percent greater in left-handed and ambidextrous
(little or no hand preference) people than in right-handed people.
Whether this enlarged callosum is due to a greater number of fibers, to
thicker fibers, or to more myelin remains to be seen. If the larger corpus
callosum is due to more fibers, the difference would be on the order of 25
million more fibers. Presumably, such a difference would have major
implications for the organization of cognitive processing in left- and right-
handers.

Synesthesia
Some variations in brain organization are idiosyncratic rather than
systematic. Synesthesia is an individual’s capacity to join sensory
experiences across sensory modalities, as discussed in Clinical Focus 15-6 ,
A Case of Synesthesia. Examples include the ability to hear colors or taste
shapes. Edward Hubbard (2007) estimated the incidence of synesthesia at
about 1 in 23 people, although for most it likely is limited in scope.
synesthesia Ability to perceive a stimulus of one sense as the sensation
of a different sense, as when sound produces a sensation of color;
literally, feeling together.
Synesthesia runs in families—the family of Russian novelist Vladimir
Nabokov, for example. As a toddler, Nabokov complained to his mother
that the letter colors on his wooden alphabet blocks were all wrong. His
mother understood what he meant, because she too perceived letters and
words in particular colors. Nabokov’s son is synesthetic in the same way.
Musician–composer Stevie Wonder is a synesthete, as were music
legends Duke Ellington and Franz Liszt and Nobel Prize–winning
physicist Richard Feynman.
 CLINICAL FOCUS 15-6

A Case of Synesthesia
Michael Watson tastes shapes. His sensory joining first came to the
attention of neurologist Richard Cytowic over dinner. After tasting a
sauce he was making for roast chicken, Watson blurted out, “There
aren’t enough points on the chicken.”

Neurologist Richard Cytowic devised this set of figures to help

Michael Watson communicate the shapes he senses when he
tastes food.

When Cytowic quizzed him about this strange remark, Watson said
that all flavors had shape for him. “I wanted the taste of this chicken to
be a pointed shape, but it came out all round. Well, I mean it’s nearly
spherical. I can’t serve this if it doesn’t have points” (Cytowic, 1998, p.
4).
Watson has synesthesia, which literally means feeling together. All his
life Watson has experienced the feeling of shape when he tastes or smells
food. When he tastes intense flavors, he reports an experience of shape
that sweeps down his arms to his fingertips. He experiences the feeling
of weight, texture, warmth or cold, and shape, just as though he were
grasping something.
 The feelings are not confined to his hands, however. Watson
experiences some taste shapes, such as points, over his whole body. He
experiences others only on the face, back, or shoulders. These
impressions are not metaphors, as other people might use when they say
that a cheese is sharp or a wine is textured. Such descriptions make no
sense to Watson. He actually feels the shapes.
Cytowic systematically studied Watson to determine whether his
feelings of shape were always associated with particular flavors and
found that they were. Cytowic devised the set of geometric figures
shown here to allow Watson to communicate which shapes he associated
with various flavors.
If you’ve shivered on hearing a particular piece of music or the noise
of fingernails scratching across a chalkboard, you have felt sound. Even
so, other sensory blendings may be difficult to imagine. How can sounds
or letters possibly produce colors? Studies of synesthetes show that the
same stimuli always elicit the same experiences for them.
The most common form of synesthesia is colored hearing. For many
synesthetes, this means hearing both speech and music in color—
perceiving a visual mélange of colored shapes, movement, and
scintillation. The fact that colored hearing is more common than other
types of synesthesia is curious.
The five primary senses (vision, hearing, touch, taste, and smell) all
generate synesthetic pairings. Most, however, are in one direction. For
instance, whereas synesthetes may see colors when they hear, they do not
hear sounds in colors. Furthermore, some sensory combinations occur
rarely, if at all. In particular, taste or smell rarely triggers a synesthetic
response like Michael Watson’s.
Because each case is idiosyncratic, synesthesia’s neurological basis is
difficult to investigate. Few studies have related it directly to brain
function or brain organization, and different people may experience it for
different reasons. Various hypotheses have been advanced to account for
synesthesia:
• Extraordinary neural connections between the sensory regions are
related in a particular synesthete.
• Activity is increased in the frontal lobe multimodal cortex, which
receives inputs from more than one sensory area.
• Particular sensory inputs elicit unusual patterns of cerebral activation.
Whatever the explanation, when it comes to certain sensory inputs,
the brain of a synesthete certainly works differently from other people’s
brains.
 15-5 REVIEW

Variations in Cognitive Organization

Before you continue, check your understanding.
1 . The two major contributors to organizational differences in individual
brains are ___________ and ___________.
2 . Differences in the cerebral organization of thinking are probably
related to differences in the ___________ that underlie different types
of cognitive processing.
3 . People who experience certain sensations in more than one sensory
modality are said to have ___________.
4 . What roles do gonadal hormones play in brain organization and
function?
Answers appear at the back of the book.

For additional study tools, visit LaunchPad: Launch Pad

www.macmillanhighered.com/launchpad/kolb5e
 15-6 Intelligence
Intelligence exerts a major influence on anyone’s thinking ability. It is
easy to identify in people and even easy to observe in other animals. Yet
intelligence is not at all easy to define. Despite a century of study,
researchers have not yet reached agreement on what intelligence entails.
We therefore begin this section by reviewing some hypotheses of
intelligence.

Concept of General Intelligence

In the 1920s, Charles Spearman proposed that although different kinds of
intelligence may exist, there is also an underlying general intelligence,
which he called the g factor. Consider for a moment what a general
intelligence factor might mean for the brain. Presumably, brains with
high or low g would have some general difference in brain architecture
—perhaps in gyral patterns, cytoarchitectonics, vascular patterns, or
neurochemistry, for example.
Cytoarchitectonics refers to brain cell organization, structure, and
distribution.
This difference could not be something as simple as size, because
human brain size (which varies from about 1000 to 2000 grams)
correlates poorly with intelligence. Another possibility is that g is related
to special cerebral connectivity or even to the ratio of neurons to glia.
Still another possibility is that g is related to the activation of specific
brain regions, possibly in the frontal lobe (Duncan et al., 2000; Gray &
Thompson, 2004).
Section 1-5 reveals fallacies inherent in correlating human brain size
with intelligence.
The results of preliminary studies of Albert Einstein’s brain implied
that cerebral connectivity and ratio of glia to neuron may be important.
Sandra Witelson and her colleagues (Witelson et al., 1999) found that
although Einstein’s brain is the same size and weight as the average male
brain, its lateral fissure is short, and both the left and the right lateral
fissures take a particularly striking upward deflection (Figure 15-21 ;
compare Figure 15-11 ). This arrangement essentially fuses the inferior
parietal area with the posterior temporal area.
 The inferior parietal cortex has a role in mathematical reasoning, so it
is tempting to speculate that Einstein’s mathematical abilities were
related to neural rearrangements in this area. But another important
difference may distinguish Einstein’s brain. Marion Diamond and her
colleagues (1985) looked at its gliato-neuron ratio versus the mean for a
control population. They found that Einstein’s ratio in the inferior
parietal cortex was higher than average: each neuron in this region had
an unusually high number of glial cells supporting it.
The glia-to-neuron ratio was not unusually high in any other cortical
areas of Einstein’s brain measured by these researchers. Possibly, then,
certain types of intelligence could be related to differences in cell
structure in localized brain regions. But even if this hypothesis proves
correct, it offers little neural evidence in favor of a general intelligence
factor.
One possibility is that g is related to the brain’s language processes,
because language ability qualitatively changes the nature of cognitive
processing in humans. So perhaps people with very good language skills
also have an advantage in general thinking ability.

FIGURE 15-21 Einstein’s Brain The lateral fissure of Einstein’s

brain takes an exaggerated upward course relative to its course in typical
brains, essentially fusing the posterior temporal regions with the inferior
parietal regions. The arrow in each hemisphere indicates Einstein’s
ascending lateral fissure as it runs into the postcentral sulcus. Republished
with permission of Elsevier Science and Technology Journals from The Exceptional Brain of
Albert Einstein, S. Witelson, D. Kigar, T. Harvey, The Lancet, June 19, 1999, Vol. 353, p. 2151.
Permission conveyed through Copyright Clearance Center, Inc.

Multiple Intelligences
Many other hypotheses on intelligence have been set forth since
Spearman’s, but few have considered the brain directly. One exception,
proposed by Howard Gardner (1983), a neuropsychologist at Harvard,
considers the effects of neurological injury on people’s behavior.
Gardner concludes that seven distinct forms of intelligence exist and that
brain injury can selectively damage any form. The idea of multiple
human intelligences should not be surprising given the varied cognitive
operations the human brain can perform.
Gardner’s seven categories of intelligence are linguistic, musical,
logical-mathematical, spatial, bodily-kinesthetic, intrapersonal, and
interpersonal. Linguistic and musical intelligence are straightforward
concepts, as is logical-mathematical intelligence. Spatial intelligence
refers to abilities discussed in this chapter, especially navigating in
space, and to the ability to draw and paint. Bodily-kinesthetic
intelligence refers to superior motor abilities, such as those exemplified
by skilled athletes and dancers.
The two types of “personal” intelligence are less obvious. They refer
to the frontal and temporal lobe operations required for success in a
highly social environment. The intrapersonal aspect is awareness of
one’s own feelings, whereas the interpersonal aspect entails recognizing
others’ feelings and responding appropriately. Gardner’s definition of
intelligence has the advantage not only of being inclusive but also of
acknowledging forms of intelligence not typically recognized by
standard intelligence tests, abilities such as theory of mind, described in
Section 15-3 .
One prediction stemming from Gardner’s analysis of intelligence is
that brains ought to differ in some way when people have more of one
form of intelligence and less of another. Logically, we could imagine that
if a person were higher in musical intelligence and lower in interpersonal
intelligence, then the brain regions for music (especially the temporal
lobe) would differ in some fundamental way from the “less efficient”
regions for interpersonal intelligence. One way to examine such
differences is to use fcMRI or DTI to identify differences in pathways, as
in the example of absolute pitch (see Figure 15-10 ).

Divergent and Convergent Intelligence

One clear difference between lesions in the parietal and temporal lobes
and lesions in the frontal lobes is in the way they affect performance on
standardized intelligence tests. Posterior lesions produce reliable and
often large decreases in intelligence test scores, whereas frontal lesions
do not. This is puzzling. If frontal lobe damage does not diminish a
person’s intelligence test score, why do people with this kind of damage
often do stupid things? The answer lies in the difference between two
kinds of intelligence.
According to J. P. Guilford (1967), traditional intelligence tests
measure convergent thinking —applying knowledge and reasoning
skills to narrow the range of possible solutions to a problem, then
zeroing in on one correct answer. Typical intelligence test items using
vocabulary words, arithmetic problems, puzzles, block designs, and so
forth all require convergent thinking. They demand a single correct
answer that can be easily scored.
convergent thinking Form of thinking that searches for a single
answer to a question (such as 2 + 2 = ?); contrasts with divergent
thinking.
In contrast, divergent thinking reaches outward from conventional
knowledge and reasoning skills to explore new, more unconventional
solutions to problems. Divergent thinking assumes a variety of possible
approaches and answers to a question rather than a single “correct”
solution. A task that requires divergent thinking is to list all the possible
uses you can imagine for a coat hanger.
divergent thinking Form of thinking that searches for multiple
solutions to a problem (how many ways can a pen be used?);
contrasts with convergent thinking.
Clearly, a person who is very good at divergent thinking might not
necessarily be good at convergent thinking and vice versa. The
distinction is useful because it helps us to understand the effects of brain
injury on thought. Frontal lobe injury is believed to interfere with
divergent thinking. The convergent thinking measured by standardized
IQ tests is often impaired in people with damage to the temporal and
parietal lobes.
Injury to the left parietal lobe in particular causes devastating
impairment in the ability to perform cognitive processes related to
academic work. People with this kind of injury may be aphasic, alexic,
and apraxic. Many have severe deficits in arithmetic ability. All such
impairments would interfere with school performance and performance
at most jobs.
Patient M. M., discussed in Section 15-4 , had left parietal lobe injury
and was unable to return to school. In contrast with people like M. M.,
those with frontal lobe injuries seldom have deficits in reading, writing,
or arithmetic. And they show no decrement in standardized IQ tests. C.
C.’s case provides a good example.
C. C. had a meningioma along the midline between the frontal lobes.
Extracting it required removing brain tissue from both hemispheres.
Before his surgery C. C. was a prominent lawyer. Afterward, although he
still had a superior IQ and superior memory, he was unable to work, in
part because he no longer had any imagination. He could not generate
the novel solutions to legal problems that had characterized his career
before the surgery. Thus, both M. M. and C. C. had problems that
prevented them from working, but their problems differed because their
injuries affected different kinds of thinking.

Intelligence, Heredity, Epigenetics, and the

Synapse
Donald Hebb proposed another way to categorize human intelligence.
Like Guilford, Hebb thought of people as having two forms, which he
called intelligence A and intelligence B. Unlike Guilford’s convergent–
divergent dichotomy, Hebb’s intelligence A refers to innate intellectual
potential, which is highly heritable: it has a strong genetic component.
Intelligence B is observed intelligence, which is influenced by
experience as well as other factors, such as disease, injury, or exposure to
environmental toxins, especially during development.
intelligence A Hebb’s term for innate intellectual potential, which is
highly heritable and cannot be measured directly.
intelligence B Hebb’s term for observed intelligence, influenced by
experience and other factors in the course of development; measured
by intelligence tests.
Hebb (1980) understood that experience can influence brain cell
structure significantly. In his view, experiences influence brain
development, and thus observed intelligence, because they alter the
brain’s synaptic organization. It follows that appropriate postnatal
experiences can enhance development of intelligence B in people with
lower than average intelligence A, whereas a poor or underresourced
environment can hinder the development of intelligence B in people with
higher than average intelligence A. The task is to identify a good and a
bad environment so as to stimulate people to reach their highest potential
intelligence.
 Review Focus 8-1. Section 8-4 recounts Hebb’s pioneering work on
enriched environments’ importance in early childhood education.
One implication of Hebb’s view of intelligence: the brain’s synaptic
organization is key. Synaptic organization is partly directed by a person’s
genes but is also affected by epigenetic factors. Variations in the
experiences to which people are exposed, coupled with variations in
genetic patterns, undoubtedly contribute to the individual differences in
intelligence that we observe—both quantitative differences (as measured
by IQ tests) and qualitative differences (as in Gardner’s view).
Hikaru Takeuchi and colleagues (2012) used f MRI to characterize
brain activation while participants performed working memory tasks of
varied complexity. Performance on IQ tests and memory are highly
correlated, so the investigators reasoned that brain activity during
memory tests might reflect brain differences related to IQ score.
Performance speed correlated with increased activation in the right
dorsolateral prefrontal cortex as well as an increase in the interaction
between the prefrontal cortex and right posterior parietal cortex. Gray
matter volume in the right dorsolateral prefrontal region correlated with
the participant’s accuracy in working memory tasks, which in turn
correlated with psychometric intelligence measures.
Others have obtained parallel results using event-related potentials
(e.g., Langer et al., 2009). The general conclusion from ERP studies is
that general intelligence is related to the efficiency of cortical networks
linking prefrontal and parietal regions. We can speculate that the
efficiency of different neural networks, as might be seen in fcMRI
studies, will underlie the variation in each of Gardner’s seven forms of
intelligence.
Section 7-2 describes ERP’s use in mapping brain function.
Finally, neuropsychological studies using tests of executive (frontal
lobe) function show an advantage for bilingual speakers relative to
monolinguals. The difference is hypothesized to reflect bilinguals’
consistent need to select language-appropriate words and to inhibit
language-inappropriate words. Further, learning two languages early in
life appears to confer an even greater advantage than acquiring a second
language later in life.
Olulade and colleagues (2015) found that, versus monolinguals,
increased gray matter volume in the frontal lobe of adults who learned
two languages before age 6 reflects this behavioral advantage. No such
difference appeared when the investigators compared individuals who
acquired an oral language and American Sign Language. The finding is
consistent with the idea that the challenge of selecting language-
appropriate words is critical. How the increased gray matter volume
correlates with other measures of intelligence is unknown, but the results
are consistent with evidence showing long-term cognitive advantages in
elderly bilinguals. This suggests a broader advantage for bilinguals than
in executive functions alone.
Focus 8-3 backs up these ideas about bilingual speakers.
 15-6 REVIEW

Intelligence
Before you continue, check your understanding.
1 . Different concepts of intelligence include Spearman’s ___________,
Gardner’s ___________, Guilford’s concepts of ___________ and
thinking, and Hebb’s ___________ and ___________.
2 . Each form of intelligence that humans possess is probably related to
the brain’s ___________ organization as well as to its ___________
efficiency.
3 . No two brains are alike. They differ, for example, in ___________,
___________, and ___________.
4 . Evidence that Hebb’s intelligence A and intelligence B can be altered
by experience is evidence of ___________ influences on brain
organization.
5 . How might intelligence be related to brain activity?
Answers appear at the back of the book.

For additional study tools, visit LaunchPad: Launch Pad

www.macmillanhighered.com/launchpad/kolb5e
 15-7 Consciousness
Our conscious experience is familiar and intimate yet remains largely a
mysterious product of the brain. Everyone has an idea of what it means
to be conscious, but like thinking and intelligence, consciousness is
easier to identify than to define. Definitions range from a mere
manifestation of complex thought processes to more slippery notions that
see it as the subjective experience of awareness or the “inner self.”
Despite the difficulty of defining consciousness, scientists generally
agree that it is a process, not a thing. And consciousness is probably not
a single process but several, such as are associated with seeing, talking,
thinking, emotion, and so on.
Consciousness is not unitary but can take various forms. A person is
not necessarily equally conscious at all stages of life. We don’t think of a
newborn baby as being conscious in the same way that a healthy older
child or adult is. Indeed, we might say that part of the maturation process
is becoming fully conscious. The level of consciousness even changes
across the span of a day as we pass through various states of drowsiness,
sleep, and waking. One trait that characterizes consciousness, then, is its
constant variability.
Section 13-3 explores sleep stages and dream states.

Why Are We Conscious?

Countless people, including neuroscience researchers, have wondered
why we experience consciousness, the mind’s level of responsiveness to
impressions made by the senses. The simplest explanation is that
consciousness provides an adaptive advantage. Either our construct of
the sensory world or our selection of behavior is enhanced by being
conscious. Consider visual consciousness.
consciousness The mind’s level of responsiveness to impressions
made by the senses.
Investigators’ conclusions from sensory deprivation experiments:
the brain inherently needs stimulation; see Figure 12-1 .
According to Francis Crick and Christof Koch (1998), an animal such
as a frog acts a bit like a zombie when it responds to visual input. Frogs
respond to small, preylike objects by snapping and to large, looming
objects by jumping. These responses are controlled by different visual
systems and are best thought of as reflexive rather than conscious. And
these visual systems work well for the frog. So why would humans need
to add consciousness?
Crick and Koch suggest that reflexive systems are fine when their
number is limited, but as their numbers grow, reflexive arrangements
become inefficient, especially when two or more systems conflict. As the
amount of information about an event increases, it becomes
advantageous to produce a single complex representation and make it
available for a sufficient time to the parts of the brain—such as the
frontal lobes—that choose among many possible action plans. This
sustained, complex representation is consciousness.
 EXPERIMENT 15-5

Question: Can people alter their movements without

conscious awareness?
Procedure

Results
 Conclusion: It is possible to dissociate behavior and conscious
awareness.
Research from C. Frith, R. Perry, & E. Lumer (1999). The neural correlations of conscious experience. Trends
in Cognitive Sciences, 3, pp. 105–114.

Of course, to survive we must retain the ability to respond quickly

and unconsciously when we need to. This reflexive ability exists
alongside our ability to process information consciously. The ventral
visual stream is conscious, but the dorsal stream, which acts more
rapidly, is not. Athletes model the unconscious action of the online
dorsal stream. To hit a baseball or tennis ball traveling at more than 100
miles per hour requires athletes to swing before they are consciously
aware of actually seeing the ball. Conscious awareness of the ball comes
just after hitting it.
In a series of experiments, Marc Jeannerod and his colleagues
(Castiello et al., 1991) found a similar dissociation between behavior and
awareness in healthy volunteers as they make grasping movements.
Experiment 15-5 illustrates a representative experiment. Participants
were required to grasp one of three rods as quickly as possible. A light
on a rod indicated it to be the correct target rod on any given trial.
On some trials, unknown to the participants, the light jumped from
one target to another. Participants were asked to report whether such a
jump had occurred. As shown in the Results section of the experiment,
although participants were able to make the trajectory correction, they
were sometimes actually grasping the correct target before they were
aware it had changed.
On some trials, the extent of dissociation between motor and vocal
responses was so great that, to their surprise, participants grasped the
target some 300 milliseconds before they emitted the vocal response. As
with baseball players, their conscious awareness of the stimulus event
occurred only after their movements took place. No thought was required
to make the movement, just as frogs catch flies without having to think
about it.
Unconscious movements are different from those consciously directed
toward a specific object, as when we reach into a bowl of jellybeans to
select a candy of a certain color. In this case, we must be aware of all the
different colors surrounding the color we want. Here the conscious
ventral stream is needed to discriminate among particular stimuli and
respond differentially to them. Consciousness, then, allows us to select
behaviors that correspond to an understanding of the nuances of sensory
inputs.

What Is the Neural Basis of

Consciousness?
Consciousness must be related in some way to neural system activity,
particularly in the forebrain. One way to investigate these systems is to
contrast two kinds of neurological conditions.
In the first condition, a person lacks conscious awareness of some
subset of information, even though he or she processes that information
unconsciously. Examples include blindsight, visual form agnosia,
implicit learning in amnesia, and visual neglect (discussed in Section 15-
2 ). Another example is obsessive-compulsive disorder, in which people
persist in some checking behavior—to see that the stove is off or the
door is locked—even though they have already checked many times.
 Focus 9-1 describes blindsight, Section 9-4 visual agnosias, Section
14-2 implicit learning in amnesia, and Section 16-4 , OCD.
All these phenomena show that stimuli can be highly processed by the
brain without entering conscious awareness. This is quite different from
the second neurological condition, in which people are consciously
aware of stimuli that are not actually there. Examples include phantom
limbs and the hallucinations of schizophrenia. In both, consciousness of
specific events, such as pain in a missing limb or hearing voices, exists
even though these events clearly are not “real.”
Focus 11-5 outlines phantom limb pain, Figure 14-20 how
amputation remaps the cortex, Focus 8-5 brain abnormalities in
schizophrenia.
We can draw two conclusions from these contrasting conditions. First,
the representation of a visual object or event is likely to be distributed
over many parts of the visual system and probably over parts of the
frontal lobes as well. Damage to different areas not only produces
different specific symptoms, such as agnosia or neglect, but can also
produce a specific loss of visual consciousness. Disordered functioning
can induce faulty consciousness, such as hallucinations. Second, because
visual consciousness can be lost, it follows that parts of the neural circuit
must produce this awareness.
In Section 15-1 , we appointed the neuron the unit of thinking. It is
unlikely, however, that the neuron can be the unit of conscious
experience. Instead, consciousness presumably is a process that emerges
from neural circuits, with greater degrees of consciousness associated
with increasingly complex circuitry.
For this reason, humans, with their highly complex brain circuits, are
often credited with a greater degree of consciousness than other animals
have. Simple animals such as worms are assumed to have less
consciousness (if any) than dogs, which in turn are assumed to have less
consciousness than humans. Brain injury may alter self-awareness in
humans, as happens in contralateral neglect, but unless a person is in a
coma, he or she retains some conscious experience.
The Glasgow Coma Scale, described in Section 1-2 , objectively
scores degrees of consciousness in brain-injured people.
Some people argue that language fundamentally changes the nature of
consciousness. Gazzaniga, for one, believes that the left hemisphere,
with its language capabilities, acts as an interpreter of stimuli (see
Section 15-4 ). He maintains that this ability is an important difference
between the functions of the two hemispheres.
Yet people who are aphasic have not lost consciousness. Although
language may alter the nature of our conscious experience, equating any
one brain structure with consciousness seems an unlikely hypothesis.
Rather, viewing consciousness as a product of all cortical areas, their
connections, and their cognitive operations holds more promise.
We end our discussion of thinking on an interesting, if speculative,
note. David Chalmers (1995) proposed that consciousness includes not
only the information the brain receives through its sensory systems but
also the information the brain has stored and presumably the information
the brain can imagine. In his view, consciousness is the end product of
all the brain’s cognitive processes.
An interesting implication of Chalmers’s notion is that as the brain
changes with experience, so does the state of consciousness. As our
sensory experiences become richer and our store of information greater,
our consciousness may become more complex. From this perspective,
some advantage may attend growing old.
 15-7 REVIEW

Consciousness
Before you continue, check your understanding.
1 . Over the course of human evolution, one characteristic of sensory
processing is that it has become more ___________.
2 . ___________ is the mind’s level of responsiveness to impressions
made by the senses.
3 . As relative human brain size and complexity have increased, so too
has our degree of ___________.
4 . Not all behavior is under conscious control. What types of behaviors
are not conscious?
Answers appear at the back of the book.

For additional study tools, visit LaunchPad: Launch Pad

www.macmillanhighered.com/launchpad/kolb5e
SUMMARY
 15-1 The Nature of Thought
The complex processes we call thinking, or cognition, are products of
both human and nonhuman brain activity. We use such words as
language and memory to describe cognitive operations, but these
concepts are abstract psychological constructs—merely inferred and not
found in discrete places in the brain. They exist but have no physical
form.
The brain carries out multiple cognitive operations—perception,
action for perception, imagery, planning, spatial cognition, and attention.
Each requires widespread activity in many cortical areas. The unit of
cognition, however, is the neuron.
 15-2 Cognition and the Association Cortex
The brain’s association cortex includes medial, dorsal, and orbital
subdivisions of the prefrontal cortex, the posterior parietal cortex, and
anterior regions of the temporal lobe. Cell assemblies in the association
cortex specifically take part in most forms of cognition.
The frontal lobes not only plan, organize, and initiate movements but
also organize our behavior over time (temporally). As a general rule, the
temporal lobes generate knowledge about objects, whereas the parietal
lobes produce varied forms of spatial cognition. Neurons in both the
temporal and the parietal lobes contribute to our ability to selectively
attend to sensory information.
Regions in the frontal and parietal lobes contain mirror neurons that
represent actions—one’s own or those of others. Such neural
representations could be used both for imitating others’ actions and for
moving faster and more accurately. A significant area of the cortex is
multisensory, allowing the brain to combine characteristics of stimuli
across sensory modalities, whether we encounter the stimuli together or
separately.
 15-3 Expanding Frontiers of Cognitive Neuroscience
Neuropsychological studies that began in the late 1800s to examine the
behavioral capacities of people and laboratory animals with localized
brain injuries did not allow investigators to study “normal” brains.
Today, noninvasive brain recording systems and imaging techniques
further the field of cognitive neuroscience, which studies the neural basis
of cognition by measuring brain activity while healthy participants
engage in cognitive tasks.
An important step in identifying the neural bases of cognition is
mapping cortical connections for the brain connectome. Two promising
imaging tools are functional connectivity magnetic resonance imaging
(fcMRI) and tractography using diffusion tensor imaging.
The cerebellum, which houses 80 percent of the human brain’s
neurons, was long believed primarily to have motor functions. Emerging
data, however, reveal cerebellar involvement in a wide range of
cognitive functions as well.
Social neuroscience, a field that combines cognitive neuroscience
with social psychology, explores how we understand others’ intentions
by constructing a theory of mind. Social neuroscience also investigates
how we develop attitudes, beliefs, and a sense of self. Using noninvasive
imaging techniques such as fMRI, researchers have shown that social
cognition primarily involves activity in the prefrontal cortex.
Neuroeconomics combines psychology, neuroscience, and economics
in seeking to understand human decision making. fMRI studies reveal
two decision-making pathways. One is slow and reflective, involving
diffuse regions of association cortex. The other is quick and reflexive,
involving the dopaminergic reward system.
 15-4 Cerebral Asymmetry in Thinking
Cognitive operations are organized asymmetrically in the left and right
cerebral hemispheres: each carries out complementary functions. The
most obvious functional difference is language, typically housed in the
left hemisphere.
Cerebral asymmetry, manifested in anatomical differences between
the two hemispheres, can be inferred from the differential effects of
injury to opposite sides of the brain. Asymmetry can also be seen in the
healthy brain and in the brain that is surgically split to relieve intractable
epilepsy. Various syndromes result from association cortex injury, among
them agnosia, apraxia, aphasia, and amnesia. Each includes the loss or
disturbance of some cognitive function.
15-5 Variations in Cognitive Organization
Unique brains produce unique thought patterns. Marked variations in
brain organization among individuals are exhibited in idiosyncratic
capacities such as synesthesia. Systematic differences in cognition exist
as well, manifested in the performance of females and males on
cognitive tests, especially on tests of spatial and verbal behavior.
Sex differences in cognition result from gonadal hormones’ actions on
cortical organization, possibly on the architecture of cortical neurons,
and ultimately on neural networks. Female and male cerebral
hemispheres exhibit marked differences in anatomical organization.
Right- and left-handers also differ in hemispheric organization. Left-
handers constitute at least three distinct groups. In one, speech appears to
reside in the left hemisphere, as it does in right-handers. The other two
groups have anomalous speech representation, either in the right
hemisphere or in both hemispheres. The reasons for these organizational
differences remain unknown.
 15-6 Intelligence
Intelligence is easy to spot but difficult to define. Obvious differences
exist across, as well as within, species, and we find varied forms of
intelligence among humans within our own culture and in other cultures.
Intelligence is unrelated to differences in brain size within a species or to
any obvious gross structural differences among members of the species.
Intelligence may be related to synaptic organization and processing
efficiency.
 15-7 Consciousness
The larger a species’ brain is relative to its body size, the more
knowledge the brain acquires. Consciousness, the mind’s level of
responsiveness to impressions made by the senses, emerges from the
nervous system’s complexity.
 KEY TERMS
anomalous speech representation, p. 551
association cortex, p. 525
attention, p. 528
binding problem, p. 527
brain connectome, p. 535
cell assembly, p. 522
cognition, p. 521
cognitive neuroscience, p. 533
consciousness, p. 556
contralateral neglect, p. 528
convergent thinking, p. 555
dichotic listening, p. 541
divergent thinking, p. 555
extinction, p. 528
hyperconnectivity, p. 535
intelligence A, p. 555
intelligence B, p. 555
mirror neuron, p. 532
neuroeconomics, p. 538
perseveration, p. 531
psychological construct, p. 521
social neuroscience, p. 536
split brain, p. 521
synesthesia, p. 551
syntax, p. 521
theory of mind, p. 536
Visit Launch Pad LaunchPad to access the e-Book, videos,
Learning Cur ✓ eLearning Curve adaptive quizzing, flashcards,
and more:
www.macmillanhighered.com/launchpad/kolb5e
CHAPTER

16

What Happens When

the Brain Misbehaves?
 Katherine Streeter

RESEARCH FOCUS 16-1 POSTTRAUMATIC STRESS DISORDER

16-1 MULTIDISCIPLINARY RESEARCH ON BRAIN AND
BEHAVIORAL DISORDERS
CAUSES OF DISORDERED BEHAVIOR
INVESTIGATING THE NEUROBIOLOGY OF BEHAVIORAL
DISORDERS
16-2 CLASSIFYING AND TREATING BRAIN AND
BEHAVIORAL DISORDERS
IDENTIFYING AND CLASSIFYING BEHAVIORAL DISORDERS
TREATMENTS FOR DISORDERS
RESEARCH FOCUS 16-2 TREATING BEHAVIORAL DISORDERS
WITH TRANSCRANIAL MAGNETIC STIMULATION
16-3 UNDERSTANDING AND TREATING NEUROLOGICAL
DISORDERS
TRAUMATIC BRAIN INJURY
CLINICAL FOCUS 16-3 CONCUSSION
STROKE
EPILEPSY
MULTIPLE SCLEROSIS
NEURODEGENERATIVE DISORDERS
ARE ALL DEGENERATIVE DEMENTIAS ASPECTS OF A SINGLE
DISEASE?
AGE-RELATED COGNITIVE LOSS
16-4 UNDERSTANDING AND TREATING PSYCHIATRIC
DISORDERS
SCHIZOPHRENIA SPECTRUM AND OTHER PSYCHOTIC
DISORDERS
MOOD DISORDERS
RESEARCH FOCUS 16-4 ANTIDEPRESSANT ACTION AND
BRAIN REPAIR
ANXIETY DISORDERS
16-5 IS MISBEHAVIOR ALWAYS BAD?
RESEARCH FOCUS 16-1

Posttraumatic Stress Disorder

Life is filled with stress. Routinely, we cope. But some events are so
physically threatening and often emotionally shattering that long-
term consequences ensue. Flashbacks and nightmares persist long
after any physical danger has passed. These symptoms can lead to
emotional numbness and a diagnosis of posttraumatic stress
disorder, or PTSD (Jorge, 2015).
Traumatic events that may trigger PTSD include violent assault,
natural or human-caused disaster, accident, and war. An estimated 1
in 6 veterans of the conflicts in Iraq and Afghanistan, many not
directly exposed to combat, developed symptoms of PTSD,
including intrusive, unwanted thoughts; avoiding thoughts related to
stressful events; negative cognitions and moods; and altered arousal
and reactivity responses. Understanding the neural basis and
identifying new PTSD treatments has spurred intense interest.
Nevertheless, treatment is often difficult, and most sufferers receive
no or little treatment.
posttraumatic stress disorder (PTsD) Syndrome characterized
by physiological arousal brought on by recurring memories and
dreams related to a traumatic event for months or years after the
event.
That a beneficial therapy is to relive a traumatic event is
counterintuitive. Yet in virtual reality (VR) exposure therapy, a
controlled virtual immersion environment combines realistic street
scenes, sounds, and odors that allow people to relive traumatic
events (Gonçalves et al., 2012). The Virtual Iraq and Afghanistan
Simulation is customized for war veterans to start with benign events
—such as children playing—and gradually add increasingly stressful
components, culminating in such traumatic events as a roadside
bomb exploding in the virtual space around an armored personnel
carrier, illustrated here.
virtual reality (VR) exposure therapy Controlled virtual
immersion environment that, by allowing individuals to relive
traumatic events, gradually desensitizes them to stress.
 To make Virtual Iraq realistic, the system pumps in smells,
stepping up from the scent of bread baking to body odor to the reek
of gunpowder and burning rubber. Speakers provide sounds while
off-the-shelf sub-woofers mounted under the subject’s chair re-create
movements. VR exposure therapy is now used prior to stress
exposure for soldiers, police, firefighters, and other first responders,
as a means of preventing PTSD (Rizzo et al., 2012).

Courtesy Albert “Skip” Rizzo, Ph.D., USC-ICT

Many unknowns related to PTSD remain, including

how stress injures the brain, especially the frontal lobes
and hippocampus (Wingenfeld & Wolf, 2014); why some
people do not develop PTSD following extremely
stressful events; and the extent to which PTSD is
associated with other health events, including previous
stressors, diabetes, and head trauma (Costanzo et al.,
2014). That said, assessment and treatment options for
most of those who endure PTSD are poor: over half of all
war veterans, for example, receive no assessment or
treatment.
current understanding of PTSD illustrates how thinking on the brain’s
role in health can shift. Largely as a result of symptoms displayed by
returning Vietnam War veterans, in 1980 the DSM-III introduced PTSD
as a mental disorder. Lynda Holmstrom and Ann Burgess (1978) as well
pointed out similarities in symptoms between war veterans and rape
victims.
A prominent feature of PTSD diagnosis is that a traumatic external
agent, rather than internal causes, is prominent in producing the
characteristic set of behavioral symptoms described in Research Focus
16-1 , Posttraumatic Stress Disorder. Neuroscientists now recognize that
the brain contributes to PTSD development and that traumatic
experiences related to policing, firefighting, and accidental events can
contribute to the condition.
The many discussions of behavioral disorders and organic disease
presented throughout this book serve both to illustrate the brain’s
organization and functioning and to exemplify how knowledge about
brain function contributes to understanding and treating brain disorder
and disease. Classifying and treating organic and behavioral conditions is
our focus in this chapter.
We know that the brain is complex. We do not yet understand all its
parts and their functions, nor is it clear how the brain produces mind, a
sense of well-being, and a sense of self. Still, significant advances have
led to the realization that while under some circumstances the brain
copes competently with life’s challenges, under other circumstances, it is
not up to the job.
To illustrate progress in studying brain and behavior over the past
century, we can contrast the theories of Sigmund Freud with present-day
views. Freud’s theories were based on his observations of patients while
not having the help of the anatomical or imaging data available today.
The underlying tenet of Freud’s theory is that our motivations are largely
hidden away in our unconscious mind. Freud posited that a mysterious,
repressive force actively withholds our sexual and aggressive
motivations from conscious awareness. He believed that mental illness
resulted from the failure of these repressive processes.
Freud proposed the three components of mind illustrated in Figure
16-1 A :
1. Primitive functions, including the “instinctual drives” of sex and
aggression, arise from the id, the part of the mind that Freud thought
operated on an unconscious level.
2. The rational part of the mind he called the ego. Freud also believed,
much of the ego’s activity to be unconscious, although experience (to
him, perceptions of the world) is conscious.
3. The superego aspect of mind acts to repress the id and to mediate
ongoing interactions between the ego and the id.
For Freudians, abnormal behaviors result from the emergence of
unconscious drives into voluntary conscious behavior. The aim of
psychoanalysis, the original talk therapy, is to trace symptoms to their
unconscious roots and thus expose them to rational judgment.
By the 1970s, scientific studies of the brain made the whole notion of
id, ego, and superego seem antiquated. Nevertheless, some resemblance
between Freud’s theory and brain theory is apparent (Figure 16-1 B). The
limbic system and brainstem have properties akin to those of the id: they
produce emotional and motivated behavior, including the will to survive
and to reproduce. The posterior and the dorsolateral frontal cortices have
properties akin to those of the ego: they allow us to learn and to solve
everyday problems. The prefrontal neocortex has properties akin to those
of the superego, enabling us to be aware of others and to learn to follow
social norms. Furthermore, as abundantly displayed in earlier chapters,
many processes underlying these functions are unconscious: they operate
outside our awareness.
Three differences between Freud’s view and present-day neuroscience
are apparent. First, we now recognize that the brain is composed of
hundreds of interacting structures, not just three. Second, we know that
the functions of these brain parts is complicated and depends upon
ongoing expression of genes, interactions of myriad chemicals, and
functioning and connections of glia and neurons. Third, we understand
that behavioral disorders have complex causes, including genetic
abnormalities, abnormalities in nervous system development over the
life-span, and environmental and epigenetic effects that modulate genetic
and developmental expression.
(A)
(B)
 FIGURE 16-1 Mind Models (A) Freud based his model of the mind,
drawn in 1933, solely on clinical observations (color added). (B) In a
contemporary brain imaging and lesioning studies map, the brainstem and
limbic system correlate with Freud’s depiction of the id, the ventral frontal
and posterior cortex with the ego, and the dorsal frontal cortex with the
superego. Information from a drawing by Mark Solms and Oliver Turnbull.

Investigating the origins and treatment of disordered behavior is

perhaps the most fascinating pursuit in studying the brain and behavior.
Once, neurologists treated organic disorders of the nervous system—
conditions such as Parkinson disease and stroke—medically.
Psychiatrists treated mental disorders such as schizophrenia and PTSD
pharmacologically. Psychological disorders were treated with counseling
and other behavioral therapies. Increasingly, practitioners are
synthesizing their insights into a unified understanding of mind and
brain, a neuropyschoanalysis that views the brain as the ultimate source
of behavior. When loved ones develop brain disorders, family members
usually become the primary caregivers and as such join practitioners as
participants, because they and their loved ones are those most affected.
neuropsychoanalysis Movement within neuroscience and
psychoanalysis to combine the insights of both to yield a unified
understanding of mind and brain.
With this synthesis of understanding about brain and behavior in
mind, we first survey how researchers investigate the neurobiology of
organic and behavioral disorders. We then examine how disorders are
classified, treated, and distributed in the population and review
established and emerging treatments both for neurological and for
psychiatric disorders.
 Multidisciplinary Research on Brain
16-1

and Behavioral Disorders

Brain research is multidisciplinary. One way to summarize methods of
studying links between brain and behavior is to consider them from the
macro level of the whole organism down to the molecular level of
neuronal excitation and inhibition. Behavioral studies by their nature
investigate the whole organism, but understanding the whole organism
requires understanding its parts—its cells, its chemistry, and its genes.
Chapter 7 surveys research methods ranging from single-cell
recordings to functional brain imaging.
Molecular biology offers neuroscientists varied approaches to studying
behavior. Scientists can breed strains of animals, such as fruit flies, fish,
or mice, with either a gene knocked out (deleted or inactivated) or a gene
inserted. Knockout technology is used both to create animal models of
human disorders and to generate treatments for neurobehavioral
disorders. Variations on this technology include methods for turning
genes on or off for periods of time. What is clear from this research is that
the genes related to disordered behavior in fruit flies, fish, and mice are
largely the same as those related to similar disordered behavior in people.
Section 3-3 reviews genetics, genetic engineering, and epigenetic
mechanisms; Section 7-5 explores techniques for measuring genetic
and epigenetic influences.
Freud was limited to probing the brain with conversation. Today, brain
imaging techniques allow behavioral neuroscientists to describe
structures and pathways in an individual brain and the changes it
undergoes during development, learning, and after damage, all without
directly accessing the brain. Understanding the brain’s structure and
function leads to understanding that individual brains differ—why, for
example, one person may have PTSD or any other disorder, whereas
another person in similar circumstances does not.

Causes of Disordered Behavior

Neuroscientists presume that abnormal brain functioning results in
disordered behavior. Evidence for brain abnormalities is relatively
straightforward in neurological disorders, and at least in a general sense,
the causes are largely known:
1. Genetic errors, as in Huntington disease
2. Epigenetic mechanisms at work prenatally, later in life, even in
succeeding generations
3. Progressive cell death resulting from neurodegenerative causes, as in
Parkinson or Alzheimer disease
4. Rapid cell death, as in stroke or traumatic brain injury
5. Loss of neural function and connections seen in disorders such as
multiple sclerosis and myasthenia gravis
Focus 3-4 describes Huntington disease’s genetic basis; Focus 5-2,
neural degeneration in Parkinson disease; Focus 2-3, symptoms and
aftereffects of stroke; and Focus 4-2, myelin breakdown in MS.
TABLE 16-1 Causes of Selected Behavioral Disorders
Cause Disorder

Genetic error Tay-Sachs disease

Hormonal anomaly Androgenital syndrome

Developmental anomaly Schizophrenia

Infection Encephalitis

Injury Traumatic brain injury

Toxins MPTP poisoning

Poor nutrition Korsakoff syndrome

Stress Anxiety disorders

Negative experience Developmental delays among Romanian orphans

In contrast to these organic neurological disorders, far less is known

about neurobiological causes of behavioral and psychiatric disorders. But
results of neuro-biological studies of pathology and newer research
methods are revealing clues to causation: changes in the brain’s structure
or activity are implicated. Table 16-1 lists the most likely causal
categories underlying behavioral disorders, micro to macro.
At the microscopic level is genetic error, such as that responsible for
Tay-Sachs disease and Huntington disease. Intermediate categories
include one-time events, such as infections, injuries, and toxins. At the
macro level, nutrition, stress, and negative experience are prominent
actors. Of course, many of these factors interact. Genetic error is probably
linked to more macro causes, such as hormonal or developmental
anomalies. Genetic vulnerability to stress, infection, or pollution may be
the immediate cause of some disorders. In other cases, no direct genetic
predisposition is needed: disordered behavior arises strictly from
epigenetic factors, such as stress and negative experiences, which
influence gene expression and function.

Investigating the Neurobiology of

Behavioral Disorders
A single brain abnormality can cause a behavioral disorder, explaining
everything about it and its treatment. Phenylketonuria (PKU) is an
example. PKU results from a defect in the gene for phenylalanine
hydroxylase (PHA), an enzyme that breaks down the amino acid
phenylalanine. Babies with PKU have elevated blood levels of
phenylalanine, leading to intellectual impairments, seizures, and other
physiological conditions. To inherit PKU, both parents must carry a
defective PHA gene. This recessive condition confers resistance to certain
fungal toxins. About 400 mutations of the PHA gene are known
(Foroozani et al., 2015).
phenylketonuria (PKu) Behavioral disorder caused by elevated
levels of the amino acid phenylalanine in the blood and resulting
from a defect in the gene for the enzyme phenylalanine hydroxylase;
the major symptom is severe developmental disability.
The Index of Disorders inside the book’s front cover lists where each
condition in Table 16-1 is discussed.
Left untreated, PKU causes severe intellectual disability, but PKU can
be treated just by restricting dietary intake of phenylalanine—foods high
in protein, including beef, fish, cheese, and soy. A strict diet in infancy
prevents brain damage by PKU, and controlled diet throughout life
ensures protection. Expectant mothers who have had PKU might provide
an in utero environment with high PHA levels, and this too can be
controlled if the mother restricts her dietary intake of phenylalanine.
Several drugs to reduce phenylalanine levels are in development.
If other behavioral disorders were as simple and well understood as
PKU, neuroscience research could quickly yield cures for them. Many
disorders do not result from a single genetic abnormality, however, and
the causes of most disorders remain conjectural. The major problem:
diagnosis of a disability is based mainly on behavioral symptoms, and
behavioral symptoms give few clues to specific neurochemical or
neurostructural causes.
This problem also appears in treating PKU. Table 16-2 lists what is
known about PKU at different levels of analysis: genetic, biochemical,
histological, neurological, behavioral, and social. The underlying problem
becomes less apparent with the procession of entries in the table. In fact,
it is not possible to predict the specific biochemical abnormality from
information at the neurological, behavioral, or social level, exactly where
the most accessible information resides.
For most psychiatric diseases, the underlying pathology is unknown.
For PKU, the distinctive smell of her baby’s urine detected by one mother
was the first link in a chain of discoveries that identified elevated PHA.
The task for future study and treatment of most behavioral disorders is to
identify biological markers that will lead to similar understandings.
Challenges to Diagnosis
Knowledge about behavioral disorders is hampered by its subjective
nature. Most diagnostic information gathered about a patient’s behavior
comes both from patients and their families. Unfortunately, people
seldom are objective observers of their own behavior or that of a loved
one. We tend to be selective in noticing and reporting symptoms. If we
believe someone has a memory problem, for example, we often notice
memory lapses that we might ordinarily ignore.
PKU: Neurobiological Pathogenesis of a
TABLE 16-2
Behavioral Disorder
Level of Known information
analysis*

Genetic Inborn metabolism error

Recessive defective gene (autosomal)

Biochemical Conversion of phenylalanine to tyrosine impaired, elevating levels of

phenylalanine and its metabolites in the blood

Abnormal Abnormal cortical lamination

tissue
Decrease in neuron size and dendritic length
Lowered spine density

Neurologica Severe intellectual impairment

l Slow growth
Seizure
Abnormal EEG

Behavioral IQ score below 50 (in 95 percent of patients)

Social, Significant loss of meaningful life and productivity

economic

Treatment Dietary intake of phenylalanine restricted

*From most to least specific

Source: Information from “Special Challenges in the Investigation of the Neurobiology
of Mental Illness, ” by G. R. Heninger, 1999, in The Neurobiology of Mental Illness (p.
90), edited by D. S. Charney, E. J. Nestler, and B. S. Bunney. New York: Oxford
University Press.

Nor are we often specific in identifying symptoms. Simply identifying

a memory problem is not sufficient. Treatment requires knowing exactly
what type of memory deficit underlies the problem. Losses of memory for
words, places, or habits—each has different underlying pathologies and
brain systems.
Sections 14-2 and 14-3 explain a range of memory deficits.
Just as patients and their loved ones make diagnosis difficult, so too do
diagnosticians. Behavioral information about patients may be interpreted
differently by general physicians, psychiatrists, neurologists,
psychologists, social workers, and others. Evaluators with different
conceptual biases shape and filter the questions they ask and the
information they gather.
One evaluator believes that a behavioral disorder is genetic; another
believes it results from a virus; and a third, that it can be traced to
repressed sexual experiences during childhood. Each makes different
types of observations and administers different kinds of diagnostic tests.
In contrast, diagnosing organic disorders is less dependent on subjective
observations than on objective experimental methods—but these too have
limitations.
Research Challenges
Even if the problems of diagnosis were solved, major obstacles to
investigating behavioral disorders would still exist. Following is a partial
list.
ORGANIZATIONAL COMPLEXITY The nervous system far
outstrips other body systems in complexity. The brain has a wider variety
of cell types than does any other body organ, and nervous system cells
and their connections are plastic: they change with experience. These
features add a whole new dimension to understanding healthy and
disordered functioning.
SYSTEMIC COMPLEXITY As our understanding of brain and
behavior has progressed, so it has become apparent that multiple receptor
systems serve widely varied functions. For example, the brain’s major
activating systems, those that employ acetylcholine, dopamine,
norepinephrine, serotonin, and GABA are diffuse, with little specificity
between biochemistry and behavior. The neurotransmitter GABA affects
some 30 percent of the brain’s synapses. When people ingest a GABA
agonist, such as a benzodiazepine, multiple effects on behavior become
apparent. So it is with most drug treatments, which may improve a target
behavior but at the same time produce varied side effects.
Figure 5-17 summarizes major neural activating systems; Figure 6-7
, how psychoactive drugs affect the GABAA receptor.
NEURONAL PLASTICITY The nervous system can adapt to extreme
stress or injury. Even the nigrostriatal dopaminergic system’s close
relation to Parkinson disease is enigmatic. It is impossible to tie dopamine
depletion to a consistent behavioral syndrome. Two people with
Parkinson disease can exhibit vastly different symptoms, even though the
common basis of the disease is a loss of neurons from the substantia nigra
(Fereshtehnejad et al., 2015). Further, only when the loss of dopamine
neurons exceeds about 60 percent to 80 percent do investigators see
clinical signs of Parkinson disease. Are those cells not all needed? That is
unlikely, but the result shows that the brain’s compensatory plasticity is
considerable. When a disease progresses slowly, the brain has a
remarkable capacity for adapting.
 Nigrostriatal Dopamine Pathways Axons of neurons in the
midbrain substantia nigra project to the basal ganglia, supplying dopamine
to maintain healthy motor behavior. Dopamine loss contributes to muscle
rigidity and dyskinesia in Parkinson disease.

COMPENSATORY PLASTICITY Even the best technology produces

uncertain relationships. Magnetic resonance imaging may show that a
person with multiple sclerosis has many nervous system lesions yet
displays few outward symptoms. Just as brain lesions do not always
produce behavioral symptoms, behavioral symptoms are not always
linked to obvious neuropathology. Clearly, people display compensatory
plasticity: they can change their behavior to adapt to neural change just as
they can display disordered behavior without obvious brain pathology.
TECHNOLOGICAL RESOLUTION Some people have notable
behavioral problems after a brain trauma, yet no obvious signs of brain
damage appear on an MRI. An infant’s brain may seem healthy only to
display severe cerebral palsy later. The resolution of a technology may
lack sufficient detail to detect subtle neuronal change, such as a drop in
dendritic spine density or injury so diffuse that it is hard to identify.
Given the current diagnostic methods for both behavioral disorders and
neuropathology, identifying disorders and their causes is seldom easy.
MODELING SIMPLICITY A major avenue for investigating the
causes of disorders is to develop and study animal models. Rats with
specific lesions of the nigrostriatal dopamine system are used to model
Parkinson disease. Animal models lead to significant advances in
understanding neural conditions and their treatment. But the view they
provide of the neurobiology behind behavioral disorders can be
oversimplified.
Section 7-7 reviews the benefits of creating animal models of
disorders.
The fact that a drug reduces symptoms does not necessarily mean that
it is acting on a key biochemical aspect of the pathology. Aspirin can get
rid of a headache, but that does not mean that the headache is caused by
the receptors on which aspirin acts. Similarly, antipsychotic drugs block
dopamine D2 receptors, but that does not mean that schizophrenia is
caused by abnormal D2 receptors. Schizophrenia quite possibly results
from a disturbance in glutamatergic systems, and for some reason
dopamine antagonists can rectify the abnormality.
MODELING LIMITATIONS Modeling human disorders is complex,
and critical thinking is imperative when you encounter media reports
about studies using animal models that point toward possible cures for
human behavioral diseases. Caution applies especially to psychiatric
disorders whose causes remain unknown. Further, many symptoms of
disorders such as schizophrenia and anxiety are largely cognitive.
Objectively identifying any cognitive processes mimicked by a laboratory
model is a difficult task.
 16-1 REVIEW
Multidisciplinary Research on Brain and Behavioral
Disorders
Before you continue, check your understanding.
1 . Neural correlates of Freud’s id, ego, and superego could be,
respectively, the ___________,___________, and ___________.
2 . Causes of disordered behavior include ___________, ___________,
___________, ___________, and ___________.
3 . For most psychiatric disorders, the causes are unknown, but
___________ is an exception.
4 . A major challenge in diagnosing disorders is that diagnosis tends to
be ___________.
5 . Describe a research conundrum for understanding brain injury.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Classifying and Treating Brain and
16-2

Behavioral Disorders
Behavioral disorders afflict millions every year. The National Institute for
Mental Disorders estimates that in a given year about one in four people
in the United States has a diagnosable behavioral disorder, and nearly half
of the population does over their lifetime. Only a minority receive
treatment of any kind, and even fewer receive treatment from a mental
health specialist. Large-scale surveys of neurological disorders show a
similar pattern of prevalence. Together, behavioral, psychiatric, and
neurological disorders are the leading cause of disability after age 15.
Behavioral disorders, traditionally classified as social, psychological,
psychiatric, and neurological, reflect the assessment and treatment roles
different professional groups play. As understanding of brain function
increases, the lines between behavioral disorders are blurring.
Figure 8-31 pegs the peak age of onset for mental disorders at 14
years.

Identifying and Classifying Behavioral

Disorders
Epidemiologists study disease distribution and causes in human
populations and help define and assess behavioral disorders of three
general types—psychoses, mood, and affect. Various professional
organizations classify disorders differently, for example, as in Table 16-3
.
Summary of DSM-5 Diagnostic Classification of
TABLE 16-3
Disorders
Diagnostic Core features and examples of specific disorders
category

Neurodevelopmenta Disorders typically manifest early; characterized by developmental

l disorders deficits that produce impairments of personal, social, or academic
functioning, including ASD, ADHD, Tourette disorder.

Schizophrenia Functioning deteriorates toward psychosis or loss of contact with

spectrum and other reality defined by delusions, hallucinations, disorganized thinking,
psychotic disorders grossly disorganized or disordered motor behavior, and negative
symptoms.

Bipolar and related Disorders placed between schizophrenia and depressive disorders,
disorders bridging two diagnostic classes, and characterized by periods of
extreme elation and/or significant depressive symptoms.

Depressive All feature sad, empty, or irritable mood, accompanied by physical

disorders and cognitive changes that significantly affect the individual’s
capacity to function. Includes major depressive disorder, dysthymia,
premenstrual dysphoric disorder.

Anxiety disorders All feature excessive fear and anxiety but differ in objects or
situations that induce fear, anxiety, or avoidance and associated
cognitive ideation. Includes generalized anxiety disorder (GAD),
specific phobia, agoraphobia, panic disorder, separation anxiety
disorder.

Obsessive- Differ from developmentally normative preoccupations and rituals by

compulsive and excessiveness or persistence beyond developmentally appropriate
related disorders periods.

Trauma- and Exposure to a traumatic or stressful event, as in PTSD, is an explicit

stressor-related diagnostic criterion.
disorders

Dissociative Disruption of and/or discontinuity of consciousness, memory,

disorders identity, emotion, perception, body representation, motor control,
and behavior, including dissociative identity disorder (multiple
personality disorder), dissociative amnesia.

Somatic symptom Physical symptoms apparently caused primarily by psychological

disorder and related rather than physiological factors; commonly encountered in medical
disorders rather than mental health settings. Includes somatic symptom
disorder, illness anxiety disorder, conversion disorder.

Feeding and eating Abnormal patterns of eating that significantly impair physical health
disorders and/or psychosocial functioning, including pica, anorexia nervosa,
bulimia nervosa, and binge-eating disorder.

Elimination Inappropriate elimination of urine or feces, usually first diagnosed in

disorders childhood or adolescence.

Sleep-wake Characterized by chronic sleep problems, including insomnia

disorders disorder, narcolepsy, sleep apneas, circadian rhythm sleep-wake
disorders, restless legs syndrome.

Sexual dysfunctions Characterized by a clinically significant disturbance in a person’s

ability to respond sexually or to experience sexual pleasure.
Includes premature or delayed ejaculation and erectile disorder in
males; female orgasmic or sexual interest/arousal disorder.

Gender dysphoria Distress accompanying the incongruence between experienced or

expressed gender and assigned gender.

Disruptive, impulse- Problems in self-control of emotions and behaviors, manifested in

control, and conduct behaviors that violate others’ rights, such as aggression, and/or
disorders conflict with societal norms and authority figures. Includes
 oppositional defiant disorder, intermittent explosive disorder,
pyromania, kleptomania.

Substance-related Encompasses 10 separate drug classes that affect the central

and addictive nervous system, and gambling disorder.
disorders

Neurocognitive Disorders dominated by impaired cognitive functioning of

disorders determinable underlying pathology and etiology, including TBI and
Alzheimer, Huntington, or Parkinson disease.

Personality Enduring pattern of pervasive and inflexible inner experience and

disorders behavior that deviates markedly from cultural expectations; onset
occurs in adolescence or early adulthood and is stable over time.
Includes paranoid personality disorder, schizoid personality
disorder, antisocial personality disorder, borderline personality
disorder, histrionic personality disorder, narcissistic personality
disorder, dependent personality disorder, obsessive-compulsive
personality disorder.

Paraphilic disorders Disorders that cause distress or impairment to the individual; a

paraphilia whose satisfaction entails harm or risk of harm to others,
including voyeuristic disorder, exhibitionistic disorder, frotteuristic
disorder, sexual masochism disorder, sexual sadism disorder,
pedophilic disorder, fetishistic disorder.

Other mental Symptoms characteristic of a mental disorder predominate but do

disorders not meet the full criteria for any other DSM mental disorder.

Medication-induced Determining causal relationships between medication exposure and

movement disorders development of movement disorders is difficult. Some may occur in
and other adverse the absence of the medication. Notably, not categorized as mental
effects of disorders are medication-induced parkinsonism, acute dystonia,
medication acute akathisia, tardive dyskinesia, antidepressant discontinuation
syndrome.

Other conditions Conditions or problems that cause significant impairment, including

that may be a focus relational problems, problems related to abuse or neglect,
of clinical attention educational and occupational problems, housing and economic
problems, problems related to crime or interaction with the legal
system.

Source: Information from Diagnostic and Statistical Manual of Mental Disorders (5th
ed.), 2013. Washington, DC: American Psychiatric Association.

The first set of criteria for diagnoses in psychiatry was developed in

1972. Since that time, three parallel sets of criteria have gained
prominence, and new versions appear periodically. One is the most recent
edition of the World Health Organization’s International Classification of
Diseases (ICD-10); another, the American Psychiatric Association’s
Diagnostic and Statistical Manual of Mental Disorders (DSM). The
newest, launched by the National Institutes of Mental Health, is the
Research Domain Criteria (RDoC). With this new classification system,
NIMH is looking to transform behavioral diagnoses by incorporating
genetics, imaging, and cognitive science, among other levels of
information.
Diagnostic and Statistical Manual of Mental Disorders (DSM) The
American Psychiatric Association’s classification system for
psychiatric disorders.
In addition, the Society for Clinical Psychology provides a list of
psychological disorders, their symptoms, and a summary of psychological
treatments. The National Institute of Neurological Disorders and Stroke
provides a list of neurological disorders, including their symptoms,
treatments, and any clinical trials that are investigating treatments.
Classification systems organize knowledge about disorders and their
treatments and are useful for decision making in such institutions as
insurance companies, courts, and schools.
Table 16-3 summarizes the classification scheme used currently in the
DSM-5. As with any attempt to classify psychiatric disorders, the DSM is
to some extent arbitrary and unavoidably depends on prevailing cultural
views. A good example is the social definition of sexual behavior viewed
as abnormal. At its inception, the DSM listed homosexual behavior as
pathological but has omitted it since 1980. With evidence solidifying
around a neural basis for the spectrum of gender identity, a similar fate
will likely befall the DSM category gender dysphoria.
Section 12-5 explores the relationship among sexual orientation,
sexual identity, and brain organization; and Section 15-5 , sex
differences in cognitive organization.
Each revision of any classification system reflects new perspectives.
For example, the DSM-5 labels all forms of autism as autism spectrum
disorder (ASD) and most forms of schizophrenia as schizophrenia
spectrum disorder. Classifying broad ranges of conditions as one
simplifies diagnosis but draws criticism for its associated loss of
descriptive power and a perceived difficulty in obtaining treatment
sensitive to the severity of particular symptoms.
Focus 8-2 describes the autism spectrum.
Among the continually emerging means of searching for indicators of
behavioral disorders, genetics and brain imaging, including MRI and
PET, stand out. Although these tools are not currently used clinically,
they are increasingly used both to classify disorders and to monitor
treatment effectiveness. But to be useful, imaging test resolution, for
example, must be sensitive enough to detect unique features of brain
disorders and specific enough to rule out similar conditions. This sets a
high bar, because many behavioral disorders display similar
abnormalities. Enlarged ventricles, indicating a loss of brain cells, may
appear in schizophrenia, Alzheimer disease, alcoholism, or head trauma,
for example.
Nonetheless, imaging technology is shedding new light on behavioral
disturbances. Imaging the brain structure, connections, and chemistry of
subjects with childhood-onset schizophrenia, for example, suggests that
the condition begins in utero and is characterized by excessive pruning of
short-distance cortical connections (Rao et al., 2015). Cortical maps
derived by Judith Rapoport and coworkers (2012) reveal that between the
ages of 13 and 18, children who developed schizophrenia showed a
remarkable loss of gray matter in the cerebral cortex (Figure 16-2 ). An
earlier study by the same group found changes in the quantity of growth
factors that influence brain development and a delayed growth rate in
white matter—on the order of 2 percent per year—in children with
schizophrenia compared with healthy children (Gogtay et al., 2008).

FIGURE 16-2 Early-Onset Schizophrenia Comparison of three-

dimensional maps derived from MRI scans reveals that, compared with
healthy teenagers aged 13 to 18 (left), patients with childhood-onset
schizophrenia (right) have widespread loss of gray matter across the
cerebral hemispheres. Courtesy of Paul Thompson and Arthur W. Toga, Laboratory of
Neuro Imaging, Keck School of Medicine of USC and Judith L. Rapoport, National Institute of
Mental Health.
 Abnormalities found throughout the brain vary by functional region
and correlate with the onset of behavioral disturbances characteristic of
schizophrenia. Not all disorders show such obvious loss of tissue but may
show abnormal blood flow or metabolism that can be detected by either
fMRI or PET. The PET images in Figure 16-3 illustrate metabolic
changes in adult-onset schizophrenia. The scan on the left reveals an
obvious abnormality in prefrontal cortex activity compared with the scan
on the right, from an adult who does not have schizophrenia. Note that
the prefrontal area does not show loss of gray matter in the MRI study of
early-onset schizophrenia reproduced in Figure 16-2 . Therefore, it is
likely that the two diseases have different origins.
Combining behavioral diagnoses with genetic analysis and
neuroimaging will move practitioners beyond symptom checklists to
objective medical diagnoses. Imaging analyses will help target treatments
to reduce the severity of such serious disorders as schizophrenia and
Alzheimer disease. Current imaging techniques do not detect all brain
pathology. It is not whether a gene is present or absent but whether that
gene is or is not expressed that is relevant to its effects. The challenge lies
in improving current techniques and in developing others that can identify
subtler nervous system abnormalities.
 Hank Morgan/Science Source

Adult-Onset Schizophrenia Note the

FIGURE 16-3

abnormally low blood flow in the prefrontal cortex

at the top of the PET scan in the brain (left) of an
adult schizophrenia patient compared (right) with
that of an adult who does not have schizophrenia.
Classification systems such as taxonomy, the branch of biology that
groups organisms according to their common characteristics and
relationships, have advanced our knowledge of brain structure and
function. Likewise, classifications of behavioral disorders produced by
the behavioral sciences have advanced understanding. Yet classification
systems have their critics. One criticism is that “just because you name a
disorder does not mean it exists.” Another is that changing societal views
result in the inclusion or exclusion of disorders, as with sexual
relationships other than heterosexuality.
 The Basics in Section 1-3 overviews taxonomy.
Naming disorders becomes problematic as well. The term idiot once
designated a person with a low IQ score. When the term became
pejorative, it was replaced with the term retarded. That term then became
pejorative, and the DSM-5 now uses the term intellectual disability.
Nevertheless, just as genetics has clarified taxonomic relationships
among animals, our growing understanding of brain function and genetics
likely will clarify the taxonomy of behavioral disorders. The NIMH’s
Research Domain Criteria project, for example, is one response to
criticisms of broad behavioral classifications such as those used in the
DSM-5.

Treatments for Disorders

An inclusive list of brain and behavioral disorders would number in the
thousands, including, on the organic side, genetic and developmental
disorders, infectious diseases, nervous system injuries, and degenerative
dementias. Behavioral disorders would include PTSD among the anxiety-
related disorders. Abnormalities may also appear via imbalances in
biochemical organization or nervous system operation. Biochemical
abnormalities include disordered proteins in cell membrane channels, low
or high neuroreceptor numbers, and low or high numbers of molecules,
especially neurotransmitters or hormones. Each disorder may be
associated with various structural changes, congenital abnormality of
neurons or glia, and neuronal death.
The conditions listed in the Index of Disorders constitute a mere
fraction of the total.
The ultimate goal for behavioral neuroscientists lies in applying their
knowledge to generate treatments that can restore a disordered brain to a
range of healthy functioning. This goal is daunting because the first task
is so difficult: learning what causes a particular behavioral disturbance.
Few behavioral disorders have a cause as simple as PKU does. Most, like
schizophrenia, are complex. A more achievable goal is to make small
advances by improving current treatments, to develop new treatments,
and to analyze disease causes. Available treatments, while extensive, fall
into four general categories:
1. Neurosurgical. The skull is opened and some intervention is performed
on the brain.
2. Electrophysiological. Brain function is modified by stimulation
through the skull.
3. Pharmacological. A chemical that affects the brain is either ingested or
injected.
4. Behavioral. Treatment manipulates the body or the experience, which
in turn influences the brain.
Neurosurgical Treatments
Neurosurgical manipulation of the nervous system is largely reparative, as
when tumors are removed or arteriovenous (AV) malformations
corrected. Typically, such neurosurgical interventions are successful.
Advances include improved imaging of a target for surgery—as the
surgery takes place—and methods that allow diseased tissue to be
destroyed without opening the skull. For example, radiosurgery uses
energy, such as X-rays directed from different sources to converge on a
target and destroy abnormal cells. The x-rays lack the energy to damage
healthy cells through which they pass: tissue is destroyed only where
multiple beams converge.
Brain tumors are the topic of Focus 3-2. AV malformation, or
angioma, is imaged on page 582 .
 Zephyr/Science Source
FIGURE 16-4 Deep Brain Stimulation X-ray of a human brain showing
electrodes implanted in the thalamus for DBS.

Treatment for Parkinson disease entails inactivating brain regions that

produce tremors and regions participating in the production of muscular
rigidity that impairs movement. An electrode is placed in the motor
thalamus and an electric current used to damage neurons responsible for
producing the unwanted effects. Alternatively, in deep brain stimulation
(DBS), an electrode fixed in place in the globus pallidus or subthalamic
nucleus is connected to an external electrical stimulator that the patient
can activate ( Figure 16-4 ). The stimulation can inactivate cells
responsible for unwanted effects and so restore more normal movement
(Knight et al., 2015).
deep brain stimulation (DBs) Neurosurgery in which electrodes
permanently implanted in the brain stimulate a targeted area with a
low-voltage electrical current to facilitate behavior.
DBS is also used experimentally to treat traumatic brain injury (TBI)
and behavioral dysfunctions such as obsessive-compulsive disorder
(OCD) and major depression (Cleary et al., 2015). Electrodes implanted
in the brain are well tolerated and remain effective for several years.
Electrical stimulation can have an activating effect and so relieve
depression or compulsive behaviors. Stimulation may also make brain
tissue more plastic and receptive to other treatments. During stimulation,
patients can learn more effective thought and behavioral patterns. For
many conditions, DBS remains an experimental option of last resort. It is
not a permanent cure: when the stimulation stops, beneficial effects are
reduced; hence the importance of coupling DBS with cognitive-
behavioral therapy.
Another highly experimental neurosurgical strategy draws on the fixed
sequence of prenatal brain development from cell division and cell
differentiation to cell migration and synaptogenesis. If a brain region is
functioning abnormally or if it is diseased or dead, as occurs in TBI or
after a stroke, it should be possible to return this region to the embryonic
state and regrow a healthy region. The use of so-called induced
neurogenesis has a science fiction ring but may someday be feasible. In
laboratory rats, for example, stem cells can be induced by neurotrophic
factors to generate new cells that can migrate to the site of an injury.
Figure 14-26 shows neurogenesis induced in a rat brain to repair a
cortical stroke.
 In the 1980s, neurosurgeons experimented with implanting fetal stem
cells in adult brains. Success was limited due to difficulties in cell
placement and connections and rejection by the patient’s immune system.
Another restorative idea comes from the discovery that multipotent stem
cells in other body regions, such as bone marrow and skin, appear capable
of manufacturing neural stem cells. Indeed, using appropriate
manipulations, any cell can potentially be returned to a stem cell state.
The advantage is that the patient’s own cells are not rejected by the
immune system.
Figure 8-8 diagrams the origins of specialized brain cells from
multipotent neural stem cells.
If people’s own multipotent stem cells prove practical for generating
neural stem cells, it should be possible to extract stem cells, place them in
a special culture medium to generate thousands or millions of cells, and
place these stem cells in the damaged brain. The cells would be instructed
to differentiate appropriately and develop the correct connections. Stem
cell transplantation is taken seriously today as a potential treatment for
disorders such as TBI and stroke, but it remains largely at an investigative
stage (Savitz, 2015).
Electrophysiological Treatments
Treating the mind by treating the body is an ancient notion. In the 1930s,
researchers used insulin to lower blood sugar and produce seizures as a
treatment for depression. By the 1950s, insulin therapy had been replaced
by electroconvulsive therapy (ECT), the first electrical brain stimulation
treatment.
ECT was developed as a treatment for otherwise untreatable
depression, and although its mode of action was not understood, it did
prove useful. Although rarely used today, ECT sometimes remains the
only treatment that works for people with severe depression. One reason
may be that it stimulates the production of a variety of neurotrophic
factors, especially BDNF (brain-derived neurotrophic factor), that in turn
restore inactive cells to a more active mode.
Neurotrophic factors, nourishing chemical compounds, support
neuronal growth, development, and viability.
Problems with ECT include the massive convulsions electrical
stimulation causes. Large doses of medication are normally required to
prevent them. ECT also leads to memory loss, a symptom that can be
troublesome with repeated treatments. A noninvasive technique,
transcranial magnetic stimulation (TMS), uses magnetic rather than
electrical stimulation. Magnetic stimulation can be applied to a localized
brain region. Anesthesia is not necessary. TMS is an FDA-approved
treatment for depression. Clinical applications, reviewed in Research
Focus 16-2 , Treating Behavioral Disorders with Transcranial Magnetic
Stimulation, are growing.
Figure 7-7 diagrams how TMS works.
RESEARCH FOCUS 16-2

Treating Behavioral Disorders with

Transcranial Magnetic Stimulation
In transcranial magnetic stimuation (TMS) a magnetic coil placed
over the scalp induces an electrical current in underlying brain
regions. TMS can be applied to localized brain regions (focal areas)
thought to be implicated in specific disorders. Manipulation of the
magnetic field can stimulate an area of cortex as small as a quarter—
the cortical surface only or deeper layers of brain tissue.

Marcello Massimini/University of Milan

In clinical therapy for depression, TMS influences neural activity
in a localized brain area.

The primary clinical use of TMS, which the U.S. Food and Drug
Administration formally approved in 2008, is for depression.
Numerous studies report positive effects using TMS, but the required
duration of treatment and the duration of beneficial effects remains
under investigation.
The effects of brief pulses of TMS do not outlive the stimulation.
Repetitive TMS (rTMS), however, which involves continuous
 stimulation for up to several minutes, produces longer-lasting effects.
What is needed to fully evaluate TMS effects in alleviating
depression is a double-blind study, in which both therapists and
patients are unaware of whether real or sham stimulation is
administered (Serafini et al., 2015).
In addition to treating depression, small but promising studies have
extended the possible benefits of TMS to schizophrenic auditory
hallucinations, anxiety disorders, neurodegenerative diseases,
hemiparesis, and pain syndrome (Wassermann & Zimmerman, 2012).
Among the problems in all studies of TMS are questions related to
the duration and intensity of stimulation and also to the area
stimulated. Each person’s brain is slightly different, so to ensure that
appropriate structures are stimulated, MRI must be performed on each
subject.
Does TMS stimulation make the brain more plastic? If so, can
learning be enhanced? The idea is, when a train of TMS is delivered,
it produces a change in cortical excitability. This change in turn
facilitates learning. Indeed, combined TMS and training can improve
the therapeutic effects of motor or cognitive training given alone
(Nevler & Ash, 2015).

Pharmacological Treatments
Several accidental discoveries, beginning in the 1950s, led to a
pharmacological revolution in the treatment of behavioral disorders:
1. The development of phenothiazines (neuroleptics) to treat
schizophrenia stemmed from a drug used to premedicate surgical
patients. In the following decades, neuroleptic drugs became
increasingly more selective, and they remain effective.
2. A new class of antianxiety drugs was invented: the anxiolytics.
Medications such as Valium quickly became—and remain—the most
widely prescribed drugs in the United States.
3. L-Dopa provided the first drug treatment for serious motor dysfunction
in Parkinson disease. Once taken, L -dopa is converted into and
replaces dopamine lost due to Parkinson disease.
The power of psychoactive drugs to change disordered behavior
revolutionized the pharmaceutical industry. The central goal is developing
drugs that can act as magic bullets to correct the chemical imbalances
found in various disorders. Research is directed toward making drugs
more selective in targeting specific disorders while producing fewer side
effects. Both goals have proved difficult to achieve.
Pharmacological treatments have significant downsides. Acute and
chronic side effects top the list, and long-term use may cause new
problems. Consider a person who receives anti-depressant medication.
The drug may ease the depression but it may also produce unwanted side
effects, including decreased sexual desire, fatigue, and sleep disturbance.
The last two effects may also interfere with cognitive functioning.
Thus, although a medication may be useful for getting a person out of
a depressed state, it may produce other symptoms that are themselves
disturbing and may complicate recovery. Furthermore, in depression
related to a person’s life events, a drug does not provide the behavioral
tools needed to cope with an adverse situation. Some psychologists say,
“A pill is not a skill.”
Section 6-2 classifies psychoactive drugs and their therapeutic
effects.
Negative side effects of drug treatments are evident in many people
whose schizophrenia is being treated with neuroleptics. Antipsychotic
drugs act on the mesolimbic dopamine system, which affects motivation,
among other functions. The side effect emerges because the drugs also act
on the nigrostriatal dopaminergic system, which controls movement.
Patients who take neuroleptics also eventually develop motor
disturbances. Tardive dyskinesia, an inability to stop the tongue, hands,
or other body parts from moving, is a motor symptom of long-term
neuroleptic administration. Side effects of movement disorders can persist
after the psychoactive medication has been stopped. Taking drugs for
behavioral disorders, then, does carry risk. Rather than magic bullets,
these medications often act like shotguns.
tardive dyskinesia Inability to stop the tongue or other body parts
from moving; motor side effect of neuroleptic drugs.
Despite their drawbacks, drugs do prove beneficial for many people.
Improved drug chemistry will reduce side effects, as will improved
delivery modes that bring a drug to a target system with minimal effects
on other systems. One improved delivery system uses nanoparticles called
liposomes, biosynthetic molecules 1 to 100 nm (nanometers, or billionths
of a meter) in size. One natural biological nanoparticle, with a radius of
about 40 nm, is the synaptic vesicle that houses a neurotransmitter for
delivery into the cell’s extracellular space. Liposomes consisting of a
synthetic vesicle with a homing peptide on the surface can, in principle,
be constructed to carry a drug across the blood–brain barrier and deliver it
to specified types of neuron or glial cells within the nervous system.

Liposome for Drug Delivery Biosynthetic vesicles can deliver

microscopic drugs or DNA to the body’s cells. Synthetic biology is a topic in
Section 7-1 .

Behavioral Treatments
Treatments for behavioral disorders need not be direct biological or
medical interventions. Just as the brain can alter behavior, behavior can
alter the brain. Behavioral treatments focus on key environmental factors
that influence how a person acts. As behavior changes in response to
treatment, the brain is affected as well.
An example is treatment for generalized anxiety disorders attributed to
chronic stress. People who endure a persistently high anxiety level often
engage in maladaptive behaviors to reduce it. While they require
immediate treatment with antianxiety medication, long-term treatment
entails changing their behavior. Generalized anxiety disorder is not
simply a problem of abnormal brain activity but also of experiential and
social factors that fundamentally alter the person’s perception of the
world.
Focus 12-3 recounts a case of generalized anxiety disorder.
Perhaps you are thinking that behavioral treatments may help
somewhat in treating brain dysfunction, but the real solution must lie in
altering brain activity. Since every aspect of behavior is the product of
brain activity, behavioral treatments do act by changing brain function. If
people can change how they think and feel about themselves or some
aspect of their lives, this change has taken place because talking about
their problems or resolving a problem alters how their brain functions. In
a sense then, a behavioral treatment is a biological intervention.
Behavioral treatments may sometimes be helped along by drug treatments
that make the brain more receptive to change through behavioral therapy.
In this way, drug treatments and behavioral treatments have synergistic
effects, each helping the other to be more effective.
Your behavior is a product of all your learning and social experiences.
An obvious approach to developing a treatment is to re-create a learning
environment that replaces a maladaptive behavior with an adaptive
behavior. Thus, the various approaches to behavioral treatment use
principles derived from experiment-based learning theory. Following is a
sampling of these approaches.
 Lea Paterson/Science Source
Systematic desensitization for a phobia, the most common among anxiety disorders, as Focus 12-3
reports.

BEHAVIOR MODIFICATION Behavioral therapies apply well-

established learning principles to eliminate unwanted behaviors.
Therapists apply principles developed in studying learning by
reinforcement in laboratory settings, including operant and classical
conditioning. For example, if a person is debilitated by a fear of insects,
rather than looking for inner causes, the behavioral therapist tries to
replace the maladaptive behaviors with more constructive ways of
behaving. These might include training the patient to relax while
systematically exposing him to unthreatening insects (butterflies)
followed by gradual exposure to more threatening insects (bees). This
form of habituation (adaption to a repeatedly presented stimulus) is called
systematic desensitization.
behavioral therapy Treatment that applies learning principles, such
as conditioning, to eliminate unwanted behaviors.
COGNITIVE THERAPY Cognitive therapy operates from the
perspective that thoughts intervene between events and emotions.
Consider responses to losing a job. One thought could be, I’m a loser, life
is hopeless. An alternative thought is, The job was a dead end. The boss
did me a favor. The former cognition might lead to depression, whereas
the latter would not. Cognitive therapies challenge a person’s self-
defeating attitudes and assumptions and are important for people with
brain injury too, because it is easy for people to think that they are crazy
or stupid after brain injury. Equally if not more powerful is cognitive-
behavioral therapy, discussed in Section 16-4 .
cognitive therapy Psychotherapy based on the perspective that
thoughts intervene between events and emotions, and thus the
treatment of emotional disorders requires changing maladaptive
patterns of thinking.
NEUROPSYCHOLOGICAL THERAPY If a relative or friend had a
stroke and became aphasic, you would expect him or her to attend speech
therapy—a behavioral treatment for an injured brain. The logic in speech
therapy is that by practicing (relearning) the basic components of speech
and language, the patient should be able to regain at least some lost
function. The same logic can apply to other types of behavioral disorders,
whether motor or cognitive.
 Therapies for cognitive disorders resulting from brain trauma or
dysfunction aim to retrain people in the fundamental cognitive processes
they have lost. Although cognitive therapy seems as logical as speech
therapy after a stroke, cognitive therapy assumes that we know what
fundamental elements of cognitive activity are meaningful to the brain.
Cognitive scientists are far from understanding these elements well
enough to generate optimal therapies. Still, neuropsychologists are
developing neurocognitive programs that can improve functional
outcomes following TBI and stroke (Mateer & Sira, 2006; Sohlberg &
Mateer, 1989). Treatment effectiveness can be improved with computer-
based tools and follow-up therapy.
EMOTIONAL THERAPY In the 1920s, Sigmund Freud developed the
idea that talking about emotional problems enables people to gain insights
into the causes of the problems and serves as treatment too. Talk cures
and other forms of psychological intervention may be broadly categorized
as psychotherapies.
Since Freud’s time, many ideas have been put forth about the best type
of therapy for emotional disorders. Key here is that for many disorders,
whether neurological or psychiatric, medical treatments are not effective
unless patients also receive psychotherapy. Indeed, the only effective
treatment in many cases lies in addressing the unwanted behaviors
directly—in acquiring the skill rather than taking the pill.
psychotherapy Talk therapy derived from Freudian psychoanalysis
and other psychological interventions.
Consider a 25-year-old woman pursuing a promising career as a
musician who suffered a traumatic brain injury in an automobile accident.
After the accident, she found that she was unable to read music. Not
surprisingly, she soon became depressed. Part of her therapy required her
to confront her disabling cognitive loss by talking about it rather than by
simply stewing over it. Only when she pursued psychotherapy did she
begin to recover from her intense depression.
For many people with emotional impairments resulting from brain
disease or trauma, the most effective treatment for depression or anxiety
is helping them adjust by encouraging them to talk about their difficulties.
Group therapy provides such encouragement and is standard treatment in
brain injury rehabilitation units.
 David Braun/Masterfile
Exercise boosts your mood because it boosts your dopamine levels.
Section 10-4 observes that practitioners have only begun to tap music’s
power as a therapeutic tool.

PHYSICAL ACTIVITY AND MUSIC AS THERAPY Exercise and

music have positive effects on peoples’ attitudes, emotional well-being,
and brain function. Physical exercise demands visual control of
movement. Music affects arousal and activates the motor and premotor
cortex. Listening to music can improve gait in Parkinson and stroke
patients and reduce pain post surgery. Learning to play a musical
instrument likewise is beneficial therapy (François et al., 2015). Singing,
a useful adjunct to rehabilitative speech therapy, enhances the ability to
enunciate. Physical activity, including dancing and playing sports,
combined with other therapies, improves well-being and counteracts the
effects of depression.
REAL-TIME FMRI Using this behavior-modification technique,
individuals learn to change their behavior by controlling their own brain
activation patterns. Real-time fMRI was first used to treat intractable
pain, which produces a characteristic brain activity pattern (deCharms,
2008). The researchers proposed that if subjects could see their brain
activity via fMRI in real time as they felt pain, they could be trained to
reduce the neural activity and lessen their pain. Real-time fMRI (rt-
fMRI) uses a form of operant conditioning in which the gradual
modification of a participant’s behavior increases the probability of
reward.
real-time fMRI (rt-fMRI) Behavior-modification technique in
which individuals learn to change their behavior by controlling their
own patterns of brain activation.
Think of rt-fMRI as a form of neural plasticity in which the individual
learns new strategies, guided by brain activation information. When
subjects decrease brain activation in regions associated with pain, they
report decreased pain perception. Conversely, through learning to increase
brain activation in these regions, they would be able to increase their pain
—although it seems unlikely that this ability would be much cultivated!
An actual potential application of rt-fMRI is in monitoring brain
activation when treatment for disorders occurs in the context of
behavioral therapy. Patients need not be consciously aware of the
therapy’s objectives: induced brain changes, whether conscious or
unconscious, can prove beneficial (Birbaumer et al., 2013).
Focus 11-5 describes an effective low-tech strategy for controlling
phantom limb pain.
VIRTUAL REALITY THERAPY The principle behind VR therapy is
that patients enter or interact with a virtual world displayed on a computer
screen or through goggles. One example is the Virtual Iraq and
Afghanistan Simulation described in Research Focus 16-1 . The
participant can experience sights, sounds, even smells that mimic
situations related to acquiring the behavioral disorder, in this case PTSD.
In modified VR therapy a patient interacts as a character in a computer
game. Winning the game necessitates making adaptive choices;
maladaptive choices result in losing the game (Shin et al., 2015).
 16-2 REVIEW
Classifying and Treating Brain and Behavioral Disorders
Before you continue, check your understanding.
1 . Three classifications of behavioral disorders are ___________,
___________, and ___________.
2 . ___________ is the study of the distribution and causes of diseases in
human populations.
3 . Developments in ___________ and ___________ have enabled their
use in identifying brain and behavior disorders.
4 . Four treatment categories for behavioral disorders are ___________,
___________, ___________, and.
5 . A therapy in which an electrode delivers stimulation directly to the
brain is called ___________.
6 . An effective replacement for electroconvulsive therapy (ECT) is
___________.
7 . Why are classification systems useful even though they are inexact?
Answers appear at the back of the book.

For additional study tools, visit : Lanch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Understanding and Treating
16-3

Neurological Disorders
In everyone’s lifetime, at least one close friend or relative will develop a
neurological disorder, even if we ourselves escape them. Disorder causes
are understood in a general sense, and for most, rehabilitative treatment
is emerging. In this section we review some common neurological
disorders: traumatic brain injury, stroke, epilepsy, multiple sclerosis, and
neurodegenerative disorders.

Traumatic Brain Injury

Traumatic brain injury (TBI), a wound to the brain that usually results
from a blow to the head, is the most common form of brain damage in
people under age 40. TBI commonly results from the head making
impact with other objects—as can occur in automobile and industrial
accidents and in sports injuries. TBI can also follow blows to the chest
that result in a rapid increase in blood pressure, which can damage the
brain indirectly. The incidence of TBI is about eight times that of breast
cancer, AIDS, spinal cord injury, and multiple sclerosis combined.
The two most important factors in the incidence of head trauma are
age and sex. Children and elderly people are more likely to injure their
head in a fall than are others, and males between 15 and 30 incur brain
injury especially in automobile and motorcycle accidents ( Figure 16-5
). A child’s chance of having significant traumatic brain injury before he
or she is old enough to drive is 1 in 30.
Section 14-5 details a dancer’s recovery from TBI.

FIGURE 16-5 Incidence Rates of Head Trauma Based on

combined reports of emergency room visits, hospitalizations, and deaths,
this chart graphs the estimated frequency of TBI in males and females
 across the life span. Information from the Centers for Disease Control. TBI in the United
States: Emergency department visits, hospitalizations, and deaths, 2004 (report).

Concussion is a critical concern for both professional and amateur

athletes, especially those who play football, ice hockey, lacrosse, soccer,
and no less for those on active military duty. Sports account for about 20
percent of TBIs, and the U.S. Army Institute of Surgical Research
reports that traumatic brain injury affects more than 1 in 5 U.S. soldiers
wounded in war.
A large-scale longitudinal study is under way in cooperation with
football and ice hockey players who have a history of concussion and
who have agreed to donate their brain for postmortem analysis.
Preliminary examination of the brains of deceased professional football
players who had a history of concussion and severe postconcussion
symptoms, described in Clinical Focus 16-3 , Concussion, reveal
extensive, diffuse loss of cerebral tissue.
In longitudinal research, over time investigators repeatedly observe
or examine subjects with respect to the study’s variable(s).
Symptoms and Outcome of Brain Trauma
TBI can cause direct damage to the brain. Trauma can disrupt the brain’s
blood supply, induce bleeding (leading to increased intracranial
pressure), cause swelling (leading to increased intracranial pressure),
expose the brain to infection, and scar brain tissue (the scar being a focus
for later epileptic seizures). The disruption in blood supply tends to be
brief, but a parallel disruption of energy production by neuronal
mitochondria, which can persist for weeks, is related to many
postconcussion behavioral symptoms.
CLINICAL FOCUS 16-3

Concussion
Early in 2011, 50-year-old former Chicago Bears defensive back
Dave Duerson shot himself in the chest and died. He left a note
asking that his brain be studied. Duerson had played 11 years in the
National Football League, won two Super Bowls, and received
numerous awards.
As a pro player he endured at least 10 concussions, but they did
not seem serious enough to cause him to leave the game. After
retiring from football, he went to Harvard and obtained a business
degree. He pursued a successful business career until he began to
have trouble making decisions and controlling his temper.
Eventually, Duerson’s business and marriage failed. After his
suicide, the Center for the Study of Traumatic Encephalopathy in
Boston did study his brain. The Center is conducting postmortem
anatomical analyses of the brains of former athletes as part of a long-
term longitudinal study.

Ann C McKee MD VA Boston/Boston University School of Medicine

Dave Duerson’s Brain Staining for tau protein highlights
degenerating brain tissue (dark brown areas) in the frontal cortex
and medial temporal lobe of these coronal sections through
Duerson’s anterior right hemisphere. Damage to the subcortical
basal ganglia in the sections’ central portions (yellowish areas)
is sparse by comparison.

Duerson’s diagnosis, chronic traumatic encephalopathy (CTE),

is a progressive degenerative disease found in individuals with a
history of multiple concussions and other closed-head injuries. (A
variant long associated with boxing is dementia pugilistica, or DP.)
chronic traumatic encephalopathy (CTE) Progressive
degenerative disease caused by multiple concussions and other
closed-head injuries, characterized by neurofibrillary tangles,
plaques, cerebral atrophy, and expanded ventricles due to cell
loss.
Concussion, the common term for mild traumatic brain injury
(MTBI), is common in sports, especially contact sports, including
American football, ice hockey, and rugby. Concussion also results
from falls in many other sports and from vehicular accidents. It is
likely that the incidence of concussion is higher than 6 per 1000
individuals.
Concussion often goes unrecognized. For those that are diagnosed,
little apparent pathology appears after relatively short periods of rest,
the usual treatment. Nevertheless, the relationship is well established
between concussion and a range of degenerative diseases that occur
later in life—dementias, including Alzheimer disease, as well as
Parkinson disease, motor neuron disease, and CTE.
The relationship between concussion in early life and later
degenerative brain disease suggests that concussion can initiate a
cascade of pathological events that over years develop into CTE.
CTE is characterized by neurofibrillary tangles, plaques, and neuronal
death. Cerebral atrophy and expanded ventricles due to cell loss are
typical in advanced cases. As shown in the illustration, researchers
test for cell death by staining for accumulation of the tau protein,
which is associated with neuronal death and so is a sensitive marker
for brain trauma.
The unknowns about CTE are many. Is just one or are many
concussions required to initiate a cascade that results in CTE? Are
individuals who get CTE especially susceptible? What constitutes a
concussion? Should blows to the head that result in no pronounced
symptoms be distinguished from blows that result in loss of
consciousness?
What we do know is that many well-known athletes, especially
football and ice hockey players, have developed CTE. Clearly, much
more care needs to be taken, beginning in childhood, to prevent
 concussion and to ensure that concussion is treated, even though what
constitutes adequate treatment remains uncertain (Rose et al., 2015).

Traumatic brain injury is commonly accompanied by a loss of

consciousness that may be brief (minutes) or prolonged (coma). Duration
of unconsciousness can serve as a measure of the severity of damage,
because it correlates directly with mortality, intellectual impairment, and
deficits in social skills. The longer coma lasts, the greater the possibility
of serious impairment or death.
Section 1-2 presents a case study on recovering consciousness
following TBI.
Two kinds of behavioral effects result from TBI: (1) impairment of
specific functions mediated by the cortex at the coup (the site of impact)
or contrecoup (opposite side) lesion, as illustrated in Figure 16-6 , and
(2) more generalized impairments from widespread trauma throughout
the brain. Discrete impairment is most commonly associated with damage
to the frontal and temporal lobes, the brain areas most susceptible to TBI.
(See tissue samples in Focus 16-3.)

FIGURE 16-6 Mechanics of TBI Pink and blue shading mark brain
regions most frequently damaged in closed-head injury. A blow can
produce a contusion both at the site of impact and on the opposite side of
the brain, owing to rebound compression.
 More generalized impairment results from minute lesions and
lacerations scattered throughout the brain. Movement of the hemispheres
in relation to one another causes tearing characterized by a loss of
complex cognitive functions, including mental speed, concentration, and
overall cognitive efficiency.
TBI patients generally complain of poor concentration or lack of
ability. They fail to do things as well as they could before the injury, even
though their intelligence is unimpaired. In fact, in our experience, people
with high skill levels seem to be the most affected by TBI, in large part
because they are acutely aware of loss of a skill that prevents them from
returning to their former competence level.
Traumatic brain injury that damages the frontal and temporal lobes
also tends to significantly affect personality and social behavior. Few
victims of traffic accidents who have sustained severe head injuries ever
resume their studies or return to gainful employment. If they do reenter
the work force, they do so at a lower level than before their accident.
One frustrating problem with traumatic brain injury is misdiagnosis:
chronic effects of injuries often are unaccompanied by any obvious
neurological signs or abnormalities in CT or MRI scans. Patients may
therefore be referred for psychiatric or neuropsychological evaluation.
MRI-based imaging techniques such as magnetic resonance
spectroscopy (MRS), however, are useful for accurate TBI diagnosis
(Reis et al., 2015).
magnetic resonance spectroscopy (MRS) Modification of MRI to
identify changes in specific markers of neuronal function; promising
for accurate diagnosis of traumatic brain injuries.
MRS, a modification of MRI, can identify changes in specific markers
of neuronal function. One such marker is N -acetylaspartate (NAA), the
second most abundant amino acid in the human brain. Assessing the level
of NAA expression provides a measure of neuronal integrity, and
deviations from normal levels (up or down) can be taken as a marker of
abnormal brain function. People with traumatic brain injury show a
chronic decrease in NAA that correlates with the severity of the injury.
Although not yet in wide clinical use, MRS is a promising tool, not only
for identifying brain abnormalities but also for monitoring cellular
response to therapeutic interventions.
Section 7-3 introduces the MRS technique.
Recovery from Traumatic Brain Injury
Recovery from head trauma may continue for 2 to 3 years and longer, but
most cognitive recovery occurs in the first 6 to 9 months. Recovery of
memory functions appears to be slower than recovery of general
intelligence, and the final level of memory performance is lower than for
other cognitive functions. People with brainstem damage, as inferred
from oculomotor disturbance, have a poorer cognitive outcome, and a
poorer outcome is probably true of people with initial dysphasias or
hemiparesis as well.
Although the prognosis for significant recovery of cognitive functions
is good, optimism about the recovery of social skills or personality traits,
areas that often show significant change, is less rosy. Findings from
numerous studies support the conclusions that quality of life—in social
interactions, perceived stress levels, and enjoyment of leisure—is
significantly reduced after TBI and that this reduction is chronic.
Attempts to develop tools to measure changes in psychosocial adjustment
in brain-injured people are few, so we must rely largely on subjective
descriptions and self-reports. Neither provides much information about
the specific causes of these problems (Block et al., 2015).

Stroke
Diagnosticians may be able to point to a specific immediate cause of
stroke, an interruption of blood flow from either blockage of a vessel or
bleeding from a vessel. This initial event, however, merely sets off a
sequence of damage that progresses, even if the blood flow is restored.
Stroke results in a lack of blood, called ischemia, followed by a cascade
of cellular events that wreak the real damage. Changes at the cellular
level can seriously compromise not only the injured part of the brain but
other brain regions as well.
ischemia Lack of blood to the brain, usually as a result of a stroke.
Focus 2-3 describes the symptoms and aftereffects of stroke.
Effects of Stroke
Consider what happens after a stroke interrupts the blood supply to a
cerebral artery. In the first seconds to minutes after ischemia, as
illustrated in Figure 16-7 , changes begin in the affected regions’ ionic
balance, including changes in pH and in the properties of the cell
membrane. These ionic changes result in several pathological events.
1. Release of massive amounts of glutamate results in prolonged opening
of calcium channels in cell membranes.
2. Open calcium channels in turn allow toxic levels of calcium to enter
the cell, not only producing direct toxic effects but also instigating
various second-messenger pathways that can harm neurons. In the
ensuing minutes to hours, mRNA is stimulated, altering protein
production in the neurons and possibly proving toxic to the cells.
Figure 5-4 shows how calcium affects neurotransmitter release;
Figure 5-15 , how metabotropic receptors can activate second
messengers.
3. Brain tissues become inflamed and swollen, threatening the integrity of
cells that may be far removed from the stroke site. As in TBI, an energy
crisis ensues as mitochondria reduce their production of ATP, resulting
in less cerebral energy.
4. A form of neural shock occurs. During this diaschisis, areas distant
from the damage are functionally depressed. Thus, not only are local
neural tissue and its function lost but areas related to the damaged
region also undergo a sudden withdrawal of excitation or inhibition.
diaschisis Neural shock that follows brain damage in which areas
connected to the site of damage show a temporary arrest of function.
5. Stroke may also be followed by changes in the injured hemisphere’s
metabolism, its glucose utilization, or both. These changes may persist
for days. As with diaschisis, the metabolic changes can severely affect
the functioning of otherwise healthy tissue. For example, after a
cortical stroke, metabolic rate has been shown to decrease about 25
percent throughout the hemisphere.
Treatments for Stroke
The ideal treatment is to restore blood flow in blocked vessels before the
cascade of nasty events begins. One clot-busting drug is tissue
plasminogen activator (t-PA), but t-PA must be administered within 3 to 5
hours to be effective. Currently, only a small percentage of stroke patients
arrive at the hospital soon enough, in large part because stroke is not
quickly identified, transportation is slow, or the stroke is not considered
an emergency.
 FIGURE 16-7 Results of Ischemia A cascade of events takes place after blood
flow is blocked as a result of stroke. Within seconds, ionic changes at the
cellular level spur changes in second-messenger molecules and RNA
production. Changes in protein production and inflammation follow and
resolve slowly, in hours to days. Recovery begins within hours to days and
continues for weeks to months or years.

Other drugs called neuroprotectants can be used to try to block the

cascade of postinjury events, but to date we have no truly effective drugs.
Clinical trials based on animal studies have generally failed, in part
because understanding what the appropriate brain targets should be is
limited.
neuroprotectant Drug used to try to block the cascade of poststroke
neural events.
Use the F.A.S.T. Test to Spot Stroke
F ace Ask for a smile to check both understanding and muscle control.

A rms Check if one arm is weak by asking the person to raise both arms.

S peech Listen for slurred speech.

T ime If you see any symptom, call 911 or the local emergency services number right
away.

When the course of the stroke leads to dead brain tissue, the only
treatments that can be beneficial are those that facilitate plastic changes in
the remaining brain. Examples are speech therapy and physical therapy.
Revolutionary approaches to stroke rehabilitation use virtual reality,
computer games, and robotic machines (Laver et al., 2015).
Still, some simple treatments are surprisingly effective. One is
constraint-induced therapy, pioneered by Edward Taub in the 1990s
(Kawakkel et al., 2015). Its logic confronts a problem in poststroke
recovery related to learned nonuse. Stroke patients with motor deficits in
a limb often compensate by overusing the intact limb, which in turn leads
to increased loss of use in the impaired limb.
Experiment 11-3 describes research with monkeys that contributed to
developing constraint-induced therapy for people.
In constraint-induced therapy, the intact limb is held in a sling for
several hours per day, forcing the patient to use the impaired limb.
Nothing about the procedure is magical: virtually any treatment that
forces patients to practice behaviors extensively is successful. An
important component of these treatments, however, is a posttreatment
contract in which the patients continue to practice after the formal therapy
is over. If they fail to do so, the chances for learned nonuse and a return
of symptoms are high.
Another common effect of stroke is loss of speech. Specific speech
therapy programs can aid in the recovery of speech. Music and singing,
mediated in part by the right hemisphere, can augment speech therapy
after left hemisphere stroke.
Therapies using pharmacological interventions (e.g., noradrenergic,
dopaminergic, cholinergic agonists) combined with behavioral therapies
provide equivocal gains in stroke patients. The bulk of evidence suggests
that patients with small gray matter strokes are most likely to show
benefits from these treatments, whereas those with large strokes that
include white matter show little benefit.
Finally, there have been many attempts to use either direct cortical
stimulation or TMS in combination with behavioral therapy as a stroke
treatment. The idea is to induce plasticity in regions adjacent to the dead
tissue with the goal of enhancing the efficiency of the residual parts of the
neuronal networks. These treatments have proved beneficial in patients
with good residual motor control, but again, those with larger injuries
show much less benefit, presumably because the residual neuronal
network is insufficient.

Epilepsy
Epilepsy is characterized by recurrent seizures, which register on an
electroencephalogram (EEG) as highly synchronized neuronal firing
indicated by a variety of abnormal waves. About 1 person in 20 has at
least one seizure in his or her lifetime, usually associated with an
infection, temperature, and hyperventilation during childhood (6 months
to 5 years of age). Most children who experience a seizure do not develop
epilepsy, which affects between 0.2 percent and 4.1 percent of the
population. Developed nations record a lower prevalence and incidence
of epilepsy compared with developing nations.
Focus 4-1 describes a diagnosis of epilepsy and shows an EEG being
recorded.
Classifying Seizures
Causes of epileptic seizures are categorized as genetic,
structural/metabolic, or unknown. Genetic epilepsy results directly from a
known genetic defect. Causes of structural/metabolic epilepsy include
brain malformations and tumors, acquired disorders such as stroke and
trauma, and infections. The unknown category encompasses causes yet to
be identified. Table 16-4 summarizes the great variety of circumstances
that appear to precipitate a seizure. The range of circumstances is striking,
but seizures do have a consistent feature: they are most likely to occur
when a person is sleeping.
 Simon Fraser/Royal Victoria Infirmary/Newcastle Upon Tyne/Science Photo
Library/Science Source
Structural or metabolic epilepsy may result from brain malformations such
as angioma, or AV malformation, shown on this dorsal view MRI. Abnormal
cerebral blood vessels (in white) form a balloonlike structure (blue area at
lower right) that caused the death of brain tissue around it in the right
occipital cortex.

Seizures are classified by the way participating neural networks are

distributed. Focal seizures arise from a synchronous, hyperactive local
brain region. Thus, focal seizures may have motor, sensory, autonomic,
and/or psychogenic features. Focal seizures are further classified as to
whether awareness is retained or altered (dyscognitive seizure).
Generalized seizures may start at a focal location, then spread rapidly
and bilaterally to distributed networks in both hemispheres. In primary
generalized epilepsy, seizures begin in more widespread neural networks.
Seizure diagnosis is improved by the use of a wearable device that
records them (Gubbi et al., 2015).
 generalized seizure Seizure that may start at a focal location then
spread rapidly and bilaterally to distributed networks in both
hemispheres.
focal seizure Seizure that arises at a synchronous, hyperactive,
localized brain region (at a focus).
People having a seizure may cycle through the four stages charted in
Figure 16-8 : (1) normal EEG record before onset; (2) onset and tonic
phase, in which the body stiffens; (3) clonic phase, in which the person
makes rhythmic movements in time with the large, highly synchronized
discharges; and (4) a period of depressed EEG activity after the seizure
ends.
For the most part, seizures self-terminate. In some cases, termed status
epilepticus, the seizure’s driving force does not abate, often due to a brain
insult or to drug withdrawal. In this life-threatening condition, drug
intervention with a fast-acting GABA agonist or glutamate antagonist is
required to end the seizure. Death due to status epilepticus is much more
common in adults than in children (26 percent vs. 3 percent,
respectively), and survivors often live with significant brain damage. The
recommended time limit before intervention is 5 minutes. Longer-lasting
seizures are unlikely to self-terminate.
People with epilepsy die unexpectedly at a rate 24 times that of the
general population. Sudden unexpected death in epilepsy (SUDEP) has no
identifiable cause (such as status epilepticus, drowning, or falling). Most
evidence suggests that SUDEP occurs during or more often after a
seizure. Respiratory and cardiac failure may be common causes, but
events leading up to SUDEP have yet to be characterized.
Factors That May Precipitate Seizures in
TABLE 16-4
Susceptible Persons
Drugs

Alcohol

Analeptics

Excessive anticonvulsants

Phenothiazines

Tricyclic antidepressants

Emotional stress
Fever

Hormonal changes

Adrenal steroids

Adrenocorticotrophic hormone (ACTH)

Menses

Puberty

Hyperventilation

Sensory stimuli

Flashing lights

Laughing

Reading, speaking, coughing

Sounds: music, bells

Sleep

Sleep deprivation

Trauma

Source: Information from J. H. Pincus & G. J. Tucker (1974). Behavioral Neurobiology

(p. 5). New York: Oxford University Press.

Treating Epilepsy
The first-line treatment for epilepsy is drugs to inhibit seizure
development and propagation. Among the diverse range of mechanisms
drugs employ to raise seizure thresholds are enhancing the action of the
inhibitory neurotransmitter GABA and stabilizing the inactive state of
sodium channels. Most people with epilepsy work with their physician to
find a drug and dosage that cause few side effects. In 30 percent to 40
percent of people with epilepsy, however, antiseizure drugs fail to
completely control the condition—intractable epilepsy. The most
common treatment for intractable epilepsy in adults is surgical resection
of epileptogenic tissue, which has a success rate of about 70 percent.
Deep-brain stimulation may prove useful for intractable epilepsy:
bilateral stimulation of the anterior thalamus has been successful in
reducing seizure frequency. While DBS shows promise, more research is
needed (Ostergard & Miller, 2014).
 FIGURE 16-8 Generalized Seizure Patterns Examples of EEG
patterns recorded during a generalized seizure. Dots on the hemispheres
below indicate the approximate recording sites. Column numbers mark the
seizure’s stages: (1) normal record before the attack; (2) onset of seizure
and tonic phase; (3) clonic phase; and (4) a period of depressed EEG
activity after the seizure ends. Abbreviations: LT and RT, left and right
temporal; LF and RF, left and right frontal; LO and RO, left and right
occipital.

Multiple Sclerosis
In multiple sclerosis (MS), the myelin that encases axons is damaged and
neuronal functions are disrupted. MS is characterized by myelin loss in
both motor and sensory tracts and nerves. The oligodendroglia that form
the myelin sheath, and in some cases the axons, are destroyed. Brain
imaging with MRI, as shown in Figure 16-9 , identifies areas of sclerosis
in the brain as well as in the spinal cord.
Remission followed by relapse is a striking feature of MS: in many
cases, early symptoms initially are followed by improvement. The course
varies, running from a few years to as long as 50 years. Paraplegia, the
classic feature of MS, may eventually confine the affected person to bed.
Worldwide, about 1 million people have MS; women outnumber men
about two to one. Multiple sclerosis is most prevalent in northern Europe
and northern North America, rare in Japan and in more southerly or
tropical countries. Depending on region, incidence of MS ranges from 2
to 150 per 100,000 people, making it one of the most common structural
nervous system diseases.
The cause or causes of MS are unknown. Proposed causes include
bacterial infection, a virus, environmental factors including pesticides, an
immune response of the central nervous system, misfolded proteins, and
lack of vitamin D. Often, multiple cases occur in a single family. Many
genes have been associated with MS, but no clear evidence indicates as
yet that MS is inherited or transmitted from one person to another.

Living Art Enterprises, LLC/Science Source

FIGURE 16-9 Diagnosing MS Imaged by MRI, discrete multiple

sclerosis lesions appear as dark patches all around the lateral ventricles
and in the brain’s white matter.
 MS destroys the myelin sheath. Sclerosis comes from the Greek word for
hardness.

Research has focused on the immune system’s relation to MS and the

possibility that MS is an autoimmune disease. The ability to
discriminate between a foreign pathogen in the body and the body itself is
central to immune system functioning. If this discrimination fails, the
immune system makes antibodies to a person’s own body, in this case, to
myelin.
autoimmune disease Illness resulting from the loss of the immune
system’s ability to discriminate between foreign pathogens in the
body and the body itself.
Section 4-4 describes another autoimmune disease, myasthenia
gravis.
As various organisms’ genomes have been sequenced, it has become
apparent that all have many genes in common. Thus the proteins found in
different organisms are surprisingly similar. And here is the problem for
the human immune system: a foreign microbe may contain proteins that
are nearly identical to the body’s own proteins. If microbe and human
have a common gene sequence, the immune system can mistakenly attack
itself, a process known as horror autotoxicus.
Many microbial protein sequences are homologous with structures
found in myelin, which leads to an attack against the microbe and a
person’s own myelin. Research showing the important role of the immune
system in MS has intensified work on developing new treatments
(Kornek, 2015). One strategy is to build up immune system tolerance by
injecting DNA-encoding myelin antigens and DNA-encoding specific
molecules in the cascade of steps that leads to oligodendroglial cell death.
That MS is more common in extreme northern and southern latitudes
has raised the possibility that inadequate direct sunlight, which is
necessary for the body to synthesize vitamin D, factors into precipitating
the condition (Sundström & Salzer, 2015). Lack of understanding
whether an acute or a longstanding deficiency is relevant complicates
identifying a possible relationship. Possibly a vitamin D deficiency
interacts with other factors to increase susceptibility to MS. For example,
a number of genes are involved in the transport and absorption of vitamin
D and variants of these genes are related to low levels of vitamin D.
Some research has suggested that MS might originate from insufficient
blood drainage from the brain, which can be improved by cleaning or
expanding veins from the brain, including the jugular, to improve
drainage. The treatment has been called liberation therapy for its potential
relief from a condition of chronic cerebrospinal venous insufficiency
(CCSVI). Internet discussion worldwide has led to Web sites advertising
treatment using vascular surgery for patients with MS. Numerous studies
are examining a plethora of questions related to CCSVI. Primary among
them: Is venous flow restricted in people with MS? Optimism about an
outcome has far outpaced the science, which questions the treatment
(Tsivgoulis et al., 2015).

Neurodegenerative Disorders
Human societies have never before undergone the age-related
demographic shifts now developing in North America and Europe. Since
1900, the percentage of older people has increased steadily. In 1900,
about 4 percent of the population had attained 65 years of age. By 2030,
about 20 percent will be older than 65—about 50 million people in the
United States alone.
Dementias affect 1 percent to 6 percent of the population older than
age 65 and 10 percent to 20 percent of those older than age 80. For every
person diagnosed with dementia, it is estimated that several others endure
undiagnosed cognitive impairments that affect their quality of life.
Currently, more than 6 million people in the United States have a
dementia diagnosis, a number projected to rise to about 15 million by
2050. By then, 1 million new U.S. cases per year will be emerging.
Extending these projections across the rest of the developed world
portends staggering social and economic costs (Khachaturian &
Khachaturian, 2015). The World Health Organization estimates that by
2050, the incidence of dementia will balloon to 135.5 million people
worldwide.
Types of Dementia
Dementia is an acquired and persistent syndrome of intellectual
impairment. Its two essential features are (1) loss of memory and other
cognitive deficits and (2) impairment in social and occupational
functioning. Dementia is not a singular disorder, but there is no clear
agreement on how to split up subtypes. Daniel Kaufer and Steven
DeKosky (1999) divide dementias into the broad categories of
degenerative and nondegenerative ( Table 16-5 ).
dementia Acquired and persistent syndrome of intellectual
impairment characterized by memory and other cognitive deficits
and impairment in social and occupational functioning.
Nondegenerative dementias, a heterogeneous group of disorders with
diverse causes, including diseases of the vascular or endocrine systems,
inflammation, nutritional deficiency, and toxins, are summarized on the
right in Table 16-5 . The most prevalent cause is vascular. The most
significant risk factors for nondegenerative dementias are chronic
hypertension, obesity, sedentary lifestyle, smoking, and diabetes. All are
as well risk factors for cardiovascular disease. Degenerative dementias,
listed on the left in the table, presumably have a degree of genetic
transmission.
We now review two degenerative dementias, Parkinson and Alzheimer
diseases. Both pathological processes are primarily intrinsic to the
nervous system, and both tend to affect certain neural systems selectively.
TABLE 16-5 Degenerative and nondegenerative Dementias
Degenerative Nondegenerative

Alzheimer disease Vascular dementias (e.g., multi-infarct

Extrapyramidal syndromes (e.g., dementia)
progressive supernuclear palsy) Infectious dementia (e.g., AIDS dementia)
Wilson disease Neurosyphilis
Huntington disease Posttraumatic dementia
Parkinson disease Demyelinating dementia (e.g., multiple
Frontal temporal dementia sclerosis)
Toxic or metabolic disorders (e.g., vitamin B12
Corticobasal degeneration
and niacin deficiencies)
Leukodystrophies (e.g.,
adrenoleukodystrophy) Chronic alcohol or drug abuse (e.g.,
Korsakoff syndrome)
Prion-related dementias (e.g., Creutzfeldt-
Jakob disease)

Source: Information from D. I. Kaufer & S. T. DeKosky (1999). Diagnostic

Classifications: Relationship to the Neurobiology of Dementia. In D. S. Charney, E. J.
Nestler, & B. S. Bunney (eds). The Neurobiology of Mental Illness (p. 642). New York:
Oxford University Press

Parkinson Disease
Parkinson disease is common. Estimates of its incidence vary up to 1.0
percent of the population, rise sharply in old age, and are certain to grow
in coming decades. The disease seems related to degeneration of the
substantia nigra and attendant loss of the neurotransmitter dopamine
produced there and released in the striatum. The disease therefore offers
insight into the roles played by the substantia nigra and dopamine in
movement control.
Figure 7-5 diagrams degeneration in the substantia nigra associated
with Parkinson symptoms.
That Parkinson symptoms vary enormously illustrates the complexity
inherent in understanding a neurological disorder. A well-defined set of
cells degenerates, yet the symptoms are not the same in every patient.
Many symptoms strikingly resemble changes in motor activity that occurs
as a consequence of aging. Thus Parkinson disease offers indirect insight
into more general problems of neural changes in aging.
Symptoms begin insidiously, often with a tremor in one hand and
slight stiffness in distal parts of the limbs. Movements may become
slower, the face becoming masklike with loss of eye blinking and poverty
of emotional expression. Thereafter the body may stoop and the gait
become a shuffle, with arms hanging motionless at the sides. Speech may
slow and become monotonous, and difficulty swallowing may cause
drooling.
Although the disease is progressive, the rate at which symptoms
worsen varies; only rarely is progression so rapid that a person becomes
disabled within 5 years. Usually 10 to 20 years elapse before symptoms
cause incapacity. A distinctive aspect of Parkinson disease is its on-
again–off-again quality: symptoms may appear suddenly and just as
suddenly disappear.
Partial remission may also occur in response to interesting or
stimulating situations. Neurologist Oliver Sacks (1998) recounted an
incident in which a stationary Parkinson patient leaped from his
wheelchair at the seaside and rushed into the breakers to save a drowning
man, only to fall back into his chair immediately afterward and become
inactive again. Remission of some symptoms in activating situations is
common but usually not as dramatic as this case. Simply listening to
familiar music can help an otherwise inactive patient get up and dance,
for example. Or a patient who has difficulty walking may ride a bicycle
or skate effortlessly. Such activities can be used as physical therapy, and
physical therapy is important because it may slow disease progression.
Sacks, whose writings enriched the neurological literature beyond
measure, died in 2015.
The four major symptoms of Parkinson disease are tremor, rigidity,
loss of spontaneous movement (hypokinesia ), and postural disturbances.
Each symptom may manifest in different body parts in different
combinations. Because some symptoms entail the appearance of
abnormal behaviors (positive symptoms) and others the loss of normal
behaviors (negative symptoms), we consider both major categories.
Positive symptoms are behaviors not typically seen in people.
Negative symptoms are the absence of typical behaviors or inability
to engage in an activity.
POSITIVE SYMPTOMS Because positive symptoms are common in
Parkinson disease, they are thought to be inhibited, or held in check, in
unaffected people but released from inhibition in the process of the
disease. Following are the three most common:
1. Tremor at rest. Alternating movements of the limbs occur when they
are at rest and stop during voluntary movements or sleep. Hand tremors
 often have a pill-rolling quality, as if a pill were being rolled between
the thumb and forefinger.
2. Muscular rigidity. Increased muscle tone simultaneously in both
extensor and flexor muscles is particularly evident when the limbs are
moved passively at a joint. Movement is resisted, but with sufficient
force the muscles yield for a short distance then resist movement again.
Thus, complete passive flexion or extension of a joint occurs in a series
of steps, giving rise to the term cogwheel rigidity. Rigidity may be
severe enough to make all movements difficult—like moving in slow
motion and being unable to speed up the process.
3. Involuntary movements. Small movements or changes in posture,
sometimes referred to as akathesia, or cruel restlessness, may
accompany general inactivity to relieve tremor and sometimes to
relieve stiffness but often occurs for no apparent reason. Other
involuntary movements are distortions of posture, such as occur during
oculogyric crisis (involuntary turns of the head and eyes to one side),
which last minutes to hours.
akathesia Small, involuntary movements or changes in posture;
motor restlessness.
NEGATIVE SYMPTOMS After detailed analysis of negative
symptoms, Jean Prudin Martin (1967) divided patients severely affected
with Parkinson disease into five groups:
1. Disorders of posture. A disorder of fixation presents as an inability or
difficulty in maintaining a part of the body in its normal position in
relation to other parts. A person’s head may droop forward or a
standing person may gradually bend forward, ending up on the knees.
Disorders of equilibrium. These disorders cause difficulties in standing
or even sitting unsupported. In less severe cases, people may have
difficulty standing on one leg, or if pushed lightly on the shoulders,
they may fall passively without taking corrective steps or attempting to
catch themselves.
2. Disorders of righting. A person in a supine position has difficulty
standing. Many advanced patients have difficulty in even rolling over.
3. Disorders of locomotion. Normal locomotion requires support of the
body against gravity, stepping, balancing while the weight of the body
is transferred from one leg to the other, and pushing forward. Parkinson
patients have difficulty initiating stepping. When they do walk, they
 shuffle with short footsteps on a fairly wide base of support because
they have trouble maintaining equilibrium when shifting weight from
one leg to the other. On beginning to walk, Parkinson patients often
demonstrate festination: they take faster and faster steps and end up
running forward.
festination Tendency to engage in a behavior, such as walking, faster
and faster.
4. Speech disturbances. One symptom most noticeable to relatives is the
almost complete absence of prosody (rhythm and pitch) in the
speaker’s voice.
5. Hypokinesia. Poverty or slowness of movement may also manifest
itself in a blankness of facial expression, a lack of blinking or of
swinging the arms when walking, a lack of spontaneous speech, or an
absence of normal fidgeting. Akinesia also manifests in difficulty
making repetitive movements, such as tapping, even in the absence of
rigidity. People who sit motionless for hours show hypokinesia in its
most striking manifestation.
COGNITIVE SYMPTOMS Although Parkinson disease is usually
viewed as a motor disorder, changes in cognition occur as well.
Psychological symptoms in Parkinson patients are as variable as the
motor symptoms. Nonetheless, a significant percentage of patients show
cognitive symptoms that mirror their motor symptoms.
Oliver Sacks (1998) reported impoverishment of feeling, libido,
motive, and attention: people may sit for hours, apparently lacking the
will to begin or continue any activity. Thinking seems generally to be
slowed and is easily confused with dementia because patients do not
appear to be processing the content of conversations. In fact, they may be
simply processing very slowly.
Cognitive slowing in Parkinson patients has some parallels to
Alzheimer disease.
CAUSES OF PARKINSONISM The ultimate cause of Parkinson
disease—loss of cells in the substantia nigra—may result from disease,
such as encephalitis or syphilis, from drugs such as MPTP, or from
unknown causes. Idiopathic causes—those related to the individual—may
include environmental pollutants, insecticides, and herbicides.
Demographic studies of patient admissions in the cities of Vancouver,
Canada, and Helsinki, Finland, show an increased incidence of patients
contracting the disease at ages younger than 40. This finding has
prompted the suggestion that water and air might contain environmental
toxins that work in a fashion similar to MPTP (1-methyl-4-
phenylpyridinium), a contaminant that has been found in synthetic heroin
and causes Parkinson disease.
Actor Michael J. Fox, a native of Canada pictured in Focus 5-2, was
diagnosed with young-onset Parkinson disease at age 30.
TREATING PARKINSON DISEASE The cure for Parkinson disease is
either to stop degeneration in the substantia nigra or to replace it. Neither
goal is achievable at present. Thus, current treatment is pharmacological
and directed toward support and comfort.
Psychological factors influence Parkinsonism’s major symptoms:
outcome is affected by how well a person copes. Patients should seek
behaviorally oriented treatment early—counseling on the meaning of
symptoms, the nature of the disease, and the potential for most patients to
lead long, productive lives. Physical therapy consists of simple measures,
such as heat and massage, to alleviate painful muscle cramps as well as
training and exercise to cope with debilitating movement changes. Used
therapeutically, music and exercise can improve other aspects of
behavior, including balance and walking, and may actually slow the
course of the disease.
The prime objective of pharmacological treatment is increasing the
activity in whatever dopamine synapses remain. L -Dopa, a precursor of
dopamine, is converted into dopamine in the brain and enhances effective
dopamine transmission, as do drugs such as amantadine, amphetamine,
monoamine oxidase inhibitors, and tricyclic antidepressants.
Anticholinergic drugs, such as atropine, scopolamine, benztropine
(Cogentin), and trihexyphenidyl (Artane), block the brain cholinergic
systems that seem to show heightened activity in the absence of adequate
dopamine activity. As the disease progresses, drug therapies become less
effective, and the incidence of side effects increases. Some drug
treatments that directly stimulate dopamine receptors have been reported
to result in increased sexuality and an increased incidence of compulsive
gambling.
Two surgical treatments described in Section 16-2 are based on the
idea that increased activity of globus pallidus neurons inhibits motor
function. A lesion of the internal part of the globus pallidus (GPi) can
reduce rigidity and tremor. Hyperactivity of GPi neurons can also be
reduced neurosurgically by electrically stimulating the neurons via deep
brain stimulation (see Figure 16-4 ). A stimulating electrode is
permanently implanted in the GPi or an adjacent area, the subthalamic
nucleus. Patients carry a small electric stimulator that they can turn on to
induce DBS and so reduce rigidity and tremor. These two treatments may
be used sequentially: when DBS becomes less effective as the disease
progresses, a GPi lesion may be induced.
A promising prospective Parkinson treatment involves increasing the
population of dopamine-producing cells. The simplest way is to
transplant embryonic dopamine cells into the basal ganglia. In the 1980s
and 1990s, this treatment reported varying degrees of success marked by
poorly conducted studies with inadequate preassessment and
postassessment procedures. A newer treatment course proposes either
transplanting stem cells that could then be induced to take a dopaminergic
phenotype or stimulating endogenous stem cells to migrate to the basal
ganglia. The advantage is that these stem cells need not be derived from
embryonic tissue but can come from a variety of sources, including the
person’s own body.

Copyright Katsuyoshi Tanaka, courtesy of the Mark Morris Dance Group

Rhythmic movement helps Parkinson patients restore the balance between
positive and negative symptoms. Patients who participate in a specially
designed Dance for PD (http://danceforparkinsons.org/ ) class for people
with Parkinson (PwP) like the one at the Mark Morris Dance Center,
pictured here, report that moving to music helps them regain muscle
 control. Exercise, including tai chi and boxing, also reinforces treatments
directed toward replacing depleted dopamine.

Figure 11-13 charts how the GPi , a structure in the basal ganglia,
regulates movement force.
All these treatments are experimental (Politis & Lindvall, 2012).
Before cell replacement will become a useful therapy, many questions
must be resolved, including which cell source is best, where in the brain
to put grafts, and how new cells can be integrated into existing brain
circuits. Stem cells are not a quick fix for Parkinson disease, but the
pioneering work on this disease will be instrumental in applying such
technology to other diseases.
Anatomical Correlates of Alzheimer Disease
Given the increasing population of elderly people and thus of Alzheimer
disease, which accounts for about 65 percent of all dementias, research is
directed toward potential causes. Personal lifestyle, environmental toxins,
high levels of trace elements such as aluminum in the blood, an
autoimmune response, a slow-acting virus, reduced blood flow to the
cerebral hemispheres, and genetic predisposition are targets of ongoing
research.
Incidence of Alzheimer disease is high in some families, making
genetic causes pertinent to understanding disease progression. Risk
factors include the presence of the Apoe4 gene, below-average IQ score,
poor education, and TBI. Presumably, better educated and/or more
intelligent people and those who carry the Apoe2 gene are better able to
compensate for cell death in degenerative dementia.
A decade ago, the only way to identify and study Alzheimer disease
was postmortem pathology examination. This approach was less than
ideal because determining which brain changes came early in the disease
and which resulted from those early changes was impossible.
Nonetheless, it became clear that widespread changes take place in
neocortex and allo-cortex and that associated changes take place in many
neurotransmitter systems. Most of the brainstem, cerebellum, and spinal
cord are relatively spared from Alzheimer’s major ravages.
The principal neuroanatomical change in Alzheimer disease is the
emergence of amyloid plaques (clumps of protein from dead neurons and
astrocytes), chiefly in allocortex and neo-cortex. Increased plaque
concentration in the cortex has been correlated with the magnitude of
cognitive deterioration. Plaques are generally considered nonspecific
phenomena in that they can be found in non-Alzheimer patients and in
dementias caused by other known events.
Focus 14-3, on Alzheimer etiology, includes a micrograph of an
amyloid plaque.
Another anatomical correlate of Alzheimer disease is neurofibrillary
tangles (accumulations of microtubules from dead cells) found in both
neocortex and allocortex, where the posterior half of the hippocampus is
affected more severely than the anterior half. Neurofibrillary tangles have
been described mainly in human tissue and have also been observed in
patients with Down syndrome and Parkinson disease and other dementias.
Neurofilaments are a type of tubule that reinforces cell structure, aids
its movement, and transports proteins.
Finally, neocortical changes that correlate with Alzheimer disease are
not uniform. As Figure 16-10 shows plainly, the cortex atrophies and can
lose as much as one-third of its volume as the disease progresses. But
cellular analyses at the microscopic level reveal that some areas,
including the primary sensory and motor cortices, especially the visual
and sensorimotor cortex, are relatively spared. The frontal lobes are less
affected than is the posterior cortex.
(A) Healthy brain

(B) Brain characteristic of Alzheimer disease

 Brain images were provided courtesy of the Nun Study, University of Minnesota

Cortical Degeneration in Alzheimer

FIGURE 16-10

Disease Brain of (A) a healthy elderly adult contrasted with (B) an

elderly adult’s brain that shows shriveling due to cell shrinkage
characteristic of Alzheimer disease.
Healthy adult pattern
Early Alzheimer disease
Advanced Alzheimer disease
Terminal Alzheimer disease
 Science Source

FIGURE 16-11 Stripped Branches Alzheimer patients’ dendritic trees degenerate

and their neurons atrophy, worsening their symptoms, including memory loss and
personality changes.

Areas of most extensive change are the neocortical association areas

and the allocortex. The entorhinal cortex is affected earliest and most
severely. Entorhinal cortex is the major information relay from the
neocortex traveling to the hippocampus and related structures, then back
to the neocortex. Entorhinal damage is associated with memory loss, an
early and enduring symptom of Alzheimer disease, and is most likely
caused by degenerative changes that take place in this area.
Many studies describe cell loss in the cortices of Alzheimer patients,
but this finding is disputed. There seems to be a substantial reduction in
large neurons, but these cells may shrink rather than disappear. The more
widespread cause of cortical atrophy appears to be a loss of dendritic
arborization (Figure 16-11 ).
In addition to cell loss and shrinkage, changes take place in the
remaining cells’ neurotransmitters. In the 1970s, researchers believed that
a treatment paralleling L -dopa treatment of Parkinson disease could be
found for Alzheimer disease. The prime candidate neurotransmitter was
acetylcholine, and one treatment developed for Alzheimer disease is
medication that increases acetylcholine levels in the forebrain. An
example, available both orally and as a skin patch, is Exelon, the brand
name for rivastigmine, a cholinergic agonist that appears to provide
temporary relief from disease progression. Unfortunately, Alzheimer has
proved far more complex, because transmitters other than ACh clearly are
changed as well. Noradrenaline, dopamine, and serotonin are reduced, as
are the NMDA and AMPA receptors for glutamate.
Figure 14-17 shows how glutamate can affect NMDA and AMPA
receptors to promote learning by association.

Are All Degenerative Dementias Aspects of

a Single Disease?
Neither Parkinson nor Alzheimer disease is related to a single brain
structure or region, although dopamine in the case of the former and
acetylcholine in the case of the latter seem more affected. Other
similarities in their pathology suggest some common neurodegenerative
processes. Donald Calne (Calne & Mizuno, 2004) noted that when
scientists traveled to Guam at the end of World War II to investigate a
reportedly widespread dementia described as similar to Alzheimer
disease, they did indeed report a high incidence of Alzheimer. Many years
later, Calne and his colleagues, also experts in Parkinson disease,
examined the same general group of people and found that they had
Parkinson disease. Calne noted that, if you look for Alzheimer symptoms
in these people, you find them and miss the Parkinson symptoms. And
vice versa.
 Biophoto Associates/Science Source

FIGURE 16-12 Midbrain Lewy Body Lewy bodies (arrow)

characteristic of Parkinson disease are found in the brain of patients with
other disorders as well.

The best-studied similarity between the two diseases is the Lewy body
( Figure 16-12 ), a fibrous ring that forms within neuronal cytoplasm and
is thought to correspond to abnormal neurofilament metabolism. Until
recently, the Lewy body was most often found in the region of the
midbrain substantia nigra and believed to be a hallmark of Parkinson
disease, as amyloid plaques were viewed as a marker of Alzheimer
disease. In fact, Lewy bodies appear in several neurodegenerative
disorders, including Alzheimer disease. There are even reports of people
with Alzheimerlike dementias who have no plaques and tangles but do
have extensive Lewy bodies in the cortex.
Lewy body Circular fibrous structure found in several
neurodegenerative disorders; forms within the cytoplasm of neurons
and is thought to result from abnormal neurofilament metabolism.
Alzheimer and Parkinson symptoms may be similar because both
diseases have similar origins. Indeed, the idea that several diseases
marked by brain degeneration—including Huntington disease, MS, and
ALS—may have a similar origin is central to prion theory, advanced in
1982 by Stanley B. Prusiner, who received the Noble Prize for his work
in 1997. Its name derived from the terms protein and infection, a prion is
an abnormally folded protein that causes progressive neurodegeneration.
 prion From protein and infection, an abnormally folded protein that
causes progressive neurodegenerative disorders.
Infection as referred to in the definition is not one caused by casual
contact.
Prions were identified during investigation of various degenerative
brain diseases in humans and other animals. Creutzfeldt-Jakob disease, a
rare human degenerative disease that progresses rapidly, gained public
prominence in the 1990s. People were contracting a similar condition
after eating beef from cattle that had displayed symptoms of bovine
spongiform encephalopathy (BSE), a degenerative brain condition
accompanied by muscle wasting. BSE in turn is similar to a condition in
sheep called scrapies (the animals scrape or scratch themselves) that also
features wasting of brain and body. Chronic wasting disease is a similar
condition found in deer and elk.
The infectious nature of such conditions was observed in the Fore tribe
of Papua New Guinea in the 1950s. A large number of Fore were dying of
a muscle-wasting condition called kuru (meaning to shake in Fore). The
Fore contracted kuru by practicing ritual cannibalism: they ate the brains
of dead relatives, which the Fore believed preserves their spirits. In an
experiment to investigate the condition, body parts from kuru victims
were fed to a chimp that contracted the disease.
The infectious agent in these conditions is a prion. Prion proteins are
found in healthy cell membranes and may play a role in attaching one cell
to another. Prion proteins also bind to metallic ions, for example, copper.
The proteins typically fold in a normal configuration but can also misfold
(Figure 16-13 ). The altered configuration causes disease.
A misfolded prion protein will attach to a healthy prion protein and
cause it to misfold. Misfolded prions tend to clump together, forming
protein aggregates that eventually result in cell death. Misfolded prions
can also infect neighboring brain and body cells, resulting in general
brain degeneration and muscle wasting. An infectious prion can pass
from one individual to another, and even from one species to another, but
only if the normal prion proteins in the two individuals are similar.
Investigations show that among several alleles of the gene that produces
normal prion proteins, some are more susceptible to misfolding than are
others. Individuals with alleles that are not susceptible to misfolding, as
are those Fore tribespeople who did not contract kuru, are resistant to
prion disease.
 © Mayo Foundation for Medical Education and Research. All r ights reserved.
FIGURE 16-13 Disease Process Left: Prion proteins typically fold into
helixes and pleated sheets. Right: In misfolding, part of the protein helix changes
into a sheet. The result is an infectious disease–causing prion.

In Parkinson disease, the misfolded protein is proposed to be alpha

synuclein. Its accumulation, largely in substantia nigra cells, is a Lewy
body (Olanow & Brundin, 2013). In Alzheimer disease, the accumulating
protein forms amyloid plaques and mainly affects cortical cells (Kumar et
al., 2015). Misfolded proteins in oligodendroglia may be responsible for
the cell demyelination characteristic of MS and ALS (Shi et al., 2015).
The prion theory opens new avenues for investigating degenerative
disease treatments, including drugs that remove prions, block prion
misfolding, or alter prion forms prone to misfolding (Asante et al., 2015).
Selective cattle breeding for prion alleles that do not produce misfolding
prevents BSE. Inserting a misfolding-resistant human prion allele into
mice renders them resistant to prion disease. Any treatment developed for
humans could potentially treat BSE in cattle, scrapie in sheep, and
wasting disease in deer and elk. Preventing prion misfolding could even
arrest, in part, degenerative consequences of traumatic brain injury and
concussion.
 Sandy Huffaker/The New York Times/Redux

Brain Workout Engaging in cognitively stimulating activities can

keep neural networks and general cognitive function from declining with
age.

Age-Related Cognitive Loss

Most people who grow old do not become demented, but virtually
everyone acquires age-related cognitive loss, even while living an active,
healthy, productive life. Aging is associated with declines in perceptual
functions, especially vision, hearing, and olfaction, and declining motor,
cognitive, and executive (planning) functions as well. Older people tend
to learn at a slower pace and typically do not attain the same mastery of
new skills as do younger adults.
Noninvasive imaging studies reveal that aging is correlated with
decreased white matter volume, probably related to myelin loss. This
condition is reparable. There is little evidence of neuronal loss in typical
aging, although a reduction in neurogenesis in the hippocampus does
occur. Compared with younger people, older people tend to activate
larger regions of their attentional and executive networks (parietal and
prefrontal cortex) when they perform complex cognitive and executive
tasks. This increased activation correlates with reduced performance on
tests of working memory as well as tests of attentional and executive
tasks.
 Two lines of evidence suggest that that age-related declines in function
can be slowed. The first is aerobic exercise to enhance general health and
improve the brain’s plasticity via increased neurogenesis, gliogenesis, and
trophic factor support. The second treatment is brain exercise employing
training strategies that enhance neural plasticity and reverse learned
nonuse. Most of us know the frustration of losing a skill—whether it’s
trigonometry or tennis—after getting out of practice. Skill loss does not
reflect dementia but simply a use-it-or-lose-it effect. Training programs
designed to stimulate plasticity in the appropriate cerebral circuitry
include motor, auditory, or visual system–based cognitive and/or
attentional training. Brain training is designed to stimulate plasticity
rather than to rehabilitate specific losses.
William Milberg and his colleagues (e.g., Kuo et al., 2005; Leritz et
al., 2011) have explored the idea that aging changes in the brain take
place in the context of the entire body’s aging. For example, dementia
may reflect a chronic cerebrovascular disorder, marginal high blood
pressure. Marginal elevations in blood pressure can lead to cerebral
microbleeds, especially in white matter. The cumulative effect of years or
even decades of tiny bleeds would lead eventually to increasingly
disturbed cognition. The condition may first appear as a mild cognitive
impairment (MCI) that slowly progresses, with cumulative microbleeds,
toward dementia.
View the progression of these microbleeds, or silent strokes, at
https://www.youtube.com/watch?v=J3fb0CaDpEk .
 16-3 REVIEW
Understanding and Treating Neurological Disorders
Before you continue, check your understanding.
1 . As the developed world’s population ages, ___________ disease will
become more common than disease.
2 . Even imaging techniques may miss pathology produced by
___________.
3 . Interruption of blood to the brain is called ___________ and if
prolonged can result in ___________.
4 . Although superficially appearing to be very different diseases,
Parkinson and Alzheimer have similarities such as ___________ and
___________ that suggest that they may be part of a common disease
spectrum.
5 . Name two strategies that can reduce or reverse neurological and
cognitive decline with aging.
Answers appear at the back of the book.

For additional study tools, visit Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 Understanding and Treating
16-4

Neurological Disorders
The DSM-5 summarizes a wide range of mental disorders. We focus on
the three general behavioral categories—psychoses, mood disorders, and
anxiety disorders—that are the best studied and understood. Figure 16-
14 summarizes their prevalence. Personal, family, and social costs are
not reflected in these statistics. Schizophrenia, bipolar disorder, and
major depression affect a smaller number of people, but their costs, in
loss of social relationships, productivity, and medical care, are
disproportionate.

FIGURE 16-14 Prevalence of Some Psychiatric Illnesses

Data from National Institutes of Mental Health,
http://www.nimh.nih.gov/health/statistics/index.shtml

Schizophrenia Spectrum and Other

Psychotic Disorders
Psychoses are psychological disorders in which a person loses contact
with reality, subject to irrational ideas and distorted perceptions. Among
the varieties of psychosis, schizophrenia is the most common and best
understood. Although it takes many forms, whether schizophrenia is a
single disorder or several disorders that share some symptoms is
uncertain. The complexity of behavioral and neurobiological factors that
characterize schizophrenia makes it especially difficult to diagnose and
classify. Understanding schizophrenia is an evolving process and far
from complete.
Diagnosing Schizophrenia
The DSM lists six diagnostic symptoms of schizophrenia:
1. Delusions—beliefs that distort reality
2. Hallucinations—distorted perceptions, such as hearing voices
3. Disorganized speech, such as incoherent statements or senselessly
rhyming talk
4. Disorganized behavior or excessive agitation
5. The opposite extreme of agitation: catatonic behavior
6. Negative symptoms, such as blunted emotions or loss of interest and
drive, all characterized by the absence of some healthy response
The DSM criteria are subjective and more helpful in clinical diagnoses
than in relating schizophrenia to objective, measurable brain
abnormalities.
Neurobiology of Schizophrenia
Although schizophrenia may produce a wide range of symptoms,
individual differences in behavioral effects exist as well. Voluminous
research related to the origins and causes of schizophrenia has emerged,
but the three lines of research summarized in this section have
transformed ideas about its genetics, its development, and its associated
brain correlates.
GENETICS It has long been recognized that genetics figures in
schizophrenia, as does environment. The more closely related an
individual is to someone diagnosed with schizophrenia, the more likely
he or she is to develop the condition. The concordance of schizophrenia
in identical twins is high: 50 percent is often cited. That the concordance
for schizophrenia is not 100 percent means that environmental factors
also play a role (Shorter & Miller, 2015).
It is also likely that many genes are associated with schizophrenia.
Mutations on a number of chromosomes (candidates are 1, 6, 8, 13, and
22) predispose an individual to schizophrenia. It is also likely that many
mutations in candidate genes on those chromosomes are involved.
Genetic studies suggest that schizophrenia is probably a family of
disorders and that the family may include other conditions, such as major
depression and bipolar disorder (Claes et al., 2012). What may be
common to the genes involved is that they contribute to brain
development and so may contribute to various abnormalities in brain
development.
DEVELOPMENT Typically, schizophrenia is diagnosed in young
adulthood, but a body of evidence suggests that it originates much
earlier, even prenatally. Its expression in adulthood must therefore await
the conclusion of a host of developmental processes that ultimately shape
the adult human brain. That schizophrenia has developmental origins has
many implications.
First, environmental factors acting through epigenetic mechanisms are
likely to influence brain development such that a subset of at-risk
individuals develops adult schizophrenia. Second, identifying
developmental factors that contribute to schizophrenia provides the best
opportunity for intervention to reduce the risks of developing it. Any
potential “cure” for schizophrenia will depend on early detection and
remediation through epigenetic mechanisms (Gebicke-Haerter, 2012).
BRAIN CORRELATES Many studies show anatomical changes in the
brain associated with schizophrenia, especially in the temporal and
frontal lobes.
1. Suggesting cell loss in these areas, the schizophrenic brain generally
has large ventricles and thinner cortex in the medial temporal regions
and frontal cortex.
2. Some aspects of neuronal and fiber composition of the temporal lobes
and the frontal lobes are changed, as indicated by changes in their
density imaged by MRI (Kong et al., 2012).
3. Alterations in neuronal structure show abnormal dendritic fields in
cells in the dorsal prefrontal regions; as shown in Figure 16-15 , in the
 hippocampus (Cho et al., 2004); and in the entorhinal cortex (Arnold
et al., 1997).
In sum, this evidence seems almost definitive in identifying
schizophrenia as a developmental brain disorder associated in the main
with alteration in the temporal and the frontal cortex. These brain regions
are associated with memory, language, and decision making.

(A)
Organized (healthy) pyramidal neurons
(B)

Disorganized (schizophrenic) pyramidal neurons

FIGURE 16-15 Organic Dysfunction (A ) Rather than the
consistently parallel orientation of hippocampal neurons typical in healthy
 brains, (B ) the orientation of hippocampal neurons in the brain of a person
with schizophrenia is haphazard. Information from J. A. Kovelman & A. B. Scheibel
(1984). A neurohistologic correlate of schizophrenia. Biological Psychiatry, 19, p. 1613.

Neurochemical Correlates of Schizophrenia

Neuroscientists also consider the neurochemical correlates of brain–
behavior relations in schizophrenia. Dopamine abnormalities were the
first to be linked to schizophrenia, through two lines of evidence. First,
most neuroleptic drugs act on the dopamine synapse was taken as
evidence that schizophrenia is a disease of heightened activity in the
ventral tegmental dopamine system. Second, drugs that enhance
dopaminergic activity, such as amphetamine, can produce psychotic
symptoms reminiscent of schizophrenia.
Neuroleptics are antipsychotic drugs described in Section 6-2 .
This dopamine theory of schizophrenia appears too simple, however,
because many other neurochemical abnormalities, summarized in Table
16-6 , are also associated with schizophrenia—in particular,
abnormalities in dopamine and dopamine receptors and in GABA and
GABA-binding sites. Recent evidence also suggests changes in the
NMDA receptor in schizophrenia, a finding that is leading to the
development of new classes of glutamate drug therapy (Pannese et al.,
2012). Patients vary widely in the extent of each abnormality, however.
How these neurochemical variations might relate to the presence or
absence of specific symptoms is not yet known.
GABA is the brain’s main inhibitory neurotransmitter.
Biochemical Changes Associated with
TABLE 16-6
Schizophrenia
Decreased dopamine metabolites in cerebrospinal fluid

Increased striatal D2 receptors

Decreased expression of D3 and D4 mRNA in specific cortical regions

Decreased cortical glutamate

Increased cortical glutamate receptors

Decreased glutamate uptake sites in cingulate cortex

Decreased mRNA for synthesizing GABA in prefrontal cortex

Increased GABAA -binding sites in cingulate cortex

 Source: Information from W. Byne, E. Kemegther, L. Jones, V. Harouthunian, and K. L.
Davis (1999). The neurochemistry of schizophrenia. In D. S. Charney, E. J. Nestler, &
B. S. Bunney. The Neurobiology of Mental Illness (p. 242). New York: Oxford
University Press.

To summarize, schizophrenia is a complex disorder associated with

abnormalities in brain structure and metabolism, especially in prefrontal
and temporal cortex, and with neurochemical abnormalities in dopa-
mine, glutamate, and GABA. Given the complexity of all these factors, it
comes as no surprise that schizophrenia is so difficult to characterize and
to treat.

Mood Disorders
The DSM-5 identifies a continuum of affective disorders, separating
bipolar and related disorders from depressive disorders (see Table 16-3 ).
The bipolar category is positioned between schizophrenia and depressive
disorders, forming a bridge between the diagnostic classes that takes into
account symptoms, family history, and genetics. Depression and mania
—our principal interests here—represent the extremes of affect. The
main symptoms of major depression are prolonged feelings of
worthlessness and guilt, disruption of normal eating habits, sleep
disturbances, a general slowing of behavior, and frequent thoughts of
suicide.
Focus 6-3 explains the threat of suicide attendant to untreated major
depression.
Mania, the opposite affective extreme from depression, is
characterized by excessive euphoria, which the subject perceives as
typical. The affected person often formulates grandiose plans and is
uncontrollably hyperactive. Periods of mania often change, sometimes
abruptly, to depression and back again to mania, a condition designated
as bipolar disorder.
mania Disordered mental state of extreme excitement.
bipolar disorder Mood disorder characterized by periods of
depression alternating with normal periods and periods of intense
excitation, or mania.
Neurobiology of Depression
Brain and environment both contribute to the complex neurobiology of
depression. Predisposing factors related to brain anatomy and chemistry
thus may contribute more to affective changes in some people, whereas
life experiences contribute mainly to affective changes in other people.
As a result, a bewildering number of life, health, and brain factors have
been related to depression. These factors include economic or social
failure, circadian rhythm disruption, vitamin D and other nutrient
deficiency, pregnancy, brain injury, diabetes, cardiovascular events, and
childhood abuse, among many others.
A major approach in neurobiological studies of depression is to ask
whether a common brain substrate exists for depression. Antidepressant
drugs acutely increase the synaptic levels of norepinephrine and
serotonin, a finding that led to the idea that depression results from
decreased availability of one or both neurotransmitters. Lowering their
levels in healthy participants does not produce depression, however. And
while antidepressant medications increase the level of norepinephrine
and serotonin within days, it takes weeks for drugs to start relieving
depression.
Among the various explanations suggested for these confounding
results, none is completely satisfactory. Ronald Duman (2004) reviewed
evidence to suggest that antidepressants act, at least in part, on signaling
pathways, such as on cAMP, in the postsynaptic cell. Neurotrophic
factors appear to affect antidepressant action and may underlie the
neurobiology of depression. Investigators know, for example, that brain-
derived neurotrophic factor (BDNF) is down-regulated by stress and up-
regulated by antidepressant medication (Wang et al., 2012).
Section 14-4 explores the relation of hormones, trophic factors, and
psychoactive drugs to neuroplasticity.
Given that BDNF acts to enhance the growth and survival of cortical
neurons and synapses, BDNF dysfunction may adversely affect
norepinephrine and serotonin systems through the loss of either neurons
or synapses. Antidepressant medication may increase BDNF release
through its actions on cAMP. Key here is that the cause of depression
probably is not merely a simple decrease in transmitter levels. Many
brain changes are related to depression.
Mood and Reactivity to Stress
A significant psychological factor in understanding depression is
reactivity to stress. Monoamines—the noradrenergic and serotoninergic
activating systems diagrammed in Figure 16-16 A —modulate hormone
secretion by the hypothalamic–pituitary–adrenal system—the HPA axis
—illustrated in Figure 16-16 B. When we are stressed, the HPA axis is
stimulated to secrete corticotropin-releasing hormone, which stimulates
the pituitary to produce adrenocorticotropic hormone (ACTH). ACTH
circulates through the blood and stimulates the adrenal medulla to
produce cortisol. Normally, cortisol helps us deal with stress. If we
cannot cope, or if stress is intense, excessive cortisol can wield a
negative influence on the brain, damaging the feedback loops the brain
uses to turn off the stress response.
HPA axis Hypothalamic–pituitary–adrenal circuit that controls the
production and release of hormones related to stress.
Section 6-5 explains the neurobiology of the stress response—how it
begins and ends.
Excessive stress early in life may be especially detrimental. During
critical periods in early childhood, abuse or other severe environmental
stress can permanently disrupt HPA axis reactivity: it becomes constantly
overactive. Overactivity in the HPA axis results in oversecretion of
cortisol, an imbalance associated with depression in adulthood. Patrick
McGowan and colleagues (2010) wondered if early experiences could
alter gene expression related to cortisol activity in the HPA axis. They
compared, postmortem, hippocampi obtained from suicide victims with a
history of childhood abuse and hippocampi from other suicide victims
with no childhood abuse or from controls. Abused suicide victims
showed decreased gene expression for cortisol receptors relative to the
controls. These results, derived from epigenetics, confirm that early
neglect or abuse alters the HPA axis for life.
This research confirms studies on the effects of stress on
hippocampal function reported in Sections 6-5 , 7-5 , and 8-4 .
(A)
 Noradrenergic system
(B)

Serotonergic system
FIGURE 16-16 Stress-Activating System (A ) Medial view showing that in the
brainstem, cell bodies of noradrenergic (norepinephrine) neurons emanate from the
locus coeruleus (top) and cell bodies of the serotonergic activating system emanate
from the raphe nuclei (bottom). (B ) When activated, the HPA axis affects mood,
thinking, and indirectly, cortisol secretion by the adrenal glands. HPA deactivation begins
when cortisol binds to hypothalamic receptors.

To summarize, the diffuse distribution of the norepinephrine- and

serotonin-activating systems makes relating depression to a single brain
structure impossible. Findings from neuro-imaging studies show that
depression is accompanied by increased blood flow and glucose
metabolism in the orbitofrontal cortex, anterior cingulate cortex, and
amygdala. Blood flow drops as the symptoms of depression remit when a
patient takes antidepressant medication (Drevets, Kishore, & Krishman,
2004). Antidepressants effectively increase the amount of serotonin in
the cortex and may also stimulate brain repair. For example, fluoxetine
(Prozac) stimulates both BDNF production and neurogenesis in the
hippocampus, resulting in a net increase in granule cells, described in
Research Focus 16-4 , Antidepressant Action and Brain Repair.
Although we have emphasized biological correlates of depression, the
best treatment need not be a direct biological intervention. Cognitive-
behavioral therapy (CBT) is an excellent—arguably the best—therapy
for depression. It focuses on challenging the patient’s beliefs and
perceptions. The objective is to identify dysfunctional thoughts and
beliefs that accompany negative emotions and to replace them with more
realistic ones.
cognitive-behavioral therapy (CBT) Problem-focused, action-
oriented, structured treatment for eliminating dysfunctional thoughts
and maladaptive behaviors.
Simply pointing out that a person’s beliefs are faulty is not likely to
be effective, however, because it probably took months or years to
develop those beliefs. The neural circuits underlying faulty beliefs must
change, just as the strategies for developing new ones must change. In a
real sense then, CBT is effective if it induces neural plasticity and
changes brain activity.
RESEARCH FOCUS 16-4

Antidepressant Action and Brain Repair

Excessive stress, poor coping skills, or both contribute to excessive
cortisol levels in the brain and to depression and anxiety. Granule
cells in the hippocampus, which are especially sensitive to cortisol,
can die when cortisol levels either are reduced, as shown in the
figure, or increased excessively.
These hippocampal cells may play a role in regulating cortisol
levels and switching off the brain’s stress response. Their absence
leaves the HPA axis unchecked. Then increased cortisol levels
contribute to more neuron death and to depression and anxiety. It’s a
vicious circle.
A remarkable finding emerged from studying how antidepressants
such as fluoxetine (Prozac) and other selective serotonin reuptake
inhibitors affect the hippocampus. The SSRIs increased neurogenesis
in the subgranular zone, cell migration into the dentate gyrus, and the
number of functioning cells there (Malberg et al., 2000).
That antidepressants take some weeks to produce their positive
effects on behavior and that new neurons take some weeks to
migrate and incorporate into the hippocampus suggest that the
antidepressants’ mechanism of action is to enhance hippocampal
function—in essence, to replace the neural switch that turns off the
stress response.
Healthy rat hippocampus

Neuronal degeneration
 Images from S. C. Spanswick and R. J. Sutherland (2010). Object-context specific memory
deficits associated with loss of hippocampal granule cells after adrenalectomy in rats.
Learning and Memory, 17:241-245. Figure 2

Luca Santarelli and colleagues (2003) used knockout mice that

lacked a specific serotonin receptor (5-HT-1A) sensitive to
fluoxetine. They exposed these mice along with mice with intact 5-
HT-1A receptors to chronic, unpredictable stress. Both groups
developed a general deterioration in their fur coat.
Chronic antidepressant treatment affected only the mice with
intact serotonin receptors, and only these mice displayed enhanced
neuro-genesis. Thus, because antidepressants activate serotonin
receptors, serotonin must participate in enhancing neurogenesis.
The literature on hippocampal neurogenesis is the most prolific in
neuroscience, represented by over 3000 papers reporting mainly on
animal models. To summarize their findings, phenomena we
perceive as bad (deprivation in infancy, conflict, stress, poor diet,
most drugs) depress neurogenesis, and phenomena we perceive as
good (exercise, enriched environment, sufficient sleep, good diet)
enhance neurogenesis. Finding the signaling pathways that enhance
neurogenesis may reveal the relationships among altered cognition,
memory, depression, and the effects of antidepressant drugs (Costa et
al., 2015).

Anxiety Disorders
We are all subject to anxiety, usually acutely in response to stress or less
commonly as chronic reactivity—an increased anxiety response—even
to seemingly minor stressors. Anxiety reactions certainly are not
pathological; they are likely an evolutionary adaptation for coping with
adverse conditions. But anxiety can become pathological and make life
miserable. Anxiety disorders are among the most common psychiatric
conditions. The DSM-5 lists 10 classes of anxiety disorders that together
affect 15 percent to 35 percent of the population at some point in their
life lives (see Figure 16-14 ).
Focus 12-3 describes symptoms of anxiety disorders; Section 6-5 ,
how stress-induced damage contributes to PTSD
Imaging studies of people with anxiety disorders record increased
baseline activity in the cingulate cortex and parahippocampal gyrus and
enhanced responsiveness to anxiety-provoking stimuli in the amygdala
and prefrontal cortex. This finding suggests excessive excitatory
neurotransmission in a circuit involving cingulate cortex, amygdala, and
the parahippocampal region. Because drugs that enhance the inhibitory
transmitter GABA are particularly effective in reducing anxiety,
researchers hypothesize that excessive excitatory neurotransmission in
this circuit is anxiety. But what causes it?
Figure 12-18 diagrams these limbic system structures and charts
their major connections.
Considerable interest has developed in investigating why some people
show pathological anxiety to stimuli to which others have a milder
response. One hypothesis, covered earlier, in the section on depression,
is that stressful experiences early in life increase susceptibility to a
variety of behavioral disorders, especially anxiety disorders.
Although anxiety disorders used to be treated primarily with
benzodiazepines, such as Valium, now they are also treated with SSRIs,
such as Prozac, Paxil, Celexa, and Zoloft. Antidepressant drugs do not
act immediately, however, suggesting that the treatments must stimulate
some gradual change in brain structure, much as these drugs act in
treating depression.
Cognitive-behavioral therapy is as effective as drugs in treating
anxiety. The most effective behavioral therapies expose and re-expose
patients to their fears. For example, treating a phobic fear of germs
requires exposing the patient repeatedly to potentially germy
environments, such as public washrooms, until the discomfort abates.
One more time: a pill is not a skill.
 16-4 REVIEW
Understanding and Treating Behavioral Disorders
Before you continue, check your understanding.
1 . Schizophrenia is a complex disorder associated with neurochemical
abnormalities in ___________, ___________, and ___________.
2 . Schizophrenia is associated with pronounced anatomical changes in
the ___________ and cortices.
3 . The monoamine-activating systems that have received the most
investigation related to understanding depression are ___________
and ___________.
4 . The most effective treatment for depression and anxiety disorders is
___________.
5 . Describe the main difficulty in linking genes to schizophrenia.
Answers appear at the back of the book.

For additional study tools, visit : Launch Pad:

www.macmillanhighered.com/launchpad/kolb5e
 16-5 Is Misbehavior Always Bad?
You know this movie plot: a person sustains a blow to the head, then
becomes a better person. Do pathological changes in brain and behavior
sometimes lead to behavioral improvement in real life? A report by Jim
Giles (2004) on Tommy McHugh’s case is thought provoking.
McHugh (1949–2012), a heroin addict, committed multiple serious
crimes and spent a great deal of time in jail. Later he had a cerebral
hemorrhage (bleeding into the brain) from an aneurysm. The bleeding
was repaired surgically with a metal clip on the leaking artery. After he
recovered from the injury, McHugh’s personality changed dramatically.
He took up painting, which he had never done before, and became a
successful artist.
To learn more and view McHugh’s art, go to
http://www.tommymchugh.co.uk .
McHugh’s injury-induced brain changes appear to have been
beneficial, but the exact nature of his brain injury has not been identified.
The metal clip in his brain precluded the use of MRI. Aspects of his
cognitive behavior suggest that he may have had frontal lobe damage.
The phenomenon in which an individual acquires a new skill after an
injury is called acquired savant syndrome. There are other reports of
people who have developed new musical or artistic talents after their
injuries (Miller et al., 2000). Corrigan and colleagues (2012) propose
that allied savant skills can be acquired by depressing inhibitory systems
in the brain so that new skill strategies can be activated. In experiments,
for example, depressing participants’ left hemispheres with TMS briefly
improved mathematical skills, which are subserved by the right
hemisphere.
The general idea of artificially manipulating the brain for the better is
controversial (Heinz et al., 2012). Influencing brain function through a
strategy loosely described as cognitive enhancement enlists current
knowledge of pharmacology, brain plasticity, brain stimulation,
neurogenetics, and other specialties to boost brain functioning. Of
course, people already use drugs to alter brain function, and the basis of
many therapies is to enhance brain function. Psychosurgical techniques
such as frontal lobotomy were based on the general idea that brain
function could be improved. As yet, however, evidence is lacking that
cognitive enhancement for the average person is better than old-
fashioned but readily available methods: learning, practice, and a healthy
lifestyle.
cognitive enhancement Brain function enhancement by
pharmacological, physiological, or surgical manipulation.
In Focus 6-1, a brief history of cognitive enhancers is context for a
trend: procuring medication prescribed for ADHD as a study aid.
 SUMMARY
Contemporary understanding of brain and behavior is providing new
insights, explanations, and treatments for brain disorders. Neurologists,
who treat organic disorders, and psychiatrists, who treat behavioral
disorders, are forging a unified understanding of mind and brain:
neuropsychoanalysis.
16-1 Multidisciplinary Research on Brain and
Behavioral Disorders
Most behavioral disorders have multiple causes—genetic, epigenetic,
biochemical, anatomical, social–environmental variables—all of them
interacting. Research methods directed toward these causes include
family studies designed to find a genetic abnormality that might be
corrected, biochemical anomalies that might be reversed by drug or
hormone therapy, anatomical pathologies that might account for
behavioral changes, and social–environmental variables.
Investigators rely increasingly on neuroimaging (fMRI, PET, TMS,
ERP) to examine brain–behavior relations in vivo in healthy participants
as well as in people with disorders. Interest in more refined behavioral
measurements is growing, especially for cognitive behavior, the better to
understand behavioral symptoms.
16-2 Classifying and Treating Brain and Behavioral
Disorders
Disorders can be classified according to presumed etiology (cause),
symptomatology, or pathology. The classification systems developed by
psychologists, psychiatrists, and neurologists overlap, and each is revised
from time to time. Clearly, better understanding the causes of disorders
will lead to better classification systems. Advances in genetics and brain
imaging will aid this effort. The table summarizes the range of available
treatments, from highly invasive neurosurgery to noninvasive
electrophysiology, from moderately invasive pharmacology to behavioral
treatments.
General Treatment Categories
Neurosurgical
Direct intervention

DBS

Stem cell transplantation

Tissue removal or repair

Electrophysiological

Noninvasive manipulation

ECT

TMS, rTMS

Pharmacological

Chemical administration

Antibiotics or antivirals

Psychoactive drugs

Neurotrophic factors

Nutrition

Behavioral

Manipulation of experience

Behavior modification

Cognitive, cognitive-behavioral therapy

Neuropsychological

Emotional therapy, psychotherapy

Physical activity, music

rt-fMRI

VR exposure and other computer-based simulations

16-3 Understanding and Treating Neurological

Disorders
If a disorder, such as depression, is presumably caused primarily by a
biochemical imbalance, treatment is likely to be pharmacological,
although brain activation with TMS also is effective and is noninvasive.
If the disorder has a suspected anatomical cause, treatment may include
removal of pathological tissue (as in epilepsy) or implanted electrodes to
activate underactive regions (as in Parkinson disease and stroke). Many
disorders require medical treatment concurrent with behavioral therapy,
including physiotherapy or cognitive rehabilitation in patients with
stroke and TBI, and cognitive-behavioral therapies for patients with
depression and anxiety disorders.
16-4 Understanding and Treating Behavioral
Disorders
The number of people who endure hidden diseases of behavior,
especially neurodegenerative disorders and stroke, is increasing as the
population of the developed world ages. Like other plagues in human
history, dementias affect not only the person with the disease but also the
caregivers, about half of whom seek psychiatric care themselves.
16-5 Is Misbehavior Always Bad?
In rare cases, people with a behavioral disorder also have some benefit.
An individual who has a brain injury, for example, may suddenly display
an artistic talent. The explanation for this acquired savant syndrome is
that depressing the brain’s inhibitory systems can activate new skill
strategies. Artificially manipulating the brain with cognitive enhancers is
a controversial approach to improving brain function.
 KEY TERMS
akathesia, p. 586
autoimmune disease, p. 584
behavioral therapy, p. 575
bipolar disorder, p. 595
chronic traumatic encephalopathy (CTE), p. 579
cognitive enhancement, p. 598
cognitive therapy, p. 575
cognitive-behavioral therapy (CBT), p. 596
deep brain stimulation (DBS), p. 572
dementia, p. 584
diaschisis, p. 580
Diagnostic and Statistical Manual of Mental Disorders (DSM), p. 569
festination, p. 586
focal seizure, p. 583
generalized seizure, p. 583
HPA axis, p. 595
ischemia, p. 580
Lewy body, p. 590
magnetic resonance spectroscopy (MRS), p. 579
mania, p. 595
neuroprotectant, p. 580
neuropsychoanalysis, p. 565
phenylketonuria (PKU), p. 565
posttraumatic stress disorder (PTSD), p. 562
prion, p. 590
psychotherapy, p. 575
real-time fMRI (rt-fMRI), p. 576
tardive dyskinesia, p. 575
virtual reality (VR) exposure therapy, p. 562

Visit Launch Pad to access the e-Book, videos, Learning

Cur ✓ e adaptive quizzing, flashcards, and more.
www.macmillanhighered.com/launchpad/kolb5e
 ANSWERS TO SECTION REVIEW SELF-TESTS
CHAPTER 1
What Are the Origins of Brain and Behavior?
REVIEW 1-1

Neuroscience in the Twenty-First Century

1 . Traumatic brain injury (TBI)
2 . central nervous system (CNS); peripheral nervous system (PNS)
3 . cerebrum; forebrain; hemispheres; brainstem
4 . inherited; learning
5 . Research on embodied behavior proposes that we understand each
other not only by listening to words but also by observing gestures
and other body language and that we think not only with silent
language but also with overt gestures and body language.
REVIEW 1-2

Perspectives on Brain and Behavior

1 . mentalism; dualism; Materialism
2 . natural selection; Charles Darwin
3 . minimally conscious state or MCS; persistent vegetative state or PVS
4 . In formulating the theory of natural selection, Darwin relied on
observation to conclude that living organisms are related and pass
traits from parents to offspring. Mendel used experimentation to show
that heritable factors underlie phenotypic variation among species.
REVIEW 1-3

Evolution of Brains and of Behavior

1 . nervous systems
2 . nerve net; bilaterally symmetrical; ganglia; chordate
3 . cladogram
4 . Humans possess the largest brain of all animals relative to body size
and the most complex brain structure.
REVIEW 1-4

Evolution of the Human Brain and Behavior

1 . common ancestor; chimpanzee
2 . hominid; Australopithecus; Homo habilis; Homo erectus
3 . encephalization quotient (EQ); counting brain cells (neurons)
4 . in any order: climate changes; changes in lifestyle skills;
physiological changes; delayed maturation or neoteny
5 . Changes in climate may have driven many physical changes in
hominids, including the nearly threefold increase in brain size from
apes to modern humans. Evidence suggests that each new hominid
species appeared after climate changes devastated old environments
and produced new ones. Eventually, modern humans evolved
adaptability sufficient to allow us to populate almost every climatic
region on earth.
REVIEW 1-5

Modern Human Brain Size and Intelligence

1 . species-typical behavior
2 . culture; memes
3 . g ; multiple intelligences
4 . In comparing different species, a larger brain correlates with more
complex behavior. In comparing individuals within a species, brain
size and intelligence are only remotely related. Rather, the complexity
of different brain regions is related to behavioral abilities. Humans,
for example, vary widely in body size and in brain size as well as in
having different kinds of intelligence. All of these factors make any
simple comparison of individuals’ brain sizes and intelligence
impossible.
CHAPTER 2
What Is the Nervous System’s Functional Anatomy?
REVIEW 2-1
Overview of Brain Function and Structure
1 . behavior; brain
2 . in any order : frontal; temporal; parietal; occipital
3 . neuroplasticity
4 . white matter; gray matter
5 . tracts; nerves
6 . Compare your diagram with Figure 2-2 B.
REVIEW 2-2

The Nervous System’s Evolutionary Development

1 . forebrain; midbrain; hindbrain
2 . behavior
3 . The forebrain has grown dramatically over the course of vertebrate
evolution. But primitive forms have not been discarded and replaced
as more complex nervous systems emerged. The forebrain’s growth
thus is an elaboration of functions already present in the other brain
regions and leads to its functioning on multiple levels.
REVIEW 2-3

The Central Nervous System: Mediating Behavior

1 . levels of function
2 . spinal cord
3 . hindbrain; midbrain; diencephalon
4 . cerebellum
5 . basal ganglia; limbic system
6 . allocortex; neocortex; sensory; motor; integrative
7 . The forebrain regulates cognitive activity, including thought and
memory, and holds ultimate control over movement (behavior).
REVIEW 2-4
Somatic Nervous System: Transmitting
Information
1 . cranial nerves; spinal (peripheral) nerves
2 . same
3 . head; internal organs and glands
4 . The law of Bell and Magendie states that sensory (afferent) spinal
nerve fibers are dorsal (in humans, posterior) and motor (efferent)
spinal fibers are ventral (in humans, anterior). This law is important
because it allows neurologists to predict the location of spinal cord
damage accurately according to changes in sensation or movement.
REVIEW 2-5

Autonomic and Enteric Nervous Systems: Visceral

Relations
1 . ganglia
2 . sympathetic; parasympathetic; in opposition
3 . The ANS operates largely outside our conscious awareness, whether
we are awake or asleep, to regulate the vegetative functions essential
to life.
4 . numbers and types of neurons and glia and of chemical transmitters
5 . microbiome; nutrients; chemicals
6 . Psychobiotics are live organisms that, when ingested in adequate
amounts, can benefit people with psychiatric illness.
REVIEW 2-6

Ten Principles of Nervous System Function

1 . in any order: olfactory system; somatic nervous system; ANS; ENS
2 . multiple levels of functioning
3 . excitation; inhibition
4 . Any individual’s perceived reality is only a rough approximation of
what is actually present. An animal’s representation of the world
depends on the nature of the information sent to the animal’s brain.
 CHAPTER 3
What Are the Nervous System’s Functional Units?
REVIEW 3-1

Cells of the Nervous System

1 . in either order: neurons; 86 billion; glia; 87 billion
2 . in either order: exciting; inhibiting
3 . in any order: sensory neurons; detect and convey incoming stimuli
into the CNS; interneurons; form links between sensory and motor
neurons; motor neurons; make muscles move
4 . in any order: ependymal cells; astrocytes; microglia; oligodendroglia;
Schwann cells; nourishing; removing waste; insulating; supporting;
repairing
5 . The main obstacle is duplicating the complexity of a mammalian
brain and its ability to change (plasticity). Advances in artificial
intelligence are bringing increasingly sophisticated robotic technology
to fruition.
REVIEW 3-2

Internal Structure of a Cell

1 . in any order: cell membrane; nucleus; endoplasmic reticulum ( or
ER); Golgi bodies; microtubules ( or tubules); vesicles
2 . proteins; in any order: channels; gates; pumps
3 . DNA; RNA; protein
4 . endoplasmic reticulum ( or ER); Golgi bodies; microtubules;
exocytosis
5 . By using most of the proteins that it makes, a cell enables itself to
interact with other cells and to modify their behavior. The collective
action of cells mediates behavior.
REVIEW 3-3

Genes, Cells, and Behavior

1 . 23; protein
2 . alleles; proteins
3 . mutation; Down syndrome; trisomy
4 . recessive; dominant
5 . Selective breeding; Cloning; transgenic
6 . Gene methylation or DNA methylation
7 . Mendelian genetics concentrates on inheritance patterns—on which
genes parents pass to their offspring and offspring pass to succeeding
generations. Epigenetics is the study of how the environment and
experience can affect the inherited genome.
CHAPTER 4
How Do Neurons Use Electrical Signals to Transmit
Information?
REVIEW 4-1

Searching for Electrical Activity in the Nervous

System
1 . René Descartes
2 . stimulation; recording
3 . in any order: how to record from the giant axons of the North
Atlantic squid; how to use an oscilloscope to measure small changes
in voltage; how to craft microelectrodes small enough to place on or
in an axon
4 . in either order: concentration gradient, from an area of relatively high
concentration to an area of lower concentration; voltage gradient,
from an area of relatively high charge to an area of lower charge
5 . Ion channels in cell membranes may open to facilitate ion movement,
close to impede ion movement, or pump ions across the membrane.
REVIEW 4-2

Electrical Activity of a Membrane

1 . resting potential; ions
2 . semipermeable; negative
3 . hyperpolarization; depolarization
4 . action potential; nerve impulse
5 . Nerve impulses travel more rapidly on myelinated axons because of
saltatory conduction: action potentials leap between the nodes
separating the glial cells that form the axon’s myelin sheath.
REVIEW 4-3

How Neurons Integrate Information

1 . excitatory postsynaptic potentials (EPSPs); inhibitory postsynaptic
potentials (IPSPs)
2 . time; space; integrates
3 . cell body; initial segment; axon
4 . Some neurons have voltage-sensitive channels on their dendrites that
allow the reverse movement of an action potential into the neurons’
dendritic fields.
REVIEW 4-4

Into the Nervous System and Back Out

1 . sensory system or sense
2 . sensory receptor cell; voltage-sensitive
3 . motor; muscles
4 . autoimmune; acetylcholine
5 . The varieties of membrane channels generate the transmembrane
charge, mediate graded potentials, and trigger the action potential.
CHAPTER 5
How Do Neurons Communicate and Adapt?
REVIEW 5-1

A Chemical Message
1 . chemical synapses; gap junction
2 . experience; learning
3 . axodendritic; axosomatic; axomuscular; axoaxonic; axosynaptic;
axoextracellular; axosecretory; dendrodendritic
4 . dendrite; cell body or soma
5 . When an action potential reaches an axon terminal, (1) a chemical
transmitter that has been synthesized and stored in the axon terminal
(2) is released from the presynaptic membrane into the synaptic cleft.
The transmitter (3) diffuses across the cleft and binds to receptors on
the post-synaptic membrane. (4) The transmitter is deactivated.
REVIEW 5-2

Varieties of Neurotransmitters and Receptors

1 . synthesis; release; receptor action; inactivation
2 . in any order: small-molecule transmitters; peptide transmitters;
gaseous transmitters; lipid transmitters
3 . in either order: acetate, choline; acetylcholinesterase or AChE
4 . lipid; postsynaptic
5 . An ionotropic receptor’s pore or channel can be opened or closed to
regulate the flow-through of ions, directly effecting rapid and usually
excitatory voltage changes on the cell membrane. Metabotropic
receptors, which are generally inhibitory and slow acting, activate
second messengers to indirectly produce changes in cell function and
structure.
REVIEW 5-3

Neurotransmitter Systems and Behavior

1 . neurotransmitter; neurotransmitter
2 . acetylcholine or ACh; acetylcholine or ACh; acetylcholine or ACh;
norepinephrine or NE
3 . in either order: serotonin or 5-HT; dopamine or DA
4 . in any order: cholinergic; dopaminergic; noradrenergic; serotonergic
5 . This idea has been attractive for a long time, because a clear
relationship exists between DA loss in the substantia nigra and
Parkinson disease and because acetylcholine and norepinephrine are
clearly related to somatic and autonomic behaviors. But for other
 neurotransmitter systems in the brain, establishing clear one-to-one
relationships has proved difficult.
REVIEW 5-4

Adaptive Role of Synapses in Learning and

Memory
1 . synapse; learning
2 . in either order: habituation; sensitization
3 . presynaptic axon terminal; sensory; calcium; less
4 . interneurons; potassium or K; calcium ions or Ca 2+
5 . posttraumatic stress disorder or PTSD; sensitization
6 . Permanent responses to frequently occurring stimuli are biologically (
or behaviorally and/or metabolically) efficient, but if stimuli change
suddenly, a lack of flexibility becomes maladaptive.
CHAPTER 6
How Do Drugs and Hormones Influence the Brain and
Behavior?
REVIEW 6-1

Principles of Psychopharmacology
1 . psychoactive drugs; psychopharmacology
2 . blood–brain barrier; brain
3 . synapses; agonists; antagonists
4 . tolerance; sensitization
5 . in any order: feces; urine; sweat; breath; breast milk
6 . (a) Drug use at home is unlikely to condition drug-taking behavior to
familiar home cues, so tolerance is likely to occur. (b) Novel cues in a
work setting may enhance conditioning and so sensitize the occasional
drug user.
REVIEW 6-2

Grouping Psychoactive Drugs

1 . in either order: behavioral; psychoactive
2 . GABA A ; Cl – or chloride ion
3 . MAO inhibitors; SSRIs
4 . endorphins
5 . release; reuptake; D 2
6 . Psychotropic drugs act on many neurotransmitters, including
acetylcho-line, anandamide, dopamine, epinephrine, glutamate,
norepinephrine, and serotonin.
REVIEW 6-3

Factors Influencing Individual Responses to Drugs

1 . disinhibition theory (also, impulse control); learning; behavioral
myopia theory
2 . Substance abuse; addiction or substance dependence
3 . psychomotor activation; mesolimbic dopamine system
4 . females; males
5 . Behavioral myopia theory suggests that intoxicated individuals are
unusually responsive to local and immediate cues, so the environment
excessively influences their behavior, while consequences go ignored.
REVIEW 6-4

Explaining and Treating Drug Abuse

1 . liking (pleasure); tolerance; wanting (craving); sensitization
2 . frontal cortex; brainstem; mesolimbic dopamine system (pathways);
basal ganglia
3 . inheritance; epigenetics
4 . drugs; other life experiences
5 . A reasonable approach to treatment views drug addiction in the same
way as chronic behavioral addictions and medical problems are
viewed: as a lifelong challenge for most people.
REVIEW 6-5
Hormones
1 . neurohormones; pituitary gland; releasing hormones; brain
2 . in either order: steroids; peptides
3 . homeostatic; gonadal; glucocorticoids
4 . anabolic ( or anabolic–androgenic) steroids; muscle mass;
masculinizing
5 . epinephrine; cortisol
6 . The hippocampus is important in ending the stress response by
regulating cortisol levels. If cortisol remains elevated by prolonged
stress, eventually it damages the hippocampus.
CHAPTER 7
How Do We Study the Brain’s Structures and Functions?
REVIEW 7-1

Measuring and Manipulating Brain and Behavior

1 . in either order: brain function; behavior; any one from among: place
learning, matching to place, landmark learning
2 . sectioning and staining; multiphoton microscope
3 . in any order: brain lesions; brain stimulation; drugs; optogenetics;
chemogenetics
4 . Brain stimulation methods include using electrical pulses, as in DBS;
magnetic fields, as in TMS; chemicals, by administering drugs; or in
the transgenic techniques of optogenetics, which employs light, and
chemogenetics, which employs synthetic drugs to interact exclusively
with designer receptors.
REVIEW 7-2

Measuring the Brain’s Electrical Activity

1 . in any order: single-cell recording; EEG; ERP; MEG
2 . action potentials
3 . graded potentials
4 . magnetic activity of many neurons; three-dimensional localization of
the cell groups generating the measured field
5 . EEG is much less expensive than MEG.
REVIEW 7-3

Anatomical Imaging Techniques: CT and MRI

1 . in either order: computed tomography or CT scan; magnetic
resonance imaging or MRI
2 . neural connections or fiber pathways; concentrations of brain
metabolites
3 . brain injury or brain damage
4 . CT produces X-ray images of one object from many angles, then uses
scanning software to combine them into a three-dimensional image of
the brain.
REVIEW 7-4

Functional Brain Imaging

1 . in any order: functional magnetic resonance imaging or fMRI;
optical tomography or fNIRS; functional positron emission
tomography or PET
2 . radioactively labeled molecules; neurochemical
3 . cerebral blood flow
4 . Resting-state images in PET and rs-fMRI can identify abnormalities
in brain function. rs-fMRI can also identify functional connections in
the resting brain.
REVIEW 7-5

Chemical and Genetic Measures of Brain and

Behavior
1 . biochemical; in either order: microdialysis; voltammetry
2 . concordance rates
3 . DNA; gene expression
4 . Epigenetic studies show that life experience can alter gene expression
and that these changes are associated with changes in neuronal
structure and connectivity. Altered neuronal organization in turn is
associated with changes in behavior.
REVIEW 7-6

Comparing Neuroscience Research Methods

1 . in any order: temporal resolution; spatial resolution; degree of
invasiveness
2 . any one or more: EEG, ERP, and/or fNIRS; inexpensive
3 . The fundamental goal of neuroscience research is to gain an
understanding of brain–behavior relationships.
REVIEW 7-7

Using Animals in Brain—Behavior Research

1 . any two in any order: stroke; ADHD; Parkinson disease;
schizophrenia
2 . whether laboratory animals have the same symptoms that humans do
3 . neural bases; treatments
4 . Using laboratory animals in research leads to concerns about animal
welfare and raises ethical issues about whether animals should be used
in research and, if so, in what types of research.
CHAPTER 8
How Does the Nervous System Develop and Adapt?
REVIEW 8-1

Three Perspectives on Brain Development

1 . behavior
2 . neural circuits
3 . any three in any order: hormones; sensory experience; injuries; genes
4 . Behaviors cannot emerge until the requisite neural structures are
sufficiently mature.
REVIEW 8-2
Neurobiology of Development
1 . neural tube
2 . neurogenesis; gliogenesis
3 . in either order: cell adhesion molecules or CAMs; tropic factors
4 . in either order: myelination; synaptic pruning
5 . Dynamic changes in frontal lobe structure (morphology) are related to
the development of intelligence.
REVIEW 8-3

Using Emerging Behaviors to Infer Neural

Maturation
1 . independent finger movements or the pincer grasp
2 . vocabulary; sound processing
3 . Piaget’s stages of cognitive development
4 . temporal lobe; basal ganglia
5 . Correlation does not prove causation.
REVIEW 8-4

Brain Development and the Environment

1 . chemoaffinity hypothesis
2 . amblyopia
3 . testosterone
4 . critical periods or sensitive periods
5 . Adolescence is a time of rapid brain change related to pubertal
hormones and psychosocial stressors, both of which make the brain
vulnerable to disorders.
CHAPTER 9
How Do We Sense, Perceive, and See the World?
REVIEW 9-1
Nature of Sensation and Perception
1 . Sensory receptors
2 . Receptive; density
3 . target in the brain
4 . subjective experience of sensation
5 . Each modality has many receptors and sends information to the
cortex to form topographic maps.
REVIEW 9-2

The Visual System’s Functional Anatomy

1 . retinal ganglion cells or RGCs
2 . P or parvocellular; M or magnocellular
3 . geniculostriate; tectopulvinar
4 . facial agnosia or prosopagnosia
5 . The dorsal stream to the parietal lobe processes the visual guidance of
movements (the how ). The ventral stream to the temporal lobe
processes the visual perception of objects (the what ).
REVIEW 9-3

Location in the Visual World

1 . small size
2 . photoreceptors; retinal ganglion cells, lateral geniculate neurons,
cortical neurons
3 . topographic map
4 . corpus callosum
5 . The fovea is represented by a larger area in the cortex than the visual
field’s periphery, and thus there is more processing of foveal
information in region V1 than of peripheral information.
REVIEW 9-4

Neuronal Activity
1 . bars of light
2 . temporal
3 . trichromatic theory
4 . opponent
5 . RGCs are excited by one wavelength of light and inhibited by
another, producing two pairs of what seem to be color opposites—red
versus green and blue versus yellow.
REVIEW 9-5

The Visual Brain in Action

1 . hemianopia
2 . scotomas
3 . monocular blindness
4 . optic ataxia
5 . Damage to the dorsal stream produces deficits in visually guided
movements. Damage to the ventral stream produces deficits in object
recognition.
CHAPTER 10
How Do We Hear, Speak, and Make Music?
REVIEW 10-1

Sound Waves: Stimulus for Audition

1 . air pressure waves or compression waves or sound waves
2 . in any order: frequency; amplitude; complexity
3 . in any order: loudness; pitch; prosody, quality or timbre
4 . temporal
5 . Delivery speed, or the number of sound segments that can be
analyzed per second, distinguishes speech and musical sounds from
other auditory inputs. Nonlanguage sounds faster than 5 segments per
second are heard as a buzz, yet we are capable of understanding
speech delivered at nearly 30 segments per second. Random or
aperiodic sounds are noise.
REVIEW 10-2

Functional Anatomy of the Auditory System

1 . ossicles or, in any order, hammer, anvil, and stirrup
2 . inner hair cells; cochlea
3 . in either order: basilar; tectorial
4 . auditory or cochlear; auditory vestibular or eighth
5 . inferior colliculus; medial geniculate nucleus
6 . The planum temporale is larger in the left hemisphere, and Heschl’s
gyrus is larger in the right. In most people, this anatomical asymmetry
correlates to a functional asymmetry: the left temporal cortex analyzes
language-related sounds, whereas the right temporal cortex analyzes
music-related ones.
REVIEW 10-3

Neural Activity and Hearing

1 . tonotopic
2 . cochlea
3 . superior olive; trapezoid body
4 . audition for action
5 . The brain detects a sound’s location via two mechanisms. Neurons in
the brainstem (hindbrain) compute the ITD, the time difference in a
sound wave’s arrival at each ear. Other neurons in the brainstem
compute IID, the difference in sound amplitude (loudness) in each ear.
REVIEW 10-4

Anatomy of Language and Music

1 . language; music
2 . in any order: Broca’s area; supplementary speech area; face area of
motor cortex
3 . Wernicke’s
4 . Broca’s
5 . in either order: perfect ( or absolute) pitch; amusic or tone deaf
6 . Three lines of evidence support the idea that language is innate: the
universality of language, the natural acquisition by children, and the
presence of syntax in all languages.
REVIEW 10-5

Auditory Communication in Nonhuman Species

1 . epigenetic mechanisms
2 . left
3 . echolocation; sonar
4 . Birdsong dialects demonstrate that the songs young birds hear
influence how they sing.
CHAPTER 11
How Does the Nervous System Respond to Stimulation and
Produce Movement?
REVIEW 11-1

A Hierarchy of Movement Control

1 . hierarchy
2 . prefrontal; premotor; motor cortex or M1
3 . brainstem
4 . spinal cord
5 . Lower-level functions in the motor hierarchy can continue in the
absence of higher-level ones, but the higher levels provide voluntary
control over movements. When the brain is disconnected from the
spinal cord then, movement can no longer be controlled at will.
REVIEW 11-2

Motor System Organization

1 . topographic; homunculus; larger
2 . motor map
3 . corticospinal; lateral corticospinal; anterior corticospinal
4 . trunk; arm; finger
5 . muscles; in either order: flexes, extends
6 . The motor cortex, M1, is organized into a set of functional categories
that encode a movement lexicon, or dictionary. Used in different
combinations, these few movements enable more complex
movements.
REVIEW 11-3

Basal Ganglia, Cerebellum, and Movement

1 . basal ganglia; force
2 . hyperkinetic; hypokinetic
3 . accuracy; skills
4 . The cerebellum compares an intended movement with the actual
movement, calculates any necessary corrections, and informs the
cortex to correct the movement.
REVIEW 11-4

Somatosensory System Receptors and Pathways

1 . hapsis; proprioception; nociception
2 . posterior; anterior
3 . pain gate
4 . periaqueductal gray matter or PAG
5 . vestibular; balance
6 . Without proprioception, sensory information about body location and
movement is lost and can be regained by only using vision.
REVIEW 11-5

Exploring the Somatosensory Cortex

1 . primary; secondary
2 . apraxia
3 . dorsal visual; ventral visual
4 . Pain perception does not depend simply on pain sensations but is a
construct of the brain.
CHAPTER 12
What Causes Emotional and Motivated Behavior?
REVIEW 12-1

Identifying the Causes of Behavior

1 . rewarding
2 . minimum level of sensory stimulation
3 . smell and taste or chemical senses
4 . In general, behavior is controlled by neural circuits that are
modulated by a wide range of factors.
REVIEW 12-2

The Chemical Senses

1 . olfactory epithelium
2 . flavor
3 . pheromones
4 . allele of the taste receptor gene TAS2R38 ; number of taste buds
5 . Any given odorant stimulates a unique pattern of receptors, and the
summed activity, or pattern of activity, produces our perception of a
particular odor.
REVIEW 12-3

Evolution, Environment, and Behavior

1 . rewards or reinforcers
2 . taste aversion learning
3 . innate releasing mechanisms or IRMs
4 . tasting
5 . When two unrelated events are experienced together, they may
inadvertently become associated. For example, unexpected pain in the
 presence of a stranger may lead to a faulty association between the
person and the pain.
REVIEW 12-4

Neuroanatomy of Motivated and Emotional

Behavior
1 . regulatory; nonregulatory
2 . hypothalamus
3 . in any order: hypothalamus; limbic system; frontal lobes
4 . in any order: dorsolateral; orbitofrontal; ventromedial
5 . amygdala
6 . hormones
7 . The limbic system stimulates emotional reactions and species-typical
behaviors, whereas the frontal lobes generate the rationale for
behavior at the right time and context, taking into account factors such
as external events and internal information.
REVIEW 12-5

Control of Regulatory and Nonregulatory Behavior

1 . in any order: lateral hypothalamus; ventrome-dial hypothalamus;
paraventricular nucleus
2 . in either order: hypothalamus; amygdala
3 . in either order: organizing; activating
4 . osmotic; hypovolemic
5 . Variations in epigenetic effects could lead to different architecture and
function of the hypothalamus among heterosexuals, homosexuals, and
transgender individuals.
REVIEW 12-6

Reward
1 . rewarding
2 . wanting; liking
3 . in any order: dopamine; opioid; benzodiazepine–GABA
4 . Intracranial self-stimulation is a phenomenon whereby animals learn
to turn on a stimulating electric current to their brain, presumably
because it activates the neural system that underlies reward.
CHAPTER 13
Why Do We Sleep and Dream?
REVIEW 13-1

A Clock for All Seasons

1 . circannual; circadian
2 . free-running; Zeitgebers
3 . any 2: light pollution; jet lag; working swing shifts; working night
shifts
4 . Circadian rhythm allows us to synchronize our behavior with our
body’s metabolic processes—so that we are hungry at optimal times
for eating, for example, and tired at optimal sleep times.
REVIEW 13-2

Neural Basis of the Biological Clock

1 . superchiasmatic nucleus or SCN
2 . retinohypothalamic; melanopsin ganglion or photosensitive retinal
ganglion
3 . shell; chemical; anatomical
4 . Experimental evidence suggests that the circadian rhythm can put a
time stamp on a behavioral event, rendering it easier to recall at the
same time in the circadian cycle that it occurred in previously.
REVIEW 13-3

Sleep Stages and Dreaming

1 . in either order: REM, rapid eye movement; NREM, non–rapid eye
movement
2 . EOG or electrooculogram; EMG or electro-myogram; EEG or
electroencephalogram
3 . five; lengthening
4 . everyone; real time
5 . Interpreting dreams is difficult because it is always possible that the
interpreter will impose his or her own explanation, or spin, on the
dreams.
REVIEW 13-4

What Does Sleep Accomplish?

1 . biological; restorative; memories
2 . Explicit; implicit
3 . place cell; NREM
4 . microsleep
5 . If a memory can be stored during waking, sleep may not be essential
for its storage.
REVIEW 13-5

Neural Bases of Sleep

1 . reticular activating system or RAS; NREM
2 . coma
3 . REM sleep
4 . subcoerulear
5 . We have separate neural systems for keeping us awake while we are
still (cholinergic) and awake when we move (serotinergic).
REVIEW 13-6

Sleep Disorders
1 . insomnia; narcolepsy
2 . drug-dependent insomnia
3 . sleep paralysis; cataplexy
4 . REM sleep behavioral disorder or REM without atonia; subcoerulear
5 . Orexin is probably only one of many factors related to waking
behavior, as animals with narcolepsy can be awake but then collapse
into sleep.
CHAPTER 14
How Do We Learn and Remember?
REVIEW 14-1

Connecting Learning and Memory

1 . Pavlovian or classical
2 . operant or instrumental
3 . implicit; explicit
4 . Episodic
5 . Memory is not localized to any particular brain circuit or region.
Rather, multiple memory circuits vary with the requirements of the
memory task.
REVIEW 14-2

Dissociating Memory Circuits

1 . in either order: hippocampus; amygdala
2 . basal ganglia
3 . Lashley searched for explicit memory in the perceptual and motor
systems of his animal subjects using invasive tests designed mostly
for implicit memory. Milner studied a patient with medial temporal
removal and used behavioral tests of both explicit and implicit
memory.
REVIEW 14-3

Neural Systems Underlying Explicit and Implicit

Memories
1 . in either order: hippocampus; neocortex ( or cortex)
2 . implicit
3 . amygdala
4 . consolidation
5 . Emotional experiences stimulate hormonal and neurochemical
activating systems that stimulate the amygdala. The amygdala in turn
modulates the laying down of memory circuits in the rest of the brain.
REVIEW 14-4

Structural Basis of Brain Plasticity

1 . long-term potentiation or LTP; long-term depression or LTD
2 . GABAergic or inhibitory
3 . in either order: synapse number; neuron number
4 . hippocampus
5 . behavioral sensitization
6 . Plastic changes in neural networks can interfere with behavior,
essentially by learning behaviors that interfere with healthy function.
Examples are addiction and PTSD.
REVIEW 14-5

Recovery from Brain Injury

1 . in any order: learn new ways to solve problems; reorganize the brain
to do more with less; replace the lost neurons
2 . in either order: direct cortical stimulation; deep brain stimulation or
DBS
3 . neurotrophic
4 . Functional improvement after brain injury reflects compensation
rather than recovery.
CHAPTER 15
How Does the Brain Think?
REVIEW 15-1

The Nature of Thought

1 . in order: attending to; identifying; making meaningful responses to
2 . language; flexibility
3 . neuron
4 . Much of human thought is verbal. Language allows us to categorize
information and provides a way to organize our behavior around time.
REVIEW 15-2

Cognition and the Association Cortex

1 . knowledge; cognition
2 . temporal; parietal
3 . in either order: plan movements; organize behavior over time
4 . Mirror
5 . Multimodal cortex allows the brain to combine characteristics of
stimuli across different sensory modalities, whether we encounter
them together or separately.
REVIEW 15-3

Expanding Frontiers of Cognitive Neuroscience

1 . cognitive neuroscience
2 . brain connectome
3 . cerebellum
4 . social interactions
5 . theory of mind
6 . decision making
7 . in any order: understanding others; understanding oneself; self-
regulation; social living
REVIEW 15-4

Cerebral Asymmetry in Thinking

1 . in either order: spatial behavior; music
2 . in either order: controlling voluntary movement sequences; language
3 . corpus callosum
4 . Because the hemispheres process information differently, they think
differently. And the existence of language in the left hemisphere
allows it to label computations and thus make inferences that the right
cannot.
REVIEW 15-5

Variations in Cognitive Organization

1 . in either order: sex; handedness
2 . neural circuits
3 . synesthesia
4 . Gonadal hormones influence brain development and shape neural
circuits in adulthood.
REVIEW 15-6

Intelligence
1 . g factor or general intelligence; multiple intelligences; convergent
and divergent; intelligence A; intelligence B
2 . structural; functional
3 . any 3, in any order: gyral patterns; cytoarchitectonics; vascular
patterns; neurochemistry
4 . epigenetic
5 . Both fMRI and ERP studies show that the efficiency of prefrontal–
parietal circuits is related to standard intelligence measures.
“Executive” function is related to gray matter volume in the frontal
lobe.
REVIEW 15-7

Consciousness
1 . complex
2 . Consciousness
3 . consciousness
4 . Movements in which speed is critical, such as hitting a pitched ball,
cannot be controlled consciously.
 CHAPTER 16
What Happens When The Brain Misbehaves?
REVIEW 16-1

Multidisciplinary Research on Brain and

Behavioral Disorders
1 . brainstem and limbic system; neocortex; dorsal frontal cortex
2 . in any order: genetic errors; epigenetic mechanisms; progressive cell
death; rapid cell death; loss of neural connections
3 . PKU or phenylketonuria
4 . subjective
5 . Brain pathology can exist without obvious clinical symptoms and
clinical symptoms without obvious pathology.
REVIEW 16-2

Classifying and Treating Brain and Behavioral

Disorders
1 . any 3 in any order: social, psychological, psychiatric, neurological
2 . Epidemiology
3 . genetics, neuroimaging
4 . in any order: neurosurgical, electrophysiological, pharmacological,
behavioral
5 . deep brain stimulation or DBS
6 . transcranial magnetic stimulation or TMS
7 . Classification systems can be revised using new information such as
that obtained from genetics and brain imaging.
REVIEW 16-3

Understanding and Treating Neurological

Disorders
1 . Alzheimer; Parkinson
2 . TBI or traumatic brain injury
3 . ischemia; stroke
4 . loss of cells from the substantia nigra; accumulation of Lewy bodies
5 . Aerobic exercise and brain training are strategies for enhancing or
stimulating neuroplasticity as we age.
REVIEW 16-4

Understanding and Treating Psychiatric Disorders

1 . in any order: dopamine, glutamate, GABA
2 . in either order: temporal; frontal
3 . in either order: norepinephrine; serotonin
4 . cognitive-behavioral therapy or CBT
5 . Many genetic and epigenetic influences contribute to every behavior,
including schizophrenia.
GLOSSARY
 A
absolutely refractory The state of an axon in the repolarizing period, during which a new action
potential cannot be elicited (with some exceptions), because gate 2 of sodium channels, which
are not voltage sensitive, are closed.
acetylcholine (ACh) First neurotransmitter discovered in the PNS and CNS; activates skeletal
muscles in the SNS; may either excite or inhibit internal organs in the ANS.
action potential Large, brief reversal in the polarity of an axon membrane.
activating system Neural pathways that coordinate brain activity through a single
neurotransmitter; its cell bodies lie in a brainstem nucleus; axons are distributed through a
wide CNS region.
addiction Desire for a drug; manifested by frequent use, leading to physical dependence in
addition to abuse; often associated with tolerance and unpleasant, sometimes dangerous,
withdrawal symptoms on cessation. Per the DSM-5, called substance use disorder.
afferent Conducting toward a CNS structure.
agonist Substance that enhances synapse function.
akathesia Small, involuntary movements or changes in posture; motor restlessness.
allele Alternative form of a gene; a gene pair contains two alleles.
alpha rhythm Regular wave pattern in an electroencephalogram; found in most people when
they are relaxed with eyes closed.
Alzheimer disease Degenerative brain disorder related to aging that first appears as progressive
memory loss and later develops into generalized dementia.
amblyopia Condition in which vision in one eye is reduced as a result of disuse; usually caused
by a failure of the two eyes to look in the same direction.
amnesia Partial or total loss of memory.
amphetamine Drug that releases the neurotransmitter dopamine into its synapse and like
cocaine, blocks dopamine reuptake.
amplitude Stimulus intensity; in audition, roughly equivalent to loudness, graphed by the
increasing height of a sound wave.
amusia Tone deafness—inability to distinguish between musical notes.
amygdala Almond-shaped collection of nuclei in the limbic system; plays a role in emotional
and species-typical behaviors.
anabolic steroid Class of synthetic hormones related to testosterone that have both muscle-
building (anabolic) and masculinizing (androgenic) effects; also called anabolic–androgenic
steroid.
androgen Class of hormones that stimulates or controls masculine characteristics and level of
sexual interest.
anencephaly Failure of the forebrain to develop.
anomalous speech representation Condition in which a person’s speech zones are located in the
right hemisphere or in both hemispheres.
anorexia nervosa Exaggerated concern with being overweight that leads to inadequate food
intake and often excessive exercising; can lead to severe weight loss and even starvation.
antagonist Substance that blocks synapse function.
anterior spinothalamic tract Pathway from the spinal cord to the thalamus that carries
information about pain and temperature.
anterograde amnesia Inability to remember events subsequent to a disturbance of the brain such
as head trauma, electroconvulsive shock, or neurodegenerative disease.
antianxiety agent Drug that reduces anxiety, including minor tranquilizers such as
benzodiazepines and sedative-hypnotic agents.
aphagia Failure to eat; may be due to an unwillingness to eat or to motor difficulties, especially
with swallowing.
aphasia Inability to speak or comprehend language despite the presence of normal
comprehension and intact vocal mechanisms. Broca’s aphasia is the inability to speak fluently
despite the presence of normal comprehension and intact vocal mechanisms. Wernicke’s
aphasia is the inability to understand or to produce meaningful language even though word
production remains intact.
apoptosis Genetically programmed cell death.
apraxia Inability to make voluntary movements in the absence of paralysis or other motor or
sensory impairment, especially an inability to make proper use of an object.
association cortex Neocortex outside primary sensory and motor cortices; functions to produce
cognition.
associative learning Linkage of two or more unrelated stimuli to elicit a behavioral response.
astrocyte Star-shaped glial cell that provides structural support to CNS neurons and transports
substances between neurons and blood vessels.
atonia Lacking tone; condition of complete muscle inactivity produced by motor neuron
inhibition.
attention Narrowing or focusing awareness to a part of the sensory environment or to a class of
stimuli.
attention-deficit/hyperactivity disorder (ADHD) Developmental disorder characterized by
core behavioral symptoms, including impulsivity, hyperactivity, and/ or inattention.
auditory flow Change heard as a person and a source of sound move relative to one another.
autism spectrum disorder (ASD) Range of cognitive symptoms from mild to severe that
characterize autism; severe symptoms include greatly impaired social interaction, a bizarre
and narrow range of interests, marked abnormalities in language and communication, and
fixed, repetitive movements.
autoimmune disease Illness resulting from an abnormal immune response by the body against
substances and tissues normally present in the body.
autonomic nervous system (ANS) Part of the PNS that regulates the functioning of internal
organs and glands.
autoreceptor Self-receptor in a neuronal membrane; that is, it responds to the same transmitter
released by the neuron.
axon Root, or single fiber, of a neuron that carries messages to other neurons.
axon collateral Branch of an axon.
axon hillock Juncture of soma and axon.
 B
back propagation Reverse movement of an action potential into the soma and dendritic field of
a neuron; postulated to play a role in plastic changes that underlie learning.
barbiturate Drug that produces sedation and sleep.
basal ganglia Subcortical forebrain nuclei that coordinate voluntary movements of the limbs and
body; connected to the thalamus and to the midbrain.
basic rest–activity cycle (BRAC) Recurring cycle of temporal packets, about 90-minute periods
in humans, during which an animal’s level of arousal waxes and wanes.
basilar membrane Receptor surface in the cochlea that transduces sound waves into neural
activity.
behavioral myopia “Nearsighted” behavior displayed under the influence of alcohol: local and
immediate cues become prominent; remote cues and consequences are ignored.
behavioral neuroscience Study of the biological bases of behavior in humans and other animals.
behavioral sensitization Escalating behavioral response to the repeated administration of a
psychomotor stimulant such as amphetamine, cocaine, or nicotine; also called drug-induced
behavioral sensitization.
behavioral therapy Treatment that applies learning principles, such as conditioning, to eliminate
unwanted behaviors.
beta (β) rhythm Fast brain wave activity pattern associated with a waking EEG.
bilateral symmetry Body plan in which organs or parts present on both sides of the body are
mirror images in appearance. For example, the hands are bilaterally symmetrical, whereas the
heart is not.
binding problem Philosophical question focused on how the brain ties single and varied sensory
and motor events together into a unified perception or behavior.
biological clock Neural system that times behavior.
biorhythm Inherent timing mechanism that controls or initiates biological processes.
bipolar disorder Mood disorder characterized by periods of depression alternating with normal
periods and periods of intense excitation, or mania.
bipolar neuron Sensory neuron with one axon and one dendrite.
blind spot Retinal region where axons forming the optic nerve leave the eye and blood vessels
enter and leave; has no photoreceptors and is thus said to be blind.
blob Region in V1 that contains color-sensitive neurons, as revealed by staining for cytochrome
oxidase.
blood–brain barrier Tight junctions between the cells that compose blood vessels in the brain,
providing a barrier to the entry of an array of substances, including toxins, into the brain.
brain connectome Map of the complete structural and functional fiber pathways of the human
brain in vivo.
brainstem Central structure of the brain; responsible for most unconscious behavior.
Broca’s area Anterior left hemisphere speech area that functions with the motor cortex to
produce movements needed for speaking.
 C
carbon monoxide (CO) Gaseous neurotransmitter; activates cellular metabolism.
cataplexy State of atonia, as in REM sleep, occurring while a person is awake and active; linked
to strong emotional stimulation.
cell adhesion molecule (CAM) A chemical molecule to which specific cells can adhere, thus
aiding in migration.
cell assembly Hypothetical group of neurons that become functionally connected via common
sensory inputs; proposed by Hebb as the basis of perception, memory, and thought.
cell body (soma) Core region of the cell containing the nucleus and other organelles for making
proteins.
central nervous system (CNS) The brain and spinal cord, which together mediate behavior.
cerebellum Major brainstem structure specialized for learning and coordinating movements;
assists the cerebrum in generating many behaviors.
cerebral cortex Thin, heavily folded film of nerve tissue composed of neurons that is the outer
layer of the forebrain. Also called neocortex.
cerebral palsy Group of disorders that result from brain damage acquired perinatally (at or near
birth).
cerebral voltammetry Technique used to identify the concentration of specific chemicals in the
brain as animals behave freely.
cerebrospinal fluid (CSF) Clear solution of sodium chloride and other salts that fills the
ventricles inside the brain and circulates around the brain and spinal cord beneath the
arachnoid layer in the subarachnoid space.
cerebrum (forebrain) Major structure of the forebrain that consists of two mirror image
hemispheres (left and right) and is responsible for most conscious behavior.
channel Opening in a protein embedded in the cell membrane that allows the passage of ions.
chemical synapse Junction at which messenger molecules are released when stimulated by an
action potential.
chemoaffinity hypothesis Proposal that neurons or their axons and dendrites are drawn toward a
signaling chemical that indicates the correct pathway.
chemogenetics Transgenic technique that combines genetics and synthetic drugs to activate
targeted cells in living tissue.
cholinergic neuron Neuron that uses acetylcholine as its main neurotransmitter; cholinergic
applies to any neuron that uses ACh as its main transmitter.
chordate Animal that has both a brain and a spinal cord.
chronic traumatic encephalopathy (CTE) Progressive degenerative disease caused by multiple
concussions and other closed-head injuries, characterized by neurofibrillary tangles, plaques,
cerebral atrophy, and expanded ventricles due to cell loss.
chronotype Individual differences in circadian activity.
circadian rhythm Day–night rhythm.
cladogram Phylogenetic tree that branches repeatedly, suggesting a taxonomy of organisms
based on the time sequence in which evolutionary branches arise.
clinical trial Consensual experiment directed toward developing a treatment.
cochlea Inner ear structure containing the auditory receptor cells.
cochlear implant Electronic device implanted surgically into the inner ear to transduce sound
waves to neural activity and allow a deaf person to hear.
cognition Act or process of knowing or coming to know; in psychology, refers to thought
processes.
cognitive-behavioral therapy (CBT) Problem-focused, action-oriented, structured treatment for
eliminating dysfunctional thoughts and maladaptive behaviors.
cognitive enhancement Brain function enhancement by pharmacological, physiological, or
surgical manipulation.
cognitive neuroscience Study of the neural bases of cognition.
cognitive therapy Psychotherapy based on the perspective that thoughts intervene between
events and emotions, and thus the treatment of emotional disorders requires changing
maladaptive patterns of thinking.
color constancy Phenomenon whereby an object’s perceived color tends to remain constant
relative to other colors, regardless of changes in illumination.
coma Prolonged state of deep unconsciousness resembling sleep.
common ancestor Forebear of two or more lineages or family groups; ancestral to both groups.
compensation Following brain damage, neuroplastic ability to modify behavior from that used
prior to the damage.
competitive inhibitor Drug, such as nalorphine and naloxone, that acts quickly to block opioid
action by competing with the opioid for binding sites; used to treat opioid addiction.
computed tomography (CT) X-ray technique that produces a static three-dimensional image of
the brain in cross section—a CT scan.
concentration gradient Difference in the relative abundance of a substance among regions of a
container; allows the substance to diffuse from an area of higher concentration to an area of
lower concentration.
conditioned response (CR) In Pavlovian conditioning, the learned response to a formerly neutral
conditioned stimulus (CS).
conditioned stimulus (CS) In Pavlovian conditioning, an originally neutral stimulus that after
association with an unconditioned stimulus (UCS) triggers a conditioned response (CR).
cone Photoreceptor specialized for color and high visual acuity.
connectome Comprehensive map of all structural connectivity (the physical wiring) in an
organism’s nervous system.
consciousness The mind’s level of responsiveness to impressions made by the senses.
consolidation Process of stabilizing a memory trace after learning.
constraint-induced therapy Procedure in which restraint of a healthy limb forces a patient to
use an impaired limb to enhance recovery of function.
contralateral neglect Ignoring a part of the body or world on the side opposite (contralateral to)
that of a brain injury.
convergent thinking Form of thinking that searches for a single answer to a question (such as 2
+ 2 = ?); contrasts with divergent thinking.
corpus callosum Band of white matter containing about 200 million nerve fibers that connects
the two cerebral hemispheres to provide a route for direct communication between them.
cortical column Anatomic organization that represents a functional unit six cortical layers deep
and approximately 0.5 mm square, perpendicular to the cortical surface.
corticospinal tract Bundle of nerve fibers directly connecting the cerebral cortex to the spinal
cord, branching at the brainstem into an opposite-side lateral tract that informs movement of
limbs and digits and a same side anterior tract that informs movement of the trunk; also called
pyramidal tract.
cranial nerve One of a set of 12 nerve pairs that control sensory and motor functions of the head,
neck, and internal organs.
critical period Developmental window during which some event has a long-lasting influence on
the brain; also, sensitive period.
cross-tolerance Reduction of response to a novel drug because of tolerance to a chemically
related drug.
culture Learned behaviors that are passed on from one generation to the next through teaching
and imitation.
cytoarchitectonic map Map of the neocortex based on the organization, structure, and
distribution of the cells.
 D
deafferentation Loss of incoming sensory input, usually due to damage to sensory fibers; also
loss of any afferent input to a structure.
decibel (dB) Measure of the relative physical intensity of sounds.
declarative memory Ability to recount what one knows, to detail the time, place, and
circumstances of events; often lost in amnesia.
deep brain stimulation (DBS) Neurosurgery in which electrodes implanted in the brain
stimulate a targeted area with a low-voltage electrical current to facilitate behavior.
delta (δ) rhythm Slow brain wave activity pattern associated with deep sleep.
dementia Acquired and persistent syndrome of intellectual impairment characterized by memory
and other cognitive deficits and impairment in social and occupational functioning.
dendrite Branching extension of a neuron’s cell membrane; greatly increases the cell’s surface
area; collects information from other cells.
dendritic spine Protrusion that greatly increases the dendrite’s surface area; typical point of
dendritic contact with the axons of other cells.
depolarization Decrease in electrical charge across a membrane, usually due to the inward flow
of sodium ions.
dermatome Body segment corresponding to a segment of the spinal cord.
Diagnostic and Statistical Manual of Mental Disorders (DSM) The American Psychiatric
Association’s classification system for psychiatric disorders.
diaschisis Neural shock that follows brain damage in which areas connected to the site of
damage show a temporary arrest of function.
dichotic listening Experimental procedure for simultaneously presenting a different auditory
input to each ear through stereophonic earphones.
diencephalon The between brain, which integrates sensory and motor information on its way to
the cerebral cortex.
diffusion Movement of ions from an area of higher concentration to an area of lower
concentration through random motion.
diffusion tensor imaging (DTI) Magnetic resonance imaging method that can image fiber
pathways in the brain by detecting the directional movements of water molecules.
dimer Two proteins combined into one.
disinhibition theory Explanation holding that alcohol has a selective depressant effect on the
brain’s frontal cortex, which controls judgment, while sparing subcortical structures
responsible for more instinctual behaviors, such as desire.
diurnal animal Organism that is active chiefly during daylight.
divergent thinking Form of thinking that searches for multiple solutions to a problem (how
many ways can a pen be used?); contrasts with convergent thinking.
dopamine (DA) Amine neurotransmitter involved in coordinating movement, attention, learning,
and in reinforcing behaviors.
dopamine hypothesis of schizophrenia Idea that excess dopamine activity causes symptoms of
schizophrenia.
dorsal stream Visual processing pathway from V1 to the parietal lobe; guides movements
relative to objects.
dorsolateral prefrontal cortex (DLPFC) Brodmann areas 9 and 46; makes reciprocal
connections with posterior parietal cortex and the superior temporal sulcus; responsible for
selecting behavior and movement with respect to temporal memory.
Down syndrome Chromosomal abnormality resulting in intellecutal impairment and other
abnormalities, usually caused by an extra chromosome 21.
drug dependence insomnia Condition resulting from continuous use of sleeping pills; drug
tolerance also results in deprivation of either REM or NREM sleep, leading the user to
increase the drug dosage.
dualism Philosophical position that both a nonmaterial mind and a material body contribute to
behavior.
dyslexia Impairment in learning to read and write; probably the most common learning disability.
 E
echolocation Identifying and locating an object by bouncing sound waves off it.
efferent Conducting away from a CNS structure.
electrical stimulation Passage of an electrical current from the uninsulated tip of an electrode
through tissue, resulting in changes in the electrical activity of the tissue.
electrical synapse See gap junction.
electrocorticography (ECoG) Graded potentials recorded with electrodes placed directly on the
brain’s surface.
electroencephalogram (EEG) Graph that records electrical activity from the brain and mainly
indicates graded potentials of many neurons.
electrographic seizures Abnormal rhythmic neuronal discharges; may be recorded by an
electroencephalogram.
embodied behavior Theory that the movements we make and the movements we perceive in
others are central to communication with others.
emotion Cognitive interpretation of subjective feelings.
emotional memory Memory for the affective properties of stimuli or events.
encephalization quotient (EQ) Jerison’s quantitative measure of brain size obtained from the
ratio of actual brain size to expected brain size, according to the principle of proper mass, for
an animal of a particular body size.
end plate On a muscle, the receptor–ion complex that is activated by the release of the
neurotransmitter acetylcholine from the terminal of a motor neuron.
endocannabinoid Class of lipid neurotransmitters, including anandamide and 2-AG, synthesized
at the postsynaptic membrane to act on receptors at the presynaptic membrane; affects
appetite, pain, sleep, mood, memory, anxiety, and the stress response.
endorphin Opioid peptide that acts as a neurotransmitter and may be associated with feelings of
pain or pleasure; mimicked by opioid drugs such as morphine, heroin, opium, and codeine.
enteric nervous system (ENS) Mesh of neurons embedded in the lining of the gut, running from
the esophagus through the colon; controls the gut.
entorhinal cortex Located on the medial temporal lobe surface; provides a major route for
neocortical input to the hippocampal formation; often degenerates in Alzheimer disease.
entrain Determine or modify the period of a biorhythm.
ependymal cell Glial cell that makes and secretes CSF; found on the walls of the brain’s
ventricles.
epidermal growth factor (EGF) Neurotrophic factor; stimulates the subventricular zone to
generate cells that migrate into the striatum and eventually differentiate into neurons and glia.
epigenetics Differences in gene expression related to environment and experience.
epinephrine (EP, or adrenaline) Chemical messenger that acts as a neurotransmitter in the CNS
and as a hormone to mobilize the body for fight or flight during times of stress.
episodic memory Autobiographical memory for events pegged to specific place and time
contexts.
estrogens Variety of sex hormones responsible for the distinguishing characteristics of the
female.
event-related potentials (ERPs) Complex electroencephalographic waveform related in time to
a specific sensory event.
evolutionary psychology Discipline that seeks to apply principles of natural selection to
understand the causes of human behavior.
excitation Increase in the activity of a neuron or brain area.
excitatory postsynaptic potential (EPSP) Brief depolarization of a neuron membrane in
response to stimulation, making the neuron more likely to produce an action potential.
explicit memory Conscious memory: subjects can retrieve an item and indicate that they know
the retrieved item is the correct one.
extinction In neurology, neglect of information on one side of the body when presented
simultaneously with similar information on the other side of the body.
extrastriate (secondary visual) cortex (V2–V5) Visual cortical areas in the occipital lobe
outside the striate cortex.
eyeblink conditioning Experimental technique in which subjects learn to pair a formerly neutral
stimulus with a defensive blinking response.
 F
facial agnosia Face blindness—the inability to recognize faces; also called prosopagnosia.
fear conditioning Conditioned emotional response between a neutral stimulus and an unpleasant
event, such as a shock, that results in a learned association.
festination Tendency to engage in a behavior, such as walking, faster and faster.
fetal alcohol spectrum disorder (FASD) Range of physical and intellectual impairments
observed in some children born to alcoholic parents.
filopod (pl. filopodia) Process at the end of a developing axon that reaches out to search for a
potential target or to sample the intercellular environment.
focal seizure Seizure that arises at a synchronous, hyperactive, localized brain region (at a
focus).
forebrain Evolutionarily the newest part of the brain; coordinates advanced cognitive functions
such as thinking, planning, and language; contains the limbic system, basal ganglia, and
neocortex.
fovea Central region of the retina specialized for high visual acuity; its receptive fields are at the
center of the eye’s visual field.
free-running rhythm Rhythm of the body’s own devising in the absence of all external cues.
frequency Number of cycles a wave completes in a given time.
frontal lobe Part of the cerebral cortex often generally characterized as performing the brain’s
executive functions, such as decision making; lies anterior to the central sulcus and beneath
the frontal bone of the skull.
functional magnetic resonance imaging (fMRI) Magnetic resonance imaging in which changes
in elements such as iron or oxygen are measured during the performance of a specific
behavior; used to measure cerebral blood flow during behavior or resting.
functional near-infrared spectroscopy (fNIRS) Noninvasive technique that gathers light
transmitted through cortical tissue to image oxygen consumption; form of optical tomography.
 G
G protein Guanyl nucleotide–binding protein coupled to a metabotropic receptor; when
activated, binds to other proteins.
gamma-aminobutyric acid (GABA) Amino acid neurotransmitter; typically inhibits neurons.
ganglia Collection of nerve cells that function somewhat like a brain.
gap junction (electrical synapse) Area of contact between adjacent cells in which ion channels
form a pore that allows ions to pass directly from one cell to the next.
gate Protein embedded in a cell membrane that allows substances to pass through the membrane
on some occasions but not on others.
gender identity The degree to which a person feels male or female.
gene DNA segment that encodes the synthesis of a particular protein.
gene (DNA) methylation Epigenetic process in which a methyl group attaches to the DNA
sequence, suppressing or enabling gene expression.
generalized anxiety disorder Persistently high levels of anxiety often accompanied by
maladaptive behaviors to reduce anxiety; thought to be caused by chronic stress.
generalized seizure Seizure that may start at a focal location then spread rapidly and bilaterally
to distributed networks in both hemispheres.
geniculostriate system Projections from the retina to the lateral geniculate nucleus to the visual
cortex.
genotype Particular genetic makeup of an individual.
glabrous skin Skin that does not have hair follicles but contains larger numbers of sensory
receptors than do hairy skin areas.
glial cell Nervous system cell that provides insulation, nutrients, and support and that aids in
repairing neurons and eliminating waste products.
glioblast Product of a progenitor cell that gives rise to different types of glial cells.
glucocorticoid One of a group of steroid hormones, such as cortisol, secreted in times of stress;
important in protein and carbohydrate metabolism.
glutamate (Glu) Amino acid neurotransmitter; typically excites neurons.
gonadal (sex) hormone One of a group of hormones, such as testosterone, that control
reproductive functions and bestow sexual appearance and identity as male or female.
graded potential Small voltage fluctuation across the cell membrane.
gray matter Areas of the nervous system composed predominantly of cell bodies and capillary
blood vessels that either collect and modify information or support this activity.
growth cone Growing tip of an axon.
growth spurt Sporadic period of sudden growth that lasts for a finite time.
gyrus (pl. gyri) A small protrusion or bump formed by the folding of the cerebral cortex.
 H
habituation Learned behavior in which the response to a stimulus weakens with repeated
presentations.
hair cell Specialized neurons in the cochlea tipped by cilia; when stimulated by waves in the
cochlear fluid, the cilia bend and generate graded potentials in inner hair cells, the auditory
receptor cells.
hapsis Perceptual ability to discriminate objects on the basis of touch.
hemisphere Literally, half a sphere, referring to one side of the cerebrum.
hertz (Hz) Measure of sound wave frequency (repetition rate); 1 hertz equals 1 cycle per second.
heterozygous Having two different alleles for the same trait.
hindbrain Evolutionarily the oldest part of the brain; contains the pons, medulla, reticular
formation, and cerebellum, structures that coordinate and control most voluntary and
involuntary movements.
hippocampus From the Greek word for seahorse ; distinctive allocortical structure lying in the
medial temporal lobe; participates in species-specific behaviors, memory, and spatial
navigation and is vulnerable to the effects of stress.
histamine (H) Neurotransmitter that controls arousal and waking; can cause the constriction of
smooth muscles; when activated in allergic reactions, constricts airway and contributes to
asthma.
homeostatic hormone One of a group of hormones that maintain internal metabolic balance and
regulate physiological systems in an organism.
homeostatic mechanism Process that maintains critical body functions within a narrow, fixed
range.
hominid General term referring to primates that walk upright, including all forms of humans,
living and extinct.
homonymous hemianopia Blindness of an entire left or right visual field.
homozygous Having two identical alleles for a trait.
homunculus Representation of the human body in the sensory or motor cortex; also any
topographical representation of the body by a neural area.
HPA axis Hypothalamic–pituitary–adrenal circuit that controls the production and release of
hormones related to stress.
Huntington disease Hereditary disease characterized by chorea (ceaseless involuntary jerky
movements) and progressive dementia, ending in death.
hydrocephalus Buildup of fluid pressure in the brain and, in infants, swelling of the head, if the
flow of CSF is blocked; can result in intellectual impairment.
hydrogen sulfide (H 2 S) Gaseous neurotransmitter; slows cellular metabolism.
hyperconnectivity Increased local connections between two related brain regions.
hyperkinetic symptom Excessive involuntary movement, as seen in Tourette syndrome.
hyperphagia Overeating that leads to significant weight gain.
hyperpolarization Increase in electrical charge across a membrane, usually due to the inward
flow of chloride or sodium ions or the outward flow of potassium ions.
hypnogogic hallucination Dreamlike event as sleep begins or while a person is in a state of
cataplexy.
hypokinesia Slowness or absence of movement.
hypokinetic symptom Paucity of movement, as seen in Parkinson disease.
hypothalamus Diencephalon structure that contains many nuclei associated with temperature
regulation, eating, drinking, and sexual behavior.
hypovolemic thirst Thirst produced by a loss of overall fluid volume from the body.
 I
implicit memory Unconscious memory: subjects can demonstrate knowledge, such as a skill,
conditioned response, or recall of events on prompting but cannot explicitly retrieve the
information.
imprinting Formation of an attachment by an animal to one or more objects or animals at a
critical period in development.
inhibition Decrease in the activity of a neuron or brain area.
inhibitory postsynaptic potential (IPSP) Brief hyper-polarization of a neuron membrane in
response to stimulation, making the neuron less likely to produce an action potential.
initial segment Area near or overlapping the axon hillock where the action potential begins.
innate releasing mechanism (IRM) Hypothetical mechanism that detects specific sensory
stimuli and directs an organism to take a particular action.
insomnia Disorder of slow-wave sleep resulting in prolonged inability to sleep.
insula Multifunctional cortical tissue located within the lateral fissure; contains language and
taste perception–related regions and neural structures underlying social cognition.
intelligence A Hebb’s term for innate intellectual potential, which is highly heritable and cannot
be measured directly.
intelligence B Hebb’s term for observed intelligence, influenced by experience and other factors
in the course of development; measured by intelligence tests.
interneuron Association cell interposed between a sensory neuron and a motor neuron; in
mammals, interneurons constitute most of the brain’s neurons.
ionotropic receptor Embedded membrane protein; acts as (1) a binding site for a
neurotransmitter and (2) a pore that regulates ion flow to directly and rapidly change
membrane voltage.
ischemia Lack of blood to the brain, usually as a result of a stroke.
 J
jet lag Fatigue and disorientation resulting from rapid travel through time zones and exposure to
a changed light–dark cycle.
 K
Klüver-Bucy syndrome Behavioral syndrome, characterized especially by hypersexuality, that
results from bilateral injury to the temporal lobe.
Korsakoff syndrome Permanent loss of the ability to learn new information (anterograde
amnesia) and to retrieve old information (retrograde amnesia) caused by diencephalic damage
resulting from chronic alcoholism or malnutrition that produces a vitamin B 1 deficiency.
 L
lateralization Localization of function primarily on one side of the brain.
law of Bell and Magendie The principle that sensory fibers are dorsal and motor fibers are
ventral.
learned taste aversion Acquired association between a specific taste or odor and illness; leads to
an aversion to foods that have the taste or odor.
learning Relatively permanent change in behavior that results from experience.
learning set Rules of the game; implicit understanding of how a problem can be solved with a
rule that can be applied in many different situations.
Lewy body Circular fibrous structure found in several neurodegenerative disorders; forms within
the cytoplasm of neurons and is thought to result from abnormal neurofilament metabolism.
light pollution Exposure to artificial light that changes activity patterns and so disrupts circadian
rhythms.
limbic system Disparate forebrain structures lying between the neocortex and the brainstem that
form a functional system controlling affective and motivated behaviors and certain forms of
memory; includes cingulate cortex, amygdala, and hippocampus, among other structures.
locked-in syndrome Condition in which a patient is aware and awake but cannot move or
communicate verbally because of complete paralysis of nearly all voluntary muscles except
the eyes.
long-term depression (LTD) Long-lasting decrease in synaptic effectiveness after low-
frequency electrical stimulation.
long-term potentiation (LTP) Long-lasting increase in synaptic effectiveness after high-
frequency stimulation.
luminance contrast Amount of light an object reflects relative to its surroundings.
 M
magnetic resonance imaging (MRI) Technique that produces a static three-dimensional brain
image by passing a strong magnetic field through the brain, followed by a radio wave, then
measuring a radio frequency signal emitted from hydrogen atoms.
magnetic resonance spectroscopy (MRS) Magnetic resonance imaging method that uses the
hydrogen proton signal to determine the concentration of brain metabolites.
magnetoencephalogram (MEG) Magnetic potentials recorded from detectors placed outside the
skull.
magnocellular (M) cell Large visual system neuron sensitive to moving stimuli and black-white
vision.
major depression Mood disorder characterized by prolonged feelings of worthlessness and guilt,
disruption of normal eating habits, sleep disturbances, a general slowing of behavior, and
frequent thoughts of suicide.
mania Disordered mental state of extreme excitement.
masculinization Process by which exposure to androgens (male sex hormones) alters the brain,
rendering it identifiably male.
materialism Philosophical position that behavior can be explained as a function of the nervous
system without recourse to the mind.
medial forebrain bundle (MFB) Tract that connects brainstem structures with various parts of
the limbic system; forms the activating projections that run from the brainstem to basal
ganglia and frontal cortex.
medial geniculate nucleus Major thalamic region concerned with audition.
medial pontine reticular formation (MPRF) Nucleus in the pons participating in REM sleep.
melatonin Hormone secreted by the pineal gland during the dark phase of the day–night cycle;
influences daily and seasonal biorhythms.
meme An idea, behavior, or style that spreads from person to person within a culture.
memory Ability to recall or recognize previous experience.
Ménière disease Disorder of the middle ear resulting in vertigo and loss of balance.
meninges Three layers of protective tissue—dura mater, arachnoid, and pia mater—that encase
the brain and spinal cord.
mentalism Explanation of behavior as a function of the nonmaterial mind.
metabolic syndrome Combinations of medical disorders, including obesity and insulin
abnormalities, that collectively increase the risk of developing cardiovascular disease and
diabetes.
metabotropic receptor Embedded membrane protein with a binding site for a neurotransmitter
linked to a G protein; can affect other receptors or act with second messengers to affect other
cellular processes, including opening a pore.
metaplasticity Interaction among different plastic changes in the brain.
microdialysis Technique used to determine the chemical constituents of extracellular fluid in
freely moving animals.
microelectrode A microscopic insulated wire or a saltwater-filled glass tube whose uninsulated
tip is used to stimulate or record from neurons.
microglia Glial cells that originate in the blood, aid in cell repair, and scavenge debris in the
nervous system.
microsleep Brief sleep period lasting a second or so.
midbrain Central part of the brain; contains neural circuits for hearing and seeing as well as
orienting movements.
mind Proposed nonmaterial entity responsible for intelligence, attention, awareness, and
consciousness.
mind–body problem Difficulty of explaining how a nonmaterial mind and a material body
interact.
minimally conscious state (MCS) Condition in which a person can display some rudimentary
behaviors, such as smiling or uttering a few words, but is otherwise not conscious.
mirror neuron Cell in the primate premotor and parietal cortex that fires when an individual
observes an action taken by another individual.
monoamine oxidase (MAO) inhibitor Antidepressant drug that blocks the enzyme monoamine
oxidase from degrading such neurotransmitters as DA, NE, and 5-HT.
monosynaptic reflex Reflex requiring one synapse between sensory input and movement.
mood stabilizer Drug for treating bipolar disorder; mutes the intensity of one pole of the
disorder, thus making the other pole less likely to recur.
motivation Behavior that seems purposeful and goal-directed.
motor neuron Cell that carries efferent information from the brain and spinal cord to make
muscles contract.
motor sequence Movement modules preprogrammed by the brain and produced as a unit.
multiple sclerosis (MS) Nervous system disorder resulting from the loss of myelin around axons
in the CNS.
mutation Alteration of an allele that yields a different version of its protein.
myelin Glial coating that surrounds axons in the central and peripheral nervous systems; prevents
adjacent neurons from short circuiting.
 N
narcolepsy Slow-wave sleep disorder in which a person uncontrollably falls asleep at
inappropriate times.
natural selection Darwin’s theory for explaining how new species evolve and how existing
species change over time. Differential success in the reproduction of different characteristics
(phenotypes) results from the interaction of organisms with their environment.
neocortex (cerebral cortex) Most recently evolved outer layer ( new bark ) of the forebrain,
composed of about six layers of gray matter; constructs our reality.
neoteny Process in which juvenile stages of predecessors become adult features of descendants;
idea derived from the observation that more recently evolved species resemble the young of
their common ancestors.
nerve Large collection of axons coursing together outside the CNS.
nerve growth factor (NGF) Neurotrophic factor that stimulates neurons to grow dendrites and
synapses and in some cases promotes the survival of neurons.
nerve impulse Propagation of an action potential on the membrane of an axon.
nerve net Simple nervous system that has no center but consists of neurons that receive sensory
information and connect directly to other neurons that move muscles.
netrin Member of the only class of tropic molecules yet isolated.
neural Darwinism Hypothesis that the processes of cell death and synaptic pruning are, like
natural selection in species, the outcome of competition among neurons for connections and
metabolic resources in a neural environment.
neural network Functional group of neurons that connects wide areas of the brain and spinal
cord.
neural plate Primitive neural tissue that gives rise to the neural tube.
neural stem cell Self-renewing multipotential cell that gives rise to any of the different types of
neurons and glia in the nervous system.
neural tube Structure in the early stage of brain development from which the brain and spinal
cord develop.
neuritic plaque Area of incomplete necrosis (dead tissue) consisting of a central protein core
(amyloid) surrounded by degenerative cellular fragments; often seen in the cortex of people
with dementias such as Alzheimer disease.
neuroblast Product of a progenitor cell that gives rise to any of the different types of neurons.
neuroeconomics Interdisciplinary field that seeks to understand how the brain makes decisions.
neuron Specialized nerve cell engaged in information processing.
neuropeptide Short (fewer than 100), multifunctional amino acid chain; acts as a
neurotransmitter and can act as a hormone; may contribute to learning.
neuroplasticity The nervous system’s potential for physical or chemical change to adapt to
environmental change and to compensate for injury.
neuroprosthetics Field that develops computer-assisted devices to replace lost biological
function.
neuroprotectant Drug used to try to block the cascade of poststroke neural events.
neuropsychoanalysis Movement within neuroscience and psychoanalysis to combine the
insights of both to yield a unified understanding of mind and brain.
neuropsychology Study of the relations between brain function and behavior, especially in
humans.
neurotransmitter Chemical with an excitatory or inhibitory effect when released by a neuron
onto a target.
neurotrophic factor A chemical compound that supports growth and differentiation in
developing neurons and may act to keep certain neurons alive in adulthood.
nitric oxide (NO) Gaseous neurotransmitter; acts, for example, to dilate blood vessels, aid
digestion, and activate cellular metabolism.
nocioception Perception of pain, temperature, and itch.
node of Ranvier The part of an axon that is not covered by myelin.
nonregulatory behavior Behavior unnecessary to the animal’s basic survival needs.
noradrenergic neuron From adrenaline, Latin for epinephrine ; a neuron containing
norepinephrine.
norepinephrine (NE, or noradrenaline) Neurotransmitter that accelerates heart rate in
mammals; found in the brain and in the sympathetic division of the ANS.
NREM (non-REM) sleep Slow-wave sleep associated with delta rhythms.
nuclei (sing. nucleus) A group of cells forming a cluster that can be identified with special stains
to form a functional grouping.
 O
obesity Excessive accumulation of body fat.
obsessive-compulsive disorder (OCD) Behavior characterized by compulsively repeated acts
(such as hand washing) and repetitive, often unpleasant, thoughts (obsessions).
occipital lobe Part of the cerebral cortex where visual processing begins; lies at the back of the
brain and beneath the occipital bone.
ocular dominance column Functional column in the visual cortex maximally responsive to
information coming from one eye.
oligodendroglia Glial cells in the CNS that myelinate axons.
operant conditioning Learning procedure in which the consequences (such as obtaining a
reward) of a particular behavior (such as pressing a bar) increase or decrease the probability of
the behavior occurring again; also called instrumental conditioning.
opioid analgesic Drug such as morphine, with sleep-inducing (narcotic) and pain-relieving
(analgesic) properties; originally called narcotic analgesic.
opponent process Explanation of color vision that emphasizes the importance of the apparently
opposing color pairs: red versus green and blue versus yellow.
optic ataxia Deficit in the visual control of reaching and other movements.
optic chiasm Junction of the optic nerves, one from each eye, at which the axons from the nasal
halves of the retinas cross to the brain’s opposite side.
optic flow Streaming of visual stimuli that accompanies an observer’s movement through space.
optogenetics Transgenic technique that combines genetics and light to excite or inhibit targeted
cells in living tissue.
orbitofrontal cortex (OFC) Prefrontal cortex behind the eye sockets (the orbits ); receives
projections from the dorsomedial nucleus of the thalamus; central to a variety of emotional
and social behaviors, including eating; also called orbital frontal cortex.
organizational hypothesis Proposal that hormonal action during development alters tissue
differentiation; for example, testosterone masculinizes the brain.
orienting movement Movement related to sensory inputs, such as turning the head to see the
source of a sound.
oscilloscope Device that serves as a sensitive voltmeter by registering changes in voltage over
time.
osmotic thirst Thirst that results from a high concentration of dissolved chemicals, or solutes, in
body fluids.
ossicle Bone of the middle ear; includes malleus (hammer), incus (anvil), and stapes (stirrup).
otoacousitic emissions Spontaneous or evoked sound waves produced within the ear by the
cochlea and escape from the ear.
 P
pain gate Hypothetical neural circuit in which activity in fine-touch and pressure pathways
diminishes the activity in pain and temperature pathways.
panic disorder Recurrent attacks of intense terror that come on without warning and without any
apparent relation to external circumstances.
parahippocampal cortex Cortex located along the dorsal medial temporal lobe surface.
paralysis Loss of sensation and movement due to nervous system injury.
paraplegia Paralysis of the legs due to spinal cord injury.
parasympathetic division Part of the autonomic nervous system; acts in opposition to the
sympathetic division—for example, preparing the body to rest and digest by reversing the
alarm response or stimulating digestion.
parietal lobe Part of the cerebral cortex that directs movements toward a goal or to perform a
task, such as grasping an object; lies posterior to the central sulcus and beneath the parietal
bone at the top of the skull.
Parkinson disease Disorder of the motor system correlated with a loss of dopamine from the
substantia nigra and characterized by tremors, muscular rigidity, and a reduction in voluntary
movement.
parvocellular (P) cell Small visual system neuron sensitive to differences in form and color.
Pavlovian conditioning Learning achieved when neutral stimulus (such as a tone) comes to elicit
a response after its repeated pairing with some event (such as delivery of food); also called
classical conditioning or respondent conditioning.
peptide hormone Chemical messenger synthesized by cellular DNA that acts to affect the target
cell’s physiology.
perception Subjective interpretation of sensations by the brain.
periaqueductal gray matter (PAG) Nuclei in the mid-brain that surround the cerebral aqueduct
joining the third and fourth ventricles; PAG neurons contain circuits for species-typical
behaviors (e.g., female sexual behavior) and play an important role in the modulation of pain.
peribrachial area Cholinergic nucleus in the dorsal brainstem having a role in REM sleep
behaviors; projects to medial pontine reticular formation.
period Time required to complete an activity cycle.
peripheral nervous system (PNS) All of the neurons in the body outside the brain and spinal
cord; provides sensory and motor connections to and from the central nervous system.
perirhinal cortex Cortex lying next to the rhinal fissure on the ventral surface of the brain.
perseveration Tendency to emit repeatedly the same verbal or motor response to varied stimuli.
persistent vegetative state (PVS) Condition in which a person is alive but unaware, unable to
communicate or to function independently at even the most basic level.
phenotype Set of individual characteristics that can be seen or measured.
phenotypic plasticity An individual’s capacity to develop into more than one phenotype.
phenylketonuria (PKU) Behavioral disorder caused by elevated levels of the amino acid
phenylalanine in the blood and resulting from a defect in the gene for the enzyme
phenylalanine hydroxylase; the major symptom is severe developmental disability.
pheromone Odorant biochemical released by one animal that acts as a chemosignal and can
affect the physiology or behavior of another animal.
phobia Fear of a clearly defined object or situation.
photoreceptor Specialized retinal neuron that transduces light into neural activity.
pituitary gland Endocrine gland attached to the bottom of the hypothalamus; its secretions
control the activities of many other endocrine glands; associated with biological rhythms.
place cell Hippocampal neuron maximally responsive to specific locations in the world.
plasticity The nervous system’s potential for physical or chemical change; enhances its
adaptability to environmental change and its ability to compensate for injury. (Also called
neuroplasticity.)
positron emission tomography (PET) Imaging technique that detects changes in blood flow by
measuring changes in the uptake of compounds such as oxygen or glucose; used to analyze
the metabolic activity of neurons.
posterior spinothalamic tract Pathway that carries fine-touch and pressure fibers.
postsynaptic membrane Membrane on the transmitter, or input, side of a synapse.
posttraumatic stress disorder (PTSD) Syndrome characterized by physiological arousal
associated with recurrent memories and dreams arising from a traumatic event that occurred
months or years earlier.
prefrontal cortex (PFC) Extensive frontal lobe area anterior to the motor and premotor cortex;
key to controlling executive functions such as planning.
preparedness Predisposition to respond to certain stimuli differently from other stimuli.
presynaptic membrane Axon terminal membrane on the transmitter, or output, side of a
synapse.
primary auditory cortex (area A1) Asymmetrical structures within Heschl’s gyrus in the
temporal lobes; receive input from the ventral region of the medial geniculate nucleus.
primary visual cortex (V1) Striate cortex in the occipital lobe that receives input from the lateral
geniculate nucleus.
priming Using a stimulus to sensitize the nervous system to a later presentation of the same or a
similar stimulus.
prion From protein and infection, an abnormally folded protein that causes progressive
neurodegenerative disorders.
procedural memory Ability to recall a movement sequence or how to perform some act or
behavior.
progenitor cell (precursor cell) Derived from a stem cell; it migrates and produces a neuron or a
glial cell.
proprioception Perception of the position and movement of the body, limbs, and head.
prosody Melodic tone of the speaking voice.
protein Folded-up polypeptide chain that serves a particular function in the body.
psyche Synonym for mind, an entity once proposed to be the source of human behavior.
psychedelic drug Drug that can alter sensation and perception; examples are lysergic acid
diethylamide (LSD), mescaline, and psilocybin.
psychoactive drug Substance that acts to alter mood, thought, or behavior; is used to manage
neuropsycho-logical illness; or is abused.
psychological construct Idea or set of impressions that some mental ability exists as an entity;
memory, language, and emotion are examples.
psychomotor activation Increased behavioral and cognitive activity: at certain levels of
consumption, the drug user feels energetic and in control.
psychopharmacology Study of how drugs affect the nervous system and behavior.
psychosurgery Any neurosurgical technique intended to alter behavior.
psychotherapy Talk therapy derived from Freudian psychoanalysis and other psychological
interventions.
pump Protein in the cell membrane that actively transports a substance across the membrane.
Purkinje cell Distinctively shaped interneuron found in the cerebellum.
pyramidal cell Distinctively shaped interneuron found in the cerebral cortex.
 Q
quadrantanopia Blindness of one quadrant of the visual field.
quadriplegia Paralysis of the legs and arms due to spinal cord injury.
quantum (pl. quanta) Amount of neurotransmitter, equivalent to the content of a single synaptic
vesicle, that produces a just-observable change in postsynaptic electric potential.
 R
radial glial cell Path-making cell that a migrating neuron follows to its appropriate destination.
rapidly adapting receptor Body sensory receptor that responds briefly to the onset of a stimulus
on the body.
rate-limiting factor Any chemical in limited supply that restricts the pace at which another
chemical can be synthesized.
real-time fMRI (rt-fMRI) Behavior-modification technique in which individuals learn to
change their behavior by controlling their own patterns of brain activation.
receptive field Sensory region that stimulates a receptor cell or neuron.
reconsolidation Process of restabilizing a memory trace after the memory is revisited.
referred pain Pain that arises in one of the internal organs but is felt on the surface of the body.
regulatory behavior Behavior motivated to meet the animal’s survival needs.
reinforcer In operant conditioning, any event that strengthens the behavior it follows.
relatively refractory The state of an axon in the later phase of an action potential during which
increased electrical current is required to produce another action potential; a phase during
which potassium channels are still open.
releasing hormone Peptide released by the hypothalamus that increases or decreases hormone
release from the anterior pituitary.
REM sleep Fast brain wave pattern displayed by the neocortical EEG record during sleep.
resting potential Electrical charge across the insulating cell membrane in the absence of
stimulation; a store of potential energy produced by a greater negative charge on the
intracellular side relative to the extracellular side.
resting-state fMRI (rs-fMRI) Magnetic resonance imaging method that measures changes in
elements such as iron or oxygen when the individual is resting (not engaged in a specific
task).
reticular activating system (RAS) Large reticulum (mixture of cell nuclei and nerve fibers) that
runs through the center of the brainstem; associated with sleep–wake behavior and behavioral
arousal; also called the reticular formation.
reticular formation Midbrain area in which nuclei and fiber pathways are mixed, producing a
netlike appearance; associated with sleep–wake behavior and behavioral arousal.
retina Light-sensitive surface at the back of the eye consisting of neurons and photoreceptor
cells.
retinal ganglion cell (RGC) One of a group of retinal neurons with axons that give rise to the
optic nerve.
retinohypothalamic tract Neural route formed by axons of photosensitive retinal ganglion cells
(pRGCs) from the retina to the suprachiasmatic nucleus; allows light to entrain the SCN’s
rhythmic activity.
retrograde amnesia Inability to remember events that took place before the onset of amnesia.
reuptake Deactivation of a neurotransmitter when membrane transporter proteins bring the
transmitter back into the presynaptic axon terminal for reuse.
rod Photoreceptor specialized for functioning at low light levels.
 S
saltatory conduction Fast propagation of an action potential at successive nodes of Ranvier;
saltatory means leaping.
schizophrenia Behavioral disorder characterized by delusions, hallucinations, disorganized
speech, blunted emotion, agitation or immobility, and a host of associated symptoms.
Schwann cell Glial cell in the PNS that myelinates sensory and motor axons.
scotoma Small blind spot in the visual field caused by migraine or by a small lesion of the visual
cortex.
scratch reflex Automatic response in which an animal’s hind limb reaches to remove a stimulus
from the surface of its body.
second-generation antidepressant Drug that acts similarly to tricyclics (first-generation
antidepressants) but more selectively on 5-HT reuptake transporter proteins; also called
atypical antidepressant.
second messenger Chemical that initiates a biochemical process when activated by a
neurotransmitter (the first messenger).
segmentation Division into a number of parts that are similar; refers to the idea that many
animals, including vertebrates, are composed of similarly organized body segments.
selective serotonin reuptake inhibitor (SSRI) Tricyclic antidepressant drug that blocks 5-HT
reuptake into the presynaptic terminal.
sensation Registration by the sensory organs of physical stimuli from the environment.
sensitization Learned behavior in which the response to a stimulus strengthens with repeated
presentations.
sensory deprivation Experimental setup in which a participant is allowed only restricted sensory
input; participants generally have a low tolerance for deprivation and may even hallucinate.
sensory neuron Cell that detects or carries sensory information into the spinal cord and brain.
serotonin (5-HT) Amine neurotransmitter; helps to regulate mood and aggression, appetite and
arousal, perception of pain, and respiration.
sexual dimorphism Differential development of brain areas in the two sexes.
sexual orientation A person’s pattern of sexual attraction—to the opposite sex or to the same sex
or to both sexes.
sleep apnea Inability to breathe during sleep, causing a sleeper to wake up to breathe.
sleep paralysis Atonia and dreaming occurring when a person is awake, usually just falling
asleep or waking up.
slow-wave sleep NREM sleep.
slowly adapting receptor Body sensory receptor that responds as long as a sensory stimulus is
on the body.
small-molecule transmitter Quick-acting neurotransmitter synthesized in the axon terminal
from products derived from the diet.
social neuroscience Interdisciplinary field that seeks to understand how the brain mediates social
interactions.
somatic marker hypothesis Proposal that marker signals arising from emotions and feelings act
to guide behavior and decision making, usually in an unconscious process.
somatic nervous system (SNS) Part of the PNS that includes the cranial and spinal nerves to and
from the muscles, joints, and skin, which produce movement, transmit incoming sensory
input, and inform the CNS about the position and movement of body parts.
somatosensory neuron Brain cell that brings sensory information from the body into the spinal
cord.
sound wave Mechanical displacement of molecules caused by changing pressure that possesses
the physical properties of frequency, amplitude, and complexity. Also compression wave.
spatial summation Addition of one graded potential to another that occur close in space.
species Group of organisms that can interbreed.
species-typical behavior Behavior that is characteristic of all members of a species, such as
walking in amphibians.
spinal cord Part of the central nervous system encased within the vertebrae (spinal column);
provides most of the connections between the brain and the rest of the body.
split brain Surgical disconnection of the hemispheres by severing the corpus callosum.
stereotaxic apparatus Surgical instrument that permits the researcher to target a specific part of
the brain.
steroid hormone Fat-soluble chemical messenger synthesized from cholesterol.
storage granule Membranous compartment that holds several vesicles containing a
neurotransmitter.
stretch-sensitive channel Ion channel on a tactile sensory neuron that activates in response to
stretching of the membrane, initiating a nerve impulse.
striate cortex Primary visual cortex (V1) in the occipital lobe; shows stripes (striations) on
staining.
striatum Caudate nucleus and putamen of the basal ganglia.
stroke Sudden appearance of neurological symptoms as a result of severely interrupted blood
flow.
substance abuse A pattern of drug use in which people rely on a drug chronically and
excessively, allowing it to occupy a central place in their life.
subunit Protein molecule that assembles with other protein molecules.
subventricular zone Lining of neural stem cells surrounding the ventricles in adults.
sudden infant death syndrome (SIDS) Unexplained death while asleep of a seemingly healthy
infant less than 1 year old.
sulcus (pl. sulci) A groove in brain matter; most are in the neocortex or cerebellum.
supplementary speech area Speech production region on the left frontal lobe dorsal surface.
suprachiasmatic nucleus (SCN) Master biological clock located in the hypothalamus just above
the optic chiasm.
sympathetic division Part of the autonomic nervous system; arouses the body for action, such as
mediating the involuntary fight-or-flight response to alarm by increasing heart rate and blood
pressure.
symptomatic seizure Identified with a specific cause, such as infection, trauma, tumor, vascular
malformation, toxic chemicals, very high fever, or other neurological disorders.
synapse Spatial junction between one neuron and another; forms the information transfer site
between neurons.
synaptic cleft Gap separating the neuronal presynaptic membrane from the postsynaptic
membrane.
synaptic vesicle Membranous compartment that encloses a quantum of neurotransmitter.
synesthesia Ability to perceive a stimulus of one sense as the sensation of a different sense, as
when sound produces a sensation of color; literally, feeling together.
syntax Ways in which words are put together; proposed to be unique to human language.
synthetic biology Design and construction of biological devices, systems, and machines not
found in nature.
 T
tardive dyskinesia Inability to stop the tongue or other body parts from moving; motor side
effect of neuroleptic drugs.
Tay-Sachs disease Inherited birth defect caused by the loss of genes that encode the enzyme
necessary for breaking down certain fatty substances; appears 4 to 6 months after birth and
results in intellectual disability, physical changes, and death by about age 5.
tectopulvinar system Projections from the retina to the superior colliculus to the pulvinar
(thalamus) to the parietal and temporal visual areas.
tectum Roof (area above the ventricle) of the midbrain; its functions are sensory processing,
particularly visual and auditory, and the production of orienting movements.
tegmentum Floor (area below the ventricle) of the midbrain; a collection of nuclei with
movement-related, species-specific, and pain perception functions.
temporal lobe Part of the cerebral cortex that functions in connection with hearing, language,
and musical abilities; lies below the lateral fissure, beneath the temporal bone at the side of
the skull.
temporal summation Addition of one graded potential to another that occur close in time.
terminal button (end foot) Knob at the tip of an axon that conveys information to other neurons.
testosterone Sex hormone secreted by the testes and responsible for the distinguishing
characteristics of the male.
thalamus Diencephalon structure through which information from all sensory systems is
integrated and projected into the appropriate region of the neocortex.
theory of mind Ability to attribute mental states to others.
threshold potential Voltage on a neural membrane at which an action potential is triggered by
the opening of sodium and potassium voltage-sensitive channels; about —50 mV relative to
extracellular surround. Also called threshold limit.
tolerance Decrease in response to a drug with the passage of time.
tonotopic representation In audition, structural organization for processing of sound waves
from lower to higher frequencies.
topographic map Spatially organized neural representation of the external world.
topographic organization Neural spatial representation of the body or areas of the sensory
world perceived by a sensory organ.
Tourette syndrome Disorder of the basal ganglia characterized by tics, involuntary vocalizations
(including curse words and animal sounds), and odd, involuntary movements of the body,
especially of the face and head.
tract Large collection of axons coursing together in the CNS.
transcranial magnetic stimulation (TMS) Procedure in which a magnetic coil is placed over
the skull to stimulate the underlying brain; used either to induce behavior or to disrupt
ongoing behavior.
transgender Possessing personal characteristics that transcend traditional gender boundaries and
corresponding sexual norms; a person’s belief that he or she was born the wrong sex.
transgenic animal Product of technology in which one or more genes from one species is
introduced into the genome of another species to be passed along and expressed in subsequent
generations.
transmitter-activated receptor Protein that has a binding site for a specific neurotransmitter and
is embedded in the membrane of a cell.
transmitter-sensitive channel Receptor complex that has both a receptor site for a chemical and
a pore through which ions can flow.
transporter Protein molecule that pumps substances across a membrane.
traumatic brain injury (TBI) Wound to the brain that results from a blow to the head.
trichromatic theory Explanation of color vision based on the coding of three primary colors:
red, green, and blue.
tricyclic antidepressant First-generation antidepressant; its chemical structure, characterized by
three rings, blocks 5-HT reuptake transporter proteins.
tropic molecule Signaling molecule that attracts or repels growth cones.
tumor Mass of new tissue that grows uncontrolled and independent of surrounding structures.
 U
unconditioned response (UCR) Unlearned, naturally occurring response to the unconditioned
stimulus (UCS), such as salivation when food is in the mouth.
unconditioned stimulus (UCS) A stimulus that naturally and automatically (unconditionally)
triggers an unconditioned response (UCR).
 V
ventral stream Visual processing pathway from V1 to the temporal lobe for object identification
and perceiving related movements.
ventricle One of four cavities in the brain that contain CSF to cushion the brain; may play a role
in maintaining brain metabolism.
ventrolateral thalamus Part of the thalamus that carries information about body senses to the
somatosensory cortex.
vertebrae (sing. vertebra) The bones that form the spinal column.
vestibular system Somatosensory system comprising a set of receptors in each inner ear that
respond to body position and to movement of the head.
virtual-reality (VR) exposure therapy Controlled virtual immersion environment that, by
allowing individuals to relive traumatic events, gradually desensitizes them to stress.
visual field Region of the visual world seen by the eyes.
visual-form agnosia Inability to recognize objects or drawings of objects.
visuospatial memory Use of visual information to recall an object’s location in space.
voltage gradient Difference in charge between two regions that allows a flow of current if the
two regions are connected.
voltage-sensitive channel Gated protein channel that opens or closes only at specific membrane
voltages.
voltmeter Device that measures the flow and the strength of electrical voltage by recording the
difference in electrical potential between two bodies.
 W
wanting-and-liking theory Explanation holding that when a drug is associated with certain cues,
the cues themselves elicit desire for the drug; also called incentive sensitization theory.
Wernicke’s area Secondary auditory cortex (planum temporale) lying behind Heschl’s gyrus at
the rear of the left temporal lobe; regulates language comprehension. Also posterior speech
zone.
white matter Areas of the nervous system rich in fatsheathed neural axons that form the
connections between brain cells.
wild type Typical allele (most common in a population).
withdrawal symptom Physical and psychological behavior displayed by an addict when drug
use ends.
 Z
Zeitgeber Environmental event that entrains biological rhythms: German for time giver.
REFERENCES
CHAPTER 1
Antón, S. C., Potts, R., & Aiello, L. C. (2014). Human evolution. Evolution of early Homo: An
integrated biological perspective. Science, 45, 1236828.
Darwin, C. (1871). The Descent of Man, and Selection in Relation to Sex. London: J. Murray.
Darwin, C. (1963). On the origin of species by means of natural selection, or the preservation of
favored races in the struggle for life. New York: New American Library. (Original work
published 1859.)
Darwin, C. (1965). The expression of the emotions in man and animals. Chicago: University of
Chicago Press. (Original work published 1872.)
Deary, I. J. (2000). Looking down on human intelligence: From psychometrics to the brain.
Oxford Psychology Series, No. 34. New York: Oxford University Press.
Dennett, D. (1978). The intentional stance. Cambridge, MA: MIT Press.
Descartes, R. (1972). Treatise on man (T. S. Hall, Trans.). Cambridge, MA: Harvard University
Press. (Original work published 1664.)
Dunbar, R. (1998). Grooming, gossip, and the evolution of language. Cambridge, MA: Harvard
University Press.
Eibl-Eibesfeldt, I. (1970). Ethology: The biology of behavior. New York: Holt, Rinehart and
Winston.
Flynn, J. R. (2012). Are we getting smarter? Rising IQ in the twenty-first century. Cambridge:
Cambridge University Press.
Fonseca-Azevedo K., & Herculano-Houzel, S. (2012). Metabolic constraint imposes tradeoff
between body size and number of brain neurons in human evolution. Proceedings of the
National Academy of Sciences United States of America, 109:18571–18576.
Gardner, H. (2006). Multiple intelligences: New horizons. New York: Basic Books.
Gardner R. A., & Gardner B. T. (1969). Teaching sign language to a chimpanzee. Science, 165,
664–672.
Gillespie-Lynch, K., Greenfield, P. M., Lyn, H., & Savage-Rumbaugh, S. (2014). Gestural and
symbolic development among apes and humans: Support for a multimodal theory of language
evolution. Frontiers in Psychology, 30, 1228.
Gordon, A. D., Nevell, L., & Wood, B. (2008). The Homo floresiensis cranium (LB1): Size,
scaling, and early Homo affinities. Proceedings of the National Academy of Sciences of the
United States of America, 105, 4650–4655.
Gould, S. J. (1981). The Mismeasure of a man. New York: Norton.
Gross, C. G. (1995). Aristotle on the brain. The Neuroscientist, 1,4, 245–250.
Hampshire, A., Highfield, R. R., Parkin, B. L., & Owen, A. M. (2012). Fractionating human
intelligence. Neuron, 76, 1225–1237.
Hebb, D. O. (1949). The organization of behavior: A neuropsychological theory. New York:
Wiley.
Herculano-Houzel. S., Avelino-de-Souza, K., Neves, K., Porfirio, J., Messeder, D., Mattos Feijo,
L., Maldonado, J., & Manger, P. R. (2014). The elephant brain in numbers. Frontiers in
Neuroanatomy. 12, 8–46.
Heron, W. (1957). The pathology of boredom. Scientific American, 196 (1), 52–56.
Herringa, R. J., Birn, R. M., Ruttle, P. L., Burghy, C. A., Stodola, D.E., Davidson, R. J., & Essex,
M. J. (2013). Childhood maltreatment is associated with altered fear circuitry and increased
internalizing symptoms by late adolescence. Proceedings of the National Academy of Sciences
of the United States of America, 110, 19119–19124.
Jacobson, E. (1932). Electrophysiology of mental activities. American Journal of Psychology, 44,
677–694.
Jerison, H. J. (1973). The evolution of the brain and intelligence. New York: Academic Press.
Johanson, D., & Edey, M. (1981). Lucy: The beginnings of humankind. New York: Warner
Books.
Kunz, A. R., & Iliadis, C. (2007). Hominid evolution of the arteriovenous system through the
cranial base and its relevance for craniosynostosis. Child’s Nervous System, 23, 1367–1377.
Lewin, R. (1998). The Origin of Modern Humans. New York: Scientific American Library.
Linge, F. R. (1990). Faith, hope, and love: Nontraditional therapy in recovery from serious head
injury, a personal account. Canadian Journal of Psychology, 44, 116–129.
Maslin, M. A., Shultz, S., & Trauth, M. H. (2015). A synthesis of the theories and concepts of
early human evolution. Philosophical Transaction of the Royal Society of London, B
Biological Sciences, 370, 20140064.
Mesoudi, A., Whiten, A., & Laland, K. N. (2006). Towards a unified science of cultural
evolution. Behavioural and Brain Sciences 29, 329–347.
Milton, K. (2003). The critical role played by animal source foods in human (Homo) evolution.
Journal of Nutrition, 133 (Suppl. 2), 3886S–3892S.
Owen, A. M. (2015). Using functional magnetic resonance imaging and electroencephalography
to detect consciousness after severe brain injury. Handbook of Clinical Neurology, 127, 277–
293.
Pickering, R., Dirks, P. H., Jinnah, Z., de Ruiter, D. J., Churchill, S. E., et al. (2011).
Australopithecus sediba at 1.977 Ma and implications for the origins of the genus Homo.
Science, 333, 1421–1423.
Potts, R., & Sloan, C. (2010). What does it mean to be human? Companion volume to the
Smithsonian National Museum of Natural History’s David H. Koch Hall of Human Origins.
Washington, DC: National Geographic Society.
Prinz, J. (2008). Is consciousness embodied? In P. Robbins and. M. Aydede (Eds.), Cambridge
Handbook of Situated Cognition. Cambridge: Cambridge University Press.
Sankararaman, S., Mallick S., Dannemann, M., Prüfer, K., Kelso, J., Pääbo, S., Patterson, N.,
Reich, D. (2014). The genomic landscape of Neanderthal ancestry in present-day humans.
Nature, 507, 354–357.
Savage-Rumbaugh, S. (1999). Ape communication: Between a rock and a hard place in origins of
language—What non-human primates can tell us. School of American Research Press.
Schiff, N. D., & Fins, J. J. (2007). Deep brain stimulation and cognition: Moving from animal to
patient. Current Opinion in Neurology, 20, 638–642.
Stedman, H. H., Kozyak, B. W., Nelson, A., Thesier, D. M., Su, L. T., Low, D. W., Bridges, C.
R., Shrager, J. B., MinughPurvis, N., & Mitchell, M. A. (2004). Myosin gene mutation
correlates with anatomical changes in the human lineage. Nature, 428, 415–418.
Tagliatela, J. P., Russell, J. L., Schaeffer, J. A., & Hopkins, W. D. (2011). Chimpanzee vocal
signaling points to a multimodal origin of human language. PLoS One, 6, e18852.
Terkel, J. (1995). Cultural transmission in the black rat: Pinecone feeding. Advances in the Study
of Behavior, 24, 119–154.
Villmoare, B., Kimbel, W. H., Seyoum, C., Campisano, C. J., DiMaggio, E. J., Rowan, J., Braun,
D. R., Arrowsmith, J. R., & Reed, K. E., (2015). Early Homo at 2.8 Ma from Ledi-Geraru,
Afar, Ethiopia. Science, 20, 1352–1355.
Watson, S. K., Townsend, S. W., Schel, A. M., Wilke, C., Wallace, E. K., Cheng, L., West, V., &
Slocombe, K. E. (2015). Vocal learning in the functionally referential food grunts of
chimpanzees. Current Biology, 5, 495–499.
Weiner, J. (1995). The beak of the finch. New York: Vintage.
Workman, A. D., Charvet, C. J., Clancy, B., Darlington, R. B., & Finlay, B. L. (2013). Modeling
transformations of neurodevelopmental sequences across mammalian species. Journal of
Neuroscience, 33, 7368–7380.
Zollikofer, C. P. (2012). Evolution of hominid cranial ontogeny. Progress in Brain Research, 195,
273–292.
CHAPTER 2
Appireddy, R. M. R., Demchuk, A. M., Goyal, M., Menon, B. K., Eesa, M., Choi, P., et al.
(2015). Endovascular therapy for ischemic stroke. Journal of Clinical Neurology, 11, 1–8.
Avetisyan, M., Schill, E. M., & Heuchkeroth, R. O. (2015). Building a second brain in the bowel.
Journal of Clinical Investigation, 125, 899–907.
Barton, R. A. (2012). Embodied cognitive evolution and the cerebellum. Philosophical
Transactions of the Royal Society B, 367, 2097–2107.
Baumann, O., Borra, R. J., Bower, J. M., Cullen, K. E., Habas, C., Ivry, R. B., et al. (2015).
Consensus paper: The role of the cerebellum in perceptual processes. Cerebellum, 14, 197–
220.
Brodmann, K. (1909). Vergleichende Lokalisationlehr der Grosshirnrinde in ihren Prinzipien
dargestellt auf Grund des Zellenbaues. Leipzig: J. A. Barth.
Farmer, A. D., Randall, H. A., & Aziz, Q. (2014). It’s a gut feeling: How the gut microbiota
affects the state of mind. Journal of Physiology, 592(14), 2981–2988.
Fiorito, G., & Scotto, P. (1992). Observational learning in Octopus vulgaris. Science, 256, 545–
547.
Gilbert, S. F., & Epel, D. (2009). Ecological developmental biology: Integrating epigenetics,
medicine, and evolution. New York: Sinauer.
Hatcher, M. A., & Starr, J. A. (2011). Role of tissue plasminogen activator in ischemic stroke.
Annals of Pharmacotherapy, 45, 364–371.
Langhorne, P., Bernhardt, J., & Kwakkel, G. (2011). Stroke rehabilitation. Lancet, 277, 1693–
1702.
Papez, J. W. (1937). A proposed mechanism of emotion. Archives of Neurology and Psychiatry,
38, 724–744.
Schmahmann, J. D. (2010). The role of the cerebellum in cognition and emotion: Personal
reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution
from theory to therapy. Neuropsychology Reviews, 20, 236–260.
CHAPTER 3
Bainbridge, M. N., Wiszniewski, W., Murdock, D. R., Friedman, J., Gonzaga-Jauregui, C., et al.
(2011). Whole-genome sequencing for optimized patient management. Science Translational
Medicine, 3, 87re3.
Balaban, E. (2005). Brain switching: Studying evolutionary behavioral changes in the context of
individual brain development. International Journal of Developmental Biology, 49, 117–124.
Bertram, R., Daou, A., Hyson, R. L., Johnson, F., & Wu, W. (2014). Two neural streams, one
voice: Pathways for theme and variation in the songbird brain. Neuroscience, 26, 806–817.
Butte, P. V., Mamelak, A., Parrish-Novak, J., Drazin, D., Shweikeh, F., Gangalum, P. R., et al.
(2014). Near-infrared imaging of brain tumors using the Tumor Paint BLZ-100 to achieve
near-complete resection of brain tumors. Neurosurgery Focus, 36(2), E1.
Casano, A. M., & Peri, F. (2015). Microglia: Multitasking specialists of the brain. Developmental
Cell, 23, 469–477.
Charney, E. (2012). Behavior genetics and postgenomics. Behavioral Brain Sciences, 35(5), 331–
358.
Chen, J. L., Andermann, M. L., Keck, T., Xu, N. L., & Ziv, Y. (2013). Imaging neuronal
populations in behaving rodents: Paradigms for studying neural circuits underlying behavior
in the mammalian cortex. Journal of Neuroscience, 33, 17631–17640.
Eddy, C. M., & Rickards, H. E. (2015). Theory of mind can be impaired prior to motor onset in
Huntington’s disease. Neuropsychology, 29, 792–798.
Gill, J. M., & Rego, A. C. (2009). The R6 lines of transgenic mice: A model for screening new
therapies for Huntington’s disease. Brain Research Reviews, 59, 410–431.
Giorgi, E. E. (2015, April). From many, one. The Scientist.
Gu, X., Cantle, J. P., Greiner, E. R., Lee, C. Y., Barth, A. M., Gao, F., et al. (2015). N17 modifies
mutant huntingtin nuclear pathogenesis and severity of disease in HD BAC transgenic mice.
Neuron, 85, 726–741.
Guerrero-Bosagna, C., & Jensen, P. (2015). Globalization, climate change, and transgenerational
epigenetic inheritance: Will our descendants be at risk? Clinical Epigenetics, 7, 8.
Herculano-Houzel, S., Manger, P. R., & Kaas, J. H. (2014). Brain scaling in mammalian
evolution as a consequence of concerted and mosaic changes in numbers of neurons and
average neuronal cell size. Frontiers in Neuroanatomy, 8 :77.
Kaati, G., Bygren, L. O., Pembrey, M., & Sjöström, M. (2007). Transgenerational response to
nutrition, early life circumstances and longevity. European Journal of Human Genetics, 15,
784–790.
Kusakari, S., Saitow, F., Ago, Y., Shibasaki, K., Sato-Hashimoto, M., Matsuzaki, Y., et al. (2015).
Shp2 in forebrain neurons regulates synaptic plasticity, locomotion, and memory formation in
mice. Molecular and Cell Biology, MCB, 35, 1557–1572.
Livet, J., Weissman, T. A., Kang, H., Draft, R. W., Lu, J., Bennis, R. A., et al. (2007). Transgenic
strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature,
450, 56–62.
Mimori, T., Nariai, N., Kojima, K., Sato, Y., Kawai, Y., Yamaguchi-Kabata, Y., et al. (2015).
Estimating copy numbers of alleles from population-scale high-throughput sequencing data.
BMC Bioinformatics, 16(Suppl. 1), S4.
Ostrom, Q. T., Gittelman, H., Liao, P., Rouse, C., Chen, Y., Dowling, J., et al. (2014). CBTRUS
statistical report: Primary brain and central nervous system tumors diagnosed in the United
 States in 2007–2011. Neuro-oncology, 16 (Suppl. 4), iv1–iv63.
Persson, M. E., Roth, L. S., Johnsson, M., Wright, D., & Jensen, P. (2015). Humandirected social
behaviour in dogs shows significant heritability. Genes, Brain and Behavior, 14, 337–344.
Ramón y Cajal, S. (1909–1911). Histologie du systeme nerveux de l’homme et des vertebres.
Paris: Maloine.
Reeve, R., van Schaik, A., Jin, C., Hamilton, T., Torben-Neilsen, B., & Webb, B. (2007).
Directional hearing in a silicon cricket. Biosystems, 87, 307–313.
Rojczyk-Gołębiewska, E., Palasz, A., Worthington, J. J., Markowski, G., & Wiaderkie w icz, R.
(2015). Neurolight: Astonishing advances in brain imaging. International Journal of
Neuroscience, 125, 91–99.
Rosenegger, D. G., & Gordon, G. R. (2015). A slow or modulatory role of astrocytes in
neurovascular coupling. Microcirculation, 22, 197–203.
Rusielewicz, T., Nam, J., Damanakis, E., John, G. R., Raine, C. S., & Melendez-Vasquez, C. V.
(2014). Accelerated repair of demyelinated CNS lesions in the absence of non-muscle myosin
IIB. Glia, 62, 580–591.
Wahlsten, D., & Ozaki, H. S. (1994). Defects of the fetal forebrain in acallosal mice. In M.
Lassonde & M. A. Jeeves (Eds.), Callosal agenesis (pp. 125–132). New York: Plenum.
Wang, X., & Guo, Z. (2015). Chlorotoxinconjugated onconase as a potential anti-glioma drug.
Oncology Letters, 9, 1337–1342.
Webb, B. (1996). A cricket robot. Scientific American, 275(6), 94–99.
Wittmeier, S., Alessandro, C., Bascarevic, N., Dalamagkidis, K., Devereux, D., Diamond, A., et
al. (2013). Toward anthropomimetic robotics: Development, simulation, and control of a
musculoskeletal torso. Artificial Life, 19, 171–193.
Wu, H., Wang, Y., Zhang, Y., Yang, M., Lv, J., Liu, J., et al. (2015). TALE nickase-mediated
SP110 knockin endows cattle with increased resistance to tuberculosis. Proceedings of the
National Academy of Sciences United States of America, 112, E1530–E1539.
CHAPTER 4
Allen, M. J., Lacroix, J. J., Ramachandran, S., Capone, R., Whitlock, J. L., et al. (2011). Mutant
SOD1 forms ion channel: Implications for ALS pathophysiology. Neurobiology of Diseases,
45, 831–838.
Bano, S., Yadav, S. N., Chaudhary, V., & Garga, U. C. (2011). Neuroimaging in epilepsy. Journal
of Pediatrics and Neuroscience, 6, 19–26.
Bartholow, R. (1874). Experimental investigation into the functions of the human brain.
American Journal of Medical Sciences, 67, 305–313.
Bender, K. J., & Trussell, L. O. (2012). The physiology of the axon initial segment. Annual
Review of Neuroscience, 35, 249–265.
Bhalla, D., Druet-Cabanac, M., Godet, B., & Preux, P.-M. (2011). Etiologies of epilepsy: A
comprehensive review. Expert Review of Neurotherapeutics, 11, 861–876.
Cao, Z. F., Burdakov, D., & Sarnyai, Z. (2011). Optogenetics: Potentials for addiction research.
Addiction Biology, 16, 519–531.
Crotty, P., Sangrey, T., & Levy, W. B. (2006). Metabolic energy cost of action potential velocity.
Journal of Neurophysiology, 96, 1237–1246.
Debanne, D. (2011). The nodal origin of intrinsic bursting. Neuron, 25, 569–570.
Descartes, R. (1972). Treatise on man (T. S. Hall, Trans.). Cambridge, MA: Harvard University
Press. (Original work published 1664.)
Duncan, J. S., Sander, J. W., Sisodiya, S. M., & Walker, M. C. (2006). Adult epilepsy. Lancet,
367, 1087–1100.
Eccles, J. (1965). The synapse. Scientific American, 21 (1), 56–66.
Fenno, L., Yizhar, O., & Deisseroth, K. (2011). The development and application of optogenetics.
Annual Review of Neuroscience, 34, 389–412.
Hodgkin, A. L., & Huxley, A. F. (1939). Action potentials recorded from inside nerve fiber.
Nature, 144, 710–711.
Legenstein, R., & Maass, W. (2011). Branch-specific plasticity enables self-organization of
nonlinear computation in single neurons. Journal of Neuroscience, 31, 10787–10802.
Liewald, J. F., Brauner, M., Stephens, G. J., Bouhours, M., Schultheis, C., Xhen, M., et al.
(2008). Optogenetic analysis of synaptic function. Nature Methods, 10, 895–902.
Mohajerani, M. H., & Cherubini, E. (2006). Role of giant depolarizing potentials in shaping
synaptic currents in the developing hippocampus. Critical Reviews in Neurobiology, 18, 13–
23.
Rezania, K., Soliven, B., Baron, J., Lin, H., Penumalli, V., & van Besien, K. (2012). Myasthenia
gravis, an autoimmune manifestation of lymphoma and lymphoproliferative disorders: Case
reports and review of literature. Leukemia and Lymphoma, 53, 371–380.
Valdueza, J. M., Doepp, F., Schreiber, S. J., van Oosten, B. W., Schmierer, K., Paul, F., et al.
(2013). What went wrong? The flawed concept of cerebrospinal venous insufficiency. Journal
of Cerebral Blood Flow and Metabolism, 33, 657–668.
Zhang, F., Aravanis, A. M., Adamantidis, A., de Lecea, L., & Deisseroth, K. (2007). Circuit-
breakers: Optical technologies for probing neural signals and systems. Nature Reviews
Neuroscience, 8, 577–581.
CHAPTER 5
Bailey, C. H., Kandel, E. R., & Harris, K. M. (2015). Structural components of synaptic plasticity
and memory consolidation. Cold Spring Harbor Perspectives in Biology. doi:
10.1101/cshperspect.a021758.
Ballard, A., Tetrud, J. W., & Langston, J. W. (1985). Permanent human parkinsonism due to 1-
methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Neurology, 35, 949–956.
Barbeau, A., Murphy, G. F., & Sourkes, T. L. (1962). Les catecholamines dans la maladie de
Parkinson. In J. de Ajuriaguerva (Ed.), Monoamines et système nerveux central. pp. 247–262.
Symposium Bel-Air, Geneva, 1961. Geneva: Georg et Ci.
Birkmayer, W., & Hornykiewicz, O. (1961). Der L-3, 4-Dioxyphenylalanin (L-DOPA) Effekt bei
der Parkinson A Kinase. Wiener Klinische, 73, 787–789.
Bosch, M., & Hayashi, Y. (2012). Structural plasticity of dendritic spines. Current Opinion in
Neurobiology, 22, 383–388.
Dere, E., & Zlomuzica, A. (2012). The role of gap junctions in the brain in health and disease.
Neuroscience and Biobehavioral Reviews, 36, 206–217.
Ehringer, H., & Hornykiewicz, O. (1960/1974). Distribution of noradrenaline and dopamine (3-
hydroxytyramine) in the human brain and their behavior in the presence of disease affecting
the extrapyramidal system. In J. Marks (Ed.), The treatment of Parkinsonism with L- dopa
(pp. 45–56). Lancaster, UK: MTP Medical and Technical Publishing.
Hamilton, T. J., Wheatley, B. M., Sinclair, D. B., Bachmann, M., Larkum, M. E., & Colmers, W.
F. (2010). Dopamine modulates synaptic plasticity in dendrites of rat and human dentate
granule cells. Proceedings of the National Academy of Sciences United States of America, 107
(42): 18185–18190.
Hebb, D. O. (1949). The organization of behavior. New York: Wiley.
Herrmann, N., Chau, S. A., Kircanski, I., & Lanctôt, K. L. (2011). Current and emerging drug
treatment options for Alzheimer’s disease: A systematic review. Drugs, 71, 2031–2065.
Lane, E. L., Björklund, A., Dunnett, S. B., & Winkler, C. (2010). Neural grafting in Parkinson’s
disease unraveling the mechanisms underlying graft-induced dyskinesia. Progress in Brain
Research, 184, 295–309.
Langston, J. W. (2008). The case of the frozen addicts. Pantheon Books, 1995. Original from the
University of Michigan, digitized August 5, 2008.
Magee, J. C., & Cook, E. P. (2000). Somatic EPSP amplitude is independent of synapse location
in hippocampal pyramidal neurons. Nature Neuroscience, 3, 895–903.
Mechoulam, R., Hanus, L. O., Pertwee, R., & Howlett, A. C. (2014). Early phytocannabinoid
chemistry to endocannabinoids and beyond. Nature Neuroscience Reviews 15, 757–764.
Moore, T. J., Glenmullen, J., & Mattison, D. R. (2014). Reports of pathological gambling,
hypersexuality and compulsive shopping associated with dopamine receptor agonist drugs.
JAMA Internal Medicine, 174, 1930–1933.
Parkinson, J. (1817/1989). An essay on the shaking palsy. In A. D. Morris & F. C. Rose (Eds.),
James Parkinson: His life and times (pp. 151–175). Boston: Birkhauser.
Sacks, O. (1976). Awakenings. New York: Doubleday.
Tréatikoff, C. (1974). Thesis for doctorate in medicine, 1919. In J. Marks (Ed.), The treatment of
Parkinsonism with L -dopa (pp. 29–38). Lancaster, UK: MTP Medical and Technical
Publishing.
Ungerstedt, U. (1971). Adipsia and aphagia after 6-hydroxydopamine induced degeneration of
the nigrostriatal dopamine system in the rat brain. Acta Physiologica (Scandinavia), 82
(Suppl. 367), 95–122.
Widner, H., Tetrud, J., Rehngrona, S., Snow, B., Brundin, P., Gustavii, B., et al. (1992). Bilateral
fetal mesencephalic grafting in two patients with Parkinsonism induced by 1-methyl-4-
phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). New England Journal of Medicine, 327, 1556–
1563.
CHAPTER 6
Aagaard, L., & Hansen, E. H. (2011). The occurrence of adverse drug reactions reported for
attention deficit hyperactivity disorder (ADHD) medications in the pediatric population: A
qualitative review of empirical studies. Neuropsychiatric Disorders and Treatments, 7, 729–
744.
Advokat, C. D., Comaty, J. E., & Julien, R. M. (2014). A primer of drug action (13th ed.). New
York: Worth.
Asarnow, J. R., Porta, G., Spirito, A., Emslie, G., Clarke, G., et al. (2011). Suicide attempts and
nonsuicidal self-injury in the treatment of resistant depression in adolescents: Findings from
the TORDIA study. Journal of the American Academy of Child and Adolescent Psychiatry, 50,
772–781.
Barth, C., Villringer, A., & Sacher, J. (2015). Sex hormones affect neurotransmitters and shape
the adult female brain during hormonal transition periods. Frontiers in Neuroscience, 20, 9–
37.
Becker, J. B., Breedlove, S. M., Crews, D., & McCarthy, M. M. (2002). Behavioral
endocrinology (2nd ed.). Cambridge, MA: Bradford.
Becker, J. B., & Hu, M. (2008). Sex differences in drug abuse. Frontiers in Neuroendocrinology,
29 (1), 36–47.
Berninger, J. P., LaLone, C. A., Villeneuve, D. L., & Ankley, G. T. (2015). Prioritization of
pharmaceuticals for potential environmental hazard through leveraging a large scale
mammalian pharmacological dataset. Environment and Toxicological Chemistry. doi:
10.1002/etc.2965. [Epub ahead of print.]
Bourgin, J., Cachia, A., Boumezbeur, F., Djemaï, B., Bottlaender, M., Duchesnay, E., et al. (2015,
March 11). Hyper-responsivity to stress in rats is associated with a large increase in amygdala
volume: A 7T MRI study. European Journal of Neuropsy-chopharmacology. [Epub ahead of
print.]
Brown, A. R., Owen, S. F., Peters, J., Zhang, Y., Soffker, M., Paull, G.C., et al. (2015). Climate
change and pollution speed declines in zebrafish populations. Proceedings of the National
Academy of Science United States of America, 112, 1237–1246.
Büttner, A. (2011). Review: The neuro-pathology of drug abuse. Neuropathology and Applied
Neurobiology, 37, 118–134.
Clauss, J. A., Avery, S. N., & Blackford, J. U. (2015, March 14). The nature of individual
differences in inhibited temperament and risk for psychiatric disease: A review and meta-
analysis. Progress in Neurobiology, 127–128, 23–45.
Comer, R. J. (2011). Fundamentals of abnormal psychology (7th ed.). New York: Worth.
Cowan, R. L., Roberts, D. M., & Joers, J. M. (2008). Neuroimaging in human MDMA (Ecstasy)
users. Annals of the New York Academy of Sciences, 1139, 291–298.
Czoli, C. D., Hammond, D., Reid, J. L., Cole. A. G., & Leatherdale. S. T. (2015). Use of
conventional and alternative tobacco and nicotine products among a sample of Canadian
youth. Journal of Adolescent Health, 57, 123–125. [Epub ahead of print.]
Di Forti, M., Sallis, H., Allegri, F., Trotta, A., Ferraro, L., Stilo, S. A., et al. (2014). Daily use,
especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.
Schizophrenia Bulletin, 40, 1509–1517.
Durell, T. M., Kroutil, L. A., Crits-Christoph, P., Barchha, N., & Van Brunt, D. E. (2008).
Prevalence of nonmedical methamphetamine use in the United States. Substance Abuse
Treatment, Prevention, and Policy, 3, 19.
Everitt, B. J. (2014). Neural and psychological mechanisms underlying compulsive drug seeking
habits and drug memories: Indications for novel treatments of addiction. European Journal of
Neuroscience, 40, 2163–2182.
Fraioli, S., Crombag, H. S., Badiani, A., & Robinson, T. E. (1999). Susceptibility to
amphetamine-induced locomotor sensitization is modulated by environmental stimuli.
Neuropsychopharmacology, 20, 533–541.
Freud, S. (1974). Cocaine papers (R. Byck, Ed.). New York: Penguin.
Grande, I., & Vieta, E. (2015). Pharmacotherapy of acute mania: Monotherapy or combination
therapy with mood stabilizers and antipsychotics? CNS Drugs, 29, 221–227.
Greely, H., Sahakian, B., Harris, J., Kessler, R. C., Gazzaniga, M., et al. (2008). Towards
responsible use of cognitive-enhancing drugs by the healthy. Nature, 456, 702–705.
Griffin, J. A., Umstattd, M. R., & Usdan, S. L. (2010). Alcohol use and high-risk sexual behavior
among collegiate women: A review of research on alcohol myopia theory. Journal of
American College Health, 58, 523–532.
Hampson, E., & Kimura, D. (2005). Sex differences and hormonal influences on cognitive
function in humans. In J. B. Becker, S. M. Breedlove, & D. Crews (Eds.), Behavioral
endocrinology (pp. 357–398). Cambridge, MA: MIT Press.
Hardee, J. E., Weiland, B. J., Nichols, T. E., Welsh, R. C., Soules, M. E., Steinberg, D. B., et al.
(2014). Development of impulse control circuitry in children of alcoholics. Biological
Psychiatry, 76, 708–716.
Hill, A. S., Sahay, A., & Hen, R. (2015, April 2). Increasing adult hippocampal neurogenesis is
sufficient to reduce anxiety and depression-like behaviors. Neuropsychopharmacology, 40,
2368–2378.
Hillemacher, T., Weinland, C., Lenz, B., Kraus, T., Heberlein, A., Glahn, A., et al. (2015). DNA
methylation of the LEP gene is associated with craving during alcohol withdrawal.
Psychoneuroendocrinology, 51, 371–377.
Isacsson, G., & Rich C. L. (2014). Antidepressant drugs and the risk of suicide in children and
adolescents. Paediatric Drugs, 16, 115–122.
Isbell, H., Fraser, H. F., Wikler, R. E., Belleville, R. E., & Eisenman, A. J. (1955). An
experimental study of the etiology of “rum fits” and delirium tremens. Quarterly Journal of
Studies on Alcohol, 16, 1–35.
Kerr, D. C., Zava, D. T., Piper, W. T., Saturn, S. R., Frei, B., & Gombart, A. F. (2015).
Associations between vitamin D levels and depressive symptoms in healthy young adult
women. Psychiatry Research, 227, 46–51.
Lajud, N., & Torner, L. (2015). Early life stress and hippocampal neurogenesis in the neonate:
Sexual dimorphism, long-term consequences and possible mediators. Frontiers in Molecular
Neuroscience, 8, 3. doi: 10.3389/fnmol.2015.00003. eCollection 2015.
Landré, L., Destrieux, C., Baudry, M., Barantin, L., Cottier, J. P., et al. (2010). Preserved
subcortical volumes and cortical thickness in women with sexual abuse-related PTSD.
Psychiatry Research, 183, 181–186.
Lee, B. Y., Park, S. Y., Ryu, H. M., Shin, C. Y., Ko, K. N., Han, J. Y., et al. (2015). Changes in
the methylation status of DAT, SERT, and MeCP2 gene promoters in the blood cell in families
exposed to alcohol during the periconceptional period. Alcohol and Clinical and Experimental
Research, 39, 239–250.
Liu, P., Lu, H., Filbey, F. M., Tamminga, C. A., Cao, Y., & Adinoff, B. (2014). MRI assessment
of cerebral oxygen metabolism in cocaine-addicted individuals: Hypoactivity and dose
dependence. NMR Biomedicine, 27, 726–732.
Lubman, D. I., Cheetham, A., & Yücel, M. (2015). Cannabis and adolescent brain development.
Pharmacology and Therapeutics, 148C, 1–16.
MacAndrew, C., & Edgerton, R. B. (1969). Drunken comportment: A social explanation.
Chicago: Aldine.
MacDonald, T. K., MacDonald, G., Zanna, M. P., & Fong, G. T. (2000). Alcohol, sexual arousal,
and intentions to use condoms in young men: Applying alcohol myopia theory to risky sexual
behavior. Health Psychology, 19, 290–298.
McCann, U. D., Lowe, K. A., & Ricaurte, G. A. (1997). Long-lasting effects of recreational
drugs of abuse on the central nervous system. The Neurologist, 3, 399–411.
McGowan, P. O., Sasaki, A., D’Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., et al. (2009).
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood
abuse. Nature Neurosciences, 12, 342–348.
Mead, E. A., & Sarkar, D. K. (2014). Fetal alcohol spectrum disorders and their transmission
through genetic and epigenetic mechanisms. Frontiers in Genetics, 5, 154–159.
Nguyen, B. M., Kim, D., Bricker, S., Bongard, F., Neville, A., Putnam, B., et al. (2014). Effect of
marijuana use on outcomes in traumatic brain injury. American Surgery, 80, 979–983.
Nugent, B. M., Tobet, S. A., Lara, H. E., Lucion, A. B., Wilson, M. E., Recabarren, S. E., et al.
(2012). Hormonal programming across the lifespan. Hormone and Metabolic Research, 44,
577–586.
Nugent, B. M., Wright, C. L., Shetty, A. C., Hodes, G. E., Lenz, K. M., Mahurkar, A., et al.
(2015). Brain feminization requires active repression of masculinization via DNA
methylation. Nature Neuroscience, 18 (5), 690–697.
Popova, S., Lange, S., Bekmuradov, D., Mihic, A., & Rehm, J. (2011). Fetal alcohol spectrum
disorder prevalence estimates in correctional systems: A systematic literature review.
Canadian Journal of Public Health, 102, 336–340.
Pouget, J. G., Shams, T. A., Tiwari, A. K., & Müller, D. J. (2014). Pharmacogenetics and
outcome with antipsychotic drugs. Dialogues in Clinical Neuroscience, 16, 555–566.
Reinstatler, L., & Youssef, N. A. (2015). Ketamine as a potential treatment for suicidal ideation:
A systematic review of the literature. Drugs, 15, 37–43.
Roberts, N. P., Roberts, P. A., Jones, N., & Bisson, J. I. (2015). Psychological interventions for
post-traumatic stress disorder and comorbid substance use disorder: A systematic review and
meta-analysis. Clinical Psychological Reviews, 38, 25–38.
Robinson, T. E., & Becker, J. B. (1986). Enduring changes in brain and behavior produced by
chronic amphetamine administration: A review and evaluation of animal models of
amphetamine psychosis. Brain Research Reviews, 11, 157–198.
Robinson, T. E., & Berridge, K. C. (2008). Incentive sensitization theory. Philosophical
Transactions of the Royal Society of London, 363, 3137–3146.
Roitman, P., Mechoulam, R., Cooper-Kazaz, R., & Shalev, A. (2014). Preliminary, open-label,
pilot study of add-on oral Δ9-tetrahydrocannabinol in chronic post-traumatic stress disorder.
Clinical Drug Investigations, 34, 587–591.
Sapolsky, R. M. (2004). Why zebras don’t get ulcers (3rd ed.). New York: Henry Holt.
Sapolsky, R. M. (2005). The influence of social hierarchy on primate health. Science, 308 (5722),
648–652.
Sevincer, A. T., & Oettingen, G. (2014). Alcohol myopia and goal commitment. Frontiers in
Psychology, 4, 169–175.
Smith, A. D., Smith, S. M., de Jager, C. A., Whitbread, P., Johnston, C., et al. (2010).
Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild
cognitive impairment: A randomized controlled trial. PLoS One, 8, e12244.
Steen, E., Terry, B. M., Rivera, E. J., Cannon, J. L., Neely, T. R., Tavares, R., et al. (2005).
Impaired insulin and insulin-like growth factor expression and signaling mechanisms in
Alzheimer’s disease: Is this type 3 diabetes? Journal of Alzheimer’s Disease, 7, 63–80.
Teixeira-Gomes, A., Costa, V. M., Feio-Azevedo, R., Bastos, M. L., Carvalho, F., & Capela, J. P.
(2015). The neurotoxicity of amphetamines during the adolescent period. International
Journal of Developmental Neuroscience, 41, 44–62.
Vevelstad, M., Oiestad, E. L., Middelkoop, G., Hasvold, I., Lilleng, P., et al. (2012). The PMMA
epidemic in Norway: Comparison of fatal and non-fatal intoxications. Forensic Science
International, 219, 151–157.
Wenger, J. R., Tiffany, T. M., Bombardier, C., Nicholls, K., & Woods, S. C. (1981). Ethanol
tolerance in the rat is learned. Science, 213, 575–577.
Whishaw, I. Q., Mittleman, G., & Evenden, J. L. (1989). Training-dependent decay in
performance produced by the neuroleptic cis (Z)-flupentixol on spatial navigation by rats in a
swimming pool. Pharmacology, Biochemistry, and Behavior, 32, 211–220.
Wilkinson, S. T., Radhakrishnan R., & D’Souza, D. C. (2014). Impact of cannabis use on the
development of psychotic disorders. Current Addiction Reports, 1 (2), 115–128.
Yager, L. M., Pitchers, K. K., Flagel, S. B., & Robinson, T. E. (2015). Individual variation in the
motivational and neurobiological effects of an opioid cue. Neuropsychopharmacology, 40,
1269–1277.
CHAPTER 7
Brown, A. R., Antle, M. C., Hu, B., & Teskey, G. C. (2011). High frequency stimulation of the
subthalamic nucleus acutely rescues neocortical movement representations and motor deficits
following 6-hydroxydopamine administration in rats. Experimental Neurology, 231, 82–90.
Bueller, J. A., Aftab, M., Sen, S., Gomez-Hassan, D. Burmeister, M., & Zubieta, J.-K. (2006).
BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects.
Biological Psychiatry, 59, 812–815.
Cacucci, F., Yi, M., Wills, T. J., Chapmans, P., & O’Keefe, J. (2008). Place cell firing correlates
with memory deficits and amyloid plaque burden in Tg2576 Alzheimer mouse model.
Proceedings of the National Academy of Sciences United States of America, 105, 7863–7868.
Caspi, A., Moffitt, T. E., Cannon, M., McClay, J., Murray, R., et al. (2005). Moderation of the
effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in
the catechol-O-methyltransferase gene: Longitudinal evidence of a gene X environment
interaction. Biological Psychiatry, 57, 1117–1127.
Damasio, H., & Damasio, A. R. (1989). Lesion analysis in neuropsychology. New York: Oxford
University Press.
Fox, P. T., & Raichle, M. E. (1986). Focal physiological uncoupling of cerebral blood flow and
oxidative metabolism during somatosensory stimulation in human subjects. Proceedings of
the National Academy of Sciences United States of America, 83, 1140–1144.
Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., et al. (2005).
Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the
National Academy of Sciences United States of America, 102, 10604–10609.
Gonzalez, C. L. R., Gharbawie, O. A., & Kolb, B. (2006). Chronic low-dose administration of
nicotine facilitates recovery and synaptic change after focal ischemia in rats.
Neuropharmacology, 50, 777–787.
Haubensak, W., Kunwar, P. S., Cai, H., Ciocchi, S., Wall, N. R., Ponnusamy, R., et al. (2010).
Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature, 468, 270–
276.
Kolb, B., & Walkey, J. (1987). Behavioural and anatomical studies of the posterior parietal cortex
of the rat. Behavioural Brain Research, 23, 127–145.
Kut, C., Chaichana, K. L., Xi, J., Raza, S. M., Ye, X., McVeigh, E. R., et al. (2015). Detection of
human brain cancer infiltration ex vivo and in vivo using quantitative optical coherence
tomography. S cience Translational Medicine 17, 292ra100. doi:
10.1126/scitranslmed.3010611.
Kwong, K. K., Belliveau, J. W., Chesler, D. A., Goldberg, I. E., Weisskoff, R. M., Poncelet, B. P.,
et al. (1992). Dynamic magnetic resonance imaging of human brain activity during primary
sensory stimulation. Proceedings of the National Academy of Sciences United States of
America, 89, 5678.
Lecendreux, M., Konofal, E., Cortese, S., & Faraone, S. V. (2015). A 4-year follow-up of
attention-deficit/hyperactivity disorder in a population sample. Journal of Clinical Psychiatry,
76, 712–719.
Lomber, S. G., & Payne, B. R. (1996). Removal of two halves restores the whole: Reversal of
visual hemineglect during bilateral cortical or collicular inactivation in the cat. Visual
Neuroscience, 13, 1143–1156.
May, L., Byers-Heinlein, K., Gervain, J., & Werker, J. F. (2011). Language and the newborn
brain: Does prenatal language experience shape the neonate neural response to speech?
 Frontiers in Psychology, 2, 1–9.
McGowan, P. O., Sasaki, A., D’Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., et al. (2009).
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood
abuse. Nature Neuroscience, 12, 342–348.
Morris, R. G. M. (1981) Spatial localization does not require the presence of local cues. Learning
and Motivation, 12, 239–260.
Mychasiuk, R., Schmold, N., Ilnytskyy, S., Kovalchuk, O., Kolb, B., & Gibb, R. (2011). Prenatal
bystander stress alters brain, behavior, and the epigenome of developing rat offspring.
Developmental Neuroscience, 33, 159–169.
National Research Council (1996). The guide for the care and use of laboratory animals.
Washington, DC: National Academy Press.
Ogawa, S., Lee, T. M., Kay, A. R., & Tank, D. W. (1990). Brain magnetic resonance imaging
with contrast dependent on blood oxygenation. Proceedings of the National Academy of
Sciences United States of America, 87, 9868–9872.
O’Keefe, J. (2006). Hippocampal neurophysiology in the behaving animal. In P. Andersen, R.
Morris, D. Amaral, T. Bliss, & J. O’Keefe (Eds.), The Hippocampus Book. (pp. 475–548).
New York: Oxford University Press.
O’Keefe, J., & Dostrovsky, J. (1971). The hippocampus as a spatial map. Brain Research, 34,
171–175.
Penfield, W., & Jasper, H. H. (1954). Epilepsy and the functional anatomy of the human brain.
Boston: Little, Brown.
Posner, M. I., & Raichle, M. E. (1997). Images of mind. New York: W. H. Freeman.
Reza, M. F., Ikoma, K., Ito, T., Ogawa, T., & Mano, Y. (2007). N200 latency and P300 amplitude
in depressed mood post-traumatic brain injury patients. Neuropsychological Rehabilitation,
17, 723–734.
Schallert, T., Whishaw, I. Q., Ramirez, V. D., & Teitelbaum, P. (1978). Compulsive, abnormal
walking caused by anticholinergics in akinetic, 6-hydroxydopamine-treated rats. Science, 199,
1461–1463.
Schlaepfer, T. E., Bewernick, B. H., Kayser, S., Mädler, B., & Coenen, V. A. (2013). Rapid
effects of deep brain stimulation for treatment-resistant major depression. Biological
Psychiatry, 73 (12), 1204–1212.
Scoville, W. B., & Milner, B. (1957). Loss of recent memory after bilateral hippocampal lesions.
Journal of Neurology, Neurosurgery, and Psychiatry, 20, 11–21.
Spinney, L. (2005). Optical topography and the color of blood. The Scientist, 19, 25–27.
Szyf, M., McGowan, P., & Meaney, M. J. (2008). The social environment and the epigenome.
Environmental Molecular Mutagenetics, 49, 46–60.
Tisdall, M. M., & Smith, M. (2006). Cerebral microdialysis: Research technique or clinical tool.
British Journal of Anaesthesia, 97, 18–25.
Van den Heuvel, M. P., & Hulshoff Pol, H. E. (2010). Exploring the brain network: A review on
resting-state fMRI functional connectivity. European Neuropsychopharmcology, 20, 519–534.
Wess, J., Nakajima, K., Jain, S. (2013). Novel designer receptors to probe GPCR signaling and
physiology. Trends in Pharmacological Sciences, 34, 385–392.
Whishaw, I. Q. (1989). Dissociating performance and learning deficits in spatial navigation tasks
in rats subjected to cholinergic muscarinic blockade. Brain Research Bulletin, 23, 347–358.
Whishaw, I. Q., & Kolb, B. (2005). The behavior of the laboratory rat. New York: Oxford
University Press.
CHAPTER 8
Agate, R. J., Grisham, W., Wade, J., Mann, S., Wingfield, J., Schanen, C., et al. (2003). Neural,
but not gonadal, origin of brain sex differences in a gynandromorphic finch. Proceedings of
the National Academy of Sciences United States of America, 100, 4873–4878.
Ames, E. W. (1997). The development of Romanian orphanage children adopted to Canada. Final
report to Human Resources Development, Canada.
Anda, R. F., Felitti, V. J., Bremner, J. D., Walker, J. D., Whitfield, C., et al. (2006). The enduring
effects of abuse and related adverse experiences in childhood: A convergence of evidence
from neurobiology and epidemiology. European Archives of Psychiatry and Clinical
Neuroscience, 256, 174–186.
Berens, A. E., & Nelson, C. A. (2015). The science of early adversity: Is there a role for large
institutions in the care of vulnerable children? Lancet, S0140-6736(14), 61131–61134.
Blumberg, S. J., Bramlett, M. D., Kogan, M. D., Schieve, L. A., Jones, J. R., et al. (2013).
Changes in prevalence of parent-reported autism spectrum disorder in school-aged US
children: 2007 to 2011–2012. National Health Statistics Reports, 65, 1–11.
Bock, J., Rether, K., Grogerr, N., Xie, L., & Braun, K. (2014). Perinatal programming of
emotional brain circuits: An integrative view from systems to molecules. Frontiers of
Neuroscience, 11, 1–15. doi: 10. 3389/fnins. 2014. 00011.
Bourgeois, J.-P. (2001). Synaptogenesis in the neocortex of the newborn: The ultimate frontier
for individuation? In C. A. Nelson & M. Luciana (Eds.), Handbook of Developmental
Cognitive Neuroscience. Cambridge, MA: MIT Press.
Bunney, B. G., Potkin, S. G., & Bunney, W. E. (1997). Neuropathological studies of brain tissue
in schizophrenia. Journal of Psychiatric Research, 31, 159–173.
Changeux, J.-P., & Danchin, A. (1976). Selective stabilization of developing synapses as a
mechanism for the specification of neuronal networks. Nature, 264, 705–712.
Chen, R., Jiao, Y., & Herskovits, E. H. (2011). Structural MRI in autism spectrum disorder.
Pediatric Research, 69, 63R–68R.
Clarke, R. S., Heron, W., Fetherstonhaugh, M. L., Forgays, D. G., & Hebb, D. O. (1951).
Individual differences in dogs: Preliminary report on the effects of early experience. Canadian
Journal of Psychology, 5 (4), 150–156.
Cowan, W. M. (1979). The development of the brain. Scientific American, 241 (3), 116.
Epstein, H. T. (1979). Correlated brain and intelligence development in humans. In M. E. Hahn,
C. Jensen, & B. C. Dudek (Eds.), Development and evolution of brain size: Behavioral
implications (pp. 111–131). New York: Academic Press.
Finegold, S. M., Molitoris, D., Song, Y., Liu, C., Vaisanen, M. L., Bolte, E., et al. (2002).
Gastrointestinal microflora studies in late-onset autism. Clinical Infective Diseases, 35, S6–
S16.
Gershon, E. S., & Rieder, R. O. (1992). Major disorders of mind and brain. Scientific American,
267 (3), 126–133.
Geschwind, D. H., & Rakic, P. (2013). Cortical evolution: Judge the brain by its cover. Neuron,
80, 633–647.
Gibb, R., Gonzalez, C., & Kolb, B. (2014). Prenatal enrichment and recovery from perinatal
cortical damage: Effects of maternal complex housing. Frontiers in Behavioral Neuroscience,
8, 223. doi: 10.3389/fnbeh.2014.00223.
Giussani, C., Roux, F. E., Lubrano, V., Gaini, S. M., & Bello, L. (2007). Review of language
organization in bilingual patients: What can we learn from direct brain mapping? Acta
Neurochir (Wien), 149, 1109–1116.
Goldstein, J. M., Seidman, L. J., Horton, N. J., Makris, N., Kennedy, D. N., Caviness, V. S., Jr., et
al. (2001). Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic
resonance imaging. Cerebral Cortex, 11, 490–497.
Guerrini, R., Dobyns, W. B., & Barkovich, A. J. (2007). Abnormal development of the human
cerebral cortex: Genetics, functional consequences and treatment options. Trends in
Neurosciences, 31, 154–162.
Halliwell, C., Comeau, W., Gibb, R., Frost, D. O., & Kolb, B. (2009). Factors influencing frontal
cortex development and recovery from early frontal injury. Developmental
Neurorehabilitation, 12, 269–278.
Harker, A., Raza, S., Williamson, K., Kolb, B., & Gibb, R. (2015). Preconception paternal stress
in rats alters dendritic morphology and connectivity in the brain of developing male and
female offspring. Neuroscience, 303, 200–210.
Harlow, H. F. (1971). Learning to love. San Francisco: Albion.
Hebb, D. O. (1947). The effects of early experience on problem solving at maturity. American
Psychologist, 2, 737–745.
Horn, G., Bradley, P., & McCabe, B. J. (1985). Changes in the structure of synapses associated
with learning. Journal of Neuroscience, 5, 3161–3168.
Hsiao E. Y., McBride, S. W., Hsien, S., Sharon, G., Hyde, E. R., McCue, T., et al. (2013).
Microbiota modulate behavioral and physiological abnormalities associated with
neurodevelopmental disorders. Cell, 155, 1451–1463.
Huttenlocher, P. R. (1994). Synaptogenesis in human cerebral cortex. In G. Dawson & K. W.
Fischer (Eds.), Human behavior and the developing brain (pp. 137–152). New York: Guilford
Press.
Juraska, J. M. (1990). The structure of the cerebral cortex: Effects of gender and the environment.
In B. Kolb & R. Tees (Eds.), The cerebral cortex of the rat (pp. 483–506). Cambridge, MA:
MIT Press.
Kinney, H. C. (2009). Brainstem mechanisms underlying the sudden infant death syndrome:
Evidence from human pathologic studies. Developmental Psychobiology, 51, 223–233.
Klein, D., Watkins, K. E., Zatorre, R. J., & Milner, B. (2006). Word and nonword repetition in
bilingual subjects: A PET study. Human Brain Mapping, 27, 153–161.
Kolb, B., & Gibb, R. (1993). Possible anatomical basis of recovery of function after neonatal
frontal lesions in rats. Behavioral Neuroscience, 107, 799–811.
Kolb, B., Mychasiuk, R., Muhammad, A., Li, Y., Frost, D. O., & Gibb, R. (2012). Experience and
the developing prefrontal cortex. Proceedings of the National Academy of Sciences United
States of America.
Kovelman, J. A., & Scheibel, A. B. (1984). A neurohistologic correlate of schizophrenia.
Biological Psychiatry, 19, 1601–1621.
Kuhl, P. K. (2011). Early language learning and literacy: Neuroscience implications for
education. Mind, Brain and Education, 5, 128–142.
Lenneberg, E. H. (1967). Biological foundations of language. New York: Wiley.
Lenroot, R. K., Gogtay, N., Greenstein, D. K., Wells, E. M., Wallace, G. L., Clasen, L. S., et al.
(2007). Sexual dimorphism of brain development trajectories during childhood and
adolescence. NeuroImage, 36, 1065–1073.
Levitin, D. J., & Rogers, S. E. (2005). Absolute pitch: Perception, coding, and controversies.
Trends in Cognitive Science, 9, 26–33.
Lorenz, K. (1970). Studies on animal and human behavior (Vols. 1 and 2). Cambridge, MA:
Harvard University Press.
Lu, L. H., Leonard, C. M., Thompson, P. M., Kan, E., Jolley, J., Welcome, S. E., et al. (2007).
Normal developmental changes in inferior frontal gray matter are associated with
improvement in phonological processing: A longitudinal MRI analysis. Cerebral Cortex, 17,
1092–1099.
Malanga, C. J., & Kosofsky, B. E. (2003). Does drug abuse beget drug abuse? Behavioral
analysis of addiction liability in animal models of prenatal drug exposure. Developmental
Brain Research, 147, 47–57.
Marin-Padilla, M. (1993). Pathogenesis of late-acquired leptomeningeal heterotopias and
secondary cortical alterations: A Golgi study. In A. M. Galaburda (Ed.), Dyslexia and
development: Neurobiological aspects of extraordinary brains (pp. 64–88). Cambridge, MA:
Harvard University Press.
Minnes, S., Singer, L. T., Min, M. O., Wu, M., Lang, A., & Yoon, S. (2014). Effects of prenatal
cocaine/polydrug exposure on substance abuse by age 15. Drug and Alcohol Dependence,
134, 201–210.
Moore, K. L. (1988). The developing human: Clinically oriented embryology (4th ed.).
Philadelphia: Saunders.
Mychasiuk, R., Gibb, R., & Kolb, B. (2011). Prenatal stress produces sexually dimorphic and
regionally specific changes in gene expression in hippocampus and frontal cortex of
developing rat offspring. Developmental Neuroscience, 33, 531–538.
Mychasiuk, R., Muhammad, A., & Kolb, B. (2014). Environmental enrichment alters structural
plasticity of the adolescent brain but does not remediate the effects of prenatal nicotine
exposure. Synapse, 68, 293–305.
National Institute on Drug Abuse (2012). http://www.drugabuse.gov/publications/research-
reports/tobacco/smoking-pregnancy—what-are-risks
Nelson, C. A., & Luciana, M. (Eds.) (2008). Handbook of developmental cognitive neuroscience,
2nd ed. Cambridge, MA: MIT Press.
Nelson, C. A., Zeanah, C. H., Fox, N. A., Marshall, P. J., Smyke, A. T., & Guthrie, D. (2007).
Cognitive recovery in socially deprived young children: The Bucharest Early Intervention
Project. Science, 318, 1937–1940.
Noble, K. G., Houston, S. M., Brito, N. H., Bartsch, H., Kan, E., Kuperman, J. M., et al. (2015).
Family income, parental education and brain structure in children and adolescents. Nature
Neuroscience, 18, 773–778.
Nordahl, C. W., Scholz, R., Yang, X., Buonocore, M. H., Simon, T., Rogers S., et al. (2012).
Increased rate of amygdala growth in children aged 2 to 4 years with autism spectrum
disorders: A longitudinal study. Archives of General Psychiatry, 69, 53–61.
Nyagu, A. I., Loganovsky, K. N., & Loganovskaja, T. K. (1998). Psychophysiological aftereffects
of prenatal irradiation. International Journal of Psychophysiology, 30, 303–311.
O’Hare, E. D., & Sowell, E. R. (2008). Imaging developmental changes in gray and white matter
in the human brain. In C. A. Nelson and M. Luciana (Eds.), Handbook of developmental
cognitive neuroscience (pp. 23–38), Cambridge, MA: MIT Press.
Overman, W., Bachevalier, J., Schuhmann, E., & Ryan, P. (1996). Cognitive gender differences in
very young children parallel biologically based cognitive gender differences in monkeys.
Behavioral Neuroscience, 110, 673–684.
Overman, W., Bachevalier, J., Turner, M., & Peuster, A. (1992). Object recognition versus object
discrimination: Comparison between human infants and infant monkeys. Behavioral
Neuroscience, 106, 15–29.
Paterson, D. S., Trachtenberg, F. L., Thompson, E. G., Belliveau, R. A., Beggs, A. H., Dranall, et
al. (2006). Multiple serotonergic brainstem abnormalities in sudden infant death syndrome.
Journal of the American Medical Association, 296, 2124–2132.
Paus, T., Keshavan, M., & Giedd, J. N. (2008). Why do so many psychiatric disorders emerge
during adolescence? Nature Reviews Neuroscience, 9, 947–957.
Payne, B. R., & Lomber, S. G. (2001). Reconstructing functional systems after lesions of cerebral
cortex. Nature Reviews Neuroscience, 2, 911–919.
Petanjek, Z., Judas, M., Simic, G., Rasin, M. R., Uylings, H. B. M., et al. (2011). Extraordinary
neoteny of synaptic spines in the human prefrontal cortex. Proceedings of the National
Academy of Sciences U S A, 108, 13281–13286.
Piaget, J. (1952). The origins of intelligence in children. New York: Norton.
Purpura, D. P. (1974). Dendritic spine “dysgenesis” and mental retardation. Science, 186, 1126–
1127.
Raizada, R. D. S., Richards, T. L., Meltzoff, A., & Kuhl, P. K. (2008). Socioeconomic status
predicts hemispheric specialization of the left inferior frontal gyrus in young children.
NeuroImage, 40, 1392–1401.
Rakic, P. (1974). Neurons in rhesus monkey cerebral cortex: Systematic relation between time of
origin and eventual disposition. Science, 183, 425.
Raza, S., Harker, A., Richards, S., Kolb, B., & Gibb, R. (2015). Tactile stimulation improves
neuroanatomical pathology but not behaviour in rats prenatally exposed to valproic acid.
Behavioural Brain Research, 282, 25–36.
Riesen, A. H. (1982). Effects of environments on development in sensory systems. In W. D. Neff
(Ed.), Contributions to sensory physiology (Vol. 6, pp. 45–77). New York: Academic Press.
Rutter, M. (1998). Developmental catch-up, and deficit, following adoption after severe global
early privation. Journal of Child Psychology and Psychiatry, 39, 465–476.
Salm, A. K., Pavelko, M., Drouse, E. M., Webster, W., Kraszpulski, M., & Birkle, D. L. (2004).
Lateral amygdala nucleus expansion in adult rats is associated with exposure to prenatal
stress. Developmental Brain Research, 148, 159–167.
Schnack, H. G., van Haren, N. E., Brouwer, R. M., Evans, A., Durston, S., Boomsma, D. I., et al.
(2014). Changes in thickness and surface area of the human cortex and their relationship with
intelligence. Cerebral Cortex, 25, 1608–1617.
Shaw, P., Greenstein, D., Lerch, J., Clasen, L., Lenroot, R., et al. (2006). Intellectual ability and
cortical development in children and adolescents. Nature, 440, 666–679.
Shingo, T., Gregg, C., Enwere, E., Fujikawa, H., Hassam, R., Greary, C., et al. (2003).
Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin.
Science, 299, 117–120.
Smyke, A. T., Zeanah, C. H., Gleason, M. M., Drury, S. S., Fox, N. A., et al. (2012). A
randomized controlled trial comparing foster care and institutional care for children with signs
of reactive attachment disorder. American Journal of Psychiatry, 169, 508–514.
Sodhi, M. S., & Sanders-Bush, E. (2004). Serotonin and brain development. International Review
of Neurobiology, 59, 111–174.
Sowell, E. R., Thompson, P. M., Leonard, C. M., Welcome, S. E., Kan, E., & Toga, A. W. (2004).
Longitudinal mapping of cortical thickness and brain growth in normal children. Journal of
 Neuroscience, 24, 8223–8231.
Sowell, E. R., Thompson, P. M., & Toga, A. W. (2004). Mapping changes in the human cortex
throughout the span of life. The Neuroscientist, 10, 372–392.
Sperry, R. W. (1963). Chemoaffinity in the orderly growth of nerve fiber patterns and
connections. Proceedings of the National Academy of Sciences United States of America, 50,
703–710.
Suomi, S. J. (2011). Risk, resilience, and gene-environment interplay in primates. Journal of the
Canadian Academy of Child and Adolescent Psychiatry, 20, 289–297.
Twitchell, T. E. (1965). The automatic grasping response of infants. Neuropsychologia, 3, 247–
259.
Wallace, P. S., & Whishaw, I. Q. (2003). Independent digit movements and precision grip
patterns in 1–5-month-old human infants: Hand-babbling, including vacuous then self-
directed hand and digit movements, precedes targeted reaching. Neuropsychologia, 41, 1912–
1918.
Weiss, S., Reynolds, B. A., Vescovi, A. L., Morshead, C., Craig, C. G., & van der Kooy, D.
(1996). Is there a neural stem cell in the mammalian forebrain? Trends in Neurosciences, 19
(9), 387–393.
Werker, J. F., & Tees, R. C. (1992). The organization and reorganization of human speech
perception. Annual Review of Neuroscience, 15, 377–402.
Yakovlev, P. E., & Lecours, A.-R. (1967). The myelogenetic cycles of regional maturation of the
brain. In A. Minkowski (Ed.), Regional development of the brain in early life. Oxford:
Blackwell.
CHAPTER 9
Bálint, R. (1909). Seelenlähmung des “Schauens,” optische Ataxie, räumliche Störung der
Aufmerksamkeit. Monatschrift für Psychiatrie und Neurologie, 25, 51–81.
Farah, M. J. (1990). Visual agnosia. Cambridge, MA: MIT Press.
Geschwind, N. (1972). Language and the brain. Scientific American, 226 (4), 78–83.
Goodale, M. A., Milner, D. A., Jakobson, L. S., & Carey, J. D. P. (1991). A kinematic analysis of
reaching and grasping movements in a patient recovering from optic ataxia. Nature, 349, 154–
156.
Hamilton, R. H., Shenton, J. T., & Coslett, H. B. (2006). An acquired deficit of audiovisual
speech processing. Brain and Language, 98, 66–73.
Hasson, U., Nir, Y., Levy, I., Fuhrmann, G., & Malach, R. (2004). Intersubject synchronization of
cortical activity during natural vision. Science, 303, 1634–1640.
Held, R. (1968). Dissociation of visual function by deprivation and rearrangement.
Psychologische Forschung, 31, 338–348.
Hubel, D. H., & Weisel, T. N. (1977). Functional architecture of macaque monkey visual cortex.
Proceedings of the Royal Society of London B, 198, Figure 23.
Jerison, H. J. (1973). The evolution of the brain and intelligence. New York: Academic Press.
Kline, D. W. (1994). Optimizing the visibility of displays for older observers. Experimental
Aging Research, 20, 11–23.
Kuffler, S. W. (1952). Neurons in the retina: Organization, inhibition and excitatory problems.
Cold Spring Harbor Symposia on Quantitative Biology, 17, 281–292.
Milner, A. D., & Goodale, M. A. (2006). The visual brain in action (2nd ed.). Oxford: Oxford
University Press.
Sacks, O., & Wasserman, R. (1987). The case of the colorblind painter. The New York Review of
Books, 34, 25–33.
Snowden, R., Thompson, P., & Troscianko, T. (2008). Basic vision: An introduction to visual
perception. Oxford: Oxford University Press.
Szentagothai, J. (1975). The “module-concept” in cerebral cortex architecture. Brain Research,
95, 475–496.
Tanaka, K. (1993). Neuronal mechanisms of object recognition. Science, 262, 685–688.
Weizkrantz, L. (1986). Blindsight: A case study and implications. Oxford: Oxford University
Press.
Wong-Riley, M. T. T., Hevner, R. F., Cutlan, R., Earnest, M., Egan, R., Frost, J., & Nguyen, T.
(1993). Cytochrome oxidase in the human visual cortex: Distribution in the developing and
the adult brain. Visual Neuroscience, 10, 41–58.
Zaidi, F. H., Hull, J. T., Peirson, S. N., Wulff, K., Aeschbach, D., et al. (2007). Short-wavelength
light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer
retina. Current Biology, 17, 2122–2128.
Zihl, J., von Cramon, D., & Mai, N. (1983). Selective disturbance of movement vision after
bilateral brain damage. Brain, 106, 313–340.
CHAPTER 10
Bermudez, P., Lerch, J. P., Evans, A. C., & Zatorre, R. J. (2009). Neuroanatomical correlates of
musicianship as revealed by cortical thickness and voxel-based morphometry. Cerebral
Cortex, 19, 1583–1596.
Boonman, A., Bumrungsri, S., & Yovel, Y. (2014). Nonecholocating fruit bats produce biosonar
clicks with their wings. Current Biology, 24, 2962–2967.
Bregman, A. S. (2005). Auditory scene analysis and the role of phenomenology in experimental
psychology. Canadian Psychology, 46, 1, 32–40.
Chomsky, N. (1965). Aspects of the theory of syntax. Cambridge, MA: MIT Press.
Clarke, G. M. (2015). The multi-channel cochlear implant: Multi-disciplinary development of
electrical stimulation of the cochlea and the resulting clinical benefit. Hearing Research, 322,
4–13.
Daniel, E. (2007). Noise and hearing loss: A review. The Journal of School Health, 77, 225–231.
Drake-Lee, A. B. (1992). Beyond music: Auditory temporary threshold shift in rock musicians
after a heavy metal concert. Journal of the Royal Society of Medicine, 85, 617–619.
Geissmann, T. (2001). Gibbon songs and human music from an evolutionary perspective. In N.
L. Wallin, B. Merker, & S. Brown (Eds.), The origins of music (pp. 103–124). Cambridge,
MA: MIT Press.
Hyde, K. L., Lerch, J. P., Zatorre, R. J., Griffiths, T. D., Evans, A. C., & Peretz, I. (2007).
Cortical thickness in congenital amusia: When less is better than more . Journal of
Neuroscience, 27, 13028–13032.
Johansson, B. B. (2012). Multisensory stimulation in stroke rehabilitation. Frontiers in Human
Neuroscience, 6, 60.
Kim, K. H. S., Relkin, N. R., Young-Min Lee, K., and Hirsch, J. (1997). Distinct cortical areas
associated with native and second languages. Nature 388, 171–174.
Knudsen, E. I. (1981). The hearing of the barn owl. Scientific American, 245 (6), 113–125.
Loeb, G. E. (1990). Cochlear prosthetics. Annual Review of Neuroscience, 13, 357–371.
Marler, P. (1991). The instinct to learn. In S. Carey and R. German (Eds.), The epigenesis of
mind: Essays on biology and cognition (p. 39). Hillsdale, NJ: Erlbaum.
Nottebohm, F., & Arnold, A. P. (1976). Sexual dimorphism in vocal control areas of the songbird
brain. Science, 194, 211–213.
Penfield, W., & Roberts, L. (1956). Speech and brain mechanisms. Oxford, London: Oxford
University Press.
Peretz, I., Kolinsky, R., Tramo, M., Labrecque, R., Hublet, C., Demeurisse, G., et al. (1994).
Functional dissociations following bilateral lesions of auditory cortex. Brain, 117, 1283–1301.
Pinker, S. (1997). How the mind works. New York: Norton.
Rauschecker, J. P. (2012). Ventral and dorsal streams in the evolution of speech and language.
Frontiers in Evolutionary Neuroscience, 4:7. doi: 10.3389/fnevo.2012.00007.
Romanski, L. M., Tian, B., Fritz, J., Mishkin, M., Goldman-Rakic, P. S., & Rauschecker, J. P.
(1999). Dual streams of auditory afferents target multiple domains in the primate prefrontal
cortex. Nature Neuroscience, 2, 1131–1136.
Sunitha Suresh, B. S., De Oliveira, G. S. Jr., & Suresh, S. (2015). The effect of audio therapy to
treat postoperative pain in children undergoing major surgery: A randomized controlled trial.
 Pediatric Surgical International, 31, 197–201.
Teie, P. U. (1998). Noise-induced hearing loss and symphony orchestra musicians: Risk factors,
effects, and management. Maryland Medical Journal, 47, 13–18.
Teng, S., & Whitney, D. (2011). The acuity of echolocation: Spatial resolution in the sighted
compared to expert performance. Journal of Visual Impairment & Blindness, 105, 20–32.
Thaler, L., Arnott, S. R., & Goodale, M. A. (2011). Neural correlates of natural human
echolocation in early and late blind echolocation experts. PLoS ONE, 6, e20162.
Thompson, C. K., Meitzen, J., Replogle, K., Drnevich, J., Lent, K. L., et al. (2012). Seasonal
changes in patterns of gene expression in avian song control brain regions. PLoS One, 7,
e35119.
Trehub, S., Schellenberg, E. G., & Ramenetsky, G. B. (1999). Infants’ and adults’ perception of
scale structures. Journal of Experimental Psychology: Human Perception and Performance,
25, 965–975.
Zatorre, R. J., Evans, A. C., & Meyer, E. (1994). Neural mechanisms underlying melodic
perception and memory for pitch. Journal of Neuroscience, 14, 1908–1919.
Zatorre, R. J., Evans, A. C., Meyer, E., & Gjedde, A. (1992). Lateralization of phonetic and pitch
discrimination in speech processing. Science, 256, 846–849.
Zatorre, R. J., Meyer, E., Gjedde, A., & Evans, A. C. (1996). PET studies of phonetic processing
of speech: Review, replication, and reanalysis. Cerebral Cortex, 6, 21–30.
CHAPTER 11
Aflalo, T. N., & Graziano, M. S. (2007). Relationship between unconstrained arm movements
and single-neuron firing in the macaque motor cortex. Journal of Neuroscience, 127, 2760–
2780.
Alessandria, M., Vetrugno, R., Cortelli, P., & Montagna, P. (2011). Normal body scheme and
absent phantom limb experience in amputees while dreaming. Consciousness and Cognition,
20, 831–834.
Alexander, R. E., & Critcher, M. D. (1990). Functional architecture of basal ganglia circuits:
Neural substrates of parallel processing. Trends in Neuroscience, 13, 269.
Asanuma, H. (1989). The motor cortex. New York: Raven Press.
Blakemore, S. J., Wolpert, D. M., & Frith, C. D. (1998). Central cancellation of self-produced
tickle sensation. Nature Neuroscience, 1, 635–640.
Bleton, J. P., Teremetz, M., Vidailhet, M., Mesure, S., Maier, M. A., Lindberg, P. G. (2014).
Impaired force control in writer’s cramp showing a bilateral deficit in sensorimotor
integration. Movement Disorders, 29, 130–134.
Brinkman, C. (1984). Supplementary motor area of the monkey’s cerebral cortex: Short- and
long-term deficits after unilateral ablation and the effects of subsequent callosal section.
Journal of Neuroscience, 4, 918–992.
Casile, A., Caggiano, V., & Ferrari, P. F. (2011). The mirror neuron system: A fresh view.
Neuroscientist, 17, 524–538.
Castellanos, F. X., Cortese, S., & Proal, E. (2014). Connectivity. Current Topics in Behavioral
Neuroscience, 16, 49–77.
Church, J. A., Fair, D. A., Dosenbach, N. U., Cohen, A. L., Miezin, F. M., Petersen, S. E., &
Schlaggar, B. L. (2009). Control networks in paediatric Tourette syndrome show immature
and anomalous patterns of functional connectivity. Brain, 32, 225–238.
Cole, J. (1995). Pride and a daily marathon. Cambridge, MA: MIT Press.
Corkin, S., Milner, B., & Rasmussen, T. (1970). Somatosensory thresholds. Archives of
Neurology, 23, 41–58.
Critchley, M. (1953). The parietal lobes. London: Arnold.
Daly, J. J., & Huggins, J. E. (2015). Brain-computer interface: Current and emerging
rehabilitation applications. Archives of Physical and Medical Rehabilitation, 96 (3 Suppl.),
S1–S7.
Davarpanah Jazi, S., Yau, M., Westwood, D. A., & Heath, M. (2015). Pantomime-grasping: The
‘return’ of haptic feedback supports the absolute specification of object size. Experimental
Brain Research, 233, 2029–2040.
Evarts, E. V. (1968). Relation of pyramidal tract activity to force exerted during voluntary
movement. Journal of Neurophysiology, 31, 14–27.
Foster, E., Wildner, H., Tudeau, L., Haueter, S., Ralvenius, W. T., Jegen, M., et al. (2015).
Targeted ablation, silencing, and activation establish glycinergic dorsal horn neurons as key
components of a spinal gate for pain and itch. Neuron, 85, 1289–1304.
Friedhoff, A. J., & Chase, T. N. (1982). Gilles de la Tourette syndrome. Advances in Neurology,
35, 1–17.
Friend, D. M., & Kravitz, A. V. (2014). Working together: Basal ganglia pathways in action
selection. Trends in Neuroscience, 37, 301–303.
Hashimoto, Y., Honda, T., Matsumura, K., Nakao, M., Soga, K., Katano, K., et al. (2015).
Quantitative evaluation of human cerebellum-dependent motor learning through prism
adaptation of hand-reaching movement. PLoS One. (3):e0119376.
Hellman, R. B., Chang, E., Tanner, J., Helms Tillery, S. I., & Santos, V. J. (2015). A robot hand
testbed designed for enhancing embodiment and functional neurorehabilitation of body
schema in subjects with upper limb impairment or loss. Frontiers in Human Neuroscience, 9,
1–26.
Hess, W. R. (1957). The functional organization of the diencephalon. London: Grune & Stratton.
Imani, S., Zagari, Z., Rezaei Zarchi, S., Jorjani, M., Nasri, S. (2015). Functional recovery of
carbon nanotube/nafion nanocomposite in rat model of spinal cord injury. Artificial Cells
Nanomedicine and Biotechnology, 10, 1–6.
Kaas, J. H. (1987). The organization and evolution of neocortex. In S. P. Wise (Ed.), Higher
brain functions (pp. 237–298). New York: Wiley.
Kaas, J. H., Stepniewska, I., & Gharbawie, O. (2012). Cortical networks subserving upper limb
movements in primates. European Journal of Physical and Rehabilitation Medicine, 48, 299–
306.
Kalueff, A. V., Aldridge, J. W., LaPorte, J. L., Murphy D. L., & Tuohimaa, P. (2007). Analyzing
grooming microstructure in neurobehavioral experiments. Nature Protocols, 25, 38–44.
Kambi, N., Halder, P., Rajan, R., Arora, V., Chand, P., et al. (2014). Large-scale reorganization of
the somatosensory cortex following spinal cord injuries is due to brainstem plasticity. Nature
Communications, 8 :5, 3602.
Kern, U., Busch, V., Rockland, M., Kohl, M., & Birklein, F. (2009). Prevalence and risk factors
of phantom limb pain and phantom limb sensations in Germany: A nationwide field survey.
Schmerz, 23, 479–488.
Lang, C. E., & Schieber, M. H. (2004). Reduced muscle selectivity during individuated finger
movements in humans after damage to the motor cortex or corticospinal tract. Journal of
Neurophysiology, 91, 1722–1733.
Lashley, K. S. (1951). The problem of serial order in behavior. In L. A. Jeffress (Ed.), Cerebral
mechanisms and behavior (pp. 112–136). New York: Wiley.
Leonard, C. M., Glendinning, D. S., Wilfong, T., Cooper, B. Y., & Vierck, C. J., Jr. (1991).
Alterations of natural hand movements after interruption of fasciculus cuneatus in the
macaque. Somatosensory and Motor Research, 9, 61–75.
Lopez-Escamez. J. A., Carey, J., Chung, W. H., Goebel, J. A., Magnusson, M., Mandalà, M., et
al. (2015). Diagnostic criteria for Ménière’s disease. Journal of Vestibular Research, 25, 1–7.
Melzack, R. (1973). The puzzle of pain. New York: Basic Books.
Melzack, R., & Wall, P. D. (1965). Pain mechanisms: A new theory. Science, 150, 971–979.
Mountcastle, V. B. (1978). An organizing principle for cerebral function: The unit module and
the distributed system. In G. M. Edelman & V. B. Mountcastle (Eds.), The mindful brain (pp.
7–50). Cambridge, MA: MIT Press.
Nudo, R. J., Wise, B. M., SiFuentes, F., & Milliken, G. W. (1996). Neural substrates for the
effects of rehabilitative training on motor recovery after ischemic infarct. Science, 272, 1791–
1794.
Panksepp, J. (2007). Neuroevolutionary sources of laughter and social joy: Modeling primal
human laughter in laboratory rats. Behavioural Brain Research, 4, 231–244.
Penfield, W., & Boldrey, E. (1958). Somatic motor and sensory representation in the cerebral
cortex as studied by electrical stimulation. Brain, 60, 389–443.
Pons, T. P., Garraghty, P. E., Ommaya, A. K., Kaas, J. H., Taum, E., & Mishkin, M. (1991).
Massive cortical reorganization after sensory deafferentation in adult macaques. Science, 252,
1857–1860.
Roland, P. E. (1993). Brain activation. New York: Wiley-Liss.
Rothwell, J. C., Taube, M. M., Day, B. L., Obeso, J. A., Thomas, P. K., & Marsden, C. D. (1982).
Manual motor performance in a deafferented man. Brain, 105, 515–542.
Sacks, O. W. (1998). The man who mistook his wife for a hat: And other clinical tales. New
York: Touchstone Books.
Thach, W. T. (2007). On the mechanism of cerebellar contributions to cognition. Cerebellum, 6,
163–167.
Therrien, A. S., Bastian, A. J. (2015). Cerebellar damage impairs internal predictions for sensory
and motor function. Current Opinion in Neurobiology, 33, 127–133.
Tinaz, S., Malone, P., Hallett, M., Horovitz, S. G. (2015). Role of the right dorsal anterior insula
in the urge to tic in Tourette syndrome. Movement Disorders, doi: 10.1002/mds.26230.
von Holst, E. (1973). The collected papers of Erich von Holst (R. Martin, Trans.). Coral Gables,
FL: University of Miami Press.
Williams, T. H., Gluhbegovic, N., & Jew, J. (2000). The human brain: Dissections of the real
brain (CD-ROM). Brain University: brain-university.com.
Windt, J. M., Harkness, D. L., & Lenggenhager, B. (2015). Tickle me, I think I might be
dreaming! Sensory attenuation, self-other distinction, and predictive processing in lucid
dreams. Frontiers in Human Neuroscience, 8, 717.
CHAPTER 12
Ackerly, S. S. (1964). A case of paranatal bilateral frontal lobe defect observed for thirty years. In
J. M. Warren & K. Akert (Eds.), The frontal granular cortex and behavior (pp. 192–218).
New York: McGraw-Hill.
Adelmann, P. K., & Zajonc, R. B. (1989). Facial efferents and the experience of emotion. Annual
Review of Psychology, 40, 249–280.
Bao, A.-M., & Swaab, D. F. (2011). Sexual differentiation of the human brain: Relation to gender
identity, sexual orientation and neuropsychiatric disorders. Frontiers in Neuroendocrinology,
32, 214–226.
Bartoshuk, L. M. (2000). Comparing sensory experiences across individuals: Recent
psychophysical advances illuminate genetic variation in taste perception. Chemical Senses,
25, 447–460.
Beatty, J. (1995). Principles of behavioral neuroscience (p. 339). Dubuque, IA: Brown &
Benchmark.
Becker, J. B., Berkley, K. J., Geary, N., Hampson, E., Herman, J. P., & Young, E. A. (2008). Sex
differences in the brain: From genes to behavior. New York: Oxford University Press.
Berridge, K. C. (1996). Food reward: Brain substrates of wanting and liking. Neuroscience and
Biobehavioral Reviews, 20, 6.
Brunetti, M., Babiloni, C., Ferretti, A., Del Gratta, C., Merla, A., et al. (2008). European Journal
of Neuroscience, 27, 2922–2927.
Buss, D. (2014). Evolutionary psychology: The new science of the mind (5th ed.). New York:
Taylor & Francis.
Butler, R. A., & Harlow, H. F. (1954). Persistence of visual exploration in monkeys. Journal of
Comparative and Physiological Psychology, 47, 257–263.
Daly, M., & Wilson, M. (1988). Homicide. New York: Aldine.
Damasio, A. R. (1999). The feeling of what happens: Body and emotion in the making of
consciousness. New York: Harcourt Brace.
Davis, M., Walker, D. L., & Myers, K. M. (2003). Role of the amygdala in fear extinction
measured with potentiated startle. Annals of the New York Academy of Sciences, 985, 218–
232.
Day, J. J., & Sweatt, J. D. (2011). Cognitive neuroepigenetics: A role for epigenetic mechanisms
in learning and memory. Neurobiology of Learning and Memory, 96, 2–12.
Dethier, V. G. (1962). To know a fly. San Francisco: Holden-Day.
Duffy, V. B., Hayes, J. E., Davidson, A. C., Kidd, J. R., Kidd, K. K., & Bartoshuk, L. M. (2010).
Vegetable intake in college-aged adults is explained by oral sensory phenotypes and TAS2R38
genotype. Chemosensory Perception, 3, 137–148.
Eisenberger, N. I., Jarcho, J. M., Lieberman, M. D., & Naliboff, B. D. (2006). An experimental
study of shared sensitivity to physical pain and social rejection. Pain, 126, 132–138.
Eisenberger, N. I., Lieberman, M. D., & Williams, K. D. (2003). Does rejection hurt? An fMRI
study of social exclusion. Science, 302, 290–292.
Everitt, B. J. (1990). Sexual motivation: A neural and behavioral analysis of the mechanisms
underlying appetitive and copulatory responses of male rats. Neuroscience and Biobehavioral
Reviews, 14, 217–232.
Field, T. M., Woodson, R., Greenberg, R., & Cohen, D. (1982), Discrimination and imitation of
facial expression by neonates. Science, 218, 179–181.
Fung, T. T., van Dam, R. M., Hankinson S. E., Stampfer, M., Willett, W. C., & Hu, F. B. (2010).
Low-carbohydrate diets and all-cause and cause-specific mortality: Two cohort studies.
Annals of Internal Medicine, 153, 289–298.
Garcia, J., & Koelling, R. A. (1966). Relation of cue to consequences in avoidance learning.
Psychonomic Science, 4, 123–124.
Garrison, K. A., Zeffiro, T. A., Scheinost, D., Constable, R. T., & Brewer, J. A. (2015, Apr 23).
Meditation leads to reduced default mode network activity beyond an active task. Cognitive
Affective Behavioral Neuroscience, 15, 712–720.
Gerkin, R.C., & Castro, J. B. (2015). The number of olfactory stimuli that humans can
discriminate is still unknown. eLife 4:e08127.
Glickman, S. E., & Schiff, B. B. (1967). A biological theory of reinforcement. Psychological
Review, 74, 81–109.
Gorski, R. A. (1984). Critical role for the medial preoptic area in the sexual differentiation of the
brain. Progress in Brain Research, 61, 129–146.
Heron, W. (1957). The pathology of boredom. Scientific American, 196 (1), 52–56.
Insel, T. R., & Fernald, R. D. (2004). How the brain processes social information: Searching for
the social brain. Annual Review of Neuroscience, 27, 697–722.
Jacob, S., Kinnunen, L. H., Metz, J., Cooper, M., & McClintock, M. K. (2001). Sustained human
chemosignal unconsciously alters brain function. Neuroreport, 12, 2391–2394.
Jacobsen, C. F. (1936). Studies of cerebral function in primates. Comparative Psychology
Monographs, 13, 1–68.
Janes, A. C., Farmer, S., Frederick, B. deB., Nickerson, L. D., & Lucas, S. E. (2014). An increase
in tobacco craving is associated with enhanced medial prefreontal cortex network coupling.
PLoS One, 9, e88228.
Janes, A. C., Nickerson, L. D., Frederick, B. deB., & Kaufman, M. H. (2012). Prefrontal and
limbic resting state brain network functional connectivity differs between biotine-dependent
smokers and non-smoking controls. Drug and Alcohol Dependence, 125, 252–259.
Klüver, H., & Bucy, P. C. (1939). Preliminary analysis of the temporal lobes in monkeys.
Archives of Neurology and Psychiatry, 42, 979–1000.
Kross, E., Berman, M. G., Mischel, W., Smith, E. E., & Water, T. D. (2011). Social rejection
shares somatosensory representations with physical pain. Proceedings of the National
Academy of Sciences United States of America, 108, 6270–6275.
LeDoux, J. (1996). The emotional brain. New York: Simon & Schuster.
Lundstrom, J. N., Boyle, J. A., Zatorre, R. J., & Jones-Gotman, M. (2008). Functional neuronal
processing of body odors differs from that of similar common odors. Cerebral Cortex, 18,
1466–1474.
MacLean, P. D. (1949). Psychosomatic disease and the “visceral brain”: Recent developments
bearing on the Papez theory of emotion. Psychosomatic Medicine, 11, 338–353.
McCarthy, M. M., Auger, A. P., Bale, T. L., De Vries, G. J., Dunn, G. A., et al. (2009). The
epigenetics of sex differences in the brain. Journal of Neuroscience, 29, 12815–12823.
Money, J., & Ehrhardt, A. A. (1972). Man and woman, boy and girl. Baltimore: Johns Hopkins
University Press.
Mozaffarinan, D., Tao Hao, M. P. H., Rimm, E. B., Willett, W. C., & Hu, F. B. (2011). Changes in
diet and lifestyle and long-term weight gain in women and men. New England Journal of
Medicine, 364, 2392–2404.
Olds, J., & Milner, P. (1954). Positive reinforcement produced by electrical stimulation of septal
area and other regions of rat brain. Journal of Comparative and Physiological Psychology, 47,
419–427.
Olsson, S. B., Barnard, J., & Turri, L. (2006). Olfaction and identification of unrelated
individuals: Examination of the mysteries of human odor recognition. Journal of Chemical
Ecology, 32, 1635–1645.
Panagiotakos, D. B., Pitsavos, C., Polychronopoulos, E., Chrysohoou, C., Zampelas, A., &
Trichopoulou, A. (2004). Can a Mediterranean diet moderate the development and clinical
progression of coronary heart disease? A systematic review. Medical Science Monitor, 10,
RA193–RA198.
Robinson, T. E., & Berridge, K. C. (2008). Incentive sensitization theory. Philosophical
Transactions of the Royal Society of London, 363, 3137–3146.
Schroeder, M., Krebs, M. O., Bleich, S., & Frieling, H. (2010). Epigenetics and depression.
Current Opinion in Psychiatry, 23, 588–592.
Seeley, R. J., & Woods, S. C. (2003). Monitoring of stored and available fuel by the CNS:
Implications for obesity. Nature Reviews Neuroscience, 4, 885–909.
Shai, I., Schwarzfuchs, D., Henkin, Y., Shahar, D. R., Witkow, S., et al. (2008). Weight loss with
a low-carbohydrate, Mediterranean, or low-fat diet. New England Journal of Medicine, 359,
229–241.
Skinner, B. F. (1938). The behavior of organisms. New York: Appleton-Century-Crofts.
Smith, D. V., & Shepherd, G. M. (2003). Chemical senses: Taste and olfaction. In L. R. Squiare,
F. E. Bloom, S. K. McConnell, J. L. Roberts, N. C. Spitzer, & M. J. Zigmond (Eds.),
Fundamental Neuroscience (2nd ed., pp. 631–667). New York: Academic Press.
Stern, K., & McClintock, M. K. (1998). Regulation of ovulation by human pheromones. Nature,
392, 177–179.
Veldhuizen, M. G., Albrecht, J., Zelano, C., Boesveldt, S., Breeslin, P., & Lundstrom, J. N.
(2011). Identification of human gustatory cortex by activation likelihood estimation. Human
Brain Mapping, 32, 2256–2266.
Wise, R. A. (1996). Addictive drugs and brain stimulation reward. Annual Review of
Neuroscience, 19, 319–340.
Woo, C.-W., Koban, L., Kross, E., Lindquist, M. A., Banich, M. T., Ruzic, L., et al. (2014).
Separate neural representations for physical pain and social rejection. Nature
Communications, 5, 5380. doi: 10.1038/ncomms6380
Woolley, C. S., Gould, E., Frankfurt, M., & McEwen, B. (1990). Naturally occurring fluctuation
in dendritic spine density on adult hippocampal pyramidal neurons. Journal of Neuroscience,
10, 4035–4039.
World Health Organization (2000). Obesity: Preventing and managing the global epidemic.
WHO Technical Report Series, No. 894, 1–253.
CHAPTER 13
Amariei, C., Tomita, M., & Murray, D. B. (2014). Quantifying periodicity in omics data.
Frontiers in Cellular Developmental Biology, 19, 2:40.
Batterink, L. J., Oudiette, D., Reber, P. J., & Paller, K. A. (2014). Sleep facilitates learning a new
linguistic rule. Neuropsychologia, 65, 169–179.
Bendix, C., Marshall, C. M., & Harmon, F. G. (2015). Circadian clock genes universally control
key agricultural traits. Molecular Plant, S1674-2052(15), 171–179.
Binkley, S. (1990). The clockwork sparrow. Englewood Cliffs, NJ: Prentice Hall.
Blumberg, M. S. (2015). Developing sensorimotor systems in our sleep. Current Directions in
Psychological Science, 24, 32–37.
Bosler, O., Girardet, C., Franc, J. L., Becquet, D., François-Bellan, A. M. (2015). Structural
plasticity of the circadian timing system: An overview from flies to mammals. Frontiers in
Neuroendocrinology, S0091-3022(15)00014-X.
Cain, S. W., McDonald, R. J., & Ralph, M. R. (2008). Time stamp in conditioned place
avoidance can be set to different circadian phases. Neurobiology of Learning and Memory, 89,
591–594.
Cain, S. W., Verwey, M., Szybowska, M., Ralph, M. R., & Yeomans, J. S. (2007). Carbachol
injections into the intergeniculate leaflet induce nonphotic phase shifts. Brain Research, 1177,
59–65.
Carter, K. A., Hathaway, N. E., & Lettieri, C. F. (2014). Common sleep disorders in children.
American Family Physician, 89, 368–377.
Chang, A. M., Aeschbach, D., Duffy, J. F., Czeisler, C. A. (2015). Evening use of light-emitting
eReaders negatively affects sleep, circadian timing, and next-morning alertness. Proceedings
of the National Academy of Sciences United States of America, 112, 232–237.
Claustrat, B., Leston, J. (2015). Melatonin: Physiological effects in humans. Neurochirurgie,
61(2–3), 77–84.
Corrêa Cde, C., Blasca, W. Q., & Berretin-Felix, G. (2015). Health promotion in obstructive
sleep apnea syndrome. International Archives of Otorhinolaryngology, 19, 166–170.
de Lavilléon, G., Lacroix, M. M., Rondi-Reig, L., & Benchenane, K. (2015). Explicit memory
creation during sleep demonstrates a causal role of place cells in navigation. Nature
Neuroscience, 18, 493–495.
Dement, W. C. (1972). Some must watch while some must sleep. Stanford, CA: Stanford Alumni
Association.
Dissel, S., Angadi, V., Kirszenblat, L., Suzuki, Y., Donlea, J., Klose, M., et al. (2015). Sleep
restores behavioral plasticity to Drosophila mutants. Current Biology, 25, 1270–1280.
Dubey, A. K., Handu, S. S., & Mediratta, P. K. (2015). Suvorexant: The first orexin receptor
antagonist to treat insomnia. Journal of Pharmacology and Pharmacothereputics, 6, 118–121.
Edwards, C. L., Ruby, P. M., Malinowski, J. E., Bennett, P. D., & Blagrove, M. T. (2013).
Dreaming and insight. Frontiers in Psychology, 24, 974–979.
Elliott, A. S., Huber, J. D., O’Callaghan, J. P., Rosen, C. L., & Miller, D. B. (2014). A review of
sleep deprivation studies evaluating the brain transcriptome. Springerplus, 3 :728.
Filevich, E., Dresler, M., Brick, T. R., & Kühn, S. (2015). Metacognitive mechanisms underlying
lucid dreaming. Journal of Neuroscience, 35, 1082–1088.
Forloni, G., Tettamanti, M., Lucca, U., Albanese, Y., Quaglio, E., Chiesa, R., et al. (2015).
Preventive study in subjects at risk of fatal familial insomnia: Innovative approach to rare
diseases. Prion, 9, 75–79.
Foulkes, D., & Domhoff, G. W. (2014). Bottom-up or top-down in dream neuroscience? A top-
down critique of two bottom-up studies. Conscious Cognition, 27, 168–171.
Freud, S. (1990). The interpretation of dreams. Leipzig and Vienna: Franz Deuticke.
Gangwisch, J. E. (2014). Invited commentary: Nighttime light exposure as a risk factor for
obesity through disruption of circadian and circannual rhythms. American Journal of
Epidemiology, 180, 251–253.
Gerhart-Hines, Z., Lazar, M. A. (2015). Circadian metabolism in the light of evolution.
Endocrinology Reviews, 36(3), 289–304. er20151007.
Gerrard, J. L., Burke, S. N., McNaughton, B. L., & Barnes, C. A. (2008). Sequence reactivation
in the hippocampus is impaired in aged rats. Journal of Neuroscience, 30, 7883–7890.
Hall, C. S., Domhoff, G. W., Blick, K. A., & Weesner, K. E. (1982). The dreams of college men
and women in 1950 and 1980: A comparison of dream contents and sex differences. Sleep, 5,
188–194.
Hobson, J. A. (2002). Sleep and dream suppression following a lateral medullary infarct: A first-
person account. Consciousness and Cognition, 11, 377–390.
Hobson, J. A. (2004). 13 dreams Freud never had: A new mind science. New York: Pi Press.
Hughes, S., Jagannath, A., Hankins, M. W., Foster, R. G., & Peirson, S. N. (2015). Photic
regulation of clock systems. Methods in Enzymology, 552, 125–143.
Jones, B. E. (1993). The organization of central cholinergic systems and their functional
importance in sleep–waking states. Progress in Brain Research, 98, 61–71.
Jouvet, M. (1972). The role of monoamines and acetylcholine-containing neurons in the
regulation of the sleep–waking cycle. Ergebnisse der Physiologie, 64, 166–307.
Kang, J. I., Park, C. I., Namkoong, K., & Kim, S. J. (2015). Associations between
polymorphisms in the NR1D1 gene encoding for nuclear receptor REV-ERBα and circadian
typologies. Chronobiology International, 32, 568–572.
Kerr, D. C., Zava, D. T., Piper, W. T., Saturn, S. R., Frei, B., & Gombart, A. F. (2015).
Associations between vitamin D levels and depressive symptoms in healthy young adult
women. Psychiatry Research, 227, 46–51.
Klinger, E. (1990). Daydreaming. Los Angeles, CA: Tarcher (Putnam).
Kreutzmann, J., Havekes, R., Abel, T., & Meerlo, P. (2015). Sleep deprivation and hippocampal
vulnerability: Changes in neuronal plasticity, neurogenesis and cognitive function.
Neuroscience.
Labrecque, N., & Cermakian N. (2015). Circadian clocks in the immune system. Journal of
Biological Rhythms, 30 (4), 277–290.
Lajoie, P., Aronson, K. J., Day, A., & Tranmer, J. (2015). A cross-sectional study of shift work,
sleep quality and cardiometabolic risk in female hospital employees. BMJ Open,
10;5(3):e007327.
Lamberg, L. (2003). Scientists never dreamed finding would shape half-century of sleep research.
Journal of the American Medical Association, 290, 2652–2654.
Lan, K. C., Chang, D. W., Kuo, C. E., Wei, M. Z., Li, Y. H., Shaw, F. Z., et al. (2015). Using off-
the-shelf lossy compression for wireless home sleep staging. Journal of Neuroscience
Methods, 246, 142–152.
Landgraf, D., Tsang, A. H., Leliavski, A., Koch, C. E., Barclay, J. L., Drucker, D. J., et al. (2015).
Oxyntomodulin regulates resetting of the liver circadian clock by food. eLife 4, e06253.
Li, Y., Ma, W., Kang, Q., Qiao, L., Tang, D., Qiu, J., et al. (2015). Night or darkness, which
intensifies the feeling of fear? International Journal of Psychophysiology, 97 (1), 46–57.
Lungato, L., Gazarini, M. L, Paredes-Gamero, E. J., Tufik, S., & D’Almeida, V. (2015).
Paradoxical sleep deprivation impairs mouse survival after infection with malaria parasites.
Malaria Journal, 14, 183.
Mahowald, M. W., & Schenck, C. H. (2015). REM sleep behaviour disorder: A window on the
sleeping brain. Brain, 138, 1131–1133.
Malcolm-Smith, S., Koopowitz, S., Pantelis, E., & Solms, M. (2012). Approach/avoidance in
dreams. Consciousness and Cognition, 21, 408–412.
Maquet, P., Laureys, S., Peigneux, P., Fuchs, S., Petiau, C., et al. (2000). Experience-dependent
changes in cerebral activation during human REM sleep. Nature Neuroscience, 3, 831–836.
Mårtensson, B., Pettersson, A., Berglund, L., & Ekselius, L. (2015). Bright white light therapy in
depression: A critical review of the evidence. Journal of Affective Disorders, 182, 1–7.
Mistlberger, R. E., & Antle, M. C. (2011). Entrainment of circadian clocks in mammals by
arousal and food. Essays in Biochemistry, 49, 119–136.
Monecke, S., Brewer, J. M., Krug, S., & Bittman, E. L. (2011). Duper: A mutation that shortens
hamster circadian period. Biological Rhythms, 26, 283–292.
Moruzzi, G., & Magoun, H.W. (1949). Brain stem reticular formation and activation of the EEG.
Electroencephalography and Clinical Neurophysiology, 1, 455–473.
Mulder, C. K., Reckman, G. A., Gerkema, M. P., & Van der Zee, E. A. (2015). Time-place
learning over a lifetime: Absence of memory loss in trained old mice. Learning and Memory,
22, 278–288.
Nelini, C., Bobbo, D., & Mascetti, G. G. (2012). Monocular learning of a spatial task enhances
sleep in the right hemisphere of domestic chicks ( Gallus gallus ). Experimental Brain
Research, 18, 381–388.
Nir, Y., & Tononi, G. (2010). Dreaming and the brain: From phenomenology to neurophysiology.
Trends in Cognitive Science, 14, 88–100.
Nobunaga, M., Obukuro, K., Kurauchi, Y., Hisatsune, A., Seki, T., Tsutsui, M., et al. (2014).
High fat diet induces specific pathological changes in hypothalamic orexin neurons in mice.
Neurochemistry International, 78, 61–66.
Osorio, I., & Daroff, R. B. (1980). Absence of REM and altered NREM sleep in patients with
spinocerebellar degeneration and slow saccades. Annals of Neurology, 7, 277–280.
Pellegrino, R., Kavakli, I. H., Goel, N., Cardinale, C. J., Dinges, D. F., Kuna, S. T., et al. (2015).
A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in
humans. Sleep, 37, 1327–1336.
Postuma, R. B., Gagnon, J. F., Tuineaig, M., Bertrand, J. A., Latreille, V., Desjardins, C., et al.
(2013). Antidepressants and REM sleep behavior disorder: Isolated side effect or
neurodegenerative signal? Sleep, 36, 1579–1585.
Quinlan, J., & Quinlan, J. (1977). Karen Ann: The Quinlans tell their story. Toronto: Doubleday.
Ralph, M. R., & Lehman, M. N. (1991). Transplantation: A new tool in the analysis of the
mammalian hypothalamic circadian pacemaker. Trends in Neurosciences, 14, 363–366.
Rasch, B., & Born, J. (2013). About sleep’s role in memory. Physiological Reviews, 93, 681–766.
Raven, P. H., Evert, R. F., & Eichorn, S. E. (1992). Biology of plants. New York: Worth
Publishers.
Reiter, R. J. (1980). The pineal and its hormones in the control of reproduction in mammals.
Endocrinology Review, 1, 120.
Richter, C. P. (1965). Biological clocks in medicine and psychiatry. Springfield, IL: Charles C
Thomas.
Roffward, H. P., Muzio, J., & Dement, W. C. (1966). Ontogenetic development of the human
sleep–dream cycle. Science, 152, 604–619.
Schenck, C. H., Bundlie, S. R., Ettinger, M. G., & Mahowald, M. W. (1986). Chronic behavioral
disorders of human REM sleep: A new category of parasomnia. Sleep, 25, 293–308.
Schmal, C., Myung, J., Herzel, H., & Bordyugov, G. (2015). A theoretical study on seasonality.
Frontiers in Neurology, 7 (6), 94.
Siegel, J. (2004). Brain mechanisms that control sleep and waking. Naturwissenschaften, 91,
355–365.
Silver, R., LeSauter, J., Tresco, P. A., & Lehman, M. N. (1996). A diffusible coupling signal from
the transplanted suprachiasmatic nucleus controlling circadian locomotor rhythms. Nature,
382, 810–813.
Smarr, B. L. (2015). Digital sleep logs reveal potential impacts of modern temporal structure on
class performance in different chronotypes. Journal of Biological Rhythms, 30, 61–67.
Valli, K., & Revonsuo, A. (2009). The threat simulation theory in light of recent empirical
evidence: A review. American Journal of Psychology, 122, 17–38.
Vanderwolf, C. H. (2002). An odyssey through the brain, behavior and the mind. Amsterdam:
Kluwer Academic.
Webb, I. C., Antle, M. C., & Mistlberger, R. E. (2014). Regulation of circadian rhythms in
mammals by behavioral arousal. Behavioral Neuroscience, 128, 304–325.
Weingarten, J. A., & Collop, N. A. (2013). Air travel: Effects of sleep deprivation and jet lag.
Chest, 144, 1394–1401.
Wijemanne, S., & Jankovic, J. (2015). Restless legs syndrome: Clinical presentation diagnosis
and treatment. Sleep Medicine, 16, (6), 678–690.
Wilson, M. A., & McNaughton, B. L. (1994). Reactivation of hippocampal ensemble memories
during sleep. Science, 265, 676–679.
Wilson, S., & Argyropoulos, S. (2005). Antidepressants and sleep: A qualitative review of the
literature. Drugs, 65, 927–947.
Zaidi, F. H., Hull, J. T., Peirson, S. N., Wulff, K., Aeschbach, D., et al. (2007). Short-wavelength
light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer
retina. Current Biology, 17, 2122–2128.
Zhang, R., Lahens, N. F., Balance, H. I., Hughes, M. E., & Hogenesch, J. B. (2014). A circadian
gene expression atlas in mammals: Implications for biology and medicine. Proceedings of the
National Academy of Sciences United States of America, 111 (45), 16219–16224.
CHAPTER 14
Bliss, T. V., & Lomo, T. (1973). Long-lasting potentiation of synaptic transmission in the dentate
are of the anaesthetized rabbit following stimulation of the perforant path. Journal of
Physiology, 232, 331–356.
Cahill, L., Babinsky, R., Markowitsch, H. J., & McGaugh, J. L. (1995). The amygdala and
emotional memory. Nature, 377, 295–296.
Candia, V., Wienbruch, C., Elbert, T., Rockstroh, B., & Ray, W. (2003). Effective behavioral
treatment of focal hand dystonia in musicians alters somatosensory cortical organization.
Proceedings of the National Academy of Sciences United States of America, 100, 7942–7946.
Chang, F.-L. F., & Greenough, W. T. (1982). Lateralized effects of monocular training on
dendritic branching in adult split-brain rats. Brain Research, 232, 283–292.
Corkin, S. (2002). What’s new with the amnesic patient H. M.? Nature Reviews Neuroscience, 3,
153–160.
Corkin, S., Amaral, D. G., Gonzalez, R. G., Johnson, K. A., & Hyman, B. T. (1997). H. M.’s
medial temporal lobe lesion: Findings from magnetic resonance imaging. Journal of
Neuroscience, 17, 3964–3979.
Damasio, A. R., Tranel, D., & Damasio, H. (1989). Amnesia caused by herpes simplex
encephalitis, infarctions in basal forebrain, Alzheimer’s disease and anoxia/ischemia. In F.
Boller & J. Grafman (Eds.), Handbook of neuropsychology (Vol. 3, pp. 149–166). New York:
Elsevier.
Davis, M. (1992). The role of the amygdala in fear and anxiety. Annual Review of Neuroscience,
15, 353–375.
Day, J. J., Kennedy, A. J., & Sweatt, J. D. (2015). DNA methylation and its implications and
accessibility for neuropsychiatric therapeutics. Annual Review of Pharmacology and
Toxicology, 55, 591–611.
Eriksson, P. S., Perfilieva, E., Bjork-Eriksson, T., Alborn, A. M., Nordborg, C., Peterson, D. A.,
et al. (1998). Neurogenesis in the adult human hippocampus. Nature Medicine, 4, 1313–1317.
Fuster, J. M. (1995). Memory in the cerebral cortex. Cambridge, MA: MIT Press.
Fuster, J. M., Bodner, M., & Kroger, J. K. (2000). Cross-modal and cross-temporal association in
neurons of frontal cortex. Nature, 405, 347–351.
Gazzaniga, M. S. (Ed.). (2000). The new cognitive neurosciences. Cambridge, MA: MIT Press.
Geschwind, N., & Galaburda, A. M. (1985). Cerebral lateralization. Cambridge, MA: MIT
Press.
Gould, E., Tanapat, P., Hastings, N. B., & Shors, T. J. (1999). Neurogenesis in adulthood: A
possible role in learning. Trends in Cognitive Sciences, 3, 186–191.
Gould, E., Tanapat, P., McEwen, B. S., Flugge, G., & Fuchs, E. (1998). Proliferation of granule
cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proceedings of
the National Academy of Sciences United States of America, 95, 3168–3171.
Hampson, E., & Kimura, D. (1988). Reciprocal effects of hormonal fluctuations on human motor
and perceptual-spatial skills. Behavioral Neuroscience, 102, 456–459.
Hebb, D. O. (1947). The effects of early experience on problem solving at maturity. American
Psychologist, 2, 737–745.
Hebb, D. O. (1949). The organization of behavior: A neuropsychological theory. New York:
Wiley.
Jacobs, B., Schall, M., & Scheibel, A. B. (1993). A quantitative dendritic analysis of Wernicke’s
area in humans: II. Gender, hemispheric, and environmental factors. Journal of Comparative
Neurololgy, 327, 97–111.
Jacobs, B., & Scheibel, A. B. (1993). A quantitative dendritic analysis of Wernicke’s area in
humans: I. Lifespan changes. Journal of Comparative Neurology, 327, 83–96.
Kaas, J. (2000). The reorganization of sensory and motor maps after injury in adult mammals. In
M. S. Gazzaniga (Ed.), The cognitive neurosciences (pp. 223–236). Cambridge, MA: MIT
Press.
Kempermann, G., Kuhn, H. G., & Gage, F. H. (1998). Experience-induced neurogenesis in the
senescent dentate gyrus. Journal of Neuroscience, 18, 3206–3212.
Kolb, B., Cote, S., Ribeiro-da-Silva, A., & Cuello, A. C. (1997). Nerve growth factor treatment
prevents dendritic atrophy and promotes recovery of function after cortical injury.
Neuroscience, 76, 1146.
Kolb, B., & Gibb, R. (2014). Searching for principles of brain plasticity and behavior. Cortex, 58,
251–260.
Kolb, B., Gibb, R., & Gorny, G. (2003). Experience-dependent changes in dendritic arbor and
spine density in neocortex vary with age and sex. Neurobiology of Learning and Memory, 79,
1–10.
Kolb, B., Gorny, G., Cote, S., Ribeiro-da-Silva, A., & Cuello, A. C. (1997). Nerve growth factor
stimulates growth of cortical pyramidal neurons in young adult rats. Brain Research, 751,
289–294.
Kolb, B., Gorny, G., Li, Y., Samaha, A. N., & Robinson, T. E. (2003). Amphetamine or cocaine
limits the ability of later experience to promote structural plasticity in the neocortex and
nucleus accumbens. Proceedings of the National Academy of Science United States of
America, 100, 10523–10528.
Kolb, B., Morshead, C., Gonzalez, C., Kim, N., Shingo, T., & Weiss, S. (2007). Growth factor–
stimulated generation of new cortical tissue and functional recovery after stroke damage to the
motor cortex of rats. Journal of Cerebral Blood Flow and Metabolism, 27, 983–397.
Lashley, K. S. (1960). In search of the engram. Symposium No. 4 of the Society of Experimental
Biology. In F. A. Beach, D. O. Hebb, C. T. Morgan, & H. T. Nissen (Eds.), The
neuropsychology of Lashley (pp. 478–505). New York: McGraw-Hill. (Reprinted from R.
Sutton (Ed.), Physiological mechanisms of animal behavior, pp. 454–482, 1951. Cambridge:
Cambridge University Press.)
LeDoux, J. E. (1995). In search of an emotional system in the brain: Leaping from fear to
emotion and consciousness. In M. S. Gazzaniga (Ed.), The cognitive neurosciences (pp. 1047–
1061). Cambridge, MA: MIT Press.
Lepage, M., McIntosh, A. R., & Tulving, E. (2001). Transperceptual encoding and retrieval
process in memory: A PET study of visual and haptic objects. Neuroimage, 14, 572–584.
LePort, A. K., Mattfeld, A. T., Dickinson-Anson, H., Falon, J. H., Stark, C. E., Kruggle, F., et al.
(2012). Behavioral and neuroanatomical investigation of Highly Superior Autobiographical
Memory (HSAM). Neurobiology of Learning and Memory, 98, 78–92.
Loftus, E. F. (1997). Creating false memories. Scientific American, 277 (3), 70–75.
MacDougall, M., & Fine, A. (2014). The expression of long-term potentiation: reconciling the
preists and the postivists. Philosophic Transactions of the Royal Society B Biological Science,
269, 20130135. doi: 10.1098/rstb.
Maguire, E. A., Gadian, D. G., Johnsrude, I. S., Good, C. D., Ashburner, J., Frackowiak, R. S., et
al. (2000). Navigation-related structural change in the hippocampi of taxi drivers. Proceedings
 of the National Academy of Sciences United States of America, 97, 4398–4403.
Mahncke, H. W., Bronstone, A., & Merzenich, M. M. (2006). Brain plasticity and functional
losses in the aged: Scientific bases for a novel intervention. Progress in Brain Research, 157,
81–109.
Markowitsch, H. J., & Staniloiu, A. (2013). The impairment of recollection in functional amnesic
states. Cortex, 49, 1494–1510.
Markowitsch, H. J. (2003). Psychogenic amnesia. Neuroimage, 20 (Suppl. 1), S132–S138.
Martin, A., Haxby, J. V., Lalonde, F. M., Wiggs, C. L., & Ungerleider, L. G. (1995). Discrete
cortical regions associated with knowledge of color and knowledge of action. Science, 270,
102–105.
Martin, P. R. (1985). Cover, Alcohol Health & Research World, 9 (Spring 1985).
McGaugh, J. (2004). The amygdala modulates the consolidation of memories of emotionally
arousing experiences. Annual Review of Neuroscience, 27, 1–28.
McKenzie, S., & Eichenbaum, H. (2011). Consolidation and reconsolidation: Two lives of
memories? Neuron, 71, 224–233.
Meloni, E. G., Gillis, T. E., Manoukian, J., & Kaufman, M. J. (2014). Xenon impairs
reconsolidation of fear memories in a rat model of post-traumatic stress disorder (PTSD).
PLoS ONE, 9(8): e106189. doi:10.1371/journal.pone.0106189.
Miller, C. A., Gavin, C. F., White, J. A., Parrish, R. R., Honasoge, A., Yancey, C. R., et al.
(2010). Cortical DNA methylation maintains remote memory. Nature Neuroscience, 13, 664–
666.
Milner, B., Corkin, S., & Teuber, H. (1968). Further analysis of the hippocampal amnesic
syndrome: 14-year follow-up study of HM. Neuropsychologia, 6, 215–234.
Mishkin, M. (1982). A memory system in the brain. Philosophical Transactions of the Royal
Society of London, Biological Sciences, 298, 83–95.
Mishkin, M., Suzuki, W. A., Gadian, D. G., & Vargha-Khadem, F. (1997). Hierarchical
organization of cognitive memory. Philosophical Transactions of the Royal Society of London,
Biological Sciences, 352, 1461–1467.
Murray, E. (2000). Memory for objects in nonhuman primates. In M. S. Gazzaniga (Ed.), The
new cognitive neurosciences (pp. 753–763). Cambridge, MA: MIT Press.
Mychasiuk, R., Muhammad, A., Ilnystskyy, S., & Kolb, B. (2013). Persistent gene expression
changes in NAc, mPFC, and OFC associated with previous nicotine or amphetamine
exposure. Behavioural Brain Research, 256, 655–661.
Mychasiuk, R., Muhammad, A., Ilnystskyy, S., Kovalchuk, O., & Kolb, B. (2015). Persistent
gene expression changes in mPFC, OFC, and hippocampus associated with adult stress.
Manuscript in submission.
Nudo, R. J., Plautz, E. J., & Milliken, G. W. (1997). Adaptive plasticity in primate motor cortex
as a consequence of behavioral experience and neuronal injury. Seminars in Neuroscience, 9,
13–23.
O’Keefe, J. (2006). Hippocampal neurophysiology in the behaving animal. In P. Andersen, R.
Morris, D. Amaral, T. Bliss, & J. O’Keefe (Eds.), The Hippocampus Book (pp. 475–548).
New York: Oxford University Press.
O’Keefe, J., & Nadel, L. (1978). The hippocampus as a spatial map. New York: Oxford
University Press.
Patihis, L., Frenda, S. J., LePort, A. K. R., Petersen, N., Nichols, R. M., Stark, C. E. L., et al.
(2013). False memories in highly superior autobiographical memory individuals. Proceedings
 of the National Academy of Sciences United States of America, 110, 20947–20952.
Purves, D., & Voyvodic, J. T. (1987). Imaging mammalian nerve cells and their connections over
time in living animals. Trends in Neurosciences, 10, 398–404.
Ragert, P., Schmidt, A., Altenmuller, E., & Dinse, H. R. (2003). Superior tactile performance and
learning in professional pianists: Evidence for meta-plasticity in musicians. European Journal
of Neuroscience, 19, 473–478.
Ramachandran, V. S. (1993). Behavioral and magnetoencephalographic correlates of plasticity in
the adult human brain. Proceedings of the National Academy of Sciences United States of
America, 90, 10413–10420.
Ramón y Cajal, S. (1928). Degeneration and regeneration of the nervous system. London:
Oxford University Press.
Reynolds, B., & Weiss, S. (1992). Generation of neurons and astrocytes from isolated cells of the
adult mammalian central nervous system. Science, 255, 1707–1710.
Robinson, T. E., & Kolb, B. (1997). Persistent structural adaptations in nucleus accumbens and
prefrontal cortex neurons produced by prior experience with amphetamine. Journal of
Neuroscience, 17, 8491–8498.
Robinson, T. E., & Kolb, B. (2004). Structural plasticity associated with drugs of abuse.
Neuropharmacology, 47 (Suppl. 1), 33–46.
Sainsbury, R. S., & Coristine, M. (1986). Affective discrimination in moderately to severely
demented patients. Canadian Journal on Aging, 5, 99–104.
Sapolsky, R. M. (1992). Stress, the aging brain, and the mechanisms of neuron death.
Cambridge, MA: MIT Press.
Schacter, D. L. (1983). Amnesia observed: Remembering and forgetting in a natural
environment. Journal of Abnormal Psychology, 92, 236–242.
Sherry, D. F., Jacobs, L. F., & Gaulin, S. J. C. (1992). Spatial memory and adaptive specialization
of the hippocampus. Trends in Neuroscience, 15, 298–303.
Sirevaag, A. M., & Greenough, W. T. (1987). Differential rearing effects on rat visual cortex
synapses: III. Neuronal and glial nuclei, boutons, dendrites, and capillaries. Brain Research,
424, 320–332.
Sirevaag, A. M., & Greenough, W. T. (1988). A multivariate statistical summary of synaptic
plasticity measures in rats exposed to complex, social and individual environments. Brain
Research, 441, 386–392.
Skinner, B. F. (1938). The behavior of organisms. New York: Appleton-Century-Crofts.
Squire, L. R., Genzel, L., Wixted, J. T., & Morris, R. G. (2015). Memory consolidation. Cold
Spring Harbor Perspectives in Biology, 7. pii: a021766. doi: 10.1101/cshperspect.a021766
Stewart, J., & Kolb, B. (1994). Dendritic branching in cortical pyramidal cells in response to
ovariectomy in adult female rats: Suppression by neonatal exposure to testosterone. Brain
Research, 654, 149–154.
Sutherland, R. J., Sparks, F. T., & Lehmann, H. (2010). Hippocampus and retrograde amnesia in
the rat model: A modest proposal for the situation of systems consolidation.
Neuropsychologia, 48, 2357–2369.
Temple, E., Deutsch, G. K., Poldrack, R. A., Miller, S. L., Tallal, P., Merzenich, M. M., et al.
(2003). Neural deficits in children with dyslexia ameliorated by behavioral remediation:
Evidence from functional MRI. Proceedings of the National Academy of Sciences United
States of America, 100, 2860–2865.
Thorndike, E. L. (1898). Animal intelligence: An experimental study of the associative processes
in animals. Psychological Review Monograph Supplements, 2, 1–109.
Tulving, E. (2002). Episodic memory: From mind to brain. Annual Review of Psychology, 53, 1–
25.
Turner, A., & Greenough, W. T. (1985). Differential rearing effects on rat visual cortex synapses:
I. Synaptic and neuronal density and synapses per neuron. Brain Research, 329, 195–203.
Walker, L. C., & Jucker, M. (2015). Neurodegenerative diseases: Expanding the prion concept.
Annual Review of Neuroscience, 38, 87–103.
Wise, R. A. (2004). Dopamine, learning and motivation. Nature Neuroscience Reviews, 5, 483–
494.
Wisniewski, T., & Goni, F. (2015). Immunotherapeutic approaches for Alzheimer’s disease.
Neuron, 85, 1162–1176.
Woollett, K., & Maguire, E. A. (2011). Acquiring “the Knowledge” of London’s layout drives
structural brain changes. Current Biology, 21, 2109–2014.
Woolley, C. S., Gould, E., Frankfurt, M., & McEwen, B. S. (1990). Naturally occurring
fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. Journal of
Neuroscience, 10, 4035–4039.
CHAPTER 15
Adolphs, R., Gosselin, F., Buchanan, T. W., Tranel, D., Schyns, P., & Damasio, A. R. (2005). A
mechanism for impaired fear recognition after amygdala damage. Nature, 433, 68–72.
Baumann, O., Borra, B. J., Bower, J. M., Cullen, K. E., Habas, C., Ivry, R. B., et al. (2015)
Consensus paper: The role of the cerebellum in perceptual processes. Cerebellum, 14, 197–
220.
Barton, R. A. (2012). Embodied cognitive evolution and the cerebellum. Philosophical
Transactions of the Royal Society B, 367, 2097–2107.
Boria, S., Fabbri-Destro, M., Cattaneo, L., Sparaci, L., Sinigaglia, C., Santelli, E., et al. (2009).
Intention understanding in autism. PLoS ONE, 4, e5596.
Calvin, W. H. (1996). How brains think. New York: Basic Books.
Carr, L., Iacoboni, M., Dubeau, M. C., Mazziotta, J. C., & Lenzi, G. L. (2003). Neural
mechanisms of empathy in humans: A relay from neural systems for imitation to limbic areas.
Proceedings of the National Academy of Sciences United States of America, 100, 5497–5502.
Castiello, U., Paulignan, Y., & Jeannerod, M. (1991). Temporal dissociation of motor responses
and subjective awareness. Brain, 114, 2639–2655.
Chalmers, D. J. (1995). The conscious mind: In search of a fundamental theory. Oxford: Oxford
University Press.
Crick, F., & Koch, C. (1998). Consciousness and neuroscience. Cerebral Cortex, 8, 97–107.
Csibra, G. (2007). Action mirroring and action understanding: An alternative account. In P.
Haggard, Y. Rosetti, & M. Kawato (Eds). Sensorimotor foundations of higher cognition:
Attention and Performance XII (pp. 453–459). Oxford: Oxford University Press.
Cytowic, R. E. (1998). The man who tasted shapes. Cambridge, MA: MIT Press.
Diamond, M. C., Scheibel, A. B., Murphy, G. M., Jr., & Harvey, T. (1985). On the brain of a
scientist: Albert Einstein. Experimental Neurology, 88, 198–204.
Duncan, J., Seitz, R. J., Kolodny, J., Bor, D., Herzog, H., Ahmed, A., Newell, F. N., & Emslie, H.
(2000). A neural basis for general intelligence. Science, 289, 457–459.
Gardner, H. (1983). Frames of mind. New York: Basic Books.
Gaulin, S. J. (1992). Evolution of sex differences in spatial ability. Yearbook of Physical
Anthropology, 35, 125–131.
Gazzaniga, M. S. (1970). The bisected brain. New York: Appleton-Century-Crofts.
Gazzaniga, M. S. (1992). Nature’s mind. New York: Basic Books.
Gazzaniga, M. S., Ivry, R. B., & Mangun, G. R. (1999). Cognitive science: The biology of the
mind. New York: Norton.
Ghanzanfar, A. A., & Schroeder, C. E. (2006). Is neocortex essentially multisensory? Trends in
Cognitive Science, 10, 278–285.
Goldstein, J. M., Seidman, J. L., Horton, N. J., Makris, N., Kennedy, D. N., et al. (2001). Normal
sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging.
Cerebral Cortex, 11, 490–497.
Gray, J. R., & Thompson, P. M. (2004). Neurobiology of intelligence: Science and ethics. Nature
Reviews Neuroscience, 5, 471–482.
Guilford, J. P. (1967). The nature of human intelligence. New York: McGraw-Hill.
Hebb, D. O. (1949). The Organization of Behavior. New York: McGraw-Hill.
Hebb, D. O. (1980). Essay on mind. Hillsdale, NJ: Lawrence Erlbaum.
Hickok, G. (2013). Do mirror neurons subserve action understanding? Neuroscience Letters, 540,
56–58.
Hickok, G. (2014). The myth of motor neurons. New York: Norton.
Hubbard, E. W. (2007). Neurophysiology of synesthesia. Current Psychiatry Reports, 9, 193–
199.
Iacoboni, M., & Dapretto, M. (2006). The mirror neuron system and the consequences of its
dysfunction. Nature Neuroscience Reviews, 7, 942–951.
Ingalhalikar, M., Smith, A., Parker, D., Satterthwaite, P. D., Elliott, M. A., Ruparel, K., et al.
(2013). Sex differences in the structural connectome of the human brain. Proceedings of the
National Academy of Sciences United States of America, 111, 823–828.
James, W. (1890). Principles of psychology. New York: Henry Holt.
Kelly, C., Biswal, B. B., Craddock, R. C., Castellanos, F. X., & Milham, M. P. (2012).
Characterizing variation in the functional connectome: Promise and pitfalls. Trends in
Cognitive Science, 16, 181–188.
Kimura, D. (1967). Functional asymmetry of the brain in dichotic listening. Cortex, 3, 163–178.
Kimura, D. (1973). The asymmetry of the human brain. Scientific American, 228 (3), 70–78.
Kimura, D. (1999). Sex and cognition. Cambridge, MA: MIT Press.
Kolb, B., & Stewart, J. (1991). Sex-related differences in dendritic branching of cells in the
prefrontal cortex of rats. Journal of Neuroendocrinology, 3, 95–99.
Kranz, G. S., Hahn, A., Kaufmann, U., Kublbock, M., Hummer, A., Ganger S., et al. (2014).
White matter microstructure in transsexuals and controls investigated by diffusion tensor
imaging. Journal of Neuroscience, 34, 15466–15474.
Langer, N., Pedroni, A., Gianotti, L. R., Hanggi, J., Knoch D., & Jancke, L. (2009). Functional
brain network efficiency predicts intelligence. Human Brain Mapping, 4, 299–307.
Lieberman, M. D. (2007). Social cognitive neuroscience: A review of core processes. Annual
Review of Psychology, 58, 259–289.
Lieberman, M. D., Berkman, E. T., & Wager, T. D. (2012). Correlations in social neuroscience
aren’t voodoo. Perspectives on Psychological Science, 33, 1393–1406.
Loui, P., Li, H. C., Hohmann, A., & Schlaug, G. (2011). Enhanced cortical connectivity in
absolute pitch musicians: A model for local hyperconnectivity. Journal of Cognitive
Neuroscience, 23, 1015–1026.
McClure, S. M., Li, J., Tomlin, D., Cypert, K. S., Montague, L. M., & Montague, P. R. (2004).
Neural correlates of behavioral preferences for culturally familiar drinks. Neuron, 44, 379–
387.
Mlodinow, L. (2009). The drunkard’s walk: How randomness rules our lives. New York: Vintage
Books.
Moran, J., & Desimone, R. (1985). Selective attention gates visual processing in the extrastriate
cortex. Science, 229, 782–784.
Mukerjee, M. (1996). Interview with a parrot [field note]. Scientific American, 274 (4), 24.
Newsome, W. T., Shadlen, M. N., Zohary, E., Britten, K. H., & Movshon, J. A. (1995). Visual
motion: Linking neuronal activity to psychophysical performance. In M. Gazzaniga (Ed.), The
cognitive neurosciences (pp. 401–414). Cambridge, MA: MIT Press.
Olulade, O. A., Jamal, N. I., Koo, D. S., Perfetti, C. A., LaSasso, C., & Eden, G. F. (2015).
Neuroanatomical evidence in support of the bilingual advantage theory. Cerebral Cortex, Jul
 16. pii: bhv152. [Epub ahead of print.]
Pepperberg, I. M. (1990). Some cognitive capacities of an African grey parrot ( Psittacus
erithacus ). In P. J. B. Slater, J. S. Rosenblatt, & C. Beer (Eds.), Advances in the study of
behavior (Vol. 19, pp. 357–409). New York: Academic Press.
Pepperberg, I. M. (1999). The Alex studies. Cambridge, MA: Harvard University Press.
Pepperberg, I. M. (2006). Ordinality and inferential ability of a grey parrot ( Psittacus erithacus )
. Journal of Comparative Psychology, 120, 205–216.
Ramachandran, V. S., & Oberman, L. M. (2006). Broken mirrors: A theory of autism. Scientific
American, 295, 62–69.
Rameson, L. T., Morellis, S. A., & Lieberman, M. D. (2012). The neural correlates of empathy:
Experience, automaticity, and prosocial behavior. Journal of Cognitive Neuroscience, 24,
235–245.
Rasmussen, T., & Milner, B. (1977). The role of early left brain injury in determining
lateralization of cerebral speech functions. Annals of the New York Academy of Sciences, 299,
355–369.
Rizzolatti, G. (2007). Mirrors on the mind. New York: Oxford University Press.
Rizzolatti, G., & Craighero, L. (2004). The mirror-neuron system. Annual Review of
Neuroscience, 27, 169–192.
Rizzolatti, G., & Fabbri-Destro, M. (2010). Mirror neurons: From discovery to autism.
Experimental Brain Research, 200, 223–237.
Sacks, O. (1989). Seeing voices. Los Angeles: University of California Press.
Sala-Llonch, R., Bartres-Faz, D., & Junque, C. (2015). Reorganization of brain networks in
aging: A review of functional connectivity studies. Frontiers in Psychology. doi:
10.3389/fpsyg.2015.00663.
Sawamoto, N., Honda, M., Okada, T., Hanakawa, T., Kanda, M., et al. (2000). Expectation of
pain enhances responses to nonpainful somatosensory stimulation in the anterior cingulate
cortex and parietal operculum/posterior insula: An event-related functional magnetic
resonance imaging study. Journal of Neuroscience, 20, 7438–7445.
Sperry, R. (1968). Mental unity following surgical disconnection of the cerebral hemispheres.
Harvey Lectures, 62, 293–323.
Stein, B. E., & Rowland, B. A. (2011). Organization and plasticity in multisensory integration:
Early and late experience affects its governing principles. Progress in Brain Research, 191,
145–163.
Stewart, J., & Kolb, B. (1994). Dendritic branching in cortical pyramidal cells in response to
ovariectomy in adult female rats: Suppression by neonatal exposure to testosterone. Brain
Research, 654, 149–154.
Takeuchi, H., Sugiura, M., Sassa, Y., Sekiguchi, A., Yomogida, Y., et al. (2012). Neural correlates
of the differences between working memory speed and simple sensorimotor speed: An fMRI
study. PLoS One, 7, e30579.
Vul, E., Harris, C., Winkielman, P., & Pashler, H. (2009). Puzzlingly high correlations in f MRI
studies of emotion, personality, and social cognition. Perspectives on Psychological Science,
4, 274–290.
Vul, E., & Pashler, H. (2012). Voodoo and circularity errors. Neuroimage, 62, 945–948.
Wada, J., & Rasmussen, T. (1960). Intracarotid injection of sodium amytal for the lateralization
of cerebral speech dominance: Experimental and clinical observations. Journal of
Neurosurgery, 17, 266–282.
Witelson, S. F., & Goldsmith, C. H. (1991). The relationship of hand preference to anatomy of
the corpus callosum in men. Brain Research, 545, 175–182.
Witelson, S. F., Kigar, D. L., & Harvey, T. (1999). The exceptional brain of Albert Einstein.
Lancet, 353, 2149–2153.
Yeo, B. T. T., Fienen, F. M., Sepulcre, J., Sabuncu, M. R., Lashkari, D., Hollinshead, M., et al.
(2011). The organization of the human cerebral cortex estimated by intrinsic functional
connectivity. Journal of Neurophysiology, 106, 1125–1165.
CHAPTER 16
American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental
Disorders (5th ed.). Washington, DC: American Psychiatric Association.
Arnold, S. E., Rushinsky, D. D., & Han, L. Y. (1997). Further evidence of abnormal
cytoarchitecture in the entorhinal cortex in schizophrenia using spatial point analyses.
Biological Psychiatry, 142, 639–647.
Asante, E. A., Smidak, M., Grimshaw, A., Houghton R., Tomlinson A., Jeelani, A., et al. (2015).
A naturally occurring variant of the human prion protein completely prevents prion disease.
Nature, 522(7557), 478–481.
Birbaumer, N., Ruiz, S., & Sitaram, R. (2013). Learned regulation of brain metabolism. Trends in
Cognitive Science, 17, 295–302.
Block, C., West, S., & Goldin, Y. (2015). Misconceptions and misattributions about traumatic
brain injury: An integrated conceptual framework. PM&R, S1934-1482(15)00279-8.
Calne, D. B., & Mizuno, Y. (2004). The neuromythology of Parkinson’s disease. Parkinsonism
and Related Disorders, 10, 319–322.
Charney, D. S., Nestler, E. J., & Bunney, B. S. (Eds.). (1999). The Neurobiology of Mental
Illness. New York: Oxford University Press.
Cho, R. Y., Gilbert, H., & Lewis, D. A. (2004). The neurobiology of schizophrenia. In D. S.
Charney & F. J. Nestler (Eds.), The Neurobiology of Mental Illnes s (2nd ed., pp. 299–310).
New York: Oxford University Press.
Claes, S., Tang, Y. L., Gillespie, C. F., & Cubells, J. F. (2012). Human genetics of schizophrenia.
Handbook of Clinical Neurology, 106, 37–52.
Cleary, D. R., Ozpinar, A., Raslan, A. M., & Ko, A. L. (2015). e Neurosurgical Focus, 38, E2.
Corrigan, N. M., Richards, T. L., Treffert, D. A., & Dager, S. R. (2012). Toward a better
understanding of the savant brain. Comprehensive Psychiatry, 53, 706–717.
Costa, V., Lugert, S., & Jagasia, R. (2015). Role of adult hippocampal neurogenesis in cognition
in physiology and disease: Pharmacological targets and biomarkers. Handbook of
Experimental Pharmacology, 228, 99–155.
Costanzo, M. E., Chou, Y. Y., Leaman, S., Pham, D. L., Keyser, D., Nathan, D. E., et al. (2014).
Connecting combat-related mild traumatic brain injury with posttraumatic stress disorder
symptoms through brain imaging. Neuroscience Letters, 577, 11–15.
deCharms, R. C. (2008). Applications of real-time fMRI. Nature Reviews Neuroscience, 9, 720–
729.
Drevets, W. C., Kishore, M. G., & Krishman, K. R. R. (2004). Neuroimaging studies of mood
disorders. In D. S. Charney & E. J. Nestler (Eds.), The Neurobiology of Mental Illness (2nd
ed., pp. 461–490). New York: Oxford University Press.
Duman, R. S. (2004). The neurochemistry of depressive disorders. In D. S. Charney & E. J.
Nestler (Eds.), The Neurobiology of Mental Illness (2nd ed., pp. 421–439). New York: Oxford
University Press.
Fereshtehnejad, S. M., Romenets, S. R., Anang, J. B., Latreille, V., Gagnon, J. F., & Postuma, R.
B. (2015). New clinical subtypes of Parkinson disease and their longitudinal progression: A
prospective cohort comparison with other phenotypes. JAMA Neurology, 72 (8), 863–873.
Foroozani, H., Abiri, M., Salehpour, S., Bagherian, H., Sharifi, Z., Alaei, M. R., et al. (2015).
Molecular characterization of QDPR gene in Iranian families with BH4 deficiency: Reporting
novel and recurrent mutations. JIMD Reports, 21, 123–128.
François, C., Grau-Sánchez, J., Duarte, E., & Rodriguez-Fornells, A. (2015). Musical training as
an alternative and effective method for neuro-education and neurorehabilitation. Frontiers in
Psychology, 6, 475–485.
Gebicke-Haerter, P. J. (2012). Epigenetics of schizophrenia. Pharmacopsychiatry, 45, Suppl. 1,
S42–S48.
Giles J. (2004). Neuroscience: Change of mind. Nature, 430, 14.
Gogtay, N., Lu, A., Leow, A. D., Klunder, A. D., Lee, A. D., Chavez, A., et al. (2008). Three-
dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using
tensor-based morphometry. Proceedings of the National Academy of Sciences U S A, 105,
15979–15984.
Gonçalves, R., Pedrozo, A.L., Coutinho, E.S., Figueira, I., & Ventura, P. (2012). Efficacy of
virtual reality exposure therapy in the treatment of PTSD: A systematic review. PLoS One, 7
(12), e48469.
Gross, C., & Hen, R. (2004). The developmental origins of anxiety. Nature Reviews
Neuroscience, 5, 545–552.
Gubbi, J., Kusmakar, S., Rao, A., Yan, B., O’Brien, T., & Palaniswami, M. (2015). Automatic
detection and classification of convulsive psychogenic non-epileptic seizures using a wearable
device. IEEE Journal of Biomedical and Health Information. [Epub ahead of print.]
Heinz, A., Kipke, R., Heimann, H., & Wiesing, U. (2012). Cognitive neuroenhancement: False
assumptions in the ethical debate. Journal of Medical Ethics, 38, 372–375.
Heninger, G. R. (1999). Special challenges in the investigation of the neurobiology of mental
illness. In D. S. Charney, E. J. Nestler, & B. S. Bunney (Eds.), The Neurobiology of Mental
Illness (pp. 89–98). New York: Oxford University Press.
Holmstrom, L. L., & Burgess, A. W. The victim of rape: Institutional reactions. Wiley-
Interscience, 1978.
Jorge, R. E. (2015). Posttraumatic stress disorder. Behavioral Neurology and Neuropsychiatry,
21, 789–805.
Kaufer, D. I., & DeKosky, S. T. (1999). Diagnostic classifications: Relationship to the
neurobiology of dementia. In D. S. Charney, E. J. Nestler, & B. S. Bunney (Eds.), The
Neurobiology of Mental Illness (p. 642). New York: Oxford University Press.
Khachaturian, Z. S., & Khachaturian, A. S. (2015, June 5). Politics of science: Progress toward
prevention of the dementia-Alzheimer’s syndrome (review). Molecular Aspects of Medicine,
43-44, 3-15.
Knight, E. J., Testini, P., Min, H. K., Gibson, W. S., Gorny, K. R., Favazza, C. P., et al. (2015).
Motor and nonmotor circuitry activation induced by subthalamic nucleus deep brain
stimulation in patients with Parkinson disease: Intraoperative functional magnetic resonance
imaging for deep brain stimulation. Mayo Clinic Proceedings, 90, 773–785.
Kong, L., Herold, C., Stieltjes, B., Essig, M., Seidl, U., et al. (2012). Reduced gray to white
matter tissue intensity contrast in schizophrenia. PLoS One, 7, e37016.
Kornek, B. (2015). An update on the use of natalizumab in the treatment of multiple sclerosis:
Appropriate patient selection and special considerations. Patient Preference and Adherence, 9,
675–684.
Kumar, J., Namsechi, R., & Sim, V. L. (2015). Structure-based peptide design to modulate
amyloid beta aggregation and reduce cytotoxicity. PLoS One, 12 ;10(6).
Kuo, H.-K., Jones, R. N., Milberg, W. P., Tennstedt, S., Talbot, L., et al. (2005). Effect of blood
pressure and diabetes mellitus on cognitive and physical functions in older adults: A
 longitudinal analysis of the advanced cognitive training for independent and vital elderly
cohort. Journal of the American Geriatrics Society, 53, 1154–1161.
Kwakkel, G., Veerbeek, J. M., van Wegen, E. E., & Wolf, S. L. (2015). Constraint-induced
movement therapy after stroke. Lancet Neurology, 14, 224–234.
Laver, K. E., George, S., Thomas, S., Deutsch, J. E., & Crotty, M. (2015). Virtual reality for
stroke rehabilitation. Cochrane Database Systems Review, Sep 7;(9):CD008349.
Leritz, E. C., Salat, D. H., Williams, V. J., Schnyer, D. M., Rudolph, J. L., et al. (2011).
Thickness of the human cerebral cortex is associated with metrics of cerebrovascular health in
a normative sample of community dwelling older adults. Neuroimage, 54, 2659–2671.
Malberg, J. E., Eisch, A. J., Nestler, E. J., & Duman, R. S. (2000). Chronic antidepressant
treatment increases neurogenesis in adult rat hippocampus. Journal of Neuroscience, 20,
9104–9110.
Martin, J. P. (1967). The basal ganglia and posture. London: Ritman Medical.
Mateer, C. A., & Sira, C. S. (2006). Cognitive and emotional consequences of TBI: Intervention
strategies for vocational rehabilitation. NeuroRehabilitation, 21, 315–326.
McGowan, P. O., & Szyf, M. (2010). Environmental epigenomics: Understanding the effects of
parental care on the epigenome. Essays in Biochemistry, 48, 275–287.
Miller, B. L., Boone, K., Cummings, J. L., Read, S. L., & Mishkin, F. (2000). Functional
correlates of musical and visual ability in frontotemporal dementia. British Journal of
Psychiatry, 176, 458–463.
National Institute of Mental Health Web site: http://www.nimh.nih.gov/health/publications/the-
numbers-count-mental-disorders-in-america/index.shtml
Nevler, N., Ash, E.L. (2015). TMS as a tool for examining cognitive processing. Current
Neurological and Neuroscience Reports, 15, 575.
Olanow, C. W., & Brundin, P. (2013). Parkinson’s disease and alpha synuclein: Is Parkinson’s
disease a prion-like disorder? Movement Disorders, 28, 31–40.
Ostergard, T., & Miller, J. P. (2014). Deep brain stimulation: New directions. Journal of
Neurosurgical Science, 58, 191–198.
Pannese, R., Minichino, A., Pignatelli, M., Delle Chiaie, R., Biondi, M., & Nicoletti, F. (2012).
Evidences on the key role of the metabotropic glutamatergic receptors in the pathogenesis of
schizophrenia: A “breakthrough” in pharmacological treatment. Reviews in Psychiatry, 47,
149–169.
Politis, M., & Lindvall, O. (2012). Clinical application of stem cell therapy in Parkinson’s
disease. BMC Medicine, 10, 1.
Rao, J., Chiappelli, J., Kochunov, P., Regenold, W. T., Rapoport, S. I., & Hong, L. E. (2015). Is
schizophrenia a neurodegenerative disease? Evidence from age-related decline of brain-
derived neurotrophic factor in the brains of schizophrenia patients and matched nonpsychiatric
controls. Neurodegenerative Diseases, 15, 38–44.
Rapoport, J. L., Giedd, J. N., & Gogtay, N. (2012). Neurodevelopmental model of schizophrenia:
Update 2012. Molecular Psychiatry, 17, 1228–1238.
Reis, C., Wang, Y., Akyol, O., Ho, W. M., Ii, R. A., Stier, G., et al. (2015). What’s new in
traumatic brain injury: Update on tracking, monitoring and treatment. International Journal of
Molecular Science, 16, 11903–11965.
Rizzo, A., Buckwalter, J. G., John, B., Newman, B., Parsons, T., Kenny, P., et al. (2012).
STRIVE: Stress Resilience in Virtual Environments: A pre-deployment VR system for
 training emotional coping skills and assessing chronic and acute stress responses. Studies in
Health and Technology Information, 173, 379–385.
Rose, S. C., Weber, K. D., Collen, J. B., & Heyer, G. L. (2015). The diagnosis and management
of concussion in children and adolescents. Pediatric Neurology, 53, 108–118.
Sacks, O. (1998). The man who mistook his wife for a hat: And other clinical tales. New York:
Touchstone.
Santarelli, L., Saxe, M., Gross, C., Surget, A., Battaglia, F., et al. (2003). Requirement of
hippocampal neurogenesis for the behavioral effects of antidepressants. Science, 301, 805–
809.
Savitz, S. I. (2015). Developing cellular therapies for stroke. Stroke, 46, 2026–2031.
Serafini, G., Pompili, M., Belvederi, M. M., Respino, M., Ghio, L., Girardi, P., et al. (2015). The
effects of repetitive transcranial magnetic stimulation on cognitive performance in treatment-
resistant depression. A systematic review. Neuropsychobiology, 71, 125–139.
Shi, Q., Chen, L. N., Zhang, B. Y., Xiao, K., Zhou, W., Chen, C., et al. (2015). Proteomics
analyses for the global proteins in the brain tissues of different human prion diseases.
Molecular Cell Proteomics, 14, 854–869.
Shin, J. H., Bog, G., Park, S., Ho, G., & Jang, S. (2015). Effects of game-based virtual reality on
health-related quality of life in chronic stroke patients: A randomized, controlled study.
Computational Biological Medicine, 63, 92–98.
Shorter, K. R., & Miller, B. H. (2015). Epigenetic mechanisms in schizophrenia. Progress in
Biophysics and Molecular Biology, 118, 1–7.
Sohlberg, M. M., & Mateer, C. (1989). Introduction to Cognitive Rehabilitation. New York:
Guilford.
Sundström, P., & Salzer, J. (2015). Vitamin D and multiple sclerosis: From epidemiology to
prevention. Acta Neurology Scandanavia Supplement, 132, 56–61.
Tsivgoulis, G., Faissner, S., Voumvourakis, K., Katsanos, A. H., Triantafyllou, N., Grigoriadis,
N., et al. (2015). “Liberation treatment” for chronic cerebrospinal venous insufficiency in
multiple sclerosis: The truth will set you free. Brain and Behavior, 5, 3–12.
Wang, J., Zhao, X., & He, M. (2012). Is BDNF a biological link between depression and type 2
diabetes mellitus? Medical Hypotheses, 79, 255–258.
Wassermann, E. M., & Zimmermann, T. (2012). Transcranial magnetic brain stimulation:
Therapeutic promises and scientific gaps. Pharmacology and Therapeutics, 133 (1), 9.
Wingenfeld, K., & Wolf, O. T. (2014). Stress, memory, and the hippocampus. Frontiers in
Neurological Neuroscience. 34, 109–120.
 NAME INDEX
Aagaard, L., 172
Abel, T., 467
Abiri, M., 565
Ackerly, Stafford, 420
Adelmann, Pamela, 424
Adinoff, B., 198
Adolphs, Ralph, 530
Aeschbach, D., 296 , 451 , 455
Aflalo, T. N., 367 , 368
Aftab, M., 236
Agate, Robert, 275
Ago, Y., 102
Aiello, L. C., 25
Akyol, O., 579
Alaei, M. R., 565
Albanese, Y., 472
Alborn, A. M., 503
Albrecht, J., 405
Aldridge, J. W., 362
Alessandria, M., 386
Allegri, F., 199
Altenmuller, E., 507
Alzheimer, Alois, 492
Amaral, D. G., 488
Amariei, C., 444
Ames, Elenor, 272
Anang, J. B., 567
Anda, Robert, 258
Andermann, M. L., 75
Angadi, V., 469
Antle, M. C., 219 , 450 , 451
Antón, S. C., 25
Appireddy, R. M. R., 45
Argyropoulos, S., 467
Aristotle, 7
Arnold, A. P., 350
Arnold, S. E., 593
Arnott, S. R., 336
Arora, V., 393
Asante, E. A., 591
Asanuma, Hiroshi, 391
Asarnow, J. R., 186
Aschoff, Jurgen, 445
Aserinsky, Eugene, 458
Ash, E. L., 573
Asperger, Hans, 255
Auburtin, Ernest, 211
Auger, A. P., 432 , 435
Babiloni, C., 434
Babinsky, R., 499
Bachevalier, Jocelyne, 264 , 274
Badiani, A., 180
Bagherian, H., 565
Bailey, C. H., 163 , 166
Balaban, E., 102
Balance, H. I., 444
Bale, T. L., 432 , 435
Bálint, R., 316
Ballard, A., 161
Ballestar, E., 237
Ballestar, M. L., 237
Banich, M. T., 394
Bano, S., 108
Bao, A. M., 435
Barantin, L., 206
Barbeau, A., 152
Barchha, N., 186
Barclay, J. L., 450
Barkovich, A. J., 277
Barnard, J., 404
Baron, J., 126
Barth, A. M., 100
Barth, C., 200
Bartholow, Roberts, 109 , 111
Barton, R. A., 52 , 536
Bartoshuk, Linda, 404
Bartres-Faz, D., 534
Bartsch, H., 246
Bastian, A. J., 378
Battaglia, F., 596
Batterink, L. J., 469
Baudry, M., 206
Bauman, O., 34 , 536
Beatty, J., 421
Becker, J. B., 178 , 179 , 194 , 435
Becquet, D., 443
Beery, Alexis, 74 , 96
Beery, Joe, 74
Beery, Noah, 74 , 96
Beery, Retta, 74
Beggs, A. H., 277
Bekmuradov, D., 183
Belleville, R. E., 177 , 178
Belliveau, J. W., 230
Belliveau, R. A., 277
Bello, L., 268
Belvederi, M. M., 573
Benchenane, K., 468
Bender, K. J., 128
Bendix, C., 444
Berens, A. E., 272
Berger, Hans, 210 , 223
Berglund, L., 448
Berman, M. G., 394
Bermudez, P., 347
Bernhardt, J., 45
Bernstein, Julius, 111
Berretin-Felix, G., 474
Berridge, Kent, 194 , 437 , 438
Berry, Chuck, 140
Berthold, A. A., 200 , 203
Bertram, R., 76
Bertrand, J. A., 467
Bewernick, B. H., 219
Bhalla, D., 108
Binkley, S., 446
Biondo, M., 594
Birbaumer, N., 576
Birkle, D. L., 271
Birklein, F., 386
Birkmayer, W., 152
Birn, R. M., 28
Biswal, B. B., 535
Bittman, E. L., 452
Bjork-Eriksson, T., 503
Bjorklund, A., 161
Blaise deB., Frederick, 439
Blakemore, Sarah, 392
Blasca, W. Q., 474
Bleich, S., 424
Blick, K. A., 462
Bliss, Timothy, 500
Block, C., 580
Blumberg, M. S., 461
Blumberg, S. J., 255
Bobbo, D., 469
Bock, J., 266
Bodner, M., 495
Boehner, John, 2
Boesveldt, S., 405
Bog, G., 576
Boldrey, E., 366
Bolte, E., 275
Bongard, F., 198
Boone, K., 598
Boonman, A., 351
Bor, D., 553
Bordyugov, G., 447
Born, J., 467
Borra, R. J., 34 , 536
Bosch, M., 167
Bosler, O., 443
Boswell, (Patient), 489 , 490
Bouhours, M., 131
Bourgeois, J. P., 257
Bourgin, J., 206
Bower, J. M., 34 , 536
Boyle, J. A., 404
Bradley, P., 270
Bramlett, M. D., 255
Braun, K., 266
Brauner, M., 131
Breeslin, P., 405
Bregman, Albert,
Bremner, J. D., 258
Brewer, J. A., 425
Brewer, J. M., 452
Brick, T. R., 476
Bricker, S., 198
Brinkman, C., 359
Brito, N. H., 246
Britten, K. H., 522
Broca, Paul, 211 , 217 , 342 , 416 , 417 , 539
Brodmann, Korbinian, 56 , 211 , 390
Bronstone, A., 513
Brouwer, R. M., 246
Brown, A. R., 219
Brundin, P., 161
Brunetti, M., 434
Buchanan, T. W., 530
Buckwalter, J. G., 562
Bucy, Paul, 422 , 423
Bueller, Joshua, 236
Bumrungsri, S., 351
Bundlie, S. R., 475
Bunney, B. G., 278
Bunney, William, 278
Buonocore, M. H., 255
Burdakov, D., 131
Burgess, Ann, 562
Burghy, C. A., 28
Burke, Chris, 101
Burmeister, M., 236
Busch, V., 386
Buss, David, 407
Butler, Robert, 400
Butte, P. V., 83
Büttner, A., 198
Byers-Heinlein, K., 210
Bygren, L. O., 105
Bygren, Lars Olov, 105
Byne, W., 594
Byron, Don, 326
Cacucci, F., 223
Cahill, L., 499
Cai, H., 221
Cain, Donald, 455
Cain, S. W., 451
Calne, Donald, 589 , 590
Calvin, William, 522
Campbell, Jeeves, 15
Campbell, Joan, 15
Campbell, Matthew, 15
Campisano, C. J., 21
Candia, Victor, 507
Cannon, J. L., 202
Cannon, M., 236
Cantle, J. P., 100
Cao, Y., 198
Cao, Z. F., 131
Cardinale, C. J., 452
Carey, J., 389
Carter, K. A., 464
Casano, A. M., 85
Caspi, A., 236
Castellanos, F. X., 363 , 535
Castiello, U., 557
Castro, J. B., 403
Caton, Richard, 111
Cermakian, N., 448
Chaichana, K. L., 232
Chalfie, Martin, 75
Chalmers, David, 557
Chand, P., 393
Chang, A. M., 455
Chang, D. W., 457
Chang, E., 386
Chang, Fen-Lei, 505
Changeux, Jean-Pierre, 257
Chapmans, P., 223
Charcot, Jean-Martin, 134 , 140
Charney, E., 98 , 104
Charvet, C. J., 26
Chau, S. A., 160
Chaudhary, V., 108
Cheetham, A., 199
Chen, C., 591
Chen, J. L., 75
Chen, L. N., 591
Chen, Y., 83
Cherubini, E., 130
Chesler, D. A., 230
Chiapelli, J., 570
Chiesa, R., 472
Cho, R. Y., 593
Chomsky, Noam, 341
Chou, Y. Y., 562
Chrétien, Jean, 63
Christine, J., 26
Chung, W. H., 389
Church, J. A., 374
Churchill, S. E., 21
Ciocchi, S., 221
Claes, S., 593
Clancy, B., 26
Clark, Graeme, 338
Clarke, G., 186
Clarke, R. S., 270
Clasen, L., 259 , 260
Clauss, J. A., 206
Claustrat, B., 454
Cleary, D. R., 572
Coenen, V. A., 219
Cohen, D., 406
Cohen, M., 407
Cole, A. G., 193
Cole, Jonathan, 382
Collen, K. D., 578
Collop, N. A., 448
Comeau, W., 276
Comer, R. J., 185
Constable, R. T., 425
Cook, E. P., 146
Cooper, B. Y., 392
Cooper, M., 403
Cooper-Kazaz, R., 190
Coristine, Marjorie, 499
Corkin, Suzanne, 392 , 488 , 489
Cormack, Allan, 226
Corrêa Cde, C., 474
Corrigan, N. M., 598
Cortelli, P., 386
Cortese, S., 363
Coslett, H. B., 287
Costa, V., 596
Costanzo, M. E., 562
Cote, S., 515
Cottier, J. P., 206
Cowan, R. L., 198
Cowan, W. M., 250
Craddock, R. C., 535
Craighero, L., 531
Crick, Francis, 556
Critchley, M., 394
Crits-Christoph, P., 186
Crombag, H. S., 180
Crotty, M., 581
Crotty, P., 125
Crutcher, M. D., 375
Csibra, G., 531
Cubells, J. F., 593
Cuello, A. C., 515
Cullen, K. E., 34 , 536
Cummings, J. L., 598
Cutlan, R., 299
Cytowic, Richard, 551
Czeisler, C. A., 455
Czoli, C. D., 193
Dager, S. R., 598
D’Alessio, A. C., 206
D’Almeida, V., 467
Daly, Martin, 407
Damanakis, E., 86
Damasio, A. R., 227 , 421 , 422 , 490
Damasio, H., 227
Danchin, A., 257
Daniel, E., 326
Dannemann, M., 22
Daou, A., 76
Darlington, R. B., 26
Daroff, R. B., 467
Darwin, Charles, 8 , 9 , 10 , 11 , 13 , 27 , 257 , 350 , 410
Davarpanah Jazi, S., 358
Davidson, A. C., 404
Davis, K. L., 594
Davis, M., 422 , 498
Day, B. L., 382
Day, J. J., 408 , 509
Daynes, Elisabeth, 22
de Jager, C. A., 185
de la Tourette, Gilles, 374
de Lavilléon, G., 468
de Mairan, Jean Jacques d’Ortous, 444
De Oliviera, G. S., Jr., 347
de Ruiter, D. J., 21
De Vries, G. J., 432 , 435
Debanne, D., 130
deCharms, R. C., 576
Deisseroth, K., 131
DeKosky, Steven, 585
Del Gratta, C., 434
Delle Chiaie, R., 594
Demchuk, A. M., 45
Dement, W. C., 458 , 459 , 461 , 465 , 474 , 475
Dere, E., 142
Descartes, René, 7 , 8 , 46 , 108 , 476
Desimone, Robert, 529
Desjardins, C., 467
Destrieux, C., 206
Dethier, Vincent, 409
Deutsch, G. K., 480
Deutsch, J. E., 581
Di Forti, M., 199
Dickinson-Anson, H., 487
DiMaggio, E. J., 21
Dinges, D. F., 452
Dinse, H. R., 507
Dirks, P. H., 21
Dissel, S., 469
Dobyns, W. B., 277
Doepp, F., 126
Domhoff, G. W., 462
Donlea, J., 469
Dosenbach, N. U., 374
Dostrovsky, J., 222
Dowling, J., 83
Drake-Lee, A. B., 325
Drazin, D., 83
Dressler, M., 476
Drevets, W. C., 596
Drnevich, J., 349
Droiuse, E. M., 271
Drucker, D. J., 450
Druet-Cabanac, M., 108
Drury, S. S., 272
Duarte, E., 576
Duerson, Dave, 578
Duffy, J. F., 455
Duffy, Valerie, 404
Duman, R. S., 596
Dunbar, Robin, 25
Duncan, J., 553
Duncan, J. S., 108
Dunn, G. A., 432 , 435
Durell, T. M., 186
Durston, S., 246
Dylan, Bob, 100
Dymoy, S., 206
Earnest, M., 299
Eccles, John C., 127 , 128
Eddy, C. M., 100
Eden, G. F., 555
Edey, M., 21
Edgerton, Robert, 192
Eesa, M., 45
Egan, J., 299
Ehrhardt, Anke, 432
Ehringer, H., 140
Eibl-Eibesfeldt, Irenäus, 5
Eichenbaum, H., 497
Einstein, Albert, 29 , 553
Eisenman, A. J., 177 , 178
Ekselius, L., 448
Elbert, T., 507
Ellington, Duke, 552
Elliott, A. S., 466
Elliott, M. A., 548 , 549
Emslie, G., 186
Enswere, E., 251
Epel, D., 36
Epstein, Herman, 264
Eriksson, P. S., 503
Essig, M., 593
Ettinger, M., 475
Evans, A. C., 246 , 345 , 347
Evarts, Edward, 368
Evenden, J. L., 179
Everitt, Barry, 195 , 434
Fair, D. A., 374
Faissner, S., 584
Falk, Dean, 26
Falon, J. H., 487
Farmer, Stacey, 439
Favazza, C. P., 572
Felitti, V. J., 258
Fenno, L., 131
Fereshtehnejad, S. M., 567
Fernald, R. D., 413
Ferraro, L., 199
Ferretti, A., 434
Fetherstonhaugh, M. L., 270
Feynman, Richard, 552
Field, M., 407
Field, Tiffany, 406
Fienen, F. M., 534
Filbey, F. M., 198
Filevich, E., 476
Fine, A., 502
Finegold, S. M., 275
Fink, Bob, 322
Fins, J. J., 13
Fiorito, Graziano, 49
Fisch, A. J., 596
Flagel, S. B., 196
Flechsig, Paul, 259 , 260
Flugge, G., 510
Flynn, J. R., 29
Fong, G. T., 191
Fonseca-Azevedo, Karina, 23 , 25
Forgays, D. G., 270
Forloni, G., 472
Foroozani, H., 565
Foster, F., 387
Foster, R. G., 451
Foulkes, D., 462
Fox, Michael J., 140 , 587
Fox, N. A., 272
Fraga, Mario, 237
Fraioli, Sabina, 180
Franc, J. L., 443
François, C., 576
François-Bellan, A. M., 443
Frankfurt, M., 434 , 509
Franklin, Benjamin, 456
Fraser, H. F., 177 , 178
Frederick, B. deB., 438
Frei, B., 185
Freud, Sigmund, 57 , 172 , 189 , 432 , 462 , 563 , 564 , 575
Frieling, H., 424
Friend, D. M., 375
Frith, C. D., 392 , 557
Fritsch, Gustav, 109 , 366
Fritz, J., 333
Frost, D., 258 , 276
Fuchs, E., 510
Fuchs, S., 468
Fuhrmann, R., 300
Fujikawa, H., 251
Fung, Teresa, 428
Fuster, Joaquin, 495
Gabrieli, J. D. E., 480
Gadian, W. A., 495 , 498
Gage, F. H., 504
Gagnon, J. F., 467 , 567
Gaini, S. M., 268
Galaburda, Albert, 253 , 480
Galvani, Luigi, 109
Gangwisch, J. E., 455
Gao, F., 100
Garcia, John, 409
Gardner, Alan, 9
Gardner, Beatrice, 9
Gardner, Howard, 29 , 553 , 554 , 555
Gardner, Randy, 466
Garga, U. C., 108
Garraghty, P. E., 393
Garrison, K. A., 425
Gaulin, S. J., 493 , 494 , 549
Gavin, C. F., 509
Gazarini, M. L., 467
Gazzaniga, Michael, 172 , 520 , 545 , 558
Gebicke-Haerter, P. J., 593
Gehrig, Lou, 134
Geissmann, Thomas, 322
Genzel, L., 497
George, S., 581
Gérard, François, 7
Gerhart-Hines, Z., 447
Gerkema, M. P., 456
Gerkin, R. C., 403
Gershon, E. S., 278
Gervain, J., 210
Geschwind, Norman, 315 , 480
Ghanzanfar, A. A., 527
Gharbawie, O., 220 , 390 , 506
Ghio, L., 573
Gianotti, L. R., 555
Gibb, Robbin, 258 , 266 , 270 , 276 , 505 , 511
Gibson, W. S., 572
Giedd, J. N., 275 , 570
Giedde, A., 345 , 347
Giffords, Gabrielle, 2
Gilbert, H., 593
Gilbert, S. F., 36
Giles, Jim, 597
Gill, J. M., 102
Gillespie, C. F., 593
Gillespie-Lynch, K., 9
Gillis, T. E., 498
Giorgi, E. E., 102
Girardet, C., 443
Giussani, Carlo, 268
Gleason, M. M., 272
Glendinning, D. S., 392
Glenmullen, J., 161
Glickman, Steve, 399
Godet, B., 108
Goebel, J. A., 389
Goel, N., 452
Gogtay, N., 260 , 570
Goldberg, I. E., 230
Goldin, Y., 580
Goldman-Rakic, P. S., 333
Goldsmith, Charlie, 551
Goldstein, Jill, 273 , 546 , 547
Golgi, Camillo, 75 , 76
Gombart, A. F., 185
Gomez-Hassan, D., 236
Gonçalves, R., 562
Goni, F., 492
Gonzalez, C., 270 , 517
Gonzalez, Claudia, 220
Gonzalez, R. G., 488
Goodale, M. A., 336
Goodale, Mel, 297 , 313 , 316 , 317
Goodkin, H. P., 377
Gordon, A. D., 21
Gordon, G. R., 84
Gorny, G., 505
Gorny, K. R., 572
Gorski, Roger, 432
Gosselin, F., 530
Gould, E., 434 , 509
Gould, Elizabeth, 503 , 510
Gould, Stephen Jay, 27
Goyal, M., 45
Grau-Sánchez, J., 576
Gray, J. R., 553
Gray, Stephen, 109
Graziano, M. S. A., 367 , 368
Greary, C., 251
Greely, H., 172
Greenberg, D., 407
Greenberg, R., 406
Greenfield, P. M., 9
Greenough, W. T., 504 , 505
Greenstein, D. K., 259 , 260
Gregg, C., 251
Greiner, E. R., 100
Griffin, J. A., 192
Griffiths, T. D., 347
Grigoriadis, N., 584
Grimshaw, A., 591
Grisham, W., 275
Grogerr, N., 266
Gross, C., 596
Gross, C. G., 7
Gu, X., 100
Gubbi, J., 582
Guerrero-Bosagna, C., 105
Guerrini, R., 277
Guilford, J. P., 554 , 555
Guo, Z., 83
Gustavii, B., 161
Guthrie, D., 272
Guthrie, Marjorie, 100
Guthrie, Woody, 100
Habas, C., 34 , 536
Halder, P., 393
Hall, Calvin, 462
Hall, Stuart, 460
Hallett, M., 374
Halliwell, C., 276
Hamilton, Roy, 287
Hamilton, T., 80
Hammond, D., 193
Hampshire, A., 29
Hampson, Elizabeth, 203 , 509
Han, J. Y., 183
Han, L. Y., 593
Hanggi, J., 555
Hankins, M. W., 451
Hankinson, S. E., 428
Hansen, E.H., 172
Hansen, Rick, 365
Hanus, R., 153
Hardee, J. E., 192
Harker, A., 266
Harkness, D. L., 392
Harlow, Harry, 271 , 400
Harmon, F. G., 444
Harouthunian, V., 594
Harris, J., 172
Harris, K. M., 163 , 166
Harvey, T., 553
Hashimoto, Y., 378
Hassam, R., 251
Hasson, U. Y., 300
Hastings, N. B., 503
Hasvold, I., 198
Hathaway, N. E., 464
Haubensak, W., 221
Haueter, S., 387
Havekes, R., 467
Hawking, Stephen, 134
Haxby, J. V., 486
Hayashi, Y., 167
Hayes, J. E., 404
He, M., 595
Heath, M., 358
Hebb, Donald O., 11 , 163 , 266 , 267 , 270 , 276 , 400 , 401 , 504 , 522 ,
524 , 525 , 555
Heberlein, A., 196
Heckman, James, 246 , 267
Heimann, H., 598
Heinz, A., 598
Held, R., 289
Hellman, R. B., 386
Helms Tillery, S. I., 386
Hen, R., 185
Heninger, G. R., 566
Henkin, Y., 428
Herculano-Houzel, S., 23 , 24 , 25 , 76 , 82
Herold, C., 593
Heron, W., 270
Heron, Woodburn, 5 , 400
Herringa, R. J., 28
Herrmann, N., 160
Hertz, Heinrich Rudolph, 323
Herzel, H., 447
Herzog, H., 553
Hess, Walter, 361 , 362
Hevner, R. F., 299
Heyer, J. B., 578
Hickok, Gregory, 531
Highfield, R. R., 29
Hill, A. S., 185
Hillemacher, T., 196
Hinshelwood, James, 480
Hirsch, J., 341
Hisatsune, A., 475
Hitzig, Eduard, 109 , 366
Ho, G., 576
Ho, W. M., 579
Hobson, J. Allan, 446 , 462 , 463 , 476 , 477
Hodes, G. E., 203
Hodgkin, Alan, 112 , 113 , 114
Hodler, Ferdinand, 463
Hogenesch, J. B., 444
Hohmann, A., 535
Holmstrom, Lynda, 562
Honasage, A., 509
Honda, T., 378
Hong, L. E., 570
Horn, Gabriel, 270
Hornykiewicz, O., 140 , 152
Horovitz, S. G., 374
Horton, N. J., 273 , 546 , 547
Houghton, R, 591
Hounsfield, Godfrey, 226
Houston, S. M., 246
Houston, Whitney, 182
Howlett, A. C., 153
Hsiao, Elaine, 275
Hsien, S., 275
Hu, B., 219
Hu, M., 194 , 435
Huber, J. D., 466
Hublet, C., 347
Hughes, M. E., 444
Hughes, S., 451
Hull, J. T., 296 , 451
Huttenlocher, Peter, 257
Huxley, Andrew, 112 , 113 , 114
Hyde, E. R., 275
Hyde, K. L., 347
Hyman, B. T., 488
Hyson, R. L., 76
Ii, R. A., 579
Iliadis, C., 26
Ilnytskyy, S., 251 , 275 , 511
Imani, S., 365
Ingalhalikar, M., 548 , 549
Insel, T., 413
Isacsson, G., 186
Isbell, H., 177 , 178
Ivry, R. B., 520
Jacob, S., 403
Jacobs, B., 508
Jacobs, L. F., 493 , 494
Jacobsen, Carlyle, 423
Jacobson, Edmond, 5
Jagannath, A., 451
Jagasia, R., 596
Jain, S., 221
Jamal, N. I., 555
James, William, 528
Jancke, L., 555
Janes, Amy, 438 , 439
Jang, S., 576
Jankovic, J., 460
Jasper, H. H., 223
Jeannerod, M., 557
Jeannerod, Marc, 557
Jegen, M., 387
Jenner, Bruce, 435
Jenner, Caitlyn, 435
Jensen, P., 101 , 105
Jerison, Harry, 22 , 23 , 303
Jin, C., 80
Jinnah, Z., 21
Joers, J. M., 198
Johanson, D., 21
John, B., 562
John, G. R., 86
Johnson, F., 76
Johnson, K. A., 488
Johnsson, M., 101
Johnston, C., 185
Jolley, J., 261
Jones, Barbara, 471
Jones, J. R., 255
Jones, L., 594
Jones, R. N., 591
Jones-Gotman, M., 404
Jorgani, M., 365
Jorge, R. E., 562
Jouvet, Michel, 472 , 475
Jucker, M., 492
Jung, Carl, 462
Junque, C., 534
Juraska, J. M., 274
Kaas, J. H., 24 , 25 , 76 , 82 , 390 , 393 , 394 , 506
Kaati, G., 105
Kalueff, A. V., 362
Kambi, N., 393
Kan, Eric, 246 , 261
Kandel, Eric, 163 , 164 , 166
Kang, J. L., 452
Kang, Q., 456
Kanner, Leo, 255
Katano, K., 378
Katsanos, A. H., 584
Katz, Bernard, 144
Kaufer, Daniel, 585
Kaufman, M. H., 438
Kaufman, M. J., 498
Kavakli, I. H., 452
Kawai, Y., 100
Kayser, S., 219
Keating, J. G., 377
Keck, T., 75
Kelley, D. D., 459
Kelly, C., 535
Kelly, Mark, 2
Kelso, J., 22
Kemegether, E., 594
Kempermann, Gerd, 504
Kennedy, A. J., 509
Kennedy, D. N., 273 , 546 , 547
Kennedy, Edward, 83
Kenny, P., 562
Kern, U., 386
Kerr, D. C., 185
Keshavan, M., 275
Kessler, R. C., 172
Keyser, D., 562
Khachaturian, A., 584
Khachaturian, Z. S., 584
Kidd, J. R., 404
Kidd, K. K., 404
Kigar, D., 553
Kim, D., 198
Kim, K. H. S., 341
Kim, N., 517
Kim, S. J., 452
Kimbel, W. H., 21
Kimura, Doreen, 203 , 509 , 541 , 546 , 547 , 548 , 549
Kinney, Hannah, 277
Kinnunen, L. H., 403
Kipke, R., 598
Kircanski, I., 160
Kirszenblat, L., 469
Kishore, M. G., 596
Klein, Denise, 268
Kleitman, Nathaniel, 458 , 461 465
Klinger, Eric, 464
Klunder, A. D., 570
Klüver, Heinrich, 422 , 423
Knight, E. J., 572
Knight, Heather, 80
Knoch, D., 555
Ko, A. L., 572
Ko, K. N., 183
Koban, L., 394
Koch, C. E., 450
Koch, Christof, 556
Kochunov, P., 570
Koelling, R. A., 409
Kogan, M. D., 255
Kohl, M., 386
Kojima, K., 100
Kolb, Bryan, 216 , 220 , 251 , 258 , 266 , 270 , 275 , 276 , 345 , 406 ,
505 , 509 , 511 , 517 , 546
Kolinsky, R., 347
Kolodny, J., 553
Kong, L., 593
Koo, D. S., 555
Koopowitz, S., 464
Kornek, B., 584
Korsakoff, Sergei, 496
Kosofsky, Barry, 276
Kovalchuk, O., 251 , 275 , 511
Kovelman, J. A., 278 , 593
Kovelman, Joyce, 278
Kozyak, B. W., 26
Kraspulski, M., 271
Kraus, T., 196
Kravitz, A. V., 375
Krebs, M. O., 424
Kreutzmann, J., 467
Krishman, K. R. R., 596
Kroger, J. K., 495
Kross, Ethan, 394
Kroutil, L. A., 186
Krug, S., 452
Kruggle, F., 487
Kuffler, Stephen, 302
Kuhl, P. K., 266
Kuhn, H. G., 504
Kühn, S., 476
Kuna, S. T., 452
Kunwar, P. S., 221
Kunz, A. R., 26
Kuo, C. E., 457
Kuo, H. K., 591
Kuperman, J. M., 246
Kurauchi, Y., 475
Kusakari, S., 102
Kusmakar, S., 582
Kut, C., 232
Kwakkel, G., 45
Kwong, K. K., 230
Labonté, B., 206
Labrecque, N., 448
Labrecque, R., 347
Lacroix, M. M., 468
Lahens, N. F., 444
Lajud, N., 206
Laland, K. N., 29
Lalonde, F. M., 486
Lamb, Mary, 455
Lamberg, L., 458
Lan, K. C., 457
Lanctôt, K. L., 160
Landgraf, D., 450
Landré, L., 206
Lang, A., 276
Lang, C. E., 361
Lange, S., 183
Langer, N., 555
Langhorne, P., 45
Langston, J. William, 161
LaPorte, J. L., 362
LaSasso, C., 555
Lashkari, D., 534
Lashley, Karl, 218 , 359 , 488 , 489
Latreille, V., 467 , 567
Laureys, S., 468
Laver, K. E., 581
Lazar, M. A., 447
Leakey, Mary and Louis, 21
Leaman, S., 562
Leatherdale, S. T., 193
LeCours, A. R., 261
LeDoux, Joseph, 422 , 498
Lee, A. D., 570
Lee, B. Y., 183
Lee, C. Y., 100
Legenstein, R., 131
Lehman, M. N, 452
Lehmann, H., 497
Leljavski, A., 450
Lenggenhager, B., 392
Lenneberg, E., 254 , 261
Lenroot, R. K., 259 , 260
Lent, K. L., 349
Lenz, B., 196
Lenz, K. M., 203
Leonard, Christiana M., 261 , 392
Leow, A. D., 570
Lepage, M., 487
LePort, A. K., 487
Lerch, J. P., 259 , 347
Leritz, E. C., 591
Leston, J., 454
Lethman, H., 213
Lettieri, C. F., 464
Levitin, D. J., 266
Levy, G., 300
Levy, W. B., 125
Lewin, R., 24
Lewis, D. A., 593
Li, H. C., 535
Li, Y., 258 , 456
Li, Y. H., 457
Liao, P., 83
Lieberman, Matthew, 536 , 537
Liewald, J. F., 131
Lin, H., 126
Lindquist, M. A., 394
Lindvall, O., 161 , 588
Linge, Fred, 2 , 13 , 14 , 34
Liszt, Franz, 552
Little, William, 363
Liu, C., 275
Liu, P., 198
Loeb, G. E., 337
Loewi, Otto, 138 , 139 , 140 , 147 , 168
Loftus, E. F., 485
Loganovskaja, T. K., 271
Loganovsky, K. N., 271
Lomber, S. G., 219
Lømø, Terje, 500
Lopez-Escamez, J. A., 389
Lorenz, Konrad, 270
Loui, Psyche, 535
Low, D. W., 26
Lu, A., 570
Lu, H., 198
Lu, L. H., 261
Lubman, D. I., 199
Lubrano, V., 268
Lucca, U., 472
Luciana, M., 257
Lugert, S., 596
Lukas, Scott E., 439
Lumer, E., 557
Lundstrom, Johan, 404
Lungato, L., 467
Lv, J., 102
Lyn, H., 9
Ma, W., 456
Maass, W., 131
MacAndrew, Craig, 192
MacDonald, G., 191
MacDonald, T. K., 191
MacDougall, M., 502
Mackler, Scott, 356 , 363
Mädler, B., 219
Magee, J. C., 146
Magnusson, M., 389
Magoun, Horace, 470
Maguire, Eleanor, 503 , 504
Mahncke, H. W., 513
Mahowald, M. W., 475
Mahurkar, A., 203
Makris, N., 273 , 546 , 547
Malach, R., 300
Malanga, Carl, 276
Malberg, J. E., 596
Malcolm-Smith, S., 464
Mallick, S., 22
Malone, P., 374
Mamelak, A., 83
Mandalà, M., 389
Manger, P. R., 24 , 25 , 76 , 82
Mangun, G. R., 520
Mann, S., 275
Manoukian, J., 498
Maquet, Pierre, 468
Marin-Padilla, M., 253
Markowitsch, Hans J., 487 , 499
Markowski, G., 75
Marler, P., 349
Marsden, C. D., 382
Marshall, C. M., 444
Marshall, P. J., 272
Mårtensson, B., 448
Martin, Alex, 486
Martin, Jean Prudin, 586
Mascetti, G. G., 469
Maslin, M. A., 25
Mateer, C. A., 575
Matsumura, K., 378
Matsuzaki, Y., 102
Mattfield, A. T., 487
Mattison, D. R., 161
May, L., 210
McBride, S. W., 275
McCabe, B. J., 270
McCarthy, M. M, 432 , 435
McClay, J., 236
McClintock, Martha, 403
McDonald, R. J., 451
McEwen, B., 434 , 509 , 510
McGaugh, James, 499
McGowan, Patrick, 206 , 237 , 595
McHugh, Tommy, 597 , 598
McIntosh, A. R., 487
McKenzie, S., 497
McLure, Samuel, 537
McNaughton, B. L., 468
McVeigh, E. R., 232
Mead, E. A., 183
Meaney, Michael, 237
Mechoulam, Raphael, 153 , 190
Meerlo, P., 467
Meitzen, J., 349
Melendez-Vasquez, C. V., 86
Meloni, E. G., 498
Meltzoff, A., 266
Melville, John, 363
Melzack, Ronald, 386 , 387
Mendel, Gregor, 10 , 11 , 74 , 96 , 98 , 104
Menon, B. K., 45
Merla, A., 434
Merzenich, Michael, 480 , 513
Mesoudi, Alex, 29
Metz, J., 403
Meyer, E., 345 , 347
Middelkoop, G., 198
Mihic, A., 183
Milberg, William, 591
Milham, M. P., 535
Miller, B. H., 593
Miller, B. L., 598
Miller, Courtney, 509
Miller, D. B., 466
Miller, J. P., 583
Miller, S. L., 480
Milliken, G. W., 369 , 505
Milner, B., 392
Milner, Brenda, 218 , 268 , 488 , 489 , 550
Milner, David, 297 , 313 , 316 , 317
Milner, Peter, 437
Milton, Katharine, 25
Mimori, T., 100
Min, H. K., 572
Min, M. O., 276
Minichino, A., 594
Minnes, S., 276
Mischel, W., 394
Mishkin, F., 598
Mishkin, Mortimer, 333 , 393 , 495 , 498
Mistlberger, R. E., 450 , 451
Mittleman, G., 179
Mizuno, Y., 589
Moffitt, T. E., 236
Mohajerani, M. H, 130
Molaison (H. M.), Henry, 488 , 491 , 495 , 513
Molitoris, D., 275
Monecke, S., 452
Money, John, 432
Moniz, Egas, 423
Monrobot, Marilyn, 80
Montagna, P., 386
Moore, T. J., 161
Moran, James, 529
Morris, Mark, 160
Morris, R. G., 497
Morris, R. G. M., 215 , 216
Morshead, C., 517
Moruzzi, Giuseppe, 470
Moser, Edvard, 223 , 494
Moser, May-Britt, 222 , 494
Mountcastle, Vernon, 391
Movshon, J. A., 522
Mozaffarian, D., 428
Muhammad, A., 251 , 258 , 275
Mulder, C. K., 456
Müller, D. J., 184
Murphy, D. L., 362
Murphy, G. F., 152
Murray, D., 444
Murray, E., 495
Murray, R., 236
Muzio, J., 459
Mychasiuk, Richelle, 237 , 251 , 258 , 275 , 276 , 510 , 511
Myers, K. M., 422
Myung, J., 447
Nabokov, Vladimir, 551
Nadel, Lynn, 493
Nakajima, K., 221
Nakao, M., 378
Nam, J., 86
Namkoong, K., 452
Nariai, N., 100
Nasri, S., 365
Nathan, D. E., 562
Neely, T. R., 202
Nelini, C., 469
Nelson, A., 26
Nelson, C. A., 257 , 272
Nestler, E. J., 596
Nevell, L., 21
Neville, A., 198
Nevler, N., 573
Newman, B., 562
Newsome, William, 522
Nguyen, B. M, 198
Nichols, T. E., 192
Nickerson, Lisa D., 438 , 439
Nicolette, F., 594
Nir, I., 300
Nir, Y., 461
Noble, Kimberly, 246
Nobunaga, M., 475
Nonneman, Arthur, 406
Nordahl, C. W., 255
Nordborg, C., 503
Nottebohm, Fernando, 350
Nudo, Randy, 369 , 370 , 505
Nugent, B. M., 203
Nyagu, A. I., 271
O’Hare, E. D., 258
O’Keefe, John, 222 , 223 , 492 , 494
Oberman, L. M., 531
Obeso, J. A., 382
O’Brien, T., 582
Obukuru, K., 475
O’Callaghan, J. P., 466
Oettingen, G., 193
Oiestad, E. L., 198
Oiu, J., 456
Olanow, C. W., 591
Olds, James, 437
Olivetti Belardino, M., 434
Olsson, S. B., 404
Olulade, O. A., 555
Ommaya, A. K., 393
Osorio, L., 467
Ostergard, T., 583
Ostrom, H. G., 83
Oudiette, D., 469
Overman, William, 264 , 274
Owen, Adrian, 13 , 29
Ozpinar, A., 572
Pääbo, S., 22
Palaniswami, M., 582
Palasz, A., 75
Paller, K. A., 469
Pannese, R., 594
Pantelis, E., 464
Papez, James, 57 , 417
Paredes-Gamero, E. J., 467
Park, C. I., 452
Park, S., 576
Park, S. Y., 183
Parker, D., 548 , 549
Parkin, B. L., 29
Parkinson, James, 140
Parrish, R. R., 509
Parrish-Novak, J., 83
Parsons, T., 562
Paterson, David, 277
Pathihis, Lawrence, 487
Paulignan, Y., 557
Paus, T., 275
Pavelko, M., 271
Pavlov, Ivan, 481
Payne, B. R., 219
Paz, M. F., 237
Pedroni, A., 555
Peigneux, P., 468
Peirson, S. N., 296 , 451
Pellegrino, R., 452
Pembrey, M., 105
Penfield, Wilder, 219 , 223 , 343 , 344 , 345 , 346 , 366 , 367 , 390
Penumalli, V., 126
Pepperberg, Irene, 523
Peretz, Isabelle, 347
Perfetti, C. A., 555
Perfilieva, E., 503
Peri, F., 85
Perry, R., 557
Persson, M. E., 101
Pertwee, L. O., 153
Petanjek, Zdravko, 258
Petiau, C., 468
Pettersson, A., 448
Peuster, A., 264
Pham, D. L., 562
Piaget, Jean, 262 , 263 , 264
Pickering, R., 21
Pignatelli, M., 594
Pincus, J. H., 582
Piper, W. T., 185
Pistorius, Martin, 5 , 13
Pitchers, K. K., 196
Plautz, E. J., 505
Poldrack, R. A., 480
Politis, M., 588
Pomplii, M., 573
Poncelet, B. P., 230
Ponnusamy, R., 221
Pons, T. P., 393
Popova, S., 183
Porta, G., 186
Posner, M. I., 232
Postuma, R. B., 467 , 567
Potkin, S. G., 278
Potts, R., 25
Pouget, J. G., 184
Presley, Elvis, 327
Preux, P. M., 108
Prinz, J., 4
Proal, E., 363
Prüfer, K., 22
Prusiner, Stanley B., 590
Purpura, Dominique, 278 , 279
Purves, D., 502 , 503
Putnam, B., 198
Qiao, L., 456
Quaglio, E., 472
Quinlan, J., 470
Quinlan, Karen Ann, 470
Quinn, T., 83
Rafferty, Mary, 109 , 111
Ragert, Patrick, 507
Raichle, M. E., 232
Raine, C. S., 86
Raizada, R. D. S, 266
Rajan, R., 393
Rakic, Pasko, 253 , 257
Ralph, Martin, 451 , 452
Ralvenius, W. T., 387
Ramachandran, Vilayanur, 386 , 506 , 507 , 508 , 531
Rameson, L. T., 536
Ramirez, V. D., 219
Ramón y Cajal, Santiago, 75 , 76 , 256 , 376 , 500
Rao, A., 582
Rao, J., 570
Rapoport, Judith, 570
Rapoport, S. I., 570
Rasch, B., 467
Raslan, A. M., 572
Rasmussen, Ted, 392 , 550
Rauschecker, J. P., 333 , 340
Ravel, Maurice, 346
Raven, P. H., 444
Ray, W., 507
Raza, S., 266
Raza, S. M., 232
Read, S. L., 598
Reazei Zarchi, S., 365
Reber, P. J., 469
Reckman, G. A., 456
Reeve, Christopher, 364 , 365 , 421
Reeve, Dana, 364
Reeve, R., 80
Regenold, W. T., 570
Rego, A. C., 102
Rehm, J., 183
Rehngrona, S., 161
Reid, J. L., 193
Reinstatler, L., 186
Reis, C., 579
Reiter, Russel, 454
Relkin, N. R., 341
Replogle, K., 349
Respino, M., 573
Rether, K., 266
Revonsuo, A., 463
Rezania, K., 126
Ribeiro-da-Silva, A., 515
Rich, C. L., 186
Richards, T. L., 266 , 598
Richter, Curt, 445 , 450 , 455
Rickards, H. E., 100
Rieder, R. O., 278
Riesen, Austin, 271
Rimm, E. B., 428
Rivera, E. J., 202
Rizzo, A., 562
Rizzolatti, Giacomo, 531 , 532
Roberts, D. M., 198
Robinson, T. E., 178 , 179 , 180 , 194 , 196 , 437 , 511
Rockland, M., 386
Rockstroh, B., 507
Rodriguez-Fornells, A., 576
Roffward, H. P., 459
Rogers, S., 255
Rogers, S. E., 266
Roitman, P., 190
Rojczyk-GoáĊbiewska, E., 75
Roland, P. E., 361
Romanski, L. M, 333
Romenets, S. R., 567
Rondi-Reig, L., 468
Ropero, S., 237
Rosen, C. L., 466
Rosenegger, D. G., 84
Roth, L. S., 101
Rothwell, John, 382
Rouse, C., 83
Roux, F. E., 268
Rowland, B. A., 527
Rudolph, J. L., 591
Ruiz, S., 576
Ruparel, K., 549
Rushinsky, D. D., 593
Rusielewicz, T., 86
Rutter, Michael, 272
Ruttle, P. L., 28
Ryan, P., 274
Ryu, H. M., 183
Sabuncu, M. R., 534
Sacher, J., 200
Sacks, Oliver, 42 , 152 , 382 , 521 , 585 , 587
Sahakian, B., 172
Sahay, A., 185
Sainsbury, R. S., 499
Saitow, F., 102
Sala-Llonch, Roser, 534
Salat, D. H., 591
Salehpour, S., 565
Sallis, H., 199
Salm, A. K., 271
Salzer, J., 584
Sander, J. W., 108
Sanders-Bush, E., 271
Sangrey, T., 125
Sankararaman, S., 22
Santarelli, Luca, 596
Santos, V. J., 386
Sapolsky, Robert, 204 , 206 , 510
Sarkar, D. K., 183
Sarnyai, Z., 131
Sasaki, A., 206
Sassa, Y., 555
Sato, Y., 100
Sato-Hashimoto, M., 102
Satterthwaite, P. D., 548 , 549
Saturn, S. R., 185
Savage-Rumbaugh, Sue, 9
Savitz, S. I., 572
Saxe, M., 596
Schacter, Daniel, 498
Schall, M., 508
Schallert, T., 219
Scheibel, Arnold, 278 , 508 , 593
Scheinost, D., 425
Schel, A. M., 9
Schellenberg, E. G., 347
Schenck, C. H., 475
Schieber, M. H., 361 , 369
Schieve, L. A., 255
Schiff, Bernard, 399
Schiff, N. D., 13
Schlaepfer, T. E., 219
Schlaug, G., 535
Schmahmann, Jeremy D., 34
Schmal, C., 447
Schmidt, A., 507
Schmierer, K., 126
Schmold, N., 251 , 275 , 276
Schnack, H. G., 246
Schnyer, D. M., 591
Scholz, R., 255
Schreiber, S. J., 126
Schroeder, C. E., 527
Schroeder, M., 424
Schuhmann, E., 274
Schultheis, C., 131
Schwarzfuchs, D., 428
Schyns, P., 530
Scotto, Pietro, 49
Scoville, William, 218 , 488 , 489
Seeley, Randy, 430
Seidl, U., 593
Seidman, L. J., 273 , 546 , 547
Seitz, R. J., 553
Seki, T., 475
Sekiguchi, A., 555
Sen, S., 236
Seneca, 248
Sepulcre, J., 534
Serafini, G., 573
Sertürner, Friedrich, 187
Setien, F., 237
Sevincer, A. T., 193
Seyoum, C., 21
Shadlen, M. N., 522
Shahar, D. R., 428
Shai, Iris, 428
Shakespeare, William, 466
Shalev, A., 190
Shams, T. A., 184
Sharifi, Z., 565
Sharon, G., 275
Shaw, F. Z., 457
Shaw, Philip, 259
Shenton, J. T., 287
Shepherd, G. M., 405
Sherman, Janet, 34
Sherry, David, 493 , 494
Shetty, A. C., 203
Shi, Q., 591
Shibasaki, K., 102
Shimomura, Osamu, 75
Shin, C. Y., 183
Shin, J. H., 576
Shingo, T., 251 , 517
Shors, T. J., 503
Shorter, K. R., 593
Shultz, S., 25
Shweikeh, F., 83
Siegel, Jerome, 475
SiFuentes, F., 369
Simon, T., 255
Singer, L. T., 276
Sira, C. S.,
Sirevaag, Anita, 504 , 505
Sisodiya, S. M., 108
Sitaram, R., 576
Sjöström, M., 105
Skinner, B. F., 408 , 483 , 484
Smarr, B. L., 452
Smidak, M., 591
Smith, A., 548 , 549
Smith, A. D., 185
Smith, D. V., 405
Smith, E. E., 394
Smyke, A. T., 272
Snow, B., 161
Sodhi, M. S., 271
Soga, K., 378
Sohlberg, M. M., 575
Soliven, B., 126
Solms, M., 464
Song, Y., 275
Soules, M. E., 192
Sourkes, T. L., 152
Sowell, Elizabeth, 258 , 261
Spanswick, S. C., 213
Sparks, F. T., 497
Spearman, Charles, 28 , 29 , 553
Sperry, Roger, 268 , 520 , 539
Spirito, A., 186
Squire, L. R., 497
Stampfer, M., 428
Staniloiu, Angelica, 487
Stark, C. E., 487
Stedman, H. H., 26
Steen, Eric, 202
Stein, B. E., 527
Stephens, G. J., 131
Stepniewska, I., 390 , 506
Stern, Karen, 403
Stewart, J., 509 , 546
Stieltjes, B., 593
Stier, G., 579
Stodola, D. E., 28
Su, L. T., 26
Sugiura, M., 555
Sundström, P., 584
Sunitha Suresh, B, S., 347
Suomi, Stephen, 271
Suresh, S., 347
Surget, A., 596
Sutherland, Robert, 213 , 497
Suzuki, M., 495 , 498
Suzuki, Y., 469
Swaab, D. F., 435
Sweatt, J., 408 , 509
Szybowska, M., 451
Szyf, Moshe, 206 , 237 , 595
Taglialatela, Jared, 9
Takeuchi, Hikaru, 555
Talbot, L., 591
Tallal, P., 480
Tamminga, C. A., 198
Tanaka, Keiji, 309 , 310
Tanapat, P., 503 , 510
Tang, D., 456
Tang, Y. L., 593
Tanner, J., 386
Tao Hao, M. P. H., 428
Taub, Edward, 581
Taube, M. M., 382
Tees, Richard, 257 , 269
Teie, P. U., 326
Teitelbaum, P., 219
Teixeira-Gomes, A., 197
Temple, E., 480
Teng, S., 336
Tennstedt, S., 591
Terkel, J., 6
Terry, B. M., 202
Teskey, Cam, 219
Testini, P., 572
Tetrud, J. W., 161
Tettamanti, M., 472
Teuher, H., 489
Thach, Tom, 377
Thaler, L., 336
Therrien, A. S., 378
Thesier, D. M., 26
Thomas, P. K., 382
Thomas, S., 581
Thompson, C. K., 349
Thompson, E. G., 277
Thompson, P. M., 258 , 261 , 553 , 570
Thorndike, Edward, 481 , 486
Tian, B., 333
Tinaz, S., 374
Tiwari, A. K., 184
Toga, Arthur W., 261 , 570
Toga, W., 258
Tomita, M., 444
Tomlinson, A, 591
Torben-Neilsen, B., 80
Torner, L., 206
Townsend, S. W., 9
Trachtenberg, F. L., 277
Tramo, M., 347
Tranel, D., 530
Trauth, M. H., 25
Tréatikoff, Constantin, 140
Treffert, D. A., 598
Trehub, Sandra, 347
Triantafyllou, N., 584
Trotta, A., 199
Trussel, L. O., 128
Tsang, A. H., 450
Tsien, Roger, 75
Tsivgoulis, G., 584
Tsutsui, M., 475
Tucker, G. J., 582
Tudeau, L., 387
Tufik, S., 467
Tuineaig, M., 467
Tulving, Endel, 487
Tuohimaa, P., 362
Turing, Alan, 8
Turk, Ivan, 322
Turner, A., 505
Turner, M., 264
Turri, L., 404
Twitchell, Tom, 260
Umstattd, M. R., 192
Ungerleider, L. G., 486
Usdan, S. L., 192
Vaisanen, M. L., 275
Valdueza, J. M., 126
Valli, K., 463
van Besien, K., 126
Van Brunt, D. E., 186
van Dam, R. M., 428
Van der Zee, E. A., 456
van Haren, N. E., 246
van Oosten, B. W., 126
van Schaik, A., 80
Vanderwolf, Case, 471
Vargha-Khadem, D. G., 495 , 498
Veldhuizen, Maria, 405
Verwey, M., 451
Vetrugno, R., 386
Vevelstad, M., 198
Vierck, C. J., 392
Villmoare, B., 21
Villringer, A., 200
von Békésy, George, 331
von Helmholtz, Hermann, 111 , 330 , 331
Voumvourakis, K., 584
Voyvodic, J. T.,
Wada, Jun, 550
Wade, J., 275
Walker, D. L., 422
Walker, J. D., 258
Walker, L. C., 492
Walker, M. C., 108
Walkey, J., 216
Wall, N. R., 221
Wall, Patrick, 386
Wallace, Alfred Russel, 8 , 9 , 10
Wallace, E. K., 9
Wallace, G. L., 260
Wallace, P. S., 260
Wang, J., 595
Wang, X., 83
Wang, Y., 102 , 579
Wassermann, E. M., 573
Water, T. D., 394
Waterman, Ian, 382
Watkins, Kate, 268
Watson, James, 96
Watson, Michael, 551 , 552
Watson, Stewart, 9
Webb, Barbara, 80
Webb, I. C., 450
Weber, S. C., 578
Webster, W., 271
Weesner, K. E., 462
Wei, M. Z., 457
Weiland, B. J., 192
Weiner, J., 6
Weingarten, J. A., 448
Weinland, C., 196
Weiss, S., 517
Weiss, Sam, 250
Weisskoff, R. M., 230
Weizkrantz, Lawrence, 284
Welcome, Suzanne E, 261
Wells, E. M., 260
Welsh, R. C., 192
Wenger, John, 178
Werker, Janet, 210 , 257
Wernicke, Karl, 342 , 343 , 347
Wess, J., 221
West, S., 580
Westwood, D. A., 358
Whishaw, I. Q., 179 , 180 , 216 , 219 , 260
Whitbread, P., 185
White, J. A., 509
Whiten, A., 29
Whitfield, C., 258
Whitney, D., 336
Wiaderkiewicz, R., 75
Widner, H., 161
Wienbruch, C., 507
Wiesing, U., 598
Wiggs, C. L., 486
Wijemanne, S., 460
Wikler, R. E., 177
Wildner, H., 387
Wilfong, T., 392
Wilke, C., 9
Wilkinson, S. T., 199
Willett, W. C., 428
Williams, V. J., 591
Williamson, K., 266
Wills, T. J., 223
Wilson, M. A., 468
Wilson, M., 407
Wilson, S., 467
Windt, J., 392
Wingenfeld, K., 562
Wingfield, J., 275
Winkler, A., 178
Wise, B. M., 369
Wise, R. A., 437
Wisniewski, T., 492
Witelson, S., 551 , 553
Witkow, S., 428
Wixted, J. T., 497
Wolf, O. T., 562
Wolpert, D. M., 392
Wonder, Stevie, 552
Wong-Riley, Margaret, 299
Woo, C. W., 394
Wood, B., 21
Woods, Stephen, 430
Woodson, R., 406 , 407
Woollett, Katherine, 503 , 504
Woolley, C. S., 434 , 509
Workman, A. D., 26
Worthington, J. J., 75
Wright, C. L., 203
Wright, D., 101
Wu, H., 102
Wu, M., 276
Wu, W., 76
Wulff, K., 296 , 451
Xhen, M., 131
Xi, J., 232
Xie, L., 266
Xu, N. L., 75
Yadav, S. N., 108
Yager, L. M, 196
Yakovlev, P. E., 261
Yamguchi-Kabata, Y., 100
Yan, B., 582
Yancey, C. R., 509
Yang, M., 102
Yang, X., 255
Yau, M., 358
Ye, X., 232
Yeo, B. T. T., 534
Yeo, Thomas, 534
Yi, M., 223
Yizhar, O., 131
Yomogida, Y., 555
Yoon, S., 276
Young, J. Z., 112
Young-Min Lee, K., 341
Youssef, N. A, 186
Yovel, Y., 351
Yücel, M., 199
Zaidi, Farhan, 296 , 451
Zajonc, Robert, 424
Zanna, M. P., 191
Zatorre, Robert, 268 , 345 , 347 , 404
Zava, D. T., 185
Zeanah, C. H., 272
Zeffiro, T. A., 425
Zelano, C., 405
Zgari, Z., 365
Zhang, B. Y., 591
Zhang, F., 444
Zhang, Y., 102
Zhao, X., 595
Zhou, W., 591
Ziao, K., 591
Zihl, Josef, 316
Zimmerman, T., 573
Ziv, Y., 75
Zlomuzica, A., 142
Zohary, E., 522
Zollikofer, C. P., 26
 SUBJECT INDEX
Note: Page numbers followed by f indicate figures; those followed by t
indicate tables.
Abducens nerve, 59 , 60 f
Ablation studies, 218 –219, 218 f
Abnormal behavior. See Brain/behavioral disorders
Absolute pitch, 324 , 535 , 535 f, 554
Absolutely refractory membrane, 122
Acetate, 149
N -Acetylaspartate, in traumatic brain injury, 579
Acetylcholine (ACh), 138 , 138 f, 148 , 155 , 157 –158, 160 f
in autonomic function, 157 –158
in brain activation, 471 , 471 f
identification of, 148
in muscle contraction, 133 –134, 133 f, 157 , 372 , 372 f
neurotoxin effects on, 176 –177, 176 f
receptors for, 155 , 155 t
in Renshaw loop, 148 , 149 f
synthesis and breakdown of, 149 –150, 150 f
Acetylcholine psychedelics, 189
Acetylcholine receptor, curare and, 176 –177
Acetylcholine synapse, drug action at, 176 –177, 176 f
Acetylcholinesterase, 160
Achromatopsia, 316
Acquired savant syndrome, 598
ACTH, 414 t, 595
Action potential, 120 –123. See also Nerve impulse
all-or-nothing response of, 124
 blocking of, 120 , 121 , 121 f
definition of, 120
measurement of, 120 , 120 f
nerve impulse and, 123 –124
phases of, 122 f
postsynaptic potentials and, 127 –130
production of, 127 –130
propagation of, 123 –124, 123 f, 125 f, 130 f
back, 130 –131
refractory periods and, 122 –123, 124
single-cell recordings of, 222 –223
Action test, 8
Activating systems, 158 –162
Activation-synthesis hypothesis, for dreams, 462 –463
Adderall, 172
Addiction. See Substance abuse, addiction in
Additive color mixing, 310 , 310 f
Adenine, 91 f, 92
Adolescence, psychiatric disorders presenting in, 275
Adrenaline (epinephrine), 138 –139, 150 , 150 f. See also
Neurotransmitters
in stress response, 204 , 205 f
Adrenocorticotropic hormone (ACTH), 414 t, 595
Affective disorders, 424 –426
Affective states. See under Emotion; Emotional
Afferent nerves, 37 , 37 f
Afferent sensory signals, 358
Africa, primate evolution in, 21 , 24 –25
Age-related cognitive loss, 591 . See also Dementia
Aggression, sex differences in, 548
Agnosia
color, 316
facial, 301
visual-form, 315 –316, 526
Agonists, 176 –177, 176 f
Agoraphobia, 425
Akathesia, 586
Akinesia, 219
Alcohol. See also Substance abuse
brain damage from, 198 , 495 –497
disinhibition and, 191 –192
fetal alcohol spectrum disorder and, 28 , 183 , 267 , 271
Korsakoff syndrome and, 495 –497
as sedative-hypnotic, 182
tolerance to, 177 –178, 178 f
Alleles, 97
dominant, 97 , 99 f
recessive, 97 , 99 f
wild-type, 97
Allocortex, 54
Alpha fetoprotein, 432
Alpha rhythms, 224 , 458
Alprazolam, 182
Alzheimer disease, 70 , 160 , 492 , 498 , 588 –591
brain abnormalities in, 85 , 167 , 588 –589, 588 f, 589 f
in Down syndrome, 100
 Parkinson disease and, 589 –590
Amacrine cells, retinal, 294 , 295 f
Amblyopia, 269
Amine neurotransmitters, 149 t, 150 , 150 f
Amines, synthesis of, 150
Amino acid(s), 92 , 93 , 93 f. See also Protein(s)
synthesis of, 150
Amino acid neurotransmitters, 149 t, 150 , 150 f
Amino groups, 93
Amnesia, 483 –484. See also Memory deficits
anterograde, 496
Boswell’s, [Patient], 490
definition of, 483
episodic, 486 –487
postencephalitic, 490
psychogenic, 487 , 487 f
retrograde, 496
surgically induced, 488 –490, 488 f
AMPA receptors, in long-term potentiation, 501 –502, 501 f
Amphetamine, 188 –189
for attention-deficit/hyperactivity disorder, 172
brain injury from, 198
as cognitive enhancer, 172
dosage of, 173 –174
hallucinogenic, 198
neuronal effects of, 510 –511
sensitization to, 178 –180
Amplification cascade, 155
Amplitude, of sound waves, 324 –326, 324 f
Amputation, cortical reorganization after, 506 –507
Amusia, 348
Amygdala, 54 f, 57 –58, 57 f, 417 f, 418 . See also Limbic system
in attention, 530
in autism spectrum disorder, 255
in eating, 418 , 430
in emotional behavior, 418 , 422 –423
in emotional memory, 482 , 498 –499, 499 f
in fear conditioning, 482 , 498 –499
neural connections of, 498 –499, 499 f
in sexual behavior, 434
Amygdalectomy, Klüver-Bucy syndrome and, 422 –423
Amyloid plaque, in Alzheimer disease, 492 , 492 f, 588
Amyotrophic lateral sclerosis (ALS), 134 , 356 , 363
Anabolic steroids, 204
Analgesics, 387
abuse of, 188
opioid, 151 , 181 t, 187 –188, 387 . See also Opioids
Anandamide, 151 –153
Anandamide psychedelics, 189 –190
Anatomical organization, of brain, 36
Anatomical orientation, of brain, 39
Anatomical terms, 38 –39
Androgen(s), 200 , 273 . See also Sex hormones
behavior and, 401
in brain development, 203 , 273 –275, 432 , 546 –549
functions of, 200 , 202
 lifelong effects of, 274 –275
neuroplasticity and, 509
sexual behavior and, 433
in sexual differentiation, 203 , 272 , 432
Androgen-insensitivity syndrome, 433
Androgenital syndrome, 433
Anencephaly, 277
Anesthesia, epidural, 387
Aneurysms, cerebral, 347
Angel dust, 182 , 190
Animal(s)
auditory communication in, 349 –351
auditory processing in, 322 , 339 –340, 339 f
chimeric, 102
cloned, 101 –102, 102 f
diurnal, 442
emotional behavior in, 410 –411
evolution of, 15 –19
experimental, 101 –102, 239 –242. See also Animal research
hearing in, 324 , 325 f
language in, 8 , 9 , 522 , 523
learning in, 408 –409
prey-killing behavior in, 399 , 401 , 406 –407
scratch reflex in, 364
singing in, 322
skilled movement in, 368
sleep in, 460 –461, 461 f, 465 , 465 f, 469
species-typical movement in, 361 –363, 362 f
 thinking in, 522 –524, 545
tool use by, 29
transgenic, 102
Animal research, 101 –102, 239 –242
in behavioral disorders, 567
benefits of, 240
conditioning in, 481 –482
limitations of, 567
regulation of, 240 –242
Animal Welfare Act, 241
Anions, 146 . See also Ion(s)
Anomalous speech representation, 551
Anorexia nervosa, 275 , 427
Anoxia, cerebral, 363
Antagonists, 176 –177, 176 f
Anterior cerebral artery, 43 , 43 f
Anterior cingulate cortex, 418 f, 419 , 526 , 537
Anterior corticospinal tract, 370 f, 371 , 371 f
Anterior, definition of, 38 , 39
Anterior horn, motor neurons in, 371
Anterior roots, 358
Anterior spinothalamic tract, 383
Anterograde amnesia, 496
Antianxiety agents, 181 –182, 181 t, 425 , 597
Anticonvulsants, 582
Antidepressants, 181 t, 185 –186
atypical, 185
hippocampal neurogenesis and, 596
 mechanism of action of, 594 , 596
monoamine oxidase inhibitors, 185
second-generation, 185
side effects of, 574
sleep and, 467
tricyclic, 185
Antipsychotics, 181 t, 184 , 184 f
side effects of, 574
Anvil, 329 , 330 f
Anxiety, 574
Anxiety disorders, 424 –426, 592 f, 597
adolescent-onset, 275
treatment of, 181 –182, 181 t, 425 , 597
Anxiety dreams, 463 –464
Anxiolytics, 181 –182, 181 t, 425 , 597
Apes, 20 . See also Primates, nonhuman
Aphagia, 429
Aphasia, 545 –546, 548
Broca’s, 227 , 343
definition of, 343
Wernicke’s, 343
Aplysia californica
habituation in, 163 , 164 f
sensitization in, 164 , 165 f
Apnea, sleep, 473 –474
Apoptosis, 198 , 257
Apraxia, 394 , 545 –546, 548
2-Arachidonoylglycerol (2-AG), 151 –152
Arachnoid layer, 37
Arachnoid membrane, 37 f
Arborization, dendritic, 254 –255, 254 f, 502 –503, 503 f
Arcuate fasciculus, 342 f, 343
Arcuate nucleus, in eating, 429 –430
Area postrema, 174 , 175 f
Arousal, in basic rest-activity cycle, 465 , 466 f
Artificial intelligence, 80 , 81
Asperger syndrome, 255
Association cells, 79 , 79 f
Association cortex, 525 –533
in attention, 528 –530
components of, 525 –526, 526 f
in imitation and understanding, 531 –532
lesions in, assessment for, 533
mirror neurons in, 532
multimodal regions of, 527 , 527 f
multisensory integration in, 527 , 527 f
neural connections to, 525 –526, 526 f
in object recognition, 525 –526, 527 f
in planning, 530 –531
in spatial cognition, 527 –528, 527 f, 528 f
Associative learning, 409
long-term potentiation and, 500 –502
Astrocytes (astroglia), 82 t, 83 –84, 146
in blood–brain barrier, 174 , 174 f
Asymmetry, cerebral. See Cerebral asymmetry
Ataxia, 34
 optic, 317 –318
Athletes, traumatic brain injury in, 577 , 578
Atoms, 88 , 89 , 89 f
Atonia, in REM sleep, 458 , 460 –461, 474 –475
Attention, 528 –530
contralateral neglect and, 529 , 530 f
deficits of, 529 –530, 530 f
definition of, 528
extinction and, 529 –530, 530 f
selective, 528 –529
vision and, 528 –529
Attention-deficit/hyperactivity disorder, 162 , 172 , 240
Attitudes, 537
Atypical antidepressants, 185 . See also Antidepressants
Auditory communication, in nonhuman species, 349 –351
Auditory cortex, 334 –335, 525 f
association cortex and, 527 f
Broca’s area in, 254 f, 262 , 342 –343, 342 f, 344 f
mapping of, 343 –346
primary, 334 , 334 f
secondary, 334
structure of, 334 –335, 334 f
supplementary speech area in, 344 –345, 344 f
tonotopic representation in, 336 –338, 337 f
Wernicke’s area in, 334 , 334 f, 342 –346, 342 f, 344
Auditory flow, 286
Auditory nerve, 333
Auditory pathways, 333 , 334 f
Auditory processing, 330 –331
Auditory receptors, 330 f, 332
Auditory system. See also Hearing; Sound
in animals, 322 , 339 –340, 339 f
auditory cortex in. See Auditory cortex
auditory pathways in, 333 , 334 f
auditory receptors in, 330 f, 332
ear in, 329 –331, 330 f, 331 f, 332 f
evolution of, 329
functions of, 329
insula in, 334 f, 335
in language processing, 340 –346
lateralization in, 334 –335, 541 –542
in movement, 333
music perception in, 327 –328, 339 –340
sensitivity of, 326 –327
sound perception in, 326 –327
speech perception in, 327 –328, 339 –340
structure of, 329 –336
Auditory vestibular nerve, 59 , 60 f
Australopithecus, 20 –22, 20 f, 21 f, 23 f
Autism spectrum disorder, 255
brain size in, 28
cerebellar dysfunction in, 34
mirror neurons in, 532
Autobiographical memory, 486 –487, 487 f
Autoimmune disease, 126 , 134 , 584
Autonomic nervous system, 36 f, 37 , 63 –64
 enteric nervous system and, 64 –65, 65 f
neurochemistry of, 157 –158, 157 f
Autoreceptors, 144
Autosomes, 96 , 97
Aversive childhood experiences, frontal lobe development and, 259
Axoaxonic synapse, 145 , 145 f
Axodendritic synapse, 145 , 145 f
Axomuscular synapse, 145 , 145 f
Axon(s), 47 , 47 f, 76 , 76 f, 77 , 78 f, 87 f
dendrites and, 76 , 76 f, 77 , 78 f, 79 –80
giant squid, electrical activity in, 112 , 112 f
growth cones of, 256 , 256 f
myelination of, 124 –125
nerve impulse along, 123 –124, 123 f, 125 f
in neural circuits, 80 . See also Neural circuits
sprouting of, 85 –86
neuroplasticity and, 502 –503, 503 f
Axon collaterals, 77 , 78 f
Axon hillocks, 77 , 78 f
Axosecretory synapse, 145 , 145 f
Axosomatic synapse, 145 , 145 f
Axosynaptic synapse, 145 , 145 f
Baby connectome, 363
Back propagation, 130 –131
Balance, vestibular system in, 388 –389, 389 f
Barbiturates, 182
Basal forebrain, in brain activation, 471 , 471 f
Basal ganglia, 54 , 54 f, 57 , 57 f
 anatomy of, 373 , 373 f
functions of, 373 –375
in memory, 489 –490, 499
in movement, 357 , 373 –375, 375 f
in Parkinson disease, 57 , 374 –375
in Tourette syndrome, 57 , 374
Bases, nucleotide, 91 f, 92
Basic fibroblast growth factor, 252
Basic rest-activity cycle (BRAC), 465 , 466 f
Basilar membrane, in hearing, 330 –331, 330 f, 332 f
Bats, echolocation in, 351 –352
Behavior, 5 –6
abnormal. See Behavioral disorders
brain development and, 247 –248
for brain maintenance, 400 –401
causes of, 399 –401
cerebral control of. See Brain/behavioral disorders
chemical senses in, 401 –406
cognitive stimulation and, 400 –401
comprehension of, 531 –532
definition of, 5
drinking, 418 , 430 –431
embodied, 4 –5
emotional, 399 , 416 –418, 421 –426. See also Emotional behavior
environmental influences on, 408 –409
evolution of, 406 –408
feeding. See Eating/feeding behavior
free will and, 399
homeostatic mechanisms and, 411
inherited, 6 , 6 f, 406 –408
innate releasing mechanisms for, 406 –407
learned, 6 , 6 f, 408 –409. See also Learning
measurement of, 211 –216
motivated. See also Motivation
neuroanatomy of, 410 –426
neural circuits and, 401
neuroanatomy and, 211 –214
nonregulatory, 412
control of, 432 –435
olfaction in, 401 –404, 403 f
overview of, 5 –6
prey-killing, 399 , 401 , 406 –407
purposeful, 409 –410
purposes of, 399 –401
regulation of
amygdala in, 418
frontal lobe in, 418 f, 419 –420
hypothalamus in, 411 –416, 429 –430, 430 f
limbic system in, 416 –418
prefrontal cortex in, 418 f, 419 –420
regulatory, 411 –412
control of, 426 –431
rewarding, 399 , 401 , 416 , 436 –439
selection of, 418 f, 419 –420
sex differences in, 548 –549
sexual, 412 , 433 –434
 species-typical, 28 , 361 –363
Behavior modification, 575
Behavioral assessment, 533
Behavioral disorders. See also Brain/behavioral disorders; Psychiatric
disorders
research methods for, 565 –567
vs. neurological disorders, 563 –564
Behavioral myopia, 192 –193
Behavioral neuroscience
definition of, 214
methodology of, 211 –244
comparisons for, 238 –239, 238 t
Behavioral sensitization, 510 –511
Behavioral stimulants, 188 –189, 189 f
Behavioral tests, 533
Behavioral therapy, 574 –576
Beliefs, 537
Bell palsy, 62
Bell-Magendie law, 61 , 62
Benzedrine, 172 , 189
Benzodiazepines, 182 , 425
Beta rhythms, 457 –458
Bias, 537
Biceps muscle, 372 , 372 f
Bilateral, definition of, 39
Bilateral symmetry, 17 , 17 f, 18 , 46
Bilingualism
cognitive advantages of, 555
 cortical areas for, 268
Binding problem, 527
Binocular vision, corpus callosum in, 304
Biological clocks, 442 , 443 –444. See also Biorhythms
eating/feeding behavior and, 450 , 455 –456
entrained, 446 –448
free-running rhythms and, 445 –446, 447 f
neural basis of, 250 –456
resetting of, 446 –448, 448
suprachiasmatic nucleus as, 450 –456, 450 f
Biorhythms, 442 –456
basic rest-activity cycle and, 465 , 466 f
biological clocks and, 443 –444. See also Biological clocks
circadian, 442 , 443 –449, 445 t, 446 f. See also Circadian rhythms
circannual, 444 , 445 t
pacemaking, 454 –455
definition of, 442
disturbances of, psychiatric symptoms in, 455 , 455 f
entrained, 446 –448, 449 f
free-running, 445 –446
genetic factors in, 452
infradian, 444 , 445 t
innate, 451 –452
jet lag and, 448 , 449 f
measurement of, 444 –445
neural basis of, 450 –456
neural transplantation and, 452 , 452 f
origins of, 442 –443
 periods of, 444
pineal gland in, 454
in plants, 443 , 444 f
recording of, 444 –445, 445 f, 446 f
retinohypothalamic tract in, 451 , 453
seasons and, 443
suprachiasmatic, 450 –456
ultradian, 445 , 445 t
Zeitgebers and, 446 –448
Bipolar cells, retinal, 294
Bipolar disorder, 186 , 594 . See also Depression
adolescent-onset, 275
drug therapy for, 181 t
mood stabilizers for, 186
Bipolar neurons, 79 , 79 f
auditory, 333
retinal, 294 , 295 f
Birdsong, 349 –351
sex differences in, 275 , 350
vs. language, 349 –350
Bitter taste, 404 –405
Black widow spider venom, 176
Blind spot
retinal, 284 , 291 , 292 , 292 f
in visual fields, 314 –315, 314 f
Blindness. See Vision impairment
Blindsight, 284
Blobs, 299 , 299 f, 312
Block span, 215
Block-tapping test, 214 f, 215
Blood vessels, cerebral, 42 –43, 43 f
Blood–brain barrier, 83 –84
drug therapy and, 174 –175
Bodily-kinesthetic intelligence, 553 –559
Body segmentation, 17 , 17 f, 18 , 59 –60, 61 f
Body size, brain size and, 22 –23, 23 f
Body symmetry, 17 , 17 f, 18
Body temperature, regulation of, 411 –412
Body weight, regulation of, 426 –430. See also Eating/feeding behavior
Bonds, 89
peptide, 93
Bone flute, 322
Bonobos. See Primates, nonhuman
Botulinum toxin, 176
Bradycardia, diving, 138
Braille, 543
Brain. See also under Cerebral; Cortical
behavioral control by. See Brain/behavior disorders
capillary network of, 174 , 174 f
chemical composition of, 88 f
cortical organization in. See also Cortical columns
environmental influences in, 266 –268, 267 f
sex differences in, 546 –549
crossed connections in, 43 , 67
Einstein’s, 552 , 553 f
electrical activity in, 109 –127. See also under Electrical
 measurement of, 222 –226
evolution of, 15 –29, 47 –50, 48 f. See also Brain development
in animals, 15 –19
culture and, 29
in humans, 19 –29
functional maintenance of, behavior and, 400 –401
functions of, 35
behavior as, 35
localized vs. distributed, 70
movement as, 35
principles of, 72
sensory processing as, 35
growth of, 250 f. See also Brain development
hemispheres of, 55 , 55 f
hierarchical organization of, 50 –58, 68 –69, 68 f, 357 –365, 390 –391
information flow in. See Information flow
integration operation of, 127 –130
lateralization in, 334 –335, 346 –347. See also Lateralization
levels of function and, 50 –58, 67 –68
mapping of. See Brain maps
masculinization of, 203 , 273 –274, 432
orientation of, 38 –39
parallel processing in, 68 –69
perceptual world created by, 66
plasticity of. See Neuroplasticity
protective structures for, 37 –40
sectioning of, 39 , 39 f, 43 –46, 43 f, 46 f
sex differences in, 202 –203, 273 –275, 273 f, 546 –549, 547 f, 549 f
 size of
environmental stimulation and, 504
intelligence and, 553 , 553 f
sex differences in, 203 , 273 f, 546 , 547 f
spinal cord integration with, 61 –62
split, studies of, 520 , 542 –543, 545
staining of, 46 –47, 47 f, 75 , 75 f, 211 , 212 f
stimulation of, 35
structure of, 3 –4, 4 f
internal features of, 43 –47, 46 f, 47 f
layers in, 47 , 47 f, 56 , 56 f. See also Cortical layers
microscopic features of, 46 –47, 46 f, 47 f
surface features of, 37 –43, 37 f
symmetry in, 18 , 46 , 46 f
terminology for, 38 –39
vascular, 42 –43, 43 f
subjective reality and, 35
summation in, 128 –130, 129 f, 130 f
Brain cells, 46 –47, 46 f, 73 –106. See also Glial cells; Neuron(s)
Brain chemistry, measurement of, 234 –235
Brain connectome, 363 , 534
Brain development, 247 –280
in autism spectrum disorder, 255
behavioral development and, 247 –248, 260 –265
brain injury and, 276
cell death in, 257
cellular commitment in, 254 f
cognitive development and, 262 –265, 262 f, 263 t, 264 f
cortical layering in, 253 –254
cortical thinning in, 258 , 258 f
critical periods in, 269 –270
drug effects on, 276 –277
enteric nervous system in, 275
environmental influences in, 266 –279
cortical organization and, 266 –268, 267 f
cultural, 29 , 36
environmental stimulation, 266 –268, 267 f, 270 –271, 555
negative experiences, 259 , 270 –271
neural connectivity and, 268 –269
prenatal, 267 , 268
gene expression in, 251
glial development in, 259 –260
growth spurts in, 263 –264
gut bacteria in, 275
hormonal influences in, 273 –275
imprinting in, 270 , 270 f
language development and, 261 –262
masculinization in, 203 , 273 –274, 432
motor development and, 260 –261, 261 f
music and, 267
myelination in, 259 –260, 259 f
neoteny and, 26 –27, 26 f
neural column formation in, 269 , 270 f
neural connectivity in, 268 –269
neural Darwinism in, 257
neural placement in, 268 –269, 270 f
 neurobiology of, 248 –260
neurogenesis in, 252 , 253 f
neuronal development in, 252 –258
neuronal differentiation in, 253 –254, 253 f
neuronal maturation in, 254 –256, 256 f
neuronal migration in, 253 –254, 253 f
neuroplasticity and, 279 –280
prenatal, stages of, 248 –250, 249 f, 250 f
in Romanian orphans, 272
in schizophrenia, 278
sensory input in, 266 –268, 267 f, 270 –271
sex differences in, 260 f
sex hormones in, 202 –204, 273 –275, 432 –433, 546 –549
sexual differentiation and, 203 , 272
socioeconomic status and, 246 , 266 –267
stages of, 253 t
stress and, 271
synaptic development in, 256
synaptic pruning in, 257 –258
tactile stimulation and, 267
time line for, 253 f
Brain imaging. See Imaging studies
Brain injury
astrocytes in, 84
behavioral testing in, 533
behavioral therapy in, 515
compensation in, 219
compensatory mechanisms in, 567 , 597 –598
critical periods for, 276
depression in, 225
developmental effects of, 276
excitation vs. inhibition in, 70 –71
frontal lobe, 55
functional asymmetry and, 539 –541
ischemic, 580
location of, functional loss and, 70
lost neuron replacement solution in, 516 –517
microglia in, 84 –85, 84 f
minimally conscious state and, 13
neurogenesis in, 516 –517
neuroplasticity in, 276 , 369 –370, 369 f, 513 –517
neuropsychological assessment in, 533
new circuit solution in, 514 –516
occipital lobe, 55
outcome in, 2 , 13
parietal lobe, 55
persistent vegetative state and, 13
recovery from, 2 , 13 –14, 513 –517
sex differences in, 547 –548, 549 f
in substance abuse, 197 –198
temporal lobe, 55
teratogens in, 252 , 276 –277
three-legged cat solution and, 514
timing of, 252
traumatic. See Traumatic brain injury
treatment of, 13 –14
Brain lesion studies, 218 –219
Brain maps, 55 , 56 f. See also Homunculus
cortical function, 343 –346, 344 f, 366 –369, 367 f
cytoarchitectonic, 56 , 56 f
electrical stimulation and, 219 –220
event-related potentials in, 224 –225, 224 f, 225 f
Flechsig’s, 259 –260
for infants, 363
movement categories in, 367 –368
place cells and, 222 –223, 222 f
of speech/language areas, 343 –346
tonotopic, 336 –338, 337 f
topographic, 288 , 288 f. See also Topographic organization
of motor cortex, 366 , 369 –370, 369 f
of visual cortex, 302 –303, 303 f
Brain size
in animals, 18 –19, 18 f, 19 f, 22 , 23 , 23 f, 24
behavior and, 22 –23, 23 f, 24 , 27 –29
body size and, 22 –23, 23 f
in chordates, 18 –19, 18 f, 19 f
climate and, 25
diet and, 25 –26
encephalization quotient and, 22 –23, 23 f
estimating, 22 –23
evolution of, 24 –26
heterochrony and, 26
intelligence and, 23 , 24 , 28 –29
neoteny and, 26 –26, 26 –27, 26 f
 in neurological disorders, 28
neuroplasticity and, 28 –29
in nonhuman primates, 22 , 23 f
packing density and, 23 , 24
radiator hypothesis and, 26
skull structure and, 26
variability in, 27 –29
Brain stimulation techniques, 13 , 13 f, 109 –111, 219 –220, 514 –516,
572 , 587
Brain surgery. See Neurosurgery
Brain tumors, 83
neurogenesis and, 252
Brain–behavior link, 3
brain development and, 260 –265. See also Brain development
brain size and, 22 –23, 23 f, 27 –29
in brain/behavioral disorders, 564 –567
causation vs. correlation and, 265
culture and, 36
dualism and, 7 –8, 8 f
evolutionary aspects of, 19 –27. See also Evolution
materialism and, 8 –12
mentalism and, 7
research methods for, 565 –567
unified theory for, 562 –564
Brain/behavioral disorders. See also specific disorders
animal models of, 567 . See also Animal research
biorhythms and, 448 , 455 , 455 f
brain abnormalities in, 570 , 570 f
 causes of, 564 –565, 565 t
classification of, 568 t–569t, 569 –571
compensatory mechanisms in, 567 , 597 –598
degenerative, 584 –591, 585 t
diagnosis of, 565 –566
epidemiology of, 568
epigenetics and, 564
neurobiology of, 565 –567
neuroimaging studies in, 570 –571, 570 f
neurological, 577 –592
vs. psychiatric, 563 –564
psychiatric, 592 –597
vs. neurological, 563 –564
research challenges for, 566 –567
research methods for, 565 –567
sleep problems in, 472 –473
treatment of, 571 –576
behavioral, 574 –576
electrophysiological, 572 –573
neurosurgical, 572
pharmacological, 573 –574. See also Drug(s)
Brain–body orientation, 38
Brainbow, 75
Brain-computer interface, 356
Brain-computer-brain interface, 356
Brain-derived neurotrophic factor, 236
in depression, 595
electroconvulsive therapy and, 572
 neuroplasticity and, 510
Brain-in-a-bottle experiment, 4 –5
Brainstem, 4 , 4 f, 41 –42, 41 f, 51 –54
in autism spectrum disorder, 255
in drinking behavior, 362
in feeding behavior, 362
function of, 51 –52
in grooming behavior, 362
injury of
in locked-in syndrome, 356 , 363
REM sleep deprivation and, 467 , 476 –477
in sexual behavior, 362
in species-typical movement, 361 –363
structure of, 51 –54, 51 f–53f
Brain-stimulation reward, 437
Breast cancer, 97
Bregma, 218
Broca’s aphasia, 227 , 343
Broca’s area, 254 f, 262 , 342 –346, 342 f, 346 f
mapping of, 343 –346, 344 f
Caenorhabditis elegans
light-sensitive ion channels in, 131
number of brain cells in, 23
Caffeine, 190
Calcitonin gene–related peptide, 157
Calcium ions. See also under Ion
endocannabinoids and, 151 –153
in habituation, 164
 in learning, 164 , 164 f
in neurotransmitter release, 143 –144
cAMP (cyclic adenosine monophosphate)
caffeine and, 190
in learning, 165 , 166 –167
Cancer, mutations in, 97
Cannabidiol, 152 –153
Cannabindoid (CB1) receptor, 152 –153
Cannabis, 152 –153, 153 , 189 –190, 198 , 199 , 236
Capillaries, in blood–brain barrier, 174 , 174 f
Carbamazepine, for bipolar disorder, 186
Carbon monoxide, as neurotransmitter, 153
Carbon monoxide poisoning, 315 –316
Carboxyl groups, 93
Card sorting tasks, 531 , 531 f, 533
Cataplexy, 475
Cations, 114 . See also Ion(s)
Caudal, definition of, 38 , 39
Caudate nucleus, 57 , 57 f, 373 , 373 f
Causation, vs. correlation, 265
CB1 receptor, 152 –153
Cell. See also specific types
components of, 86 –97, 87 f
electrical properties of, 109 –127
function of, protein structure and, 86
internal structure of, 86 –96
nerve. See Glial cells; Neuron(s)
nucleus of, 87 f, 90 , 91 –92
 as protein factory, 87 –90
Cell assemblies, in cognition, 523 –525
Cell body, 76 , 76 f
Cell cultures, 75
Cell death, programmed, 198 , 257
Cell membrane, 87 , 90 , 90 f. See also Membrane
absolutely refractory, 122
depolarization of, 119 –122, 122 f
electrical activity in, 111 –127
hyperpolarization of, 119 –122, 119 f, 122 f
ion movement across, 114 –115, 114 f
permeability of, 87 , 114 –116, 114 f
phospholipid bilayer of, 90 f, 92
relatively refractory, 122
repolarization of, 122 f
structure of, 90 –91, 90 f
Cell migration, 253 –254
Cell-adhesion molecules, 256
Cellular commitment, in brain development, 254 f
Central nervous system, 3 –4. See also Brain; Spinal cord
development of, 247 –280. See also Brain development
evolution of
in animals, 15 –19
in humans, 19 –29
functional organization of, 36 –37, 36 f, 50 –58, 67 –68
hierarchical organization of, 50 –58, 68 –69, 68 f, 357 –365, 390 –391
neurotransmission in, 158 –162
sensory and motor divisions in, 69
 structure of, 3 –4
Central pain, 385
Central sulcus, 41 f, 42 , 55 , 55 f
Cerebellar agenesis, 34
Cerebellar dysfunction, in autism spectrum disorder, 34
Cerebellar homunculus, 375 –376, 376 f
Cerebellum, 4 , 18 –19
anatomy of, 375 –376, 376 f
in cognition, 535 –536
evolution of, 18 –19, 19 f
functions of, 34 , 52 –54
in movement, 52 –54, 375 –378, 376 f–378f
structure of, 41 f, 42 , 51 f, 52 f
topographic organization of, 375 –376, 376 f
Cerebral aneurysms, 347
Cerebral anoxia, 363
Cerebral aqueduct, 44
Cerebral arteries, 43 , 43 f
Cerebral asymmetry, 68 , 334 –335. See also Lateralization
anatomical, 539 , 540
auditory processing and, 541 –542
cognition and, 540 –545
dichotic listening and, 541
functional, 334 –335
handedness and, 334 –335, 549 –551
hypotheses for, 543 –545
inferential thinking and, 545
language and, 334 –335, 543 –545
 movement and, 543 –545
music and, 346 –347, 541
in neurological patients, 540 –541
in normal brain, 541 –542
overlapping functions and, 543
in split-brain patients, 520 , 542 –543, 545
visual processing and, 541 –542, 542 f. See also Visual fields
Cerebral circulation, 42 –43, 43 f
Cerebral cortex, 40 –42, 40 f, 54 –56. See also specific subunits ( e.g. ,
Motor cortex) and under Cortical
connections of, 56
development of, 253 f. See also Brain development
developmental thinning of, 258 , 258 f
layers of. See Cortical layers
neocortex, 54
sensory and motor divisions in, 69
structure and function of, 54 –56, 55 f
top-down processing in, 56
Cerebral hemispheres, 4 , 4 f, 40 , 40 f, 55 , 55 f
evolution of, 18 –19, 19 f
surgical removal of, 42
symmetry/asymmetry of, 18 , 46 , 46 f, 68 , 334 –335, 539 –546. See
also Cerebral asymmetry
Cerebral ischemia, 580 , 581 f
Cerebral microbleeds, dementia and, 591
Cerebral palsy, 363
Cerebral ventricles, 8 , 44 , 44 f
Cerebral voltammetry, 235
Cerebrospinal fluid, 44
 flow of, 82
functions of, 82
in hydrocephalus, 82
in meningitis, 42
production of, 82
shunts for, 82
Cerebrum, 4 , 4 f, 18 –19, 19 f, 41 , 41 f, 42 . See also under Cerebral
Cervical spine, 60 , 61 f
Channelrhodopsins, 131
Channels. See Ion channels
Chemical bonds, 89
Chemical messengers. See Neurotransmitters
Chemical synapses, 141 –142, 142 f. See also Synapses
Chemistry basics, 88 –89
Chemoaffinity hypothesis, 268 –269, 270 f
Chemogenetics, 221
Children
brain maps for, 363
dendritic spine density in, 258
Chimeric animals, 102
Chimpanzees, 15 , 20 , 20 f. See also Primates, nonhuman
Chlamydomonas reinhardtii, light-sensitive ion channels in, 131
Chloride ions. See also under Ion(s)
movement of, 114 f, 115 –116
resting potential and, 116 –119, 117 f
Chlorpromazine, for schizophrenia, 184 f
Choline, 149
Cholinergic neurons, 156 –158
Cholinergic system, 157 –158, 160 , 160 f
Chordates, 16 f, 18 –19, 18 f, 19 f. See also Spinal cord
Chromosomes, 91 –92, 91 f, 96 , 103 –105
abnormalities of, 100 , 101 f
histones and, 103 –104
number of, 97 f
abnormal, 100 , 101 f
sex, 96 –97, 97 f
sex differences and, 548
Chronic cerebrospinal venous insufficiency, multiple sclerosis and, 584
Chronic traumatic encephalopathy, 578
Chronotypes, 452 , 453
Cigarette smoking, nicotine addiction in, 193 , 438 –439
Cilia, of hair cells, 330 , 332 f, 336 –337
Cingulate cortex, 57 , 57 f
Circadian genes, mutations in, 453
Circadian rhythms, 442 , 443 –449, 445 t. See also Biorhythms
cognitive, 455 –456
emotional, 456
entrained, 446 –448
free-running, 445 –446, 446 f
pacemaking, 452 –454
Circannual rhythms, 444 , 445 t
pacemaking, 454 –455
Circulation, cerebral, 42 –43, 43 f
Cladogram, 17 f, 18 , 18 f
Classes, taxonomic, 16 , 16 f
Classical conditioning, 481 –482, 482 f. See also Conditioning
 in substance abuse, 177 –178, 195
Clinical trials, 14
Clorazepam, 182
Cloning, 101 –102, 102 f
Closed head injury. See Traumatic brain injury
Cocaine, 172 , 189 , 189 f, 198
Coccygeal spine, 60 , 61 f
Cochlea, 329 –330, 330 f–332f
hair cells of, 330 , 330 f, 332 , 332 f, 336 –337
Cochlear implants, 337 –338, 337 f
Cochlear nucleus, 333 , 334 f
Codominance, 97
Codons, 93
Cognition, 521 –560
age-related changes in, 591
in animals, 522 –524, 545
association cortex in, 525 –533
attention in, 528 –530
cell assemblies in, 523 –525
cerebellum in, 535 –536
cerebral asymmetry in, 539 –546
characteristics of, 521 –522
convergent vs. divergent thinking and, 554
definition of, 521
emotion and, 526
evolution of, 522
imitation and, 531 –532
inferential thinking in, cerebral asymmetry and, 545
 intelligence and, 553
language and, 521 –522
multisensory integration in, 527 , 527 f
neural circuits in, 522 –525
neural unit of thought in, 522 –525
object knowledge in, 526 –528
planning and, 530 –531
psychological constructs in, 520
sequential thinking and, 521 –522
sex differences in, 203 , 546 –549, 547 f–549f
sleep deprivation and, 466 –467
social, 536 –538
spatial, 527 –528, 527 f, 528 f
sex differences in, 546 –549
in split-brain patients, 520 , 542 –543, 545
studies of, 533 –536. See also Cognitive neuroscience
Cognitive development, 262 –265, 262 f, 263 t, 264 f
cultural aspects of, 29
Cognitive enhancement, 172 , 598
Cognitive neuroscience, 533 –538
applications of, 536 –538
methods of, 533 –536
Cognitive organization. See Brain; Cerebral asymmetry; Topographic
organization
Cognitive rhythms, 455 –456
Cognitive stimulation
behavior and, 400 –401
brain development and, 272
 brain size and, 504
in learning, 504 –505, 505 f
Cognitive therapy, 575
Cognitive-behavioral therapy
for anxiety disorders, 597
for depression, 186 , 596
Cogwheel rigidity, 586
Colliculus, 53 , 53 f, 69
inferior, 333 , 334 f
Color agnosia, 316
Color blindness, 311
Color constancy, 313
Color mixing
additive, 310 , 310 f
subtractive, 310 , 310 f
Color vision, 310 –313
afterimages in, 312
blobs in, 299 , 299 f, 312
impaired, 311 , 316
opponent-process theory of, 311 –313, 311 f, 312 f
rods and cones in, 293 , 293 f, 294 f
subtractive color mixing and, 310
trichromatic theory of, 310 –311
Columns. See Cortical columns
Coma, 470
reticular activating system in, 470
Common ancestor, 15 , 20 , 22 , 22 f
Compensation, in lesion studies, 219
Competitive inhibitors, 187 –188
Complex cells, of visual cortex, 307 , 307 f
Complex tones, 326
Computed tomography (CT), 226 –227, 227 f
Computer–brain interface, 356
COMT gene, 236
Concentration gradient, 114 , 114 f
Concordance rate, 235
Concrete operational stage, of cognitive development, 263 , 263 t
Concurrent discrimination, 264 f, 265 , 274
Concussion, 578 , 581 , 582 . See also Traumatic brain injury
Conditioned stimulus, 482
Conditioning
classical (Pavlovian), 481 –482, 482 f
eye-blink, 481 –482, 482 f
fear, 481 –482, 498 –499
in learning, 408 –409
operant (instrumental), 482 –483
respondent, 481 –482
in substance abuse, 178 , 195
Cones (photoreceptors), 293 –294, 293 f, 294 f
Congenital adrenal hyperplasia, 433
Connectome
baby, 363
brain, 534
definition of, 363
Conscious memory. See Memory, explicit
Consciousness, 556 –558
 definition of, 556
nonunitary nature of, 476 –477
sleep and, 476 –477
Conservation, in cognitive development, 262 f, 263 , 263 t
Consolidation, of memory, 467 –468, 497 –498
Constraint-induced therapy, 370
Contralateral, definition of, 39
Contralateral neglect, 529 –530, 530 f
Contrecoup injury, 578 –579, 579 f
Convergent thinking, 554
Copulatory behavior. See Sexual behavior
Copycat (cloned cat), 102 , 102 f
Cornea, 291 , 291 f
Coronal, definition of, 39
Coronal section, 39 f, 43 –44, 43 f, 44 f
Corpus callosum, 43 f, 45 , 46 f
absence of, 103 , 103 f
handedness and, 551
severing of, cognitive effects of, 542 –543
visual, 304 , 304 f
Correlation, vs. causation, 265
Corsi block-tapping test, 214 f, 215
Cortex. See under Cerebral cortex; Cortical
Cortical columns, 269 , 270 f, 298
definition of, 298
ocular dominance, 269 , 270 f, 308 –309, 309 f, 312 , 312 f
orientation, 308 –309, 312 , 312 f
in temporal lobe, 309 –310, 309 f
 in visual cortex, 269 , 270 f, 308 –309, 309 f
Cortical function mapping, 343 –346, 344 f, 367 –368
Cortical layers, 47 , 47 f, 56 , 56 f, 69 , 359
development of, 253 –254
in motor cortex, 56 , 359
in neocortex, 359
in occipital cortex, 299 –300, 299 f
Cortical lobes, 55 , 55 f. See also Frontal lobe; Occipital lobe; Parietal
lobe; Temporal lobe
Cortical mapping, 343 –346, 344 f, 366 . See also Brain maps
homunculus and, 366 , 366 f. See also Homunculus
Cortical organization
environmental influences in, 266 –268, 267 f
sex differences in, 546 –549
Cortical thickness
developmental changes in, 258 , 258 f
intelligence and, 259 –260, 259 f
language and, 258 , 258 f, 261 f
musical ability and, 348
sex differences in, 546 , 547 f
Corticospinal tracts, 370 –371, 370 f
Cortisol, in stress response, 205 –207, 206 f, 595
Coup injury, 578 –579, 579 f
Crack cocaine, 189 f, 198
Cranial nerves, 41 f, 59 , 60 f
Creativity, hyperconnectivity and, 535
Creolization, 341 –342
Critical periods
 for brain development, 269 –270
for brain injury, 276
for gene expression, 105
for language acquisition, 341
Crossed neural connections, 43 , 67
Cross-tolerance, 182
cryptochrome gene, 453
CT scans, 226 –227, 227 f
Cultural bias, 537
Cultural influences, on brain development, 29 , 36
Cultures, cell, 75
Curare, 176 –177
Current, electrical, 110
Cyclic adenosine monophosphate (cAMP)
caffeine and, 190
in learning, 165 , 166 –167
Cytoarchitectonic maps, 56 , 56 f. See also Brain maps
Cytochrome P450 enzymes, 175
Cytosine, 91 f, 92
Daily rhythms. See Circadian rhythms
Date rape drugs, 182
Daydreams, 464
Deafferentiation, 382
Deafness, cochlear implants for, 337 –338, 337 f
Decibel (dB), 325
Decision making, 538
Declarative memory, 484 , 485 t
Deep brain stimulation, 13 , 13 f, 219 –220, 516 , 572 , 587
 for epilepsy, 582 –583
for Parkinson disease, 375
Deinstitutionalization, antipsychotics and, 184 , 184 f
Delayed matching-to-sample test, 495 , 495 f
Delayed-alternation task, 495 , 495 f
Delayed-response test, 495 , 495 f
Delta receptors, 187
Delta rhythms, 458
Dementia
Alzheimer, 70 , 160 , 492 , 498 , 588 –591
brain abnormalities in, 85 , 167 , 588 –589, 588 f, 589 f
in Down syndrome, 100
Parkinson disease and, 589 –590
concussion and, 578
definition of, 585
degenerative vs. nondegenerative, 585 , 585 t
marginal high blood pressure and, 591
types of, 585 t
Dementia pugilistica, 578
Dendrites, 76 , 76 f, 77 , 78 f, 79 –80, 87 f, 131
arborization (branching) of, 254 , 254 f, 502 –503, 503 f
changes in, 502 –503, 503 f. See also Neuroplasticity
development of, 254 –255, 254 f
Dendritic spines, 77 , 78 f, 87 f, 167
age-related density of, 258
growth of, 254 –255, 254 f, 502 –503, 503 f
in learning, 167
Dendrodendritic synapse, 145 , 145 f
Deoxyribonucleic acid (DNA), 91 –92, 91 f
methylation of, 104 , 104 f, 251 , 432
modification of, 104 , 104 f
Dependence. See Substance abuse
Depolarization, 119 –122, 119 f
Depolarizing potentials, 130
Depression, 162 , 184 –185, 186 , 424 , 594 –596
adolescent-onset, 275
in bipolar disorder, 594
in brain injury, 225
major, 162 , 184 –185, 186
neurobiology of, 594 –595
seasonal, 448
sleep problems in, 473
stress and, 595 –596
treatment of, 596
antidepressants in, 181 t, 185 , 186 , 467 , 574 , 594 , 596 . See also
Antidepressants
deep brain stimulation in, 572
electroconvulsive therapy in, 186 , 572
transcranial magnetic stimulation in, 220 , 220 f, 573 , 573 f
Dermatomes, 60 , 61 f, 359
Designer drugs, 221
Deuteranopia, 311
Development
brain. See Brain development
cognitive, 262 –265, 262 f, 263 t, 264 f
gene expression in, 251
 growth spurts in, 263 –264
language, 254 f, 258 , 261 –262, 341
motor, 260 –261, 261 f
prenatal
cross-species similarities in, 248 –250, 248 f
sexual differentiation in, 203 , 272
Developmental disability
brain abnormalities in, 278 –279
causes of, 278 –279, 279 t
in fetal alcohol spectrum disorder, 183
in phenylketonuria, 565
Dextroamphetamine, 172
Diabetes mellitus, 202
Diagnostic and Statistical Manual of Mental Disorders (DSM-5), 181 ,
568 t–569t, 569 –570
Diaschisis, 580
Diazepam, 182
Dichotic listening, 541
Diencephalon, 48 , 48 f, 51 , 51 f, 53 –54, 53 f
Diet. See also Nutrition
brain size and, 25 –26, 25 f
depression and, 184 –185
epigenetic effects of, 105
multiple sclerosis and, 126
weight-loss, 428
Diffusion, 114 –116
in neurotransmitter deactivation, 144
Diffusion tensor imaging, 229 , 229 f
 in tractography, 534 , 535 , 535 f
Digestive system, eating control and, 427 , 429 f
Dimers, 453
Disinhibition theory, 191 –192
Displacement task, 264 , 264 f
Distal, definition of, 39
Distributed hierarchical model, 68 , 68 f
Distributed reinstatement theory, 497
Diurnal animals, 442
Divergent thinking, 554
Diving bradycardia, 138
DNA, 91 –92, 91 f
methylation of, 104 , 104 f, 251 , 432
modification of, 104 , 104 f
Dr. Death, 198
Dominant alleles, 97 , 99 f
Domino effect, in action potential propagation, 123 f, 124
Domoic acid poisoning, 197 , 197 f
L -Dopa, 150 , 150 f, 152 , 573 , 587
Dopamine, 150 , 150 f, 159 f, 160 –161. See also Neurotransmitters
in attention-deficit/hyperactivity disorder, 240 , 241
in enteric nervous system, 158
in memory, 498
in movement, 375
in Parkinson disease, 140
receptors for, 155 , 155 t
reward and, 437 –438, 437 f
in schizophrenia, 161 , 184
 stimulants and, 188
in substance abuse, 192 , 193 , 195
Dopamine hypothesis, 184
Dopamine neuron transplant, 161
for Parkinson disease, 516 , 587 –588
Dopaminergic system, 159 f, 160 –161, 567 f
Dopa-responsive dystonia, 74
Dorsal, definition of, 38 , 39
Dorsal roots, 61 , 62 f
Dorsal visual stream, 69 –70, 69 f, 297 , 300 f, 313 , 527 f
as how pathway, 297 , 317 –318
injury of, 317 –318
location of, 527 f
secondary somatosensory cortex in, 393 –394
in vision for action, 527 f
Dorsolateral prefrontal cortex, 258 , 526 f
theory of mind and, 536
Dorsomedial nucleus, 54
Dorsomedial prefrontal cortex, 418 f, 419
Dorsomedial thalamic nucleus, 53 f, 54
Dosage, 173 –174
Down syndrome, 100 , 101 f
DREADD, 221
Dreams, 461 –464
activation-synthesis hypothesis for, 462 –463
anxiety, 463 –464
avoidance vs. approach behavior in, 463 –464
content of, 461 –464
 evolutionary hypothesis for, 463 –464
function of, 463 –464
hallucinations and, 476 –477
lucid, 464 , 476
in memory storage, 468
in REM sleep, 458 , 461 –464
Drinking behavior, 430 –431
amygdala in, 418
water intoxication and, 431
Drosophila melanogaster, learning in, 166 –167, 167 f
Drowsy state, 458
Drug(s)
of abuse. See Substance abuse
adverse effects of, 574
agonist/antagonist, 176 –177, 176 f
for behavioral disorders, 573 –574
blood–brain barrier and, 174 –175
classification of, 181 t
cross-tolerance to, 182
designer, 221
dosage of, 173 –174
effects of, variability in, 176 –180
as environmental contaminants, 175
excretion of, 175
groupings of, 181 –191, 181 t
individual responses to, 191 –194
mechanism of action of, 175 f, 176 –177, 176 f
metabolism of, 175
 movement disorders due to, 574
neuroplasticity and, 510 –511, 511 f
prenatal exposure to, brain injury from, 276 –277
psychoactive, 173
antianxiety agents, 181 –182, 181 t, 425 , 597
antidepressants, 181 t, 185 , 186 . See also Antidepressants
antipsychotics, 181 t, 184 , 574
grouping of, 181 –191
mood stabilizers, 181 t, 186
names of, 181
opioid analgesics, 181 t, 187 –188
psychedelic/hallucinogenic stimulants, 181 t, 189 –190
psychotropics, 181 t, 188 –190
sedative-hypnotics, 181 –182, 181 t, 473
routes of administration for, 173 –174, 173 f
sensitization to, 178 –180, 510 –511
Drug Addiction Treatment Act of 2000, 196
Drug dependence, 193
Drug manipulation studies, 220
Drug tolerance, 177 –178
Drug-dependency insomnia, 473
Drug-induced behavioral sensitization, 510 –511
Drug-induced psychosis, 184 , 198 , 199 , 236
DSM-5 (Diagnostic and Statistical Manual of Mental Disorders), 5 th
ed., 181 , 568 t–569t, 569 –570
Dualism, 7 –8, 8 f
Dunce, 166
Dura mater, 37 , 37 f
Dynorphins, 187
Dyskinesias, 373 –374
Dyslexia, 480
Dystonia(s)
focal hand, 507
selective, 375
E cells, 452
Ear. See also under Auditory
structure of, 329 –331, 330 f, 331 f, 332 f
in vestibular system, 388 –389, 389 f
Eardrum, 329 , 330 f
Eating disorders, 275 , 427
Eating/feeding behavior
amygdala in, 418 , 430 , 430 f
aversive behavior in, 409 , 438 , 438 f
biological clocks and, 450 , 455 –456
cognitive factors in, 430
dieting and, 428
digestive system and, 427 –428, 429 f
eating disorders and, 427
environmental factors in, 427
of fly, 409 –410
hedonic reactions in, 438 , 438 f
hypothalamus in, 399
prefrontal cortex in, 430
regulation of, 426 –430
reward and, 437 –438
Echolocation
 in bats, 351 –352
in blind people, 335
Economic decision making, 538
Ecstasy (MDMA), 190 , 198
EEG. See Electroencephalography (EEG)
Efferent nerves, 37 , 37 f
Efferent sensory signals, 358
Ego, 563
Elderly, cognitive loss in, 591 . See also Dementia
Electrical activity
in brain, measurement of, 222 –226
in cell membrane, 111 –127
early studies of, 109 –113
in giant axon of squid, 112
recording of
electroencephalographic, 108 , 111 . See also
Electroencephalography (EEG)
microelectrodes in, 113 –114
oscilloscope in, 113
single-cell, 133 f
voltmeter in, 110 , 111
during sleep, 457 f, 458 –459, 458 –459
stimulation of, 109 –111
voltage gradient and, 114 –115
Electrical charges, 114 –116
Electrical potentials, 110
action, 120 –123. See also Action potential
definition of, 110
 excitatory postsynaptic, 127 –130, 129 f, 130 f, 164
graded, 119 –120, 119 f
EEG recording of, 223 –224, 223 f
summation of, 128 –130, 129 f, 130 f
inhibitory postsynaptic, 127 –130, 129 f, 130 f
miniature postsynaptic, 144
resting, 116 –119, 117 f
threshold, 120
Electrical recording studies, 110 , 111
Electrical self-stimulation, 219
Electrical stimulation studies, 109 –111
Electrical synapses, 142 , 145 –146
Electricity, 110
early studies of, 109 –113
Electroconvulsive therapy, 186 , 572
Electrocorticography (ECoG), 223
Electrodes, 110
Electroencephalography (EEG), 108 , 111 , 210 –211, 223 –224
alpha rhythms in, 458
applications of, 223 –224
beta rhythms in, 458
in brain mapping, 223 f, 224 –225
definition of, 111
delta rhythms in, 458
desynchronized tracings in, 470
event-related potentials and, 224 –225, 224 f
in graded potential recording, 223 –224, 223 f
in sleep studies, 223 f, 224 , 457 –459, 457 f, 459 f, 470 –472
 vs. magnetoencephalography, 226
in waking state, 457 –458, 457 f, 459 f, 471
Electrographic seizures, 108
Electrolytic lesions, 218 –219
Electromyography, in sleep studies, 457 , 457 f
Electron, 88 , 89 , 110
Electron microscope, 140 –141, 141 f
Electrooculography, in sleep studies, 457 , 457 f
Elements, chemical, 88 , 88 f
Elephants, brain size in, 22 , 23 f, 24
Eliminative materialism, 12
Embodied behavior, 4 –5
Embryonic disc, 249 , 249 f
Embryos
cross-species similarities in, 248 –250, 248 f
development of, 248 –252, 249 f, 250 f
preformation and, 248
Emotion
anterior cingulate cortex and, 526
definition of, 398
expression of, 410 –411, 421 –422, 537
regulation of, 537
Emotional behavior, 399 , 416 –418, 421 –426
abnormal, 424 –426
amygdala in, 57 –58, 57 f, 418 , 422 –423
in animals, 410 –411
control of, 537
expressive, 410 –411, 421 –422
 facial expressions and, 423 –424
generation of, 421 –422
James-Lange theory of, 421
limbic system in, 57 –58, 57 f, 416 –418, 417 f
overview of, 421 –422
prefrontal cortex in, 423 –424
somatic marker hypothesis for, 421 –422
tone of voice and, 424
Emotional disorders, 424 –426
Emotional memory, 499 , 499 f
Emotional pain, 398
Emotional rhythms, 456
Emotional therapy, 575
Empathy, 536
Encephalitis, 42
L-dopa for, 150 , 150 f, 152
memory loss in, 490
Encephalization, 18
Encephalization quotient (EQ), 22 , 23 f
End foot, 77 , 78 f
End plates, 133 , 133 f, 134
Endocannabinoids, 151 –153
Endocrine glands, 202 –206. See also Hormones and specific glands
regulation of, 200 –201, 201 f, 412 –415. See also Hypothalamus
Endolymph, 388
Endomorphins, 187
Endoplasmic reticulum, 87 f, 90 , 93
Endorphins, 151 , 187
Endothelial cells, in blood–brain barrier, 174 , 174 f
Enkephalins, 151 , 187
Enteric nervous system, 37 , 64 –65
autonomy of, 158
in brain development, 275
neurotransmitters of, 158
Entorhinal cortex
in Alzheimer disease, 589
in memory, 491 –492, 491 f
Entrainment, 446 –448, 449 f
Environment, epigenetics and, 11 . See also Epigenetics
Environmental enrichment
behavior and, 400 –401
brain development and, 270 –271
brain size and, 504
intelligence and, 555
in learning, 504 –505, 505 f
Enzymes, 93 –94
Ependymal cells, 82 , 82 t
Epidemiology, 568
Epidermal growth factor, 252
in brain injury, 516
Epidural anesthesia, 387
Epigenetic code, 103 –105
Epigenetic drift, 237
Epigenetics, 11
applications of, 237
autism spectrum disorders and, 255
 brain/behavioral disorders and, 564
changes across populations and, 237
critical periods and, 105
DNA modification and, 104 , 104 f
frontal lobe development and, 258 –259, 271
histone modification and, 103 –104, 104 f
intelligence and, 555
life experiences and, 235 , 237
neuroplasticity and, 511
neurotoxins and, 196
phenotypic plasticity and, 36 , 103 –105
reflective vs. reflexive systems and, 538
RNA modification and, 103 –104, 104 f
schizophrenia and, 593
sex hormones and, 274 –275, 432
sexual orientation and, 435
stress effects and, 237 , 271
substance abuse and, 196
synaptic organization and, 555
twin studies and, 237
Epilepsy, 108 , 581 –583. See also Seizures
brain surgery for, 343 , 345
Epinephrine (adrenaline), 138 –139, 138 f, 150 , 150 f. See also
Neurotransmitters
in stress response, 204
Episodic memory, 467 , 486 –487, 487 f
Equilibrium, vestibular system in, 388 –389, 389 f
Estradiol, in brain masculinization, 432
Estrogen. See also Sex hormones
activating effects of, 433
in brain development, 203 , 273 –275, 546 –549
in brain masculinization, 432
cognitive function and, 203
functions of, 203
lifelong effects of, 274 –275
neuroplasticity and, 509 , 509 f
sexual behavior and, 433
Event-related potentials, 224 –225, 224 f, 225 f
vs. magnetoencephalography, 226
Evolution
of behavior, 406 –408
of brain, 15 –29, 47 –50, 48 f
brain–behavior link and, 19 –27
of cognition, 522
common ancestor in, 15 , 20 , 22 , 22 f
culture and, 29
Darwin’s theory of, 8 –12
dreams and, 463 –464
hierarchical organization of nervous system and, 36 –37
of language, 8 , 322 , 340 –342
of music, 322
natural selection and, 8 –12
neoteny and, 26 –27
radiator hypothesis and, 26
of sex differences, 548 –549
Evolutionary psychology, 407 –408
Excitation, vs. inhibition, 70 –71, 80
Excitatory postsynaptic potentials, 127 –130, 129 f, 130 f
in habituation, 164
Excitatory synapses, 146 , 146 f
Executive functions, of frontal lobe, 419 –420
Exelon (rivastigmine), 492
Exercise, therapeutic benefits of, 576
Expectations, 537
Experimental animals, 101 –102, 239 –242. See also Animal research
Explicit memory. See Memory, explicit
Extensors, 372
External ear canal, 329 , 330 f
Extinction, 529 –530, 530 f
Extracellular fluid, 87 f, 90
Extracellular recordings, 222
Extrastriate cortex, 299 , 300 f
Eye. See also under Vision; Visual
structure of, 289 –291, 291 f
Eyeblink conditioning, 481 –482, 482 f
Facial agnosia, 301
Facial expressions
innate releasing mechanisms for, 407 , 407 f
interpretation of, 424 , 530
loss of, 423 –424
production of, 423 –424
Facial nerve, 59 , 60 f
Facial paralysis, 62
False memories, 485 , 487
Families, taxonomic, 16 , 16 f
Farsightedness, 290 –291
Fatal familial insomnia, 472
Fear conditioning, 481 –482, 498 –499
Fear, emotional memory and, 498 –499
Feedback loops, hormonal, 414 –415, 415 f
Feeding behavior. See Eating/feeding behavior
Festination, 586
Fetal alcohol spectrum disorder, 28 , 183 , 267 , 271
Fight-or-flight response, 63 , 157 –158, 204 , 205 f
Filopodia, 167 , 256 , 256 f
Fissures, 41 f, 42
Flehmen, 403 f
Flexors, 372
Flies, feeding behavior of, 409 –410
Flocculus, 375 –376, 376 f
Fluid homeostasis, 430 –431
Fluoxetine, 185 , 186 , 596
Flupentixol, sensitization to, 180
Flynn effect, 29
FMRI, real-time, 576
Focal hand dystonia, 507
Focal seizures, 582
Follicle-stimulating hormone (FSH), 414 t
Foraging, brain size and, 25 –26, 25 f
Forebrain, 4 , 4 f, 48 , 48 f, 54 , 54 f
in movement initiation, 358 –361, 360 f, 361 f
structure of, 54 , 54 f
Foreign languages
cortical localization for, 268
learning of, 340 –341
Formal operational stage, of cognitive development, 263 , 263 t
Fovea, retinal, 289 –292, 291 f, 302 , 303 f
Free-running rhythms, 445 –446
Frequency, of sound waves, 323 –324, 324 f, 326
in music, 328 , 328 f
Frontal, definition of, 39
Frontal leukotomy, 423 –424, 423 f
emotional behavior after, 423 –424
Frontal lobe, 41 f, 55 , 55 f
agenesis of, 420
in association cortex, 525 –526, 526 f, 527 f
in attention, 529
in cognition, 522 , 529
development of, 258 –259, 259 f
epigenetic effects on, 258 –259, 271
executive functions of, 419 –420
injuries of, 55
amnesia and, 487 , 495
divergent thinking and, 554
emotion and, 421 –422
loss of libido and, 436
in memory, 495
in planning, 531
in schizophrenia, 278
in sequential movement, 522
 in sexual behavior, 436
structure and function of, 55 , 55 f, 418 f, 419 –420
Frontal lobotomy, 423 –424, 423 f
emotional behavior after, 43 –424
Fruit foraging, brain size and, 25 , 25 f
Functional brain imaging, 229 –234
Functional connective magnetic resonance imaging (fcMRI), 534 –535,
534 f
Functional levels, 50 –58, 67 –68
Functional magnetic resonance imaging (fMRI), 230 –231, 230 f
in brain mapping, 534 –535, 534 f
real-time, 576
resting-state, 231
Functional near-infrared spectroscopy (fNIRS), 210 , 231 –232, 231 f
Fundamental frequency, 326 , 326 f, 328
Fusiform face area, 301
g factor, 28 , 553
G proteins, 154 , 154 f
GABA (gamma-aminobutyric acid), 150 , 151 f, 566
receptors for, 155 , 155 t
GABAA receptor, drug effects at, 182
Gamma-hydroxybutyric acid (GHB), 182
Ganglia, 18
basal. See Basal ganglia
parasympathetic, 63 –64
posterior-root, 381 –382, 381 f
sympathetic, 63 –64
Ganglion cells
 melanopsin, 453
on-center/off-center, 305 –306, 306 f, 307 f
retinal. See Retinal ganglion cells
Gap junctions, 142 , 142 f, 145 –146
Gaseous neurotransmitters, 153
Gastrointestinal function, enteric nervous system and, 64 –65, 65 f
Gastrointestinal system, eating control and, 427 –428, 429 f
Gate theory of pain, 386 –387, 387 f
Gated ion channels, 95 , 95 f, 117 –119, 121 f, 122 f. See also Ion
channels
Gender differences. See Sex differences
Gender identity, 435
Gene(s), 10 –11, 91 –92, 96 –105
alleles and, 97 , 99 f
identification of, 236
transcription of, 93 f
Gene expression, 10 –11, 97 , 103 , 103 f
critical period for, 105
definition of, 236 , 251
in development, 251
epigenetics and, 11 , 103 –105, 236 –237. See also Epigenetics
measurement of, 236 –237
methylation and, 251 , 251 f, 432
Gene knockout, 102
Gene methylation, 104 , 104 f, 251 , 432
General intelligence, 28 –29, 553
General stimulants, 190
Generalized anxiety disorder, 425 , 574 , 597 . See also Anxiety
disorders
Generalized seizures, 582
Genetic code, 93 , 93 f
Genetic diseases
diagnosis of, 74
inheritance of, 98 –100
Genetic engineering, 101 –102, 102 f
Genetic mutations, 97 –100
beneficial, 98
disease-causing, 98 –100
learning and, 166 –167, 167 f
in selective breeding, 101
Genetic studies, 235 –237
Genetic testing, 74
Geniculate nuclei. See Lateral geniculate nucleus; Medial geniculate
nucleus
Geniculostriate pathway/system, 296 , 296 f, 297 –298, 297 f, 298 f
Genome sequencing, 74
Genotype, 10 , 96
Genus, 16 , 16 f
Ghrelin, 202
Giant axon of squid, electrical activity in, 112 , 112 f
Giant depolarizing potentials, 133
Glabrous skin, sensory receptors in, 379
Glasgow Coma Scale, 13
Glial cells, 46 , 47 f, 80 –85, 146
in blood–brain barrier, 173
definition of, 80
development of, 259 –260
 formation of, 252
functions of, 82 t
in nerve repair, 85 –86, 85 f
properties of, 82 t
radial, 253 , 253 f
types of, 80 –85, 82 t
Glial uptake, in neurotransmitter deactivation, 144
Glioblasts, 250
Gliogenesis, 252
Gliomas, 83
Globus pallidus, 57 , 57 f, 373 , 373 f
electrode placement in, 572 , 587
in movement, 375 , 376 f
in Parkinson disease, 375 , 587
Glomeruli, olfactory, 402 f, 403
Glossopharyngeal nerve, 59 , 60 f
Glucocorticoids, 202 . See also Hormones
neurotoxicity of, 510
Glucose, in eating behavior, 427
Glutamate, 150 , 151 f
in domoic acid poisoning, 197
in long-term potentiation, 501 –502, 501 f
neurotoxicity of, 197
receptors for, 155 , 155 t
Glutamate psychedelics, 190
Glutamate receptor, 197
Glycine, 150
receptors for, 155 , 155 t
Goal trackers, 195 –196
Golgi body, 87 f, 90 , 94 –95, 94 f
Gollin figure test, 484 , 484 f
Gonadal hormones. See Sex hormones
Graded potentials, 119 –120, 119 f
EEG recording of, 223 –224, 223 f
summation of, 128 –130, 129 f
Grammar, universal, 341 –342, 521
Grasping
development of, 260 –261, 261 f
hapsis and, 380 , 380 f
movements in, 360 –361, 361 f
vision in, 300 , 313 , 316 , 316 f, 317 f
Gray matter, 43 , 43 f, 46 –47, 47 f
layers of, 56 , 56 f
periaqueductal, 53 , 53 f
in pain, 388
in reticular formation, 52
sex differences in, 546 , 547 f
spinal, 62 f
thickness of, language development and, 258 , 258 f, 261 , 261 f, 262
Great apes, 20 . See also Primates, nonhuman
Grooming behavior, 362
Growth cones, 256 , 256 f
Growth factors, 84
in brain development, 252
neuroplasticity and, 84 , 510
Growth hormone (GH), 414 t
Growth spurts, 263 –264
Guanine, 91 f, 92
Gustation, 404 –406
Gut bacteria, 65
in brain development, 275
Gynandromorphs, 275
Gyrus, 42 , 55 , 55 f
Heschl’s, 334 , 334 f, 347 , 347 f
Gyrus fornicatus, 38
Habituation, 163 –164, 164 f, 500
dendritic spines in, 167
Hair cells
in auditory system, 330 , 330 f, 332 , 332 f, 336 –337
in vestibular system, 388 , 389 f
Hairy skin, sensory receptors in, 379
Hallucinations
dreams and, 476 –477
hypnogogic, 475
in schizophrenia, 278
in substance abuse, 198
Hallucinogenic amphetamine, 198
Halorhodopsin, 131
Hammer, 329 , 330 f
Handedness, cortical organization and, 334 –335, 549 –551
Hapsis, 380 , 380 f
Haptic-proprioceptive pathway, 382 –383, 383 f
Harrison Narcotics Act of 1914, 196
Head direction cells, 494
Head trauma. See Traumatic brain injury
Headaches, migraine, scotoma in, 284
Hearing. See also Auditory system; Sound
in animals, 324 , 325 f
evolution of, 329
mechanics of, 329 –331, 330 f–332f
movement and, 333
neural activity in, 336 –340
in owls, 339 , 339 f
Hebb synapse, 163
Hebb-Williams mazes, 266 –267, 266 f
Helix
DNA, 91 f, 92
protein, 93 , 93 f
Hemianopia, homonymous, 314
Hemispherectomy, 42
Hemispheres. See Cerebral hemispheres
Hemispheric connectivity, 534
environmental influences in brain development and, 268 –269
gender differences in, 548
Hemorrhagic stroke, 45
Hemp plant, 152 –153
Heritability. See Inheritance
Heroin, 187 , 187 f, 188
synthetic, parkinsonian symptoms from, 161
Herpes simplex encephalitis, amnesia in, 490
Hertz (Hz), 323 –324
Heschl’s gyrus, 334 , 334 f
 in music processing, 347 , 347 f
Heterochrony, 26
Heterosexuality, 434 –435
Heterozygous alleles, 97
Hibernation, circannual rhythms and, 454 –455
Hierarchical organization, of nervous system, 50 –58, 68 –69, 68 f, 357 –
365, 390 –391
High blood pressure, dementia and, 591
Higher vocal control center, in birds, 350 –351, 351 f
Highly superior autobiographical memory, 487
Hindbrain, 48 , 48 f, 51 , 51 f, 52 –53, 52 f
Hippocampus, 54 f, 57 –58, 57 f, 417 , 417 f
antidepressants and, 185
in domoic acid poisoning, 197 f
epigenetic differences in, 237
in learning, 212 , 213
in memory, 212 , 213
in consolidation, 497 –498
explicit, 497 –498
spatial, 492 –494, 493 f, 494 f
mood and, 595 –596
neurogenesis in, 503 –504, 504 f
antidepressants and, 596
place cells in, 222 –223, 222 f, 468 , 494 , 494 f
in schizophrenia, 278
in sleep, 468
spatial cells in, 494
stress and, 185 , 205 –206, 205 f, 595 –596
Histamine, 149
receptors for, 155 , 155 t
Histones, 103 –104
Home environment. See also Environmental enrichment
experimental effects of, 179
Homeostatic hormones, 201 , 202
Homeostatic mechanisms, 411 , 411 f
Homicide, 407
Hominids, 20 –21
Homo erectus, 21 , 21 f, 22 , 24 f, 26
Homo floresienses, 21
Homo habilis, 21 , 21 f, 25
Homo neanderthalensis, 21 –22, 21 f
music-making by, 322
Homo sapiens, 16 . See also Humans
evolution of, 19 –29
Homonymous hemianopia, 314
Homosexuality, 434 –435
Homozygous alleles, 97
Homunculus
cerebellar, 375 –376, 376 f
motor, 366 , 366 f, 371
somatosensory, 390 –391, 391 f
Horizontal cells, retinal, 294 , 295 f
Horizontal, definition of, 39
Horizontal section, 39 f
Hormones, 139 , 202 –206
in brain development, 273 –275
 classification of, 201 –202
cognitive function and, 203
early studies of, 200
eating behavior and, 427 –430
feedback loops for, 414 –415, 415 f
functions of, 200 , 201 –202
glucocorticoid, 202
neurotoxicity of, 510
homeostatic, 201 , 202
neuropeptide, 150 –151
neuroplasticity and, 509 –510, 509 f
organizational hypothesis and, 203
peptide, 201
pituitary, 200 , 210 f, 414 , 414 t
receptors for, 201 –202, 201 f
regulation of, 200 –201, 201 f, 412 –415, 413 f–415f. See also
Hypothalamus
releasing, 414 , 414 t
sex (gonadal). See Sex hormones
stress, 204 –206, 205 f, 206 f, 595 –596, 595 f
target glands of, 200 , 201 f
thyroid, 414 –415, 414 t
Horror autotoxicus, 584
HPA axis, stress effects on, 595 –596
Humans
apes and, 20 , 20 f
as chordates, 18 –19, 19 f
early ancestors of, 20 –21, 21 f
 evolution of. See also Evolution
as hominids, 20 –21
as primates, 20 , 20 f
taxonomy of, 16 –17, 16 f
Huntington disease, 99 f, 100 , 102 , 373 –374
Hydrocephalus, 82
Hydrogen bonds, 89
Hydrogen sulfide, as neurotransmitter, 153
Hyperactivity, 162
in attention-deficit/hyperactivity disorder, 162 , 240
in brain stimulation studies, 220
Hypercomplex cells, of visual cortex, 307 , 308 f
Hyperconnectivity, 535
Hyperglycemia, 202
Hyperkinetic rats, 220
Hyperkinetic symptoms, 374
Hyperopia, 290 –291
Hyperphagia, 429
Hyperpolarization, 119 –122, 119 f
Hypertension, dementia and, 591
Hypnogogic hallucinations, 475
Hypoactivity, in brain stimulation studies, 220
Hypocretin, 475
Hypoglossal nerve, 59 , 60 f
Hypoglycemia, 202
Hypokinesia, 586
Hypokinetic rats, 220
Hypokinetic symptoms, 374
Hypothalamic-pituitary-adrenal (HPA) axis, stress effects on, 595 –596
Hypothalamus, 53 –54, 53 f
amygdala and, 418 –419
in behavior generation, 416 , 417 f
in biorhythms, 450 –452
electrical stimulation of, 219
in feeding behavior, 399 , 429 –430, 430 f
in homeostasis, 411 –415, 411 f
in hormone regulation, 412 –415, 413 f–415f
limbic system and, 416 –418
neurohormone secretion by, 200 , 201 f
in nonregulatory behaviors, 412
pituitary gland and, 412 –415, 414 f, 595 –596
in regulatory behaviors, 411 –412
in sexual behavior, 434 , 435 f
in sexual orientation, 434 –435
in stress response, 204 , 205 f, 206 f
in temperature regulation, 411 –412
Hypovolemic thirst, 431
Id, 563
Illusions, perceptual, 288 , 288 f
Imagination, 554
Imaging studies, 226 –234, 238 –239, 238 t
anatomical, 226 –229
in brain mapping, 533 –536, 534 f
in brain/behavioral disorders, 570 –571, 570 f, 579
functional, 229 –234
in traumatic brain injury, 578 , 579
Imitation, 531 –532
Immune system, 84
Implicit memory. See Memory, implicit
Imprinting, 270 , 270 f
Incentive sensitization theory, 194 –196
Induced neurogenesis, 572 , 587 –588
Infants, brain maps for, 363
Inferential thinking, cerebral asymmetry and, 545
Inferior colliculus, 53 , 53 f, 69 , 333 , 334 f
Inferior, definition of, 38 , 39
Information flow
in brain, 296 , 296 f
Descarte’s theory of, 108 –109
electrical activity and, 111 , 112 f
in somatosensory system, 358 –359
in visual system, 296 , 296 f
Infradian rhythms, 444 , 445 t
Inheritance
of dominant traits, 97 , 99 f
of genetic diseases, 98 –100
of intelligence, 555
Mendelian, 98 –100, 99 f
of recessive traits, 97 , 99 f
Inherited behavior, vs. learned behavior, 6 , 6 f
Inherited traits, 10 –11, 98 –100, 99 f
Inhibition, vs. excitation, 70 –71, 80
Inhibitory postsynaptic potential, 127 –130, 129 f, 130 f
Inhibitory synapses, 146 , 146 f
Innate releasing mechanisms, 406 –407
Insomnia, 473
brainstem injury and, 476 –477
drug-dependency, 473
fatal familial, 472
Instrumental (operant) conditioning, 482 –483
Insula, 334 f, 335
in gustation, 405
Insulin, 202
Integration, in neurons, 127 –131
Intellectual disability, 571
Intellectual potential, 555
Intelligence, 552 –556. See also Cognition
animal, 522 –524
artificial, 80 , 81
bodily-kinesthetic, 553
brain size and, 23 , 24 , 28 –29, 553 , 553 f
convergent, 554
cortical thickness and, 259 –260, 259 f
divergent, 554
epigenetics and, 555
frontal lobe development and, 259 , 259 f
general, 28 –29, 553
heritability of, 555
intellectual potential and, 555
interpersonal, 553 –554
linguistic, 553
logical-mathematical, 553
 multiple, 29 , 553 –554
musical, 553 , 554
network efficiency and, 555
observed, 555
spatial, 553
synaptic organization and, 555
Intelligence A, 555
Intelligence B, 555
Intelligence tests, 554
Interaural time difference, 338 –339
Interblobs, 299
Intergeniculate leaflet, 450 , 451
International Classification of Diseases (WHO), 569
Interneurons, 78 , 79 , 79 f
motor, 371 –372
Interpersonal intelligence, 553 –554
Intoxication, toxin action at synapses in, 176 –177
Intracellular fluid, 87 f, 90
Intracellular recordings, 222
Intracranial self-stimulation, 437
Intrapersonal intelligence, 553 –554
Invertebrates, learning in, 49
Ion(s), 88 , 89 , 89 f
electrical charge of, 114 –116, 114 f
movement of, 114 –116
Ion channels, 95 , 95 f, 117 –118, 117 f
gated (voltage-sensitive), 95 , 95 f, 117 –119, 121 –122, 121 f, 122 f
in learning, 164 , 164 f, 165 f
 light-sensitive, 131
in muscle contraction, 133 –134, 133 f
in nerve impulse production, 125 , 133 f
in sensitization, 164 –166, 165 f
in sensory processing, 133 , 133 f
stretch-sensitive, 133
transmitter-sensitive, 133
Ion pumps, 95 , 95 f, 117 –119, 117 f
Ionic bonds, 89
Ionotropic receptors, 153 , 153 f
Ipsilateral, definition of, 39
Iris, 219 f, 291
Ischemia, cerebral, 580
Ischemic stroke, 45 , 580
Itch, 364 , 385
James-Lange theory, 421
Jerison’s principle of proper mass, 303
Jet lag, 448 , 449
Kainic acid poisoning, 197
Kappa receptors, 187
Ketamine, 182 , 190 , 197
as antidepressant, 186
Kingdoms, taxonomic, 16 , 16 f
Klonopin, 182
Klüver-Bucy syndrome, 422 –423
Knee jerk reflex, 50 –51, 384 –385, 384 f
Knock-in/knockout technology, 102
Korsakoff syndrome, 495 –497
Landmark-learning task, 215 , 216 f
Landmarks, visual processing of, 301 , 527 –528
Language. See also Speech
in animals, 8 , 9 , 522 , 523
bilingualism and
cognitive advances of, 555
cortical areas for, 268
birdsong and, 349 –351
Braille and, 543
Broca’s area for, 254 f, 262 , 342 –346, 342 f, 346 f
mapping of, 343 –346, 344 f
cognitive functions of, 521 –522
consciousness and, 558
cortical development and, 258
cortical localization of, 70 , 334 –335, 342 –346, 543 –545
mapping of, 343 –346
for second languages, 268
sodium amobarbital test for, 550
creolization of, 341 –342
development of, 254 f, 261 –262, 341
evolution of, 8 , 322 , 340 –342
genetic aspects of, 341
handedness and, 334 –335, 549 –551
lateralization for, 334 –335, 543 –545
movement and, 543 –545
music and, 322 , 327 , 345
in newborns, functional near-infrared spectroscopy and, 210
pidgin, 342
 processing of, 340 –346
properties of, 328
second
cortical localization for, 268
learning of, 340 –341
self-regulation and, 537
sex differences in, 546 –549
as sound, 327 –328
structural uniformity of, 340 –342
syntax of, 341 –342, 521 –522
vs. birdsong, 349 –350
Wernicke’s area for, 334 , 334 f, 342 f, 343 –346
mapping of, 343 –346, 344 f
Language acquisition, critical period for, 341
Language deficits
in autism spectrum disorder, 255
in carbon monoxide poisoning, 315
Language test, 8
Lark chronotype, 451 –452, 453
Latent content, of dreams, 462
Lateral corticospinal tract, 370 f, 371 , 371 f
Lateral, definition of, 38 , 39
Lateral fissure, 41 f, 42 , 55 , 55 f
Lateral geniculate nucleus, 53 f, 54 , 297 –298, 298 f, 302 –303, 302 f,
303 f
receptive field of, 302 –303
Lateral hypothalamus, in eating, 429
Lateral sulcus, 43 f
Lateral ventricles, 43 f
Lateralization, 334 –335. See also Cerebral asymmetry
for auditory processing, 541
for cognition, 539 –546
handedness and, 334 –335, 549 –551
for language, 334 –335, 543 –545
for music, 346 –347, 541
overlapping functions and, 305 , 306 f, 543
in split-brain patients, 520 , 542 –543, 545
for visual processing, 540 , 542 f. See also Visual fields
Law of Bell and Magendie, 61 , 62
L-dopa, 150 , 150 f, 152 , 573 , 587
Learned behavior, 6 , 6 f, 408 –409
Learned taste aversion, 409
Learned tolerance, 178
Learning, 6 , 481 –483. See also Memory
associative, 409 , 500
behavior and, 408 –409
cognitive enhancers and, 172
conditioning in, 408 –409, 481 –483, 482 f. See also Conditioning
definition of, 163 , 481
dendritic spines in, 167
enriched experience in, 504 –505, 505 f
habituation in, 163 –164, 164 f, 500
hippocampus in, 212 , 213
in invertebrates, 49
long-term potentiation and, 500 –502
mutations affecting, 166 –167, 167 f
 neurogenesis in, 504 –505
neuronal changes in, 166 –167
neuroplasticity and, 35 –36, 270 –271, 500 –502, 508 . See also
Neuroplasticity
object-reversal, 274
preparedness and, 409
second messengers in, 165 f, 166 –167
sensitization in, 164 –166, 165 f
sites of, 485
during sleep, 466 –467, 468 –469
studies of, 481 –483
in substance abuse, 178 , 192 , 195
synapses in, 163 –168
loss or formation of, 166 –167
structural changes in, 166 –167
visuospatial, 493
Learning disabilities, 480
Left-handedness. See also Cerebral asymmetry
cortical organization and, 334 –335, 549 –551
lateralization and, 334 –335
Lens, 291 , 291 f
in refractive errors, 290 –291
Leptin, 202
Lesion studies, 218 –219
Lesions, brain. See Brain injury
Leukotomy, frontal, emotional behavior after, 423 –424
Levels of function, 50 –58, 67 –68
Lewy body, 590 , 590 f
Liberation therapy, 584
Libido, loss of, 436
Life forms, classification of, 16 –17, 16 f
Light
circadian rhythms and, 446 –448
perception of, 290
properties of, 290 , 290 f
receptors for, 286 , 289 –294, 291 f, 293 f, 294 f
retinal ganglion cells as, 296 , 302 , 451
in seasonal affective disorder, 448
wave form of, 290 , 290 f
Light pollution, 447
Light-sensitive ion channels, 131
Limbic system, 54 , 54 f, 57 –58, 57 f, 416 –418
in eating, 418 , 430
in sexual behavior, 434
structure and function of, 416 –418, 417 f
Linguistic intelligence, 553
Lipid transmitters, 151 –153
Lithium, for bipolar disorder, 186
Little disease, 363
Lobectomy, temporal, Klüver-Bucy syndrome and, 422
Lobotomy, frontal, 423 –424, 423 f
emotional behavior after, 423 –424
Locked-in syndrome, 5 , 13 , 356 , 363
Logical-mathematical intelligence, 553
Loglio vulgaris
electrical activity in, 112
 giant axon of, electrical activity in, 112 f
Longitudinal fissure, 41 f, 42 , 55 , 55 f
Long-term depression, 501
Long-term memory, 486
Long-term potentiation, 500 –502, 501 f
Lordosis, in copulation, 434
Lou Gehrig disease, 134 , 356 , 363
Loudness, 324 –325, 324 f, 325 f
detection of, 338 –339
of music, 328
LSD (lysergic acid diethylamide), 190
Lucid dreaming, 464 , 476
Lumbar spine, 60 , 61 f
Luminance contrast, 284 f, 306 –307, 306 f
Luteinizing hormone (LH), 414 t
Lysosomes, 87 f, 90
M cells, 295 –298, 295 f, 451
Magnetic resonance imaging (MRI), 227 –229, 228 f, 534 –535
in diffusion tensor imaging, 229 , 229 f
functional, 230 –231, 230 f
in brain mapping, 534 –535, 534 f
real-time, 576
resting-state, 231
Magnetic resonance spectroscopy (MRS), 229 , 579
Magnetoencephalography (MEG), 226 , 507
Magnocellular (M) cells, 295 –298, 295 f, 451
Magnocellular nucleus of medulla, in sleep, 472
Major depression. See Depression
Malnutrition, epigenetic effects of, 105
Mania, 162 , 186 , 594 . See also Bipolar disorder
Manifest content, of dreams, 462
MAO inhibitors, 185
Maps. See Brain maps
Marijuana, 153 , 189 –190, 198 , 199 , 236
Masculinization, of brain, 203 , 273 –274, 432
Matching-to-place learning task, 215 , 216 f
Mate selection, 407 –408
Materialism, 8 –12
eliminative, 12
religion and, 14
Mathematical intelligence, 553
Mating behavior. See Sexual behavior
MDMA (ecstasy), 190 , 198
Medial, definition of, 38 , 39
Medial forebrain bundle, 412 , 413 f
reward and, 437
Medial geniculate nucleus, 333 , 334 f
Medial lemniscus, 383 , 383 f
Medial pontine reticular formation (MPRF), in REM sleep, 471 –472,
471 f, 472 f, 473 f
Medial preoptic area, in sexual behavior, 434
Medial temporal region, in explicit memory, 491 –497
Medial thalamus, in memory, 495 –497, 499 f
Median raphe, in brain activation, 471 , 471 f
Mediterranean diet, 428
Medulla, 53 , 53 f
Melanopsin, 451 , 453
Melanopsin ganglion cells, 453
Melatonin
biorhythms and, 454 –455
in sleep, 470
Membrane
basilar, in hearing, 330 –331, 330 f, 331 f, 332 f
cell. See Cell membrane
postsynaptic, 142 , 142 f, 144 –145
presynaptic, 142 , 142 f, 143
refractory, 122 –123, 124
tectorial, of inner ear, 330 , 330 f
Membrane potential. See Electrical potentials
Membrane proteins, 94 f, 95 , 95 f
Memes, 29
Memory. See also Learning
accuracy of, 485
autobiographical, 486 –487
basal ganglia in, 489 –490, 499
brain areas for, 70
classification of, 483 –485, 485 t
consolidation of, 467 –468, 497 –498
reconsolidation in, 497
declarative, 484 , 485 t
definition of, 481
distribution of, 486 , 486 f
emotional, 499 , 499 f
encoding in, 485
episodic, 467 , 486 –487, 487 f
erasing, 498
explicit, 484 –485, 485 t
consolidation of, 497 –498
deficits in, 487
long-term potentiation and, 500 –502
Mishkin model of, 495 –497, 497 f, 498
neural circuits for, 491 –497, 491 f, 499 f
NREM sleep and, 468
false, 485 , 487
hippocampus in, 212 , 213
implicit, 467 , 483 –484, 485 t
deficits in, 489 –490
Mishkin model of, 498 , 498 f
neural circuits for, 498 , 498 f
NREM sleep and, 468 –469
labile stage of, 467
limbic system in, 57
long-term, 486
medial temporal region in, 491 –497, 498 f
medial thalamus in, 495 –497, 498 f
multiple process theories of, 468
parahippocampal cortex in, 491 –492, 491 f
personal, 486 –487, 487 f
priming of, 485
procedural, 484 , 485 t
processing of, 486
recall of, 467
 sequential process theories of, 468
short-term, 486
tests of, 495 , 495 f
sites of, 486 , 486 f
spatial, hippocampus in, 492 –494, 493 f, 494 f
storage of, 486
neuroplasticity and, 500 –509
during sleep, 468 –469
structural basis of, 500 –513. See also Neuroplasticity
studies of, 483 –485
terminology of, 485 t
visuospatial, 492
Memory deficits
in Alzheimer disease, 492 , 498 . See also Alzheimer disease
in amnesia, 483 –484, 486 –487, 487 f. See also Amnesia
brain lesions and, 488 –490
explicit-memory, 488 –489
implicit-memory, 489 –490
in Korsakoff syndrome, 495 –497
normal age-related, 591
in Parkinson disease, 489 –490
in substance abuse, 198
Memory trace, 481 , 488
Menarche. See Menstruation
Ménière disease, 389
Meninges, 37 , 37 f
Meningiomas, 83
Meningitis, 40 , 42
Menstruation
cognitive function and, 203
as infradian biorhythm, 444
neuroplasticity and, 509 , 509 f
synchronized cycles in, 403
Mental illness. See Psychiatric disorders
Mental impairment. See Developmental disability
Mentalism, 7 , 12
Mescaline, 190
Mesencephalon (midbrain), 48 , 48 f, 51 , 51 f, 53 , 53 f
Mesolimbic dopaminergic system, 160 –161, 375 , 375 f
reward and, 437 , 437 f
structure and function of, 437 , 437 f
in substance abuse, 195
Messenger RNA, 93 , 93 f
Met allele, 236
Metabolic syndrome, 442 , 447 , 448
Metabolism, drug, 175
Metabotropic receptors, 153 –155, 154 f
Metaplasticity, 512
Metastatic brain tumors, 83
Metencephalon, 48 , 48 f
Methamphetamine, 189
Methylation, 104 , 104 f, 251 , 432
Methylphenidate, 172
Microbiome, 65
in brain development, 275
Microdialysis, 235 , 235 f
Microelectrodes, 113 –114
Microfilaments, 87 f, 90
Microglia, 82 t, 84 –85
in neuron repair, 85 –86
Microscope, electron, 140 –141
Microsleep, 466
Microtubules, 94 –95, 94 f
Microvilli, of taste buds, 405 , 405 f
Midbrain, 48 , 48 f, 51 , 51 f, 53 , 53 f
Middle cerebral artery, 43 , 43 f
Migraine, scotoma in, 286 –287
Migration, neuronal, 253 –254
Mild cognitive impairment, 492 , 591
Milner-Goodale experiment, 316 –317, 317 f
Mind, 7 . See also Consciousness
Freud’s theory of, 563
Mind-body problem, 8
Miniature postsynaptic potentials, 144
Minimally conscious state, 13
Minor tranquilizers, 182
Mirror neurons, 532
Mirror-drawing task, 214 f, 215
Mishkin model
of explicit memory, 495 –497, 497 f, 498 , 498 f
of implicit memory, 498 , 498 f
Mitochondria, 87 f, 90 , 143
Molecules, 89
Monkeys. See Primates, nonhuman
Monoamine oxidase (MAO) inhibitors, 185
Monocular blindness, 314
Monosodium glutamate (MSG), neurotoxicity of, 197 , 198
Monosynaptic reflex, 384
Mood disorders, 592 f, 594 –596. See also Bipolar disorder; Depression
Mood stabilizers, 181 t, 186
Morphine, 151 , 187 –188, 187 f
abuse of, 188
for pain, 387
Morris task, variations on, 215 –216, 216 f
Motivation
allocortex in, 54
amygdala in, 434
definition of, 398
neuroanatomy of, 410 –426
in nonregulatory behavior, 412
in regulatory behavior, 411 –412
sexual, 434 , 435 f
Motor cortex, 366 –372, 366 f
association cortex and, 527 f
corticospinal tracts and, 370 –371
injuries of, 369 –370
layers of, 56 , 56 f, 359 . See also Cortical layers
mapping of, 366 , 369 –370
movement categories in, 367 –368
neuroplasticity in, 505 –507, 506 f
posttraumatic reorganization of, 369 –370, 369 f
primary, 360 –361
 in skilled movement, 368 –369
supplementary, 366
topographic organization of, 56 , 366 , 366 f, 369 –370
in animals, 505 –506, 506 f
changes in, 369 –370, 369 f, 505 –507, 506 f
Motor development, 260 –261, 261 f
Motor end plate, 133 , 133 f
Motor function. See also Movement
separation from sensory function, 5 , 51 , 69
Motor homunculus, 366 , 366 f, 371
Motor neurons, 78 , 79 , 79 f, 371 –372
in muscle contraction, 133 –134, 133 f, 372
Motor pathways, efferent nerves in, 37 , 37 f
Motor sequences, 360 –361, 360 f, 361 f
Motor skills. See also Movement, skilled
learning of, explicit vs. implicit memory in, 484
Motor system. See also Movement
basal ganglia in, 373 –375, 373 f
cerebellum in, 375 –378, 376 f–378f
corticospinal tracts in, 370 –371, 370 f, 371 f
as efferent system, 358
motor cortex in, 366 , 366 f
motor neurons in, 371 –372
in muscle control, 133 –134, 133 f, 372 , 372 f
organization of, 366 –372
in pianists, 507
in skilled movements, 368 –369
 somatosensory system and, 358 –359, 390 –394. See also
Somatosensory system
Motor training, neuroplasticity and, 507
Movement, 355 –396
accuracy of, 376 –378, 377 f, 378 f
brainstem in, 361 –363
cerebellar control of, 52 –54, 52 f, 376 –378, 377 f, 378 f
cerebral asymmetry and, 543 –545
force of, basal ganglia and, 373 –375, 375 f
forebrain in, 358 –361, 360 f, 361 f
globus pallidus in, 375 , 375 f
hierarchical control of, 357 –365
experimental evidence for, 361
hindbrain in, 52 f, 53
imitation of, 532
inhibition of, 70 –71
initiation of, 360 –361, 360 f, 361 f
integrated control of, 61 –62
involuntary
drug-induced, 574
in Parkinson disease, 586
language and, 543 –545
learning and, 507
modeling of, 367 –368
motor sequences in, 360 –361, 360 f, 361 f
neurotransmitters in, 156 –157
orienting, 53 , 69
within perceptual world, 66
 posterior roots in, 358
prefrontal cortex in, 360 , 360 f, 361 , 361 f
premotor cortex in, 360 , 360 f, 361
primary cortex in, 360 –361, 360 f, 361
production of, nerve impulses in, 133 –134, 133 f
sensory input in, 69 –70, 376 –378, 381 –382, 390 –394. See also
Somatosensory system
sequential, 522
skilled, 368 –369
brain injury and, 369 –370
sleep and, 476 –477
sound in, 333
species-typical, 361 –363, 362 f
spinal circuits in, 364
spinal cord in, 364 –365
timing of, cerebellum in, 376 –378
understanding meaning of, 532
urge-to-action system and, 374
ventral roots in, 61
vision in, 313 , 316 , 316 f, 317 f, 382
visual perception of, 313
Movement categories, 367 –368
Movement disorders
basal ganglia in, 373 –374
drug-induced, 574
hyperkinetic symptoms in, 374
hypokinetic symptoms in, 374
MPTP, parkinsonian symptoms from, 161
MRI. See Magnetic resonance imaging (MRI)
mRNA, 93 , 93 f
MSG, neurotoxicity of, 197 , 198
Mu receptors, 187
Müller-Lyer illusion, 288 , 288 f
Multimodal neurons, 418
Multiple intelligences, 29 , 553 –554
Multiple sclerosis, 125 , 126 , 583 –584
as autoimmune disease, 126
Murder, 407
Muscle contraction, nerve impulses in, 133 –134, 133 f
Muscle control, 372
Muscle end plates, 133 , 133 f, 134
Muscular rigidity, in Parkinson disease, 586
Music
brain development and, 267
cerebral asymmetry for, 346 –347, 541
cortical thickness and, 348
evolution of, 322 , 340 –342
genetic aspects of, 347 –348
language and, 322 , 327 , 345
patterns of, detection of, 348
perfect pitch and, 324 , 535 , 535 f
processing of, 346 –348, 541
properties of, 328
as sound, 327 –328
sound waves in, 328 , 328 f
vs. speech, 327
Music processing, 346 –348
Music therapy, 348
Musical intelligence, 553 , 554
Musicians
focal hand dystonia in, 507
learning in, 507
motor skills in, 507
Mutations. See Genetic mutations
Myasthenia gravis, 134 , 177
Myelencephalon, 48 , 48 f
Myelination
axonal, 124 –125, 124 f
development of, 259 f, 260 f
loss of, in multiple sclerosis, 126 , 583 , 583 f
progression of, 259 –260, 260 f
Myopia, 290 , 291
Nalorphine, 187
Naloxone, 187
Nanotechnology, for spinal cord injuries, 365
Narcolepsy, 473 –474
sleep paralysis in, 474 –475
Narcotics. See Opioids
Nasal retina, 295 , 296 f
Natural selection, 8 –12. See also Evolution
behavior and, 406 –408
Navigational skills, 301 , 527 –528
Neanderthals, 21 –22, 21 f
music-making by, 322
Near-infrared spectroscopy (NIRS), functional, 123 f, 231 –232, 231 f
Nearsightedness, 290 , 291
Negative pole, 110
Neglect, contralateral, 529 –530
Neocortex, 54 . See also Cerebral cortex
in cognition, 535 –536
layers in, 359
Neoteny, 26 –27, 26 f
Nerve(s), 47 , 47 f
afferent, 37 , 37 f
cranial, 59 , 60 f
efferent, 37 , 37 f
peripheral, 60
regeneration of, in spinal cord injury, 365
spinal, 60 –61, 61 f, 358
Nerve cells. See Neuron(s)
Nerve growth factor, neuroplasticity and, 510 , 515
Nerve impulse, 123 –124. See also Action potential
definition of, 123 –124
input from
integration of, 127 –131
summation of, 128 –130, 129 f, 130 f
in muscle contraction, 133 –134, 133 f
production of, sensory input in, 132 –133, 133 f
saltatory conduction of, 125 –128, 125 f
Nerve injuries, repair of, 85 –86, 85 f, 365
Nerve net, 17 , 17 f, 76
Nerve roots, 61 , 62 f
Nervous system
autonomic, 36 f, 37 , 63 –64, 157 –158, 157 f
enteric nervous system and, 64 –65, 65 f
neurochemistry of, 157 –158, 157 f
cells of, 46 –47, 46 f, 47 f. See Glial cells; Neuron(s)
central. See Central nervous system
in chordates, 18 –19, 19 f
development of, 247 –280. See also Brain development
enteric, 37 , 64 –65, 65 f
autonomy of, 158
in brain development, 275
neurotransmitters of, 158
evolution of, 47 –49, 48 f. See also Evolution
in animals, 15 –19, 16 f–19f
in humans, 19 –29
functional organization of, 36 –37, 36 f, 37 f
functions of, principles of, 66 –71, 72
hierarchical organization of, 50 –58, 68 –69, 68 f, 357 –365, 390 –391
layers of. See Cortical layers
parasympathetic, 63 –64, 157 –158, 204 , 205 f
neurotransmission in, 157 –158
in rest and digest response, 157 –158, 204 –205
peripheral, 3 , 3 f, 4 , 36 –37, 36 f, 60
somatic, 36 f, 37 , 59 –63, 156 –157
connections of, 61 , 62 f
cranial nerves in, 59 , 60 f
neurotransmission in, 156 –157
sensory and motor divisions of, 69
 spinal nerves in, 60 –61, 61 f
structure of, 3 –4, 3 f
sympathetic, 63 –64
neurotransmission in, 157 –158
in stress response, 157 –158, 204 –206, 205 f
Netrins, 256
Neural circuits, 47 , 47 f, 76 –80, 76 f, 78 f, 522 –525
behavior and, 401
as cell assemblies, 523 –525
in cognition, 522 –525
crossed, 43 , 67
efficiency of, intelligence and, 555
environmental influences on, 268 –269
excitation and inhibition in, 70 –71, 80
in habituation, 163 –164, 164 f
hyperconnectivity of, 535
modification of, 502 –503, 503 f. See also Neuroplasticity
in movement, 364
novel, creation of, 503 –504, 505 f. See also Neurogenesis;
Neuroplasticity
in ocular dominance columns, 309 , 309 f
in sensitization, 164 –166, 165 f
spinal, 364
in visual system, 268 –269, 309 , 309 f
Neural columns. See Cortical columns
Neural connectivity, 534
environmental influences in brain development and, 268 –269
gender differences in, 548
Neural Darwinism, 257
Neural development. See Brain development
Neural groove, 249 , 249 f
Neural organization
afferent vs. efferent pathways in, 37 , 37 f
functional, 36 –37, 36 f, 37 f
hierarchical, 50 –58, 68 –69, 68 f, 357 –365, 390 –391
plastic patterns of, 35 –36. See also Neuroplasticity
Neural plate, 249 , 249 f
Neural processing, hierarchical vs. parallel circuits in, 68 –69
Neural relays, in sensory systems, 287
Neural shock, 580
Neural stem cells, 250 –252
transplantation of, 161 , 452 , 452 f, 516 , 572 , 587 –588
Neural streams, 69 –70, 69 f
Neural tube, 249 , 249 f, 250 f
Neural tube defects, 277
Neuritic plaque, in Alzheimer disease, 492 , 492 f, 588
Neuroblasts, 250
Neurodegenerative disorders, 583 –591. See also Alzheimer disease;
Dementia; Parkinson disease
Neuroeconomics, 538
Neurogenesis, 252 , 253 f, 503 –504, 505 f. See also Neuroplasticity
antidepressants and, 596
in brain injury, 516 –517
induced, 572 , 587 –588
Neurohormones, 200 , 201 f
Neuroimaging studies, 226 –234, 238 –239, 238 t
 anatomical, 226 –229
in brain mapping, 533 –536, 534 f
in brain/behavioral disorders, 570 –571, 570 f, 579
functional, 229 –234
in traumatic brain injury, 578 , 579
Neurological disorders, 577 –592. See also Brain/behavioral disorders
brain size and, 28
organic, 564
vs. psychiatric disorders, 563 –564
Neuron(s), 3 , 46 –47, 46 f, 47 f. See also Cell
axons and, 47 , 47 f, 76 , 76 f, 77 , 78 f. See also Axon(s)
bipolar, 79 , 79 f
auditory, 333
retinal, 294 , 295 f
in Caenorhabditis elegans, 23
cell body of, 76 , 76 f
cholinergic, 156 –158
components of, 86 –96
connections between, 47 , 47 f, 77 –80, 78 f, 79 f See also Neural
circuits
culture of, 75
death of, 257
dendrites of, 76 , 76 f, 77 , 78 f, 79 –80
differentiation of, 253 –254, 254 f
abnormal, 277
electrical activity in, 109 –127. See also under Electrical
evolution of, 16 –17
excitation of, 70 –71, 80
excitatory, 80
functions of, 46 , 76 , 78 –79
shape/size and, 79 –80, 79 f
generation of. See Neurogenesis; Neuroplasticity
glial cell repair of, 85 –86
growth and development of, 252 –258
information flow through, 77 –78, 79 f
inhibition of, 70 –71, 80
inhibitory, 63 –64, 70 –71, 80
interneurons, 78 , 79 , 79 f
labeling of, 75 , 211 , 212 f
longevity of, 77
maturation of, 254 –256, 254 f
migration of, 253 –254, 253 f
mirror, 532
motor, 78 , 79 , 79 f, 371 –372
in muscle contraction, 133 –134, 133 f, 372
multimodal, 418
noradrenergic, 162
number of, 76
origin of, 250 –252, 251 f
packing density of, 23
plasticity of. See Neuroplasticity
posterior-root ganglion, 381 –382, 381 f
properties of, 76
proteins in, 93
rainbow, 75
repair of, 85 –86, 85 f
 retinal, 289 , 294 –298, 295 f
receptive fields for, 302 –303
sensory, 78 , 79 , 79 f
sex differences in, 546 –547, 547 f
shape of, 79 –80
neuroplasticity and, 502 –503
somatosensory, 79 , 79 f, 381 –382, 381 f
staining of, 75 , 75 f, 78 f
structure of, 76 f, 77 –78
summation in, 128 –130, 129 f, 130 f
transplantation of, 161 , 452 , 452 f, 516 , 572 , 587 –588
types of, 78 –79, 79 f
as unit of cognition, 522 –525, 529
ventrolateral thalamic, 383
Neuron theory, 76
Neuronal migration, 253 –254, 253 f
Neuronal networks, 77 , 79 –80, 79 f. See also Axon(s); Neural circuits
Neuropeptides, 150 –151, 151 t
Neuroplasticity, 35 –36, 67 , 76 , 162 –163
adolescent-onset psychiatric disorders and, 275
in adults, 267
axonal sprouting in, 502 –503, 503 f
in brain development, 279 –280
in brain disorders, 566 –567
in brain injury, 276 , 369 f, 513 –517
brain size and, 28 –29
cerebellar agenesis and, 34
compensatory, 566 –567, 597 –598
 constraint-induced therapy and, 370
definition of, 28 , 36
dendritic changes and, 502 –503, 503 f
drug-induced, 510 –511, 511 f
environmental stimulation and, 270 –271, 504 –505, 505 f
epigenetics and, 36 , 103 –105
experience-dependent, 508
frontal lobe and, 258 –259
growth factors and, 84 , 510 , 510 t
hormones and, 509 –510, 509 f
learning and, 35 –36, 270 –271, 500 –502, 508
long-term potentiation and, 500 –502, 501 f
memory storage and, 500 –509
metaplasticity and, 512
modification of existing circuits in, 502 –503, 503 f
of motor cortex, 369 –370, 369 f
motor training and, 505 –507, 506 f, 507
neurogenesis in, 503 –504, 505 f
neurotrophic factors in, 510 , 510 t
phenotypic plasticity and, 36
principles of, 511 –513
of somatosensory cortex, 392 –393, 393 f
structural basis of, 500 –513
synaptic change in, 163 , 502 –503, 503 f
Neuroprosthetics, 356
Neuroprotection, 37 –40, 37 f, 581
Neuropsychoanalysis, 564
Neuropsychological testing, 214 –215, 533
Neuropsychological therapy, 575
Neuropsychology, 211
Neuroscience
cognitive, 533 –538
applications of, 536 –538
methods of, 533 –536
social, 536 –538
Neurosurgery, 572
frontal lobotomy, 423 –424, 423 f
for Parkinson disease, 587 –588
split brain studies and, 520 , 542 –543, 545
Neurotoxic lesion studies, 219
Neurotoxins
drugs as, 197 –199
epigenetics and, 196
mechanism of action of, 176 –177, 176 f, 197 t
Neurotransmission
in central nervous system, 158 –162
drug effects on, 175 f, 176 –177, 176 f
in somatic nervous system, 156 –157
steps in, 143 –144, 143 f, 144 f, 175 –176, 175 f
Neurotransmitters, 138 –140. See also specific types
actions of, 144
activating systems for, 158 –162
amine, 149 t, 150
amino acid, 149 t, 150 , 151 f
autoreceptors for, 144
behavior and, 146
 classification of, 148 –153
deactivation of, 144
definition of, 139
degradation of, 144
diffusion of, 144
evolution of, 146
gaseous, 153
glial uptake of, 144
identification of, 147 –148, 147 f
interaction of, 156
in learning, 162 –167, 164 f, 165 f
lipid, 151 –153
peptide, 150 –151, 151 t
properties of, 147 –148
putative, 148
quanta of, 144
receptors for, 153 –156, 153 f, 154 f. See also Receptor(s)
activation of, 143 –144, 143 f
release of, 143 , 144 f
regulation of, 145 –146
reuptake of, 144
second messengers and, 154 –155, 154 f
small-molecule, 149 –150, 158 –162
synthesis and storage of, 143 , 143 f, 149 –150, 150 f
types of, 147 –156
Neurotrophic factors, 236 , 251
for brain injury, 516 –517
in depression, 595
 electroconvulsive therapy and, 572
in induced neurogenesis, 572
neuroplasticity and, 510 , 510 t
Neutrons, 89
Nicotine, 176 , 176 f
addiction to, 193 , 438 –439. See also Substance abuse
in learning, 220
Nicotinic acetylcholine receptor, 157 , 157 f, 176 , 176 f
Night terrors, 464
Night vision, age-related decline in, 294
Nigrostriatal dopaminergic system, 159 f, 160
Nitric oxide, 153
NMDA receptors, in long-term potentiation, 501 –502, 501 f
Nociception, 380 , 380 f, 382 –388, 383 f
Nodes of Ranvier, 124 f, 125
Noise, 326
Nomenclature, anatomical, 38 –39
Nonmatching-to-sample task, 264 f, 265
Nonregulatory behaviors, 412
control of, 432 –435
Non-REM sleep. See NREM sleep
Nontasters, 404 –405
Noradrenergic neurons, 162
Noradrenergic system, 159 f, 161 –162
Norepinephrine (noradrenaline), 138 f, 139 , 150 , 150 f, 161 –162. See
also Neurotransmitters
in depression, 596
receptors for, 155 , 155 t
Norepinephrine psychedelics, 190
Norrbotten (Sweden), epigenetic influences in, 105
Notes, musical, frequencies of, 328 , 328 f
Notochord, 18
NREM sleep, 458 –461, 459 f, 465 . See also Sleep
disorders of, 473 –474
memory storage during, 468 –469
vs. REM sleep, 459 –461
Nuclear membrane, 87 f, 90
Nucleotide bases, 91 f, 92
Nucleus, 47
arcuate, in eating, 429 –430
caudate, 57 , 57 f
cell, 87 f, 90 , 92
cochlear, 333 , 334 f
dorsomedial thalamic, 53 f, 54
lateral geniculate, 53 f, 54 , 297 –298, 298 f, 302 –303, 302 f, 303 f
medial geniculate, 333 , 334 f
paraventricular, in eating, 429
raphe, 451
red, 53 , 53 f, 84 f
sensory, 69
subcoerulear, 472
suprachiasmatic, 450 –456, 450 f
thalamic, 69
Nucleus accumbens, 375
behavioral sensitization and, 511
Nucleus robustus archistriatalis, in birds, 350 –351, 351 f
Nutrition. See also Diet
brain size and, 25 –26, 25 f
depression and, 184 –185
epigenetic effects of, 105
multiple sclerosis and, 126
Nystagmus, 314
Obesity, 426 –427
biologic clocks and, 447 , 448
dieting and, 428
metabolic syndrome and, 442 , 447 , 448
Object knowledge, 526 –527
Object location, in visual system, 302 –304, 302 f, 303 f
Object manipulation, mental, 527 f, 528 , 528 f
Object permanence, 262 , 262 f, 263 t
Object position test, 493 , 493 f
Object recognition, 69 –70, 526 –527
Object-reversal learning, 274
Obsessive-compulsive disorder, 597 . See also Anxiety disorders
serotonin in, 162
Occipital lobe, 41 f, 55 , 55 f
in association cortex, 525 –526, 527 f
injury of, 55
structure and function of, 55 , 55 f
visual regions of, 299 –300, 299 f
Ocular dominance columns, 269 , 270 f, 308 –309, 309 f, 312 , 312 f
Oculogyric crisis, 586
Oculomotor nerve, 59 , 60 f
Off-center ganglion cells, 305 –306, 306 f, 307 f
Olfaction, 401 –404, 402 f, 403 f
in animals, 403
in humans, 404
Olfactory bulbs, 41 f, 58 f, 402 f, 403
Olfactory epithelium, 402 , 402 f
Olfactory nerve, 59 , 60 f
Olfactory pathways, 403
Olfactory receptors, 402 –403, 402 f
Olfactory system, 58 , 58 f, 401 –404, 402 f
accessory, 403
Oligodendroglia, 82 t, 85 , 124
On-center ganglion cells, 305 –306, 306 f, 307 f
Operant (instrumental) conditioning, 482 –483
Opioids, 151 , 181 t, 187 –188, 387
abuse of, 188
physical effects of, 187
synthetic, 187
Opium, 187 , 187 f
Opponent-process theory, 311 –313, 312 f
Optic ataxia, 317 –318
Optic chiasm, 295 , 296 f
Optic disc, 291 , 291 f, 292
swelling of, 292
Optic flow, 286
Optic nerve, 59 , 60 f, 291 , 292 , 295 , 296 f
inflammation of, 292
Optic neuritis, 292
Optical tomography, 210 , 231 –232, 231 f
Optogenetics, 131 , 221
Orbital prefrontal cortex, 526 f
Orbitofrontal cortex, 418 f, 419
in eating, 430
in gustation, 405
in olfaction, 403 , 403 f
Orders, taxonomic, 16 , 16 f
Orexin, 475
Organ of Corti, 330 , 330 f
hair cells of, 330 , 330 f, 332 f, 336 –337
Organelles, 90
Organic neurological disorders, 564
Organizational hypothesis, 203
Organophosphates, 177
Orientation, to sound, 338 –339, 339 f
Orientation columns, 308 –309, 312
Orientation detectors, 307
Orienting movements, 53 , 69
Oscilloscope, 113 , 113 f
Osmotic thirst, 431
Ossicles, 329 , 330 f
Otoconia, 388
Otolith organs, 388 , 389 f
Oval window, 329 , 330 f
Ovarian hormones
activating effects of, 433
in brain development, 203 , 273 –275, 546 –549
cognitive function and, 203
 functions of, 203
neuroplasticity and, 509 , 509 f
sexual behavior and, 433
Overtones, 326 , 326 f
Overweight, 426 –427
Owl, hearing in, 339 , 339 f
Owl chronotype, 451 –452, 453
Oxytocin, 413 , 415 f, 416
P cells, 295 –298, 295 f
Pacemakers. See also Biological clocks
circadian rhythms as, 452 –454
circannual rhythms as, 454 –455
Packing density, 23 , 24
Pain, 385 –388, 387 f, 388 f
central, 385
emotional, 398
expectation of, 537
gate theory of, 386 –387, 387 f
perception of, 385 , 387 f
phantom-limb, 385 , 386
referred, 388 , 388 f
response to, 385 –387
treatment of, 387 –388
Pain gate, 386 –387, 387 f
Panic disorder, 425 , 597 . See also Anxiety disorders
Papaver somniferum, 187 , 187 f
Papez circuit, 417
Papilledema, 292
Parahippocampal cortex, 416
in memory, 491 –492, 491 f
Parallel processing, 68 –69, 68 –70
Paralysis, 86 , 364 , 365 . See also Spinal cord injury
facial, 62
Paramethoxymethamphetamine (PMMA), 198
Parasympathetic nervous system, 63 –64
neurotransmission in, 157 –158
in rest and digest response, 157 –158, 204 –205
Paraventricular nucleus, in eating, 429
Parietal lobe, 41 f, 55 , 55 f
in association cortex, 525 –526, 527 f
in attention, 529 , 530
in cognition, 525 –526, 528 , 529 , 530
injury of, 55
in spatial cognition, 528
structure and function of, 55 , 55 f
Parietal reach region, 301
Parkinson disease, 42 , 57 , 71 , 140 , 374 –375, 585 –588
Alzheimer disease and, 590
basal ganglia in, 374 –375
causes of, 587
deep brain stimulation for, 375
globus pallidus in, 375
L-dopa for, 150 , 150 f, 152 , 573 , 587
lesion studies of, 218 –219
Lewy bodies in, 590 , 590 f
memory deficits in, 489 –490, 498
 neuron transplant for, 516 , 587 –588
prevalence of, 585
progression of, 586
symptoms of, 219 , 585 –586
toxins and, 161
treatment of, 150 , 150 f, 152 , 572 , 573 , 587 –588
tremor in, 140 , 161 , 586
Parrots, cognition in, 522 , 545
Parvocellular (P) cells, 295 –298, 295 f
Patellar reflex, 50 –51, 384 –385, 384 f
Pavlovian conditioning, 481 –482. See also Conditioning
in substance abuse, 195
PCP (phencyclidine), 182 , 190 , 197
Peptide bonds, 93
Peptide hormones, 201 . See also Hormones
Peptide transmitters, 150 –151, 151 t
Perception, 35 , 288
subjective reality and, 35
Perceptual illusions, 288 , 288 f
Perceptual world, creation of, 66
Perfect pitch, 324 , 535 , 535 f, 554
Periaqueductal gray matter, 53 , 53 f
in pain, 388
Peribrachial area, in REM sleep, 471 –472, 471 f, 472 f, 473 f
period gene, 453
Periodic limb movement in sleep, 460
Periods, in activity cycle, 444
Peripheral nervous system, 3 , 3 f, 4 , 36 –37, 36 f, 60
Peripheral vision, 292 , 292 f
Perirhinal cortex, in memory, 491 –492, 491 f
Perseveration, 531
Persistent vegetative state, 13
Personal memory, 486 –487, 487 f
PET scan, 232 –234
in auditory cortex mapping, 345 –346
Peyote, 190
Phagocytosis, 84
Phantom-limb pain, 385 , 386
Phencyclidine (PCP), 182 , 190 , 197
Phenotype, 9 , 96
Phenotypic plasticity, 36 , 103 –105
Phenylketonuria (PKU), 565 , 566 t
Pheromones, 403 , 403 f, 412
Phobias, 425 , 597 . See also Anxiety disorders
Phosphenes, 220
Phospholipid bilayer, 90 f, 91
Photoreceptors, 286 –287, 289 –294, 291 f, 293 f, 294 f
retinal ganglion cells as, 296 , 302 , 451
Photosensitive retinal ganglion cells, 451 , 453
Phototherapy, for seasonal affective disorder, 448
Phyla, 16 , 16 f
Physical activity, therapeutic benefits of, 576
Physostigmine, 177
Phytocannabinoids, 152 –153
Pia mater, 37
Piaget’s cognitive theory, 262 –264, 262 f, 263 t
Pianists. See also Musicians
motor skills in, 507
Picrotoxin, 182
Pidgin, 342
Pigments, in rods vs. cones, 293
Pincer grip, 360 –361
movements in, 361 f
Pineal gland, 7 –8, 8 f, 46
in biorhythms, 450 , 454 –455
blood–brain barrier and, 174 , 175 f
melatonin secretion by, 454 –455
in sleep, 470
Pinna, 329 , 330 f
Pitch, 324 , 324 f, 328
perception of, 336 –338
perfect (absolute), 324 , 535 , 535 f, 554
Pituitary gland, 200 , 201 f
blood–brain barrier and, 174 , 175 f
definition of, 412
hormones of, 200 , 201 f, 414 , 414 t
hypothalamus and, 412 –415, 414 f, 595 –596
structure and function of, 414 , 414 f
PKU (phenylketonuria), 565 , 566 t
Place cells, 222 –223, 222 f, 468 , 494 , 494 f
Place-learning task, 216 f
Planning, 530 –531
Plants, biorhythms in, 443 , 444 f
Planum temporale, 334 , 334 f
Plaque
in Alzheimer disease, 85 , 492 , 492 f, 588
in multiple sclerosis, 126
Plasticity
neural. See Neuroplasticity
phenotypic, 36 , 103 –105
Pleasure, reward and, 436 –439
Plexus, 65
PMMA (paramethoxymethamphetamine), 198
Poisoning
carbon monoxide, 315 –316
domoic acid, 197
kainic acid, 197
MPTP, 161
toxin action at synapses in, 176 –177
Polar molecule, 89
Polypeptide chains, 93 , 93 f. See also Protein(s)
Pons, 53 , 53 f
Poppy, opium, 187 , 187 f
Positive pole, 110
Positron emission tomography (PET), 232 –234
in auditory cortex mapping, 345 –346
Posterior cerebral artery, 43 , 43 f
Posterior, definition of, 38 , 39
Posterior roots, 358
Posterior spinothalamic tract, 383 , 383 f
Posterior-root ganglion neurons, 381 –382, 381 f
Postsynaptic membrane, 142 , 142 f, 143 –144
Postsynaptic potentials
excitatory/inhibitory, 127 –130, 129 f, 130 f
miniature, 144
Posttraumatic stress disorder (PTSD), 164 –165, 206 , 424 , 562 , 597
Potassium ion(s). See also under Ion(s)
resting potential and, 116 –119, 117 f, 119 f
Potassium ion channels, in sensitization, 165 , 165 f
Potentials. See Electrical potentials
Poverty, brain development and, 246 , 266 –267
Power grasp, 361 f
Power grip, 361
Precursor cells, 250
Preformation, 248
Prefrontal cortex, 419 –420
association, 525 –533
in behavior selection, 419 –420
dorsolateral, 258 , 526 f
theory of mind and, 536
dorsomedial, 418 f, 419
in eating, 430
in emotional behavior, 423 –424
executive functions of, 360 , 419 –420
in memory, 498 , 498 f
in movement, 360 , 360 f, 361 , 361 f
orbital, 526 f
in planning, 360 , 530 –531
structure of, 418 f, 419 –420, 419 f, 526 , 526 f
ventromedial, 418 f, 419 , 526 f
Pregnancy, alcohol use in, 28 , 183 , 267 , 271
Premotor cortex, 418 , 418 f
in memory, 498 , 498 f
in movement initiation, 360 , 360 f, 361
Prenatal influences, in brain development, 267 , 268
Preoperational stage, of cognitive development, 263 , 263 t
Preparedness, 409
Presbyopia, 290
Presynaptic membrane, 142 , 142 f, 143
Prey-killing behavior, 399 , 401 , 406 –407
Primary auditory cortex, 334 , 334 f. See also Auditory cortex
Primary motor cortex, 360 –361, 360 f. See also Motor cortex
Primary protein structure, 94 f
Primary visual cortex. See Visual cortex, primary (striate)
Primates
characteristics of, 20
humans as, 20 , 20 f. See also Humans
nonhuman
brain size in, 22 , 23 f
classification of, 20 , 20 f
evolutionary link to humans and, 15 , 20 , 22
language in, 8
music and, 322
relationships among, 20 , 20 f
Priming, 485
Principle of proper mass, 22 , 303
Procedural memory, 484 , 485 t
Progenitor cells, 250
Programmed cell death, 198 , 257
Prolactin, 250 , 414 , 414 t
Proper mass principle, 303
Proprioception, 380 , 380 f
loss of, 382
Prosencephalon, 48 , 48 f
Prosody, 328 , 424
Prosopagnosia, 301
Protanopia, 311
Protein(s), 94 –96
amino acids in, 92 , 93 , 93 f, 94 f, 150
cell function and, 86
definition of, 93
destinations of, 94 –956, 94 f
enzyme, 93 –94
export of, 94 –95, 94 f
genes coding for. See Gene(s)
membrane, 94 f, 95 , 95 f
shape-changing, 95 , 95 f
structure of, 93 –94, 94 f
synthesis of, 91 –92, 93 f
transport of, 94 f, 95
transporter, 143
Protein channels. See Ion channels
Protein receptors, 95 , 95 f
Protons, 89
Proximal, definition of, 39
Prozac, 186 , 187
Psilocybin, 190
Psyche, 7
Psychedelics, 181 t, 189 –190
Psychiatric disorders, 592 –597. See also Brain/behavioral disorders
adolescent-onset, 275
anxiety, 181 –182, 181 t, 424 –426, 592 f, 597 . See also Anxiety
disorders
mood, 592 f, 594 –596. See also Bipolar disorder; Depression
psychotic, 184 , 592 –594, 592 f. See also Schizophrenia
types of, 592 f
vs. neurological disorders, 564 –565
Psychoactive drugs. See Drug(s); Substance abuse
Psychoanalysis, 563
Psychobiotics, 65
Psychogenic amnesia, 487 , 487 f
Psychological constructs, 520
Psychology, evolutionary, 407 –408
Psychomotor activation, in substance abuse, 193
Psychopathology. See Psychiatric disorders
Psychopharmacology. See also Drug(s)
definition of, 172
principles of, 173 –181
Psychosis, 184 , 592 –594, 592 f. See also Schizophrenia
adolescent-onset, 275
amphetamine, 184
drug-induced, 199 , 236
Psychosurgery, 423 –424, 423 f. See Neurosurgery
emotional behavior after, 423 –424
Psychotherapy, 575
Psychotropics, 181 t, 188 –190
Puffer fish, 120
Pulvinar, 298
Pumps, ion, 95 , 95 f, 116 –119, 117 f
Pupil, 291 , 291 f
Pure tones, 326
Purkinje cells, 79 , 79 f
Pursuit-rotor task, 484 , 484 f
Putamen, 57 , 57 f, 373 , 373 f
Putative neurotransmitter, 148
Puzzle box, 482 –483, 483 f
Pyramidal cells, 79 , 79 f, 80
Pyramidal tracts, 370 –371, 370 f, 371 f
Pyriform cortex, 58
Quadrantanopia, 314 , 314 f
Quadriplegia, 364 , 365 . See also Spinal cord injury
Quanta, 144
Quaternary protein structure, 94 f
Radial glial cells, 253 , 253 f
Radiator hypothesis, 26
Radiosurgery, 571
Rainbow neurons, 75
Raphe nucleus, 451
Rapid eye-movement sleep. See REM sleep; Sleep
Rapidly adapting receptors, 381
Rasmussen encephalitis, 42
Rate-limiting factor, 150
Rats, behavioral analysis of, 215 –216
Real-time fMRI, 576
Recency memory task, 214 f, 215
Receptive fields, 286 , 302 –303, 302 f
of lateral geniculate nucleus, 302 –303
overlapping, 305 , 306 f
of primary visual cortex, 305 –308, 307 f, 308 f
in shape perception, 305 –310, 306 f–308f, 307 f, 308 f
Receptor(s), 95 , 95 f
auditory, 330 f, 332
autoreceptors, 144
ionotropic, 153 , 153 f
light, 289 –294, 291 f, 293 f, 294 f
metabotropic, 153 –155, 154 f
neurotransmitter, 153 –156, 154 f
activation of, 143 –144, 143 f
olfactory, 402 –403, 402 f
rapidly adapting, 381
sensory, 132 –133, 285 –287, 379 –381
density of, 286 –287
sensitivity of, 286 –287
slowly adapting, 381
small-molecule transmitter, 155 , 155 t
somatosensory, 379 –381
subtypes of, 155 –156, 155 t
taste, 405
transmitter-activated, 143 –144
vestibular, 388 –389, 389 f
Recessive alleles, 97 , 99 f
Reconsolidation, of memory, 497
Recreational drugs. See Drug(s); Substance abuse
Red nucleus, 53 , 53 f, 84 f
Referred pain, 388 , 388 f
Reflective vs. reflexive systems, 538
Reflexes
knee jerk, 384 –385
monosynaptic, 384
patellar tendon (knee jerk), 50 –51, 384 f
scratch, 364
spinal, 51 , 364 , 384 –385, 384 f
Refractive errors, 290 –291
Refractory membrane, 122
Refractory periods, 122 –123, 124
Regional cooling, 219
Regulatory behaviors, 411 –412
control of, 426 –431
Reinforcers, 408
Relatively refractory membrane, 122
Releasing hormones, 414 , 415 f
Religion, science and, 14
REM sleep, 458 –461. See also Sleep
atonia in, 458 , 460 –461, 474 –475
basic rest-activity cycle and, 465
definition of, 458
deprivation of, 467
disorders of, 474 –476
 dreaming in, 461 –464. See also Dreams
implicit memory and, 468 –469, 469 f
memory storage during, 469
neural basis of, 471 –472, 471 f–473f
vs. NREM sleep, 459 –461
without atonia, 476 –477
REM sleep behavioral disorder, 467 , 475 –476
Renshaw loop, 148 , 149 f
Repetitive transcranial magnetic stimulation, (rTMS), 220 , 220 f, 573
Reproduction, sex hormones in, 202 . See also Sex hormones
Research methods, 211 –244, 565 –567
comparison of, 238 –239, 238 t
Respondent conditioning, 481 –482
Rest and digest response, 157 –158, 204 –205
Rest-activity cycle, 465
Resting potential, 116 –119, 117 f
Resting-state fMRI, 231
Restless legs syndrome, 460
Reticular activating system, 470 , 470 f
Reticular formation, 52 , 53 f
Retina, 291 , 291 f
blind spot in, 284 , 291 , 291 f, 292 , 292 f
nasal, 295 , 296 f
receptive fields in. See Receptive fields
temporal, 295 , 296 f
Retinal ganglion cells, 294 –298, 295 f
lateral geniculate nuclei and, 297 –298, 298 f, 302 –303, 302 f, 303 f
on-center/off-center, 305 –306, 306 f, 307 f
 as photoreceptors, 296 , 302 , 451
photosensitive, 451 , 453
receptive field of, 302 –303, 302 f, 305 –308, 306 f
in shape perception, 305 –308, 306 f
Retinal neurons, 289 , 294 –298, 295 f
receptive fields for, 302 –303, 302 f, 305 –308, 306 f
Retinohypothalamic tract, 296 , 451 , 453
Retrograde amnesia, 496
Rett syndrome, 255
Reuptake, of neurotransmitters, 144
Reward
behavior and, 399 , 400 , 416 , 436 –439
in conditioning, 481 –482
wanting and liking and, 437
Rhombencephalon (hindbrain), 48 , 48 f, 51 , 51 f, 52 –53, 52 f
Rhythms, biological. See Biorhythms
Ribonucleic acid (RNA), 92 , 93 , 93 f
modification of, 104 , 104 f
Ribosomes, 93
Right-handedness. See also Cerebral asymmetry
cortical organization and, 334 –335, 549 –551
lateralization and, 334 –335
Rigidity, in Parkinson disease, 585
Ritalin, 172
Rivastigmine (Exelon), 492
RNA, 92 , 93 , 93 f
modification of, 104 , 104 f
Robots, 80 , 80 f, 81
Robustus archistriatalis, in birds, 350 –351, 351 f
Rods (photoreceptors), 293 –294, 293 f
Romanian orphans, brain development in, 272
Rostral, definition of, 38 , 39
Round window, 330 , 330 f
Routes of administration, 173 –174, 173 f
Rubin’s vase illusion, 288 , 288 f
rutabaga gene, 166
Saccule, 388 , 389 f
Sacral spine, 60 , 61 f
Sagittal, definition of, 39
Sagittal section, 39 f, 45 –46, 46 f
Saltatory conduction, 125 , 125 f
Salts, 89 . See also under Ion(s)
Savant syndrome, 598
Schizophrenia, 277 , 278 , 592 –594, 592 f
adolescent-onset, 275
adult-onset, 570 , 570 f
biochemical changes in, 594 t
brain abnormalities in, 570 , 570 f, 593 , 593 f
definition of, 161
diagnosis of, 592
dopamine in, 161 , 184
drug therapy for, 181 t, 184 , 184 f
early-onset, 570 , 570 f
epigenetics in, 593
imaging studies in, 570 –571, 570 f
neurochemistry of, 594
 serotonin in, 162
symptoms of, 592
transcranial magnetic stimulation for, 573
Schwann cells, 82 t, 85 –86, 85 f
in neuron repair, 85 –86
Science, religion and, 14
Sclera, 291
Scotomas, 314 , 314 f
migraine, 284
Scratch reflex, 364
Seasonal affective disorder, 448
Second languages
cortical localization for, 268
learning of, 340 –341
Second messengers, 154 –155, 154 f
in learning, 165 f, 166 –167
Secondary auditory cortex, 334 . See also Auditory cortex
Secondary protein structure, 94 f
Secondary (extrastriate) visual cortex, 299 , 299 f, 300 f. See also Visual
cortex
Second-generation antidepressants, 185
Sections, of brain, 39 f, 43 –46, 43 f, 46 f
Sedative-hypnotics, 181 –182, 181 t
insomnia and, 473
Segmentation, 18
Seizures, 108 , 581 –583
brain surgery for, 343 , 345
focal, 582
 generalized, 582
Selective attention, 528 –529
Selective awareness, 284
Selective breeding, 101
Selective dystonias, 375
Selective serotonin reuptake inhibitors (SSRIs), 185 , 186 . See also
Antidepressants
side effects of, 574
Self-concept, 537
Self-recognition, 536 –537
Self-regulation, 537
Semicircular canals, 388 , 389 f
Sensation, 286 –288. See also Sensory function and specific senses
vs. perception, 288
Sensitive periods
for brain development, 269 –270
for brain injury, 276
for gene expression, 105
for language acquisition, 341
Sensitization, 164 –166, 165 f, 167
behavioral, 510 –511
dendritic spines in, 167
drug, 178 –180, 510 –511
habituation to, 163 –164, 164 f, 167 , 500
Sensorimotor stage, of cognitive development, 263 , 263 t
Sensory coding and representation, 287 –288
Sensory cortex
association cortex and, 527 , 527 f
 layers of, 56 , 56 f. See also Cortical layers
Sensory deprivation, 5 , 400 –401, 400 f
Sensory function
dorsal roots in, 61
integrated control of, 61 –62
midbrain in, 51 , 53
motor control and, 69 –70
neural streams in, 69 –70, 69 f
for object recognition, 69 –70, 527
separation from motor function, 5 , 51 , 69
Sensory input
in brain development, 266 –268, 267 f, 270 –271
habituation to, 163 , 164 f
integration of, 127 –131
in movement, 376 –378, 381 –382. See also Somatosensory system
in nerve impulse production, 132 –133, 133 f
summation of, 128 –130, 129 f, 130 f
Sensory neurons, 78 , 79 , 79 f
Sensory nuclei, 69 . See also Nucleus
Sensory pathways, afferent nerves in, 37 , 37 f
Sensory perception, 35
subjective reality and, 35
Sensory processing, 285 –288
synesthesia in, 551 –552
Sensory receptors, 132 –133, 379 –381. See also specific types
density of, 286 –287
sensitivity of, 286 –287
Sensory systems
 coding and representation in, 287 –288
distinguishing between, 287 –288
neural relays in, 287
receptive fields in, 286
receptors in, 285 –287
Serotonergic system, 159 f, 162
Serotonin, 150 , 162 . See also Neurotransmitters
in brain activation, 471 , 471 f
in depression, 596 . See also Selective serotonin reuptake inhibitors
(SSRIs)
in enteric nervous system, 158
receptors for, 155 , 155 t
in sudden infant death syndrome, 277
synthesis of, 150
Serotonin psychedelics, 190
Serotonin synapse, antidepressant action at, 185 f, 186
Setpoint, in temperature regulation, 411
Sex chromosomes, 96 –97, 97 f
sex differences and, 548
Sex determination, 203 , 432 , 433
brain development and, 203
disorders of, 433
Sex differences
in addiction, 193 –194
in behavior, 548 –549
in birdsong, 275
in brain development, 273 –375, 273 f
in brain injury, 547 –548, 549 f
 in brain size, 546 , 547 f
in cognition, 203 , 546 –549, 547 f–549f
in cortical thickness, 546 , 547 f
evolution of, 548 –549
in language, 546 –549
in neural connectivity, 548
in neuron structure, 546 –547, 547 f
Sex hormones, 202 , 203 . See also Hormones
activating effects of, 433
behavior and, 401
in brain development, 203 , 273 –275, 432 , 546 –549
cognitive function and, 203 , 546 –549
epigenetic changes and, 274 –275, 432
function of, 202
lifelong effects of, 274 –275
neuroplasticity and, 509 , 509 f
organizing effects of, 432
sexual behavior and, 433
in sexual differentiation, 203 , 272 , 432
steroid, 201
target glands of, 200 –201, 201 f
Sexual behavior, 412 , 433
amygdala in, 434
cerebral cortex in, 436
cognitive influences in, 436
frontal lobe in, 436
hypothalamus in, 434 , 435 f
loss of libido and, 436
 motivational, 434 , 435 f
neural circuits and, 401
neural control of, 434
sex hormones and, 434
sexual identity and, 434 –435
sexual orientation and, 434 –435
Sexual dimorphism, 272 , 432 . See also Sex determination
Sexual identity, 434 –435
Sexual orientation, 434 –435
gender identity and, 435
Shape perception, 305 –310, 305 f–310f
Shift work, biorhythms and, 447 –448
Shock, neural, 580
Short-term memory, 486
tests of, 495 , 495 f
Shunts, cerebrospinal fluid, 82
Side chains, 93
SIDS (sudden infant death syndrome), 162 , 474
Sight. See Vision
Sign trackers, 195 –196
Simple cells, of visual cortex, 307 , 307 f
Singing, 322 , 345 , 347 , 576
by birds, 275 , 349 –351
carbon monoxide poisoning and, 315
Single nucleotide polymorphism (SNP), 97 –98
Single-cell recordings, 222 –223
Skilled-reaching tasks, 216 , 217 f
Skin
 sensory receptors in, 379 –381
two-point sensitivity in, 379 , 379 f
Skinner box, 408 , 408 f, 483
Slave oscillators, in suprachiasmatic nucleus, 452 –453, 453 f, 455
Sleep, 456 –478
alpha rhythms in, 458
in animals, 460 –461, 461 f, 465 , 465 f, 469
antidepressants and, 467
in basic rest-activity cycle, 465 , 466 f
beta rhythms in, 458
as biological adaptation, 465
brainstem injury and, 467 , 476 –477
circadian rhythms and, 442 , 443 –449, 445 t, 446 f
consciousness and, 476 –477
delta rhythms in, 458
in depression, 473
dreaming in, 461 –464. See also Dreams
drowsy state in, 458
duration of, 456 –457, 465 , 465 f
electroencephalography in, 457 , 470 –472
energy conservation and, 465
function of, 464 –469
hippocampus in, 468 f
learning during, 468 –469
medial pontine reticular formation in, 471 –472, 471 f, 472 f
melatonin in, 470
in memory storage, 469
microsleep and, 466
 neural basis of, 470 –472
normal variations in, 456 –457
NREM, 458 –461, 459 f, 465
disorders of, 473 –474
explicit memory and, 468 , 468 f
peribrachial area in, 471 –472, 471 f–473f
pineal gland in, 470
REM, 458 –461, 465
atonia in, 460 –461, 474 –475
definition of, 458
deprivation of, 467
disorders of, 474 –476
memory storage during, 468 , 468 f
neural basis of, 471 –472, 471 f–473f
without atonia, 476 –477
as restorative process, 466 –467
reticular activating system in, 470
slow-wave, 458 , 459 f
stages of, 457 –458, 459 f
waking and, 470 –471
Sleep aids, insomnia and, 473
Sleep apnea, 473 –474
Sleep deprivation
brainstem injury and, 476 –477
REM, 467
Sleep disorders, 460 , 473 –476
genetic factors in, 453
of NREM sleep, 473 –474
 of REM sleep, 474 –476
Sleep paralysis, 474 –475
Sleep studies, 223 f, 224 , 457 –458, 457 f, 459 f, 470 –472
electroencephalography in, 470 –472
electromyography in, 457 , 457 f
electrooculography in, 457 , 457 f
Sleeping sickness, 42
Sleep-producing substance, 470
Sleepwalking, 459
Slowly adapting receptors, 381
Slow-wave sleep, 458 , 459 f. See also NREM sleep
Small-molecule neurotransmitters, 149 –150, 149 t, 158 –162
receptors for, 155 , 155 t
Smell. See under Olfaction; Olfactory
Smoking, nicotine addiction in, 193 , 438 –439
Social cognition, 537 –538
mirror neurons in, 532
Social neuroscience, 536 –538
Social phobia, 597 . See also Anxiety disorders
Socioeconomic status, brain development and, 246 , 266 –267
Sodium amobarbital test, 550
Sodium ions. See also under Ion(s)
resting potential and, 117 –119, 117 f, 119 f
Sodium-potassium pump, 117 , 118
Solitary tract, 405
Soma, 76 , 76 f
Somasomatic connections, 146
Somatic marker hypothesis, 421 –422
Somatic nervous system, 36 f, 37 , 59 –63
connections of, 61 , 62 f
cranial nerves in, 59 , 60 f
neurotransmission in, 156 –157
sensory and motor divisions of, 69
spinal nerves in, 60 –61, 61 f
Somatosensory cortex, 390 –394
anatomy of, 390 , 391 f
in gustation, 405
hierarchical organization of, 390 –391
homunculus of, 390 –391, 391 f
injury of, 392 –393
plasticity of, 392 –393, 393 f
primary, 390
secondary, 390 , 393 –394
topographic organization of, 390 –391, 391 f, 393 f
Somatosensory neurons, 79 , 79 f
Somatosensory receptors, 379 –381, 389 f
distribution and density of, 379
haptic, 380 , 380 f
nociceptive, 380 , 380 f
proprioceptive, 380 , 380 f
rapidly adapting, 381
slowly adapting, 381
types of, 389 f
Somatosensory system, 379 –394
as afferent system, 358
anterior spinothalamic tract in, 383
 in balance, 388 –389
dorsal spinothalamic tract in, 383 f
functions of, 379
in hapsis, 380
medial lemniscus in, 383 , 383 f
motor system and, 358 –359, 390 –394
in nociception, 380 , 385 –388
overview of, 379
in pain perception, 388
pathways to brain in, 382 –384
in perception and movement, 379 –394
in pianists, 507
posterior spinothalamic tract in, 383
posterior-root ganglion neurons in, 381 –382, 381 f
in proprioception, 380 , 382
receptor distribution in, 379
segregation and synthesis in, 391
somatosensory cortex in, 390 –394. See also Somatosensory cortex
spinal reflexes and, 384 –385, 384 f
ventral spinothalamic tract in, 383 f
ventrolateral thalamus in, 383 , 383 f
vestibular system in, 388 –389, 389 f
Sorting tasks, 531 , 531 f, 533
Sound. See also Auditory system; Hearing
language as, 327 –328. See also Language
localization of
in bats, 351 –352
in humans, 338 –339, 339 f
 loudness (intensity) of, 324 –325, 324 f, 325 f, 328
detection of, 338 –339
music as, 327 –328. See also Music
patterns of, detection of, 339 –340
perception of, 326 –327
pitch of, 324 , 324 f, 328
perception of, 336 –338
properties of, 323 –327, 324 f
source of, detection of, 339 –340, 339 f
timbre (quality) of, 324 f, 328
Sound waves, 323 –329
amplitude of, 324 –325, 324 f, 325 f. See also Loudness
complexity of, 324 f, 326
curves of, 336 –337, 336 f
cycles of, 323 , 324 f
definition of, 323
frequency of, 323 –324, 324 f, 326 . See also Pitch
production of, 323 , 323 f, 324 f
Spatial cells, in hippocampus, 222 –223, 222 f, 468 , 494 , 494 f
Spatial cognition, 527 –528, 527 f, 528 f
sex differences in, 549
Spatial intelligence, 553
Spatial localization, visual, 302 –304, 302 f, 303 f
Spatial memory, hippocampus in, 492 –494, 493 f, 494 f
Spatial orientation, of brain, 38
Spatial summation, 129 , 129 f
Special K (ketamine), 182 , 190 , 197
Species, 9 , 16 , 16 f
 between-species vs. within-species comparisons and, 28
Species-typical behavior, 28
motor, 361 –363
Specific phobias, 507 . See also Anxiety disorders
Speech. See also Language
acquisition of, 254 f, 261 –262
Broca’s area for, 254 f, 262 , 342 –346, 342 f, 346 f
cortical localization of, 342 –346
mapping of, 343 –346
lateralization for, 334 –335, 543 –545
motor aspects of, 543 –545
motor sequences in, 360 , 360 f
musicality of, 328
perception of, 327 –328
production of, 342 f, 343 , 344 –345
rate of, 327
vs. music, 327 , 345
Wernicke’s model of, 342 –346, 342 f
Speech arrest, 344 –345
Speech discrimination, 339 –340
Speech patterns, detection of, 339 –340
Speech-sound discrimination task, in brain mapping, 345 –346, 346 f
Speed (methamphetamine), 189
Spider venom, 176
Spina bifida, 277
Spinal accessory nerve, 59 , 60 f
Spinal anesthesia, 387
Spinal cord, 3 , 50 –51
 evolution of, 18 , 47 –49, 48 f
functions of, 364
integrated, 61 –62
interneurons in, 371 –372
motor neurons in, 371 –372
orientation of, 38
posterior-root ganglia in, 381 –382, 381 f
segments of, 60 –61, 61 f, 358 –359
spinal nerves and, 60 –61, 61 f
structure of, 60 –61, 61 f, 358 –359
Spinal cord injury, 86 , 365
dorsal vs. ventral root damage in, 61 , 62 f
emotion in, 421 , 421 f
nerve regeneration in, 365
permanence of, 86
treatment of, 365
unilateral, somatosensory deficits in, 383 f, 384
Spinal nerves, 60 –61, 61 f, 358 –359
Spinal reflexes, 51 , 364 , 384 –385, 384 f
Spine
segments of, 60 –61, 61 f, 358 –359
structure of, 358 –359
Spinothalamic tracts, 382 –384, 383 f
Split-brain studies, 520 , 542 –543, 545
SRY gene, 203
SSRIs (selective serotonin reuptake inhibitors), 185 , 186 . See also
Antidepressants
Staining, brain tissue, 46 –47, 47 f, 75 , 75 f, 78 f, 211 , 212 f
Stellate cells, 79 , 79 f
Stem cells, neural, 250 –252
transplantation of, 161 , 452 , 452 f, 516 , 572 , 587 –588
Stereotaxic apparatus, 218 , 218 f
Steroid hormones, 201 . See also Hormones
anabolic, 204
neurotoxicity of, 510
Stimulants, 188 –190, 189 f
brain damage from, 198
general, 190
psychedelic/hallucinogenic, 189 –190, 198
Stimulus
conditioned, 482
unconditioned, 482
Stimulus equivalence, 309
Stirrup, 329 , 330 f
Storage granules, 142 , 142 f
Stress
anxiety and, 597
brain development and, 271
depression and, 595 –596
epigenetic changes and, 237 , 271
frontal lobe development and, 259
hippocampus and, 185 , 205 –206, 205 f, 595 –596
hypothalamic-pituitary-adrenal axis (HPA) and, 595 –596
neuronal death and, 510
posttraumatic stress disorder and, 206
Stress response, 204 –206, 205 f, 206 f
 activation of, 204 –205, 205 f
hormones in, 204 –206, 205 f, 206 f, 595 –596, 595 f
termination of, 205 –206
Stretch-sensitive channels, 133
Striate cortex. See Visual cortex, primary (striate)
Striatum, 235 , 373 , 373 f
Stroke, 43 , 45 , 580 –581
mild cognitive impairment and, 591
sleep disturbances after, 476 –477
stem cell transplant for, 572
Subcoerulear nucleus, in sleep, 472 , 473 f
Subcortical regions, 46 , 46 f
Subsong, 350
Substance abuse, 191 –200
addiction in, 193
definition of, 193
dopamine in, 193 , 195
neural basis of, 194 –196
psychomotor activation in, 193
sex differences in, 193 –194
treatment of, 196 –197
types of, 195 –196
withdrawal in, 193
adolescent-onset, 275
behavior and, 191 –192
brain damage from, 197 –198
conditioning in, 178 , 195
criminalization of, 196 –197
 definition of, 193
disinhibition and, 191 –192
dopamine in, 193
epigenetics and, 196
genetic factors in, 196
learning in, 192
narcotics in, 188
psychomotor activation in, 193
psychotic symptoms in, 199 , 236
rates of, 196 , 197 f
reward and, 438 –439
risk factors for, 196
sensitization in, 178 –180, 510 –511
tolerance in, 177 –178, 178 f
treatment of, 196 –197
twin studies of, 196
wanting-and-liking theory of, 194 –196
Substantia nigra, 42 , 53 , 53 f
in Alzheimer disease, 590
electrode placement in, 218 , 218 f
in Parkinson disease, 140 , 587 , 590
Subtraction, in positron emission tomography, 233 , 233 f
Subtractive color mixing, 310 , 310 f
Subunits, 154 , 155
Subventricular zone, 250
Sudden infant death syndrome (SIDS), 162 , 277 , 474
Suicide, antidepressant-related, 186
Sulci, 41 f, 42 , 55 , 55 f
Summation, 128 –130, 129 f, 130 f
ions in, 129 –130
spatial, 129 , 129 f
temporal, 129 , 129 f
Superego, 563
Superior colliculus, 53 , 53 f, 69
Superior, definition of, 38 , 39
Superior olive, 333 , 334 f
Supertasters, 404 –405
Supplementary speech area, 344 –345, 344 f
Suprachiasmatic nucleus
in biorhythms, 450 –456, 450 f
slave oscillators in, 452 –453, 453 f, 455
structure of, 451 , 451 f
transplantation of, 452 , 452 f
Surgery. See Neurosurgery
Swimming pool tasks, 215 –216, 216 f
Sympathetic nervous system, 63 –64
neurotransmission in, 157 –158
in stress response, 157 –158, 204 –206, 205 f
Synapses, 77 , 78 f
axoaxonic, 145 , 145 f
axodendritic, 145 , 145 f
axomuscular, 145 , 145 f
axosecretory, 145 , 145 f
axosomatic, 145 , 145 f
axosynaptic, 145 , 145 f
chemical, 141 –142, 142 f
 dendrodendritic, 145 , 145 f
drug action at, 175 f, 176 –177, 185 , 185 f
electrical, 142 , 145 –146
excitatory, 146 , 146 f
formation of, 257 , 502 –503. See also Neuroplasticity
Hebb, 163
inhibitory, 146 , 146 f
in learning, 163 –167, 507 . See also Learning
plasticity of, 162 –163, 502 –504, 503 f. See also Neuroplasticity
structure of, 140 –142, 142 f
types of, 145
Synaptic cleft, 141 , 142 f
Synaptic organization, intelligence and, 555
Synaptic pruning, 257 –258, 257 f
Synaptic transmission. See Neurotransmission
Synaptic vesicles, 141 , 142 f
Synesthesia, 288 , 551 –552
Syntax, 521 –522
definition of, 521
uniformity of, 341 –342
Systematic desensitization, 575
Tactile stimulation
brain development and, 267
sensory processing in, 132 –133, 133 f
Tardive dyskinesia, 574
Taste, 404 –405
reactions to, 437 –438, 438 f
Taste aversions
 behavior in, 437 –438, 438 f
learned, 409
Taste buds, 404 , 405 , 405 f
Taste preferences, 409
Taxonomy, 16 –17, 16 f
Tay-Sachs disease, 98 –99
Tectopulvinar pathway, 296 , 296 f, 298
Tectorial membrane, of inner ear, 330 , 330 f
Tectum, 53 , 53 f
Tegmentum, 53 , 53 f
Telencephalon, 48 , 48 f
Telodendria, 77 , 78 f
Temperature perception, 380 , 382 –388
Temperature regulation, 411 –412
Temporal auditory cortex, 334
tractography of, 534 , 535 , 535 f
Temporal lobe, 41 f, 55 , 55 f
in association cortex, 525 –526, 527 f
in cognition, 525 –526, 527
injury of, 55
in memory, 494 –495, 498 f
neural columns in, 309 –310, 309 f
in shape perception, 309 –310
structure and function of, 55 , 55 f
in visual system, 300 –301, 300 f, 309 –310
Temporal lobectomy, Klüver-Bucy syndrome and, 422
Temporal retina, 295 , 296 f
Temporal summation, 129 , 129 f
Teratogens, 252 , 276 –277
Terminal button, 77 , 78 f
Terminology, anatomical, 38 –39
Tertiary protein structure, 94 f
Testes-determining factor, 548
Testosterone, 200 . See also Sex hormones
behavior and, 401
in brain development, 203 , 273 –275, 432 , 546 –549
functions of, 200 , 202
lifelong effects of, 274 –275
neuroplasticity and, 509
sexual behavior and, 434
in sexual differentiation, 203 , 272 , 432 , 433
Tetrahydrocannabinol (THC), 152 –153, 189 –190, 198 , 199
Tetrodotoxin, 120
Thalamic nuclei, 69
Thalamus, 53 , 53 f, 54
association cortex and, 525
electrode placement in, 572
in gustation, 405
medial, in memory, 495 –497, 498 f
in olfaction, 402 f, 403
ventrolateral, 383 , 383 f
Theory of mind, 536
Thermoregulation, 411 –412
Thiamine deficiency, in Korsakoff syndrome, 495 –497
Thinking. See Cognition; Thought
Thirst. See also Drinking behavior
 hypovolemic, 431
osmotic, 431
Thoracic spine, 60 , 61 f
Thorndike’s puzzle box, 482 –483, 483 f
Thought. See also Cognition
characteristics of, 521 –522
neural unit of, 522 –525, 524 f, 529
as psychological construct, 520
Three-legged cat solution, 514
Threshold potential, 120
Thymine, 91 f, 92
Thymus gland, in myasthenia gravis, 134
Thyroid gland, 415 –416, 415 f
Thyroid hormones, 414 t, 415 –416
Thyroid-stimulating hormone (TSH), 414 t
Tickling, 392
Tight junctions, in blood–brain barrier, 174 , 174 f
Timbre, 324 f, 328
Tissue plasminogen activator (t-PA), 45 , 580 –581
Tolerance, drug/alcohol, 177 –178, 178 f
Tone deafness, 348
Tone of voice, 328 , 424
Tongue, taste receptors on, 405 , 405 f
Tonotopic representation, 336 –338, 337 f
Top-down processing, 56
Topographic maps, 288 , 288 f
Topographic organization. See also Brain maps; Homunculus
of auditory cortex, 343 –346
 of cerebellum, 375 –376
definition of, 367
experience-based changes in, 369 –370, 506 f, 508
of motor cortex, 366 , 366 f, 369 –370
changes in, 369 –370, 369 f, 505 –507, 506 f
of somatosensory cortex, 390 –391, 391 f, 393 f
of visual cortex, 302 –303, 303 f
Touch, sensory processing in, 132 –133, 133 f
Tourette syndrome, 57 , 71 , 374
Tower of Hanoi test, 247 , 247 f
t-PA (tissue plasminogen activator), 45 , 580 –581
Tractography, 534 , 535 , 535 f
Tracts, 47 , 47 f, 61 , 62 f, 358 . See also specific types
Tranquilizers
insomnia and, 473
minor, 182
Transcranial magnetic stimulation (TMS), 220 , 220 f, 573 , 573 f
repetitive, 220 , 573
Transcription, 92 , 93 f, 104
Transcription-translation-inhibition feedback loop, 453
Transfer RNA, 93
Transgender, 435 , 534
Transgenic animals, 102
Translation, 93 , 93 f, 104
in transcription-translation-inhibition feedback loop, 453
Transmembrane proteins, 95 , 95 f
Transmitter-activated receptors, 143 –144
Transmitter-sensitive channels, 133
Transplantation, of neurons, 161 , 452 , 452 f, 516 , 572 , 587 –588
Transporters, 143
Transsexuals, 435 , 534
Trapezoid body, 333 , 334 f
Traumatic brain injury, 2 –3, 13 –14, 577 –580, 577 f. See also Brain
injury
in athletes, 577 , 578
chronic traumatic encephalopathy (CTE) and, 578
concussion and, 577 , 578
diagnosis of, 579
incidence of, 577 , 577 f
mechanics of, 577 –579, 579 f
neuroplasticity in, 513 –517
recovery from, 513 –517, 580
symptoms of, 577 –579
Tremor, in Parkinson disease, 140 , 161 , 586
Triceps muscle, 372 , 372 f
Trichromatic theory, 310 –311
Tricyclic antidepressants, 185 . See also Antidepressants
Trigeminal nerve, 59 , 60 f
Trisomy 21 , 100 , 101 f
Tritanopia, 311
tRNA, 93
Trochlear nerve, 59 , 60 f
Trophic factors, 252
for brain injury, 516 –517
neuroplasticity and, 510 , 510 t
Tropic molecules, 256
Tubules, 90
Tumors, brain, 83
Tuning curves, 336 –337, 336 f
Tuning fork, 323 , 323 f, 324 f
Twin studies
epigenetics and, 237
of substance abuse, 196
Two-point sensitivity, 379 , 379 f
Tyrosine, 150 , 150 f
Ultradian rhythms, 445 , 445 t
Umami receptor, 405
Unconditioned response, 482
Unconditioned stimulus, 482
Unconscious memory. See Memory, implicit
Uracil, 93
Urge-to-action system, 374
Utricle, 388 , 389 f
Vagus nerve, 59 , 60 f, 65
Val allele, 236
Valium, 182
Valproate, for bipolar disorder, 186
Ventral, definition of, 38 , 39
Ventral roots, 61 , 62 f
Ventral spinothalamic tract, 383 f
Ventral thalamus, in memory, 498 , 498 f
Ventral visual stream, 69 –70, 69 f, 297 , 300 f, 527 f
injury of, 315 –316, 316 f
location of, 526
 in object recognition, 526 , 527 f
secondary somatosensory cortex in, 394
as what pathway, 297 , 315 –316, 316 f
Ventricles, 8 , 44 , 44 f
Ventrolateral thalamic neurons, 383
Ventrolateral thalamus, 383 , 383 f
Ventromedial hypothalamus
in eating, 429 , 430 f
in sexual behavior, 434
Ventromedial prefrontal cortex, 418 f, 419 , 526 f
Verbal fluency, sex differences in, 546 –549
Vertebrae, 59 –60, 61 f, 359 . See also under Spinal
Vertigo, 389
Vesicles, synaptic, 141 , 142 f
Vestibular system, 388 –389, 389 f
Virtual Afghanistan, 576
Virtual Iraq, 562 , 576
Virtual reality exposure therapy, 562 , 576
Vision
attention and, 528 –529
binocular, corpus callosum in, 304
color, 310 –313. See also Color vision
light in, 290
in movement, 382
neuropsychology of, 314 –317
night, age-related decline in, 294
peripheral, 292 , 292 f
refractive errors and, 290 –291
 shape perception in, 305 –310, 305 f–310f
spatial localization in, 302 –304
Vision impairment, 314 –317
agnosia and, 301 , 315 –316
in carbon monoxide poisoning, 315 –316
echolocation in, 335
monocular blindness and, 314
refractive errors and, 290 –291
Visual agnosia, 315 –316
in Klüver-Bucy syndrome, 422 –423
Visual cortex
association cortex and, 527 , 527 f
complex cells of, 307 , 307 f
hypercomplex cells of, 307 , 308 f
ocular dominance columns in, 269 , 270 f, 308 –309, 309 f, 312 , 312 f
primary (striate), 296 , 296 f, 297 f, 299 , 299 f
processing in, 307 –309
in shape perception, 307 –309
topographic organization of, 302 –303, 303 f
secondary (extrastriate), 299 , 299 f
simple cells of, 307 , 307 f
Visual fields, 295 –296, 301 –304, 301 f
blindness of, 284 , 314 –315, 314 f
cerebral asymmetry and, 542 , 542 f
Visual illuminance, 294
Visual pathways, 295 –296, 296 f
geniculostriate, 296 , 296 f, 297 –298, 297 f, 298 f
tectopulvinar, 296 , 296 f, 298
Visual recognition task, 493 , 493 f
Visual streams. See Dorsal visual stream; Ventral visual stream
Visual system, 283 –319
anatomy of, 289 –301
chemoaffinity in, 268 –269, 270 f
coding of location in, 302 , 302 f, 303 f
corpus callosum in, 304
dorsal, 313
how function of, 297 , 300 , 313
impairment of, 317 –318
lateralization in, 541 –542, 542 f. See also Visual fields
in movement, 313 , 316 , 316 f, 382
movement perception and, 313
neural connectivity in, 268 –269
neural streams in, 69 –70, 69 f
neuronal activity in, 304 –313
ocular dominance columns in, 269 , 270 f, 308 –309, 309 f, 312 , 312 f
ocular structures in, 289 –291, 291 f
parallel processing in, 68 –70, 69 f
photoreceptors in, 219 f, 289 –294, 294 f, 296 f
primary (striate) cortex in, 296 , 296 f, 297 f, 299 , 299 f, 302 –303,
303 f, 307 –309. See also Visual cortex, primary (striate)
receptive fields in, 302 –303, 302 f, 305 –308
retinal neurons in, 294 –298, 294 f, 295 f
secondary (extrastriate) cortex in, 299 , 300 f
secondary visual cortex in, 299 f
segregated visual input in, 297 –298, 298 f
temporal lobe in, 300 –301, 300 f, 309 –310
 topographic maps in, 302 –303, 303 f
visual pathways in, 295 –296, 296 f, 297 –298, 298 f
visual streams in, 297 –298, 300 f, 314 –317, 394 , 526 , 527 f. See
also Dorsal visual stream; Ventral visual stream
what function of, 297 , 300
impairment of, 315 –316
where function of, 298
Visual-form agnosia, 315 –316, 526
Visuospatial learning, 493
Visuospatial memory, 492
Vitamin B1 deficiency, in Korsakoff syndrome, 495 –497
Vitamin D deficiency
depression and, 185
multiple sclerosis and, 126 , 584
Vocal tone, 328 , 424
Volt, 110
Voltage gradient, 114 –115
Voltage-sensitive ion channels, 117 –119, 121 –122, 121 f, 122 f. See
also Ion channels
Voltmeter, 111
Vomeronasal organ, 403
Vomiting, 174
Waking state, 457 –458, 476 –477. See also Sleep
electroencephalogram in, 457 f, 459 f, 470 –471
Wanting-and-liking theory, 194 –196, 437
Water, chemistry of, 89
Water intoxication, 431
Wave effect, 111 , 111 f
Waves
 light, 290 , 290 f
sound, 323 –329
Weight, regulation of, 426 –430. See also Eating/feeding behavior
Weight-loss strategies, 428
Wernicke’s aphasia, 343
Wernicke’s area, 334 , 334 f, 342 –346, 342 f
mapping of, 343 –346, 344 f
White matter, 43 f, 44 , 47 f
in reticular formation, 52
spinal, 62 f
Wild-type alleles, 97
Wisconsin Card Sorting Task, 531 , 531 f, 533
Withdrawal symptoms, 193
Women. See Sex differences
World Health Organization, 569
Xanax, 182
Xenon, in memory erasing, 498
Y chromosome, SRY gene of, 203
Yips, 375
Zeitgebers, 446 –448
INDEX OF DISORDERS*
Each disorder name is followed by the section(§) and/or Focus feature
number (s) where information appears.
A
▀ Addiction: §2-3, §6-3, §7-2, §12-4, §12-6
▀ Affective disorders: Focus 12-1, §16-4
▀ Agenesis: of cerebellum, Focus 2-1; of frontal lobe,
Focus 12-2
▀ Agnosias: §9-2, §9-5
▀ Akathesia: §16-3
▀ Akinesia: §7-1, §16-3
▀ Alcohol myopia: §16-3
▀ Alzheimer disease: §2-5, §5-3, §6-4, Focus 14-3, §16-3
▀ Amblyopia: §8-4
▀ Amnesia: §7-1, §14-2, Focus 14-2, §15-7
▀ Amusia: Focus 10-6
▀ Amyotrophic lateral sclerosis (ALS): Focus 4-4, Focus 11-1
▀ Androgen insensitivity syndrome: Focus 12-5
▀ Androgenital syndrome: Focus 12-5
▀ Anencephaly: §8-4
▀ Aneurysm: Focus 10-5
▀ Anorexia nervosa: §12-5
▀ Anterograde amnesia: Focus 14-4
▀ Anxiety disorders: §6-2, §6-3, Focus 12-3, §16-4
▀ Aphagia: §12-5
▀ Aphasias: §7-3, §10-4, Focus 15-5
▀ Apraxia: §11-5
▀ Arteriovenous malformations: §16-2, §16-3
▀ Ataxia: §9-5
▀ Attention-deficit/hyperactivity disorder (ADHD): Focus 6-1, Focus 7-
4
▀ Autism spectrum disorder (ASD): Focus 8-2, §8-4, Focus 15-3
▀ Autoimmune disease: Focus 4-2, §16-3
B
▀ Behavioral sensitization: §6-1, §6-4, §14-4
▀ Bell palsy: Focus 2-4
▀ Bipolar disorder: §6-2, §16-4
▀ Blindsight: Focus 9-1, §15-7
▀ Brain tumors: Focus 3-2, §7-3
C
▀ Carbon monoxide poisoning: Focus 9-4
▀ Cataplexy: §13-6
▀ Catatonic posture: §16-3
▀ Cerebral aneurysm: Focus 10-5
▀ Cerebral palsy: Focus 11-2
▀ Chronic traumatic encephalopathy: Focus 16-3
▀ Cognitive disorders: §7-4, Focus 8-4, §8-5, §15-7, §16-3
▀ Color-deficient vision: Focus 9-3
▀ Coma: §1-2, §6-2, §7-2, §13-5, §16-3
▀ Concussion: Focus 16-3
▀ Contralateral neglect: §15-2
D
▀ Deafness: §10-3
▀ Deafferentation: §11-4, §14-4
▀ Dementia: §2-6, §5-3, §7-1, §7-2, §7-4, §7-5, Focus 14
-3, §16 -3
▀ Depression: §5 -3, Focus 6-3, Focus 7-2, §12-4, Focus 16-2, §16-4
▀ Developmental disability: Focus 6 -2, §8 -4, Focus 11-2, §16-1
▀ Developmental disorders: Focus 7-4, Focus 8-3, Focus 14-1, Focus
15-3, §15-3, §16-1, §16-2, §16-3
▀ Diaschisis: §16-3
▀ Dopa-responsive dystonia: Focus 3-1
▀ Down syndrome: §3-3, §8-4
▀ Drug-dependency insomnia: §13-6
▀ Drug-induced behavioral sensitization : see Behavioral sensitization
▀ Drug-induced psychosis: Focus 6-4, Focus 7-3
▀ Dyskinesia: Focus 5-3, §5-3, Focus 11-2, §11-3, §16-2
▀ Dyslexia: Focus 14-1
▀ Dystonia: Focus 14-5
E
▀ Encephalitis: §2-2
▀ Environmental deprivation: Focus 8-1, §8-4, Focus 8-
4, §16-1
▀ Epigenetic factors: §1-2, §2-1, §3-3, §6-4, §7-5, §8-2,
§12-5, Focus 13-3, §14-4, §15-3, §15-6, §16-1, §16-3
▀ Epilepsy: Focus 4-1, §7-2, Focus 10-3, Focus 15-5, §16-3
▀ Extinction: §15-2
F
▀ Fetal alcohol spectrum disorder (FASD): Focus 6-2, §14-4
▀ Festination: §16-3
▀ Focal seizure: §16-3
▀ Frontal leucotomy: §12-4
G
▀ Genderd ysphoria: Table 16-3 ; see also §12-5
▀ Generalized anxiety: §12-4, §16-4
▀ Generalized seizure: §16-3
▀ Genetic disorders: §1-2, Focus 3-1, §3-3, Focus 4-4, Focus 5-2, §6-4,
§7-5, §8-2, §8-4, §10-4, §12-5, §13-6, §15-5, §16-1, §16-2, §16-3, §16-
4
▀ Glioma: Focus 3-2
H
▀ Hallucinations: §6-2, Fo c us 6-4, Focus 8-5, §13-6, §15-7
▀ Hemianopia: §9-5
▀ Hemorrhagic stroke: Focus 2-3
▀ Hormonal disorders: §7-5, § 8-4, §12-5, §16-1, §16-2,
§16-4
▀ Huntington disease: Focus 3-4
▀ Hydrocephalus: §3-1
▀ Hyperopia: §9-2
▀ Hyperphagia: §12-5
▀ Hypnogogic hallucinations: §13-6
▀ Hypovolumic thirst: §12-5
I
▀ Idiopathic seizure: §16-3
▀ Insomnia: §13-6
▀ Ischemia: Focus 2-3, §16-3
J
▀ Jet lag: §13-1
K
▀ Klüver—Bucy syndrome: §12-4
▀ Korsakoff syndrome: Focus 14-4
L
▀ Language disorders: §7-1, Focus 8-2, §8-3, §8-4, §10-3, §10-4, Focus
14-1, §15-1, §15-4
▀ Learning disabilities: Focus 7-4, §8-4, Focus 14-1
▀ Locked-in syndrome: Focus 11-1, §11-1
▀ Lou Gehrig’s disease (ALS): Focus 4-4, Focus 11-1
M
▀ Major depression: §5-3, Focus 6-3, Focus 7-2, §12-4, Focus 16-2
▀ Mania: §5-3, §6-2, §16-4
▀ Memory deficits: §7-1, Focus 7-2, §14-2, §14-3, Focus 14-3
▀ Mèniére disease: §11-4
▀ Meningioma: Focus 3-2
▀ Meningitis: §2-2
▀ Metabolic syndrome: Focus 13-1, §13 -1
▀ Metastatic tumor: Focus 3 -2
▀ Migraine: Focus 9-1
▀ Mild cognitive impairment: Focus 14-3, §16-3
▀ Minimally conscious state (MCS): §1-2
▀ Monocular blindness: §9 -5
▀ Mood disorders: §12-4, §16-4
▀ MPTP poisoning: Focus 5-4, §16 -1
▀ Multiple sclerosis (MS): Focus 4-2, §6-2, §1 6 -3
▀ Myasthenia gravis: §4-4, §6 -1
▀ Myopia: §9-2
N
▀ Narcolepsy: §3-6
▀ Neglect: §5-2, §5-7
▀ Neurodegenerative disease: §6-3
▀ Neurotoxins: Focus 5-2, §5-3, §6-4, §6-1, §6 -2, §6 -3
▀ Night terrors: §3-3
O
▀ Obesity: §2-5
▀ Obsessive-compulsive disorder (OCD): §5-3, §2-4, §5-7, §6-2
▀ Optic ataxia: §9-5
▀ Osmotic thirst: §2-5
▀ Otoacoustic emissions: Focus 10-2
P
▀ Pain: §6-2, §11-4, Focus 12-1, §16-2, §16-3
▀ Panic disorder : Focus 12-3
▀ Paralysis: Focus 2-4, §3-1
▀ Paraplegia : §11-1, Focus 11-3
▀ Parkinson disease: §2-3, Focus 5-2, Focus 5 -3, Focus 5-4, §5-3, §7-1,
§7-5, §11-3, §16-3
▀ Perseveration: §15-2
▀ Persistent vegetative state: §1-2
▀ Phantom limb pain: Focus 11-5, §11-5
▀ Phenylketonuria (PKU): §8-4, §16-1
▀ Phobias : Focus 12-3, §16-2
▀ Postictal depression: §16-3
▀ Posttraumatic stress disorder (PTSD): §5-4, §6-5, §12-4, Focus 16-1
▀ Presbyopia: §9-2
▀ Prion disease: §16-3
▀ Psychos is: §6-2, Focus 6-4, Focus 7-3, §16-2, §16-3
Q
▀ Quadrantanopia: §9-5
▀ Quadriplegia: §11-1
 R
▀ Restless legs syndrome (RLS): Focus
13-4
▀ Retrograde amnesia: Focus 14-4
S
▀ Schizophrenia: §5-3, § 6-1, §6-2, Focus 6-4, §7-1, §7-4, §7-5, Focus
7-3, Focus 8-5, §16-2, §16-4
▀ Scotoma : Focus 9-1, §9-5
▀ Seasonal affective disorder (SAD): Focus 13-2
▀ Seizure: Focus 4-1, Focus 10-3, §16-3
▀ Sleep apnea : Focus 13-5
▀ Sleep paralysis: §13-6
▀ Spina bifida: §8-4
▀ Spinal-cord injury: §2-4, §6-2, Focus 11-3, §11-4, §12-3
▀ Split-brain syndrome : Focus 15-1, §15-4
▀ Stress §2-5, §6-5, §7-5, §8-2, §8-4, §12-4, §6-1, §16-2, §16-3, §16-4
▀ Stroke: §2-3, §7-1, §7-3, §7-5, §7-7, §16 -3
▀ Substance abuse: §2-3, §6-3, §12-4, §12-6
▀ Sudden infant death syndrome (SIDS): §5-3, §8-4, Focus 13-5
▀ Suicide: Focus 6-3, §7-5, §16-4
▀ Symptomatic seizure: §16-3
▀ Synesthesia: §9-1, §15-5, Focus 15-6
T
▀ Tardive dyskinesia: §16-2
▀ Tay—Sachs disease: §3-3, §16-1
▀ Tourette syndrome: §2-3, Focus 11-4
▀ Traumatic brain injury (TBI): Focus 1-1, §7-1, §7-5, §14-5, §16-3
▀ Tumors : Focus 3-3, §7-3
V
▀ Vertigo: §11-4
▀ Visual-form agnosia: §9-5, §15-7
▀ Visual illuminance: Focus 9-2
W
▀ Water intoxication: §12-5
* For a summary of general treatment categories, see the
Chapter 16 Summary. For a summary of research
techniques, see Tables 7-1 and 7-2 .
Study Smarter with LearningCurve!
What is
LearningCurve is a cutting-edge study tool designed to increase your
understanding and memory of the core concepts in every chapter. Based
on insights from the latest learning and memory research, the
LearningCurve system pairs multiple-choice and fill-in-the-blank
questions with instantaneous feedback and a rich array of study tools
including videos, animations, and lab simulations.
The LearningCurve system is adaptive, so the quiz you take is
customized to your level of understanding. The more questions you
answer correctly, the more challenging the questions become. Best of all,
the e-Book of An Introduction to Brain and Behavior, Fifth Edition, is
fully integrated, so you can easily review the text as you study and
answer questions.
LearningCurve is a smart and fun way to master each chapter and
prepare for your exam.
 is available as part of the LaunchPad
for An Introduction to Brain and
Behavior, Fifth Edition. To find out
more or purchase access, go to
http://www.macmillanhighered.com/launchpad/kolbintro5e
 AN INTRODUCTION TO BRAIN AND
BEHAVIOR, Fifth Edition
LaunchPad for An Introduction to Brain and Behavior, Fifth Edition
Available July 2016 at
http://www.macmillanhighered.com/launchpad/kolbintro5e
Each chapter in LaunchPad for An Introduction to Brain and Behavior,
Fifth Edition features a collection of activities carefully chosen to help
master the major concepts. The site serves students as a comprehensive
online study guide, available any time, with opportunities for self-
quizzing that include instant feedback, exam preparation, and further
exploration of topics from the textbook. For instructors, all units and
activities can be instantly assigned, and students’ results and analytics
are collected in the Gradebook.

FOR STUDENTS
▀ Full e-Book of An Introduction to Brain and Behavior, Fifth Edition
▀ LearningCurve
▀ Video Activities
▀ Summative Quizzes
▀ Neuroscience Tool Kit Activities
▀ Interactive Flashcards

FOR INSTRUCTION
▀ Lecture Slides
▀ Chapter Figures, Photos, and Tables
▀ Downloadable Diploma Computerized Test Bank
▀ Instructor’s Resources