BIOPSYCHOLOGY 8e

John P.J. Pinel

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Topics
10.1 Causes of Brain Damage

10.2 Neuropsychological Diseases

10.3 Animal Models of Human

Neuropsychological Diseases

10.4 Neuroplastic Responses to Nervous

System Damage: Degeneration,
Regeneration, Reorganization, and
Recovery
10.5 Neuroplasticity and the Treatment of
Nervous System Damage
Causes of Brain Damage

• Brain tumors

• Cerebrovascular
disorders

• Closed-head injuries

• Infections of the brain

• Neurotoxins

• Genetic factors

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Brain Tumors
• A tumor (neoplasm) is a mass of
cells that grows independently of
the rest of the body – a cancer
• 20% of brain tumors are
meningiomas – encased in
meninges
• Encapsulated, growing within
their own membranes
• Usually benign, surgically
removable

• Most brain tumors are infiltrating

• About 10% of brain tumors are
metastic – the originate elsewhere,
usually the lungs
Cerebrovascular Disorders

• Stroke – A sudden-onset
cerebrovascular event that
causes brain damage
– Cerebral hemorrhage
(bleeding in the brain)
– Cerebral ischemia
(disruption of blood
supply)
• Third leading cause of death
in the U.S. and most common
cause of adult disability

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Cerebrovascular Disorders
• Cerebral hemorrhage (bleeding in the
brain)
– Aneurysm – a weakened point
in a blood vessel that makes a
stroke more likely; may be
congenital (present at birth) or
due to poison or infection
• Cerebral ischemia (disruption of blood
supply)
– Thrombosis – a plug forms in
the brain
– Embolism – a plug forms
elsewhere and moves to the
brain
– Arteriosclerosis – wall of blood
vessels thicken, usually due to
fat deposits

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Damage Due to Cerebral Ischemia

• Does not develop immediately

• Most damage is a consequence of excess neurotransmitter
release – especially glutamate
• Blood-deprived neurons become overactive and release
glutamate
• Glutamate overactivates its receptors, especially NMDA
receptors leading to an influx of Na+ and Ca2+
• lnflux of Na+ and Ca2+ triggers
• the release of still more glutamate
• a sequence of internal reactions that ultimately kill the
neuron

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Damage Due to Cerebral Ischemia

• Ischemia-induced
brain damage:
• takes time
• does not occur
equally in all parts of
the brain
• mechanisms of
damage vary with
the brain structure
affected

FIGURE 10.5: The cascade of events by which

the stroke-induced release of glutamate kills
neurons

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Closed-Head Injuries
• Brain injuries due to blows that do not
penetrate the skull – the brain collides
with the skull
• Contrecoup injuries – contusions
are often on the side of the brain
opposite to the blow
• Contusions – closed-head injuries that
involve damage to the cerebral circulatory
system; hematoma (bruise) forms
• Concussions – when there is disturbance
of consciousness following a blow to the
head and no evidence of structural
damage
•While there is no apparent brain damage
with a single concussion, multiple
concussions may result in a dementia
referred to as “punch-drunk syndrome” Copyright ©
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Infections of the Brain
• Encephalitis – the resulting
inflammation of the brain by an
invasion of microorganisms
• Bacterial infections
• Often lead to abscesses, pockets
of puss
• May inflame meninges, creating
meningitis
• Treatwith penicillin and other
antibiotics

• Viral infections
• Some preferentially attack neural
tissues
• Some can lie dormant for years
 eurotoxins

• May enter general circulation from the GI tract or lungs, or

through the skin
• Toxic psychosis – chronic insanity produced by a neurotoxin
• The Mad Hatter – hat makers often had toxic psychosis due to
mercury exposure
• Some antipsychotic drugs produce a motor disorder called
tardive dyskinesia
• Some neurotoxins are endogenous (produced by the body)
• e.g., auto-immune disorders
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Genetic Factors

• Most neuropsychological
diseases of genetic origin are
associated with recessive
genes--why?
• Down syndrome:
• 0.15% of births, probability
increases with advancing
maternal age
• Extra chromosome 21
created during ovulation
• Characteristic disfigurement,
mental retardation, other
health problems

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Programmed Cell Death

All six causes of brain

damage produce damage,
in part, by activating
apoptosis

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Neuropsychological Diseases

• Epilepsy
• Parkinson’s disease
• Huntington’s disease
• Multiple sclerosis
• Alzheimer’s disease

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Epilepsy

• Primary symptom is seizures, but not

all who have seizures have epilepsy
• Epileptics have seizures generated by
their own brain dysfunction
• Affects about 1% of the population
• Difficult to diagnose due to the
diversity and complexity of epileptic
seizures

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Epilepsy

• Types of seizures
• Convulsions – motor seizures
• Some are merely subtle changes of thought,
mood, or behavior
• Causes
• Brain damage
• Genes – over 70 known so far
• Faults at inhibitory synapses
• Diagnosis
• EEG – electroencephalogram
• Seizures associated with high amplitude
spikes

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Epilepsy

• Seizures often preceded by an aura,

such as a smell, hallucination, or
feeling
• Aura’s nature suggests the epileptic focus
• Warns epileptic of an impending seizure
• Partial epilepsy – does not involve the
whole brain
• Generalized epilepsy – involves the
entire brain

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Partial Seizures

Simple Complex
• Symptoms are primarily • Often restricted to the
sensory or motor or temporal lobes
both (Jacksonian (temporal lobe epilepsy)
seizures) • Patient engages in
• Symptoms spread as compulsive and
epileptic discharge repetitive simple
spreads behaviors
(automatisms)
• More complex behaviors
seem normal

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Generalized Seizures

• Grand mal
• Loss of consciousness and
equilibrium
• Tonic-clonic convulsions
• Rigidity (tonus)
• Tremors (clonus)
• Petit mal
• Not associated with convulsions
• A disruption of consciousness
associated with a cessation of
ongoing behavior

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Parkinson’s Disease
•AAlmost no dopamine
movement disorderin ofthe
substantia
middle and nigra
old ageof affecting
Parkinson’s
about .5% of patients
the population
•Tremor
Autopsies often
at rest is reveal
the mostLewy
bodies (protein
common symptom clumps)
of thein
the substantia
full-blown nigra
disorder
•Dementia
Treated temporarily with L-
is not typically
dopa
seen
• No
Linked to cause
single about 10 different
gene mutations
• Associated with
•degeneration
Deep brain stimulation
of the of
subthalamic
substantia nucleus
nigra; these
reduces symptoms,
neurons but
release dopamine
effectiveness
to the striatumslowly
of the basal
declines over months or
ganglia
years

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Multiple Sclerosis

• A progressive disease that attacks CNS

myelin, leaving areas of hard scar tissue
(sclerosis)
• Nature and severity of deficits vary with the
nature, size, and position of sclerotic lesions
• Periods of remission are common
• Symptoms include visual disturbances,
muscle weakness, numbness, tremor, and
loss of motor coordination (ataxia)

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Multiple Sclerosis

• Epidemiological studies
find that incidence of MS
is increased in those
who spend childhood in
a cool climate
• MS is rare among
Africans and Asians
• Only some genetic
predisposition and only
one chromosomal locus
linked to MS with any
certainty

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Alzheimer’s Disease

• Most common cause of dementia – likelihood of

developing it increases with age
• Progressive, with early stages characterized by
confusion and a selective decline in memory
• Definitive diagnosis only at autopsy – must
observe neurofibrillary tangles and amyloid
plaques

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 Alzheimer’s Disease
• Several genes associated with
early-onset AD synthesize
amyloid or tau, a protein found
in the tangles
• Which comes first, amyloid
plaques or neuro-fibrillary
tangles? Genetic research on
early-onset AD supports
amyloid hypothesis (amyloid
first)
• Decline in acetylcholine levels
is one of the earliest signs of
AD
• Effective treatments not yet
available
• Immunotherapy is
promising in animal models
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 Animal Models of Human Neuropsychological
Diseases
• Experiments regarding
neuropathology are not usually
possible with human subjects
• Animal models are often utilized, for
example:
• Kindling model of epilepsy
– Experimentally induced
seizure activity
• Transgenic mouse model of
Alzheimer’s
– Mice producing human
amyloid
• MPTP model of Parkinson’s
– Drug-induced damage
comparable to that seen in PD

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Kindling Model of Epilepsy

• A series of periodic brain stimulations eventually

elicits convulsions: the kindling phenomenon

• Neural changes are permanent

• Produced by stimulation distributed over

time

• Convulsions are similar to those seen in some

forms of human epilepsy – but they only occur
spontaneously if kindled for a very long time

• Kindling phenomenon is comparable to the

development of epilepsy (epileptogenesis) seen
following a head injury

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Transgenic Mouse Model of Alzheimer’s Disease

• Only humans and a few related primates

develop amyloid plaques
• Transgenic – genes of another species
have been introduced
• Genes accelerating human amyloid
synthesis introduced in mice
• Plaque distribution comparable to that in
AD
• Unlike humans, no neurofibrillary tangles

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MPTP Model of Parkinson’s Disease

The Case of the Frozen

Addicts:
• Synthetic heroin produced the
symptoms of Parkinson’s
• Contained MPTP
• MPTP causes cell loss in the
substantia nigra, like that seen in
PD
• Animal studies led to the finding
that deprenyl can retard the
progression of PD

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Neuroplastic Responses to Nervous System Damage

• Degeneration – deterioration
• Regeneration – regrowth of
damaged neurons
• Reorganization
• Recovery

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Neural Degeneration

• Cutting axons (axotomy) is

a common way to study
responses to neuronal
damage

• Anterograde: degeneration
of the distal segment –
between the cut and
synaptic terminals

• Retrograde: degeneration
of the proximal segment –
between the cut and cell
body

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Neural Regeneration

• Does not proceed

successfully in mammals and
other higher vertebrates –
capacity for accurate axonal
growth is lost in maturity

• Regeneration is virtually
nonexistent in the CNS of
adult mammals and unlikely,
but possible, in the PNS

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Neural Regeneration in the PNS

• If the original Schwann cell

myelin sheath is intact,
regenerating axons may
grow through them to their
original targets
• If the nerve is severed and
the ends are separated,
they may grow into
incorrect sheaths
• If ends are widely
separated, no meaningful
regeneration will occur

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Neural Reorganization

Reorganization of primary sensory and

motor systems has been observed in
laboratory animals following
• Damage to peripheral nerves
• Damage to primary cortical areas
Lesion one retina and remove the other –
V1 neurons that originally responded to
lesioned area now responded to an
adjacent area – remapping occurred
within minutes
Studies show large scale of reorganization
possible

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Cortical Reorganization Following Damage in
Humans

Brain-imaging studies indicate

there is continuous competition
for cortical space by functional
circuits
• e.g. Auditory and
somatosensory input may be
processed in formerly visual
areas in blinded individuals

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Mechanisms of Neural Reorganization

The human brain

• Strengthened existing connections due to a
release from inhibition?
• Consistent with speed and localized
nature of reorganization
• Establishment of new connections?
• Magnitude can be too great to be
explained by changes in existing
connections

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Recovery of Function after Brain Damage

• Difficult to conduct controlled

experiments on populations of brain-
damaged patients
• Can’t distinguish between true
recovery and compensatory changes
• Cognitive reserve – education and
intelligence – thought to play an
important role in recovery of function
– may permit cognitive tasks to be
accomplished in new ways
• Adult neurogenesis may play a role
in recovery

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Neuroplasticity and the Treatment of Nervous
System Damage

• Reducing brain damage by

blocking neurodegeneration
• Promoting recovery by
promoting regeneration
• Promoting recovery by
transplantation
• Promoting recovery by
rehabilitative training

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Reducing Brain Damage by Blocking
Neurodegeneration

• Various neurochemicals
can block or limit
neurodegeneration

Apoptosis Nerve growth Estrogens

inhibitor protein factor

• Neuroprotective molecules
tend to also promote
regeneration

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Promoting CNS Recovery by Promoting Regeneration

• While regeneration does not normally occur in CNS,

experimentally it can be induced, directing growth of
axons by:
• Schwann cells
• Olfactory ensheathing cells

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Promoting Recovery by Neurotransplantation

• Transplanting fetal tissue

• Fetal substantia nigra cells
used to treat MPTP-treated
monkeys (PD model)
• Treatment was successful
• Limited success with humans
• Transplanting stem cells
• e.g. Embryonic stems cells
implanted into damaged rat
spinal cord
• Rats with spinal damage with
improved mobility

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Promoting Recovery by Rehabilitative Training

• Monkeys recovered hand function

from induced strokes following rehab
training
• Constraint-induced therapy in stroke
patients – tie down functioning limb
while training the impaired one –
creates a competitive situation to
foster recovery
• Facilitated walking as an approach
to treating spinal injury

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Phantom Limbs: Neuroplastic Phenomena

• Ramachandran’s hypothesis:
phantom limb caused by
reorganization of the somato-sensory
cortex following amputation
• Amputee feels a touch on his face
and also on his phantom limb (due to
their proximity on somatosensory
cortex)
• Amputee with chronic phantom limb
pain gets relief through visual
feedback: view in mirror of his intact
hand unclenching as seen in mirror
box

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 Watch: My Tumor and Welcome to It
Watch: Genetic Counseling
Watch: Alzheimer’s and Dementia

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Acknowledgments
Slide Image Description Image Source

template lightning ©istockphoto.com/Soubrette

template background texture ©istockphoto.com/Hedda Gjerpen

Ch10 image Image of brain ©iStockphoto.com/Hayden Bird

3, 4, 10, 18, 19, 21, 36 brain ©istockphoto.com/Stephen Kirklys

5, 6 woman observing & taking notes ©istockphoto.com/Claudio Arnese

8 Figure 10.5 Pinel 8e, p. 244

9 car on road ©iStockphoto.com/slobo

12 two babies ©istockphoto.com/schwester

13, 29, 31, 33 book ©istockphoto.com/Carmen Martínez Banús

14 person thinking ©istockphoto.com/akurtz

15-17 colored smoke ©istockphoto.com/Wolfgang Amri
20 man in shadow (black and white) ©istockphoto.com/blackred

22 father and son ice skating ©istockphoto.com/Nikolay Suslov

23 elderly couple sitting on bench ©istockphoto.com/Iain Sarjeant

24 senior adult with hands covering face ©istockphoto.com/Duncan Walker

24 Figure 10.13 Pinel 8e, p. 252

25 hand holding rat ©iStockphoto.com/sidsnapper

26, 27 white rat ©iStockphoto.com/Elena Butinova

26 blue sky & clouds ©istockphoto.com/kertlis

27 DNA ©istockphoto.com/Mark Evans

28 notebook ©istockphoto.com/stockcam

28 yellow pad ©istockphoto.com/DNY59

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Acknowledgments
Slide Image Description Image Source

30 Figure 10.15 Pinel 8e, p. 256

32 Figure 10.16 Pinel 8e, p. 257

34 PET scan ©istockphoto.com/BanksPhotos

35 neuron ©istockphoto.com/ktsimage

37, 40 stem cell ©istockphoto.com/luismmolina

39 head - woman ©istockphoto.com/Angel Herrero de Frutos

41 chimpanzee smiling ©istockphoto.com/Eric Isselée

42 Figure 10.23 Pinel 8e, p. 265

43 laptop ©istockphoto.com/CostinT

43 table and wall ©istockphoto.com/David Clark

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