T h e Ox f o r d H a n d b o o k o f

E E G F R E QU E N C Y
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The Oxford Handbook of

EEG
FREQUENCY
Edited by
PHILIP GABLE, MATTHEW MILLER,
EDWARD BERNAT
 Great Clarendon Street, Oxford, OX2 6DP,
United Kingdom
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 Contents

List of Contributors ix
Foreword xiii
Preface xv

PA RT I 
1. Introduction: Methods for Collecting EEG Data for Frequency
Analyses in Humans  3
Philip A. Gable and Matthew W. Miller
2. Logic behind EEG Frequency Analysis: Basic Electricity and
Assumptions  15
Kyle J. Curham and John J. B. Allen

3. From Neural Oscillations to Cognitive Processes  40

Andreas Keil and Nina Thigpen
4. Time-​Frequency Decomposition Methods for Event-​Related
Potential Analysis  65
Selin Aviyente
5. Time Frequency Analyses in Event-​Related Potential
Methodologies  88
Anna Weinberg, Paige Ethridge,
Belel Ait Oumeziane, and Dan Foti
6. The Relationship Between Evoked and Induced EEG/​MEG
Changes: Going Beyond Labels  115
Ali Mazaheri
7. Frequency Analysis of the Monkey Neocortical Local
Field Potential  131
Steven L. Bressler
vi   Contents

PA RT I I 
8. Gamma Activity in Sensory and Cognitive Processing  145
Daniel Strüber and Christoph S. Herrmann
9. Frontal Midline Theta as a Model Specimen of Cortical Theta  178
James F. Cavanagh and Michael X Cohen
10. The Role of Alpha and Beta Oscillations in the Human EEG during
Perception and Memory Processes  202
Sebastian Michelmann, Benjamin Griffiths,
and Simon Hanslmayr
11. Theory and Research on Asymmetric Frontal Cortical Activity as
Assessed by EEG Frequency Analyses  220
Eddie Harmon-​Jones, Taylor Popp, and Philip A. Gable
12. Oscillatory Activity in Sensorimotor Function  259
Bernadette C. M. van Wijk

PA RT I I I 
13. EEG Frequency Development across Infancy and Childhood  293
Kimberly Cuevas and Martha Ann Bell
14. Developmental Research on Time-​Frequency Activity in
Adolescence and Early Adulthood  324
Stephen M. Malone, Jeremy Harper, and William G. Iacono
15. Theta-Beta Power Ratio: An Electrophysiological Signature of
Motivation, Attention and Cognitive Control  352
Dennis J. L. G. Schutter and J. Leon Kenemans
16. Cortical Source Localization in EEG Frequency Analysis  377
Wanze Xie and John E. Richards
17. Frequency Characteristics of Sleep  401
Alpár S. Lázár, Zsolt I. Lázár, and Róbert Bódizs
18. A Review of Oscillatory Brain Dynamics in Schizophrenia  434
Kevin M. Spencer
19. EEG Frequency Techniques for Imaging Control Functions
in Anxiety  464
Jason S. Moser, Courtney Louis, Lilianne Gloe,
Stefanie Russman Block, and Spencer Fix
 Contents   vii

PA RT I V 
20. Bivariate Functional Connectivity Measures for Within-​and
Cross-​Frequency Coupling of Neuronal Oscillations  495
J. Matias Palva and Satu Palva
21. Multivariate Methods for Functional Connectivity Analysis  514
Selin Aviyente
22. Brain Stimulation Approaches to Investigate EEG Oscillations  532
Florian H. Kasten and Christoph S. Herrmann
23. Parameterizing Neural Field Potential Data  563
Bradley Voytek

Index 579
 List of Contributors

John J. B. Allen, Distinguished Professor of Psychology, Department of Psychology,

University of Arizona, Tucson, AZ
Selin Aviyente, Professor, Department of Electrical and Computer Engineering,
Michigan State University, East Lansing, MI
Martha Ann Bell, University Distinguished Professor, Department of Psychology, Virginia
Tech, Blacksburg, VA
Róbert Bódizs, Senior Research Fellow, Semmelweis University, Institute of Behavioural
Sciences, Budapest, Hungary
Steven L. Bressler, Professor, Center for Complex Systems and Brain Sciences, Department
of Psychology, Florida Atlantic University, Boca Raton, FL
James F. Cavanagh, Associate Professor, Department of Psychology, University of New
Mexico, Albuquerque, NM
Michael X Cohen, Assistant Professor, Donders Centre for Neuroscience & Radboud
University Medical Center, Nijmegen, Netherlands
Kimberly Cuevas, Associate Professor, Department of Psychological Sciences,
University of Connecticut, Storrs, CT
Kyle J. Curham, Department of Psychology, University of Arizona, Tucson, AZ
Paige Ethridge, Department of Psychology, McGill University, Montreal, QC, Canada
Spencer Fix, Department of Psychology, University of Maryland College Park, College
Park, MD
Dan Foti, Associate Professor, Department of Psychological Sciences, Purdue University,
West Lafayette, IN
Philip A. Gable, Associate Professor of Psychology, Department of Psychological and
Brain Sciences, University of Delaware, Newark, DE
Lilianne Gloe, Department of Psychology, College of Social Science, Michigan State
University, East Lansing, MI
Benjamin Griffiths, School of Psychology, University of Birmingham, Edgbaston,
Birmingham, UK
x   LIST OF CONTRIBUTORS

Simon Hanslmayr, Professor, Centre for Cognitive Neuroimaging, School for Neuroscience
and Psychology, University of Glasgow, UK
Eddie Harmon-​Jones, Professor, School of Psychological Science, University of New
South Wales, Sydney, Australia
Jeremy Harper, Department of Psychiatry and Behavioral Sciences, University of
Minnesota, Minneapolis, MN
Christoph S. Herrmann, Professor, Experimental Psychology Lab, Carl von Ossietzky
University, Oldenburg, Germany
William G. Iacono, Professor, Department of Psychology, University of Minnesota,
Minneapolis, MN
Florian H. Kasten, Experimental Psychology Lab, Carl von Ossietzky University,
Oldenburg, Germany
Andreas Keil, Professor of Psychology, Department of Psychology and Center for the
Study of Emotion & Attention, University of Florida, Gainesville, FL.
J. Leon Kenemans, Professor, Biopsychology and Psychopharmacology, Utrecht
University, Utrecht, Netherlands
Alpár S. Lázár, Associate Professor, School of Health Sciences, University of East
Anglia, Norwich, UK
Zsolt I. Lázár, Assistant Professor, Faculty of Physics, Babeş-​Bolyai University, Cluj-​
Napoca, Romania
Courtney Louis, Department of Psychology, College of Social Science, Michigan State
University, East Lansing, MI
Stephen M. Malone, Research Assistant Professor and Co-​investigator, Minnesota
Center for Twin & Family Research, University of Minnesota, Minneapolis, MN
Ali Mazaheri, Associate Professor, School of Psychology, University of Birmingham,
Edgbaston, Birmingham, UK
Sebastian Michelmann, Princeton Neuroscience Institute, Princeton, NJ
Matthew W. Miller, Associate Professor, School of Kinesiology, Auburn University,
Auburn, AL
Jason Moser, Professor, Department of Psychology College of Social Science, Psychology,
Michigan State University, East Lansing, MI
Belel Ait Oumeziane, Department of Psychological Sciences, Purdue University, West
Lafayette, IN
 LIST OF CONTRIBUTORS    xi

J. Matias Palva, Research Director, Department of Neuroscience and Biomedical

Engineering, Aalto University, Helsinki
Satu Palva, Professor, Centre for Cognitive Neuroimaging, School of Psychology and
Neuroscience, University of Glasgow, Glasgow
Taylor Popp, Carnegie Mellon University, Pittsburgh, PA
John E. Richards, Professor, Department of Psychology, University of South Carolina,
Columbia, SC
Stefanie Russman Block, Department of Psychology, College of Social Science, Michigan
State University, East Lansing, MI
Dennis J. L. G. Schutter, Professor, Experimental Biopsychology of Motivation and
Emotion, Utrecht University, Utrecht, Netherlands
Kevin M. Spencer, Research Health Scientist, Veterans Affairs Boston Healthcare
System; and Associate Professor of Psychiatry, Harvard Medical School, Boston, MA
Daniel Strüber, Adjunct Professor, Experimental Psychology Lab, Carl von Ossietzky
University, Oldenburg, Germany
Nina Thigpen, Research Scientist at Google X, The Moonshot Factory, Mountain
View, CA.
Bernadette C. M. Van Wijk, Marie Curie Research Fellow at the University of Amsterdam,
Amsterdam, Netherlands
Bradley Voytek, Associate Professor, Department of Cognitive Science, UC San Diego,
San Diego, CA
Anna Weinberg, Assistant Professor, Department of Psychology, McGill University,
Montreal, QC, Canada
Wanze Xie, Assistant Professor, School of Psychological and Cognitive Sciences, Peking
University, Beijing, China
 Foreword

Steven J. Luck

When Hans Berger conducted his pioneering human EEG recordings in the 1920s, his
first major discovery was the alpha rhythm, a 10-​Hz oscillation that grew larger when the
subject’s eyes were closed. A few years later, Lord Adrian (my intellectual great-​great-​
grandfather) showed that the alpha rhythm also varied according to whether the subject
was focusing intensely or daydreaming. Thus the study of EEG oscillations was born.
But this area of research underwent a protracted childhood, because the scientists
of the mid-​twentieth century could not easily see smaller oscillations amidst the cha-
otic twists and turns of the scalp EEG. To pull out specific neural processes from the
complex and noisy EEG, they began to use signal averaging techniques that can isolate
the brain potentials that are triggered by specific events such as the onset of a light (the
event-​related potentials or ERPs). However, these techniques assume that the phase of
the signal is constant across trials, and the application of signal averaging to EEG data
eliminates or hopelessly distorts oscillating activity. Indeed, for the first 30 years of my
own research career, I viewed the alpha rhythm as a nuisance that should be suppressed
lest it contaminate my precious ERP waveforms.
All of this began to change in the 1980s and 1990s, partly driven by high-​profile studies
of local field potential oscillations in animals and partly driven by the application of
time-​frequency analysis methods to human EEG recordings. The brain oscillations that
were obscured by signal averaging could now be visualized and quantified. A new gen-
eration of researchers began studying human EEG oscillations and linking them with
microelectrode data from animals and computational models of brain dynamics.
In science, the introduction of a new approach often leads to a burst of progress
followed by the realization that things are not as simple as they seem. The new wave of
oscillation research followed this common path, with the discovery of important new
phenomena being accompanied by conceptual and methodological challenges. One
such challenge—​related to the famous Heisenberg Uncertainty Principle—​is that pre-
cision in the time-​domain is inversely related to precision in the frequency domain. The
more precisely you determine the frequency of an oscillation, the less you can say about
when the oscillation was present.
A second important challenge is the difficulty of distinguishing between bona fide
oscillations and other kinds of neural events. Part of the genius of the Fourier transform
xiv   Foreword

is that any waveform—​whether or not it contains oscillations—​can be reconstructed by

summing together a set of sinusoids. As a result, when you apply a method such as the
Fourier transform to a time-​domain signal such as the EEG, you will always see activity
at some frequencies, whether or not the signal is actually oscillating. And what if the
brain is oscillating, but not in a sinusoidal manner? This can lead to completely artifac-
tual results, such as the apparent coupling of the amplitude of one frequency with the
phase of another frequency.
A third key challenge is the interpretation of brain oscillations. Virtually any system
containing multiple interconnected parts will oscillate when energy is introduced.
Those oscillations can be essential to the function of the system, as when the sound of a
single violin fills a concert hall or when a clock keeps perfect time. But oscillations can
also be a sign of trouble, as when a bridge shakes violently following an earthquake or
when a seizure spreads throughout the brain. The fact that the brain oscillates, and that
the oscillations vary across states or tasks, does not mean that the oscillations them-
selves are playing a functional role in the brain’s computations. They may be epiphe-
nomenal. Or they may be fundamental. Distinguishing between these possibilities may
require invasive recordings in animals or experimental manipulations of oscillations via
brain stimulation.
The study of EEG oscillations has reached a key point in its development. The appli-
cation of time-​frequency methods to EEG data is now commonplace, aided by open
source data analysis packages such as FieldTrip and EEGLAB. Labs that eschewed
these methods for many years—​including my own—​are now examining oscillations
alongside traditional event-​related potentials. However, this success means that more
researchers are using time-​frequency analyses without understanding the challenges
involved in properly quantifying and interpreting oscillatory activity. As a result, this
edited volume has appeared at the perfect time.
The chapters in this volume will give scientists of all career stages the knowledge
they need to understand how oscillations arise in the brain, how they can be accurately
quantified, and how they can be appropriately interpreted. I encourage readers to think
deeply about the many important issues that are raised in these chapters, especially with
regard to the three challenges I have outlined. But if you think deeply and follow the
“best practices” described in this volume, you will be able to see brain activity that would
otherwise be invisible. And you may make important new discoveries about the human
mind and brain.
 Preface

Motivation

The time is ripe for a comprehensive book on the array of historical and cutting-​edge
frequency and time-​frequency approaches to studying EEG/​ERP because of the wide-​
spread interest in frequency research. There is a great need for a book organizing the di-
verse and important methods of EEG frequency analyses and interpreting the resultant
measures.
One stream of research comes from traditional (band-​based) frequency analyses.
Likewise, understanding the cutting-​edge frequency analyses which may not be familiar
to many EEG researchers is increasingly important for investigators applying frequency
analyses. However, there is a major need for a comprehensive handbook on analyses
within this domain. Although research has been rapidly accumulating over the last
decade, there has not been sufficient organization of research on the topic. We believe
this comprehensive handbook is increasingly necessary to help delineate the boundaries
of the area, the major scientific questions that need to be addressed, and the core theor-
etical frameworks that can guide future research and development.
Thus, a specific goal of this book is to bring together these various scientific
perspectives and research approaches within a single reference volume that provides an
integrated, cutting-​edge overview of the current state of the field. This volume comprises
contributions from leading researchers within various allied disciplines.
The use of electroencephalography (EEG) to study the human mind has seen tre-
mendous growth across a vast array of disciplines due to increased ease of use and
affordability of the technology. EEG is a non-​invasive measure of electrical brain ac-
tivity. Typically, researchers investigate the EEG signal using either time-​domain (e.g.,
ERP) analyses or frequency analyses. Several books have examined practicalities of
conducting ERP analyses and interpreting various ERP measures. However, a compre-
hensive book has yet to be developed organizing the numerous ways to process EEG
frequency and interpreting frequency measures linked to cognitive, affective, and motor
processes.
We (editors Philip, Matt, and Ed) felt a great need for a book organizing the diverse
and fascinating methods of EEG frequency analyses and interpreting the resultant
measures. Frequency analyses provide unique assessments of neural functioning,
neural connectivity, and “resting” neural activity studied by EEG researchers. Further,
xvi   Preface

frequency-​domain measures are reliably associated with cognitive, affective, and motor
processes of great interest to neuroscientists and psychological scientists. For example,
asymmetrical activation of the frontal cortex as measured by the inverse of alpha-​band
activity is closely linked with motivation and emotion. In addition, analyses examining
the synchrony of EEG frequencies recorded from different scalp locations allow
researchers to examine brain connectivity without having to incur the costs of magnetic
resonance imaging.

ORIGIN

As EEG frequency researchers, we wanted a resource that introduced the myriad ways
in which EEG frequency analyses are being investigated. This volume began while the
lead editor, Philip, was on sabbatical and seeking to begin a new chapter in his career.
During that time, he visited with Matt Miller and the project quickly developed into a
collaborative project. After developing the project more, Matt and Philip brought Ed
Bernat on board.
As individual editors, we each had areas of expertise in EEG frequency research, but
in developing this volume, we quickly discovered that each of our individual areas of
expertise were far different from each other. Three editors were necessary to even try
to cover the breadth of EEG frequency research being conducted. In addition, we did
not want to create a handbook that focused on EEG frequency research specifically in
emotion, cognition, or clinical applications. Instead, we wanted to provide a survey of
the breadth of work being conducted with EEG frequency research. Try as we might, we
also acknowledge this handbook will inevitably fail to cover everyone’s interest across all
topics. To that end, we hope to receive feedback from readers so that future editions of
this handbook can be expanded to encompass the ever-​growing field of EEG frequency
research.
Together, the project has been a long labor, but well worth the time and effort to de-
velop the resource. We have been especially excited to work with leading experts in the
field as they develop chapters for the volume. We are excited for you as the reader to see
what we have gotten to see throughout the editing process: the excitement and develop-
ment of EEG frequency research across a wide range of fields and programs of research.

ORGANIZATION

To aid in reading the handbook, much thought and structuring has been given to the
organization of the chapters. As a whole, the book provides a systematic summary of
EEG frequency analyses and applications. Individual chapters give depth to each type
 Preface   xvii

of frequency analysis and interpretation of resultant measures. Chapters are organized

into three sections.
The first section of the book is focused on basics of EEG frequency research and
linking frequency analyses to other components of EEG research, such as event-​related
potential (ERP) components and the fundamentals of inference from EEG recording.
For the second section, contributors focus on specific EEG frequency components that
are commonly studied using traditional frequency bands of activity to study specific
psychological processes related to cognition, motivation, and perception. The third
section focuses on EEG frequency analyses in special populations and altered states. The
fourth section of the handbook concludes with chapters focused on advancing method-
ology used in EEG frequency research.
The initial chapters in the first section describe methods for collecting EEG data for
frequency analyses in humans as well as the basics of electrical activity and assumptions
regarding the EEG signal. Following these chapters, contributors consider how the
oscillations in the EEG signal may give rise to psychological phenomena, and how
ERPs can be decomposed into time-​frequency components. The chapters go on to con-
sider the relationships between evoked (ERP-​related) and induced EEG activity before
shedding light upon frequency analyses of LFPs in non-​human primates, which may
inform frequency analyses of human EEG. The second section begins with the role of
gamma oscillations in cognitive and sensory processing. Then, frontal midline theta,
which is often linked to cognitive control, is addressed, followed by the role of alpha and
beta oscillations in perception and memory. Next, research on asymmetries in frontal
alpha oscillations are linked with motivation, followed by a description of the role of
oscillatory activity in sensorimotor function. Moving into the third section of the book,
the first chapter in this section focuses on changes in EEG frequency throughout in-
fancy, childhood, adolescence, and early adulthood. Next, follows an examination of
the ratio of theta to beta power in motivation and attentional control as they relate to
normal and abnormal behavior. Then, the characteristics of the oscillations in persons
with schizophrenia are described, followed by an examination of how frequency
analyses clarify control processes in people with anxiety. The concluding section of the
handbook begins with specialized frequency analyses for source localization and brain
connectivity before concluding with chapters describing how to manipulate oscillatory
activity with brain stimulation and how to parameterize neural field potential data to,
for example, tease apart true oscillations from aperiodic signals.

LIMITATIONS OF THE
CURRENT VOLUME

As with any book, the current volume is not a complete work on the topic of EEG fre-
quency analyses. In addition, this is not the first book on EEG frequency research. Many
xviii   Preface

excellent books have been published this topic. Here we mention what the current book
does not include and refer the reader to additional resources available in other books.
One of the most inspiring resources for us as editors is Steven J. Luck and Emily
S. Kappenman’s Oxford Handbook on Event-​Related Potential Components. This book
has been used in our courses and labs, as well as by countless other EEG researchers. It
focuses on the excellent work that has investigated the spectrum of ERP components
derived from EEG research. We were inspired to build a similar handbook that would
cover EEG frequency analyses. The current book does not address ERP research in
much detail. The closest chapters addressing ERP research are Chapters 4 and 5. For
those desiring a more comprehensive volume on ERP analyses, please see Luck and
Kappenman.
Another extraordinary resource is Mike X. Cohen’s Analyzing Neural Time Series
Data: Theory and Practice. This book has served as the primary resource for many EEG
researchers, including us, to learn how to conduct time-​frequency analyses, and to teach
our students how to perform the analyses. The book is particularly helpful in guiding
the reader from the mathematical bases of frequency analyses to the implementation
of these analyses in MATLAB. These analyses are referenced throughout our book and
include fast Fourier transforms, complex Morlet wavelet convolution, intertrial phase
clustering, surface Laplacian filtering, phase-​and power-​based connectivity measures,
and cross-​frequency coupling. Chapters in our book that address these “how-​to” topics
include Chapters 4, 5, 19, 20, 21, and 23.
Finally, Chapter 1 of this volume describes how to collect EEG data. For readers
who which to have greater detail about implementing and collect EEG from human
participants, we recommend Dickter and Kieffaber’s EEG Methods for the Psychological
Sciences. This book is an excellent resource for researchers beginning to implement EEG.
Pa rt I
 Chapter 1

INTRODU C T I ON
Methods for Collecting EEG Data for Frequency
Analyses in Humans

PHILIP A. GABLE AND MATTHEW W. MILLER

1.1  Chapter Aims

This chapter aims to provide a structure for readers to understand the methodology
behind collecting EEG (electroencephalography) presented in the subsequent chapters.
It is important to first understand the research methods involved in recording EEG fre-
quency before delving into more advanced frequency analyses and the interpretations.
As researchers, we focus this first chapter on a brief introduction to the topic of EEG
methodology and scientific practices. To begin, however, we feel it is important to lay
down definitions for terms used throughout the book.

1.2  Definitions of EEG

Frequency Research

EEG refers to the recording of electrical brain activity from the human scalp. It is one
of the most common methods for measuring brain functioning in areas of mind, brain,
and behavior science. EEG data contain rhythmic activity or waves that may reflect
neural oscillations, or fluctuations in the excitability of populations of neurons (more
on this later). These rhythmic fluctuations are typically described using two main
descriptors. The first is frequency, which is the speed of the wave, and it is measured
in hertz (Hz), which is the number of wave cycles per second. The second is power,
which is the squared amplitude of the wave. The greater the power of an oscillation, the
greater the energy of that oscillation. All of the chapters in this work discuss frequency
4    PHILIP A. GABLE and MATTHEW W. MILLER

with most referencing power. Sometimes researchers investigate the phase of the wave,
which is the position of the wave measured in radians or degrees. Many of the chapters
included here discuss phase.
The brain produces rhythms in multiple frequencies, which can be isolated from
the raw EEG signal using multiple techniques described by Curhamn & Allen in
Chapter 2, and Voytek in Chapter 23). Different psychological processes are linked to
different frequencies, which are often grouped into bands. The most commonly studied
bands include delta (1–​4 Hz), theta (4–​8 Hz), alpha (8–​12 Hz), beta (13–​30 Hz), and
gamma (lower gamma 30–​80 Hz; upper gamma 80–​150 Hz). While these are not the
only frequency bands, these are the bands most typically associated with processes
of mind and behavior measured by EEG. Importantly, these bands are not defined
without reason, but instead reflect biological changes at the cellular level (see Cohen,
2014 and Buzsaki, 2006 for reviews). However, these bands are not rigid and may vary
depending on individual differences, such as brain development, structure, and chem-
istry. Chapters in the second section of this work note how different frequency bands are
associated with cognitive, motivational, and sensorimotor processes.
These definitions are by no means complete. Individual chapters provide more pre-
cise definitions of terms used. With this initial framework, readers should be able to
venture into subsequent chapters focusing in more detail on these definitions. Because
EEG is a rather complex measure, we focus in more detail on the physiological basis and
scientific methods used to record and process EEG.

1.3  Physiological Basis of EEG

EEG is measured because all nerve cells communicate using electrical signals, sending
information throughout the brain and to the rest of the body. Within a neuron, an action
potential is an electrical wave that runs from the axon hillock at the cell body to the axon
terminals. At the axon terminals, the action potential causes neurotransmitter to be
released. This neurotransmitter crosses the synaptic gap and binds to receptors on the
membrane of the postsynaptic cell. Binding to the receptor causes voltage changes by
activating ion channels or second messengers that either excite or inhibit the postsynaptic
neuron. The summation of this voltage change in the membrane of the dendrites and cell
body of the postsynaptic neuron is called a postsynaptic potential. Postsynaptic potentials
tend to occur locally, rather than moving down the axon. This allows postsynaptic
potentials to summate rather than to cancel, resulting in voltage changes that have larger
amplitudes and can be recorded on the cortical surface or at the scalp.
When tens of thousands to millions of neurons are excited or inhibited at the same
time, the voltage change outside the cell (extracellular potential) can be recorded at the
scalp using EEG, which measures the sum of electrical activity from excitatory and in-
hibitory postsynaptic potentials over this collection of neurons. The activity can only be
recorded on the scalp surface because tissue (cerebrospinal fluid, meninges, skull, and
 INTRODUCTION   5

skin) between the neurons and scalp conducts the electrical signal. In addition, for elec-
trical activity to be projected to the scalp, cellular alignment must be precisely arranged
in parallel so that their effects cumulate to project the electrical activity to the scalp (see
Curhamn & Allen, Chapter 2; Keil & Thigpen, Chapter 3). Neurons must be arranged
so that the cluster of neurons all have dendrites at one pole and axons departing at the
opposite pole. This arrangement is called an open field and occurs when neurons are
organized in layers. The cortex, cerebellum, and parts of the thalamus tend to have this
open field arrangement of neurons resulting from pyramidal cells.

1.4  A Dual Nature

Due to the electrical basis of the EEG signal, EEG has excellent ability to tell us when
something is happening in the brain. This is called temporal resolution and is one of
the greatest strengths of the EEG signal. The EEG signal measures neural activity at the
accuracy of milliseconds, which allows for the ongoing measurement of psychological
processes as they unfold (Luck, 2014).
However, the EEG signal is limited in its ability to measure where something is
occurring. This is called spatial resolution and is one of the greatest weaknesses of the
EEG signal. Depending on where the source of the EEG signal is generated, the orien-
tation of the open field neurons might not be parallel to the scalp, thus generating EEG
signals in multiple directions. In addition, resistors (e.g., the skull) in the tissue between
the neurons and scalp can cause the EEG signal to spread out. Because of the volume
conduction through the head, as well as the orientation of the pyramidal cells emitting
the signal, the spatial location of the signal is difficult to ascertain. As Keil and Thigpen
(Chapter 3) note, a difference in frequency power between two experimental conditions
could be the result of a different number of neurons activated, the temporal order in
which they were activated, or neurons with different orientations being activated. To
address EEG’s limited spatial resolution, cortical source localization techniques have
been developed and are reviewed by Xie and Richards (Chapter 19). In sum, using an
analogy from Steve Luck’s ERP Boot Camp, the EEG signal is like being able to see every
frame of a movie as it unfolds. However, because of the low spatial resolution, the movie
appears a bit blurry.

1.5  EEG Equipment and Recording

The earliest method of EEG measurement was implemented by Hans Berger in the
late 1920s. In his early experiments, he used two sponges soaked in saline connected
to an amplifier (Berger, 1929). While the equipment and processing of EEG signal has
advanced considerably since that time, the basic components remain similar. EEG
6    PHILIP A. GABLE and MATTHEW W. MILLER

electrodes are placed on or near the head, the signal from the electrode is transmitted to
an amplifier, and the signal is digitized and recorded.
In psychological research labs, EEG is usually recorded from 32, 64, 128, or more
electrodes. In other research (e.g., sleep, nonhuman) fewer electrodes (2–​8 electrodes)
is more typical. When larger numbers of electrodes are used, electrodes are mounted in
an electrode cap or net. When fewer electrodes are used, electrodes may be positioned
individually on the head using a bonding agent. Electrodes can either be wet electrodes
or dry electrodes. Wet electrodes are made of silver, silver-​chloride, or tin, and a con-
ductive gel or liquid is placed inside or around the electrode. Dry electrode systems
use electrodes coated in gold, silver, or nickel, and place electrodes directly on the scalp
without a conductive medium. Wet electrodes generally have higher signal quality, but
dry electrodes may be preferred when high impedance levels are tolerable, or when re-
cording for long periods.
Electrode systems will have active or passive electrodes. Active electrodes con-
tain a small pre-​amplification unit directly attached to the conductive metal in
the electrode. This allows the EEG signal picked up at the sensor to be immedi-
ately amplified before additional environmental noise can be introduced. Passive
electrodes do not have amplification at the electrode, and instead carry the signal to
an amplifier about a meter away. Compared to passive electrodes, active electrodes
minimize noise introduced during signal transmission, tolerate high impedance re-
cording, and reduce participant preparation time. Passive electrodes have a lower
profile to benefit transcranial magnetic stimulation over the cap and can be used
inside an MRI bore.
Electrode placement is predominantly based on the 10–​20 system (Jasper, 1958).
Electrodes are named using the first letter to refer to the brain region under the electrode
from anterior to posterior (e.g., Fp—​frontal pole, F—​frontal, C—​central, P—​parietal,
T—​temporal, O—​occipital). Numbers following the letter are used to indicate the lateral
position of the electrodes. Ascending odd numbers indicate sites more lateral over the
left hemisphere of the brain, whereas ascending even numbers indicate sites more lateral
over the right hemisphere of the brain. The letter Z is used to designate medial sites. In
addition to the recording electrodes, EEG also requires a ground electrode, which assists
in reducing electrical noise, as well as a reference electrode placed on the head or face.
The raw EEG signal is usually filtered during recording. Signals below 0.1 Hz or above
200 Hz are removed because the frequency bands of interest fall within this range.
A filter at 60 Hz (in North and South America) or 50 Hz (in Europe, Asia, and Africa)
may also be used to further reduce electrical noise from alternating current.

1.6  Artifacts

The quality of the EEG is crucial to EEG frequency analysis. To best record EEG signal
reflecting brain activity, researchers must remove signal that occurs because of anything
other than neural activity. Signal that is not naturally present is called artifact. These
 INTRODUCTION   7

can be biological (e.g., muscle movement) or nonbiological (e.g., electrical noise). Much
artifact can by eliminated by taking preventative measures. Artifact that cannot be
prevented should be removed.
Muscle artifact, or electromyography (EMG), is one of the most common types of
artifacts and is usually high in frequency (100–​500 Hz). Usually, this falls outside of the
frequency range typically investigated by researchers. However, some muscle artifact
may seep into lower frequencies. Researchers can reduce muscle artifact by instructing
participants to limit their muscle movements. Muscle artifact that does occur can be
removed through visual inspection, filtering, and automatic artifact detection algo-
rithm. It should be noted that some muscle artifact may be related to the experiment
(e.g., sensorimotor studies). In such cases, it may be beneficial to measure EMG at the
site movement is expected (e.g., the hand), then control for it in analyses.
Eye movements are another common type of artifact. The eyeball is polarized which
causes large artifact in the form of voltage changes resulting from moving the eyes. Like
dealing with muscle artifact, eye movement artifact can be removed from signal using
recordings near the eyes called electro-​oculograms (EOG). One pair of EOG electrodes
are placed above and below the eye, while another pair is placed just lateral to either eye
on the temple. Eye blinks also create eye movement artifact. It is preferable to correct
blink artifact using an artifact reduction algorithm based on regression, principal com-
ponent analyses, or independent component analyses.
Artifacts occurring in the environment are the result of nonbiological factors. The
most common sources of these artifacts are the result of external electrical noise coming
from compact fluorescent lightbulbs, data hubs, or electrical junctions. Grounding will
aid in reducing these sources of noise, as will electromagnetically shielded rooms.

1.7  Frequency Processing

Once an EEG signal is recorded, the raw data must go through several processing
steps before it is in a format useable in analyses. The raw signal is collected in the
time-​domain but must be converted into a frequency-​domain representation. One
way this can be accomplished is in the form of a power spectrum, which collapses fre-
quency data across time to map the frequencies present. A frequency analysis can be
conducted over windows that are minutes, seconds, or milliseconds in length; these are
called epochs. Epochs that are seconds or minutes can be analyzed for power spectra
using a Fourier transform, which decomposes a signal into a series of sine and cosine
functions of various frequencies. The function of each frequency begins with its own
phase. A Fourier transformation assumes that the epoch repeats infinitely forward
and infinitely backward in time. A process called windowing is used to prevent artifact
created from the Fourier transform. However, windowing can also introduce artifact
and data loss into the frequency analysis. Overlapping epochs is a way to prevent dis-
continuity, data loss near the ends of the epoch, and to help meet the assumptions of the
Fourier transform in windowing.
8    PHILIP A. GABLE and MATTHEW W. MILLER

One of the most common forms of signal frequency processing is to use a fast
Fourier transform (FFT). An FFT provides the spectrum of frequency power for a
period, which is often averaged across a range of frequencies comprising a band (e.g.,
theta). It also provides a spectrum of phase. The power spectrum reflects the energy
of each frequency determined by the squared amplitude of the wave. The phase spec-
trum reflects the phase in radians or degrees of the sine or cosine wave at each interval
(e.g., 1/​T). Most frequency analyses focus exclusively on frequency power. However,
there is increasing interest in examining the phase of frequencies (e.g., see Michelmann,
Griffiths, & Hanslmayr, Chapter 10; Palva & Palva, Chapter 20). Crucially, the FFT has
two limitations: it poorly depicts changes in the frequency spectrum over time, and it
assumes the EEG data are stationary during the period to which the FFT is applied. To
overcome these limitations, time-​resolved frequency decomposition techniques are
growing in popularity, particularly wavelet analyses (e.g., complex Morlet wavelets),
which reveal changes in power at various frequencies with excellent temporal precision
(see Aviyente, Chapter 4; Weinberg, Ethridge, Oumeziane, & Foti, Chapter 5).

1.8  Experimental Design

Regardless of the EEG recording and processing, researchers need to be considerate of

experimental design. In any experiment, researchers should manipulate a single vari-
able at a time to ensure internal reliability, but this procedure is challenging in EEG
research. This follows because manipulating one variable between conditions may inad-
vertently change a second variable between conditions that affects EEG. For example, if
an experimental condition attempts to manipulate participants’ motivation while they
are physically responding to stimuli, then EEG linked to motivation may change (see
Harmon-​Jones, Popp, & Gable, Chapter 11) but so may the vigor of their responses and
EEG linked to sensorimotor function (see van Wijk, Chapter 12). Thus, it is crucial that
researchers attempt to experimentally control for such factors in their experimental de-
sign or statistically account for them by collecting covariates, such as EMG to index the
vigor of motor responses.

1.8.1 Reproducibility in Electrophysiology: Challenges

and Recommendations
A scientific discipline benefits from reproducible results because they strengthen
confidence that they reflect the way a system operates under certain conditions.1

1  There have been special issues in the International Journal of Psychophysiology and Psychophysiology

devoted to reproducibility and, relatedly, open science in cognitive electrophysiology, and readers are
encouraged to read these special issues (Kappenman & Keil, 2017; Larson & Moser, 2017).
 INTRODUCTION   9

We use Goodman, Fanelli, and Ioannidis’s (2016) definition of reproducible results

as “obtaining the same results from the conduct of an independent study whose
procedures are as closely matched to the original experiment as possible” (pp. 2–​3).
Although there are different definitions of what it means to obtain “the same results”
(Open Science Collaboration, 2015), we hope that closely matched studies yield
effects with confidence intervals that overlap substantially (for details on using confi-
dence intervals in EEG studies, see Groppe [2017]), thus allowing us to make precise
inferences about the true size of the effect being studied. Since reproducible results are
crucial for a discipline, it is important to consider what can be done to obtain them.
We discuss several research practices that increase the likelihood that an original re-
sult will be reproducible and that subsequent studies reproduce the original result,
as well as challenges faced by cognitive electrophysiology researchers attempting
to do so.

1.9  Pre-​R egister Specific Hypotheses

Each study should test specific hypotheses because results that confirm hypotheses
are more likely to be true than results based on exploratory analyses (Ioannidis, 2005).
Thus, it is crucial that researchers do not rewrite their hypotheses to fit with their results,
a practice known as HARKing (hypothesizing after results are known), as it exaggerates
the confidence the reader has that the results are true. One method to avoid HARKing
is pre-​registering hypotheses using the Open Science Framework (osf.io), aspredicted.
org, or other repositories. However, formulating specific hypotheses for cognitive elec-
trophysiology studies can be difficult, especially if researchers want to frame them stat-
istically. For example, a researcher may be confident in predicting that an experimental
condition will affect EEG activity, but they may struggle to define “EEG activity” as
a dependent variable. In ERP studies, this is less of a concern because the dependent
variables (ERP components) are well-​characterized (Kappenman & Luck, 2012); how-
ever, there are fewer well-​characterized time-​frequency variables. Although researchers
can be vague about defining their time-​frequency variables, they should then use stat-
istical analyses with strict corrections for multiple comparisons (see Cohen, 2014). This
reduces the likelihood of making Type I errors, but consequently increases the likeli-
hood of making Type II errors. (Researchers may also consider data-​driven region-​of-​
interest approaches; see Brooks et al., 2017). Therefore, time-​frequency analyses will
benefit from having well-​defined dependent variables (Indeed, this was an initial im-
petus for this book!).
For example, if a researcher believes an experimental manipulation is likely to influence
EEG activity related to cognitive control, they can have a clearly defined dependent vari-
able of oscillatory activity in the theta frequency bandwidth measured from frontal mid-
line electrodes over a certain time (Cavanagh & Cohen, Chapter 9). In a pre-​registration,
researchers should use a more precise definition of their dependent variable than “frontal
10    PHILIP A. GABLE and MATTHEW W. MILLER

midline theta”. For example, they could specify that they will determine the wavelet of 4–​
8 Hz that exhibits the greatest peak power between 200 and 600 ms after stimulus onset
at electrode Fz for each participant, and then compute the average power of this wavelet
during the 200–​600 ms time epoch at Fz. They could also introduce some flexibility into
the specification of the dependent variable by noting that they will choose a different band-
width, epoch, and/​or electrode if the grand average time-​frequency plot (averaged across
all conditions) reveals an unexpected time-​frequency and/​or scalp distribution. In this
example, the average across all conditions avoids biasing the analysis in favor of choosing
a time-​frequency window exhibiting differences between conditions. Besides reducing
HARKing and facilitating the specification of dependent variables, pre-​registration is cru-
cial for holding researchers accountable to their research design, statistical analyses, and
sample size; however, none of these positive features of pre-​registration work if researchers
deviate from their pre-​ registration without properly noting the deviation (Claesen
et al., 2019).

1.10  Increase Power and Conduct

A Priori Power Calculations

Another way that researchers can increase the likelihood that study results are reprodu-
cible is by increasing the power of their studies (Ioannidis, 2005). Alarmingly, Button
and colleagues’ (2013) analysis of neuroscience studies found their average power was
very low (8–​31%). There are two general ways that researchers can increase the power of
their studies. First, researchers should attempt to maximize the effect they are studying
and minimize its variance (i.e., increase the standardized effect size). This can be done
by using strong experimental manipulations and reliable dependent variables, such
as those discussed in this work. Additionally, researchers should increase the signal
to noise ratio in their studies by optimizing the number of trials and collecting good
EEG data (Cohen, 2017; Luck, 2014).2 Further, when possible, researchers should use
within-​subjects designs, which is already the case in many cognitive electrophysi-
ology studies. Second, researchers should collect larger samples, which is particu-
larly important when testing between-​subjects effects or within-​between subject
interaction effects. Cognitive electrophysiology studies can require a lot of time to
collect and process data, so collecting more participants may seem burdensome, es-
pecially for researchers investigating small–​medium effects. For example, a two-​tailed

2 
A good way for researchers to benefit the field (and their citation count) may be for them to establish
the number of trials required for different time-​frequency variables in different paradigms, which has
been done for ERP variables (e.g., Rietdijk et al., 2014). It is worth noting that simply adding more trials
may not increase the signal to noise ratio, since participants may fidget more toward the end of long data
collections, consequently increasing noise.
 INTRODUCTION   11

dependent t-​test for an effect size of dz =​0.35, an alpha =​.05, and power =​.90 requires
88 participants, according to G*Power 3.1.9.4 (Faul et al., 2009). Indeed, it is likely that
researchers will often find themselves studying small-​medium effects. Specifically,
when researchers conduct a priori power calculations to determine their sample sizes,
they should assume that the effect sizes in the extant literature are inflated, due to pub-
lication bias by researchers and journals (i.e., only publishing significant results) (for
a more detailed discussion on sample size calculations in EEG studies, see Larson &
Carbine, 2017). Although it is difficult to collect and process large samples, it is crucial
to the reproducibility of cognitive electrophysiology studies. To reduce the demands
large sample sizes impose, researchers who mentor doctoral students, review for and
sit on the editorial boards of journals, are involved in hiring decisions about faculty and
post-​doctoral researchers, and are involved in promotion and tenure decisions should
reconsider expectations about the speed of science and the number of publications (for
further discussion on these issues, see Bradley (2017) and Yeung [2019]). Also, if a re-
searcher is concerned about allocating a lot of time to a study that may not yield signifi-
cant results, they can conduct a sequential analysis where they pause data collection
after a pre-​specified sample has been collected and then determine whether to continue
data collection based on if the incremental results are significant (given an adjusted
alpha level) and if the incremental results suggest an effect size that is too small to be of
interest (Lakens, 2014).

1.11  Make Methods, Materials,

and Data Open

In addition to pre-​registered hypotheses and adequately powered studies, researchers

should also make their methods, materials, and data accessible3. In so doing, they
will allow other researchers to “methodologically reproduce” the original study
(Goodman et al., 2016), which should increase the likelihood of observing the same
results. Researchers should make their stimuli and stimulus presentation scripts
available and include specific details about instructions given to participants and the
equipment used for the study. Further, researchers should also make signal and stat-
istical processing scripts available and provide their data when possible so that other
researchers can attempt to reproduce analyses or explore new ones. There are various
ways to provide this information, including on the Open Science Framework and
GitHub (github.com).

3 
There is a special issue in the International Journal of Psychophysiology devoted to open science in
human electrophysiology, and readers are encouraged to read it (Clayson, Keil, & Larson, 2022).
12    PHILIP A. GABLE and MATTHEW W. MILLER

1.12  Replicate and Expand

The recommendations were made to increase the likelihood that researchers’ ori-
ginal results will be reproducible, but the recommendations also apply to researchers
attempting to reproduce original results. Crucially, researchers attempting to repro-
duce original results should also attempt to replicate and expand an original finding
(Cohen, 2017), preferably increasing the sample size by two and half times the ori-
ginal (Simonsohn, 2015). Specifically, cognitive electrophysiology will benefit if most
studies include an attempt to reproduce an original result and then add a new result
(e.g., by adding a new experimental condition). With results from replication attempts,
more precise estimates about the direction and size of effects can be made. Of course,
it is nearly impossible to reproduce a study methodologically. For example, different
researchers may have different criteria for manually rejecting trials, and different in-
dependent component analyses may yield different components. However, researchers
can still come quite close to a methodological reproduction, especially if methods and
materials are available for them to use. A challenge for cognitive electrophysiologists
is that they often employ different signal processing methods, such as subtracting or
not subtracting the ERP from an epoch of EEG data prior to convolving the data with
a wavelet. To this end, researchers should use the same methods as the original study,
unless a different method is clearly superior. Of course, whether a different method is
clearly superior is debatable; thus it is incumbent upon the researcher conducting the
methodological reproduction to state their case in a compelling way.

1.13  Explore

Some of the most exciting and reproducible effects in cognitive electrophysiology have
been discovered by accident (e.g., Kutas & Federmeier, 2011), meaning that they would
not have occurred if researchers had only conducted confirmatory research testing a
priori hypotheses. Thus, it is imperative that researchers conduct exploratory analyses
in addition to confirmatory analyses. However, results from exploratory analyses should
be clearly labeled as such to avoid misleading readers to having excessive confidence in
the result. Ideally, then, a study will test pre-​registered confirmatory hypotheses that
replicate and expand an original result and conduct exploratory analyses. Compelling
results from the exploratory analyses can then serve as a priori hypotheses in future
confirmatory research. Finally, some of the most exciting exploratory research may
come from analyzing old data in new ways. For example, Voytek (Chapter 23) proposes
exciting new analytical methods that researchers can apply; his signal processing scripts
are freely available (https://​voytek​lab.com/​code), and researchers can use these scripts
to analyze their old data or other openly available data.
 INTRODUCTION   13

References
Berger, H. (1929). Über das Elektrenkephalogramm des Menschen. Archiv für Psychiatrie und
Nervenkrankheiten, 87, 527–​570. https://​doi.org/​10.1007/​BF0​1797​193.
Bradley, M. M. (2017). The science pendulum: from programmatic to incremental—​and back?
Psychophysiology, 54, 6–​11. doi: 10.1111/​psyp.12608
Brooks, J. L., Zoumpoulaki, A., & Bowman, H. (2017). Data-​driven region-​of-​interest selection
without inflating Type I error rate. Psychophysiology, 54, 100–​113. doi: 10.1111/​psyp.12682
Buzsáki, G. (2006). Rhythms of the brain. Oxford University Press.
Button, K. S., Ioannidis, J. P. A., Mokrysz, C., Nosek, B. A., Flint, J., Robinson, E. S. J., & Munafò,
M. R. (2013). Power failure: Why small sample size undermines the reliability of neurosci-
ence. Nature Reviews Neuroscience, 14, 365–​376. doi:10.1038/​nrn3475
Claesen, A., Gomes, S., Tuerlinckx, F., & Vanpaemel, W. (2019). Comparing dream to
reality: An assessment of adherence of the first generation of preregistered studies. PsyArXiv
[online]. https://​doi.org/​10.1098/​rsos.211​037
Clayson, P. E., Keil, A., & Larson, M. J. (2022). Open science in human electrophysiology.
International Journal of Psychophysiology, 174, 43–​46. https://​doi.org/​10.1016/​j.ijpsy​
cho.2022.02.002
Cohen, M. X. (2014). Analyzing neural time series data: Theory and practice. MIT Press.
Cohen, M. X. (2017). Rigor and replication in time-​frequency analyses of cognitive elec-
trophysiology data. International Journal of Psychophysiology, 111, 80–​87. doi: 10.1016/​
j.ijpsycho.2016.02.001
Faul, F., Erdfelder, E., Buchner, A., & Lang, A. (2009). Statistical power analyses using G*Power
3.1: Tests for correlation and regression analyses. Behavior Research Methods, 41, 1149–​1160.
doi:10.3758/​BRM.41.4.1149
Goodman, S. N., Fanelli, D., & Ioannidis, J. P. A. (2016). What does research reproducibility
mean? Science Translational Medicine, 8, 341ps12. doi: 10.1126/​scitranslmed.aaf5027
Groppe, D. M. (2017). Combatting the scientific decline effect with confidence (intervals).
Psychophysiology, 54, 139–​145. doi: 10.1111/​psyp.12616
Ioannidis, J. P. A. (2005). Why most published research findings are false. PLoS Medicine, 2,
e124. doi: 10.1371/​journal.pmed.0020124
Jasper, H. H. (1958). The ten-​ twenty electrode system of the International Federation.
Electroencephalography and Clinical Neurophysiology, 10, 371–​375.
Kappenman, E. S., & Keil, A. (2017). Introduction to the special issue on recentering
science: Replication, robustness, and reproducibility in psychophysiology. Psychophysiology,
54, 3–​5. doi: 10.1111/​psyp.12787
Kappenman, E. S., & Luck, S. J. (Eds.) (2012). The Oxford handbook of event-​related potential
components. Oxford University Press.
Kutas, M. & Federmeier, K. D. (2011). Thirty years and counting: Finding meaning in the N400
component of the event-​related brain potential (ERP). Annual Review of Psychology, 62, 621–​
647. doi: 10.1146/​annurev.psych.093008.131123
Lakens, D. (2014). Performing high-​powered studies efficiently with sequential analyses.
European Journal of Social Psychology, 44, 701–​7 10. doi: 10.10002/​ejsp.2023
Larson, M. J. & Carbine, K. A. (2017). Sample size calculations in human electrophysiology
(EEG and ERP) studies: A systematic review and recommendations for increased rigor.
International Journal of Psychophysiology, 111, 33–​41. doi: 10.1016/​j.ijpsycho.2016.06.015
14    PHILIP A. GABLE and MATTHEW W. MILLER

Larson, M. J. & Moser, J. S. (2017). Rigor and replication: Toward improved best practices in
human electrophysiology research. International Journal of Psychophysiology, 111, 1–​4.
doi: 10.1016/​j.ijpsycho.2016.12.001
Luck, S. J. (2014). An introduction to the event-​related potential technique (2nd ed.). MIT Press.
Open Science Collaboration. (2015). Estimating the reproducibility of psychological science.
Science, 349, aac4716. doi: 10.1126/​science.aac4716
Rietdijk, W. J., Franken, I. H., & Thurik, A. R. (2014). Internal consistency of event-​related
potentials associated with cognitive control: N2/​P3 and ERN/​Pe. PLoS One, 17, e102672.
doi: 10.1371/​journal.pone.0102672
Simonsohn, U. (2015). Small telescopes: detectability and the evaluation of replication results.
Psychological Science, 26, 559–​569. https://​doi.org/​10.1177/​09567​9761​4567​341
Yeung, N. (2019). Forcing PhD students to publish is bad for science. Nature Human Behaviour,
3, 1036. doi: 10.1038/​s41562-​019-​0685-​4
 CHAPTER 2

L O GIC BEHI ND E E G
F REQU ENCY A NA LYSI S
Basic Electricity and Assumptions

KYLE J. CURHAM AND JOHN J. B. ALLEN

2.1  Introduction

The brain is an electrochemical machine. Although nerve cells differ greatly in their
size and morphology, all pass messages using electrical signals, sending information
throughout the brain and to the rest of the body via the spinal cord. Within any neuron,
an action potential is a wave of electrical activity that travels along the nerve membrane.
Action potentials are triggered by the summation of input from other neurons using
chemical neurotransmitters, which create voltage potential changes in the post-​synaptic
neuron. Surface-​recorded EEG is blind to the activity of single neurons but can non-​
invasively measure the electrical activity resulting from summated excitatory and in-
hibitory post-​synaptic potentials over millions of these signals in humans. EEG has
excellent temporal resolution, but poor spatial resolution; it can tell us when something
is happening in the brain, but not precisely where it is happening.
EEG gives an incomplete picture of the electrical activity occurring in the brain. The
cortex is the outermost layer of the brain, and the primary generator of the electrical
activity we measure with EEG. Our ability to detect cortical activity largely depends
on the parallel arrangement of cortical pyramidal neurons. When millions of parallel
neurons fire simultaneously, their electrical activity adds together to generate a signal
large enough to detect at the scalp. However, when neural populations fire incoherently,
or when they are not arranged in a parallel formation, the electrical activity does not
add constructively, so there is no observed signal at the scalp. This chapter introduces
basic concepts in electricity in signal processing, with some practical considerations
for data collection and analysis, to help readers understand EEG measurement and
interpretation.
16    KYLE J. CURHAM and JOHN J. B. ALLEN

2.2  Electricity—​Voltage, Current,

and Resistance

Every physical thing is made up of atoms, which in turn are made up of fundamental
particles including protons, neutrons, and electrons. Protons have a positive charge,
neutrons have a neutral charge, and electrons have a negative charge. Charges of the
same sign repel, and opposite charges attract. A few simple experiments demonstrate the
existence of electrical charge. For example, rubbing a balloon on a wool sweater makes
the balloon negatively charged as electrons move from the wool to the balloon (Figure
2.1). The degree of attraction or repulsion between two point charges is proportional
to the product of the charges divided by the inverse squared distance between them.
Therefore, when the electron-​rich balloon is brought into proximity of the electron-​
poor wool, or any neutral surface such as a piece of paper or the wall, the balloon will
be attracted. If you subsequently rub a second balloon in the same way, the two balloons
will repel each other since they are both negatively charged.
Most of the time, atoms have equal numbers of protons and electrons. However,
atoms can become ionized when electrons are removed or added, resulting in a net
charge. Electricity is the phenomenon that describes the behavior and movement of
charge. In general, it doesn’t matter whether it is the electrons or ions that are moving.
The flow of charge can be accomplished either by the transfer of electrons from atom to
atom, or, in the case of electrophysiology, by the diffusion of charged ions across cellular
membranes.
The degree to which electrons are free to move from atom to atom varies by material
type. For example, in metals, the outermost electrons are so loosely bound that they
freely move in the space between atoms at room temperature. Because these unbound
electrons are free to travel from atom to atom, they are called free electrons. The relative
mobility of electrons within a material is known as electrical conductivity. Conductivity
is determined by the types of atoms in a material, and how the atoms are linked to-
gether with one another. Materials with few or no free electrons are called insulators,
and materials with many free electrons are called conductors. The directed motion of
electrons is called electrical current. Just like water flowing through a pipe, electrons
move within the empty space between atoms. Under normal conditions, the motion of
free electrons in a conductor is random, with no particular direction or speed. However,
electrons can be influenced to move in a coordinated fashion through a conductive ma-
terial by supplying a voltage. Voltage is the “pressure” that pushes on free electrons to
cause them to flow. The ability of a current to flow from one location to another depends
on the resistance. In insulating materials, such as glass or rubber, electrons have little
freedom to move from atom to atom. The less freedom electrons have to move from
atom to atom, the greater the resistance to the flow of charge. A conductor’s resistance
generally increases as its length increases or its diameter decreases. It is again useful to
refer to the water analogy: water can flow more easily through a short, wide pipe than a
long, narrow pipe. The international system of units (SI) of current is called the ampere.
 LOGIC BEHIND EEG FREQUENCY ANALYSIS    17

(a)

Positive Charges and Electrons are

Present in Equal quantities in the
Sweater and the Ballon

(b)

Electrons are Transferred

from the Sweater to the Balloon

Figure 2.1  Before rubbing the balloon against the sweater (A), no net accumulation of electrons
exists on the balloon. After rubbing the balloon on the sweater (B), the balloon has accumulated an
excess of electrons, and the resultant negative charge of the balloon and positive charge of the sweater
creates a force of attraction sufficient to keep the balloon from being pulled to the ground by gravity.
Figure credit: K. Ehrmann.
18    KYLE J. CURHAM and JOHN J. B. ALLEN

Table 2.1 Guide to electrical symbols and terminology

Symbol Term Definition Unit

E Voltage Electromotive force Volts (V)

I Current Rate of flow Amperes (A)
R Resistance Opposition to current Ohm (Ω)
C Capacitance Ratio of the change in charge Farad (F)
to the change in voltage
P Power Rate of work Watt (w)
W Energy Ability to do work Watt-​second (Joule)

One ampere is defined as one coulomb of charge (or 6 × 1018 electrons) flowing past a
given point in a conductor in one second. The volt is the unit of pressure, that is, the
amount of electromotive force (EMF) required to push a current of one ampere through a
conductor with a resistance of one ohm, or 1 volt/​ampere.
When resistance is high, electrons tend to gather on one side of the insulating material
and the positive ions tend to gather on the other, effectively storing potential energy in
an electric field. At some point, the voltage across the material will exceed a threshold
known as the dielectric constant, at which point current begins to flow. This tendency
for high resistance to result in charge separation is known as capacitance. The amount of
charge stored in the capacitor is directly proportional to the surface area of the dielectric
(the electrical insulator polarized by the electric field) (Table 2.1).

2.3  Circuits

An electrical circuit consists of closed conductive paths between circuit elements.

Elements may consist of resistors, capacitors, voltage sources, or current sources.
Electrical components may be wired in series or parallel with each other (Figure 2.2).
In many cases, circuits consist of some complex combination of series and parallel
components. However, these circuits may often be represented by simpler equivalent
circuits with identical electrical properties.
To gather some intuition for the flow of current in simple circuits, we refer back to
the water analogy. The resistance increases as the pipe gets longer. This is equivalent to
stringing together multiple resistors in series. The rule to combine resistors in series is
additive:

Rseries = R1 + R2 + …+ Rn
 LOGIC BEHIND EEG FREQUENCY ANALYSIS    19

(a) R1

+
V1 R2

R3
(b)

+
V1 R1 R2 R3

Figure 2.2  Simple series (left) and parallel (right) circuits. Circuit components labeled with R
indicate resistors. Circuit components labeled with V indicate voltage sources.

Conversely, adding multiple resistors in parallel will decrease the overall resistance:

1 1 1 1
= + + …+
R parallel R1 R2 Rn

As more “pipes” are added, the water has more paths to escape, decreasing the overall
resistance to flow. Capacitors wired in series or parallel follow the same rules, but
reversed:

1 1 1 1
= + + …+
Cseries C1 C2 Cn

C parallel = C1 + C2 + …+ Cn

Most circuits are some complex combination of series and parallel. We can approach
these circuits one piece at a time, deriving a new equivalent circuit at each step
(Figure 2.3).
The next few sections explore examples of equivalent circuit representations, and
we use equivalent circuit representations to learn the voltages and currents at every
point in the original complex circuit. We later show how models of neurons can
be represented as a simple equivalent circuit of capacitors, resistors, and voltage
sources.
20    KYLE J. CURHAM and JOHN J. B. ALLEN

(a) R1

+
V1 R1 R2 R3

(b) R1

+
V1 Req

(c) R1

+
V1 Req

Figure 2.3  Reducing a complex circuit (left) to a simple equivalent circuit (right). In an inter-
mediate step, we combine parallel resistors 2 and 3 (middle). Next, we combine resistor 1 with the
equivalent resistor from the intermediate step.

2.4  Direct current

Circuits come in two basic flavors: direct current (DC) and alternating current (AC).
The difference depends on whether the voltage and current change directions over
time. DC circuits maintain currents flowing in a constant direction within a closed
loop, whereas AC circuits have current that repeatedly reverses direction. A DC electric
source feeds from one terminal to a set of circuit elements and then back to the other
terminal, in a complete circuit. Figures 2.2 and 2.3 are both DC circuits due to their con-
stant voltage power source. Note some resistors are connected in parallel, while others
are connected in series. At each step, we can combine resistors according to the rules in
Section 2.3 to derive a simpler equivalent circuit.
Some circuits may contain both resistors and capacitors. These are known as RC
circuits. In a simple circuit with one resistor and one capacitor in series, the capacitor
must discharge through the resistor. This discharge occurs at an exponential rate
determined by the RC time constant. The time constant indicates the number of seconds
for the capacitor to become 63.2% charged, or, equivalently, the time for current flow
 LOGIC BEHIND EEG FREQUENCY ANALYSIS    21

to have slowed by 63.2% from its starting value. This choice of time constant has an in-
tuitive explanation: at any moment in time, the rate of change in voltage is equal to the
voltage divided the time constant. For example, a 1 mF cap and a 1 kΩ resistor yields a
time constant of one second. If the capacitor is charged to 5 volts, the voltage will fall at
a rate of 5 V/​s. If the capacitor is charged to 2 volts, the voltage will fall at a rate of 2 V/​s.

2.5  Alternating Current

In contrast to DC signals, some sources of electricity produce AC, where voltages and
currents periodically reverse direction and switch back and forth between positive and
negative polarity. The electricity that comes from an American wall outlet is an example
of AC. The current in North America is 120 VAC and changes direction 60 times per
second. AC circuits can exhibit more interesting behaviors than DC circuits. For ex-
ample, at low frequencies, a capacitor acts like an open circuit, so no current flows in the
dielectric. However, when driven by an AC source, a capacitor will only accumulate a
limited amount of charge before the potential difference changes polarity and the charge
is returned to the source. The higher the frequency, the less charge will accumulate and
the smaller the opposition to the current.
Both resistors and capacitors resist the flow of current when a voltage is applied.
However, unlike in DC circuits, resistance may be frequency dependent. Frequency-​
dependent resistance is known as impedance, a complex-​valued quantity that can be
broken into two parts: magnitude (the ratio of the voltage amplitude to the current
amplitude) and phase (quantifies how much the current lags the voltage). Alternatively,
we can break impedance down into its real and imaginary parts. Like in DC circuits,
the real part of the impedance acts like resistance, resisting the flow of electric current.
The imaginary part is called reactance, and it quantifies the opposition to a change in
the current of a capacitive circuit element. Ideal capacitors are purely reactive, that is,
they have zero resistance, and the impedance of a resistor is purely real, or resistive.
Note this implies the current in a capacitor always lags the voltage by 90°. Impedance
devices add like resistors in a DC circuit. For a set of components in series, the total im-
pedance is the sum of the component impedances. To obtain the impedance of parallel
circuit components, the inverse total impedance is given by the sum of the inverses of
the component impedances.
Using different combinations of resistors and capacitors, RC circuits can be used to
attenuate some frequencies, while allowing others to propagate through the circuit un-
affected. For example, wiring a resistor in series with a load, and a capacitor in parallel
with the same load, significantly attenuates high-​frequency signals. Conversely, wiring
a resistor in parallel with the load, and the capacitor in series, attenuates low-​frequency
signals. In Figure 2.4, at low frequencies, the reactance of the capacitor will be very large
compared to the resistance of the resistor. This means that the voltage across the cap-
acitor will be much larger than the voltage across the resistor. At high frequencies the
22    KYLE J. CURHAM and JOHN J. B. ALLEN

reverse is true: the voltage across the resistor is larger than across the capacitor. In other
words, low frequencies pass to the output, and high frequencies are attenuated. This is
known as a low-​pass RC filter. Similarly, we can construct a high-​pass filter by swapping
the resistor and capacitor. The frequency cutoff for these filters is determined by the
time-​constant of the circuit, which is derived from the resistance and capacitance. The
cutoff frequency for an RC circuit is:

1
fc =
2πRC

In the low-​pass configuration, frequencies just above the cutoff are attenuated to half
their original amplitude. Conversely, in the high-​pass configuration, frequencies just
below the cutoff are attenuated to half amplitude. The amount of attenuation increases
as you move farther beyond the cutoff frequency. Figure 2.4 shows the amplitude roll-​off
as a function of frequency for a low-​pass filter.

(a)

R1

Vin C1 Vout

(b) Bode Diagram

0
Magnitude (dB)

—10

—20

—30
0
Phase (deg)

—45

—90

Frequency (Hz)

Figure 2.4  Low-​pass RC filter (left). The parallel arm with the capacitor provides a low im-
pedance path for high frequency signals. However, the capacitor saturates for low-​frequency
signals, providing a high-​impedance path. Low-​frequencies signals are thus preferentially
observed at Vout. Frequency response of the low-​pass RC filter (right). The signal is not appre-
ciably attenuated below the cutoff frequency of 50 Hz (shown in red). At frequencies just above
50 Hz, the signal magnitude is cut in half. As frequency increases, the amount of attenuation
increases.
 LOGIC BEHIND EEG FREQUENCY ANALYSIS    23

2.6  Hodgkin–​Huxley Model

We can use a simple circuit model to describe the electrical properties of neurons,
including the initiation and propagation of action potentials. Action potentials are the
result of the diffusion of sodium and potassium ions across neural membranes. The
Hodgkin–​Huxley model treats each component of a neuron as an electrical element in
the circuit (Figure 2.5), where current is propagated by the movement of ions across cell
membranes.
The cell membrane is represented by a capacitance (Cm). Cellular membranes are
highly resistive, and act as a dielectric material due to their relatively impermeability.
In the absence of special proteins called ion channels, ions like sodium and potassium
are unable to diffuse across the membrane, effectively turning the membrane into the
dielectric of a capacitor. As ionic currents add or subtract from the charge accumulating
inside the neuron, ions line up along the cell membrane. The differing concentration
of ions on either side of the membrane results in a net voltage potential, represented by
voltage sources (En). To maintain these concentration gradients, neurons have active
sodium-​potassium pumps that exchange two sodium ions into the extracellular space
for three potassium ions in the intracellular space.
Sodium and potassium ion channels are represented by electrical conductances (GNA,
GK) that depend on both voltage and time. As the voltage potential increases, the per-
meability of the membrane is selectively modulated, that is, conductance is increased,
for specific ion species. The flux of sodium or potassium ions across the membrane is
represented by ionic currents (Ip). Since the membrane is not perfectly impermeable,
leak channels are also included, represented by another conductance (GL).
The Hodgkin–​Huxley circuit model exhibits similar dynamics to real neurons. The
amount of injected current controls the emergence of a stable limit cycle. For a suffi-
ciently large input current, the circuit will exhibit repeating “action potentials” at a min-
imum firing rate. This means that either the neuron is not firing at all (corresponding
to zero frequency) or is firing at the minimum firing rate. Increasing the injected
current beyond the minimum threshold increases the firing rate of the neuron. When

Vm
inside
INa IK IL

GNa GK GL
CM

ENa EK EL

outside

Figure 2.5  Equivalent circuit diagram for the Hodgkin–​Huxley model.

©2003 James M. Bower and David Beeman.
24    KYLE J. CURHAM and JOHN J. B. ALLEN

the neuron fires, a series of channel activations occur to produce the action potential.
As the membrane potential approaches threshold, sodium ion channels begin to rap-
idly open, depolarizing the membrane (i.e., discharging the capacitor). The influx of
sodium changes the voltage gradient between the intracellular and extracellular space,
increasing the membrane potential. Once the polarity of the potential changes direction
(when enough sodium ions have crossed the membrane), sodium ion channels begin
to deactivate (decreasing sodium conductance). As the sodium channels close, potas-
sium channels begin to open (increasing potassium conductance), resulting in an efflux
of potassium ions to the extracellular space, restoring the membrane potential to the
resting state following a brief hyperpolarization.

2.7  Filtering

As discussed, simple RC circuits can selectively attenuate certain components or

features of a signal, and not others. This is known as filtering. Filters come in a variety of
forms (RC circuits, mechanical and optical filters, digital signal processing, etc.). Here
we examine two of the most common digital filters used in electrophysiology. The re-
sponse of a system to a brief input signal, or impulse, is called the impulse response. The
impulse response of a finite impulse response (FIR) filter settles to zero in finite time.
Given a finite sample of nonzero input values, an FIR filter will always yield a finite
sample of nonzero output values. This contrasts with an infinite impulse response (IIR)
filter, which does not settle in finite time. The RC filters seen in Section 2.6 are examples
of IIR filters since the capacitors (or inductors) in the RC filter never completely relax
following an impulse.

2.8  Analog-​to-​Digital
Signal Conversion

Most FIR filters are implemented using digital signal processing. Our discussion of elec-
tricity thus far has dealt with analog signals, which are continuous in both time and in
voltage. An economy of representation can be achieved by sampling discrete points in
both the time and voltage domains, a process of creating a digital signal, which has a tem-
poral resolution determined by the sampling rate and a voltage resolution determined
by the resolution of the analog-​to-​digital converter (Figure 2.6). For example, a 16-​bit
converter will allow 1016 of 65,536 discrete voltage values, and a sampling rate of 1,000
Hz will allow one value every millisecond.
With sufficiently large sampling rates, a digital signal can closely approximate the
analog signal it is attempting to represent (Figure 2.7). However, several considerations
 LOGIC BEHIND EEG FREQUENCY ANALYSIS    25

2 Discrete-time sampled 2 Digitally sampled (3 bits)

1.5 1.5
1 1
0.5 0.5
0
µV

0
–0.5 –0.5
–1 –1
–1.5 –1.5
–2 –2
0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2
Seconds Seconds

Figure 2.6  A signal sampled at 20 Hz. Discrete-​time sampling (left panel) allows for con-
tinuous y-​axis (μV) values, whereas digitally-​sampled signals (right panel) must use a limited
number of y-​axis values. The three bit converter illustrated here (right panel) allows for 23 =​8 dis-
tinct values, providing only a coarse approximation of the signal voltage. The right panel depicts
the discrete sample value (red circle) and the 3-​bit digital equivalent (red line), and the discrep-
ancy (dashed vertical black lines).

are essential to ensure signal fidelity when digitizing an analog waveform. In order to
recover all components of a periodic waveform, it is necessary to use a sampling rate at
least twice the highest waveform frequency. This is known as the Nyquist sampling rate,
and it determines whether or not aliasing will occur. Similarly, for a given sampling rate,

20 Hz Sampling 40 Hz Sampling 100 Hz Sampling

2 2 2
1 1 1
4 bits
µV

0 0 0
—1 —1 —1
—2 —2 —2
0 0.5 1 1.5 2 0 0.5 1 1.5 2 0 0.5 1 1.5 2

2 2 2
1 1 1
5 bits

0 0 0
µV

—1 —1 —1
—2 —2 —2
0 0.5 1 1.5 2 0 0.5 1 1.5 2 0 0.5 1 1.5 2

2 2 2
1 1 1
8 bits

0 0 0
µV

—1 —1 —1
—2 —2 —2
0 0.5 1 1.5 2 0 0.5 1 1.5 2 0 0.5 1 1.5 2
Seconds Seconds Seconds

Figure 2.7  A comparison of a signal (black line) sampled (red line) at three sampling rates (20,
40, 100 Hz) and using three different converter resolutions (4-​bit, 5-​bit, and 8-​bit) that allow for
16, 32, and 128 distinct μV values. Low bit-​resolution was used here for illustrative purposes; com-
mercial converters are typically 12-​bit (4,096 values) or 16-​bit (65,536 values).
26    KYLE J. CURHAM and JOHN J. B. ALLEN

Signal Aliasing

18Hz @ 20 samples/s

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Time (s)

Figure 2.8  Signal aliasing due to insufficient sampling rate. Samples from an 18-​Hz signal were
sampled at a rate of 20 Hz. Identical samples are obtained for a 2-​Hz sine wave sampled at 20 Hz.
These digitized signals are indistinguishable from each other.

the highest frequency signal that can be represented is one-​half the sampling rate, and
this is known as the Nyquist frequency. Aliasing occurs when the set of samples obtained
from the analog signal are indistinguishable from samples from a lower-​frequency
signal. For example, in Figure 2.8, an 18-​Hz signal is sampled at 20 Hz, well below the
Nyquist sampling rate. For this 20-​Hz sampling rate, the Nyquist frequency is 10 Hz.
Although the signal is in fact an 18-​Hz signal, the sampled signal appears as a 2-​Hz sine
wave, so the signal is not well characterized. In general, signals that are x Hz above the
Nyquist frequency will appear as a signal x Hz below the Nyquist frequency. Sampling
above the Nyquist frequency will prevent aliasing but may still not characterize the
signal well in the time domain. As a general guideline, it is recommended to sample at
least 5× the highest frequency of interest to get a good signal.

2.9  Digital Filtering

FIR and IIR digital filters can be used to process digital signals. A simple moving average
is an example of an FIR filter. If we take the average across the last five data samples
and shift the five-​sample window forward by one sample at each timestep, the result is
a moving average window. We can denote the value of the filtered signal (x) at the nth
timepoint using summation notation:

2
1
y (n) = ∑ 5 x (n − k )
k = −2
 LOGIC BEHIND EEG FREQUENCY ANALYSIS    27

We can take this one step further, using a different weight for each sample in the
moving average window (h) of width M +​1:

M /2
y (n) = ∑ h (k ) x (n − k )
k = − M /2

This result is exactly the impulse response when the input signal x is an impulse, that
is, one at the middle timestep and zero at all other timesteps. Note the filter output will
clearly be zero outside the range of the window, demonstrating that this is in fact an FIR
filter. Figure 2.9 shows the output of a moving average filter, given a noisy input signal.
The summation operation described is known as convolution. In general, convolu-
tion indicates the amount of overlap of one function or kernel (h) as it is shifted over
another function (x). In these examples, the convolution is simple to compute. However,

(a) Moving Average FIR filter

Raw
Filtered

0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1
Time (s)
(b) 1st-Order Filter with 50 Hz Cutoff
Raw
Filtered

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

Time (s)

Figure 2.9  Moving average FIR filter (top). A window size of 15 ms was convolved with noisy
data to obtain the filtered signal. Low-​pass IIR filter with 50 Hz cutoff (bottom).
28    KYLE J. CURHAM and JOHN J. B. ALLEN

in practice, it can be computationally expensive. In the next section, we show how to

efficiently evaluate convolutions using an advanced signal-​processing technique called
the Fourier transform.

2.10  Frequency Domain

In general, signals may have both AC and DC components. For example, you may see
an AC signal that oscillates around a nonzero mean (a DC offset). Arbitrary complex
signals may be approximated by the sum of two or more simpler signals. For example,
we can synthesize a complex signal my summing together multiple sine waves of various
frequencies. Fourier analysis is the reverse process—​decomposing a signal into its con-
stituent parts. The Fourier series approximates any complex periodic signal as a finite
weighted sum of sine waves of various frequencies. The more sine waves included in
the summation, the better the Fourier series can approximate the signal. In the limit
that the number of frequencies included in the summation goes to infinity, the Fourier
series converges to the Fourier transform. In this case, we can describe the signal as a
continuous distribution, or spectrum, of frequencies, along with the phases at which
each sine wave begins. The Fourier series can be applied to a wide array of mathem-
atical, physical, and signal processing problems. Fourier analysis is now widely used
across several domains, including audio, images, radar, sonar, X-​ray crystallography,
and more.
Rather than analyzing signals as a function of time, Fourier analysis allows us to
study their properties as a function of frequency. Signals that are localized in the time
domain have Fourier transforms that are spread out across the frequency domain, and
vice versa. For example, the Fourier transform of a pure sine wave is a single point in
the frequency domain (Figure 2.10, bottom). Points in the frequency domain may be
characterized by properties such as power and phase, which are of interest for EEG
analyses. The absolute value of a given frequency component of the Fourier series
indicates the “amount” of that frequency present in the original signal. The squared
absolute value is the signal power. The power spectrum describes how signal power
varies as a function of frequency. EEG signals typically follow a 1/​f trend, such that
low frequencies have more power compared to high frequencies. However, the power
spectrum may vary as a function of individual differences and task demands. Changes
in power at a frequency may be due to alterations in the slope of the EEG frequency
spectrum, or modulations in frequency-​specific oscillatory activity (see Chapters 9, 10,
and 23). Similarly, the phase spectrum of the signal can be extracted from the Fourier
series. The signal phase indicates the amount of “shift” in each of the basis sine waves
(for more info, see Chapter 7).
The Fourier transform is invertible. Given the power and phase spectrum, it is pos-
sible to reconstruct the original time-​domain signal. Moreover, it is possible to compute
the Fourier transform of a signal, perform mathematical operations in the frequency
 LOGIC BEHIND EEG FREQUENCY ANALYSIS    29

(a) Three Sinusoids (10, 20 & 30 Hz)

1

amplitude 0.5

0
—0.5

—1
0 100 200 300 400 500 600 700 800 900 1000
time (ms)

Superposition of Sinusoids
4
amplitude

0
—2

—4
0 100 200 300 400 500 600 700 800 900 1000
time (ms)
Power Spectral Density
0
Power (dB)

–100

–200
–300

–400
0 5 10 15 20 25 30 35 40 45 50
frequency (Hz)
(b) Sinusoid

0 .1 .2 .3 .4 .5 .6 .7 .8 .9 1
Time (s)
Power Spectral Density
0
-50
Power (dB)

-100
-150
-200
-250
-300
-350
0 5 10 15 20 25 30 35 40 45 50
Frequency (Hz)

Figure 2.10  Constructing a complex signal from the superposition of sinusoids (top). The
power spectrum of the signal show distinct peaks at the frequencies of the component sinusoids.
A single sinusoid corresponds to a single peak in the power spectrum (bottom).

domain to alter the power and phase spectrum, and then compute the inverse Fourier
transform to convert back to the time domain. For every mathematical operation
in the time-​domain, there is a corresponding equivalent operation in the frequency-​
domain. In some cases, operations may be easier to perform in one domain or another.
This makes the Fourier transform very powerful. For example, convolution in the time-​
domain is equivalent to multiplication in the frequency domain.
30    KYLE J. CURHAM and JOHN J. B. ALLEN

To sum up: compute the Fourier transform of the time-​domain signal and filter
weights, multiply them in the frequency domain, and compute the inverse Fourier
transform to obtain a filtered signal.

2.11  Windowing

The Fourier transform assumes the signal is periodic and includes sine waves of infinite
period. However, EEG recording epochs are finite, spanning just seconds or minutes.
Clearly low frequencies cannot be captured by data segments smaller than the period of
the signal. For example, a segment of 250 ms will contain only a half-​cycle of a 2-​Hz sine
wave. In contrast, a 50-​Hz waveform would complete 10 full cycles within the allotted
window. A general rule guideline to determine an adequate window size is to take 3–​5
times the period of the lowest frequency of interest.
Window functions are often used to examine small segments of data from a longer
signal to study transient events that have may have different spectral properties than
other surrounding data segments. Windows are usually constructed such that they are
zero-​valued outside of the interval, symmetric around the middle of the interval, and
tapering away to zero at the edge of the window. Several types of window functions are
commonly used in EEG frequency analysis, including Hann, Hamming, and Gaussian
windows. The duration of the window is application specific and is governed by
requirements such time and frequency resolution.
However, we cannot perfectly resolve both time and frequency simultaneously.
Time and frequency are conjugate variables, which are coupled such that knowledge
of one makes knowledge of the other uncertain. Therefore, there is a tradeoff between
time and frequency resolution, such that good time resolution comes at the expense
of frequency resolution, and vice versa. As the window shrinks to zero width, short
tones become clicks, with no discernable frequency. Clicks can be perfectly localized
in time, but the frequency is undefined. As the window gets large compared to the
signal length, it becomes impossible to localize a signal in time, but the frequency
can be easily determined. Time-​frequency analyses balance the time-​frequency reso-
lution tradeoff.

2.12  Time-​Frequency Analysis

Frequency analyses are restricted to stationary signals. That is, the spectral
characteristics do not change over time. However, EEG signals change as a function of
state and task demands, which can vary over time. Time-​frequency analyses are used
to study the non-​stationary characteristics of psychophysiological signals. Rather than
analyzing signals in one domain—​time or frequency—​signal properties are localized to
points or pixels in a two-​dimensional time-​frequency plane.
 LOGIC BEHIND EEG FREQUENCY ANALYSIS    31

The simplest method to obtain a time-​frequency representation of data is to compute

the Fourier transform over a small sliding window that is chosen to be just wide enough
to resolve the lowest frequency of interest. This approach yields local information about
the signal, including frequency and phase content. This method is known as the short
time Fourier transform (STFT) and can be used to obtain the power and phase of the
signal at each point in the time-​frequency plane.
The wavelet transform is slightly more advanced, considering the time-​frequency
trade-​off that comes with windowing. This method convolves the signal with a set
of complex gaussian-​windowed sinusoids. When the similarity between the signal
and wavelet is high, the convolution term is large. A family of wavelets of varying
frequency and duration are constructed and convolved with the EEG signal to find
points of peak similarity. The amplitude and phase of the signal can be obtained
from the transform by computing the magnitude and angle of the complex wavelet
coefficients. Unlike the STFT, the resolution of the wavelet transform has different
properties at different frequencies. As frequency increases, the wavelets get shorter,
effectively decreasing the window width. This leads to better time-​resolution at the
cost of worse frequency resolution (­figure 11). In general, the wavelet transform has
better time-​resolution at high frequencies and better frequency resolution at low-​
frequencies. For a more in-​depth look at the wavelet transform, see ­chapters 12 and
13in Cohen (2014).
Time-​ frequency decompositions provide a new way to identify
psychophysiologically relevant components. While traditional time-​ domain
methods could reveal components that occur at different timepoints, they cannot
distinguish between components that occur at different frequencies at the same
time-​point. However, once the time-​frequency decomposition is obtained, new
analyses may be performed that were not possible with pure time-​domain or

Wavelets Power Spectrum

4 Hz
8 Hz
16 Hz

–1 –.8 –.6 –.4 –.2 0 .2 .4 .6 .8 1 0 5 10 15 20 25

Time (s) Frequency (Hz)

Figure 2.11  Wavelet time-​frequency resolution trade-​off. Higher-​frequency wavelets (yellow)

are more precise in time (left), but less precise in frequency (right). Conversely, low frequency
wavelets (blue) have poor time resolution (left) but good frequency resolution (right).
32    KYLE J. CURHAM and JOHN J. B. ALLEN

frequency-​domain approaches. For example, the phase consistency between two

or more channels over time is often used to infer frequency-​specific connectivity
between regions. Inter-​channel phase synchrony is evaluated by computing the
covariance between the phases of two or more channels at a given frequency (see
Chapter 20). Time-​frequency analysis allows for the identification of event-​related
time-​locked changes that are not phase-​locked; such changes would not appear in
traditional time-​domain analyses using signal averaging to create event-​related
potentials (cf. Trujillo & Allen, 2007).

2.13  Practical Considerations for EEG

2.13.1 EEG Signal Artifacts

EEG is used to record electrical activity originating in the cerebral cortex, although it
also detects electrical activity arising from sources other than the brain. EEG signals
are highly sensitive and are easily influenced by electrical activity in the surrounding
environment. Artifacts in EEG signals come in at least two distinct varieties: physio-
logical and non-​physiological noise. EEG signals generated by the body, but that are
not cerebral in origin, are deemed physiological noise. Sources of physiological arti-
fact include muscle movements, eye blinks, tongue movements, respiration sway, elec-
trocardiographic activity, jaw clenching, etc. Conversely, non-​physiological artifacts
arise from sources outside the body, such as electronic noise, amplifier saturation, or
loose electrodes. For example, thermal noise due to the random motion of electrons
in resistive components, flicker due to irregularities in contact pins, and burst due to
semiconductor impurities are common sources of noise. The most obvious electronic
noise is flicker due to power-​line interference, appearing at 60 Hz in North America
and 50 Hz in much of the rest of the world. When the electrical impedance at the scalp-​
electrode interface is high (>5 kΩ), resulting in a poor connection, the electrode is
more sensitive to these noise sources. To judge the acceptability of the scalp imped-
ance for obtaining good quality signals, it is important to consider the input impedance
of the amplifier. Contemporary high impedance amplifiers mitigate the susceptibility
to electronic noise, as the fidelity of the observed EEG signal is directly related to the
average impedance of the target and the reference electrode, and inversely related to
the amplifier input impedance (Ferree et al., 2001). Thus some equipment can produce
high quality signals with scalp impedances that may be higher than the often-​used 5 kΩ
standard.
There are multiple strategies to handle EEG recording artifacts: use of a ground
electrode to remove noise that presents similarly across all electrodes, artifact rejec-
tion to remove electrodes or segments of data that are corrupted by noise, and artifact
correction to separate signal from noise without sacrificing data.
 LOGIC BEHIND EEG FREQUENCY ANALYSIS    33

2.13.2  Grounding
Ground electrodes are used for common mode rejection: parts of the signal shared
across all electrodes are removed from the recording. A good ground connection is crit-
ical to reducing the impact of external noise sources. Impedances for all electrodes are
compared to the ground electrode. Therefore, if the ground impedance is high, good
impedances will not be possible on any other electrodes. However, electrical interfer-
ence may persist even after ensuring good electrode impedances and secure grounding.
Therefore, data rejection and correction are often used to handle residual artifacts
during offline processing.

2.13.3 Artifact Rejection
Artifact removal may consist of rejecting entire segments of data, or individual
electrodes from the recording. While the basic strategy is to identify data corrupted by
artifact and exclude it from future analysis, it is not a trivial task. The determination of
whether a signal is sufficiently corrupted by noise to justify removal is time consuming,
subjective, and may vary by researcher. Moreover, significant training is required to
learn to correctly identify different sources of noise. Judgements must also be made as to
whether each artifact should be removed, even if it is correctly identified. In some cases,
a filter may be used to attenuate electronic noise. For example, a 60-​Hz artifact from
power-​lines may be removed from EEG recordings using a notch filter, which allows
frequencies lower and higher than the specified frequency-​band to pass unaffected,
while significantly attenuating the artifact (e.g., between 55–​65 Hz). However, filtering
may not be an optimal solution for all artifacts. For example, blink timing is related to
information processing (Stern et al., 1984), and blink rate is correlated to dopamine
release (Taylor et al., 1999), although recent work has called this into question (Dang
et al., 2017). However, many researchers remove data segments with eyeblinks due to
the large artifact they produce in frontal EEG channels. If the phenomenon of interest is
correlated to these physiological artifacts, it is possible to inadvertently remove valuable
data and miss the psychophysiological phenomenon.
Sometimes artifacts may be localized to a single bad channel. In this case, remove
only that channel from the recording and keep the remaining data. Many researchers
examine the standard deviation of the signal to automatically detect bad electrodes. If
it exceeds a threshold much larger than would be expected for a quality EEG signal, the
channel is marked bad. If a channel is marked bad and it is required for a planned EEG
analysis, the missing data can be interpolated. Interpolation uses information from the
surrounding electrodes to guess what the signal would have been if there were a good
electrode at that location. A popular choice is spherical spline interpolation (Perrin
et al., 1989).
34    KYLE J. CURHAM and JOHN J. B. ALLEN

2.13.4 Artifact Correction
If possible, EEG researchers want to retain as much signal as possible and thus avoid
removing noisy signals from data analyses. Several algorithms exist to attempt to
separate signal from noise, thereby sparing valuable data. The three most common
approaches are linear regression, independent component analysis (ICA), and principal
component analysis (PCA).
Linear regression is by far the simplest method to remove ocular artifacts. Ocular
artifacts typically have much higher amplitude than the EEG signals generated by neural
sources. For the purpose of regression, the tiny EEG signals are assumed to be noise rela-
tive to the ocular artifacts. Blinks are assumed to affect electrodes in a linear combination,
such that electrodes closer to ocular channels have a larger weight than electrodes farther
from ocular channels. Once the optimal weights are calculated, a weighted composite of
the ocular artifact is subtracted from each of the EEG electrodes (cf. Gratton et al., 1983),
yielding EEG that should be (mostly) free of the artifact. However, it requires the ocular
artifacts to be linearly dependent and normally distributed, which generally is not the case.
This approach is fast and simple, but sometimes inaccurate, which introduces another
source of residual artifact. Errors in the regression get “subtracted into” the recording.
ICA is a blind source separation technique, unmixing a multivariate signal into a set
of additive components (Delorme et al., 2010). Unlike linear regression, independent
components (ICs) are assumed to be non-​Gaussian and statistically independent from
each other. However, ICA can only separate linearly mixed sources, and even when the
sources are not independent, ICA will return maximally independent components.
In many cases, a subset of the ICs will capture artifacts such as ocular and motor
components. Components are determined to be artifact or signal based on their simi-
larity with the topography and time course of known artifacts. This can be determined
based on experimenter ratings or algorithmically using spatial and temporal features
of eye blinks, vertical and horizontal eye movements, and discontinuities in the EEG
time series (Mognon et al., 2011). Artifactual components may also be identified auto-
matically based on a supervised machine learning approach trained from expert ratings
on a large corpus of EEG data (Winkler et al., 2014). ICA is more useful than linear re-
gression because it can extract more than just ocular components, also capturing loose
electrodes and muscle artifacts equally well. Once the bad components are identified,
the signal can be reconstructed without the artifacts.
Other blind source separation techniques similar to ICA can be used in a similar
manner. PCA is like ICA in that it separates the data into a set of linearly independent
components. However, these components are additionally assumed to be mutually or-
thogonal (i.e., uncorrelated with each other).

2.13.5  Referencing
Voltage is always measured between two points. It does not make sense to talk about the
potential at a particular EEG electrode without first defining a reference potential (i.e.,
 LOGIC BEHIND EEG FREQUENCY ANALYSIS    35

an arbitrarily chosen “zero”). A common reference is usually chosen for all electrodes, to
which all potentials recorded at each electrode are measured. The reference needs to be
chosen carefully because the electrical activity under the reference site will be reflected
in the activity at every other electrode. If the reference is not neutral, artifacts will be
introduced due to the activity at the reference site. The reference electrodes should be
placed on a presumed electrically neutral area. In many cases, researchers choose an
electrode over the mastoid part of the temporal bone, or the left or right earlobe.
In reality, there are no electrically neutral points to choose as a reference. However,
it is possible to construct a virtual reference that is more likely to be electrically neutral
than any single EEG electrode. For example, choosing the left or right mastoid alone
results in a systematic decrease of EEG amplitude in the electrodes which are closer to
the reference site. The “linked” mastoids reference is obtained by using the average of
both left and right mastoid electrodes as the reference level. This resolves the left/​right
asymmetry that would normally occur. Another popular choice is the average reference
when the number of electrodes is large (typically >32). The average reference is obtained
by subtracting the mean potential across all EEG electrodes from each electrode at each
time-​point. Theoretically, if we could obtain measurements sampling equally around
a sphere containing the brain, then electric dipoles picked up by the electrodes would
average out to zero, and the average reference would be a truly neutral point (Bertrand
et al., 1985). However, this is a practical impossibility because the ventral surface is in-
accessible for electrode placement. Still, by averaging the electrical activity across the
entire scalp, the “responsibility” is distributed over all electrodes, rather than only one
or two of them.
However, prominent deflections at any given scalp location can differ dramatically
depending on the chosen reference scheme, affecting both the amplitude and latency
of the recorded signal. Not all researchers use the same reference, leading to problems
in the comparability between datasets. Fortunately, it is possible to convert from one
reference to another with a simple mathematical transformation. Note the potential
difference between two electrodes does not depend on the chosen reference. If your ana-
lysis is only concerned with comparisons between two electrodes, then the reference is
irrelevant. A simple analogy is measuring height above sea level. A change in sea level
does not change the shape of the landscape or the relative elevation between any two
points. Thus, if there is a change in sea level, we can readjust to the new reference level by
simply subtracting the change in elevation from every point. Similarly, we can transform
between different references by subtracting the potential at the chosen reference site.
Other transformations can be used to obtain a reference-​free representation of EEG
signals. This is usually achieved using the scalp Laplacian, sometimes called the Current
Source Density (CSD). Technically, the scalp Laplacian relates current generators within
an electrical conductor to the second spatial derivative of the potential at each elec-
trode. Approximately, the scalp-​Laplacian at a given electrode is obtained subtracting
the potentials of all neighboring sites weighted by their inverse distance. In other words,
the scalp Laplacian measures how extreme the potential at one electrode is compared
to the average of its neighboring electrodes. This intuitive description is complicated by
the fact that scalp electrode montages do not form a flat grid of evenly spaced electrodes.
36    KYLE J. CURHAM and JOHN J. B. ALLEN

Cz AR LM CSD
Open
Closed

Figure 2.12  Topography of alpha power under eyes open (top) and eyes closed (bottom)
conditions as a function of transformation (Cz, average (AR), or linked mastoid (LM) reference
or current source density (CSD) transformation) from a sample of over 2400 resting recordings.
Power values at each site represent natural-​log transformed values; thus, negative numbers rep-
resent mean power values less than one. Each transformation is scaled independently, but within
each transformation, eyes open and closed data are plotted on the same scale. Only the CSD
transformation confines occipital alpha to occipital leads, whereas the other three montages show
reflected alpha at frontal regions, visible most clearly by a comparison of frontal leads under eyes
closed compared to eyes open recordings.
Figure modeled after Smith et al., 2017.

Instead, they conform to the nearly spherical geometry of the scalp. However, the
Laplacian can still be efficiently computed using spherical spline interpolation
(Delorme & Makeig, 2004). The scalp Laplacian has the added advantage of addressing
volume conduction. Electrical fields originating from any particular neuronal structure
will influence the electrical potential throughout the brain and surrounding physio-
logical tissue. As a result, EEG electrodes detect a mixture of activity from across the
whole brain, rather than directly under the recording site. Critically, the scalp Laplacian
minimizes the influence of this effect since the Laplacian is close to zero when a signal
is shared similarly across several electrodes (cf. Smith et al., 2017). Figure 2.12 shows a
comparison across referencing schemes .

2.14  Conclusion

A basic understanding of electricity and signal processing is vital to EEG data collection
and interpretation. Investigators need to report clearly how they acquired and analyzed
the data, and consumers need to be able to evaluate the methods and claims critically.
There are many steps to be taken in acquiring and processing EEG signals, from net ap-
plication and impedance checking, to grounding and referencing, to artifact detection
 LOGIC BEHIND EEG FREQUENCY ANALYSIS    37

and correction, to data processing and analysis methods in the time and frequency
domains. This chapter provided a basic introduction to these concepts, but more in-
formation can be obtained from several guidelines papers (Picton et al., 2000; Keil
et al., 2014).

Glossary

Aliasing:  When an analog signal is insufficiently sampled, the digitized signal may be indis-
tinguishable from samples from a lower-​frequency signal.
Ampere:  The SI unit of electric current. It is defined as one coulomb of charge per second.
Analog signal:  A continuous time-​varying signal that may vary in frequency, amplitude,
and phase.
Analog-​to-​digital converter:  System that converts an analog signal into a digital signal.
Capacitance:  Ratio of the change in an electric charge to the change in electric potential.
A property that quantified a materials ability to store electric charge.
Conductivity:  Property that quantifies how strongly a material conducts electric current.
Conductor:  A material that allows the flow of electric current.
Conjugate variables:  Pairs of variables that cannot be precisely estimated simultaneously.
Knowledge of one variable necessitates uncertainty in the other variable. Time and fre-
quency are examples of conjugate variables.
Convolution:  A mathematical operation that indicates the amount of overlap of one function
or kernel as it is shifted over another function.
Cutoff frequency:  Frequency at which the signal power is reduced by half. The amount of at-
tenuation increases as you move farther from the cutoff.
Current:  The directed motion of electrons or electric charge.
Digital signal:  A discrete sequence of finite values that represent a signal.
Electric field:  The force per unit charge at each point in space.
Electricity:  Phenomenon that describes the behavior and movement of electric charge.
Electromotive force (EMF):  The rate at which energy is drawn from a 1 A current source,
measured in volts.
Finite impulse response (FIR) filter:  A filter whose impulse response settles to zero in fi-
nite time.
Free electrons:  Any electron that is free to move under the influence of an electric or mag-
netic field.
Impedance: Measures the opposition to an electric current when a voltage is applied.
Impedance is equal to resistance in a DC circuit.
Impulse response:  The output of a circuit when presented with a brief input signal.
Insulator:  A material that does not allow the flow of electric current.
Ionization:  The acquisition or loss of electrons in an atom or a molecule, resulting in a net
positive or negative charge.
Nyquist frequency:  Half of the sampling rate of a digital signal. It is the highest frequency that
can be accurately sampled for a given sampling rate.
Nyquist sampling rate:  In order to adequately digitize an analog signal, it should be sampled
at least twice the highest frequency of interest.
38    KYLE J. CURHAM and JOHN J. B. ALLEN

Phase spectrum:  A measure of signal phase versus frequency.

Potential energy:  The energy stored by an object due to electric charge.
Power spectrum:  A measure of signal power versus frequency.
RC time constant:  The time required to charge a capacitor to 63.2% of the applied DC voltage.
Reactance:  Material property that measures the resistance to a change in current or voltage.
Resistance:  Property that quantifies how strongly a material resists electric current.
Sampling rate:  Rate at which discrete samples are acquired for a digital signal.
Volt:  The amount of EMF required to push a current of one ampere through a conductor with
a resistance of one ohm, or 1 volt/​ampere.
Voltage:  Difference in electric potential between two points.

References
Bertrand, O., Perrin, F., & Pernier, J. (1985). A theoretical justification of the average reference in
topographic evoked potential studies. Electroencephalography and Clinical Neurophysiology,
62(6), 462–​464.
Cohen, M. X. (2014). Analyzing neural time series data: theory and practice. MIT press.
Dang, L. C., Samanez-​Larkin, G. R., Castrellon, J. J., Newhouse, P. A., Zald, D. H., Perkins, S.
F., & Ronald, L. (2017). Spontaneous eye blink rate (EBR) is uncorrelated with dopamine
D2 receptor availability and unmodulated by dopamine agonism in healthy adults. ENeuro,
4(5), 1–​11.
Delorme, A. & Makeig, S. (2004). EEGLAB: An open source toolbox for analysis of single-​
trial EEG dynamics including independent component analysis. Journal of Neuroscience
Methods, 134(1), 9–​21. https://​doi.org/​10.1016/​j.jneum​eth.2003.10.009
Delorme, A., Sejnowski, T. J., & Makeig, S. (2010). Enhanced detection of artifacts in EEG
data using higher-​order statistics and independent component analysis. NeuroImage, 34(4),
1443–​1449. https://​doi.org/​10.1016/​j.neu​roim​age.2006.11.004.Enhan​ced
Ferree, T. C., Luu, P., Russell, G. S., & Tucker, D. M. (2001). Scalp electrode impedance, infec-
tion risk, and EEG data quality. Clinical Neurophysiology, 112(3), 536–​544.
Gratton, G., Coles, M. G., & Donchin, E. (1983). A new method for off-​line removal of ocular
artifact. Electroencephalography and Clinical Neurophysiology, 55(4), 468–​484.
Keil, A., Debener, S., Gratton, G., Junghöfer, M., Kappenman, E. S., Luck, S. J., Luu, P., Miller,
G. A., & Yee, C. M. (2014). Committee report: Publication guidelines and recommendations
for studies using electroencephalography and magnetoencephalography. Psychophysiology,
51(1), 1–​21.
Mognon, A., Jovicich, J., Bruzzone, L., & Buiatti, M. (2011). ADJUST: An automatic EEG arti-
fact detector based on the joint use of spatial and temporal features. Psychophysiology, 48(2),
229–​240. https://​doi.org/​10.1111/​j.1469-​8986.2010.01061.x
Perrin, F., Pernier, J., Bertrand, O., & Echallier, J. F. (1989). Spherical splines for scalp potential
and current density mapping. Electroencephalography and Clinical Neurophysiology, 72(2),
184–​187. https://​doi.org/​10.1016/​0013-​4694(89)90180-​6
Picton, T. W., Bentin, S., Berg, P., Donchin, E., Hillyard, S. A., Johnson, R., . . . Taylor, M. J.
(2000). Guidelines for using human event-​related potentials to study cognition: recording
standards and publication criteria. Psychophysiology, 37(2), 127–​152. http://​www.ncbi.nlm.
nih.gov/​pub​med/​10731​765
 LOGIC BEHIND EEG FREQUENCY ANALYSIS    39

Smith, E. E., Reznik, S. J., Stewart, J. L., & Allen, J. J. (2017). Assessing and conceptualizing
frontal EEG asymmetry: An updated primer on recording, processing, analyzing, and
interpreting frontal alpha asymmetry. International Journal of Psychophysiology, 111, 98–​114.
Stern, J. A., Boyer, D., & Schroeder, D. (1994). Blink rate: A possible measure of fatigue. Human
Factors, 36(2), 285–​297. https://​doi.org/​10.1177/​001​8720​8940​3600​209
Stern, J. A., Walrath, L. C., & Goldstein, R. (1984). The endogenous eyeblink. Psychophysiology,
21(1), 22–​33.
Trujillo, L. T., and Allen, J. B. (2007). Theta EEG dynamics of the error-​related negativity.
Clinical Neurophysiology, 118(3), 645–​668
Taylor, J. R., Elsworth, J. D., Lawrence, M. S., Sladek, J. R. Jr, Roth, R. H., & Redmond, D. E. Jr.
(1999). Spontaneous blink rates correlate with dopamine levels in the caudate nucleus of
MPTP-​treated monkeys. Experimental Neurology, 158(1), 214–​220.
Winkler, I., Brandl, S., Horn, F., Waldburger, E., Allefeld, C., & Tangermann, M. (2014). Robust
artifactual independent component classification for BCI practitioners. Journal of Neural
Engineering [online], 11(3), 035013. https://​doi.org/​10.1088/​1741-​2560/​11/​3/​035​013
 CHAPTER 3

F ROM NEU RAL O S C I L L AT I ONS

TO C O GNITIVE PRO C E S SE S

ANDREAS KEIL AND NINA THIGPEN

3.1  Oscillations in Complex

Systems: An Overview

Cyclical rhythms are a hallmark property of natural systems, from the movement of
the planets to the sleep and wake cycles of mammals, to neuronal membranes. Such
rhythmic variation, if it occurs repeatedly across time, is called an oscillation. The back-​
and forth of tree branches on a windy day, ocean waves, and the rhythmic song of choir
frogs are further examples for natural oscillations. As such, the notion of oscillations
seems fairly straightforward: they occur in complex systems, in which many connected
units interact, and they reflect activity perceived as recurrent, or rhythmic. However, a
woman strolling on an ocean beach will soon realize that although waves break repeat-
edly and somewhat predictably, they also vary in terms of their exact timing, duration,
size, and shape. This seems to be different from the orbit of our planet earth around the
sun, or the vibrations of crystalline matter—​rhythms that are regular and fixed enough
for us to measure time on their basis. These latter are typically referred to as “periodic
oscillations”, which are a sequence of recurring events (often taking the shape of a wave
when measured), each of which has identical, constant, duration. Although periodic
oscillations are well defined in the language of mathematics (e.g., the sine function),
the examples at the start of the chapter show that the concept of periodicity may not be
as clear-​cut in natural systems. For example, the duration of solar years is not constant
when measured with precision, and even clock-​setting crystal oscillators change their
rhythm with temperature. Thus, periodicity may be a continuous dimension ranging
from more periodic (the solar year) to less periodic (the tides) rhythms, rather than
representing a qualitative (yes/​no) feature. In fact, various natural systems are likely to
 FROM NEURAL OSCILLATIONS TO COGNITIVE PROCESSES    41

oscillate in different fashion, and the same system may display oscillatory behavior at
different levels of complexity when challenged in different ways.
Identifying how a complex system oscillates may go a long way towards its char-
acterization. As a consequence, the natural sciences have developed an impres-
sive toolbox for detecting, quantifying, and understanding oscillatory activity, and
to separate it from non-​oscillatory phenomena. This chapter discusses how these
concepts are applied to fundamental problems in cognitive neuroscience, and ask
what the significance is of oscillatory activity for human behavior and cognition? It
also asks how we should define and conceptualize brain oscillations, and how they
can be measured and interpreted. We address these questions in the light of current
research, with a focus on electrophysiological recordings in human beings and ex-
perimental animals.

3.2  Brain Oscillations and

Behavior—​an Example

After over a decade of testing, in 1927 Hans Berger conducted the earliest in vivo
recordings of electric fields from the human brain using his new invention, the electro-
encephalograph (Berger, 1929). Upon visual inspection of these first brain wave (elec-
troencephalography, or EEG) recordings, Berger decided that the most salient feature
of the EEG was its change in frequency content when the participant performed a task
or was stimulated (often by being touched with a glass probe). Most prominently, Berger
identified “first-​order waves” oscillating at a rate of 10 cycles/​second (i.e., 10 Hertz
(Hz), today referred to as alpha waves) and faster “second-​order waves” oscillating at
about 20–​30 Hz (today referred to as beta waves). Even without the ability to average
across trials, and in the absence of digitally supported spectral analysis, Berger and his
colleagues (i.e., his family; his wife Ursula von Bülow was his technical assistant and
frequent test participant, along with himself, and his son, Klaus) made a striking ob-
servation: whenever a person was at rest, for example, with their eyes closed, first-​order
waves characterized by large-​amplitude regular activity at 10 Hz dominated the EEG.
However, touching the person with a glass probe, asking them to open their eyes, or
just addressing them and asking a question led to a dramatic blocking of these alpha
waves, which were replaced by faster and lower-​amplitude EEG readings. This effect,
referred to as “alpha blocking” has since been replicated thousands of times, and is still
used today in clinical usage of EEG in neurology and psychiatry to assess the status
of global brain electric states (Başar & Güntekin, 2012). Furthermore, this observa-
tion opened an avenue for experimental studies of EEG-​behavior relations, in which
participants are asked to respond to experimenter-​defined task demands, and changes
in the EEG are measured as a dependent variable (Klimesch et al., 2005). In addition
to testing hypotheses about brain function, these variables possess practical value for
42    ANDREAS KEIL and NINA THIGPEN

testing hypotheses about behavioral and cognitive processes, their time course, and
about specific characteristics of the participant or the environment, of interest in clinical
and translational studies.

3.3  Quantifying and Categorizing

Brain Oscillations

Oscillatory activity is typically described by quantifying its frequency, amplitude

(power), and phase (Figure 3.1). Frequency refers to the rate of repetition of the oscil-
latory event (e.g., action potentials emitted by a neuron, or epileptic spikes in the EEG
signal) and is measured in Hz, the number of events per second. Amplitude reflects the
magnitude of the oscillatory signal at a given frequency, analogous to measuring the
height of ocean waves. Power (e.g., microvolts squared) is often used instead of amp-
litude to describe the magnitude of an oscillation. This reflects the fact that the com-
putation of spectral magnitude usually involves an integral across time, which may
be thought of as an area under the curve at a given frequency, resulting in a squared
unit of measurement. Thus, in many cases, depending on scaling and other normaliza-
tion steps, power values given in published research may be roughly equivalent to the
squared amplitude of the oscillatory signal.
The phase of an oscillation is a measure of its position in time, relative to a pre-​defined
cycle, or relative to a reference oscillation at the same frequency. Because oscillations
are by definition cyclic and recurrent, phase is measured using circular metrics, typic-
ally in degrees or radians of arc. For example, a phase of 90 degrees (1/​2 Pi) may indi-
cate that the oscillation at this point in time is at its peak, going down, 180 degrees (Pi)
may indicate that it is transitioning through zero, and 270 degrees may indicate that it
is at its minimum, going up. In neuroscience studies, phase is often used to quantify
the amount of temporal correspondence or similarity between two signals, measured

Different power Same power Same power

Same phase Different phase Different phase
Same frequency Same frequency Different frequency

Figure 3.1 Illustration of oscillatory power, phase, and frequency. Oscillations are

characterized these three properties and can independently vary along these three dimensions.
 FROM NEURAL OSCILLATIONS TO COGNITIVE PROCESSES    43

during different trials or at different locations (i.e., phase-​locking, phase synchrony)

[cross ref Chapter 20 Makeig and Palva]. We discuss phase-​locking later in this chapter.
There are different ways for computing the oscillatory content of a signal, many of
which are discussed in this volume [cross ref Chapter 23 Allen and Voytek]. Broadly,
there are two main groups of methods for estimating spectral events in neural time
series data. First, methods that result in a spectral representation, or frequency-​domain
representation. In these representations, frequency (in Hz) is plotted along the x-​axis,
and spectral power (or phase) along the y-​axis. Power (and phase) values for each fre-
quency in the spectrum are obtained by integrating the information across all time
points entering the spectral analysis, which often is a variant of the well-​known Fourier
transform that uses sine and cosine functions as templates for quantifying the os-
cillatory content of a time-​varying neural signal such as EEG or local field potentials.
A second approach is used when researchers wish to retain information on the changes
in oscillatory activity in their signal over time. Many methods exist for obtaining such
a time-​frequency representation, in which time is typically plotted on the x-​axis, fre-
quency along the y-​axis, and a colormap or 3rd dimension in the figure is used to rep-
resent spectral power or amplitude for each time point and frequency. Often, this type
of data analysis is used when the data set contains a substantial number of trials, locked
to events (e.g., the onsets of a stimulus, the time of a motor action). Then, the time-​
frequency representations of each trial are compared and/​or averaged. Figure 3.2 shows
an example of the change in oscillatory power during a complex sequence of visual cues
and behaviors as participants perform a working memory task. Wavelet analysis is a
popular approach for obtaining time-​frequency representations in studies of oscillatory
brain activity, but many other methods exist (see Chapter 4). For a practical introduc-
tion, we recommend Cohen’s Analyzing Neural Time Series Data (2014).

Fixation Memory Mask Task Array Response

Array

1.2
Frequency (Hz)

30 1.1

20 1
0.9
10
0.8
0 1 2 3 4 5 6 7 8
Time (seconds)

Figure 3.2  Oscillatory changes during a working memory task. Time-​frequency decompos-
ition of the EEG activity recorded at sensor Pz over a 9-​s trial in which participants memorized
the orientation of two gratings. They then viewed a mask, a task array, and finally were asked to
indicate if the orientation of an item in the task array matched an item in the memory set. Each
task element prompts specific time-​frequency dynamics. For example, alpha-​band activity (8–​
12Hz) is highest during the fixation period before the start of the trial, and during the retention
interval when viewing the mask.
44    ANDREAS KEIL and NINA THIGPEN

A useful approach for a classification of the brain’s oscillatory activity is the widely-​
adopted nomenclature first introduced by Robert Galambos (1992). Considering brain
oscillation across several species, Galambos distinguished:

1. spontaneous oscillations, which are not related to external stimuli;

2. evoked oscillations, which are elicited and precisely time-​locked to the onset of an
external stimulus;
3. emitted oscillations, which are time-​locked to a stimulus that was expected but
then did not occur; and
4. induced oscillations, which are prompted by a stimulus but are not time-​and
phase-​locked to its onset.

Investigators new to the field are often curious about how different types of oscillations
should be analyzed and interpreted in terms of hypotheses regarding a specific behav-
ioral, cognitive, or neural process. To address these questions, it may be helpful to con-
sider the different types of dependent variables that may be used in studies of oscillatory
brain activity during cognitive processing.

3.4  Characterizing Brain Oscillations

in the Context of Cognitive Tasks

The mathematical foundations of extracting power and phase from time domain neural
signals as described earlier are straightforward and yield estimates of power at a given
frequency, in a given time period, at a specific sensor. What is less clear is the functional
and neurophysiological interpretation of differences in power, especially in population-​
level signals, such as local field potentials (LFPs), intra-​and extracranial EEG, and MEG.
These signals reflect the synchronous synaptic (dominantly post-​synaptic) currents of a
large number (at least several tens of thousands in the case of EEG/​MEG) of neurons
which need to be aligned favorably (in parallel) to create measurable extracranial elec-
tric fields (Olejniczak, 2006). Thus, a difference between two experimental conditions,
say in EEG alpha-​band power, may reflect differences in the number of neurons
engaged in the respective cognitive process, but it may also represent a combination of
differences in active population size, amount of dendritic engagement at each neuron,
orientation of neurons involved, and temporal synchronization of the post-​synaptic
events. Neural mass power in a given frequency band is therefore difficult to map dir-
ectly onto a physiological or cognitive concept, emphasizing the need for research that
links measures of oscillatory brain activity to robust cognitive or behavioral processes,
across different levels of observation (i.e., from single neurons to large populations).
In addition to measuring spectral power, researchers may use approaches that capit-
alize on additional spectral information, often the phase of the signal. Many algorithms
 FROM NEURAL OSCILLATIONS TO COGNITIVE PROCESSES    45

exist for quantifying the similarity of the phase across different observations, such as
experimental trials, time points, or channels. The resulting metrics are referred to as
indices of phase-​locking or phase coherency. These variables are often used to estimate
the strength of oscillatory interactions across recordings sites (e.g., inter-​site phase
locking, often considered a proxy of connectivity), the stability of the temporal pro-
file of oscillations across repeated trials (e.g., phase-​locking value), or the interactions
between different frequencies within or across recordings sites (e.g., phase-​amplitude
coupling (Chapter 20). Thus, a wide range of hypotheses and, increasingly, formal com-
putational models of neurophysiological processes can be tested using these different
variables, each of which may reflect entirely different facets of oscillatory brain activity.
Later in this chapter we present examples for using these markers across a wide range of
research questions in cognitive neuroscience.

3.5  What’s in a Band? the Traditional

Demarcation Of Oscillatory Events
By Frequency

In the many decades since Berger’s and many others’ discoveries, brain oscillations have
been traditionally divided into frequency bands in the 1–​4 Hz range (delta), 4–​8 Hz
(theta), 8–​12 Hz (alpha), 12–​30 Hz (beta), and >30 Hz (gamma), with some variability in
the demarcation of these bands. These frequency bands have been consistently observed
at the level of spike trains, local field potentials, and EEG/​MEG, making them apparent
in multivariate analyses and meta-​analyses across studies and even species (Lopes da
Silva, 1991). The peak frequency in each of these bands is similar across bats, mice, rats,
cats, dogs, horses, dolphins, macaques, and humans, despite the range of brain size and
axon length across these species (Buzsáki et al., 2013). Given this phylogenetic stability, it
has been suggested that the traditional frequency bands (and perhaps their logarithmic
distance from one another) represent fundamental mechanisms underlying specific
neurocomputations and behaviors (Steriade et al., 1990). Klimesch (1999) highlights
the variability and task-​dependency of these frequencies, however, with examples for
gamma-​like oscillations in the traditional beta band, and overlap between alpha and
beta band oscillations, along with pronounced inter-​individual differences. Similarly,
limitations of assigning specific functional roles to oscillations in one of the traditional
bands have been made apparent by phenomena in which oscillations continuously
transition from one traditional band into another during the same task (Donner &
Siegel, 2011).
Some of the stated confusion about these observations may be reflective of
researchers’ desire to equate oscillatory activity in one frequency range with a cat-
egory of cognition of behavior, defined in the language of cognitive psychology, such
46    ANDREAS KEIL and NINA THIGPEN

as “alpha-​blocking reflects attention”, “gamma reflects feature binding”, and similar

notions. Such interpretations, which may be seen as examples for the problematic
approach of reverse inference (Poldrack, 2011), have been considered less fruitful than,
and have increasingly been replaced by, research aiming to characterize specific oscilla-
tory correlates of a specific, quantifiable, behavior. With the advent of neurostimulation
and neuromodulation techniques such as transcranial magnetic stimulation (TMS),
direct current stimulation, neurofeedback, etc., recent research has also attempted to
establish the causal role of oscillatory brain activity for specific cognitive and behavioral
processes (Herrmann et al., 2016; Chapter 22 this volume). To understand how oscilla-
tory activity relates to cognition, it is helpful to consider the rich neurophysiological lit-
erature based on work in experimental animals. This body of work has begun to outline
neuromechanistic accounts for the emergence of brain oscillations and their relation to
behavior. Importantly, these studies help to overcome the focus on one spatial scale (e.g.
oscillations at membranes, in action potential, in circuits, or areas), and instead describe
the rhythmic interplay between these levels of observation.

3.6  Oscillations at Different Levels of

Observation: From Single Neurons to
Neural Populations

Since the inception of brain electrophysiology, researchers measuring electrical

potentials from individual neurons, or from groups of neurons, have noted the oscil-
latory character apparent in neural time series (Bernstein, 1868; Marrazzi & Lorente
de No, 1944). Spatial scales of these observations are typically categorized into the
microscale, mesoscale, and macroscale, where microscale refers to processes at single
neurons, mesoscale to small functional units such as cortical columns, and macroscale
to population responses of several tens of thousands of neurons (Nunez & Srinivasan,
2006). Recent work increasingly focused on interactions between oscillations across
these levels of observation, for example, by linking the rate of action potentials (spikes)
to oscillatory events at different spatial scales, and at different temporal rates (Lisman
& Jensen, 2013; Schroeder & Lakatos, 2009). Although a comprehensive review of this
literature is outside the scope of this chapter, a number of neurophysiological and com-
putational principles of oscillatory processes within and across different scales are now
widely accepted. These principles are discussed next.
At the core of many theories of brain oscillations is the observation that time
series of action potentials (i.e., spike trains) tend to contain bursts of spikes. A burst
represents a rapid sequence of action potentials, a group in time, which may vary in
temporal rate, providing one potential source of oscillatory pace making. The frequency
at which bursts occur (i.e., the inter-​burst interval) has also been shown to relate to
 FROM NEURAL OSCILLATIONS TO COGNITIVE PROCESSES    47

neurophysiological and behavioral processes, thus providing a second way for action
potentials to temporally organize downstream neural—​and ultimately behavioral—​
processes (Gütig, 2014). Such a temporal organization may be propagated in space if
neurons act as coupled oscillators, facilitating specific phase relationships among
the units of a functional network of connected neurons. Many such “coupled oscil-
lator” models of neural oscillations exist, aiming to explain how temporal signatures
are shared among populations of neurons (Moon et al., 2015; Naze et al., 2015). Recent
empirical work as well as work in computational modeling has converged to suggest
that such coupling involves not only action potentials but a range of mechanisms that
also involve subthreshold and synaptic events, along with potential changes at glia cells
(Buzsáki et al., 2012).
It is now well established that spike timing, that is, the timing of action potentials,
is related to synaptic oscillations measured by local field potentials, likely both driving
and being driven by these synaptic fields. This research has also demonstrated that
subthreshold oscillations at membranes and post-​ synaptic potentials constrain
the spiking rate of individual neurons and may also play a role in coordinating the
firing among different neurons (Mazzoni et al., 2010). This is important because it
demonstrates the interplay of all-​ or-​
nothing neuronal communication and post-​
synaptic events, opening avenues for research that identifies the convergent versus
complementary roles of oscillations at different levels, within and across neurons, in be-
havioral and cognitive processes.
Research in human participants has increasingly made use of intracranial data
obtained from patients under pre-​surgical evaluation for neurological disorders, with
implanted sensor arrays (Parvizi & Kastner, 2018). In these studies, one striking dis-
crepancy arises between levels of observation regarding the frequency content of
intracranial recordings vis-​à-​vis extracranial recordings. Intracranial recordings, for
example, electrocorticogram (ECoG) data, tend to contain robust high-​frequency
oscillations (Osipova et al., 2008), which are small and less reliably observed in extra-
cranial recordings such as EEG or MEG (Yuval-​Greenberg et al., 2008). This salient
difference between intracranial and scalp recordings may reflect the orders of magni-
tude difference in the summation of electrical potentials that comprise each signal. For
example, the local field potential recorded from an intra-​cranially sensor embedded
in cortical tissue is thought to measure the extracellular electrical fluctuations of a few
hundreds to thousands of neurons, while EEG data is thought to require synchrony
across a few millimeters of cortex before any fluctuations are observed on the scalp
(Nunez & Srinivasan, 2006). Based on simulations and in vitro studies, some authors
suggest that postsynaptic changes at dendritic trees of 40,000 to 100,000 pyramidal cells
are required to cause EEG changes in the 1–​2 microvolt range—​if the dendrites of these
neurons are oriented in parallel, generating an open electric field, required for extra-
cranial measurement. By contrast, ECoG and LFP data are thought to reflect activity
in differentially oriented cells, including contributions from interneurons, pyramidal
cells, and glial cells (Buzsáki et al., 2012). Thus, EEG oscillations reflect activity in a more
specific subset of neurons than ECoG and LFP but integrated over a wider distribution
of space.
48    ANDREAS KEIL and NINA THIGPEN

Inter-​scale oscillatory interactions also depend on the strength of the sensory

input. Studies in macaque monkeys have shown that increasing the luminance con-
trast of a visual stimulus similarly affected spike trains, local field potential in intra-
cranial electrodes over V1, and MEG signals, up to a contrast level of 60%. However,
at levels above 60% luminance contrast, nonlinearities were observed: The MEG
gamma continued to increase but the LFP gamma saturated, and in fact decreased with
increasing contrast. Only the gamma frequency recorded at the macroscale (i.e., MEG,
which continued to increase at luminance contrast levels above 60%) was correlated
with perceptual performance (Hadjipapas et al., 2015). This is an example of how tem-
poral summation across a wide spatial distribution (reflected in MEG recordings)
reflects different activity from spikes or the LFP. Finally, it is worth noting that the rela-
tionship between spatial integration across neurons, measured through correlation of
spike counts between neurons, and EEG power has also been shown to be nonlinear,
such that higher spike-​count correlations predict high and low EEG amplitude, while
low spike-​count correlations are observed during time windows where intermediate
EEG amplitudes are observed (Snyder et al., 2015).
In summary, although systematic relations exist between neural oscillations at
different levels of observation, it is not advisable to test hypotheses regarding one
level of observation by measuring at another level. Inter-​scale interactions however
provide a promising area of research for understanding the neuromechanistic role of
neural oscillations. They also represent an important source of constraints for compu-
tational models of brain function, in turn to be tested by multi-​scale empirical studies.
Researchers studying macroscopic oscillations in humans may generate more precise,
and more mechanistic hypotheses regarding these measurements when considering re-
search at the micro-​and mesoscale. Thus, by manipulating the nature of the stimulus,
for example, its intensity or temporal frequency, specific mesoscopic circuits can be
challenged and experimentally isolated, dramatically increasing the neurophysiological
specificity of extracranial signals such as EEG or MEG. This technique is increasingly
used and further emphasizes the benefits of developing hypotheses for human re-
search based on the animal model. However, as is the case with the majority of imaging
modalities (Boynton, 2011), not all robust and neurophysiologically meaningful metrics
of oscillatory brain activity are linearly related to the behavioral indices measured in the
same task. This long-​standing conundrum in cognitive neuroscience research may also
be explained by the non-​overlap of processes observed at different spatial scales, further
highlighting the importance of multi-​scale studies.

3.7  Brain Oscillations and their Role

in Behavior: A Conceptual Overview

From its inception, the study of brain oscillations and their role in cognition has been
multi-​disciplinary, with a strong emphasis not only on physiological measurements,
 FROM NEURAL OSCILLATIONS TO COGNITIVE PROCESSES    49

but also on mathematical analysis and modeling, as well as behavioral observations.

The resulting literature can be daunting for its extent, scope, and methodological com-
plexity. Therefore, readers may benefit from a brief overview of key concepts, providing
scaffolding for integrating current findings, and context for making sense of the wide
range of theoretical notions related to oscillatory brain dynamics.

3.7.1 Hebbian Cell Assemblies and Brain Oscillations

Adapting behavior based on experience is arguably one of the most essential functions
of the human brain. Donald Hebb’s (1949) classical theory in conjunction with theories
of oscillatory brain activity are often used to account for this function. In these views,
the brain’s ability to form oscillatory networks comprising groups of neurons depends
on a principle of association known as Hebb’s second rule. This rule postulates that the
synchronous activation of two cells or cell systems produces a facilitation of excitatory
connections between them such that in the future activity of the one element produces
a residual excitation of the other. A cell assembly refers to a distributed network of
neurons that are bound together by the temporal synchronization of their sub-​threshold
membrane potentials and/​or firing rates (Singer et al., 1990). Importantly, neuronal
cell assemblies may be synchronized at local scales, separated in the millimeter range,
but also at distances that span distinct cortical lobes (Pulvermuller & Fadiga, 2010).
Theoretical and methodological advances in the neurosciences, including the discovery
of long-​term potentiation (Bliss & Lømo, 1973), whereby the responses of a post-​synaptic
cell are facilitated by oscillatory stimulation, have largely validated Hebb’s notion, while
also offering more detailed analyses of the physiological substrates that underlie the for-
mation of oscillatory networks through experience (Nadel & Maurer, 2018).
Today, the ability of neurons to form networks based on coincidence of firing patterns
can be explained at the molecular level (Andersen et al., 2017; Harris & Littleton,
2015), for example by reference to the unique properties of NMDA (N-​Methyl-​D-​
Aspartate) and AMPA (α-​amino-​3-​hydroxy-​5-​methyl-​4-​isoxazolepropionic acid) glu-
tamate receptors (Henley & Wilkinson, 2016). Additional physiological mechanisms for
coincidence-​based network formation have been elucidated, such as the dual sensitivity
of L-​type calcium channels to back-​propagating action potentials and pre-​synaptic exci-
tatory currents (Nanou & Catterall, 2018). Importantly, neuronal cell assemblies may be
synchronized at local scales, separated in the millimeter range, but also at distances that
span distinct cortical lobes. Hebb’s original suggestion (1949) held that reverberating
activity within cell assemblies constituted a transient percept or memory trace that can
become more consolidated with the passage of time. The concept of reverberation, by
providing a metaphorical notion of how oscillatory phenomena arise, has stimulated
a large body of work, which in turn has identified a plethora of mechanisms for net-
work organization and oscillatory brain activity, beyond temporal synchrony (Morone
et al., 2017).
50    ANDREAS KEIL and NINA THIGPEN

3.7.2 Complex System Theory and Nonlinear Dynamics

With the advent of powerful digital computers, conceptual frameworks that had been
elusive because of their computational complexity, became increasingly popular.
One group of concepts with strong implications for the study of oscillatory brain
activity drew from theories of complex systems (“chaos theory”) and nonlinear dy-
namics (Elbert et al., 1994). Applied to brain oscillations, these approaches de-
scribe fluctuations among different elements, often in so-​called non-​equilibrium
conditions, where some form of energy or environmental constraint affects a com-
plex, macroscopic system (Fuchs et al., 2000). Research conducted using this frame-
work demonstrates that dynamics in complex systems may be characterized by the
interaction of some quantifiable and continuous variable, and the effect that it exerts
on the collective system state. In one flavor of nonlinear system research, the col-
lective system state is measured by one dominant parameter, the order parameter,
taken to index the high-​level formulation of the system (Haken et al., 1985), whereas
variables that can change the nature of the system dynamics are referred to as the
“control parameter”. When the control parameter reaches a particular value, the
macroscopic system undergoes a phase transition and acquires a qualitatively novel
set of properties. Once it is established, the new high-​level order parameter may “en-
slave” the lower components—​a phenomenon demonstrated in everyday life when
the clapping of a large audience determines the clapping frequency of individual
members in the audience.
Metrics of nonlinear dynamics such as largest Lyapunov coefficients or the
Grassberger–​Procaccia dimension (Elbert et al., 1994) have been used to characterize
neural time series, aiming to capture dynamics above and beyond the periodic, sine-​
wave-​like, and stationary cycles that are assumed by linear methods such as the Fourier
transform. In addition, approaches inspired by nonlinear systems research have made
important contributions by emphasizing the role of oscillatory phase, and by providing
tools for visualizing and analyzing nonlinear interactions among and between
populations of neurons (Breakspear, 2017). Currently, some of these methods, such as
phase space portraits, experience a renewed popularity and are applied in studies of
motor preparation, perception, and awareness (Baria et al., 2017).

3.7.3 Spatio-​Temporal Patterns and Travelling Waves

Although oscillatory patterns are most easily visualized as changes in magnitude over
time, researchers have recognized for a long time that the spatial dimension of oscil-
latory activity also plays a crucial role in characterizing oscillatory processes. Walter
Freeman, one of the first researchers to explore this topic in depth, established a math-
ematical model in which spatio-​temporal patterns consisting of mesoscopic “phase
cones”—​ moving two-​ dimensional Gaussian fields with systematically changing
 FROM NEURAL OSCILLATIONS TO COGNITIVE PROCESSES    51

oscillatory phase—​represent the nature of an odorant presented to the rabbit olfactory

system (Freeman, 1991).
Current research has addressed this topic using refined mathematical tools and high-​
resolution electrophysiological recordings. As a result, traveling oscillatory waves of
neural activity have been found at many different frequencies, across wide spectrum of
brain areas. Spreading over cortical or subcortical tissue as time passes, these waves have
been related to many different behaviors, ranging from sensory to motor processing
(Muller et al,, 2018).

3.7.4 Oscillatory Hierarchies
Many prominent models of the functional role of oscillatory brain activity have
considered interactions between oscillations at different temporal rates. A classical
model of working memory proposed that hippocampal neurons encode memory con-
tent using timed gamma-​frequency bursts, which in turn receive their temporal struc-
ture from the phase of low-​frequency oscillations in the theta band (Lisman & Jensen,
2013). This account has received substantial support as well as extension and refinement
based on computational and empirical studies.
In another widely recognized account, systematic relations across different
frequencies are used by the brain to organize the interplay between behavioral and cog-
nitive processes—​the concept of “active sensing” emphasizes the active aspect of per-
ceptual sampling (Schroeder et al., 2010). Examples for such active sensing include
whisking and sniffing in rodents and saccadic sampling of visual scenes in primates. In
all these cases, perception is tightly linked to the motor activity that causes the stimu-
lation of sensory receptors as it initiates inflow of information through the sensory
pathways. Each afferent volley of information meets ongoing brain states hypothesized
to be partly determined by past experience and current goals, as well as the physiological
properties of the tissue. In these hypothetical hierarchies, neural oscillations at lower
frequencies (such as alpha or theta, 4–​8 Hz as defined in adults) may provide temporal
structure for higher-​frequency phenomena, for example, beta-​(13–​30 Hz) or gamma-​
band (>30 Hz) oscillations. In a similar vein, studies in macaque monkey visual cortex
have suggested that high-​amplitude gamma oscillations more likely occur during spe-
cific phases of the alpha cycle (Bonnefond & Jensen, 2015). These findings have been
taken to indicate that alpha phase represents the excitability of the neural tissue, pos-
sibly aligning excitability of sensory cortices with other events such as expectancy or
memory-​driven signals (Kizuk & Mathewson, 2016; Mathewson et al., 2011).

3.7.5 Synchrony and Oscillatory Communication

Most contemporary models of oscillatory brain activity emphasize the potential
of rhythmic processes for organizing neural activity in time and space and thus for
providing a mechanism for integrative coding across spatially separated units (neurons,
52    ANDREAS KEIL and NINA THIGPEN

columns, areas; Buzsáki & Draguhn, 2004). In earlier theories of oscillatory activity,
temporal synchrony was seen as the crucial feature for coding information that belongs
together but is distributed between different neurons or populations of neurons (von
der Malsburg & Buhmann, 1992). This notion is readily aligned with the Hebbian per-
spective discussed earlier, adding to the appeal it has held for many decades. At the
microscopic and mesoscopic level, synchronous firing in local circuits, especially in the
gamma frequency range, has been proposed as a mechanism for cognitive processes
as diverse as gestalt perception, predictive coding, motor preparation, and selective
attention (Bauer et al., 2014; Keil et al., 2001).
Extending the concept of synchrony to long-​range communication and integration, re-
cent work focuses on the interaction between local and inter-​area (long-​range) synchrony,
increasingly on oscillatory interactions across different frequencies (Chapter 20). For in-
stance, oscillatory activity in the theta range (4–​8 Hz) has been traditionally hypothesized
as a potential mechanism for transmitting information between distant brain areas
(Klimesch et al., 2005; Sarnthein et al., 1998). Empirical evidence in rodents, cats, and non-​
human primates supports this notion, with theta oscillations characterizing long-​range
signaling in large-​scale networks, including the hippocampus, the amygdaloid, complex,
and extensive cortical areas, during tasks that involve learning and memory (Popescu
et al., 2009). Similar findings exist for alpha-​band oscillations, discussed now as carriers
of prediction signals from higher-​order to sensory cortices. Importantly, the concept of
synchrony in the context of these inter-​area communications has been extended beyond
zero-​lag co-​activation at different sites, and has instead identified inter-​area interactions
by the extent to which the phase lag between two recording sites is consistent over time,
that is, so-​called inter-​site phase locking (Brovelli et al., 2004).
Together, local-​and inter-​area oscillations hold great promise for informing and
constraining network-​based models of human cognition. Because of their compati-
bility with findings obtained in the animal model, and the ability to relate neural activity
across different levels of observation, indices of oscillatory brain activity also represent
powerful dependent variables in cognitive neuroscience studies. The following example
illustrate these benefits by selectively reviewing examples for such studies and address
processes of perception, attention, learning, and memory.

3.8  Example 1: Alpha-​Band

Changes During Perception and
Selective Attention

As discussed, oscillatory activity in the alpha frequency band is typically observed

during stimulus-​absent conditions such as resting or sitting with the eyes closed (Berger,
1929; Pfurtscheller, 1989). Many early studies established the robust relationship be-
tween alpha power changes and perceptual tasks, demonstrating that high-​alpha states
tend to be blocked following events such as the opening of the eyes, the presentation
 FROM NEURAL OSCILLATIONS TO COGNITIVE PROCESSES    53

of a visual cue, or the direction of attention toward a salient visual stimulus (Adrian &
Matthews, 1934; Klimesch, 1999; Pfurtscheller et al., 1996). Low levels of alpha power to-
gether with alpha phase also predict heightened performance in near-​threshold detec-
tion tasks, where participants report weak sensory events (Mathewson et al., 2011; Weisz
et al., 2014). This evidence supports a long-​held notion that scalp-​recorded alpha activity
reflects a cortical state in which little sensory information is received (Pfurtscheller,
1992), mediated perhaps via a thalamic gating mechanism (Steriade et al., 1990).
Other findings are consistent with this notion.: Presenting a cue that directs attention
to one hemifield prompts reduction of alpha power in the contralateral hemisphere
(Foxe & Snyder, 2011). By contrast, alpha power over ipsilateral sensors (representing
the ignored hemifield) remains stable (Thut et al., 2006), or increases (Kelly et al., 2006),
taken to suggest suppression of irrelevant information. This interpretation is consistent
with research examining attention to target items embedded in a rapid serial visual pres-
entation stream of distractors. Accurate identification of rapidly presented targets amid
non-​targets is associated with higher pre-​target alpha power (Petro & Keil, 2015). Thus,
high alpha power may index behavioral states that benefit performance by reducing the
processing of irrelevant sensory information (Klimesch et al., 2006). Importantly, these
attention-​related changes in alpha power are associated with faster and more accurate
responses for the task, suggesting that they possess a functional role in the active selec-
tion of target stimulus features (Foxe & Snyder, 2011).
A further role of alpha oscillations during attention tasks is under consideration in
the context of predictive coding. This has become a current topic in cognitive neuro-
science. Increased alpha power and heightened inter-​site phase-​locking during target
anticipation are proposed as a mechanism that optimizes the temporal organization of
sensory processing and thus facilitates the sensory analysis of expected, task-​relevant,
visual stimuli (Samaha et al., 2015). Several of the different proposed functions of alpha-​
band oscillations during perception and attention are not mutually exclusive and have
given rise to the idea that the alpha frequency is used by a wide range of neural processes,
in the service of different cognitive and behavioral goals (Chapter 10).

3.9  Example 2: Learning and Memory

Work in the animal model abundantly demonstrates that associative learning induces
Hebbian plasticity in widely distributed brain networks, both sub-​cortical and cor-
tical (Pape & Paré , 2010). These memory formation processes can be conceptualized as
changes in the neural communication between nearby and distant brain loci, which dy-
namically sculpt neural signaling pathways at multiple levels of analysis. Recent findings
suggest that neuronal oscillations are ideally suited to support the flexible formation
of such network-​level changes in neural architecture (Popescu et al., 2009), including
those that support the acquisition and extinction of fear memories (Paré et al., 2002).
In addition, computational models using simulated agents in artificial evolutionary
environments show that network oscillations provide a fitness advantage, insofar as
54    ANDREAS KEIL and NINA THIGPEN

they help to promote rapid switches in perception and attention (Heerebout & Phaf,
2010). Oscillatory signals may therefore play an important role in the critical changes
that occur when a previously innocuous stimulus acquires relevance for controlling
behavior (Headley & Weinberger, 2011). At the level of neuronal populations, the as-
sociative principles that guide the formation of a newly acquired memory (e.g., the
association between light and electric shock during classical fear conditioning) must ef-
fectively coordinate activity between neural representations of the conditioned stimuli
(the light) and the systems that code biological value of the unconditioned event (the
shock). Although conditioning-​induced changes in neuroarchitecture and function
occur on multiple spatio-​temporal scales (Maren & Quirk, 2004), ranging from in-
dividual neurons to cortical sheets, and from minutes to days, the notion of a cell as-
sembly (Hebb, 1949) provides the necessary conceptual framework for bridging across
these multi-​scale phenomena. Oscillatory synchronization between distributed neur-
onal assemblies in specific frequency bandwidths appears to represent a highly plaus-
ible substrate for synaptic plasticity transfer, that is, storing newly acquired memories
as changes in synaptic weights (Paré et al., 2002). In particular, increased large-​scale
synchrony between subcortical and cortical networks may be crucial in producing the
experience-​dependent changes in the representation of fear-​conditioned cues.
Another example is provided by a series of studies conducted by Walter Freeman and
his colleagues (reviewed in Skarda & Freeman, 1987) in the olfactory system of the rabbit.
The basic paradigm involves the placement of an 8 × 8 electrode grid onto the olfactory
bulb in order to record electrocorticography (ECoG) signals associated with different
odorant stimuli. To begin with, each odorant elicits a pattern of wave activity that appears
as aperiodic noise with variability across trials. However, after the animal learns to asso-
ciate an odor with a motivationally relevant outcome, for example, the delivery of food or
aversive tactile stimulation, neural activity at the olfactory bulb undergoes a state tran-
sition whereby the odor comes to elicit a discriminant spatiotemporal pattern of ampli-
tude across the electrode grid array. The learning-​related establishment of a new global
response pattern then acts to enslave the output of individual neurons (Freeman, 1994).
Freeman interprets such selective changes in spatiotemporal amplitude as embodying
the affective meaning of a stimulus for the animal, with meaning changing in accordance
with the momentary relevance of a stimulus (e.g., an animal responds differently to an
odorant associated with food once it is fed to satiety). A mechanism for stimulus selective
changes in the output of olfactory neurons is provided by alterations of synaptic effi-
ciency and neuropil structure, guided by Hebbian principles of association.

3.10  Example 3: Generating Brain

Oscillations by Periodic Stimulation

Rhythmic modulation of stimulus contrast or luminance at a constant rate over a period

of time evokes oscillatory field responses in the visual cortex at the same frequency
 FROM NEURAL OSCILLATIONS TO COGNITIVE PROCESSES    55

as the modulation rate of the stimulus, often including higher harmonics—​integer

multiples of the stimulation frequency. The harmonic responses depend on the duty
cycle, the stimulation method, and the complexity of the stimulus array (Norcia et al.,
2015). In the visual domain, large-​scale frequency-​following responses evoked by peri-
odic stimulation are referred to as steady-​state visual evoked potentials (ssVEPs). These
driven oscillations are best quantified in the frequency or the time-​frequency-​domain,
where they can be reliably separated from noise and quantified as the spectral power in
a narrow frequency range. Several studies have demonstrated that the flicker-​evoked
ssVEP is predominantly generated in the primary visual and to some extent in adjacent,
higher order, cortices (Müller et al., 1997; Wieser & Keil, 2011). Interestingly, a number of
studies have suggested different neural sources for the fundamental frequency and the
higher harmonics, although these findings await replication and further interpretation
(Kim et al., 2010). Generally, the ssVEP can easily be driven in lower-​tier (retinotopic)
visual cortices using high-​contrast luminance modulation governed by a rapid square-​
wave (on-​off) stimulation. For studies of higher-​order cognitive processes, however,
researchers may periodically modulate specific stimulus dimensions other than lumi-
nance or contrast, while holding these lower-​level properties constant (or varying them
randomly). Such an approach evokes ssVEPs in brain areas sensitive to the particular
feature or stimulus dimension of interest (Giabbiconi et al., 2016; McTeague et al., 2015).
For example, stimulation techniques have been used that isolate the ssVEP response to
face identity generated in higher order visual areas such as the fusiform cortex (Rossion
& Boremanse, 2011).
A related issue often discussed in the context of driven oscillations is the question to
what extent ssVEPs can be regarded as a linear superposition of transient ERPs, or al-
ternatively represent a nonlinear response that possesses properties beyond the linear
combination of individual brain responses (Capilla et al., 2011; Regan, 1989). A similar
current debate exists between the view that driven oscillations represent a temporal
alignment or “entrainment” of oscillations that are already present spontaneously, and
the alternative view that driven oscillations represent newly shaped waveforms, on
top of ongoing oscillations (Keitel et al., 2019). Initial studies in the field have argued
that observing higher harmonics when using harmonically simple (e.g., sinusoidal)
modulation of luminance or contrast is considered evidence of nonlinearity, thus
providing evidence for perspectives emphasizing resonance and entrainment (Regan,
1989). Subsequent work has examined the extent to which ssVEPs can be explained by
properties of transient ERPs, and has observed that especially with square wave (on-​
off) modulation, ssVEPs may be modeled by transient ERP features with satisfactory
accuracy (Capilla et al., 2011), providing evidence for a superposition perspective. The
interpretation of these findings is not straightforward, however, because transient brain
responses themselves represent a combination of individual trials that vary greatly in
latency (phase) and amplitude, limiting their use for unambiguously explaining the
generating mechanism underlying ssVEPs. In line with this notion, other studies have
reported that the ssVEP amplitude is poorly predicted by single-​trial power changes
at the driving frequency, but is best predicted by locking of the single-​trial phase with
56    ANDREAS KEIL and NINA THIGPEN

5
.4 cd/m2
–5
μV2
5 .7
4.9 cd/m2
–5 .2
5
70.7 cd/m2
–5
–200 0 200 400 600
Time (ms)

Figure 3.3  Effects of stimulus intensity on inter-​trial phase locking of driven oscillations.
Participants viewed sinusoidal gratings flickering at 15 Hz. Gratings varied in luminance, with
40 low-​luminance trials (.4 cd/​m2), 40 medium-​luminance trials (4.9 cd/​m2), and 40 high-​
luminance trials (70.7 cd/​m2). Each colored line represents one single trial from sensor Oz. Inter-​
trial phase locking increases with increasing luminance, whereas the overall magnitude of the
signal within the single trials does not change. The increased phase-​locking is associated with
increases in 15-​Hz power of the trial-​averaged signal, as depicted in the topographies shown on
the right.
Data from Thigpen et al., 2018.

the driving stimulus across trials (Moratti et al., 2007). Figure 3.3 shows an example
of this phenomenon as it interacts with stimulus intensity, demonstrating increasing
phase alignment of single trial EEG traces with increasing stimulus contrast. The de-
bate of entrainment versus superposition perspectives is ongoing, and ssVEPs (be-
cause of their known frequency and pronounced signal) are well suited for examining
competing hypotheses regarding the interaction of ongoing oscillations and sensory
events.

3.11  Conclusions and

Outlook: Elements of a Conceptual
Framework of Oscillatory
Brain Activity

This chapter aimed to illustrate how studies of oscillatory brain activity provide rich
opportunity for testing hypotheses relating brain function to cognitive processes.
Measuring oscillatory activity during cognitive task performance opens avenues into
developing and testing neuromechanistic accounts of some of the most central building
blocks of human behavior and experience. In conclusion, we discuss challenges for this
field moving forward, and provide key concepts towards an integrative framework of
oscillatory brain activity in the study of cognition.
 FROM NEURAL OSCILLATIONS TO COGNITIVE PROCESSES    57

3.11.1 Oscillations as Epiphenomena, and Other Challenges

A long-​standing debate in the field centers around the question to what extent brain
oscillations possess a primary functional role, as opposed to arising from other non-​
oscillatory processes as a by-​product, or epiphenomenon (Buzsáki & Draguhn, 2004).
For example, does a spike burst represent an oscillation, or a mere sequence of individual
events? The question of functional relevance has been difficult to address because the
required ground truth, for example, “there is an oscillation at 11.5 Hz”, is often something
the researcher wishes to establish, rather than something that can be used as a premise.
Current research leverages causal manipulations such as electric micro-​stimulation in
experimental animals, synchronized to the phase of ongoing oscillations to determine if
altering a robustly measured ongoing oscillation affects the animal’s behavior in a system-
atic fashion (Tehovnik et al., 2006). Such data, challenging to obtain because it requires
predicting the phase of the oscillatory signal over time, would present direct evidence
supporting a causal role of oscillatory activity. Other approaches underway in several
laboratories use similar causal manipulation, as well as driven oscillations, to address this
question.
Additional challenges for researchers using metrics of oscillatory activity are rooted
in the fact that highly complex data arrays that may contain sensors, conditions, time
points, trials, etc., tend to get further inflated when adding a frequency dimension. This
triggered attempts towards using multivariate methods, machine learning methods, or
other approaches, all aiming at reducing the dimensionality of the data without losing
information that is relevant to addressing the empirical question of interest]. The
resulting methodological diversity has not only been enriching for the field, but also
often prevented direct comparisons of results from different laboratories, and thus has
been regarded as one obstacle towards reproducing and replicating findings. Ongoing
efforts to improve the training of next-​generation researchers are expected to address
this issue, by adding computer science, digital signal processing, and advanced statistics
to undergraduate and graduate curricula. Current trends of expressing hypotheses in
terms of mathematical models that can be explicitly tested and gradually improved are
crucial in this respect and are readily applied to indices of oscillatory brain activity. As
with many other fields in the biomedical sciences, (re-​)establishing a culture of knowing
the history of the field, of systematic and programmatic research, and of applying
rigorous methods is an obvious goal in research on brain oscillations. The following key
concepts summarize areas of conceptual progress in the field and provide avenues for
future research.

3.11.2 Oscillations as Drivers of Plasticity

Brain oscillations are widely considered reflections of network activity, but growing
support is also evident for their role in mediating neuroplastic changes that result in
58    ANDREAS KEIL and NINA THIGPEN

the formation of networks, local and distributed. The high signal-​to-​noise ratio of many
frequency-​domain measures and the resulting potential for trial-​by-​trial analyses may
be leveraged to quantify neural changes that occur over the course of an experimental
session (McTeague et al., 2015). Such an approach complements trial averaging, which
is still the dominant approach in cognitive neuroscience, and sheds light on adaptation
dynamics and plasticity in response to the experimental situation, processes of high
ecological validity and with substantial clinical relevance.

3.11.3 Oscillations as Pacemakers for Cognition

and Behavior
A substantial body of research addresses the role of low-​frequency oscillatory brain
activity for embedding and organizing neural, cognitive, and motor processes.
Cornerstone results from this line of research include that perceptual and motor per-
formance varies in a rhythmic fashion: recurrent time windows exist, in which cogni-
tion and motor action can be optimally initiated and executed, interspersed with time
windows of reduced performance (VanRullen, 2016). Relating these behavioral rhythms
to brain oscillations holds promise for advancing models of the temporal organization
of cognitive processing.

3.11.4 Oscillations as Carriers of Communication Signals

Several chapters in this volume address the potential of oscillatory activity in lower-​
frequency bands such as alpha or theta for integrating information in space, and for
mediating the neural communication between units, local and distal (Chapters 9, 10,
and 20). Establishing the functional role of oscillatory phenomena in neural commu-
nication, across levels of observation, will greatly benefit from emerging multimodal
and multi-​species methods, including new recording and stimulation techniques,
well suited to cross-​validate observations and combine measurement and stimulation
approaches (Adesnik, 2018).

3.11.5 Oscillations as Organizing Principles

for Regulating Complex System States
From a perspective of complex systems, a major function of brain oscillations lies in
representing macroscopic states that emerge from systematic nonlinear interactions
between units at the microscopic and mesoscopic level. Increasingly, computational
models exist, which make quantitative predictions for how these different levels interact.
For example, in-​silico studies have leveraged the steady increase in computing capacity
 FROM NEURAL OSCILLATIONS TO COGNITIVE PROCESSES    59

to offer alternative models of inter-​scale nonlinear interactions, which may provide crit-
ical predictions to be tested in empirical work (Neymotin et al., 2013).

3.11.6 Oscillations as Substrate of Representations

in Perception and Memory
Finally, oscillations have been long regarded as a candidate mechanism for coding
percepts and memories. As discussed, oscillatory dynamics provide a unifying way for
describing diverse mechanisms involved in these cognitive processes, including the
spatio-​temporal dynamics and plastic changes within and between neuronal ensembles.
They offer a parsimonious account for integrating activity across distributed functional
units without invoking the widely criticized top-​down versus bottom-​up dichotomy (Awh
et al., 2012). Current developments in cognitive science and experimental psychology to
increasingly rely on computational modeling will facilitate the integration of experimental
observations from the level of brain oscillations to the level of task performance.
In summary, brain oscillations have opened exciting new avenues in the study of cog-
nitive and behavioral processes. Beyond mere measurements of power in a specific fre-
quency band, recent developments have provided the research community with tools
that allow us to visualize the dynamic interplay among different frequencies, quantify
the role of phase in coding information, and assess the rhythmic interactions between
distal brain areas. Together with rapid theoretical and computational advances, these
tools will continue to provide unique insights into brain systems dynamics and their re-
lation to behavior and experience.

References
Adesnik, H. (2018). Cell type-​specific optogenetic dissection of brain rhythms. Trends in
Neurosciences, 41(3), 122–​124. https://​doi.org/​10.1016/​j.tins.2018.01.001
Adrian, E. D. & Matthews, B. H. (1934). The Berger rhythm: Potential changes from the oc-
cipital lobes in man. Brain, 57(4), 355–​385.
Andersen, N., Krauth, N., & Nabavi, S. (2017). Hebbian plasticity in vivo: Relevance
and induction. Current Opinion in Neurobiology, 45, 188–​192. https://​doi.org/​10.1016/​
j.conb.2017.06.001
Awh, E., Belopolsky, A. V., & Theeuwes, J. (2012). Top-​down versus bottom-​up attentional con-
trol: A failed theoretical dichotomy. Trends in Cognitive Sciences, 16(8), 437–​443. https://​doi.
org/​10.1016/​J.Tics.2012.06.010
Baria, A. T., Maniscalco, B., & He, B. J. (2017). Initial-​state-​dependent, robust, transient
neural dynamics encode conscious visual perception. PLOS Computational Biology, 13(11),
e1005806. https://​doi.org/​10.1371/​jour​nal.pcbi.1005​806
Başar, E. & Güntekin, B. (2012). A short review of alpha activity in cognitive processes and
in cognitive impairment. International Journal of Psychophysiology, 86(1), 25–​38. https://​doi.
org/​10.1016/​j.ijpsy​cho.2012.07.001
60    ANDREAS KEIL and NINA THIGPEN

Bauer, M., Stenner, M.-​P., Friston, K. J., & Dolan, R. J. (2014). Attentional modulation of alpha/​
beta and gamma oscillations reflect functionally distinct processes. Journal of Neuroscience,
34(48), 16117–​16125. https://​doi.org/​10.1523/​JNEURO​SCI.3474-​13.2014
Berger, H. (1929). Über das Elektrenkephalogramm des Menschen. Archiv Für Psychiatrie Und
Nervenkrankheiten, 87, 527–​570.
Bernstein, J. (1868). Ueber den zeitlichen Verlauf der negativen Schwankung des Nervenstroms.
Archiv für die gesamte Physiologie des Menschen und der Tiere, 1(1), 173–​207. https://​doi.org/​
10.1007/​BF0​1640​316
Bliss, T. V. P. & Lømo, T. (1973). Long-​lasting potentiation of synaptic transmission in the den-
tate area of the anaesthetized rabbit following stimulation of the perforant path. The Journal
of Physiology, 232(2), 331–​356. https://​doi.org/​10.1113/​jphys​iol.1973.sp010​273
Bonnefond, M. & Jensen, O. (2015). Gamma activity coupled to alpha phase as a mechanism
for top-​down controlled gating. PLOS ONE, 10(6), e0128667. https://​doi.org/​10.1371/​jour​nal.
pone.0128​667
Boynton, G. M. (2011). Spikes, BOLD, attention, and awareness: A comparison of electro-
physiological and fMRI signals in V1. Journal of Vision, 11(5), 12–​12. https://​doi.org/​10.1167/​
11.5.12
Breakspear, M. (2017). Dynamic models of large-​scale brain activity. Nature Neuroscience,
20(3), 340–​352. https://​doi.org/​10.1038/​nn.4497
Brovelli, A., Ding, M., Ledberg, A., Chen, Y., Nakamura, R., & Bressler, S. L. (2004). Beta
oscillations in a large-​scale sensorimotor cortical network: directional influences revealed
by Granger causality. Proceedings of the National Academy of Sciences of the United States of
America, 101(26), 9849–​9854. (15210971).
Buzsáki, G., Anastassiou, C. A., & Koch, C. (2012). The origin of extracellular fields and
currents—​EEG, ECoG, LFP and spikes. Nature Reviews Neuroscience, 13(6), 407–​420.
https://​doi.org/​10.1038/​nrn3​241
Buzsáki, G. & Draguhn, A. (2004). Neuronal oscillations in cortical networks. Science,
304(5679), 1926–​1929. https://​doi.org/​10.1126/​scie​nce.1099​745
Buzsáki, G., Logothetis, N., & Singer, W. (2013). Scaling brain size, keeping timing: Evolutionary
preservation of brain rhythms. Neuron, 80(3), 751–​764. https://​doi.org/​10.1016/​j.neu​
ron.2013.10.002
Capilla, A., Pazo-​Alvarez, P., Darriba, A., Campo, P., & Gross, J. (2011). Steady-​state visual
evoked potentials can be explained by temporal superposition of transient event-​related
responses. PLoS One, 6(1), e14543. https://​doi.org/​10.1371/​jour​nal.pone.0014​543
Cohen, M. X. (2014). Analyzing neural time series data: Theory and practice. MIT Press.
Donner, T. H. & Siegel, M. (2011). A framework for local cortical oscillation patterns. Trends in
Cognitive Sciences, 15(5), 191–​199. https://​doi.org/​10.1016/​j.tics.2011.03.007
Elbert, T., Ray, W. J., Kowalik, Z. J., Skinner, J. E., Graf, K. E., & Birbaumer, N. (1994). Chaos
and physiology: Deterministic chaos in excitable cell assemblies. Physiology Review,
74(1), 1–​47.
Foxe, J. J. & Snyder, A. C. (2011). The role of alpha-​band brain oscillations as a sensory
suppression mechanism during selective attention. Frontiers in Psychology, 2, 154. https://​
doi.org/​10.3389/​fpsyg.2011.00154
Freeman, W. J. (1991). The physiology of perception. Scientific American, 264, 78–​87.
Freeman, W. J. (1994). Role of chaotic dynamics in neural plasticity. Progress in Brain Research,
102, 319–​333.
 FROM NEURAL OSCILLATIONS TO COGNITIVE PROCESSES    61

Fuchs, A., Jirsa, V. K., & Kelso, J. A. (2000). Theory of the relation between human brain ac-
tivity (MEG) and hand movements. Neuroimage, 11(5 Pt 1), 359–​369. https://​doi.org/​10.1006/​
nimg.1999.0532
Galambos, R. (1992). A comparison of certain gamma-​band (40 Hz) brain rhythms in cat
and man. In E. Basar & T. Bullock (Eds.), Induced rhythms in the brain (pp. 103–​122).
Springer.
Giabbiconi, C.-​M., Jurilj, V., Gruber, T., & Vocks, S. (2016). Steady-​state visually evoked poten-
tial correlates of human body perception. Experimental Brain Research, 234(11),1–​11. https://​
doi.org/​10.1007/​s00​221-​016-​4711-​8
Gütig, R. (2014). To spike, or when to spike? Current Opinion in Neurobiology, 25, 134–​139.
https://​doi.org/​10.1016/​j.conb.2014.01.004
Hadjipapas, A., Lowet, E., Roberts, M. J., Peter, A., & De Weerd, P. (2015). Parametric variation
of gamma frequency and power with luminance contrast: A comparative study of human
MEG and monkey LFP and spike responses. NeuroImage, 112, 327–​340. https://​doi.org/​
10.1016/​j.neu​roim​age.2015.02.062
Haken, H., Kelso, J. A., & Bunz, H. (1985). A theoretical model of phase transitions in human
hand movements. Biological Cybernetics, 51(5), 347–​356.
Harris, K. P. & Littleton, J. T. (2015). Transmission, development, and plasticity of synapses.
Genetics, 201(2), 345–​375. https://​doi.org/​10.1534/​genet​ics.115.176​529
Headley, D. B. & Weinberger, N. M. (2011). Gamma-​band activation predicts both associative
memory and cortical plasticity. Journal of Neuroscience, 31(36), 12748–​12758. https://​doi.org/​
10.1523/​JNEURO​SCI.2528-​11.2011
Hebb, D. (1949). The organization of behavior: A neuropsychological theory. Wiley.
Heerebout, B. T. & Phaf, R. H. (2010). Good vibrations switch attention: An affective function
for network oscillations in evolutionary simulations. Cognitive, Affective, & Behavioral
Neuroscience, 10(2), 217–​229. https://​doi.org/​10.3758/​CABN.10.2.217
Henley, J. M. & Wilkinson, K. A. (2016). Synaptic AMPA receptor composition in develop-
ment, plasticity and disease. Nature Reviews Neuroscience, 17(6), 337–​350. https://​doi.org/​
10.1038/​nrn.2016.37
Herrmann, C. S., Strüber, D., Helfrich, R. F., & Engel, A. K. (2016). EEG oscillations: From
correlation to causality. International Journal of Psychophysiology, 103, 12–​21. https://​doi.org/​
10.1016/​j.ijpsy​cho.2015.02.003
Keil, A., Gruber, T., & Muller, M. M. (2001). Functional correlates of macroscopic high-​
frequency brain activity in the human visual system. Neuroscience and Biobehavioral
Reviews, 25(6), 527–​534.
Keitel, C., Keitel, A., Benwell, C. S. Y., Daube, C., Thut, G., & Gross, J. (2019). Stimulus-​driven
brain rhythms within the alpha band: The attentional-​modulation conundrum. Journal of
Neuroscience, 39(16), 3119–​3129. https://​doi.org/​10.1523/​JNEURO​SCI.1633-​18.2019
Kelly, S. P., Lalor, E. C., Reilly, R. B., & Foxe, J. J. (2006). Increases in alpha oscillatory power
reflect an active retinotopic mechanism for distracter suppression during sustained visuo-
spatial attention. Journal of Neurophysiology, 95(6), 3844–​3851. https://​doi.org/​10.1152/​
jn.01234.2005
Kim, Y.-​ J., Grabowecky, M., Paller, K. A., & Suzuki, S. (2010). Differential roles of
frequency-​following and frequency-​doubling visual responses revealed by evoked neural
harmonics. Journal of Cognitive Neuroscience, 23(8), 1875–​1886. https://​doi.org/​10.1162/​
jocn.2010.21536
62    ANDREAS KEIL and NINA THIGPEN

Kizuk, S. A. D. & Mathewson, K. E. (2016). Power and phase of alpha oscillations reveal an
interaction between spatial and temporal visual attention. Journal of Cognitive Neuroscience,
29(3), 480–​494. https://​doi.org/​10.1162/​jocn_​a_​01​058
Klimesch, W. (1999). EEG alpha and theta oscillations reflect cognitive and memory perform-
ance: A review and analysis. Brain Research Reviews, 29(2), 169–​195. https://​doi.org/​10.1016/​
S0165-​0173(98)00056-​3
Klimesch, W., Sauseng, P., & Hanslmayr, S. (2006). EEG alpha oscillations: The inhibition-​
timing hypothesis. Brain Research Reviews, 53(1), 63–​88.
Klimesch, W., Schack, B., & Sauseng, P. (2005). The functional significance of theta and upper
alpha oscillations. Experimental Psychology, 52(2), 99–​108.
Lisman, J. E., & Jensen, O. (2013). The theta-​gamma neural code. Neuron, 77(6), 1002–​1016.
https://​doi.org/​10.1016/​j.neu​ron.2013.03.007
Lopes da Silva, F. (1991). Neural mechanisms underlying brain waves: from neural membranes
to networks. Electroencephalography and Clinical Neurophysiology, 79(2), 81–​93. https://​doi.
org/​10.1016/​0013-​4694(91)90044-​5
Maren, S. & Quirk, G. J. (2004). Neuronal signalling of fear memory. Nature Reviews
Neuroscience, 5(11), 844–​852. https://​doi.org/​10.1038/​nrn1​535
Marrazzi, A. S. & Lorente de No, R. (1944). Interaction of neighboring fibres in myelinated
nerve. Journal of Neurophysiology, 7(2), 83–​101. https://​doi.org/​10.1152/​jn.1944.7.2.83
Mathewson, K. E., Lleras, A., Beck, D. M., Fabiani, M., Ro, T., & Gratton, G. (2011). Pulsed out
of awareness: EEG alpha oscillations represent a pulsed-​inhibition of ongoing cortical pro-
cessing. Frontiers in Psychology, 2, 99. https://​doi.org/​10.3389/​fpsyg.2011.00099
Mazzoni, A., Whittingstall, K., Brunel, N., Logothetis, N. K., & Panzeri, S. (2010).
Understanding the relationships between spike rate and delta/​gamma frequency bands of
LFPs and EEGs using a local cortical network model. NeuroImage, 52(3), 956–​972. https://​
doi.org/​10.1016/​j.neu​roim​age.2009.12.040
McTeague, L. M., Gruss, L. F., & Keil, A. (2015). Aversive learning shapes neuronal orientation
tuning in human visual cortex. Nature Communications, 6, 7823. https://​doi.org/​10.1038/​nco​
mms8​823
Moon, J.-​Y., Lee, U., Blain-​Moraes, S., & Mashour, G. A. (2015). General relationship of
global topology, local dynamics, and directionality in large-​scale brain networks. PLoS
Computational Biology, 11(4), e1004225. https://​doi.org/​10.1371/​jour​nal.pcbi.1004​225
Moratti, S., Clementz, B. A., Gao, Y., Ortiz, T., & Keil, A. (2007). Neural mechanisms of evoked
oscillations: stability and interaction with transient events. Human Brain Mapping, 28(12),
1318–​1333. https://​doi.org/​10.1002/​hbm.20342
Morone, F., Roth, K., Min, B., Stanley, H. E., & Makse, H. A. (2017). Model of brain activa-
tion predicts the neural collective influence map of the brain. Proceedings of the National
Academy of Sciences of the United States of America, 114(15), 3849–​3854. https://​doi.org/​
10.1073/​pnas.162​0808​114
Muller, L., Chavane, F., Reynolds, J., & Sejnowski, T. J. (2018). Cortical travelling
waves: mechanisms and computational principles. Nature Reviews Neuroscience, 19(5), 255–​
268. https://​doi.org/​10.1038/​nrn.2018.20
Müller, M. M., Teder, W., & Hillyard, S. A. (1997). Magnetoencephalographic recording of
steady-​state visual evoked cortical activity. Brain Topography, 9(3), 163–​168.
Nadel, L. & Maurer, A. P. (2018). Recalling Lashley and reconsolidating Hebb. Hippocampus,
0(  0), 1–​18. https://​doi.org/​10.1002/​hipo.23027
 FROM NEURAL OSCILLATIONS TO COGNITIVE PROCESSES    63

Nanou, E. & Catterall, W. A. (2018). Calcium channels, synaptic plasticity, and neuropsychi-
atric disease. Neuron, 98(3), 466–​481. https://​doi.org/​10.1016/​j.neu​ron.2018.03.017
Naze, S., Bernard, C., & Jirsa, V. (2015). Computational modeling of seizure dynamics using
coupled neuronal networks: Factors shaping epileptiform activity. PLoS Computational
Biology, 11(5), e1004209. https://​doi.org/​10.1371/​jour​nal.pcbi.1004​209
Neymotin, S. A., Hilscher, M. M., Moulin, T. C., Skolnick, Y., Lazarewicz, M. T., & Lytton, W. W.
(2013). Ih tunes theta/​gamma oscillations and cross-​frequency coupling in an in silico CA3
model. PLoS One, 8(10), e76285. https://​doi.org/​10.1371/​jour​nal.pone.0076​285
Norcia, A. M., Appelbaum, L. G., Ales, J. M., Cottereau, B. R., & Rossion, B. (2015). The steady-​
state visual evoked potential in vision research: A review. Journal of Vision, 15(6), 4–​4.
https://​doi.org/​10.1167/​15.6.4
Nunez, P. L., & Srinivasan, R. (2006). Electric fields of the brain (2nd ed.). Oxford
University Press.
Olejniczak, P. (2006). Neurophysiologic basis of EEG. Journal of Clinical Neurophysiology,
23(3), 186–​189. https://​doi.org/​10.1097/​01.wnp.000​0220​079.61973.6c
Osipova, D., Hermes, D., & Jensen, O. (2008). Gamma power is phase-​locked to posterior
alpha activity. PLoS One, 3(12), e3990. https://​doi.org/​10.1371/​jour​nal.pone.0003​990
Pape, H.-​C., & Paré, D. (2010). Plastic synaptic networks of the amygdala for the acquisition,
expression, and extinction of conditioned fear. Physiological Reviews, 90(2), 419–​463. https://​
doi.org/​10.1152/​phys​rev.00037.2009
Paré, D., Collins, D. R., & Pelletier, J. G. (2002). Amygdala oscillations and the consolidation
of emotional memories. Trends in Cognitive Sciences, 6(7), 306–​314. https://​doi.org/​10.1016/​
S1364-​6613(02)01924-​1
Parvizi, J. & Kastner, S. (2018). Promises and limitations of human intracranial electroenceph-
alography. Nature Neuroscience, 21(4), 474. https://​doi.org/​10.1038/​s41​593-​018-​0108-​2
Petro, N. M. & Keil, A. (2015). Pre-​target oscillatory brain activity and the attentional blink.
Experimental Brain Research, 233(12), 3583–​3595. https://​doi.org/​10.1007/​s00​221-​015-​4418-​2
Pfurtscheller, G. (1989). Spatiotemporal analysis of alpha frequency components with the ERD
technique. Brain Topography, 2(1–​2), 3–​8.
Pfurtscheller, G. (1992). Event-​related synchronization (ERS): An electrophysiological correlate
of cortical areas at rest. Electroencephalography and Clinical Neurophysiology, 83, 62–​69.
Pfurtscheller, G., Stancak, A., Jr., & Neuper, C. (1996). Event-​related synchronization (ERS) in
the alpha band-​-​an electrophysiological correlate of cortical idling: A review. International
Journal of Psychophysiology, 24(1–​2), 39–​46.
Poldrack, R. A. (2011). Inferring mental states from neuroimaging data: From reverse inference
to large-​scale decoding. Neuron, 72(5), 692–​697. https://​doi.org/​10.1016/​j.neu​ron.2011.11.001
Popescu, A. T., Popa, D., & Paré, D. (2009). Coherent gamma oscillations couple the amygdala
and striatum during learning. Nature Neuroscience, 12(6), 801–​807. https://​doi.org/​10.1038/​
nn.2305
Pulvermuller, F., & Fadiga, L. (2010). Active perception: Sensorimotor circuits as a cortical
basis for language. Nature Reviews Neuroscience, 11(5), 351–​360. https://​doi.org/​10.1038/​
nrn2​811
Regan, D. (1989). Human brain electrophysiology: Evoked potentials and evoked magnetic fields
in science and medicine. Elsevier.
Rossion, B., & Boremanse, A. (2011). Robust sensitivity to facial identity in the right human
occipito-​temporal cortex as revealed by steady-​state visual-​evoked potentials. Journal of
Vision, 11(2), 16. https://​doi.org/​10.1167/​11.2.16
64    ANDREAS KEIL and NINA THIGPEN

Samaha, J., Bauer, P., Cimaroli, S., & Postle, B. R. (2015). Top-​down control of the phase of
alpha-​band oscillations as a mechanism for temporal prediction. Proceedings of the National
Academy of Sciences, 112(27), 8439–​8444. https://​doi.org/​10.1073/​pnas.150​3686​112
Sarnthein, J., Petsche, H., Rappelsberger, P., Shaw, G. L., & von Stein, A. (1998). Synchronization
between prefrontal and posterior association cortex during human working memory.
Proceeding of the National Academy of Sciences of the United States of America, 95(12),
7092–​7096.
Schroeder, C. E., & Lakatos, P. (2009). Low-​frequency neuronal oscillations as instruments of
sensory selection. Trends in Neuroscience, 32(1), 9–​18. https://​doi.org/​10.1016/​j.tins.2008.09.012
Schroeder, C. E., Wilson, D. A., Radman, T., Scharfman, H., & Lakatos, P. (2010). Dynamics
of active sensing and perceptual selection. Current Opinion in Neurobiology, 20(2), 172–​176.
https://​doi.org/​10.1016/​j.conb.2010.02.010
Singer, W., Gray, C., Engel, A., König, P., Artola, A., & Brocher, S. (1990). Formation of cortical
cell assemblies. Cold Spring Harbor Symposium on Quantitative Biology, 55, 939–​952.
Skarda, C. A., & Freeman, W. J. (1987). How brains make chaos in order to make sense of the
world. Behavioral and Brain Sciences, 10(2), 161–​173. https://​doi.org/​10.1017/​S01405​25X0​
0047​336
Snyder, A. C., Morais, M. J., Willis, C. M., & Smith, M. A. (2015). Global network influences on
local functional connectivity. Nature Neuroscience, 18(5), 736–​743. https://​doi.org/​10.1038/​
nn.3979
Steriade, M., Gloor, P., Llinás, R. R., Lopes da Silva, F. H., & Mesulam, M.-​M. (1990). Basic
mechanisms of cerebral rhythmic activities. Electroencephalography and Clinical
Neurophysiology, 76(6), 481–​508. https://​doi.org/​10.1016/​0013-​4694(90)90001-​Z
Tehovnik, E. J., Tolias, A. S., Sultan, F., Slocum, W. M., & Logothetis, N. K. (2006). Direct
and indirect activation of cortical neurons by electrical microstimulation. Journal of
Neurophysiology, 96(2), 512–​521. https://​doi.org/​10.1152/​jn.00126.2006
Thigpen, N. N., Bradley, M. M., & Keil, A. (2018). Assessing the relationship between pupil diam-
eter and visuocortical activity. Journal of Vision, 18(6), 7–​7. https://​doi.org/​10.1167/​18.6.7
Thut, G., Nietzel, A., Brandt, S. A., & Pascual-​ Leone, A. (2006). Alpha-​ band
electroencephalographic activity over occipital cortex indexes visuospatial attention bias
and predicts visual target detection. Journal of Neuroscience, 26(37), 9494–​9502.
VanRullen, R. (2016). Perceptual cycles. Trends in Cognitive Sciences, 20(10), 723–​735. https://​
doi.org/​10.1016/​j.tics.2016.07.006
von der Malsburg, C. & Buhmann, J. (1992). Sensory segmentation with coupled neural
oscillators. Biological Cybernetics, 67(3), 233–​242.
Weisz, N., Wühle, A., Monittola, G., Demarchi, G., Frey, J., Popov, T., & Braun, C. (2014).
Prestimulus oscillatory power and connectivity patterns predispose conscious somatosen-
sory perception. Proceedings of the National Academy of Sciences, 111(4), E417–​E425. https://​
doi.org/​10.1073/​pnas.131​7267​111
Wieser, M. J. & Keil, A. (2011). Temporal trade-​off effects in sustained attention: Dynamics
in visual cortex predict the target detection performance during distraction. Journal of
Neuroscience, 31(21), 7784–​7790. https://​doi.org/​10.1523/​JNEURO​SCI.5632-​10.2011
Yuval-​Greenberg, S., Tomer, O., Keren, A. S., Nelken, I., & Deouell, L. Y. (2008). Transient
induced gamma-​band response in EEG as a manifestation of miniature saccades. Neuron,
58(3), 429–​441.
 CHAPTER 4

TIME-​F REQU E NC Y
DE C OM P OSITION MET H OD S
F OR EVENT-​R E L AT E D
P OTENTIAL A NA LYSI S

SELIN AVIYENTE

4.1  Introduction

EEG reflects the electrical activity of a collection of neural populations in the brain.
As such, it reflects the superposition of different simultaneously acting dynamical
systems. When a large number of parallel-​oriented cortical neurons receive the same
repetitive synaptic input, their synchronous activity produces extracellular rhythmic
field potentials. These electrical fields are volume conducted throughout the brain and
recorded as EEG from the scalp (Nunez & Srinivasan, 2006). In recent years, it has been
suggested that this synchronization optimizes relations between spike-​mediated “top-​
down” and “bottom-​up” communication, both within and between brain areas. This
optimization might have particular importance during motivated anticipation of, and
attention to, meaningful events and associations and in response to their anticipated
consequences (Von Stein et al., 2000; Fries et al., 2001; Salinas & Sejnowski, 2001; Makeig
et al., 2004). This new theory of cortical and scalp-​recorded field dynamics requires new
data analysis approaches for spatially distributed event-​related EEG dynamics.
The standard analysis method to study EEG in an event-​related fashion is to focus
on event-​related potentials (ERPs) by averaging. ERPs are positive or negative voltage
deflections seen in the averages of EEG epochs time-​locked to a class of repeated stimulus
or response events. However, this approach assumes that ERPs are superimposed on
ongoing background EEG “noise” with amplitude and phase distributions that are
completely unrelated to the task. This view of ERPs has been challenged in the last two
decades. First, time-​frequency analysis of single-​trial EEG signals shows that EEG is
66   SELIN AVIYENTE

not solely random noise; rather, there are event-​related changes in the magnitude and
phase of EEG oscillations at specific frequencies (Makeig et al., 2004). The early work in
this area focused on spectral analysis of EEG signals, which breaks down the oscillatory
EEG waveforms into sinusoids at different frequencies, reflecting the role of different
frequency bands in cognitive function. Second, ERPs themselves may represent tran-
sient phase resetting of ongoing EEG by experimental events, leading to transient time-​
and phase locking of frequency specific oscillations (Makeig et al., 2004; Makeig et al.,
2002). Makeig and colleagues (2002) have introduced the event-​related brain dynamics
framework, which emphasizes the spectral decomposition of single-​trial event-​related
EEG epochs in order to separately examine event-​related changes in the magnitude
and phase of oscillations at different frequencies. However, spectral analysis assumes
stationarity of the signal, in spite of the fact that information processing in the brain is
mostly reflected by fast dynamic changes in EEG. Even though the Fourier transform
provides a complete representation of the time series, the resulting power spectrum is
only interpretable for stationary signals; non-​stationarities are encoded in the phase
spectrum, which is typically impossible to interpret visually. Spectral analysis is only
capable of reflecting the average or global frequency content, rather than illustrating the
local activity. The non-​stationarities in the EEG signal are the primary motivation for
methods that can capture simultaneously the variation of signal energy across time and
frequency.
Time-​ frequency analyses of EEG provide additional information about neural
synchrony not apparent in ongoing EEG activity or in ERPs. They can tell us which
frequencies have the most power at different time points and how their phase
synchronizes across time and space. Thus, using time-​frequency analyses, we can assess
changes in power and synchronization of EEG within or between spatial locations
across trials with respect to the onset of tasks. However, it is important to note that time-​
frequency analysis cannot by itself determine the cause of the changes in EEG power,
that is, whether the change is due to changes in the magnitude of the oscillations or to
changes in their degree of synchronization (Yeung, 2004; Roach & Mathalon, 2008).
The goal of this chapter is to give an overview of different time-​frequency analysis
tools for both quantifying the changes in EEG power across time and frequency and the
changes in phase synchrony across time, frequency, and space. The different methods
discussed in this chapter can be divided into three categories: linear, nonlinear, and
data-​driven or adaptive methods. The first category of methods focus on simple exten-
sion of Fourier transform to the non-​stationary signal that is, short-​time Fourier trans-
form or sliding window approach, and the continuous wavelet transform. The second
category of methods focus on Cohen’s class of time-​frequency distributions (TFDs) that
compute the spectrum of the time-​varying auto-​correlation function of the signal, ra-
ther than the signal itself. In this manner, these distributions are highly nonlinear but
offer high-​resolution visualizations of EEG dynamics. The last category of methods
stem from recent advances in signal processing that focus on sparse signal represen-
tation. The two methods reviewed under this category are matching pursuit (MP) and
empirical mode decomposition (EMD).
 TIME-FREQUENCY DECOMPOSITION METHODS    67

4.2  Linear Time-​Frequency

Decomposition Methods

4.2.1 Short-​Time Fourier Transform

The earliest method that allowed for the time-​frequency representation of a signal’s
energy distribution was the short-​time Fourier transform (STFT), also known as the
windowed Fourier transform. It relies on an estimation of power spectra, through
Fourier transform, for short time windows shifted along the time axis. The basic idea
of STFT is to break up the signal into small time segments and Fourier analyze each
time segment to determine the frequencies that existed in that segment. The totality
of such spectra indicates how the spectrum is varying with time. STFT is a linear
time-​frequency transform that correlates the signal with a family of waveforms that
are well-​concentrated in time and frequency, compared to standard spectral analysis,
which correlates the signal with eternal sinusoids resulting in good frequency local-
ization at the expense of poor time localization. For a signal x (t ) , its STFT can be
expressed as:1

S (t , ω ) = ∫ x ( τ ) g ( τ − t ) e − jωτ dτ, (4.1)

where g ( τ ) is the window function. The localization of information provided by STFT

depends on the time-​frequency spread of the window g .
The choice of the length and shape of the window function are the two critical issues in
applying STFT to EEG signals. The first problem is usually addressed by considering the
existing trade-​off between time and frequency resolution determined by the length of
the window function. This trade-​off, known formally as the uncertainty principle, states
that as the length of the window increases in time, localization in time or time reso-
lution goes down while the localization in frequency (frequency resolution) increases
(Cohen, 1995). Similarly, if the window length decreases, time resolution increases at
the expense of frequency resolution. In practice, the length of the window is usually
selected by trying different window lengths in order to obtain an optimal trade-​off. This
optimal length is highly dependent on the underlying signal’s properties, such as the
rate with which it changes. The second issue of selecting the shape of the window has
been addressed in a more rigorous way with the resolution of some common windows
mathematically formulated (Mallat, 1999). For numerical applications, the window
function is usually selected as a symmetric and real function. By choosing an appro-
priate window function, one can obtain localization around the time point of interest, t.
For good time-​frequency resolution, the ratio of the first sidelobes to the peak of the

1 
All integrals are from −∞ to ∞ unless otherwise noted.
68   SELIN AVIYENTE

window function should be large, that is, the rate of decay the window function in the
frequency domain, G (ω ), should be fast. Some common window functions include
the rectangular, Hamming, Hanning, and Gaussian window functions. Rectangular
windows have the worst frequency resolution due to the sharp transition of the window
function. Gaussian window achieves the best joint time and frequency localization as it
meets the lower bound of the uncertainty principle. In STFT, the duration of the time
window is fixed in contrast to the wavelet transform, which in turn provides uniform
frequency resolution. STFT is a complex valued time-​frequency representation, and an
energy distribution can be obtained as| S (t , ω ) |2 , known as the spectrogram.

4.2.2  Continuous Wavelet Transform

Continuous wavelet transforms (CWT) describe a class of spectral decomposition
methods that are conceptually related to the STFT. Unlike STFT, where the signals
are decomposed into localized sinusoids, in the wavelet transform the signals are
decomposed in terms of “small waves” of limited duration with an average value of zero.
The wavelet transform of a signal x (t ) is given by:

1  τ −t
W (t , s ) = ∫ x ( τ ) ψ*  dτ, (4.2)
s  s 

where ψ is the wavelet function and s is the scale parameter. Similar to STFT defined
in Eq. 4.1, the wavelet transform finds the decomposition of a given signal in terms of
time-​frequency atoms. However, in this case, the time-​frequency atoms are the time-​
shifted and scaled versions of the mother wavelet, ψ . For this reason, wavelet transform
should be thought of as a time-​scale decomposition rather than a TFD, as the signal is
not decomposed in terms of sinusoids across different frequencies. One of the major
differences between STFT and CWT is the time-​frequency localization. In STFT, the
frequency localization is uniform due to the fixed window size. On the other hand, for
CWT the time resolution is variable, with shorter time windows for higher frequencies
and longer time windows for lower frequencies. This variable time resolution closely
matches the structural properties of ERP signals and has made CWT an attractive
choice for time-​frequency analysis of ERPs (Roach & Mathalon, 2008; Demiralp et al.,
2001; Polikar et al., 2007). Using CWT, the ERP can be decomposed across several or-
thogonal functions, wavelets, with overlapping time courses at different scales.
While any number of wavelet functions can be used for ERP analysis, the wavelet
must provide a biologically plausible fit to the signal being modeled. Some commonly
used wavelets for EEG and ERP analysis are real wavelets, such as splines, and analytic
wavelets, such as the Morlet wavelet and the Generalized Morse Wavelet (GMW). In
particular, the analytic wavelets are useful to obtain both energy and phase information
of the underlying oscillations. The Morlet wavelet is one that has been commonly used
 TIME-FREQUENCY DECOMPOSITION METHODS    69

for EEG/​ERP analysis. The Morlet wavelet is defined as a complex sinusoid tapered by a
Gaussian given as:

t2
−
ψ (t ) = e j 2 π ft
e 2 σ2
, (4.3)

where σ is the width of the Gaussian and is reciprocally related to the frequency in order
to retain the wavelet’s scaling properties. By this scaling, one obtains the same number
of significant wavelet cycles at all frequencies. Thus, the Morlet wavelet transform has
a different time and frequency resolution at each scale. Therefore, at high frequencies
the temporal resolution of a wavelet is better than at low frequencies. However, the in-
verse is true for the frequency resolution of the wavelet transform. Convolution with
the complex Morlet wavelet results in a complex-​valued signal from which instantan-
eous power and phase can be extracted at each time point. Wavelet convolution can be
conceptualized as a template matching or bandpass filtering. Convolutions with Morlet
wavelets can be computed for multiple frequencies in order to yield a time-​frequency
representation. Since Morlet wavelet is a complex function, the corresponding wavelet
transform is also complex, where the real part corresponds to the bandpass filtered
signal and the imaginary part corresponds to Hilbert transform of the signal. There are
several advantages of Morlet wavelets for EEG/​ERP analysis (Cohen, 2018). One is that
the Morlet wavelet is Gaussian shaped in the frequency domain and the absence of sharp
edges minimizes ripple effects. Second, the results of Morlet convolution retain the tem-
poral resolution of the original signal. Third, wavelet convolution is computationally
efficient and can be implemented using the fast Fourier transform. The wavelet power
spectrum, also known as the scalogram, can be obtained as | W (t , s ) |2 .

4.3  Nonlinear Time-​Frequency

Analysis: Cohen’s Class of
Time-​Frequency Distributions

For a signal, x (t ), a bilinear TFD, C (t, ω ), from Cohen’s class can be expressed as
(Cohen, 1995):

 τ  τ  j θu − θt − τω)
C (t , ω ) = ∫∫∫ φ (θ, τ ) x  u +  x *  u −  e ( du dθ dτ, (4.4)
 2  2

where φ (θ, τ ) is the kernel function in the ambiguity domain (θ, τ ). Unlike linear
transforms, which first multiply the signal with a time-​limited window function before
70   SELIN AVIYENTE

computing its Fourier transform, Cohen’s class of distributions compute the Fourier
transform of the local autocorrelation function. In this manner, the signal acts like a
window on itself. The kernel φ (θ, τ ) acts like a filter on this local autocorrelation
function and determines which parts to preserve. TFDs represent the energy distri-
bution of a signal over time and frequency, simultaneously. Some of the most desired
properties of TFDs are the energy preservation, the marginals, and the reduced interfer-
ence. Some common TFDs used for EEG and ERP analysis include the Wigner distribu-
tion and its filtered versions (Tağluk et al., 2005; Abdulla & Wong, 2011).

4.3.1  Wigner Distribution

The Wigner distribution is defined as:

 τ  τ
W (t , ω ) = ∫ x  t +  x *  t −  e − jωτ dτ, (4.5)
 2  2

where x (t ) is the signal and τ is the time lag variable. The Wigner distribution
computes the Fourier transform of the local autocorrelation of the signal as the kernel
φ (θ, τ ) = 1. As the kernel acts as an all pass filter, Wigner distribution keeps the whole
autocorrelation function before transforming it. This provides a high time-​frequency
resolution. In fact, it has been shown that the Wigner distribution provides the highest
time-​frequency resolution among all Cohen’s class of TFDs (Cohen, 1995). It overcomes
some of the shortcomings of the spectrogram as there is no dependency on the choice
of the window. Moreover, the Wigner distribution provides accurate instantaneous fre-
quency estimates and is an accurate energy distribution as it satisfies the marginals.
However, Wigner distribution is a bilinear function of signals. Therefore, Wigner dis-
tribution of multi-​component signals or mono-​component signals with curved time-​
frequency supports will be cluttered by spurious terms called cross-​terms. The existence
of cross-​terms may decrease the interpretability of the TFD. ERPs, like other non-​
stationary signals, require an analysis technique that is free from cross-​terms.

4.3.2  Reduced Interference Distributions (RIDs)

In order to reduce cross-​terms that appear in the Wigner distribution, the past twenty
years demonstrates a move towards using reduced interference distributions (RIDs),
designed using kernel functions φ (θ, τ )  1 for θτ  0 , which concentrate the energy
across the auto-​terms, and satisfy the energy preservation and the marginals (Jeong &
Williams, 1992). The kernel function φ (θ, τ ) is usually designed in the ambiguity plane
as the auto-​terms tend to be close to the origin and the cross-​terms away from the origin
 TIME-FREQUENCY DECOMPOSITION METHODS    71

of the ambiguity plane. This allows for interpretation of the kernel function as a low-​
pass filter that attempts to reject the cross-​terms and leave the auto-​terms unchanged.
The shape of the filter can be adapted to the analysis of the desirable signal components
depending on the nature of the signal. For RIDs, φ (θ, τ ) = h (θτ ), where h is a monot-
onously decreasing function to ensure that the parameterization function is a low-​pass
filter in the ambiguity plane. Depending on the canonical form of h, the resultant RIDs
have different cross-​term rejection capabilities. Some commonly used RIDs include
Choi–​Williams (CW) (Jeong & Williams, 1992), B-​distribution (Zhao et al., 1990),
Born–​Jordan, and Zhao–​Atlas–​Marks (Zhao et al., 1990).
Since these distributions will be implemented in discrete-​time, discrete-​time TFD of
size 2N + 1 × 2N + 1 can be defined as:

N N
 n +n  − jω n −n
TFD (n, ω; ψ ) = ∑ ∑ x (n + n ) x (n + n ) ψ  − 2
n1 =− N n2 =− N
1
*
2
1 2
, n1 − n2  e ( 1 2 ) , (4.6)


where ψ is the discrete-​time kernel in the time and time-​lag domain. The most commonly
used discrete-​time kernel for EEG/​ERP analysis is the binomial kernel, which is given by
m 
ψ (n, m) = 2 −m 
m  for n ≤ m .
n +  2
 2

4.4  Data-​Driven or Adaptive

Time-​Frequency Representations

Unlike the first two types of time-​frequency transforms, the methods reviewed in this
section do not directly result in time-​frequency energy distributions, but rather result
in a description of the ERP dynamics as a sum of a few numbers of distinct components.
These components may be either data-​driven, that is, derived directly from the signals,
or selected from a large dictionary of atoms. Usually, these components are localized
in time and frequency and thus can be thought of as a decomposition of the event-​
related EEG signals into a few distinct time-​frequency elements. Thus, the resulting
components can be visualized using any transform discussed in the previous sections
to obtain a time-​frequency spectrum. For this reason, these are sometimes considered
as time-​frequency analysis tools in the literature. By the nature of the algorithms used to
derive these components, these methods are nonlinear. The first one of these methods,
EMD, is data-​driven and the resulting components usually represent the different fre-
quency bands of EEG. The second method, MP, can be thought of as an extension of
wavelet transform. However, unlike the wavelet functions, which usually form an
72   SELIN AVIYENTE

orthonormal basis for the signal space, the time-​frequency atoms used in MP form an
overcomplete dictionary. This means that the set of functions used to express the signal
is more than necessary. This overcompleteness results in sparse representation of the
EEG/​ERP signals. These atoms are pre-​determined similar to the wavelet transform and
can be selected by the user based on the characteristics of the signals. Some example
atoms could be a combination of sinusoids and wavelets, Gabor functions, etc. This ef-
ficiency in representation of the signals with a few time-​frequency atoms comes at the
expense of computational complexity. Unlike wavelet transform, which is computation-
ally efficient, MP usually relies on greedy algorithms (Mallat & Zhang, 1993; Tropp &
Gilbert, 2007).

4.4.1  Empirical Mode Decomposition

EMD is a fully adaptive, data-​driven approach that decomposes a signal into oscillations
inherent to the data, referred to as intrinsic mode functions (IMFs) (Huang et al., 1998).
Finding the IMFs is equivalent to finding the band-​limited oscillations underlying the
observed signal. Extracting the IMFs is similar to finding the harmonic components in
Fourier analysis. However, the IMF is much more general than the harmonic component
since it can be modulated both in amplitude and frequency, while a harmonic compo-
nent has constant amplitude and frequency. The amplitude and frequency modulations
are possible because the decomposition depends on the local characteristic time scale
of the data. Because the decomposition depends on the local characteristic time scale,
EMD is suitable for application to non-​stationary signals such as ERPs. The EMD algo-
rithm decomposes the signal x (t ) as x (t ) = ∑ i =1 Ci (t ) + r (t ) where Ci (t ) , i = 1, …, M
M

are the IMFs and r (t ) is the residue. The algorithm can be described as follows:

1. Let x (t ) = x (t ) .
2.  Identify all local maxima and minima of x (t ) .
3. Find two envelopes emin (t ) and emax (t ) that interpolate through the local
minima and maxima, respectively.
1
( )
4. Let d (t ) = x (t ) − emin (t ) + emax (t ) as the detail part of the signal.
2
5. Let x (t ) = d (t ) and go to step 2 and repeat until d (t ) becomes an IMF. The two
IMF criteria are: a) the number of extrema and the number of zero-​crossings must
either be equal or differ at most by one; b) At any point, the mean value of the en-
velope defined by the local maxima and the envelope defined by the local minima
is zero.
6. Compute the residue r (t ) = x (t ) − d (t ) and go back to step 1 until the energy of
the residue is below a threshold.
 TIME-FREQUENCY DECOMPOSITION METHODS    73

Although EMD has the ability to extract ERP components, it suffers from the mode
mixing problem (Huang et al., 2003). That is, the different time-​frequency components
may not directly correspond to the different IMFs, which makes it difficult to deter-
mine the distinct ERP components. To overcome the problem of mode mixing, Wu
and Huang (2009) recommend ensemble EMD (EEMD), a noise-​assisted data-​analysis
method. The output of EEMD is a set of IMFs generated from ensemble means of trials
by repeating EMD on the same signal with different sets of Gaussian noise. A further
potential drawback of EMD has been put forth by Flandrin and colleagues (2004), who
showed that EMD behaves as a dyadic filter bank. This poses the concern that EMD
may naturally lead to such a decomposition in all data, which implies that important
oscillations may not be identified if they do not adhere to a dyadic frequency relation-
ship with one another.
Once the IMFs are obtained, Hilbert spectral analysis, also known as Hilbert–​Huang
Transform (HHT), can be used to evaluate the frequency content of each IMF. Hilbert
spectral analysis provides the instantaneous frequency of each IMF. According to Huang
and colleagues (2011), the instantaneous frequency could represent the nonlinear and
non-​stationary signals without resorting to the mathematical artifact of harmonics. Like
measuring ERPs, averaging IMFs across trials provides event-​related modes (ERMs).
Based on the instantaneous frequency of ERMs, ERP components can be extracted by
summing ERMs (Cong et al., 2009; Williams et al., 2011; Wu et al., 2012) or using an
ERM within a frequency range.

4.4.2 Matching Pursuit

The MP algorithm, originally proposed by Mallat and Zhang (1993), relies on an adaptive
approximation of a signal by means of waveforms chosen from a very large and redun-
dant dictionary of functions. MP provides high-​resolution signal analysis with good
resolution in time-​frequency space and allows for parametric description of both peri-
odic and transient signal features. It is suitable for analysis of non-​stationary signals and
for the investigation of dynamic changes of brain activity. MP aims at obtaining a sparse
linear representation of a signal, x (t ) , in terms of functions, g i (sometimes referred
to as atoms), from an overcomplete dictionary, D , using an iterative search algorithm
(Mallat & Zhang, 1993):

M
x (t ) = ∑ ai g i (t ) . (4.7)
i =1

The problem of choosing M functions, which explain the largest proportion of en-
ergy of a given signal, is a computationally complex problem and is known to belong to
the class of non-​deterministic polynomial-​time hard (NP-​hard) problems. MP offers a
tractable suboptimal solution, obtained by an iterative algorithm.
74   SELIN AVIYENTE

In the first step of the iterative procedure, we choose the element of the dictionary
that gives the largest inner product with the signal, that is, g 1 = argmax g i ∈D x , g i . This
first element of the dictionary is subtracted from the signal to obtain the residue. The
iterative procedure is repeated on the subsequent residual, R k x . This procedure can be
summarized as:

1.  Define the 0th order residual as R0 x = x .

2. For the k th order residual, R k x , select the best atom such that the inner product
between the residual and the atom is maximized

g k = argmax g i ∈D R k x , g i . (4.8)

3. Compute the residue R k +1 x as

R k +1 x = R k x − R k x , g k g k . (4.9)

4. After M iterations, the following linear representation is obtained:

x = ∑ R k x , g k g k + R M +1 x. (4.10)
k =1

The procedure converges to x in the limit, that is, x = ∑ k =1 R x , g k g k and

∞
k

preserves signal energy. From this representation, one can derive a TFD of a signal’s en-
ergy by adding Wigner distributions of selected atoms.
The overcomplete dictionary, D , can be designed to fit the class of signals at hand.
Two important requirements for a dictionary are its descriptive power, that is, its
ability to represent the signals of interest with relatively few atoms (sparsity), and its
interpretability, that is, that the parameters indexing the atoms convey information.
Although overcomplete dictionaries do not provide uniqueness of decomposition,
they have more descriptive power than more classical, orthogonal dictionaries, such
as wavelets. Regarding interpretability, the choice of atoms and their parameters is
motivated by the types of activities that will be encountered. The dictionary is fur-
thermore supposed to depend continuously on the parameter space (even though
for numerical reasons, this space will obviously be discretized). This constraint is
imposed only for ease of presentation, but the approach could be generalized, at the
cost of some added complexity. For analyzing EEG and ERP signals, previous work
has shown that Gabor logons represent the signals with few coefficients (Durka &
Blinowska, 2001; Brown et al., 1994; Aviyente, 2007) . Gabor logons also have the
advantage of being the most concentrated signals on the time-​frequency plane,
 TIME-FREQUENCY DECOMPOSITION METHODS    75

achieving the lower bound of the time-​bandwidth product. A dyadic Gabor dic-
tionary also allows for computationally effective implementation and has been used
widely in EEG analysis.

4.4.3 Multichannel Matching Pursuit

The principle of MP can easily be generalized to the simultaneous decomposition of
( )
multiple signals, X = x1 , x 2 , …, x r of r signals into atoms from the same overcomplete
dictionary, D. This approach is sometimes referred to as the multichannel MP (MMP)
or simultaneous MP in the literature, since it is usually applied to multiple signals
collected over multiple channels/​sensors or trials (Gribonval et al., 2008; Lelic et al.,
2011; Sieluzycki et al., 2008). Unlike the original MP, MMP represents every component
x l of X as a weighted sum of the same elements from the overcomplete dictionary and
thus tries to achieve joint sparsity of a collection of signals for a given dictionary. The al-
gorithm can be described as follows:

1.  Define for each signal l the 0th order residual as R0 x l = x l .

2. For the kth order residual, R k x l , select the best atom such that the total inner
product between the atom and the residuals in each signal is maximized

r
argmax g i ∈D ∑ R k x l , g i . (4.11)
l =1

3. Compute the residue R k +1 x l for all signals:

R k +1 x l = R k x l − R k x l , g k g k . (4.12)

4. After M iterations, the following linear representation is obtained for each

signal:
M
x l = ∑ R k x l , g k g k + R M +1 x l . (4.13)
k =1

Different implementations of MMP have been employed for ERP analysis, that is,
evoked activity MP (EMP) and induced activity MP (IMP) (Bénar et al., 2009). In EMP,
the atoms are determined to maximize the correlation with the average signal, and the
amplitude is adapted to the individual trials. In this manner, the method accounts for
amplitude variability across trials, but not for variability in the parameter space. IMP,
on the other hand, maximizes the average energy across trials. Durka and colleagues
76   SELIN AVIYENTE

(2005) have also proposed an alternative approach for simultaneous time-​frequency

parametrization of multiple EEG recordings by applying the standard MP algorithm
to the average of multichannel EEGs. This approach reduces the computational com-
plexity by a factor of r at the expense of favoring data with equal phases in all of the
channels.

4.5  Illustration of Different

Time-​Frequency Methods for
ERP Analysis

This section illustrates the performance of some of the time-​frequency analysis methods
discussed earlier for an example ERP signal. In particular, we focus on the error-​related
negativity (ERN), a neurophysiological marker of performance monitoring. ERN is a
negative deflection in the ERP that peaks within 100 ms of an erroneous response at
frontocentral recording sites (Moser, 2017; Moran et al., 2015). The ERN is generally
considered to be an index of cognitive control-​related performance monitoring that is
involved in coordinating optimal responding following mistakes. For the purpose of
this illustration, we consider ERP obtained by averaging across trials recorded at the
FCz electrode for one subject.
First, we compare the performance of linear and nonlinear time-​frequency energy
distributions, namely the continuous wavelet transform with the Morlet wavelet, and
RID with the binomial kernel. From Figure 4.1, a typical ERN waveform with a negative
potential occurring in the first 100 ms can be seen, along with different TFDs. From both

4
μV

Time 0
–4
–600 –400 –200 0 200 400

Binomial 10
Hz

RID
Amplitude
0
High
Morlet 10
Hz

Wavelet
0 Low
Time (ms)

Figure 4.1  Time-​frequency Analysis of ERN waveform. From top to bottom: ERN signal in the
time domain, reduced interference distribution (binomial kernel), continuous wavelet transform
with Morlet wavelet.
 TIME-FREQUENCY DECOMPOSITION METHODS    77

distributions, it is clear that there is high energy corresponding to ERN and P3e, P300
following the error response. The biggest difference between the different distributions
is the time and frequency resolution of this component in the time-​frequency plane. For
RID, there are two distinct time-​frequency components; one during ERN localized in
the theta band (4–​8Hz) and another distributed in time up till 400 ms in the delta (0–​2
Hz) band. Morlet wavelet produces a distribution that captures the theta band activity
without highlighting the delta band energy. It can be seen from these results that RID
has the better time and frequency resolution, whereas the wavelet transform has poorer
time and frequency localization. From this comparison, it can be concluded that RID
provides better delineation of different ERP components. The results of the CWT may
be improved by changing the wavelet type and wavelet scales. Unlike RID, which does
not depend on the selection of any parameters, CWT is highly dependent on the user
provided parameter values.
Next, we compare the performance of data-​driven component extraction methods,
EMD and MP. Figure 4.2 illustrates the first four IMFs, along with their Hilbert spectra.
This figure shows that the first two IMFs correspond to the ERN time interval, whereas
the third and fourth IMFs correspond to the P3e potential. The corresponding time-​
frequency energy distribution has a high energy concentration in the 100–​200 ms and
300–​400 ms time intervals within the delta frequency band. These components corres-
pond to the P3e. However, the ERN component is not easily detected from this distribu-
tion as it has less energy than P3e.
In a similar manner, Figure 4.3 illustrates an MP spectrum obtained using a Gabor
dictionary. The dictionary is constructed using Gabor functions, that is, Gaussian
window functions shifted in time and modulated in frequency. The figure illustrates the
time-​frequency localization of the selected atoms. The figure also shows a high energy
atom in the 100–​200 ms time interval in the delta band. There are also Gabor functions
with negative weights in the 0–​100 ms time window around 10–​12 Hz frequency band.
This corresponds to ERN time window and alpha frequency band.
From these comparisons, it can be seen that RID is the best in terms of separating
different ERP oscillations from each other with high resolution. The component-​
based methods work better in separating different oscillatory components, such as
the IMFs extracted from EMD. However, EMD is not a true time-​frequency energy
distribution method, as it does not produce an actual spectrum like RID. The current
method of visualizing IMFs in the time-​frequency plane relies on the Hilbert trans-
form of extracting the individual envelope and instantaneous frequency for each IMF.
As the Hilbert transform is not a true time-​frequency localization method, the IMFs
can also be transformed to the time-​frequency plane using different distributions to
obtain higher-​resolution visualizations. MP, on the other hand, is highly dependent on
the selected dictionary atoms. The more suitable the dictionary is for the underlying
signal, the sparser the resulting representation. In this particular example, MP wrongly
detects alpha components for the ERN time window while missing the theta activity for
the same time window. As EMD is data-​driven and independent of priors, it performs
better than MP for ERP analysis.
78   SELIN AVIYENTE

(a) Empirical Mode Decomposition

Showing 4 out of 4 IMFs
20
Signal

–20
–0.2 –0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
5
IMF 1

–5
–0.2 –0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
10
IMF 2

–10
–0.2 –0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
10
IMF 3

–10
–0.2 –0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
2
IMF 4

–2
–0.2 –0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
10
Residual

–10
–0.2 –0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
Time (second)
(b) 100
40
35
80
30
Frequency (Hz)

25 60
20
15 40

10
20
5
0
–0.2 –0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
Time (second)

Figure 4.2 Empirical mode decomposition for ERP signal: (A) The first four intrinsic
mode functions (IMFs) extracted from the ERP signal. (B) The time-​frequency spectrum
corresponding to the extracted IMFs.
 TIME-FREQUENCY DECOMPOSITION METHODS    79

Time frequency Representation of Weights

400

12
300

10
200

8
Frequency (Hz)

100

6
0

4 –100

2 –200

–0.2 –0.1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
Time (second)

Figure 4.3  Time-​frequency analysis using matching pursuit with a Gabor dictionary.

4.6  Time-​Frequency-​Based Phase

Synchrony Analysis

Although time-​frequency energy distribution is effective for studying the spectral con-
tent of EEG and ERP oscillations, most of the current approaches focus only on the
magnitude spectrum of the oscillations and ignore the phase information. Recent re-
search shows that ERPs result from event-​related partial phase resetting of ongoing os-
cillatory activity along with transient increases in the magnitude of oscillations that are
time-​locked to the experimental events (Roach & Mathalon, 2008; Makeig et al., 2004).
Therefore, it is important to characterize the change in phase information across time
and frequency.
Phase synchrony quantifies the relation between the temporal structures of the
signals, regardless of signal amplitude (Rosenblum et al., 2000; 2001). Two signals
are said to be synchronous if their rhythms coincide. The amount of synchrony be-
tween two signals is usually quantified by first estimating the instantaneous phase
of the individual signals around the frequency of interest. Traditionally, the instant-
aneous phase of a given signal is estimated first, and then the phase synchrony is
quantified using statistical measures. Conventionally, the instantaneous phase is
estimated using the Hilbert transform. However, the Hilbert transform does not
80   SELIN AVIYENTE

provide any selectivity in frequency, the whole range of frequencies is considered

to define the instantaneous phase. Therefore, if the signal is broadband, such as
in the case of EEG signals, it is necessary to pre-​filter it in the frequency band of
interest before applying the Hilbert transform, in order to get a proper phase esti-
mate. However, this method relies heavily on the proper selection of the bandpass
filter and may suffer from estimation bias. In order to address the shortcomings of
the Hilbert transform, different time-​frequency transforms have been used to esti-
mate instantaneous phase.

4.6.1 Wavelet-​Based Phase Estimation

One common time-​ frequency based phase estimation approach employs CWT
(Lachaux et al., 1999), in which the phase of the signals is extracted from the coefficients
of their continuous wavelet transform using a complex wavelet function, such as the
Morlet wavelet at the target frequency. These coefficients are the result of a convolu-
tion of the original signal with a time-​shifted and frequency-​modulated Gaussian
function as:

Wx (t , f ) = ∫ x (u ) ψ t*, f (u ) du (4.14)
−∞

where ψ t*, f (u ) represents the complex conjugate of the wavelet function. Using the
( u − t )2
−
Morlet wavelet ψ t , f (u ) =
j 2 π f (u − t )
fe e 2 σ2
, the phase spectrum of x (t ) can be
evaluated as follows:

 W (t , f ) 
Φx (t , f ) = arg  x  . (4.15)
 Wx (t , f ) 

This method of computing time-​frequency phase estimation has been shown to

yield similar results with respect to the Hilbert transform with the main difference
being the increased frequency resolution offered by CWT (Le Van Quyen et al.,
2001). The main shortcoming of the CWT-​based method is the non-​uniform reso-
lution across time and frequency, which results in biased phase estimates (Aviyente
et al., 2011).

4.6.2 EMD-​Based Phase Estimation

More recently, EMD-​and RID-​based phase synchrony estimates have been proposed.
While HHT provides a time-​frequency energy distribution, EMDs have also been used
 TIME-FREQUENCY DECOMPOSITION METHODS    81

for quantifying phase synchrony between signal pairs. A problem with current syn-
chrony detection methods such as the Hilbert transform is that they depend on a priori
selection of bandpass filters. In response to this problem, EMD-​based phase synchrony
measures have been defined (Rutkowski et al., 2008; Looney et al., 2009; Sweeney-​Reed
& Nasuto, 2007; Mutlu & Aviyente, 2011). In most of these approaches, the IMFs for
each time series were extracted individually and were compared individually against
the IMFs from the other time series for computing phase synchrony. This approach
has multiple shortcomings. First, the IMFs from the different time series do not neces-
sarily correspond to the same frequency, thus making it hard to compute exact within-​
frequency phase synchronization across different EEG channels. Second, the different
time series may end up having different numbers of IMFs, which makes it difficult to
match the different IMFs for synchrony computation. Finally, Looney and colleages
(2009) showed that univariate EMD is not robust under noise and may suffer from
mode mixing, which refers to the phenomenon of different modes (or frequencies)
existing in a single IMF due to noise or intermittent signal activity.
Recently, extensions of EMD to the multivariate case have been developed including
Complex EMD (Tanaka & Mandic, 2007), Rotation Invariant EMD (RIEMD)
(Altaf et al., 2007), and Bivariate EMD (BEMD) (Rilling et al., 2007). These complex
extensions of EMD decompose data from different sources simultaneously. Looney and
colleages (2009) showed that the IMFs obtained in this fashion are matched, not only in
number, but also in frequency overcoming problems of uniqueness and mode mixing,
and first suggested the idea of using bivariate EMD to compute phase synchrony be-
tween two signals and the BEMD was shown to perform better than univariate EMD for
quantifying bivariate synchrony. However, this approach still has some shortcomings, as
the frequency bands corresponding to IMFs from different bivariate pairs are not neces-
sarily the same. As such, this method is mostly limited to bivariate synchrony analysis
and is not as easily generalizable to the whole brain synchrony analysis. Moreover, the
multivariate extensions of EMD have been shown to be computationally expensive for
computing functional connectivity across the whole brain (Mutlu & Aviyente, 2011).

4.6.3 RID-​Based Phase Estimation

In recent work, we have shown the effectiveness of RID-​based phase synchrony
estimates compared to Hilbert-​and CWT-​based estimates (Aviyente & Mutlu, 2011;
Aviyente et al., 2011; Sponheim et al., 2011; Aviyente et al., 2017). As most members of
Cohen’s class of TFDs are real-​valued, they do not preserve the phase information. For
this reason, we introduce a complex TFD, the Rihaczek distribution, to extract time-​and
frequency-​dependent phase estimates. Rihaczek introduced the complex energy distri-
bution and gave a plausibility argument based on physical grounds (Rihaczek, 1968).
1
For a signal, x (t ) , Rihaczek distribution is expressed as C (t , ω ) = x (t ) X * (ω ) e − jωt ,
2π
82   SELIN AVIYENTE

where X * (ω ) is the complex conjugate of the Fourier transform of the signal and
C (t, ω ) measures the complex energy of a signal around time, t and frequency, ω . The
complex energy density function provides a fuller appreciation of the properties of
phase-​modulated signals that is not available with other TFDs. Rihaczek distribution
is a bilinear, time-​and frequency-​shift covariant, complex-​valued TFD belonging to
Cohen’s class. This distribution satisfies the marginals and preserves the energy of the
signal. Rihaczek distribution provides both a time-​varying energy spectrum as well as a
phase spectrum, and thus is useful for estimating the phase synchrony between any two
signals. One of the disadvantages of Rihaczek distribution, similar to other quadratic
TFDs, is the existence of cross-​terms for multicomponent signals. In order to get rid of
these cross-​terms, in previous work (Aviyente et al., 2011), we proposed to apply a kernel
function such as the CW kernel to filter the cross-​terms. The resulting distribution can
be written as:
 (θτ)2   θτ 
C (t , ω ) = ∫ ∫ exp  − exp  j  A (θ, τ ) e (
− j θt + τω )
 dτ dθ,(4.16)
 σ   2
  
CWkernel Rihaczekkernel
θτ
j
where e is the kernel function for the Rihaczek distribution. This new distribution,
2

which will be referred to as RID–​Rihaczek, will have an equivalent time-​frequency kernel

( θτ )2 θτ
e 2 . Since this kernel satisfies the constraints, φ (θ, 0) = φ (0, θ ) = φ (0, 0) = 1,
−
φ (θ, τ ) = e
j
σ

the corresponding distribution will both satisfy the marginals and preserve the en-
ergy, as well as be a complex energy distribution at the same time. The value of σ can
be adjusted to achieve a desired trade-​off between resolution and the number of cross-​
terms retained. The phase estimates from RID-​Rihaczek distribution can be obtained as
 C (t , ω ) 
φ (t , ω ) = arg   . This phase estimate has been shown to be more robust to noise
 C (t , ω ) 
and has uniformly high resolution in time and frequency compared to wavelet-​based
phase estimates (Aviyente & Mutlu, 2011).

4.6.4 Different Measures of Phase Synchrony

Once the phase difference between two signals is estimated through a time-​frequency-​
based method, it is important to quantify the amount of synchrony. The most common
scenario for the assessment of phase synchrony entails the analysis of the synchron-
ization between pairs of signals. In the case of noisy oscillations, the length of stable
segments of the relative phase gets very short; further, the phase jumps occur in both
directions, so the time series of the relative phase φ x , y (t ) looks like a biased random
walk (unbiased only at the center of the synchronization region). Therefore, the direct
analysis of the unwrapped phase differences φ x , y (t ) has been used seldomly. As a re-
sult, phase synchrony can only be detected in a statistical sense. Two different indices
 TIME-FREQUENCY DECOMPOSITION METHODS    83

have been proposed to quantify the synchrony based on the relative phase difference,
that is, φ x , y (t ) is wrapped into the interval [0, 2π ) . The first index uses an information-​
theoretic criterion to quantify synchronization. This measure studies the distribu-
tion of φ x , y (t ) by partitioning the interval [0, 2π ) into L bins and comparing it with
the distribution of the cyclic relative phase obtained from two series of independent
phases. This comparison is carried out by estimating the Shannon entropy of both
distributions, that is, that of the original phases, and that of the independent phases, and
computing the normalized difference (Quiroga et al., 2002). The second metric, phase
synchronization index, is also known as the mean phase coherence and computed as
1 N −1 jΦ (t )
( ) ( )
< cos Φxy (t ) > 2 + < sin Φxy (t ) > 2 = ∑ e xy k . It is a measure of how the rela-
N k =0
tive phase is distributed over the unit circle. If the two signals are phase synchronized,
the relative phase will occupy a small portion of the circle and mean phase coherence
is high. This measure is equal to 1 for the case of complete phase synchronization and
tends to zero for independent oscillators.
These different measures of synchrony can be used to quantify three different types
of synchronization from EEG/​ERP signals, depending on the application. The major
difference between the different implementations of phase synchrony is whether the
consistency of phase differences is measured across time, trials, or channels. Phase
Locking Value (PLV) quantifies the consistency of the phase differences across trials
1 N
( )
between two channels as follows: PLV (t , ω ) = ∑ exp jφkx , y (t , ω ) , where k is the
N k =1
trial number and N is the number of trials. This measure is also known as the inter-​
channel phase synchrony (ICPS). It is commonly used to estimate phase-​locking in ex-
perimental situations, common in neurocognitive studies, where a subject is presented
with a sequence of similar stimuli. Single trial phase-​locking value (S-​PLV), on the
other hand, allows us to measure the significance of synchronies in single trials, and
does not depend on block repetition of events. The variability of phase-​difference is
not measured across trials, but across successive time-​steps, around a target latency.
Specifically, a smoothed or S-​PLV is defined for each individual trial. Finally, inter-​trial
phase synchrony (ITPS) quantifies the consistency of phase values for a given frequency
band at each point in time over trials, in one particular electrode. ITPC is defined as
1 N
( )
ITPC (t , ω ) = ∑ exp jφk (t , ω ) , where N is the number of trials and φk (t, ω ) is the
N k =1
phase of the k th trial for each time and each frequency point. ITPC thus reflects the
extent to which oscillation phase values are consistent over trials at that point in time-​
frequency plane. Note that this measure of phase coherence does not differentiate be-
tween possible biophysical mechanisms underlying phase consistency, such as phase
reset or phase “smearing”. Rather, this measure simply indicates the statistical prob-
ability of increased phase consistency between trial and baseline epochs.
84   SELIN AVIYENTE

4.7  Summary

This chapter reviewed some of the basic time-​frequency methods for analyzing ERP
dynamics. We first introduced the different transforms that have been used to analyze
the transient ERP activity. These transforms can be divided into three categories: linear
methods such as STFT and CWT, data-​adaptive methods such as EMD, and nonlinear
methods such as Cohen’s class of distributions. Although the overall goal of all of
these methods is to determine the dynamics of transient activity, the mathematical
principles upon which they rely are quite different. These differences in mathematical for-
mulation lead to different computational complexities. Therefore, it is important to under-
stand how the different methods can be used for different applications and purposes. For
example, if the goal is to visualize the energy distribution of the transient ERP activity in
time and frequency simultaneously, then Cohen’s class of distributions (such as the RID)
performs the best. Even though this method is the most complex in terms of computa-
tional complexity, it offers very high time-​frequency resolution, which in turn provides
a way to delineate different ERP components from each other. However, if the goal is
to obtain a compact representation of the ERP signals in terms of a few physiologically
meaningful components, then data-​adaptive methods like EMD and MP are more suit-
able and computationally efficient. This chapter also shows how the same mathematical
transforms can be used to study ERP dynamics through both energy distributions and
phase synchrony in the time-​frequency domain. While the energy distributions focus
on the univariate activity, that is, dynamics within a certain brain region or electrode,
the phase synchrony quantifies the dynamics across brain regions. In this manner, it is
possible to obtain a better understanding of ERP timing, synchronization across time,
frequency, and space.

REFERENCES
Abdulla, W. & Wong, L. (2011). Neonatal EEG signal characteristics using time frequency ana-
lysis. Physica A: Statistical Mechanics and its Applications, 390(6), 1096–​1110.
Altaf, M. U. B., Gautama, T., Tanaka, T., & Mandic, D. P. (2007). Rotation invariant complex
empirical mode decomposition. In 2007 IEEE international conference on acoustics, speech
and signal processing-​ICASSP’07, vol. 3 (pp. III–​1009). IEEE.
Aviyente, S. (2007). Compressed sensing framework for EEG compression. In Proceedings
of IEEE/​SP: 14th workshop on statistical signal processing (pp. 181–​184). IEEE. Doi: 10.1109/​
SSP.2007.4301243.
Aviyente, S., Bernat, E. M., Evans, W. S., & Sponheim, S. R. (2011). A phase synchrony measure
for quantifying dynamic functional integration in the brain. Human Brain Mapping,
32(1), 80–​93.
Aviyente, S. & Mutlu, A. Y. (2011). A time-​frequency-​based approach to phase and phase syn-
chrony estimation. IEEE Transactions on Signal Processing, 59(7), 3086–​3098.
 TIME-FREQUENCY DECOMPOSITION METHODS    85

Aviyente, S., Tootell, A., & Bernat, E. M. (2017). Time-​frequency phase-​synchrony approaches
with ERPs. International Journal of Psychophysiology, 111, 88–​97.
Bénar, C. G., Papadopoulo, T., Torrésani, B., & Clerc, M. (2009). Consensus matching pursuit
for multi-​trial EEG signals. Journal of Neuroscience Methods, 180(1), 161–​170.
Brown, M. L., Williams, W. J., & Hero, A. O. (1994). Non-​orthogonal Gabor representa-
tion of biological signals. In Proceedings of ICASSP ’94: IEEE international conference
on acoustics, speech and signal processing, vol. 4 (pp. IV/​305-​IV/​308). IEEE. doi: 10.1109/​
ICASSP.1994.389742.
Cohen, L. (1995). Time-​frequency analysis, vol. 778. Prentice Hall.
Cohen, M. X. (2018). A better way to define and describe Morlet wavelets for time-​frequency
analysis. bioRxiv [online], 397182.
Cong, F., Sipola, T., Huttunen-​Scott, T., Xu, X., Ristaniemi, T., & Lyytinen, H. (2009). Hilbert-​
Huang versus Morlet wavelet transformation on mismatch negativity of children in uninter-
rupted sound paradigm. Nonlinear Biomedical Physics, 3(1), 1.
Demiralp, T., Ademoglu, A., Istefanopulos, Y., Başar-​Eroglu, C., & Başar, E. (2001). Wavelet
analysis of oddball p300. International Journal of Psychophysiology, 39(2–​3), 221–​227.
Durka, P. J. & Blinowska, K. J. (2001). A unified time-​frequency parametrization of EEGs. IEEE
Engineering in Medicine and Biology, 20(5), 47–​53.
Durka, P. J., Matysiak, A., Montes, E. M., Valdés Sosa, P., & Blinowska, K. J. (2005).
Multichannel matching pursuit and EEG inverse solutions. Journal of Neuroscience
Methods, 148(1), 49–​59.
Flandrin, P., Rilling, G., & Goncalves, P. (2004). Empirical mode decomposition as a filter
bank. IEEE Signal Processing Letters, 11(2), 112–​114.
Fries, P., Reynolds, J. H., Rorie, A. E., & Desimone, R. (2001). Modulation of oscillatory neur-
onal synchronization by selective visual attention. Science, 291(5508), 1560–​1563.
Gribonval, R., Rauhut, H., Schnass, K., & Vandergheynst, P. (2008). Atoms of all channels,
unite! Average case analysis of multi-​channel sparse recovery using greedy algorithms.
Journal of Fourier Analysis and Applications, 14(5–​6), 655–​687.
Hassanpour, H., Mesbah, M., & Boashash, B. (2004). Time-​frequency feature extraction of
newborn EEG seizure using SVD-​based techniques. EURASIP Journal on Applied Signal
Processing, 2004, 2544–​2554.
Huang, N. E., Shen, Z., Long, S. R., Wu, M. C., Shih, H. H., Zheng, Q., et al. (1998). The empir-
ical mode decomposition and the Hilbert spectrum for nonlinear and non-​stationary time
series analysis. Proceedings of the Royal Society of London. Series A: Mathematical, Physical
and Engineering Sciences, 454(1971), 903–​995.
Huang, N. E., Wu, M-​L., Qu, W., Long, S. R., & Shen, S. S. P. (2003). Applications of Hilbert–​
Huang transform to non-​stationary financial time series analysis. Applied Stochastic Models
in Business and Industry, 19(3), 245–​268.
Huang, Y. X., Schmitt, F. G., Hermand, J-​ P., Gagne, Y., Lu, Z. M., Liu, Y. L.,
et al. (2011). Arbitrary-​order Hilbert spectral analysis for time series possessing scaling
statistics: Comparison study with detrended fluctuation analysis and wavelet leaders.
Physical Review E, 84(1), 016208.
Jeong, J. & Williams, W. J. (1992). Kernel design for reduced interference distributions. IEEE
Transactions on Signal Processing, 40(2), 402–​412.
Lachaux, J-​P., Rodriguez, E., Martinerie, J., & Varela, F. J. (1999). Measuring phase synchrony in
brain signals. Human Brain Mapping, 8(4), 194–​208.
86   SELIN AVIYENTE

Lelic, D., Gratkowski, M., Hennings, K., & Drewes, A. M. (2011). Multichannel matching pur-
suit validation and clustering—​a simulation and empirical study. Journal of Neuroscience
Methods, 196(1), 190–​200.
Le Van Quyen, M., Foucher, J., Lachaux, J-​P., Rodriguez, E., Lutz, A., Martinerie, J., & Varela, F.
J. (2001). Comparison of Hilbert transform and wavelet methods for the analysis of neuronal
synchrony. Journal of Neuroscience Methods, 111(2), 83–​98.
Looney, D., Park, C., Kidmose, P., Ungstrup, M., & Mandic, D. P. (2009). Measuring phase
synchrony using complex extensions of EMD. In 2009 IEEE/​SP 15th workshop on statistical
signal processing (pp. 49–​52). IEEE.
Makeig, S., Debener, S., Onton, J., & Delorme, A. (2004). Mining event-​related brain dynamics.
Trends in Cognitive Sciences, 8(5), 204–​210,
Makeig, S., Westerfield, M., Jung, T-​P., Enghoff, S., Townsend, J., Courchesne, E., & Sejnowski,
T. J. (2002). Dynamic brain sources of visual evoked responses. Science, 295(5555), 690–​694.
Mallat, S. (1999). A wavelet tour of signal processing. Elsevier.
Mallat, S. G. & Zhang, Z. (1993). Matching pursuits with time-​frequency dictionaries. IEEE
Transactions on Signal Processing, 41(12), 3397–​3415.
Moran, T. P., Bernat, E. M., Aviyente, S., Schroder, H. S., & Moser, J. S. (2015). Sending mixed
signals: Worry is associated with enhanced initial error processing but reduced call for sub-
sequent cognitive control. Social Cognitive and Affective Neuroscience, 10(11), 1548–​1556.
Moser, J. S. (2017). The nature of the relationship between anxiety and the error-​related nega-
tivity across development. Current Behavioral Neuroscience Reports, 4(4), 309–​321.
Mutlu, A. Y. & Aviyente, S. (2011). Multivariate empirical mode decomposition for quantifying
multivariate phase synchronization. EURASIP Journal on Advances in Signal Processing,
2011(1), 615717.
Nunez, P. L. & Srinivasan, R. (2006). Electric fields of the brain: The neurophysics of EEG. Oxford
University Press.
Polikar, R., Topalis, A., Green, D., Kounios, J., & Clark, C. M. (2007). Comparative multiresolution
wavelet analysis of ERP spectral bands using an ensemble of classifiers approach for early diag-
nosis of Alzheimer’s disease. Computers in Biology and Medicine, 37(4), 542–​558.
Quiroga, R. Q., Kraskov, A., Kreuz, T., & Grassberger, P. (2002). Performance of different syn-
chronization measures in real data: a case study on electroencephalographic signals. Physical
Review E, 65(4), 041903.
Rihaczek, A. (1968). Signal energy distribution in time and frequency. IEEE Transactions on
Information Theory, 14(3), 369–​374.
Rilling, G., Flandrin, P., Gonçalves, P., & Lilly, J. M. (2007). Bivariate empirical mode decom-
position. IEEE signal processing letters, 14(12), 936–​939.
Roach, B. J. & Mathalon, D. H. (2008). Event-​related EEG time-​frequency analysis: An over-
view of measures and an analysis of early gamma band phase locking in schizophrenia.
Schizophrenia Bulletin, 34(5), 907–​926.
Rosenblum, M., Pikovsky, A., Kurths, J., Schäfer, C., & Tass, P. A. (2001). Phase synchroniza-
tion: From theory to data analysis. In F. Moss & S. Gielen (Eds.), Handbook of biological
physics: Neuro-​informatics and neural modelling, vol. 4 (pp. 279–​321). Elsevier.
Rosenblum, M., Tass, P., Kurths, J., Volkmann, J., Schnitzler, A., & Freund, H-​J. (2000).
Detection of phase locking from noisy data: Application to magnetoencephalography. In
K. Lehnertz, C. E. Elger, J. Arnhold, & P. Grassberger (Eds.), Proceedings of the workshop on
chaos in brain (pp. 34–​51). World Scientific.
 TIME-FREQUENCY DECOMPOSITION METHODS    87

Rutkowski, T. M., Mandic, D. P., Cichocki, A., & Przybyszewski, A. W. (2008). EMD approach
to multichannel EEG data-​the amplitude and phase synchrony analysis technique. In D-​S.
Huang, D. C. Wunsch II, D. S. Levine, & K-​H. Jo (Eds.), Proceedings of the international
conference on intelligent computing: Advanced intelligent computing theories and applications.
With aspects of theoretical and methodological issues (pp. 122–​129). Springer.
Salinas, E. & Sejnowski, T. J. (2001). Correlated neuronal activity and the flow of neural infor-
mation. Nature Reviews Neuroscience, 2(8), 539.
Sieluzycki, C., Konig, R., Matysiak, A., Kus, R., Ircha, D., & Durka, P. J. (2008). Single-​trial
evoked brain responses modeled by multivariate matching pursuit. IEEE Transactions on
Biomedical Engineering, 56(1), 74–​82.
Sponheim, S. R., McGuire, K. A., Kang, S. S., Davenport, N. D., Aviyente, S., Bernat, E. M., &
Lim, K. O. Evidence of disrupted functional connectivity in the brain after combat-​related
blast injury. Neuroimage, 54, S21–​S29, 2011.
Sweeney-​Reed, C. M. & Nasuto, S. J. (2007). A novel approach to the detection of synchron-
isation in EEG based on empirical mode decomposition. Journal of Computational
Neuroscience, 23(1), 79–​111.
Tağluk, M. E., Çakmak, E. D., & Karakaş, S. (2005). Analysis of the time-​varying energy of
brain responses to an oddball paradigm using short-​term smoothed Wigner–​Ville distribu-
tion. Journal of Neuroscience Methods, 143(2), 197–​208.
Tanaka, T. & Mandic, D. P. (2007). Complex empirical mode decomposition. IEEE Signal
Processing Letters, 14(2), 101–​104.
Tropp, J. A. & Gilbert, A. C. (2007). Signal recovery from random measurements via orthog-
onal matching pursuit. IEEE Transactions on Information Theory, 53(12), 4655–​4666.
Von Stein, A., Chiang, C., & König, P. (2000). Top-​down processing mediated by interareal
synchronization. Proceedings of the National Academy of Sciences, 97(26), 14748–​14753.
Williams, N., Nasuto, S. J., & Saddy, J. D. (2011). Evaluation of empirical mode decomposition
for event-​related potential analysis. EURASIP Journal on Advances in Signal Processing,
2011(1), 965237.
Wu, C-​H., Lee, P-​L., Shu, C-​H., Yang, C-​Y., Lo, M-​T., Chang, C-​Y., & Hsieh, J-​C. (2012).
Empirical mode decomposition-​based approach for intertrial analysis of olfactory event-​
related potential features. Chemosensory Perception, 5(3–​4), 280–​291.
Wu, Z. & Huang, N. E. (2009). Ensemble empirical mode decomposition: A noise-​assisted data
analysis method. Advances in Adaptive Data Analysis, 1(1), 1–​41.
Yeung, N., Bogacz, R., Holroyd, C. B., & Cohen, J. D. (2004). Detection of synchronized
oscillations in the electroencephalogram: An evaluation of methods. Psychophysiology,
41(6), 822–​832.
Zhao, Y. L., Atlas, E., & Marks, R. J. (1990). The use of cone-​shaped kernels for generalized
time-​frequency representations of nonstationary signals. IEEE Transactions on Acoustics,
Speech, and Signal Processing, 38(7), 1084–​1091.
 CHAPTER 5

T IM E FREQU EN C Y A NA LYSE S
IN EVENT-​R E L AT E D
P OTENTIAL M ETH OD OL O G I E S

ANNA WEINBERG, PAIGE ETHRIDGE,

BELEL AIT OUMEZIANE, AND DAN FOTI

5.1  Introduction

Event-​related potentials (ERPs) are powerful tools for measuring the dynamics of
human brain activity, and they have been used for decades to measure sensory, cog-
nitive, motor, and emotion-​related processes—​as well as individual differences in
these processes—​across the lifespan (Cohen, 2014; De Haan, 2013; Hajcak et al., 2012;
Kappenman & Luck, 2016; Luck, 2014). ERPs are defined by voltage fluctuations in the
ongoing electroencephalogram (EEG) that are time-​locked to specific events. As we
discuss further in the studies we describe, these events can be the onset of an external
stimulus (e.g., a picture, tone, or feedback about performance), or the generation of
motor response (e.g., a button press).
Typically, tasks are designed so that these events are repeated across multiple trials,
which are then averaged within conditions, presumably canceling out substantial
amounts of trial-​level noise and yielding the “prototypical” waveform that is common
across trials (Figure 5.1A shows an example waveform). Specific ERP components are
then identified within these averaged waveforms, and they are quantified numeric-
ally as deviations from a pre-​event baseline period. A component is defined “a set of
voltage changes that are consistent with a single neural generator site and that sys-
tematically vary in amplitude across conditions, time, [and] individuals,” (Luck, 2014,
p. 68). Thus, an ERP component is a portion of the overall waveform—​often, a peak
deflection in the waveform—​that captures the brain response (or set of processes) that
are of interest. ERPs are typically described in terms of their amplitude (measured in
 TIME FREQUENCY ANALYSES    89

Figure 5.1  (A) Example data depicting how multiple underlying ERP components (left) con-
tribute to the observed grand averaged ERP waveforms (middle), which are then compared
across conditions (right). (B) ERPs elicited by feedback delivery on the social incentive delay task.

microvolts; µV), polarity (positive or negative), latency (measured in milliseconds; ms),

and scalp topography (where on the scalp the component is maximal). Amplitude refers
to the difference between activity occurring at some point following an event of interest
and an average pre-​event baseline period (e.g., 200 ms prior to stimulus onset), and
latency refers to the time from stimulus onset to some specific peak activity. Naming
90    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

conventions then frequently reflect both the polarity and latency of the component.
Thus, the P3 is the third major positive-​going peak in the ERP waveform after a stimulus
is presented (and often peaks in the neighborhood of 300 ms, hence the common alter-
native name “P300”). At times, ERP components receive functionally descriptive names
(e.g., the error-​related negativity or ERN).
Because they measure the electrical activity of the brain, the speed of which
approaches the speed of light, ERPs capture neural responses in the time-​frame in which
cognition occurs. This millisecond temporal resolution makes it theoretically possible
to isolate dozens of individual neural processes that occur in even very close temporal
proximity. ERPs have thus been particularly useful in studies requiring high temporal
resolution to identify, for example, the transition from sensory-​driven stimulus pro-
cessing to higher-​order cognitive functions (De Cesarei & Codispoti, 2006; Wiens
et al., 2011), or specific cognitive or affective impairments in a given diagnostic group
(Duncan et al., 2009; Kuperberg et al., 2018).
In comparison with other neuroimaging modalities, EEG techniques are well-​
suited as assessment tools. EEG/​ERP data collection is relatively efficient, economical,
noninvasive, (Kappenman & Luck, 2016), and is well-​tolerated by most participants
across the developmental spectrum (De Haan, 2013). While ERP studies have tradition-
ally been conducted in tightly controlled environments to minimize noise and electrical
interference, advances in technology have allowed for progress in ERP data collection
outside the laboratory and in remote field settings (Tarullo et al., 2017). Additionally,
few contraindications exist for EEG research: for example, people with braces, pregnant
women, and awake infants—​all of whom are frequently excluded from MRI studies—​
typically can participate in EEG studies, making it feasible to collect neuroimaging data
from large and relatively diverse groups of participants. Finally, multiple studies over the
years have explored the psychometric properties of ERPs and found them to be highly
reliable measures of neural activity, comparable to other common assessment methods
both in terms of internal consistency and test-​retest reliability (Baldwin, Larson, &
Clayson, 2015; Ethridge & Weinberg, 2018; Foti et al., 2016; Kujawa et al., 2018; Weinberg
& Hajcak, 2011).
Naturally, these strengths are accompanied by a number of limitations. The
assumption underlying measurement of ERP components in the time domain is that
(a) each component represents distinct sensory and/​or cognitive processes (or a small
set of related processes), and (b) components reflect the activity of a single brain region
(or a small network of closely related brain regions). In line with these assumptions,
ERP components are typically scored based on where on the scalp and when in time
specific peaks in the waveform occur, taking the average amplitude within a specified
time window or the peak deflection (Figure 5.1A). This technique reduces the multi-​
dimensional EEG signal down to two dimensions, and has many advantages (Cohen,
2014; Luck, 2014). Yet the reality of neural activity is that multiple sensory, cogni-
tive, affective, and motor processes can and do occur simultaneously. Because the
observed trial-​averaged waveform represents the sum of all activity measured at a
particular site on the head within a particular time-​window, ERPs representing these
 TIME FREQUENCY ANALYSES    91

unique processes are summed together in the waveform. Figure 5.1B shows how mul-
tiple observed components that overlap both spatially and temporally contribute to
the grand averaged waveform. Traditional component-​scored methods make it dif-
ficult to isolate the contribution each underlying component makes to the observed
average ERP.
Additionally, the electrical signals captured by ERPs are conducted through the brain,
meninges, skull, and scalp, and this signal is subject to spread as it seeks paths of low
resistance; precise identification of primary neural contributors to any one component
is therefore often difficult, particularly for brain regions that are relatively far from the
scalp. Furthermore, neural activity recorded from an electrode exterior to the skull
can reflect the simultaneous and summed activation of many, many thousands—​even
millions—​of neurons (Luck, 2014). Combined with the difficulty of effectively isolating
different components, this can often make source localization of time-​domain ERP
components a dicey proposition (Cohen, 2014).
Processing techniques that isolate unique sources of systematic variance within the
trial-​averaged waveform may allow for both more accurate identification of distinct
neuroelectric signals and better description of their anatomical origins. These signals
can be differentiated based on their temporal and spatial variance, as is done with typical
time-​window averages as well as more advanced techniques like principal component
analysis (PCA) and independent components analysis (ICA; Dien, Spencer, & Donchin,
2003; Foti, Weinberg, Dien, & Hajcak, 2011; Spencer, Dien, & Donchin, 2001). Critically,
distinct neural signals can also be differentiated based on their spectral properties. This
is because the electrical activity measured by the EEG contains rhythmic oscillations.
These oscillations reflect fluctuations in the activity of populations of neurons, and
the different properties of these oscillations can be helpful in differentiating cognitive
operations.
Oscillations are described by their frequency, power, and phase. Frequency describes
the speed of the oscillation, or how many times a sine wave repeats, or cycles, in a given
period of time, and is measured in hertz (Hz). A wave that repeats four times per second
has a frequency of 4 Hz, a wave that repeats 50 times per second has a frequency of 50
Hz, and a wave that repeats once every two seconds has a frequency of 0.5 Hz. Power is
a measure of how much energy is present in a frequency band and is represented as the
amplitude (or height) of the peaks, squared. Finally, phase is measured in degrees, or
radians, and is a measure of when in time any given part of the sine wave exists. EEG
data, as well as the ERPs derived from these EEG data, are composed of oscillations at
multiple frequencies, each present with different relative power at different time-​points.
Time-​frequency techniques then attempt to deconvolve, or separate, these signals, to
identify, for example, how much power is present at a given frequency at specific points
in time.
There are many different signal processing techniques available for decomposing
neuroelectric signals to describe the spectral characteristics of ERPs, including moving
window Fourier transforms, wavelet transforms, and Cohen’s class of time-​frequency
distributions. These all involve representing a given ERP waveform in terms of a set
92    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

of sine waves, each of which is characterized by different frequencies, phases, and

amplitudes. Each technique uses different mathematical formulae to do so and makes
different assumptions about the nature of the oscillatory signal presumed to underlie
the ERP waveform (e.g., Bruns, 2004; Cohen, 2014; Luck, 2014). For a full discussion of
these—​and their relative strengths and weaknesses—​see e.g., Aviyente, this volume, Keil
& Thigpen, this volume? Voytek, this volume. However, a general caveat is that many of
these techniques also involve a loss of temporal precision—​one of the chief advantages
of the ERP technique (Cohen, 2014; Luck, 2014)—​though this matters more for some
experiments than others, and there are techniques available to improve temporal preci-
sion (Aviyente et al., 2006).
In terms of their application to ERPs, time-​frequency techniques are particularly
useful when the signals overlap both temporally and spatially, therefore making these
signals indistinguishable in the time domain (Bernat, Malone, Williams, Patrick, &
Iacono, 2007; Bernat, Nelson, Steele, Gehring, & Patrick, 2011; Bernat, Williams, &
Gehring, 2005; Cohen, Elger, & Ranganath, 2007; Herrmann, Rach, Vosskuhl, & Strüber,
2014; Kolev, Demiralp, Yordanova, Ademoglu, & Isoglu-​Alkaç, 1997). In such instances,
assessment of the differing spectral characteristics of overlapping ERP components is
useful for distinguishing multiple underlying processes that give rise to the observed
waveform. Additionally, insofar as populations of neurons in different regions of the
brain may fire at different frequencies, the time-​frequency components identified in this
way may correspond more closely to distinct sources underlying event-​related brain ac-
tivity (Foti, Weinberg, Bernat, & Proudfit, 2015).
In what follows, we review literature demonstrating the ways in which time-​
frequency signal processing techniques have been useful in shedding new light on
several common ERP components, helping to answer research questions that would
be difficult to address solely within the time domain. We focus here on the mismatch
negativity (MMN), the P3, the error-​related negativity (ERN), and the feedback-​related
negativity (FN)/​reward positivity (RewP). We conclude with a practical example of how
to apply time-​frequency techniques to ERP data and present new analyses of some of
our prior time-​domain work with the FN/​RewP.

5.2  The Mismatch Negativity (MMN)

The temporal resolution of ERPs makes them well suited for studying the earliest
stages of sensory processing. One widely studied sensory ERP component is the
MMN, a neural index of change detection that is automatically elicited by a de-
viant stimulus presented within a repetitive sequence (Näätänen, 1995; Näätänen,
Paavilainen, Rinne, & Alho, 2007). While the MMN can be elicited within any
sensory modality, it is commonly studied as part of auditory processing. For ex-
ample, within a sequence of repeating standard tones, the presentation of a tone
that differs with regard to pitch, duration, or some other stimulus characteristics
 TIME FREQUENCY ANALYSES    93

will automatically elicit the MMN. The auditory MMN typically occurs between
150 and 250 ms following the deviant stimulus and is maximal at frontocentral
electrodes, with a smaller positive-​going potential often apparent at temporal/​
mastoid electrodes. While MMN morphology is dependent upon the stimulus
characteristics, studies generally indicate that the MMN emanates from a combin-
ation of activity in supratemporal and frontal cortical regions (i.e., “temporal” and
“frontal” MMN subcomponents), likely related to pre-​p erceptual stimulus pro-
cessing and involuntary attentional switch, respectively (Alho, 1995). In addition
to the large basic neuroscience literature applying the MMN to the study of sen-
sory functioning, individual differences in MMN amplitude have been examined
with regard to cognitive decline in aging, and cognitive impairment in psychiatric
disorders (Näätänen et al., 2011). For example, the MMN is reduced by approxi-
mately one standard deviation among individuals with schizophrenia (Umbricht
& Krljes, 2005). This impact of schizophrenia on MMN amplitude is equivalent
to approximately 30 years of cognitive aging (i.e., the MMN of an individual with
schizophrenia at age 20 is comparable to that of a non-​psychotic individual at age
50; (Kiang, Braff, Sprock, & Light, 2009). Overall, traditional time-​domain analyses
of MMN amplitude have been useful for examining the time course of early sensory
processing and deficits therein.
Complementing these time-​domain studies, time-​frequency studies have been
useful for isolating the temporal and frontal subcomponents of the MMN, as well as
contextualizing individual differences in MMN amplitude. The frontal portion of the
MMN has been linked primarily to an increase in theta power (i.e., the amplitude of
theta waves across trials), whereas the temporal portion has been linked to theta phase
coherence (i.e., the alignment of theta waves across trials; also see Chapter 9) but not
to theta power (Fuentemilla, Marco-​Pallarés, Münte, & Grau, 2008; Ko et al., 2012).
Time-​frequency approaches have also helped clarify the nature of impaired sen-
sory processing in schizophrenia. While a reduced frontal MMN in schizophrenia is
well-​documented, there is some evidence from time-​domain analyses that the tem-
poral (mastoid) subcomponent may be less affected (Baldeweg, Klugman, Gruzelier,
& Hirsch, 2002). Subsequent studies in schizophrenia have used time-​frequency
approaches to clarify how abnormal MMN amplitude is explained by alterations in
theta power and phase coherence. For example, one study found that time-​domain
MMN amplitude was strongly correlated with frontal theta power among healthy
controls but not among individuals with schizophrenia, suggesting a decoupling be-
tween these signals (Hong, Moran, Du, O’Donnell, & Summerfelt, 2012). Other work
shows that reduced MMN in schizophrenia is characterized by reductions in both
theta power and phase coherence, with differential deficits based on the type of deviant
stimulus (Lee et al., 2017). Thus, time-​frequency decomposition of the MMN has been
useful for teasing apart distinct neurological signals involved in sensory processing
that would be difficult to capture within the time domain, with relevance to both basic
science and clinical applications.
94    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

5.3  The P3

The P3 was first reported by Sutton and colleagues (1965) and has since been
among the most well-​researched components in the ERP literature (Polich, 2012). It is
among the canonical ERP components in that it is commonly observed across a wide
range of stimuli and laboratory tasks, generally manifesting as the third major positive-​
going deflection in the waveform and maximal at parietal electrodes. A P3 is typically
elicited by stimuli that are relatively salient in the local context due to being infrequent,
unexpected, or because they are designated “targets” that are task-​relevant. Thus, the P3
is often present within the waveform for most ERP studies, even if it is not the compo-
nent of primary interest. When the P3 is among the primary outcomes measures, one of
the most common laboratory paradigms used is the “oddball” task (Donchin, Ritter, &
McCallum, 1978). During an oddball task, participants are asked to respond to or other-
wise keep track of a designated target stimulus and otherwise disregard other non-​target
stimuli (i.e., standard stimuli). In the case of a two-​stimulus, auditory oddball task, for
example, two different tones may be presented within an ongoing sequence, with dif-
ferential likelihood (e.g., 80% for standards, 20% for targets). Participants are required
to distinguish between these tones by responding to the occurrence of the target (e.g.,
button press or mentally counting) and not responding to the standard (Polich & Kok,
1995). Discriminating this infrequent target stimulus from the frequently occurring
standard elicits a robust P3, which is increased (i.e., more positive) for the target vs.
standard stimuli (Polich, 2012). Many studies also distinguish between the P3a and P3b
subcomponents, which are clearly differentiated on three-​stimuli oddball tasks which
include frequent standard, infrequent target, and infrequent novel stimuli (i.e., a third
stimulus type that is novel and task-​irrelevant). In this case, the classic parietal P3 in
response to target stimuli is referred to as the P3b, in order to distinguish it from an
overlapping, frontocentral positivity to novel stimuli that is referred to as the P3a, (or
Novelty P3; Simons, Graham, Miles, & Chen, 2001; N. Squires, Squires, & Hillyard,
1975). Broadly, the P3a is thought to reflect frontal lobe functioning in response to nov-
elty, whereas the P3/​P3b is thought to reflect temporal-​parietal brain activity associated
with attention and memory processing (Polich, 2007). For the remainder of this chapter,
we generally use the term “P3” rather than “P3b.”
Some theoretical accounts of the P3 within the oddball task posit that it captures
the updating of an individual’s mental representation prompted by incoming stimuli
(i.e., Context Updating Theory; Donchin, 1981). Following an initial sensory input, it
is thought that an attention-​driven comparison between the current stimulus and pre-
vious mental representation in working memory is made. If no change in stimulus
attributes have been distinguished, the prior mental representation or “schema” of
the stimulus is maintained, thereby evoking sensory potentials. However, when a
new stimulus attribute is perceived (e.g., a target) the mental representation of the
stimulus context in working memory is updated to elicit the P3 (Donchin et al., 1986).
 TIME FREQUENCY ANALYSES    95

P3 amplitude has been shown to be influenced by a number of factors, including cog-

nitive load demands (i.e., reduced P3 amplitude when under high cognitive load) and
target stimulus probability (i.e., increased P3 amplitude to relatively rare stimuli). For
example, people who performed a primary task with varying cognitive demands while
also engaging in a secondary oddball task showed that increasing the primary tasks’ dif-
ficulty attenuated P3 amplitude to targets on the oddball task (Isreal, Chesney, Wickens,
& Donchin, 1980; Wickens, Kramer, Vanasse, & Donchin, 1983). Furthermore, detecting
a target from a standard stimulus within the oddball paradigm elicits a robust P3 ampli-
tude that potentiates as the global and local sequence probability for the target decreases
(Duncan‐Johnson & Donchin, 1977; K. Squires, Wickens, Squires, & Donchin, 1976).
While there is a long history of examining P3 amplitude using traditional time-​
domain techniques, studies have also applied time-​frequency techniques to decompose
spectral properties of the P3. This is relevant in part because, in comparison to standard
stimuli, target stimuli on an oddball task often elicit broad modulation of the ERP wave-
form that spans the P2-​N2-​P3-​Slow Wave complex. Thus, the P3 occurs in the context
of these other, overlapping neural signals that are also sensitive to stimulus properties,
and for some questions it may be helpful to isolate the unique portions of the waveform
that reflect context updating vs. other aspects of stimulus processing. Initial work in this
domain showed that the oddball response is comprised of a progression from theta-​to
delta-​band activity (Başar-​Eroglu, Başar, Demiralp, & Schürmann, 1992; Kolev et al.,
1997). Subsequent analyses applied principal components analyses to time-​frequency
plots in order to isolate a specific spectral subcomponent. The oddball response is
characterized by an early, low-​frequency component (1 Hz at 150 ms), followed by mul-
tiple delta-​theta responses corresponding to the rise and peak of the time-​domain P3
(1–​3 Hz, from 400 to 600 ms), and ultimately resolving with a second low-​frequency
component (1 Hz from 600 to 800 ms) (Bernat et al., 2007).
Decomposing the oddball response in this manner has also been fruitful for clarifying
the nature of individual differences in P3 amplitude in clinical populations. For example,
it is well-​established that time-​domain P3 amplitude is reduced among individuals with
externalizing psychopathology, such as alcohol use disorder (Polich, Pollock, & Bloom,
1994). In one study examining a clinically heterogeneous community sample, reduced
time-​ domain P3 was common across conduct disorder, attention-​ deficit/​
hyper-
activity disorder, oppositional defiant disorder, and substance use disorder (Gilmore,
Malone, Bernat, & Iacono, 2010). As expected, the diagnostic groups were also gener-
ally associated with reduced power in multiple spectral subcomponents spanning 0.5–​3
Hz and 200–​900 ms. Critically, reduced power in a specific delta subcomponent (1 Hz,
400–​600) differentiated the externalizing groups from controls, even after considering
time-​domain P3 amplitude. That is, this precise spectral subcomponent exhibited a
stronger relationship with the clinical phenotype than the time-​domain P3, which by
definition is a composite of these multiple spectral subcomponents. Other work has
examined reduced P3 amplitude in schizophrenia, which is well-​documented (Jeon &
Polich, 2003). Incorporating time-​frequency analyses, however, showed that total delta-​
band activity to oddball stimuli (including phase-​locked and non-​phase-​locked) is
96    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

intact among individuals with schizophrenia (Ergen, Marbach, Brand, Başar-​Eroğlu,

& Demiralp, 2008). This has potentially important implications for the interpret-
ation of reduced time-​domain P3: rather than a reduced neural response per se, the
time-​frequency analyses suggest that schizophrenia may be characterized by greater
temporal jitter in the neural response, which manifests as a reduced peak in the trial-​
averaged waveform. Together, these studies show how a reduced P3 amplitude in clin-
ical populations can be explained by multiple abnormalities in the neural signal, which
are not readily apparent in the time domain.

5.4  The Error-​R elated

Negativity (ERN)

Rapidly identifying the mistakes that we make and altering our behavior in response
to these errors is critical for adaptive functioning. The error-​related negativity (ERN;
also referred to as the error negativity or Ne) is an ERP component that has commonly
been used to study neural processes associated with identifying and adapting to errors
(Falkenstein, Hohnsbein, Hoormann, & Blanke, 1991; Gehring, Goss, Coles, Meyer,
& Donchin, 1993). The ERN is a response-​locked ERP often elicited in speeded reac-
tion tasks that peaks approximately 100 ms following erroneous responses, is max-
imal at frontocentral electrode sites, and is thought to be generated in medial frontal
cortex regions including the anterior cingulate cortex (ACC; for reviews see Gehring
et al., 2011; Holroyd & Coles, 2002; Olvet & Hajcak, 2008). Time-​frequency analyses
have contributed to our knowledge of the unique structure of the ERN (Bernat et al.,
2005; Munneke, Nap, Schippers, & Cohen, 2015; Riesel, Weinberg, Moran, & Hajcak,
2012; Yordanova, Falkenstein, Hohnsbein, & Kolev, 2004), have elucidated possible
mechanisms by which it is generated (Luu, Tucker, & Makeig, 2004; Trujillo & Allen,
2007), and have provided empirical support for some existing theories of its functional
significance (Cavanagh, Cohen, & Allen, 2009; Cavanagh, Zambrano‐Vazquez, &
Allen, 2012; Luu & Tucker, 2001; Luu, Tucker, Derryberry, Reed, & Poulsen, 2003).
With regard to the structure of the component, time-​frequency analyses have
identified how the ERN is both linked to, and separable from, other related ERP
components (Cavanagh et al., 2012; Di Gregorio, Maier, & Steinhauser, 2018; Gehring
& Willoughby, 2004; Steele et al., 2016; Yordanova et al., 2004). For instance, it has been
debated whether neural responses to errors (ERN) and to correct responses (correct-​
related negativity; CRN or Nc), which overlap in time and scalp topography, reflect
the same or distinct processes (Vidal, Hasbroucq, Grapperon, & Bonnet, 2000). While
evidence indicates that the ERN and CRN demonstrate similar characteristics in the
time-​domain, frequency analyses have identified error-​specific signals with unique
scalp topographies (Yordanova et al., 2004), suggesting that the ERN and CRN are not
identical processes and may have distinct neural generators. Specifically, Yordanova and
 TIME FREQUENCY ANALYSES    97

colleagues (2004) identified a delta-​frequency component (1.5–​3.5 Hz) that was specific
to erroneous responses, as well as a theta-​frequency component (4–​8 Hz) that emerged
for both erroneous and correct responses but demonstrated different scalp topographies
depending on accuracy and response side (left or right hand). Similarly, time-​frequency
analyses have been used to demonstrate distinctions between the ERN and the error-​
related positivity (Pe) by demonstrating that the Pe can emerge in the absence of an ERN
(Di Gregorio et al., 2018; Steele et al., 2016), as well as between the ERN and the feedback
negativity (FN, see Section 5.5) by identifying distinct scalp topographies of the ERN
and FN (Gehring & Willoughby, 2004). Nevertheless, theta frequency activity that is
common to several ERP components (ERN, CRN, FN, and N2) has been interpreted
to mean that each of these ERPs reflects similar (though not identical) neural processes
related to performance monitoring and behavioral control (Cavanagh & Shackman,
2015; Cavanagh et al., 2012).
Time-​frequency analyses are also uniquely placed to enhance our understanding of
the mechanisms by which the ERN is generated. The classic view of ERPs suggests that
they reflect phasic bursts of neural activation, while more recently it has been suggested
that ERPs might reflect phase-​resetting of ongoing oscillatory activity (see Keil &
Thigpen, this volume). Although some argue that time-​frequency techniques cannot
distinguish between these two hypotheses (Yeung, Bogacz, Holroyd, & Cohen, 2004;
Yeung, Bogacz, Holroyd, Nieuwenhuis, & Cohen, 2007), evidence suggests that the
ERN is best explained by the combination of an amplitude increase and phase-​resetting
(Trujillo & Allen, 2007). This is an important contribution, partly because under-
standing how the ERN is generated provides insight into its functional significance. For
example, Cavanagh and colleagues (2009) suggested that theta oscillatory dynamics
reflected in the ERN may represent a mechanism by which neural regions responsible
for performance monitoring and for cognitive control communicate with each other
(see Chapter 3 for a discussion of neural oscillations; Keil & Thigpen).
As with all of the ERPs discussed in this chapter, understanding how the ERN is
associated with individual difference variables is an active area of research. Time-​
window analyses of ERN responses have identified links between the ERN and multiple
forms of psychopathology, including generalized anxiety disorder (GAD) (Weinberg,
Olvet, & Hajcak, 2010), obsessive compulsive disorder (Endrass et al., 2010; Riesel,
Kathmann, & Endrass, 2014), substance use disorder (Euser, Evans, Greaves-​Lord,
Huizink, & Franken, 2013), and depression (Weinberg, Liu, & Shankman, 2016). Time-​
frequency analyses have begun to meaningfully advance our understanding of such
individual differences. For instance, Cavanagh and colleagues (2017) determined that
error-​related theta power was a unique predictor of GAD status over and above the
time-​window scored ERN, and when they included theta network dynamics in their
model, they were able to classify clinical participants with an impressive 66% accuracy.
These data suggest that time-​frequency analyses may have a powerful role to play in
using neural data to classify clinical populations. While time-​frequency analyses have
led to several critical advances in our understanding of the ERN, as noted here, this is
likely to remain a fruitful avenue of continued study.
98    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

5.5  The Feedback Negativity (FN)/​

Reward Positivity (RewP)

In addition to endogenous performance monitoring, optimization of behavior depends

on the ability to discriminate positive (e.g., monetary gain, correct performance feed-
back, positive interpersonal feedback) from negative (e.g., monetary losses, incorrect
performance feedback, negative interpersonal feedback) external environmental feed-
back. A substantial body of research on neural discrimination of favorable vs. unfavor-
able feedback has used an ERP component called, variously, the feedback negativity
(FN), the feedback-​related negativity (FRN), or the reward positivity (RewP) (Foti &
Weinberg, 2018; Foti et al., 2011; Hajcak, Moser, Holroyd, & Simons, 2006; Holroyd,
Nieuwenhuis, Yeung, & Cohen, 2003; Miltner, Braun, & Coles, 1997). This component
peaks approximately 250–​300 ms at frontocentral recording sites following the pres-
entation of feedback (Miltner et al., 1997), and has often been studied in the context
of laboratory gambling tasks, in which individuals make responses in order to win or
lose money on each trial. Feedback indicating monetary gains, losses, or non-​gains is
presented following response selection.
Traditionally, the FN/​RewP was viewed as a negative-​going component (thus the em-
phasis on “negativity” in the name) and a member of a broader class of medial-​frontal
negativities (MFNs) that includes the ERN (Gehring & Willoughby, 2004; Miltner et al.,
1997). This negative peak, which like other MFNs has been thought to be generated by
the ACC (Gehring & Willoughby, 2002; Potts, Martin, Burton, & Montague, 2006) via
phasic input from the midbrain dopamine system (Holroyd & Coles, 2002), was thought
to be observed following unfavorable outcomes (e.g., feedback indicating monetary
losses) and absent following favorable outcomes (e.g., feedback indicating monetary
gain). This perspective suggests a binary differentiation of losses from non-​losses,
reflecting the activity of a single cognitive process (Hajcak et al., 2006; Kreussel et al.,
2011). More recent data suggests, however, that the difference between neural responses
to losses and gains may also be driven in part by a substantial positive-​going deflec-
tion in the waveform elicited by favorable outcomes that is absent following unfavorable
outcomes (i.e., the reward positivity; Baker & Holroyd, 2011; Bernat et al., 2011; Bogdan,
Santesso, Fagerness, Perlis, & Pizzagalli, 2011; Carlson, Foti, Harmon-​Jones, Mujica-​
Parodi, & Hajcak, 2011; Foti et al., 2011; Harper, Olson, Nelson, & Bernat, 2011; Hewig
et al., 2010; Holroyd, Krigolson, & Lee, 2011; Holroyd, Pakzad-​Vaezi, & Krigolson, 2008).
A possible explanation for these conflicting views is that the trial-​averaged component
following feedback reflects the activity of two independent but overlapping processes: a)
a negative deflection in the waveform, which is enhanced following loss feedback but
not reward feedback, and b) a positive deflection that is enhanced following reward
feedback and decreased following losses (e.g., Bernat, Nelson, & Baskin-​Sommers,
2015; Bernat et al., 2011; Carlson et al., 2011; Foti et al., 2011). An increased (underlying)
negative-​going component and a decreased (underlying) positive-​going component
 TIME FREQUENCY ANALYSES    99

might then summate to create the observed negative-​going component following feed-
back indicating losses that had typically been observed in the time domain (i.e., the
classic FN/​FRN/​MFN).
Studies using time-​frequency methods to explore neural activity in this time-​window
have tended to bear this out, as there is evidence that activity in both the theta-​and
delta-​bands make unique contributions to the amplitude of the FN/​RewP (Bernat
et al., 2015; Bernat et al., 2011). In particular, theta activity in this time range appears
to be primarily sensitive to loss/​negative outcomes, with losses eliciting enhanced ac-
tivity compared to gains in this frequency range (Bernat, Nelson, Holroyd, Gehring, &
Patrick, 2008; Bernat et al., 2011; Gheza, De Raedt, Baeken, & Pourtois, 2018; Harper
et al., 2011; L. Nelson, Patrick, Collins, Lang, & Bernat, 2011; Olson, Harper, Golosheykin,
Bernat, & Anokhin, 2011; Webb et al., 2017). Delta has more often been linked to activity
in the time-​range of the P3 that follows the FN/​RewP at more parietal sites (Gehring
& Willoughby, 2002; Holroyd & Coles, 2002; Miltner et al., 1997). However, there is
increasing evidence that delta activity also underlies the observed reward positivity
occurring in the time-​range and spatial location of the FN/​RewP (Bernat et al., 2015;
Bernat et al., 2008; Foti, Weinberg, Bernat, & Proudfit, 2014; Harper et al., 2011). Indeed,
delta activity in this time-​range is enhanced for gains compared to losses (Bernat et al.,
2015; Bernat et al., 2008; Bernat et al., 2011; Cavanagh, 2015; Cavanagh, Masters, Bath,
& Frank, 2014; Foti, Weinberg, et al., 2014; Gheza et al., 2018; Harper et al., 2011; Leicht
et al., 2013; L. Nelson et al., 2011; Olson et al., 2011; Pornpattananangkul & Nusslock,
2016; Webb et al., 2017), and appears to drive the reward positivity observed in the trial-​
averaged waveforms (Bernat et al., 2015; Foti et al., 2011; Harper et al., 2011).
The activity of these two frequency bands also appears to be dissociable, insofar as the
differences between loss and gain activity in the theta and delta band tend to be at best
weakly correlated (e.g., Bernat et al., 2015; Bernat et al., 2011; Foti, Weinberg, et al., 2014).
Moreover, source analysis suggests unique generators, with loss-​related theta localizing
to the ACC and gain-​related delta to a possible source in the basal ganglia (Foti,
Weinberg, et al., 2014). Combined, these data suggest that changes in theta and delta are
not yoked expressions of the same underlying process, but instead may represent dis-
tinct cognitive processes and contributions to the FN/​RewP (Bernat et al., 2015; Bernat
et al., 2008; Bernat et al., 2011; Gheza et al., 2018; Harper et al., 2011; Olson et al., 2011).
Consistent with this, theta response to losses appears to reflect a relatively low-​level re-
sponse to negative outcomes that is frequently insensitive to stimulus parameters and
experimental context (Bernat et al., 2015; Bernat et al., 2011; Harper et al., 2011; Watts,
Bachman, & Bernat, 2017; Watts & Bernat, 2018). This increased theta (Section 5.4)
appears to then act as a signal to recruit attentional and executive resources to respond
to mistakes, novelty, and negative feedback (Aviyente, Tootell, & Bernat, 2017; Cavanagh
& Frank, 2014; Cavanagh et al., 2012; Van Noordt, Campopiano, & Segalowitz, 2016; van
Noordt, Desjardins, Gogo, Tekok-​Kilic, & Segalowitz, 2017). In contrast, in monetary
reward paradigms, delta appears sensitive not only to loss vs. gain distinctions, but also
higher-​level secondary stimulus attributes, such as magnitude (Bernat et al., 2015), con-
text (Bernat et al., 2015; Watts & Bernat, 2018), expectancy violations (Cavanagh, 2015;
100    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

Gheza et al., 2018; Watts et al., 2017), and reward uncertainty (Gheza et al., 2018) and
thus may reflect more elaborative processing of the feedback beyond the most salient
dimension of the stimuli (see, however: Leicht et al., 2013).
Identification of dissociable and functionally distinct processes in the time-​window
of the FN/​RewP has also proven to be useful in studies seeking to understand indi-
vidual differences in neural responses to feedback, including describing develop-
mental influences on more specific neural processes, as well as identifying specific
cognitive-​affective deficits in clinical samples. For instance, there is evidence from
MRI research that brain regions supporting the neural response to rewards undergo
considerable developmental changes from childhood through adolescence and into
adulthood. In particular, fMRI studies tend to find an adolescent-​specific peak in
striatal activation to reward feedback (Braams, van Duijvenvoorde, Peper, & Crone,
2015; J. R. Cohen et al., 2010; Ernst et al., 2005; Galvan et al., 2006; Somerville, Hare,
& Casey, 2011; Van Leijenhorst et al., 2009). Most studies examining developmental
changes in the FN/​RewP, however, have failed to find evidence for an adolescent-​
specific peak, or indeed even significant developmental changes (Kujawa et al.,
2018; Larson, South, Krauskopf, Clawson, & Crowley, 2011; Lukie, Montazer-​Hojat,
& Holroyd, 2014; Santesso, Dzyundzyak, & Segalowitz, 2011); but see also (Arbel,
McCarty, Goldman, Donchin, & Brumback, 2018). In a recent study of 8–​17-​year-​old
participants, however, Bowers and colleagues (2018) examined both time-​domain
ERPs and time-​frequency-​derived theta and delta band activity. They found that,
consistent with previous work, the time-​domain-​scored RewP was not associated
with participants’ age. Yet, theta power—​which was enhanced for losses relative to
gains—​decreased with age, whereas delta power—​which was greater for gains than
losses—​increased. In a study investigating whether family history of psychopath-
ology might influence these normative developmental effects, we also collected
a sample of never-​depressed daughters of mothers with or without a history of de-
pression (Ethridge et al., 2021). In this sample, we found that the association between
delta power and daughters’ developmental stage differed depending on maternal risk
status. For daughters of mothers who had never been depressed, increased develop-
ment was associated with increases in delta power following rewards. For daughters
of mothers with a history of depression, increased development was associated with
decreased delta power following rewards, suggesting high-​risk daughters may become
increasingly vulnerable across the course of adolescence. This effect was not observed
for power in the theta frequency.
Work identifying functional differences between delta and theta activation in re-
sponse to external feedback has laid the foundation for identifying specific cognitive and
affective deficits in various psychopathological groups. For instance, there is extensive
data suggesting that individuals high on externalizing-​proneness (including alcohol and
substance use/​abuse, rule-​breaking, and personality measures) show broad and non-​
specific amplitude reductions in multiple ERPs (Hall, Bernat, & Patrick, 2007; Polich
et al., 1994). This work has been further clarified by time-​frequency decompositions
suggesting these individuals do not in fact show deficits related to theta power elicited
 TIME FREQUENCY ANALYSES    101

by loss feedback; instead, these group differences seem to be driven by reductions in

delta activity elicited by rewarding feedback (Bernat et al., 2011).
A great deal of work has also examined the FN/​RewP in individuals with depres-
sion or at risk for depression (including work from our own groups). Multiple pre-
vious studies employing monetary guessing tasks have reported that depressed
participants as well as those at risk for depression are characterized by abnormal FN/​
RewPs (Bress, Smith, Foti, Klein, & Hajcak, 2011; Foti, Carlson, Sauder, & Proudfit,
2014; Foti & Hajcak, 2009; Kujawa, Proudfit, & Klein, 2014; Weinberg, Liu, Hajcak,
& Shankman, 2015; Weinberg & Shankman, 2016). However, because many of these
studies measured the FN/​RewP as a difference score, it is unclear whether these results
reflect aberrant neural response to rewards, to losses, or to both. Time-​frequency
investigations have been helpful in clarifying the locus of dysfunction. For instance,
in one study we worked on, greater symptoms of depression were associated specif-
ically with more blunted reward-​related delta—​no such association was found with
loss-​related theta (Foti et al., 2015). Similarly, another study indicated that blunted
delta activity following reward feedback prospectively predicted the onset of depres-
sion in an adolescent sample—​independently of other risk factors (B. Nelson et al.,
2018). We also found that stress exposure—​an important predictor of depression—​
specifically blunted reward-​related delta, and not theta, power; and that decreased
delta power prior to an acute stressor predicted heightened physiological responses to
that stressor (Ethridge et al., 2020).
Additionally, reduced reward-​related delta may be helpful in identifying distinct
symptom profiles. A recent study found that, within a depressed group, symptoms of
anxiety and depression showed dissociable correlations with punishment-​elicited theta
power and reward-​elicited delta power (Cavanagh, Bismark, Frank, & Allen, 2018), such
that symptoms of depression were uniquely associated with decreased reward-​elicited
delta power. In contrast, one study found depression to be associated with blunted mid-
line theta modulation (Mueller, Panitz, Pizzagalli, Hermann, & Wacker, 2015), while
Webb and colleagues (2017) found that depressed adolescents showed increased loss-​
related theta, but no differences in gain-​related delta. A theme across these studies is
that the time-​domain FN/​RewP generally represents a composite of frontocentral
theta-​and delta-​band activity. The relative contribution of these frequency bands to the
observed ERP score, however, will be different across tasks, sample characteristics, and
study contexts, such that a change in FN/​RewP amplitude can be explained by modula-
tion of theta activity, delta activity, or a combination of both—​a question which time-​
frequency decompositions can answer directly.

5.6  Example: Social Reward Processing

As a practical example of how to apply time-​frequency analyses to averaged ERP data,

we revisit recently published findings on social reward processing (Ait Oumeziane,
102    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

Schryer-​Praga, & Foti, 2017). ERP data were collected from 27 adults during a social
incentive delay task, a modified version of the commonly used monetary incentive
delay task (Knutson, Westdorp, Kaiser, & Hommer, 2000; B. K. Novak, Novak, Lynam,
& Foti, 2016; K. D. Novak & Foti, 2015). The task is designed to tease apart anticipa-
tory and consummatory stages of reward processing. On each trial, participants are first
presented with a cue indicating whether it is an incentive or neutral trial. On incen-
tive trials, participants have the opportunity to earn a reward by rapidly responding to
a target stimulus (and are punished for slow reaction times), whereas on neutral trials
participants break even regardless of their reaction time. Following their behavioral re-
sponse to the target stimulus, participants are then shown feedback indicating the result
of that trial (i.e., win or loss on incentive trials, break-​even on neutral trials). On the
traditional monetary version of the task the rewards are nominal amounts of money,
yet more recently a social reward version has been developed in which the “wins” are
instead positive social feedback putatively administered by the experimenter. In a re-
cent study, it was shown that social reward feedback elicits a RewP and feedback-​P3
(described as such in order to differentiate it from the oddball P3, described earlier) that
is of similar morphology and amplitude to monetary reward feedback (Ait Oumeziane
et al., 2017). These original analyses focused exclusively on traditional time-​domain
approaches to scoring the RewP and feedback-​P3. Here, we revisit these data using time-​
frequency analysis.
The time-​domain ERP waveforms and scalp topographies are presented in Figure
5.1A. Consistent with previous research, social reward (“wins”) elicited a more
positive-​going waveform than social punishment (“losses”). The RewP difference
score (contrasting the valence of uncertain feedback: win vs. loss) peaked at 325 ms,
whereas the feedback-​P3 difference score (contrasting the salience of uncertain vs.
certain feedback: win vs. break-​even, loss vs. break-​even) peaked at approximately 400
ms. A challenge in isolating the RewP and feedback-​P3 in this case, however, is that
the waveform to social rewards is modulated within a relatively broad time window
of approximately 200–​800 ms at centroparietal electrodes, thereby encompassing
the P2-​RewP-​P3-​Slow Wave complex. It is unclear whether the difference between
conditions represents multiple, overlapping effects or is instead better interpreted as
a single, sustained increase in the ERP waveform. These possibilities are difficult to
disentangle using traditional time-​window averages but can be addressed using time-​
frequency analysis. Building upon previous time-​frequency decompositions of the
RewP (Bernat et al., 2011; Foti et al., 2015), we sought to isolate three distinct neural
responses:

1. RewP-​delta: an increase in delta power to wins vs. losses at approximately 300 ms

and at central electrodes;
2. FN-​theta: an increase in theta power to losses vs. wins at approximately 300 ms
and at frontocentral electrodes; and
3. Feedback-​P3-​delta: an increase in delta power to wins vs. break-​even outcomes at
approximately 400 ms and at parietal electrodes.
 TIME FREQUENCY ANALYSES    103

For illustrative purposes, we focus here on the P3 to wins; a similar pattern of results was
also observed for the P3 to losses.
Standard signal processing procedures were applied to the data, including re-​
referencing to the mastoid electrodes, filtering from 0.1–​30 Hz, ocular correction,
and artifact rejection (for details, see Ait Oumeziane et al., 2017). The continuous
EEG was segmented relative to the onset of feedback stimuli using a relatively broad
time window of −1500 to 1500 ms, allowing for edge artifacts (i.e., distortion of the
signal near the edges of the window following time-​frequency transform; note this
is a broader time-​window than is typical for most ERP research). ERP averages were
created for each of the three conditions (win, loss, break-​even), and then the time-​
frequency transform was applied. Complex Morlet wavelets were calculated within
BrainVision Analyzer (Brain Products), using a frequency range of 0.5–​20 Hz and
linear steps of 0.25 Hz. A relatively narrow frequency range was chosen here due to the
a priori focus on activity in the delta and theta bands, whereas a broader range could be
chosen for more exploratory analyses. The Morlet parameter was set at c =​3.5 (i.e., 3.5
cycles in the wavelet), and wavelet functions were normalized using Gabor normaliza-
tion. Baseline correction was performed for each wavelet layer using a baseline window
of −500 to −300 ms; the average amplitude in the baseline window was subtracted
from each time point in the layer. These time-​frequency transforms were applied to
the averaged ERP data for each subject and then averaged across subjects to create the
grand averaged spectrogram.
Of interest were two contrasts: wins vs. losses, which ought to elicit reward-​related
delta (RewP) and loss-​related theta (FN) from approximately 200–​400 ms; and win vs.
break even, which ought to elicit delta-​band activity in the time range of the feedback-​
P3 (300–​500 ms). The spectrogram for the win vs. loss contrast is presented in Figure
5.2. As expected, activity in the delta frequency band was increased for wins vs. losses
(the red portion of the spectrogram within the delta band), which peaked at approxi-
mately 2.5 Hz and 295 ms. Overlapping with this response was an increase in activity
within the theta frequency band for losses vs. wins (the blue portion of the spectrogram
within the theta band), which peaked at approximately 5.25 Hz and at 235 ms. Both of
these responses occurred within the time range of the FN/​RewP but at distinct fre-
quency bands, presenting the opportunity to extract separate scores for each. We scored
the delta and theta responses by extracting wavelet layers centered at 2.5 Hz and 5.25 Hz,
respectively. Wavelet layers yield a waveform representing power at that frequency band
over time, which can then be scored by taking a time-​window average of peak score
akin to time-​domain ERPs (Figure 5.2, right). We scored each response as the average
power within a 50-​ms window surrounding the peak of the win minus loss difference,
which was somewhat different for each frequency band: 270–​320 ms for delta and 210–​
260 ms for theta. Notably, these wavelets each exhibited more focal scalp topographies
than the time-​domain FN/​RewP, with maxima at frontocentral electrodes. To maintain
consistency with the time-​domain FN/​RewP, we scored the delta and theta responses
at electrode Cz. The effects of condition (win vs. loss) were significant for both delta
(t(26) =​3.04, p < .01) and theta (t(26) =​3.11, p < .01). Critically, the difference scores
104    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

Cz: Win - Loss Theta layer at 5.25 Hz

Theta
Delta layer at 2.5 Hz

Delta

Pz: Win - Break Even

Delta layer at 1.75 Hz

Theta

Delta

Figure 5.2 Time-​frequency analysis of the reward positivity elicited by the social incen-
tive delay task. Top: The contrast of wins versus losses, isolating delta-​and theta-​band activity
corresponding to the time-​domain FN/​RewP. Bottom: The contrast of wins versus break-​even
outcomes, isolating delta-​band activity corresponding to the feedback-​P3.

for delta and theta were also both significantly correlated with the time-​domain RewP
difference score (Table 5.1). As is common in the literature, the delta and theta effects
were not significantly correlated with one another, further suggesting that they each
capture a distinct portion of the FN/​RewP.
The analogous spectrogram for the win vs. break-​even contrast is presented in Figure
5.2. In comparison with the FN/​RewP analyses, here we expected to find prominent
delta-​band activity corresponding to the feedback-​P3. As seen in the spectrogram,
activity in the delta band was indeed increased for wins vs. break-​even outcomes, an
effect which peaked at 1.75 Hz and at 365 ms. We extracted the wavelet layer at 1.75 Hz
and scored this delta response as the average power from 340–​390 ms. This wavelet
exhibited a scalp topography highly similar to the time-​domain feedback-​P3, with a
peak at centroparietal electrodes. To be consistent with our time-​domain analyses, we
scored this delta effect at electrode Pz. The increase in delta-​band activity for win vs.
break-​even outcomes was statistically significant (t(26) =​7.90, p < .001), and the delta-​
band difference score was significantly correlated with the time-​domain feedback-​P3
difference score (Table 5.1).
 TIME FREQUENCY ANALYSES    105

Table 5.1 Correlations between time-​domain and time-​frequency scores of social

reward processing
Reward Positivity Feedback-​P3
Delta Theta Time Delta
Time Domain (2.5 Hz) (5.25 Hz) Domain (1.75 Hz)

FN/​RewP Time Domain —​

Delta (2.5 Hz) .39 —​
Theta (5.25 Hz) −.40 −.04 —​
Feedback-​P3 Time Domain .47 .14 −.12 —​
Delta (1.75 Hz) .16 .00 −.14 .71 —​

Note: FN/​RewP variables are the contrast of win vs. loss; feedback-​P3 variables are the contrast of win
vs. break-​even. Coefficients are Spearman’s rho. Values in bold are significant at p < .05.

It is notable that superior separation of the FN/​RewP and feedback-​P3 was achieved
in this case by using time-​frequency analyses as compared to traditional time-​domain
analyses. Specifically, the time-​domain FN/​RewP and feedback-​P3 were significantly
correlated with one another despite being scored at non-​overlapping time windows
(300–​350 ms and 370–​420 ms) and electrodes (Cz and Pz). This was not the case for the
time-​frequency measures: the FN-​theta and RewP-​delta scores were not significantly
correlated with the time-​domain feedback-​P3 score, and P3-​delta scores were not sig-
nificantly correlated with the time-​domain FN/​RewP scores. We further tested this
pattern of specificity using multiple regression, predicting each time-​domain ERP from
the three time-​frequency variables. When entered as simultaneous predictors, time-​
domain FN/​RewP amplitude was significantly predicted by a combination of RewP-​
delta (β =​.46, p < .05) and FN-​theta (β =​−.38, p < .05), but not P3-​delta (β =​.11, p =​.53).
Conversely, time-​domain feedback-​P3 amplitude was significantly predicted only by
P3-​delta (β =​.66, p < .001) and not by RewP-​delta (β =​.15, p=​.33) or FN-​theta (β=​ −.15,
p =​.28). Thus, time-​frequency analysis facilitated the isolation of three distinct neural
signals involved in social reward processing that would have been difficult to achieve
solely within the time domain, where signal overlap is more problematic in this experi-
mental context.
The example described shows how time-​frequency analyses can aid in the interpret-
ation of traditional ERP effects. In these data, positive social feedback modulated the
ERP waveform in a time-​range spanning the FN/​RewP and P3, which overlapped with
each other. The traditional time-​domain approach of scoring these ERPs as the average
amplitude within separate time windows could not adequately address the problem of
component overlap. Time-​frequency decomposition, on the other hand, was able to iso-
late three distinct signals: RewP-​delta, FN-​theta, and P3-​delta. Similar to the time do-
main, these three signals were all sensitive to outcome type: RewP-​delta and FN-​theta
106    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

were modulated by outcome valence, and P3-​delta was modulated by outcome certainty.
In contrast with the time domain, however, these three signals achieved superior sep-
aration: RewP-​delta and FN-​theta each captured unique portions of the time-​domain
FN/​RewP component, and they were unrelated to the time-​domain P3 component.
Likewise, P3-​delta was strongly related to the time-​domain P3 component but was unre-
lated to the time-​domain FN/​RewP component. Overall, time-​frequency analyses help
us rule out the interpretation that social reward broadly increases the ERP waveform in
a nonspecific fashion; instead, this broad modulation clearly represents a composite of
multiple neural signals. This also lays the groundwork for more precise characterization
of individual differences, whereby we would expect specific associations with the time-​
frequency variables (which are relatively uncorrelated) as compared to the time-​domain
variables (which have substantial overlap).
Comprehensive descriptions of different methodological approaches are covered
in other chapters (e.g., Chapter 4, this volume). However, one important step to con-
sider is whether to conduct these analyses on single-​trial or averaged data, as was done
in our practical description earlier. As noted, ERPs are typically derived from averages
composed of data from multiple trials. This practice reflects the typically low signal-​
to-​noise ratio of ERPs: the amplitude of many ERPs is no more than a few µV, while
the amplitude of “background” neuroelectric signals (see chapter 6, this volume),
other electrophysiological signals, and electrical interference from non-​ biological
sources can be closer to tens of µV. When averaged together, this presumably randomly
distributed noise cancels itself out, whereas the systematic signal, or ERPs, in the data
will not, resulting in a legible ERP component. Single-​trial analysis of ERP data typically
requires relatively large-​amplitude components (e.g., the P3). However, time-​frequency
techniques can in some cases make data more amenable to single-​trial analysis, as
electrical “noise” often has distinct spectral properties from the signal of interest. For
instance, in studies interested in how error or feedback processing might influence trial-​
level adjustments of behavior, time-​frequency techniques could allow the researcher to
focus narrowly on theta and delta power on each trial, with higher frequency activity
(e.g., alpha, 60-​Hz line noise) isolated from these signals. Nonetheless, it is common
practice to conduct time-​frequency decompositions on averages of many trials. And be-
cause averages improve signal-​to-​noise ratio, they are also a helpful basis for identifying
spectral power at different frequency ranges, particularly in exploratory research where
the spectral characteristics of ERPs are less well-​understood. As is often the case, the op-
timal method will depend on the research question.

5.7  Conclusions

ERPs are powerful and flexible tools for understanding sensory, cognitive, and af-
fective processes in the brain, but they are not without limitations. As discussed, time-​
frequency techniques can be helpful in addressing some of these limitations. They can
 TIME FREQUENCY ANALYSES    107

better leverage the multi-​dimensional nature of EEG data—​and, in principle, better rep-
resent the underlying neural signals—​by accounting for not only voltage changes over
time and site on the scalp, but also frequency, power, and phase, and may reveal mul-
tiple dissociable processes folded within the time-​window-​scored ERP. However, time-​
frequency techniques are not a magic bullet. As is discussed at length in other chapters,
time-​frequency decompositions can reduce temporal precision, a chief advantage of the
ERP technique (though, as described in Chapter 4, there are techniques to minimize
this loss). When applied to trial-​averaged ERP data, time-​frequency decompositions
are best thought of conceptually as isolating potentially relevant ERP subcomponents.
That is, it should be possible to “recreate” the pattern of observed ERP findings within
the time-​frequency domain, perhaps based on a combination of activity across multiple
frequency bands. The time-​frequency measures may be more precise than their time-​
domain counterparts to the extent that they isolate the relevant neural signal of interest,
but in cases where there is no apparent modulation of the ERP waveform across ex-
perimental conditions, it is unlikely that time-​frequency approaches will uncover “new”
findings. Therefore, we encourage the reader to think of time-​frequency decompositions
applied to ERP data as the conceptual equivalent of deriving subscales within a self-​
report questionnaire, which can often enhance the precision of measurement and help
clarify the nature of associations with other measures. This is particularly useful where
there are already well-​established associations between a time-​domain ERP and an ex-
ternal measure (e.g., clinical diagnosis, behavior, or personality trait), whereby time-​
frequency decompositions can help explain the nature of those associations. Thus,
time-​frequency analyses can be an effective approach for revisiting published data or
extending the results of prior studies.

REFERENCES
Ait Oumeziane, B., Schryer-​ Praga, J., & Foti, D. (2017). “why don't they ‘like’me
more?”: Comparing the time courses of social and monetary reward processing.
Neuropsychologia, 107, 48–​59.
Alho, K. (1995). Cerebral generators of mismatch negativity (MMN) and its magnetic counter-
part (MMNm) elicited by sound changes. Ear and hearing, 16(1), 38–​51.
Arbel, Y., McCarty, K. N., Goldman, M., Donchin, E., & Brumback, T. (2018). Developmental
changes in the feedback related negativity from 8 to 14 years. International Journal of
Psychophysiology.
Aviyente, S., Tootell, A., & Bernat, E. M. (2017). Time-​frequency phase-​synchrony approaches
with ERPs. International Journal of Psychophysiology, 111, 88–​97.
Baker, T., & Holroyd, C. (2011). Dissociated roles of the anterior cingulate cortex in reward and
conflict processing as revealed by the feedback error-​related negativity and N200. Biological
Psychology, 87, 25–​34.
Baldeweg, T., Klugman, A., Gruzelier, J. H., & Hirsch, S. R. (2002). Impairment in frontal but
not temporal components of mismatch negativity in schizophrenia. International Journal of
Psychophysiology, 43(2), 111–​122.
108    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

Baldwin, S. A., Larson, M. J., & Clayson, P. E. (2015). The dependability of electrophysiological
measurements of performance monitoring in a clinical sample: A generalizability and deci-
sion analysis of the ERN and P e. Psychophysiology, 52(6), 790–​800.
Başar-​Eroglu, C., Başar, E., Demiralp, T., & Schürmann, M. (1992). P300-​response: possible
psychophysiological correlates in delta and theta frequency channels. A review. International
Journal of Psychophysiology, 13(2), 161–​179.
Bernat, E., Malone, S., Williams, W., Patrick, C., & Iacono, W. (2007). Decomposing delta, theta,
and alpha time-​frequency ERP activity from a visual oddball task using PCA. International
Journal of Psychophysiology, 64(1), 62–​74.
Bernat, E., Nelson, L., & Baskin-​Sommers, A. (2015). Time-​Frequency Theta and Delta
Measures Index Separable Components of Feedback Processing in a Gambling Task.
Psychophysiology, 52(5), 626–​637.
Bernat, E., Nelson, L., Holroyd, C., Gehring, W., & Patrick, C. (2008). Separating cognitive
processes with principal components analysis of EEG time-​frequency distributions. Paper
presented at the Proceedings of SPIE.
Bernat, E., Nelson, L., Steele, V., Gehring, W., & Patrick, C. (2011). Externalizing psychopath-
ology and gain–​loss feedback in a simulated gambling task: Dissociable components of brain
response revealed by time-​frequency analysis. Journal of abnormal psychology, 120(2), 352.
Bernat, E., Williams, W., & Gehring, W. (2005). Decomposing ERP time-​frequency energy
using PCA. Clinical Neurophysiology, 116(6), 1314–​1334.
Bogdan, R., Santesso, D., Fagerness, J., Perlis, R., & Pizzagalli, D. (2011). Corticotropin-​
Releasing Hormone Receptor Type 1 (CRHR1) Genetic Variation and Stress Interact to
Influence Reward Learning. The Journal of Neuroscience, 31(37), 13246–​13254.
Bress, J., Smith, E., Foti, D., Klein, D., & Hajcak, G. (2011). Neural response to reward and de-
pressive symptoms in late childhood to early adolescence. Biological Psychology, 89(1), 156–​
162. doi:doi.org/​10.1016/​j.biopsycho.2011.10.004
Carlson, J., Foti, D., Harmon-​Jones, E., Mujica-​Parodi, L., & Hajcak, G. (2011). The neural pro-
cessing of rewards in the human striatum: Correlation of fMRI and event-​related potentials.
NeuroImage, 57, 1608–​1616. doi:10.1016/​j.neuroimage.2011.05.037
Cavanagh, J. F. (2015). Cortical delta activity reflects reward prediction error and related behav-
ioral adjustments, but at different times. NeuroImage, 110, 205–​216.
Cavanagh, J. F., Bismark, A. W., Frank, M. J., & Allen, J. J. (2018). Multiple Dissociations be-
tween Comorbid Depression and Anxiety on Reward and Punishment Processing: Evidence
from Computationally Informed EEG. Computational Psychiatry, 1–​17.
Cavanagh, J. F., Cohen, M. X., & Allen, J. J. B. (2009). Prelude to and resolution of an error: EEG
phase synchrony reveals cognitive control dynamics during action monitoring. Journal of
Neuroscience, 29(1), 98–​105. doi:10.1523/​jneurosci.4137-​08.2009
Cavanagh, J. F., & Frank, M. J. (2014). Frontal theta as a mechanism for cognitive control.
Trends in cognitive sciences, 18(8), 414–​421.
Cavanagh, J. F., Masters, S. E., Bath, K., & Frank, M. J. (2014). Conflict acts as an implicit cost in
reinforcement learning. Nature communications, 5, 5394.
Cavanagh, J. F., & Shackman, A. J. (2015). Frontal midline theta reflects anxiety and cogni-
tive control: Meta-​analytic evidence. Journal of Physiology –​Paris, 109, 3–​15. doi:10.1016/​
j.jphysparis.2014.04.003
Cavanagh, J. F., Zambrano‐Vazquez, L., & Allen, J. J. (2012). Theta lingua franca: A common
mid‐frontal substrate for action monitoring processes. Psychophysiology, 49(2), 220–​238.
Cohen, M. (2014). Analyzing neural time series data: theory and practice: MIT press.
 TIME FREQUENCY ANALYSES    109

Cohen, M., Elger, C., & Ranganath, C. (2007). Reward expectation modulates feedback-​related
negativity and EEG spectra. NeuroImage, 35(2), 968–​978.
Di Gregorio, F., Maier, M. E., & Steinhauser, M. (2018). Errors can elicit an error positivity
in the absence of an error negativity: Evidence for independent systems of human error
monitoring. NeuroImage, 172, 427–​436. doi:10.1016/​j.neuroimage.2018.01.081
Dien, J., Spencer, K. M., & Donchin, E. (2003). Localization of the event-​related potential nov-
elty response as defined by principal components analysis. Cognitive Brain Research, 17(3),
637–​650.
Donchin, E. (1981). Surprise!. . . surprise? Psychophysiology, 18(5), 493–​513.
Donchin, E., Ritter, W., & McCallum, W. (1978). Cognitive psychophysiology: The endogenous
components of the ERP. Event-​related brain potentials in man, 349–​411.
Duncan‐Johnson, C. C., & Donchin, E. (1977). On quantifying surprise: The variation of event‐
related potentials with subjective probability. Psychophysiology, 14(5), 456–​467.
Endrass, T., Schuermann, B., Kaufmann, C., Spielberg, R., Kniesche, R., & Kathmann,
N. (2010). Performance monitoring and error significance in patients with obsessive-​
compulsive disorder. Biological Psychology, 84, 257–​263. doi:10.1016/​j.biopsycho.2010.02.002
Ergen, M., Marbach, S., Brand, A., Başar-​Eroğlu, C., & Demiralp, T. (2008). P3 and delta
band responses in visual oddball paradigm in schizophrenia. Neuroscience letters, 440(3),
304–​308.
Ethridge, P., & Weinberg, A. (2018). Psychometric Properties of Neural Responses to Monetary
and Social Rewards across Development. International Journal of Psychophysiology, in press.
Euser, A. S., Evans, B. E., Greaves-​Lord, K., Huizink, A. C., & Franken, I. H. A. (2013).
Diminished error-​related brain activity as a promising endophenotype for substance use
disorders: Evidence from high-​risk offspring. Addiction Biology, 18(970-​984). doi:10.1111/​
adb.12002
Falkenstein, M., Hohnsbein, J., Hoormann, J., & Blanke, L. (1991). Effects of crossmodal
divided attention on late ERP components: II. Error processing in choice reaction
tasks. Electroencephalography & Clinical Neurophysiology, 78(6), 447–​ 455. doi:10.1016/​
0013-​4694(91)90062-​9
Foti, D., Carlson, J., Sauder, C., & Proudfit, G. (2014). Reward dysfunction in major de-
pression: Multimodal neuroimaging evidence for refining the melancholic phenotype.
NeuroImage, 101, 50–​58.
Foti, D., & Hajcak, G. (2009). Depression and reduced sensitivity to non-​rewards versus
rewards. Biological Psychology, 81(1), 1–​8. doi:10.1016/​j.biopsycho.2008.12.004,
Foti, D., Perlman, G., Hajcak, G., Mohanty, A., Jackson, F., & Kotov, R. (2016). Impaired error
processing in late-​phase psychosis: Four-​year stability and relationships with negative
symptoms. Schizophrenia research, 176(2-​3), 520–​526.
Foti, D., & Weinberg, A. (2018). Reward and feedback processing: State of the field, best
practices, and future directions. In.
Foti, D., Weinberg, A., Bernat, E., & Proudfit, G. (2014). Anterior cingulate activity to mon-
etary loss and basal ganglia activity to monetary gain uniquely contribute to the feedback
negativity. Clinical Neurophysiology.
Foti, D., Weinberg, A., Bernat, E., & Proudfit, G. (2015). Anterior cingulate activity to monetary
loss and basal ganglia activity to monetary gain uniquely contribute to the feedback nega-
tivity. Clin Neurophysiol, 126(7), 1338–​1347. doi:10.1016/​j.clinph.2014.08.025
Foti, D., Weinberg, A., Dien, J., & Hajcak, G. (2011). Event‐related potential activity in the basal
ganglia differentiates rewards from nonrewards: Temporospatial principal components
110    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

analysis and source localization of the feedback negativity. Human brain mapping, 32(12),
2207–​2216.
Fuentemilla, L., Marco-​Pallarés, J., Münte, T., & Grau, C. (2008). Theta EEG oscillatory activity
and auditory change detection. Brain research, 1220, 93–​101.
Gehring, W., Goss, B., Coles, M. G. H., Meyer, D. E., & Donchin, E. (1993). A neural system for
error detection and compensation. Psychological Science, 4(6), 385–​390. doi:10.1111/​j.1467-​
9280.1993.tb00586.x
Gehring, W., Liu, Y., Orr, J. M., & Carp, J. (Eds.). (2011). The error-​related negativity (ERN/​Ne).
New York, NY: Oxford University Press.
Gehring, W., & Willoughby, A. (2002). The medial frontal cortex and the rapid pro-
cessing of monetary gains and losses. Science, 295(5563), 2279–​2282. doi:10.1126/​
science.1066893
Gehring, W., & Willoughby, A. (2004). Are all medial frontal negativities created equal?
Toward a richer empirical basis for theories of action monitoring. Errors, conflicts, and the
brain. Current opinions on performance monitoring, 14, 20.
Gheza, D., De Raedt, R., Baeken, C., & Pourtois, G. (2018). Integration of reward with cost
anticipation during performance monitoring revealed by ERPs and EEG spectral
perturbations. NeuroImage, 173, 153–​164.
Gilmore, C., Malone, S., Bernat, E., & Iacono, W. (2010). Relationship between the P3 event‐
related potential, its associated time‐frequency components, and externalizing psychopath-
ology. Psychophysiology, 47(1), 123–​132.
Hajcak, G., Moser, J., Holroyd, C., & Simons, R. (2006). The feedback-​related negativity reflects
the binary evaluation of good versus bad outcomes. Biological Psychology, 71(2), 148–​154.
doi:10.1016/​j.biopsycho.2005.04.001
Hall, J. R., Bernat, E. M., & Patrick, C. J. (2007). Externalizing psychopathology and the error-​
related negativity. Psychological science, 18(4), 326–​333.
Harper, J., Olson, L., Nelson, L., & Bernat, E. (2011). Delta-​Band Reward Processing Occurring
During the Feedback-​Related Negativity (FRN). Poster presented at annual meeting of the
Society for Psychophysiological Research. Boston, MA.
Herrmann, C. S., Rach, S., Vosskuhl, J., & Strüber, D. (2014). Time–​frequency analysis of event-​
related potentials: a brief tutorial. Brain topography, 27(4), 438–​450.
Hewig, J., Kretschmer, N., Trippe, R., Hecht, H., Coles, M., Holroyd, C., & Miltner, W. (2010).
Hypersensitivity to reward in problem gamblers. Biological psychiatry, 67(8), 781–​783.
Holroyd, C., & Coles, M. (2002). The neural basis of human error processing: Reinforcement
learning, dopamine, and the error-​related negativity. Psychological review, 109(4), 679–​709.
doi:10.1037//​0033-​295X.109.4.67
Holroyd, C., Krigolson, O., & Lee, S. (2011). Reward positivity elicited by predictive cues.
Neuroreport, 22(5), 249.
Holroyd, C., Nieuwenhuis, S., Yeung, N., & Cohen, J. (2003). Errors in reward prediction are
reflected in the event-​related brain potential. Neuroreport, 14(18), 2481–​2484. doi:10.10 97/​
01.wnr.0 0 0 0 0 9 9 6 01.414 03.a
Holroyd, C., Pakzad-​Vaezi, K., & Krigolson, O. (2008). The feedback correct-​related posi-
tivity: sensitivity of the event-​related brain potential to unexpected positive feedback.
Psychophysiology, 45(5), 688–​697. doi:10.1111/​j.1469-​8986.2008.00668.x
Hong, L. E., Moran, L. V., Du, X., O’Donnell, P., & Summerfelt, A. (2012). Mismatch negativity
and low frequency oscillations in schizophrenia families. Clinical Neurophysiology, 123(10),
1980–​1988.
 TIME FREQUENCY ANALYSES    111

Isreal, J. B., Chesney, G. L., Wickens, C. D., & Donchin, E. (1980). P300 and tracking diffi-
culty: Evidence for multiple resources in dual‐task performance. Psychophysiology, 17(3),
259–​273.
Jeon, Y. W., & Polich, J. (2003). Meta‐analysis of P300 and schizophrenia: Patients, paradigms,
and practical implications. Psychophysiology, 40(5), 684–​701.
Kappenman, E. S., & Luck, S. J. (2016). Best practices for event-​related potential research in
clinical populations. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 1(2),
110–​115.
Kiang, M., Braff, D. L., Sprock, J., & Light, G. A. (2009). The relationship between preattentive
sensory processing deficits and age in schizophrenia patients. Clinical Neurophysiology,
120(11), 1949–​1957.
Knutson, B., Westdorp, A., Kaiser, E., & Hommer, D. (2000). FMRI visualization of brain ac-
tivity during a monetary incentive delay task. NeuroImage, 12(1), 20–​27.
Ko, D., Kwon, S., Lee, G.-​T., Im, C. H., Kim, K. H., & Jung, K.-​Y. (2012). Theta oscillation related
to the auditory discrimination process in mismatch negativity: oddball versus control para-
digm. Journal of Clinical Neurology, 8(1), 35–​42.
Kolev, V., Demiralp, T., Yordanova, J., Ademoglu, A., & Isoglu-​Alkaç, Ü. (1997). Time–​
frequency analysis reveals multiple functional components during oddball P300.
Neuroreport, 8(8), 2061–​2065.
Kreussel, L., Hewig, J., Kretschmer, N., Hecht, H., Coles, M., & Miltner, W. (2011). The influence
of the magnitude, probability, and valence of potential wins and losses on the amplitude of
the feedback negativity. Psychophysiology, 49, 207–​219. doi:10.1111/​j.1469-​8986.2011.01291.x
Kujawa, A., Carroll, A., Mumper, E., Mukherjee, D., Kessel, E., Olino, T., . . . Klein, D. (2018).
A longitudinal examination of event-​ related potentials sensitive to monetary reward
and loss feedback from late childhood to middle adolescence. International Journal of
Psychophysiology, 132, 323–​330.
Kujawa, A., Proudfit, G., & Klein, D. (2014). Neural reactivity to rewards and losses in offspring
of mothers and fathers with histories of depressive and anxiety disorders. Journal of ab-
normal psychology, 123(2), 287.
Larson, M. J., South, M., Krauskopf, E., Clawson, A., & Crowley, M. J. (2011). Feedback and re-
ward processing in high-​functioning autism. Psychiatry research, 187(1-​2), 198–​203.
Lee, M., Sehatpour, P., Hoptman, M. J., Lakatos, P., Dias, E. C., Kantrowitz, J. T., . . . Javitt, D. C.
(2017). Neural mechanisms of mismatch negativity dysfunction in schizophrenia. Molecular
psychiatry, 22(11), 1585.
Leicht, G., Troschütz, S., Andreou, C., Karamatskos, E., Ertl, M., Naber, D., & Mulert, C. (2013).
Relationship between oscillatory neuronal activity during reward processing and trait im-
pulsivity and sensation seeking. PloS one, 8(12), e83414.
Luck, S. J. (2014). An introduction to the event-​related potential technique: MIT press.
Lukie, C. N., Montazer-​Hojat, S., & Holroyd, C. B. (2014). Developmental changes in the re-
ward positivity: An electrophysiological trajectory of reward processing. Developmental
cognitive neuroscience, 9, 191–​199.
Luu, P., & Tucker, D. M. (2001). Regulating action: Alternating activation of midline frontal
and motor cortical networks. Clinical Neurophysiology, 112(7), 1295–​ 1306. doi:10.1016/​
S1388-​2457(01)00559-​4
Luu, P., Tucker, D. M., Derryberry, D., Reed, M., & Poulsen, C. (2003). Electrophysiological
responses to errors and feedback in the process of action regulation. Psychological Science,
14(1), 47–​53. doi:10.1111/​1467-​9280.01417
112    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

Luu, P., Tucker, D. M., & Makeig, S. (2004). Frontal midline theta and the error-​related nega-
tivity: Neurophysiological mechanisms of action regulation. Clinical Neurophysiology, 115,
1821–​1835. doi:10.1016/​j.clinph.2004.03.031
Miltner, W., Braun, C., & Coles, M. (1997). Event-​related brain potentials following incorrect
feedback in a time-​estimation task: Evidence for a “generic” neural system for error detec-
tion. Journal of Cognitive Neuroscience, 9(6), 788–​798. doi:10.1162/​jocn.1997.9.6.788
Mueller, E. M., Panitz, C., Pizzagalli, D. A., Hermann, C., & Wacker, J. (2015). Midline theta
dissociates agentic extraversion and anhedonic depression. Personality and Individual
Differences, 79, 172–​177.
Munneke, G.-​J., Nap, T. S., Schippers, E. E., & Cohen, M. X. (2015). A statistical comparison of
EEG time-​and time-​frequency domain representations of error processing. Brain Research,
1618(222-​230). doi:10.1016/​j.brainres.2015.05.030
Näätänen, R. (1995). The mismatch negativity: a powerful tool for cognitive neuroscience. Ear
and hearing, 16(1), 6–​18.
Näätänen, R., Kujala, T., Kreegipuu, K., Carlson, S., Escera, C., Baldeweg, T., & Ponton, C.
(2011). The mismatch negativity: an index of cognitive decline in neuropsychiatric and
neurological diseases and in ageing. Brain, 134(12), 3435–​3453.
Näätänen, R., Paavilainen, P., Rinne, T., & Alho, K. (2007). The mismatch negativity (MMN)
in basic research of central auditory processing: a review. Clinical Neurophysiology, 118(12),
2544–​2590.
Nelson, B., Infantolino, Z., Klein, D., Perlman, G., Kotov, R., & Hajcak, G. (2018). Time-​
frequency reward-​related delta prospectively predicts the development of adolescent-​onset
depression. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 3(1), 41–​49.
Nelson, L., Patrick, C., Collins, P., Lang, A., & Bernat, E. (2011). Alcohol impairs brain reactivity
to explicit loss feedback. Psychopharmacology, 1–​10.
Novak, B. K., Novak, K. D., Lynam, D. R., & Foti, D. (2016). Individual differences in the time
course of reward processing: stage-​specific links with depression and impulsivity. Biological
Psychology, 119, 79–​90.
Novak, K. D., & Foti, D. (2015). Teasing apart the anticipatory and consummatory pro-
cessing of monetary incentives: An event‐related potential study of reward dynamics.
Psychophysiology, 52(11), 1470–​1482.
Olson, L., Harper, J., Golosheykin, S., Bernat, E., & Anokhin, A. (2011). Development of the
Feedback Negativity in early adolescence: A longitudinal study of time-​frequency theta and
delta components. Poster presented at the 2011 meeting of the Society for Psychophysiological
Research.
Olvet, D. M., & Hajcak, G. (2008). The error-​related negativity (ERN) and psychopath-
ology: Toward an endophenotype. Clinical Psychology Review, 28(8), 1343–​1354. doi:10.1016/​
j.cpr.2008.07.003
Polich, J. (2007). Updating P300: an integrative theory of P3a and P3b. Clinical Neurophysiology,
118(10), 2128–​2148.
Polich, J. (2012). Neuropsychology of P300. Oxford handbook of event-​ related potential
components, 159–​188.
Polich, J., & Kok, A. (1995). Cognitive and biological determinants of P300: an integrative re-
view. Biological Psychology, 41(2), 103–​146.
Polich, J., Pollock, V., & Bloom, F. (1994). Meta-​analysis of P300 amplitude from males at risk
for alcoholism. Psychological bulletin, 115(1), 55.
 TIME FREQUENCY ANALYSES    113

Pornpattananangkul, N., & Nusslock, R. (2016). Willing to wait: Elevated reward-​processing

EEG activity associated with a greater preference for larger-​ but-​
delayed rewards.
Neuropsychologia, 91, 141–​162.
Potts, G., Martin, L., Burton, P., & Montague, P. (2006). When things are better or worse than
expected: the medial frontal cortex and the allocation of processing resources. Journal of
Cognitive Neuroscience, 18(7), 1112–​1119.
Riesel, A., Kathmann, N., & Endrass, T. (2014). Overactive performance monitoring in
obsessive-​compulsive disorder is independent of symptom expression. European Archives of
Psychiatry and Clinical Neuroscience, 264, 707–​7 17. doi:10.1007/​s00406-​014-​0499-​3
Riesel, A., Weinberg, A., Moran, T., & Hajcak, G. (2012). Time course of the error-​potentiated
startle and its relationship to error-​related brain activity. Journal of Psychophysiology, 27(2),
51–​59. doi:10.1027/​0269-​8803/​a000093
Santesso, D. L., Dzyundzyak, A., & Segalowitz, S. J. (2011). Age, sex and individual
differences in punishment sensitivity: Factors influencing the feedback‐related negativity.
Psychophysiology, 48(11), 1481–​1489.
Simons, R. F., Graham, F. K., Miles, M. A., & Chen, X. (2001). On the relationship of P3a and
the Novelty-​P3. Biological Psychology, 56(3), 207–​218.
Spencer, K. M., Dien, J., & Donchin, E. (2001). Spatiotemporal analysis of the late ERP
responses to deviant stimuli. Psychophysiology, 38(2), 343–​358.
Squires, K., Wickens, C., Squires, N., & Donchin, E. (1976). The effect of stimulus sequence on
the waveform of the cortical event-​related potential. Science, 193(4258), 1142–​1146.
Squires, N., Squires, K., & Hillyard, S. (1975). Two varieties of long-​latency positive waves
evoked by unpredictable auditory stimuli in man. Electroencephalography and clinical
neurophysiology, 38(4), 387–​401.
Steele, V. R., Anderson, N. E., Claus, E. D., Bernat, E. M., Rao, V., Assaf, M., . . . Kiehl, K. A.
(2016). Neuroimaging measures of error-​processing: Extracting reliable signals from event-​
related potentials and functional magnetic resonance imaging. NeuroImage, 132, 247–​260.
doi:10.1016/​j.neuroimage.2016.02.046
Tarullo, A. R., Obradović, J., Keehn, B., Rasheed, M. A., Siyal, S., Nelson, C. A., & Yousafzai, A.
K. (2017). Gamma power in rural Pakistani children: Links to executive function and verbal
ability. Developmental cognitive neuroscience, 26, 1–​8.
Trujillo, L. T., & Allen, J. J. B. (2007). Theta EEG dynamics of the error-​related negativity.
Clinical Neurophysiology, 118, 645–​668. doi:10.1016/​j.clinph.2006.11.009
Umbricht, D., & Krljes, S. (2005). Mismatch negativity in schizophrenia: a meta-​analysis.
Schizophrenia research, 76(1), 1–​23.
Van Noordt, S. J., Campopiano, A., & Segalowitz, S. J. (2016). A functional classifica-
tion of medial frontal negativity ERPs: Theta oscillations and single subject effects.
Psychophysiology, 53(9), 1317–​1334.
van Noordt, S. J., Desjardins, J. A., Gogo, C. E., Tekok-​Kilic, A., & Segalowitz, S. J. (2017).
Cognitive control in the eye of the beholder: electrocortical theta and alpha modulation
during response preparation in a cued saccade task. NeuroImage, 145, 82–​95.
Vidal, F., Hasbroucq, T., Grapperon, J., & Bonnet, M. (2000). Is the ‘error negativity’ specific to
errors? Biological Psychology, 51, 109–​128. doi:10.1016/​S0301-​0511(99)00032-​0
Watts, A. T., Bachman, M. D., & Bernat, E. M. (2017). Expectancy effects in feedback pro-
cessing are explained primarily by time-​frequency delta not theta. Biological Psychology, 129,
242–​252.
114    ANNA WEINBERG, PAIGE ETHRIDGE, BELEL AIT OUMEZIANE, and DAN FOTI

Watts, A. T., & Bernat, E. M. (2018). Effects of reward context on feedback processing as
indexed by time‐frequency analysis. Psychophysiology, e13195.
Webb, C., Auerbach, R., Bondy, E., Stanton, C., Foti, D., & Pizzagalli, D. (2017). Abnormal
neural responses to feedback in depressed adolescents. Journal of abnormal psychology,
126(1), 19.
Weinberg, A., & Hajcak, G. (2011). Longer term test–​retest reliability of error‐related brain ac-
tivity. Psychophysiology, 48(10), 1420–​1425.
Weinberg, A., Liu, H., Hajcak, G., & Shankman, S. (2015). Blunted neural response to rewards
as a vulnerability factor for depression: Results from a family study. Journal of abnormal
psychology, 124(4), 878.
Weinberg, A., Liu, H., & Shankman, S. A. (2016). Blunted neural response to errors as a
trait marker of melancholic depression. Biological Psychology, 113, 100–​107. doi:10.1016/​
j.biopsycho.2015.11.012
Weinberg, A., Olvet, D. M., & Hajcak, G. (2010). Increased error-​ related brain ac-
tivity in generalized anxiety disorder. Biological Psychology, 85, 472–​ 480. doi:10.1016/​
j.biopsycho.2010.09.011
Weinberg, A., & Shankman, S. (2016). Blunted reward processing in remitted melancholic de-
pression. Clinical Psychological Science, in press.
Wickens, C., Kramer, A., Vanasse, L., & Donchin, E. (1983). Performance of concurrent
tasks: a psychophysiological analysis of the reciprocity of information-​processing resources.
Science, 221(4615), 1080–​1082.
Yeung, N., Bogacz, R., Holroyd, C. B., & Cohen, J. D. (2004). Detection and synchronized
oscillations in the electroencephalogram: An evaluation of methods. Psychophysiology, 41,
822–​832. doi:10.1111/​j.1469-​8986.2004.00239.x
Yeung, N., Bogacz, R., Holroyd, C. B., Nieuwenhuis, S., & Cohen, J. D. (2007). Theta phase
resetting and the error-​ related negativity. Psychophysiology, 44, 39–​ 49. doi:10.1111/​
j.1469-​8986.2006.00482.x
Yordanova, J., Falkenstein, M., Hohnsbein, J., & Kolev, V. (2004). Parallel systems of error pro-
cessing in the brain. NeuroImage, 22, 590–​602. doi:10.1016/​j.neuroimage.2004.01.040
 CHAPTER 6

THE REL ATI ONSH I P

BET WEEN EVOKE D A ND
INDU CED EE G /​ME G
CHANG E S
Going Beyond Labels

ALI MAZAHERI

6.1  INTRODUCTION

For more than a century now researchers have been examining the electrical potentials
and magnetic fields measured at the scalp to understand what is happening inside our
brains when we perform various cognitive tasks. Researchers’ primary approach is to
characterize how the electro/​magnetoencephalogram (E/​MEG) signal changes in re-
sponse to a particular “event”, whether it be a button press or the onset of an auditory
tone. These changes are historically labelled as either evoked or induced, with each label
making assumptions about the origins of the change. The rationale behind evoked ac-
tivity is that the brain produces a new response as a consequence of processing the event.
This response is both time-​locked and phase-​locked to the experimental event. Induced
activity, on the other hand, assumes that the brain has ongoing brain activity (i.e., ac-
tivity that is always there) independent of any additive activity, and the event modulates
this ongoing activity, in a time-​locked, but not necessarily phase-​locked manner. My
hope is that the reader, through what I discuss in this chapter, will understand that these
“labels” (while at times useful) can paint an incomplete picture of what is going on in the
brain during cognitive processing. According to Andy Warhol, “The moment you label
something, you take a step—​I mean, you can never go back again to seeing it unlabeled”.
I further argue that for the field to move forward in gaining a richer understanding of
116   ALI MAZAHERI

the link between brain and cognition, we need to rethink how we label the different
types of EEG responses.

6.2  EVOKED AND INDUCED: THE

ASSUMPTION AND LABELS

The evoked potential approach assumes a large component of the electrophysiological

signals detected at the scalp is not related to the processing of the phenomena under in-
vestigation. Here, we need to average multiple trials (Figure 6.1) of EEG epochs centered
around the experimental event to extract the “event”-​related EEG signal, called the
event-​related potential (ERP) for EEG measurements, and event-​related fields (ERF)
for magnetoencephalography (MEG) measurements. The ERP/​F reflects neural ac-
tivity precisely time and phase-​locked in response to an event. The peaks and troughs in
the ERP waveform, which often follow a stereotypical temporal pattern of positive and
negative voltage deflections, are classified as “components”. Researchers theorize that
these components map onto various task-​relevant cognitive processes (Kappenman &
Luck, 2011).
The evoked potential approach explicitly ignores the ongoing activity present in the
EEG, as well as changes that although are time-​locked to an experimental event, are not
necessarily phase-​locked to it. This is because of the rather critical assumption (and
one this chapter spends considerable effort arguing against) that non-​phase locked ac-
tivity disappears in the averaging of event locked data epochs due to the deconstructive
interference of random phases (Figure 6.1B). Capturing changes to the ongoing ac-
tivity in EEG, as well as responses that are time-​locked but not necessarily phase-​
locked requires averaging the time-​frequency spectra of multiple EEG trials centered
on the experimental event (Figure 6.1C). The time-​frequency characterization of the
ongoing EEG activity works particularly well since the signals contain rhythms, that
is, oscillatory activity in characteristic frequency ranges (i.e., bands) including theta
(3–​7 Hz), alpha (8–​13), beta (14–​20 Hz), and gamma (30–​100 Hz), with each band often
exhibiting specific spatial distributions over the scalp (Siegel et al., 2012). The ampli-
tude of an oscillation refers to the size of its (positive or negative) peak relative to some
baseline.
The experimentally driven increase in the amplitude of a frequency band is often
referred to as an event-​related synchronization (ERS). The ERS terminology is based on
the fact that when the activity of neurons becomes synchronized, the spatial summation
of the post-​synaptic potentials results in an amplitude increase (Pfurtscheller & Lopes
da Silva, 1999). Conversely, desynchronization of the neuronal population firing
results in the cancellation of post-​synaptic potentials, and as such, a drop in oscilla-
tory amplitude within a frequency band, sometimes referred to as event-​related de-
synchronization (ERD). Much like the ERP components, the task-​related changes
 RELATIONSHIP BETWEEN EVOKED AND INDUCED EEG/MEG CHANGES    117

phase-locked non phase-locked

activity activity
(a)

(b) Time domain average of epochs

(c)

Average time-frequency spectra of epochs

60
Frequecy
(Hz)

30

10

–0.2 0 0.5
Time (S)

Figure 6.1  (A) The onset of an event (e.g., auditory stimulus) can evoke activity that is both
phase and time-​locked to the onset of the event as well as induce activity that is time-​locked but
not phase-​locked. (B) Time-​domain averaging of multiple data epochs would result in the at-
tenuation of the non-​phase locked activity due to destructive interference. The activity remaining
after the averaging reflects the brain’s transient phase-​locked response to an event.
118   ALI MAZAHERI

in oscillatory amplitudes map on to different facets of cognition (Siegel et al., 2012;

Hanslmayr et al., 2016).

6.3  Going beyond Evoked and

induced: the origin of the changes

Besides the methodologically different approaches needed to extract each type of

change, evoked and induced activity are also thought to reflect different processes
occurring in the brain in response to an outside event. One rather now-​classic frame-
work (Pfurtscheller & Lopes da Silva, 1999) proposes that evoked changes (i.e., ERPs)
are assumed to occur because of event locked changes of afferent activity into cor-
tical neurons. On the other hand changes in oscillatory power of the ongoing EEG are
hypothesized to emerge due to the interaction of neurons and interneurons that control
the frequency components of the ongoing activity.

6.4  UNLabeling the labels: the

relationship between evoked and
ongoing activity

The rather traditional view of evoked and ongoing activity (Figure 6.2) is that they re-
flect rather separate distinct neural phenomena. According to this view, the evoked ac-
tivity that always has a consistent phase-​locked to the onset of an experimental event
rides on top of the ongoing activity. This is also sometimes referred to as the “additive
view” of how ERPs are generated. Taken to the extreme, it is possible to view the evoked
activity as completely independent of the ongoing activity (figure 6.3A). An alternate
theory, referred to as a phase-​resetting theory (figure 6.3B), postulates that there is no
additive evoked activity elicited by the onset of an event, but that rather, the ongoing ac-
tivity adjusts its phase to the onset of the experimental event (Makeig et al., 2002). Here,
by averaging trials locked to the event, the ongoing activity before the onset of the event
which has random phases is averaged out, while the event-​related phase perturbed ac-
tivity emerges as the evoked response.
Given that the predominant ongoing activity in the EEG signal is the alpha rhythm,
it is believed that its phase-​reset (or adjustment) to the onset of the experimental
event plays a particular role in the formation of evoked responses (Makeig et al., 2002;
Klimesch et al., 2007; Gruber et al., 2005; Hanslmayr et al., 2006). However, the phase-​
reset of the ongoing rhythms is not exclusive to the alpha activity, with the theta rhythm
 RELATIONSHIP BETWEEN EVOKED AND INDUCED EEG/MEG CHANGES    119

“Induced” activity “Evoked” activity

Cortex Cortex

RE RE

RE RE

TCR TCR

TCR TCR

Ascending Brain stem Ascending Brain stem

afferents afferents afferents afferents

Figure 6.2 Schema for the generation of induced (ERD/​ERS) and evoked (ERP) activity
whereby the former is highly frequency-​specific.
Adapted from Pfurtscheller & Lopes da Silva, 1999.

also proposed to be involved in the formation of specific evoked responses such as the
error-​related negativity (Luu et al., 2004).
There has been a fair amount of controversy over whether phase-​resetting can
account for the formation of ERPs (Mazaheri & Jensen, 2006). The primary evidence
for the occurrence of a phase-​reset is that the phase of the ongoing activity at the time
of the evoked response would be consistent across trials. However, the addition of
a signal with a consistent phase across trials (i.e., a traditional additive evoked re-
sponse) would also make the phase of the ongoing activity appear consistent across

The two models of evoked response

generation
(a) Additive Model (b) Phase Resetting

Figure 6.3  The additive versus phase-​resetting theory of evoked response generation. (A) The
additive theory assumes that evoked and ongoing activities are distinct neuronal phenomena.
The experimental event “evokes” an additive, phase-​locked response in each trial. (B) According
to the phase-​resetting view, the ongoing and evoked activity are the same neuronal phenomena,
with no “new” additive response. Here the phases of the ongoing background oscillations be-
come aligned (phase-​reset or partial phase-​reset) to an experimental event. The phase-​locked
(i.e., adjusted) oscillatory activity emerges as an evoked component when averaging the event-​
locked trials.
120   ALI MAZAHERI

Single Trials Phases

p=0.79 p<0.001
Average Evoked Potential Power Changes
+
10 μV 10
– p = 0.12

Number
0
– 0 +
–200 800ms Power Relative to Baseline

Figure 6.4  Model of generation. The upper left of the figure shows 20 superimposed trials of
a model evoked potential consisting of a single cycle of activity added to ongoing activity of the
same frequency with variable phase and amplitude. Below is given the average evoked potential
over 100 trials. At the upper right are the polar plots showing the phase distributions of the fre-
quency of the evoked potential (and background activity) during the baseline and at the middle
of the evoked potential. There is significant phase synchronization at the time of the evoked po-
tential. At the bottom is a histogram of the power measurements in the middle of the evoked po-
tential across the 100 trials (because of the Mortlet filtering effect this gives the maximum power).
There is no significant change in power.
Reprinted by permission from Mazaheri & Picton, 2005.

trials (Figure 6.4) (Mazaheri & Picton, 2005; van Diepen & Mazaheri, 2018; Yeung
et al., 2004).
Moreover, a rather convincing argument has been raised that the additive and phase-​
resetting model cannot be mathematically distinguished at the scalp level without inva-
sive electrophysiological recordings (Telenczuk et al., 2010).
While the additive and phase-​resetting theories offer a contradictory account of
evoked and ongoing activity, they do share two common elements. Both theories
assume across-​ trials averaging results in the attenuation of ongoing activity.
However, this assumption has been challenged. There is now compelling evidence
that the alpha rhythm, the dominant ongoing signal detected at the scalp, is non-​
sinusoidal, and across-​trials averaging never really makes it go away. This obser-
vation greatly blurs the line between evoked and ongoing activity. Furthermore,
it is important to note that the additive and phase-​resetting debate has exclusively
focused on the early-​stimulus evoked responses (P1, N1, or the ERN) and fails to
provide a complete account for the brain responses occurring 200 ms after an ex-
perimental event. These sustained responses (Figure 6.5), often lasting 100–​200 ms,
are believed to reflect neural processing related to high-​level cognitive constructs
ranging from working memory representation (Ikkai et al., 2010) to language com-
prehension (Kutas & Federmeier, 2011).
 RELATIONSHIP BETWEEN EVOKED AND INDUCED EEG/MEG CHANGES    121

High capacity Low capacity

–2μV –2μV

–200 200 600 1,000 –200 200 600 1,000

+2μV +2μV Two items

Four items
Two items
with to distractors

Figure 6.5  Grand averaged ERP difference waves (contralateral activity minus ipsilateral ac-
tivity) timelocked to the memory array averaged across the lateral occipital and posterior parietal
electrode sites and divided across the high and low memory capacity groups.
From Vogel et al., 2005.

6.4.1 Amplitude Asymmetry/​Baseline Shifts—​A Unifying

Perspective?
Ongoing activity has been assumed to average out because it has traditionally been
viewed to be amplitude symmetric in nature, that is, its peaks and troughs modulate at
the same rate (Figure 6.6A).
While we are still seeking a complete understanding of the neural origin of the
scalp electrophysiological signals (Cohen, 2017), the general consensus is that they
are generated through synchronized post-​synaptic current in the dendrites of pyr-
amidal cells (Hämäläinen et al., 1993). Here the EEG reflects the potentials by these
currents, while MEG captures the magnetic fields. For an oscillation to have sym-
metric amplitude fluctuations the intracellular currents propagating forward to-
wards the soma (here let us arbitrarily designate this as the peak of the oscillation)
must have the same magnitude as the current coming back from the soma (here
assume the trough of the oscillation). However, given the asymmetric placement of
channels responsible for the depolarization and repolarization current it is unlikely
that the two currents would have the same magnitude when summed up across
many synchronized neurons with the same orientation (Mazaheri & Jensen, 2008;
Nikulin et al., 2007).
An alternative way to view ongoing activity is that is it amplitude asymmetric, with
greater variability in amplitude fluctuations at the peak versus the trough (Figure
6.6B). One critical consequence of amplitude asymmetric ongoing activity is that it will
not simply average out to zero when summed across trials. Moreover, any systematic
suppression or enhancement of the amplitude of the ongoing activity time-​locked to an
event would result in the amplitude envelope of the ongoing activity emerging as a slow
evoked response when averaging across trials.
122   ALI MAZAHERI

(a) (b)

100 ms

(c) (d)

ER ER

Figure 6.6  The amplitude modulation of neuronal oscillatory activity is conventionally viewed
as being symmetric at approximately zero. (B) We propose that the amplitude modulations of the
oscillatory activity are asymmetric such that the peaks are more strongly modulated than the
troughs. For the 10 Hz alpha activity, this could be explained by bouts of activity every ~100 ms.
(C) The conventional view ignoring asymmetric modulations of oscillatory activity would mean
that averaging across trials (the arrow representing the start of the evoked response) would not
result in the generation of slow fields. (D) As a direct consequence of amplitude asymmetry, a
depression (or increase) in alpha activity in response to a stimulus will result in the generation of
slow fields when multiple trials are averaged. Adapted from Mazaheri and Jensen (2008).

6.4.2 Empirical Evidence Supporting Amplitude Asymmetry

A seminal study by Nikulin and colleagues (2007) provided evidence that the ongoing
alpha rhythm is “amplitude asymmetric”, specifically referred by them as having a “zero-​
mean”. They went further to propose that a critical consequence of an amplitude asym-
metric ongoing rhythm is that any systematic fluctuations in its amplitude would show
up as slow responses (they referred to these as baseline shifts) when averaged across
trials (Figure 6.7).
Following up Nikulin and colleagues, Mazaheri and Jensen (2008) developed a simple
measure to quantify the amplitude of an oscillation by comparing the variance of its
peaks with the variance of the troughs (see Figure 6.8).
Moreover, we were able to demonstrate that the degree of amplitude asymmetry of
an oscillation is directly related to the amplitude of the evoked response generated by
its modulation. Specifically, we presented a simple check-​board stimulus across many
trials, and then separated the trials into high amplitude of post-​stimulus activity, and
 RELATIONSHIP BETWEEN EVOKED AND INDUCED EEG/MEG CHANGES    123

400
0

Amplitude [fT/cm]
–400
–800
40
20
0
–20
1 2 3 4
Time (seconds)

Figure 6.7  Baseline shifts in ongoing oscillations. Upper trace: spatially filtered (with inde-
pendent component analysis) broadband signal from a channel above the right sensorimotor
area during rest. Lower trace: the mean values in three time intervals. Clearly, there are baseline
shifts in the ongoing activity associated with oscillations changing from large to small and back
to large amplitude. If many epochs with similar amplitude dynamics are averaged, oscillatory
patterns would disappear whereas the baseline shifts would remain leading to the appearance of
an evoked response.
Nikulin et al., 2007.

low amplitude. We found that despite the stimulus being the same, the sorting of the
trials based on alpha amplitude resulted in the formation of slow-​evoked responses
(Figure 6.9). Across participants the amplitude, and polarity of these slow responses was
highly correlated with the direction of the amplitude asymmetry of the ongoing alpha
activity. Thus we were able to demonstrate (albeit with simple grating stimuli) that it was
(in principle) possible to form slow-​evoked responses in the trial averaged EEG epochs
if there were systematic changes in the amplitude of the ongoing alpha activity.
Mazaheri and Jensen (2010) proposed four prerequisites for linking modulations of
oscillatory activity to evoked component generation.

1. The ongoing MEG/​EEG oscillations must be modulated in amplitude by the

stimuli or event.
2. This amplitude modulation of the ongoing activity must correlate with the time
course of the evoked response (over trials or subjects).
3. The ongoing oscillations must have an amplitude asymmetry.
4. The magnitude and/​or polarity of the amplitude asymmetry must relate to the
amplitude and/​or polarity of the evoked responses (over trials or subjects).

6.4.3 Making the Past as Important as the Future

One rather intriguing consequence of having ongoing activity that never averages out is
that the amplitude of the pre-​event oscillatory activity could modulate the amplitude of
the post-​event-​related potentials, when baseline subtracting the event-​related potentials
(Figure 6.10).
124   ALI MAZAHERI

(a)
S1(t) = A(t)(1+sin(2πft) + noise AFAindex = 0.96

Amplitude
8–12 Hz

(b) S (t) = A(t)sin(2πft) + noise

2 AFAindex = –0.96

Amplitude
8–12 Hz

(c)
S3(t) = A(t)+sin(2πft) + noise AFAindex = –0.07

Amplitude
8–12 Hz

Peaks
Throughs

Figure 6.8  Various simulations in which surrogate signals were used to test the AFAindex.
(A) The signal, s1(t), was designed to have an amplitude asymmetry. The amplitude modulation
was determined by a slower signal A(t). Clearly the peaks (red dots) are more modulated than the
troughs (blue dots) yielding a strong AFAindex. (B) The signal, s2(t), was designed such that the
slow modulations, A(t), affected the alpha rhythm in a multiplicative manner. Thus peaks and
troughs are modulated symmetrically over time yielding an AFAindex close to 0. (C) In signal
s3(t) slow modulations were added to the alpha oscillations (DC-​like offset of the signal). This
affected peaks and troughs in the same direction producing an AFAindex close to 0.
Adapted from Mazaheri & Jensen, 2008.

Iemi and colleagues’ (2019) comprehensive study systematically examined the re-
lationship of pre-​stimulus power of oscillatory, amplitude asymmetry, and the for-
mation of evoked responses. In particular, Iemi and colleagues’ (2019) focused on
differentiating the impact of pre-​stimulus functional inhibition (a sensory state being
in a less-​responsive state) from amplitude asymmetry on both the early and late sensory
evoked responses.
Here, with functional inhibition, the authors were referring to the currently widely
held view that an increase in alpha activity in a sensory system reflects its functional
inhibition and consequently results in attenuated evoked responses (evidence recently
reviewed in Van Diepen et al., 2019). They found that the early evoked (<0.200 s: e.g.,
the C1/​N1 components) were indeed modulated by the amplitude of the pre-​stimulus
 RELATIONSHIP BETWEEN EVOKED AND INDUCED EEG/MEG CHANGES    125

30% low α trials 30% low α trials

20
30% high α trials

Frequency (Hz)
10 40

(fT2/Hz)
Power
30% high α trials
20

–40
10

–0.5 0 0.5
Time (s)

Figure 6.9  Time-​frequency representations of the trials with the 30% lowest and 30% highest
modulations of alpha power (TFRs baseline corrected; −0.6 < t < −0.1 s) in a representative sub-
ject. The respective ERFs (right) reveal a clear difference in the sustained modulation with respect
to low-​(thin line) and high-​alpha-​power changes (thick line).
Adapted from Mazaheri & Jensen, 2008.

(a) Zero-mean oscillations (b) Non-zero-mean oscillations

Amp

Stimulus
Onset
ERD ERS
ERP

Figure 6.10 Ongoing activity (amplitude), event-​

related oscillations (ERS/​
ERD) and
potentials (ERP) (see text for details).
The vertical line indicates stimulus onset, while the horizontal line indicates zero signal strength. Yellow and blue
represent states of strong and weak prestimulus power, respectively. Reprinted from Iemi et al, 2019.
126   ALI MAZAHERI

alpha activity, independent of the direction of amplitude asymmetry. However, they

found a strong relationship between amplitude asymmetry of the pre-​stimulus ac-
tivity and the late evoked components. These results taken together suggest high
pre-​stimulus alpha likely causes a suppression of early evoked responses since the
neurons producing these responses are in an inhibited stated, while the amplitude of
asymmetry property of alpha activity impacts the formation of the later slow evoked
responses.
The results discussed so far strongly question the old dogma that ongoing and
evoked activity are distinct independent neural phenomena. However, while the
studies demonstrate that it is possible to generate slow evoked potentials through
modulations of the amplitude of the ongoing activity (without any “new” additive ac-
tivity), it is still unclear if this mechanism applies to cognitively relevant event-​related
responses.

Can Amplitude Asymmetry Explain the Emergence

6.4.4 
of the Most Cognitive of ERPs?
As mentioned earlier, the CDA is a slow sustained response proposed to reflect the
neural representation of an item in working memory. It is often elicited through a para-
digm where participants are presented with a bilateral array of colored squares and
instructed to memorize the location of the items in the hemifield indicated by the arrow
(i.e., test array). The success of memorizing the items in the test array is then subse-
quently assessed a second later through the presentation of another array that is either
identical to the test array or missing one of the items. The CDA is derived by averaging
epochs locked to the onset of the test array and subtracting the contralateral ERPs from
the left.
The amplitude of the CDA is modulated by the number of items held in working
memory (Vogel et al., 2005) However, the neural origins of the CDA are still rather a
mystery. Moreover, the same paradigm has also been found to elicit robust modulations
of alpha activity that are also modulated by the number of items held in working
memory (Sauseng et al., 2009). In addition, just like the CDA, the degree of lateralized
alpha modulation also seems to correlate with the individual differences in working
memory. This suggests some overlap between the neural processes underlying the CDA
and the alpha modulation.
A study published by Van Dijk and colleagues (2010) explored the link between
changes in alpha activity and the CDA, and found them to be quite linked together.
Specifically, they observed that both the degree of alpha suppression across individuals,
as well as their degree of alpha amplitude asymmetry correlated very strongly with the
amplitude of the CDA. Moreover, the alpha modulation and the CDA had a remarkably
similar topography over the scalp. These observations taken together could suggest that
the CDA and the alpha modulation during the period that the items are held in working
memory are one and the same thing.
 RELATIONSHIP BETWEEN EVOKED AND INDUCED EEG/MEG CHANGES    127

What are the consequences of re-​labelling the CDA as a change in ongoing ac-
tivity rather than a purely additive response? For one thing, this could have profound
implications on how we believe the brain carries out working memory processes. As
mentioned, one popular view of the role of alpha modulation in cognition is the
suppression of task-​irrelevant regions (Van Diepen et al., 2019). Thus, the CDA, rather
than being an additive neural process involved in memory maintenance, could instead
be reflecting the inhibition of task-​irrelevant brain areas. Additionally, unifying on-
going and event-​related activity has the potential to mechanistically account for some
rather intriguing ERP findings, for which the origins of the responses remain a mystery.
For example, a now-​classic study (Otten et al., 2006) found that the amplitude of slow
event-​related potentials locked to the onset of a cue, but peaking before the onset of a
word to be remembered, could predict if the word was later remembered. By linking
the slow ERPs to the modulation of ongoing alpha activity, one simple interpretation of
the observed difference between the remembered versus forgotten words could be that
alpha activity is higher (i.e., the brain is in a more inhibited state) prior to the onset of
forgotten words. This is indeed in line with several experiments observing pre-​stimulus
alpha oscillations to modulate perception (van Dijk et al., 2008) as well as reflect slips of
sustained attention (Bengson et al., 2012).

Does Amplitude Asymmetry Explain the Emergence

6.4.5 
of Most Cognitive of ERPs?
While I hope that thus far this chapter demonstrates that modulations of ongoing ac-
tivity that is amplitude asymmetric can produce sustained ERPs, the jury is still out on
whether the ongoing and evoked activity, particularly the slow late components, are
one and the same. Fukuda and colleagues (2015) challenged this view by observing that,
while alpha modulation and CDA are tightly linked, they do appear to uniquely con-
tribute to individual differences between working memory capacity. Specifically, the
authors reasoned if the alpha suppression and CDA are two sides of the same neural
phenomena they should also show the same relationship to individual differences
in working memory performance. However, they found that each signal appeared to
uniquely contribute to individual differences in working memory capacity.
More recently, Bae & Luck (2018) went further and used a decoding approach to in-
vestigate the specific roles alpha modulation and the slow sustained response could play
in attention and working memory. They found modulations in the ongoing alpha ac-
tivity to be associated with the spatial location of attended stimuli, whereas the ampli-
tude and spatial distribution of the slow-​sustained ERPs were sensitive to orientation.
Interestingly, they proposed that the ERP and alpha modulation, while serving distinct
roles, reflect attentional mechanisms that prevent interference, rather than the actual
WM representation.
While these studies certainly do not rule out that the modulation of ongoing activity
could be a significant contributor to the formation evoked responses, they do suggest
128   ALI MAZAHERI

the presence of additive activity involved in WM maintenance. In addition, the mech-

anism underlying amplitude asymmetry of alpha activity is also applicable to other fre-
quency bands. This means that while the alpha rhythm is the predominant oscillation
making up the ongoing activity, there could also be other rhythms present, such as the
delta and theta rhythms (Stefanics et al., 2010), whose event-​related modulation likely
impacts the formation of evoked responses.

6.5  FINAL THOUGHTS

I would certainly not advocate any researchers to dismiss the event-​related averaging
approach in exchange for looking at changes in the brain’s ongoing activity. However,
strictly viewing ongoing activity and evoked responses as separate unique entities is
implicitly believing the brain was doing nothing before the onset of the experimental
event. Such a view is particularly limited when it comes to trying to understand how the
brain tries to make sense of the outside world.
As an example of how the brain endeavors to make sense of the world, one rather in-
fluential theory proposes that the brain is constantly making predictions about what
is going to happen next (reviewed in detail in Friston, 2010). Specifically, this theory,
referred to as “predictive coding”, postulates that brain sets expectations and predictions
about upcoming sensory input and then subsequently updates these expectations after
the onset of the sensory input. Here, the discrepancy between the expectation and actual
sensory input is referred to as prediction error. While evoked responses can reveal in-
formation about the degree of prediction error and the perceived mismatch between ex-
pectation and reality, they are not directly informative about the neurophysiology of the
predictive processes themselves, since, by definition, the evoked response emerges after
the sensory input. By removing the separate labels (going back to the Warhol quote) of
evoked responses and ongoing activity, it is possible to get a richer, but at the same time
more parsimonious, picture of the neural processes underlying cognition.
Finally, I paraphrase Warhol for one last time: I hope some of the mystery behind
event-​related responses and ongoing activity is gone, but the amazement is just starting.

REFERENCES
Bae, G.-​Y. & Luck, S. J. (2018). Dissociable decoding of spatial attention and working memory
from EEG oscillations and sustained potentials. The Journal of Neuroscience, 38(2), 409–​422.
Bengson, J. J., Mangun, G. R., & Mazaheri, A. (2012). The neural markers of an imminent
failure of response inhibition. NeuroImage, 59(2), 1534–​1539.
Cohen, M. X. (2017). Where does EEG come from and what does it mean? Trends in
Neuroscience, 40(4), 208–​218.
Friston, K. (2010). The free-​ energy principle: A unified brain theory? Nature Reviews
Neuroscience, 11(2), 127–​138.
 RELATIONSHIP BETWEEN EVOKED AND INDUCED EEG/MEG CHANGES    129

Fukuda, K., Mance, I., & Vogel, E. K. (2015). α-​power modulation and event-​related slow wave
provide dissociable correlates of visual working memory. The Journal of Neuroscience, 35(41),
14009–​14016.
Gruber, W. R., Klimesch, W., Sauseng, P., & Doppelmayr, M. (2005). Alpha phase synchroniza-
tion predicts P1 and N1 latency and amplitude size. Cerebral Cortex, 15(4), 371–​377.
Hämäläinen, M., Hari, R., Ilmoniemi, R. J., Knuutila, J., & Lounasmaa, O. V. (1993).
Magnetoencephalography: Theory, instrumentation, and applications to noninvasive
studies of the working human brain. Reviews of Modern Physics, 65, 413.
Hanslmayr, S., Klimesch, W., Sauseng, P., Gruber, W., Doppelmayr, M., Freunberger, R.,
Pecherstorfer, T., & Birbaumer, N. (2006). Alpha phase reset contributes to the generation of
ERPs. Cerebral Cortex, 17(1), 1–​8.
Hanslmayr, S., Staresina, B. P., & Bowman, H. (2016). Oscillations and episodic
memory: Addressing the synchronization/​ desynchronization conundrum. Trends in
Neuroscience, 39(1), 16–​25.
Iemi, L., Busch, N. A., Laudini, A., Haegens, S., Samaha, J., Villringer, A., & Nikulin, V. V.
(2019). Multiple mechanisms link prestimulus neural oscillations to sensory responses.
Elife, 8, e43620.
Ikkai, A., McCollough, A. W., & Vogel, E. K. (2010). Contralateral delay activity provides a
neural measure of the number of representations in visual working memory. Journal of
Neurophysiology, 103(4), 1963–​1968.
Kappenman, E. S., & Luck, S. J. (Eds.). (2011). Oxford handbook of event-​related potential
components. Oxford University Press.
Klimesch, W., Sauseng, P., Hanslmayr, S., Gruber, W., & Freunberger, R. (2007). Event-​related
phase reorganization may explain evoked neural dynamics. Neuroscience & Biobehavioral
Reviews, 31(7), 1003–​1016.
Kutas, M. & Federmeier, K. D. (2011). Thirty years and counting: Finding meaning in the N400
component of the event-​related brain potential (ERP). Annual Review of Psychology, 62,
621–​647.
Luu, P., Tucker, D. M., & Makeig, S. (2004). Frontal midline theta and the error-​related nega-
tivity: neurophysiological mechanisms of action regulation. Clinical Neurophysiology, 115(8),
1821–​1835.
Makeig, S., Westerfield, M., Jung, T. P., Enghoff, S., Townsend, J., Courchesne, E., & Sejnowski,
T. J. (2002). Dynamic brain sources of visual evoked responses. Science, 295(5555), 690–​694.
Mazaheri, A. & Jensen, O. (2006). Posterior α activity is not phase-​reset by visual stimuli.
Proceedings of the National Academy of Sciences of the United States of America, 103(8),
2948–​2952.
Mazaheri, A. & Jensen, O. (2008). Asymmetric amplitude modulations of brain oscillations
generate slow evoked responses. The Journal of Neuroscience, 28(31), 7781–​7787.
Mazaheri, A. & Jensen, O. (2010). Rhythmic pulsing: Linking ongoing brain activity with
evoked responses. Frontiers in Human Neuroscience [online], 4(177). doi: 10.3389/​
fnhum.2010.00177
Mazaheri, A. & Picton, T. W. (2005). EEG spectral dynamics during discrimination of auditory
and visual targets. Brain Research Cognitive Brain Research, 24(1), 81–​96.
Nikulin, V. V., Linkenkaer-​Hansen, K., Nolte, G., Lemm, S., Müller, K. R., Ilmoniemi, R. J., &
Curio, G. (2007). A novel mechanism for evoked responses in the human brain. European
Journal of Neuroscience, 25(10), 3146–​3154.
Otten, L. J., Quayle, A. H., Akram, S., Ditewig, T. A., & Rugg, M. D. (2006). Brain activity be-
fore an event predicts later recollection. Nature Neuroscience, 9(4), 489–​491.
130   ALI MAZAHERI

Pfurtscheller, G. & Lopes da Silva, F. H. (1999). Event-​related EEG/​MEG synchronization and

desynchronization: Basic principles. Clinical Neurophysiology, 110(11), 1842–​1857.
Sauseng, P., Klimesch, W., Heise, K. F., Gruber, W. R., Holz, E., Karim, A. A., Glennon,
M., . . . Hummel, F. C. (2009). Brain oscillatory substrates of visual short-​term memory cap-
acity. Current Biology, 19(21), 1846–​1852.
Siegel, M., Donner, T. H. & Engel, A. K. (2012). Spectral fingerprints of large-​scale neuronal
interactions. Nature Reviews Neuroscience, 13(2), 121–​134.
Stefanics, G., Hangya, B., Hernádi, I., Winkler, I., Lakatos, P., & Ulbert, I. (2010). Phase entrain-
ment of human delta oscillations can mediate the effects of expectation on reaction speed.
The Journal of Neuroscience, 30(41), 13578–​13585.
Telenczuk, B., Nikulin, V. V. & Curio, G. (2010). Role of neuronal synchrony in the generation
of evoked EEG/​MEG responses. Journal of Neurophysiology, 104(6), 3557–​3567.
van Diepen, R. M., Foxe, J. J., & Mazaheri, A. (2019). The functional role of alpha-​band ac-
tivity in attentional processing: The current zeitgeist and future outlook. Current Opinion in
Psychology, 29, 229–​238.
van Diepen, R. M. & Mazaheri, A. (2018). The caveats of observing inter-​trial phase-​coherence
in cognitive neuroscience. Scientific Reports, 8(1), 2990.
van Dijk, H., Schoffelen, J. M., Oostenveld, R., & Jensen, O. (2008). Prestimulus oscillatory ac-
tivity in the alpha band predicts visual discrimination ability. The Journal of Neuroscience,
28(8), 1816–​1823.
van Dijk, H., van der Werf, J., Mazaheri, A., Medendorp, W. P., & Jensen, O. (2010). Modulations
in oscillatory activity with amplitude asymmetry can produce cognitively relevant event-​
related responses. Proceedings of the National Academy of Sciences of the United States of
America, 107(2), 900–​905.
Vogel, E. K., McCollough, A. W., & Machizawa, M. G. (2005). Neural measures reveal indi-
vidual differences in controlling access to working memory. Nature, 438(7067), 500–​503.
Yeung, N., Bogacz, R., Holroyd, C. B., & Cohen, J. D. (2004). Detection of synchronized
oscillations in the electroencephalogram: An evaluation of methods. Psychophysiology,
41(6), 822–​832.
 CHAPTER 7

F REQU ENCY ANA LYSI S OF

THE MONKEY NEO C ORT I C A L
L O CAL FIELD P OT E NT IA L

STEVEN L. BRESSLER

7.1  Introduction

The neocortex of the macaque monkey is very similar to that of the human in its archi-
tectonics. The six neocortical laminae show similar variation with region in the monkey
and human. In fact, it appears that all mammalian species share a common microstruc-
ture, which makes distinguishing neuroanatomical slices from different mammalian
species under the microscope nearly impossible. What appears to be more different be-
tween the macaque monkey and human neocortices is at the macroscopic level. Overall,
the number of neocortical areas is larger in the human brain, and the between-​area
connectivity is more complex. However, the macroscopic structure of the two species is
highly similar in certain systems, for example, the visual system.
The similarity between the human and macaque monkey neocortex was first
recognized for the visual system, where neocortical oscillations are a prominent product
of the visual architecture of both humans and monkeys. Visual neocortical local field
potentials (LFPs) show oscillations in both low-​frequency (delta, theta, and alpha) and
high-​frequency (beta and gamma) bands. Many studies report the importance of the
neocortical LFP oscillations in the boundary frequency region between the low beta
(13–​20 Hz) and alpha (8–​12 Hz) frequency bands for top-​down neocortical processing
in vision (Liang et al., 2002; Bressler et al., 1993; Bressler et al., 2007; Engel & Fries, 2010;
Bressler & Richter, 2015; Bastos et al., 2015; Richter et al.,2018), and in the theta (4–​7 Hz)
and gamma (above >30 Hz) bands for bottom-​up visual processing (Markov et al., 2013;
Bastos et al., 2015; Michalareas et al., 2016).
A great deal of research has also involved oscillatory activity in the prefrontal cortex
of the macaque monkey, which has important analogies to the human prefrontal cortex,
132   STEVEN L. BRESSLER

which is the most developed of all the mammalian species and is therefore unique.
The macaque monkey prefrontal cortex is clearly different from that of the human,
but it shares many of the same features. As working memory is an essential compo-
nent of different cognitive functions requiring the prefrontal cortex in both macaque
monkeys and humans (Miller et al., 2018), studies of working memory in the macaque
monkey prefrontal cortex are essential for understanding human working memory.
Monkey studies first demonstrated a role for prefrontal neocortical oscillatory activity
in working memory (Siegel et al.,2009), and these provided the theory that neocortical
oscillations are important for working memory processes in the beta-​alpha and gamma
bands (Pesaran et al., 2002; Salazar et al., 2012; Antzoulatos & Miller, 2016). This specu-
lation has now been verified (discussed later; see also Lundqvist et al.,2016, 2018; Miller
et al., 2018).
The study of working memory oscillations in the monkey prefrontal cortex gives
impetus to the investigation of prefrontal neocortical oscillations in human working
memory (D’Esposito et al., 1995), and recent human studies demonstrate the import-
ance of prefrontal oscillatory activity in human working memory (Jensen et al., 2007;
Alekseichuk et al., 2016). Research by Miller and colleagues (2018) involving macaque
monkeys verifies that working memory oscillations exist in the theta, alpha-​beta, and
gamma frequency bands. These oscillations are best studied in monkeys, which dem-
onstrate excellent working memory capability, have associated oscillations that can be
studied invasively, and which have a prefrontal neuroanatomy that is similar to humans.
Questions about working memory and high-​frequency (beta and gamma) oscillations
tend to be addressed using monkeys due to the relatively low signal-​to-​noise ratio at
higher frequencies in the human electroencephalogram (EEG) (Crone et al., 2006). The
purpose of this report is to present evidence on neocortical oscillations from the ma-
caque monkey engaged in cognitive functions that rely on working memory.

7.2  Dendrites, Oscillations,

and Cognition

Transmembrane ionic currents contribute to the extracellular field. Synaptic activity

is often the most important physiological source of extracellular current flow. The
dendrites and soma of a neuron are treelike and have an electrically conducting in-
terior surrounded by a permeable but insulating membrane. Transmembrane current
flows into the dendrites of neocortical neurons at excitatory synapses due to electro-
motive forces created by neurotransmitter molecules acting on postsynaptic receptor
molecules, or out of the synaptic regions at inhibitory synapses. In either case, current
flows down the length of the dendritic shaft, across the dendritic membrane, and
completes a current loop through the extracellular space. The extracellular current loops
give rise to extracellular potential differences that are detected as the LFP (Freeman,
 FREQUENCY ANALYSIS OF THE MONKEY    133

1975; Buzsaki et al., 2012). The MEG is thought to arise from those same currents
passing through the dendritic shafts of the same neurons (Murakami & Okada, 2006).
Oscillatory activity is a prominent feature of both electric and magnetic signals, higher
frequency oscillations likely reflecting interactions of excitatory and inhibitory neurons
(Kopell, 2000).
There is growing recognition that the dendrites of neocortical neurons are thus es-
sential for the genesis of neocortical oscillations, and there is speculation that the dy-
namics of cognitive processing, including working memory (Voytek & Knight, 2015),
depends on oscillations. However, the recording and characterization of dendritic ac-
tivity is problematic. It is usually not possible to record from single dendrites of neurons
in the brain due to their thinness, or from the dendritic trees of single neurons due to the
lack of extracellular potentials from single-​neuron dendrites. Also, neither the single-​
neuron dendritic branch response nor the single-​neuron dendritic tree response can be
extracted from the compound dendritic response. For these reasons, much of neuro-
physiology has focused on the action potential (spike) as the essential neuronal signal.
This focus is not because of the neuron doctrine, which, holding only that the neuron is
the central signaling cell in the nervous system, is neutral with respect to the parts of the
neuron that carry out particular aspects of that signaling.
Dendritic activity, and hence oscillatory activity, is typically recorded at the popula-
tion level—​from groups of neurons rather than from single neurons. In most neurons,
the resultant sum of synaptic actions from an entire dendritic tree, contributed to by
thousands of synaptic potentials, is delivered to the initial segment of the axon, where
it causes the resultant axonal membrane potential to be graded in intensity. The mem-
brane potential of the initial segment has a low threshold for generating a spike because
voltage-​sensitive Na +​membrane channels are concentrated there. The recorded axonal
membrane potential may be supra-​threshold if the membrane potential is above the
threshold, in which case spike trains are generated and travel down the axon, or sub-​
threshold, in which case the axon may be affected but no spike trains are generated.
The spike trains may contribute to the neuronal synchronization underlying the LFP
(Murthy & Fetz, 1996).
The EEG, electrocorticogram (ECoG), intracranial EEG (iEEG),
magnetoencephalogram (MEG), and LFP signals all are generated by the dendritic ac-
tivity of neuronal populations, and all display oscillations. Except for the MEG, which
is magnetic, all these signals are electric and are recorded with respect to a reference
potential. The EEG and MEG are usually recorded from outside the cranium, whereas
the ECoG, iEEG, and LFP are recorded from inside the cranium. The ECoG is recorded
from outside the cortical tissue, whereas the iEEG and LFP are recorded from inside
the cortex. The iEEG is recorded from macroscopic electrodes and the LFP is usually
recorded with indwelling microelectrodes. The LFP recording may be monopolar, in
which case a single microelectrode records the LFP, or it may be bipolar, in which case
the LFP is the difference in potential between two nearby microelectrodes. In fact, the
LFP is often recorded from the same microelectrodes used to record neuronal spikes,
134   STEVEN L. BRESSLER

and at the same time (Perelman & Ginosar, 2007; Salazar et al., 2012). However, the LFP
typically shows oscillations whereas they are usually not obvious in spike activity.
Since these signal types all reveal oscillatory activity, which is considered by many to
be essential for cognition in the brain (Voytek & Knight, 2015), and are typically present
when humans perform cognitive tasks, the dendritic activity of neurons in the brain
should not be overlooked in the search for neural correlates of cognition, even though it
cannot currently be studied in the single neuron. Oscillations in the summed dendritic
activity of neuronal populations are strongly related to cognitive function in the neo-
cortex (Donner & Siegel, 2011).

7.3  Phase Coupling and Causality

in Sensorimotor Systems

The somatosensory-​motor system provides a useful example of neocortical coord-

ination during a cognitive task performed by the macaque monkey. LFP oscillations
recorded from somatosensory and motor sites in the macaque monkey neocortex
are phase coupled in the beta frequency band during the time in the task that a self-​
generated hand press cues the monkey by somatosensation that a visual stimulus (0
msec) is soon to appear on a visual display screen. The stimulus is subsequently per-
ceptually discriminated as part of a visual pattern discrimination task requiring hand
musculature control (Brovelli et al., 2004). LFPs from specific site pairs in primary and
secondary somatosensory cortices, and primary and secondary motor cortex, become
beta-​phase-​coupled (phase synchronized) when the hand press cue is active (Figure 7.1).
The presence of beta oscillations in sensorimotor cortex is consistent with the theory
that beta oscillations signal maintenance of the current sensorimotor state (Engel &
Fries, 2010) since sensorimotor coordination (LFP phase coupling) is likely present
throughout this time. The pattern of somatosensory-​motor site-​pair coupling is con-
sistent with execution of the hand press cue: somatosensory input is fed to the primary
somatosensory cortex and motor output is transmitted from the primary motor cortex
to the motor spinal cord to execute the hand press. In addition to phase coupling, con-
ditional spectral Wiener–​Granger (WG) causality (Ding et al., 2006) was also measured
on the same set of sensorimotor LFP recordings. The resulting pattern of sensorimotor
neocortical site-​pair neural causality also supports a sensorimotor feedback loop for
execution of the hand press cue, with influences that are directed to the primary som-
atosensory cortex from somatosensory inputs, and from there to the primary motor
cortex, with feedback loops between primary and secondary somatosensory cortices,
and between primary and secondary motor cortices, signaling modulatory influences
(Figure 7.1).
The fact that the observed oscillations are in the beta frequency band suggests
that sensorimotor neocortical neurons are coordinated in anticipation of making a
 FREQUENCY ANALYSIS OF THE MONKEY    135

(a) Coherence Graph Granger Causality Graph

Cs Cs
IPs IPs
6 6
2 1 Scales 2 1
4 4
Granger
3 Coherence 3
Causality
0.5 0.25
As As
0.4 0.2
5 0.3 0.15 5
STs 0.2 0.1 STs
Ls Ls
0.1 0.05

(b) Coherence Graph Granger Causality Graph

4 4
Cs Cs
As As
IPs IPs

1 2 3 Ls 1 2 3 Ls

Figure 7.1 Prestimulus beta-​ frequency coherence and (conditional spectral Wiener-​ )

Granger causality graphs derived from the sensorimotor cortices of two monkeys (M1, left
hemisphere; M2, right hemisphere). A self-​generated hand press cues the monkey that a visual
stimulus is soon to appear on a visual display screen. The stimulus is subsequently perceptually
discriminated as part of a visual pattern discrimination task (Brovelli et al., 2004). In each case,
the pattern of synchronization (coherence) and Granger causality of beta-​band oscillations from
primary and secondary somatosensory and motor cortices is consistent with execution of the
hand press cue: somatosensory input is fed to the primary somatosensory cortex and motor
output is transmitted from the primary motor cortex to the motor spinal cord to execute the
hand press.

sensorimotor decision in similar manner to the coordination of motor neocortical

neurons during steady muscle contractions and steady holding periods following
phasic movements as reported by numerous literature studies (e.g., Engel & Fries,
2010). Thus, when the monkey makes a hand press on the lever, sensorimotor neo-
cortical neurons are coordinated in anticipation of the monkey making the subse-
quent sensorimotor decision. The observation of conditional spectral WG causality
from neurons at one sensorimotor neocortical site to those at another site appears to
indicate more than the observation of phase coupling alone by suggesting that sen-
sorimotor neocortical neurons causally influence each other as part of that deci-
sion. Finally, the reported results are consistent with accumulating evidence that
oscillations in the beta frequency band have a distinct physiological role and that they
provide an effective means of controlling spike timing, thereby coordinating informa-
tion transfer across brain regions and supporting spike-​timing dependent plasticity
(Engel & Fries, 2010).
136   STEVEN L. BRESSLER

7.4  Phase Coupling and Causality

in Visual Neocortex

LFPs, simultaneously recorded from the striate and extrastriate (V4—​visual area 4 and
TEO—​temporal-​occipital area) visual cortices prior to appearance of the visual stimulus
in the same visual pattern discrimination task (Bressler & Richter, 2015), also show os-
cillatory activity in the beta frequency range. The same phase-​coupling and neural caus-
ality metrics have been computed from the visual LFPs as from somatosensory-​motor
LFPs. The main finding is that extrastriate–​striate site pairs are beta-​frequency phase
coupled and carried by strong top-​down (extrastriate-​to-​striate) beta influences, in an-
ticipation of visual processing (Figures 7.2 and 7.3). Furthermore, behavioral context is
conveyed to primary visual cortex prior to appearance of the visual stimulus (Richter
et al., 2018). Thus, information about the visual stimulus appears in the visual cortex

(a)

power (dB μV) power (dB μV)

40 2
power (dB μV)

Residual
30
V1/V2

1
20
0
10 20 30 40 50 60 70 80 90
(b)
40 2
power (dB μV)
Extrastriate

Residual
30 1
20
0
10 20 30 40 50 60 70 80 90
(c)
0.05
Coherence

0
10 20 30 40 50 60 70 80 90
(d)
0.04

0.02
GC

0
10 20 30 40 50 60 70 80 90
Frequency (Hz)

Figure 7.2  Prestimulus beta-​frequency power, coherence, and (conditional spectral Wiener-​
Granger causality spectra of V1/​V2 and V4/​TEO LFPs. (A) Average striate power spectrum over
sites (black line ± s.e.m.), and the residual power spectrum after 1/​f removal (red line ± s.e.m.) for
V1 sites. (B) Average extrastriate power spectrum over sites and monkeys (black line ± s.e.m.),
and the residual power spectrum after 1/​f removal (red line ± s.e.m.) for the V4/​TEO sites.
(C) Average coherence spectrum over V1/​V2-​extrastriate site pairs ± s.e.m. for V1/​V2-​extrastriate
pairs. (D) Average top-​down (red line ± s.e.m.), and bottom-​up (blue line ± s.e.m.) GC spectra for
V1-​extrastriate pairs. Shaded grey rectangular region denotes the frequencies (8–​23 Hz) where
top-​down and bottom-​up sGC were significantly different (p<0.001).
 FREQUENCY ANALYSIS OF THE MONKEY    137

M1 GC M2
0.20

0.15

0.10

0.05

M1 Coh M2
0.20

0.15

0.10

0.05

Figure 7.3  Prestimulus beta-​frequency coherence and top-​down (conditional spectral Wiener-​
)Granger causality maps. Top: Maps of the recording sites for M1 and M2. V1/​V2 electrode
locations are marked by yellow circles, and extrastriate (V4 and TEO) locations by gray circles.
Middle: enlarged maps of visual cortex showing top-​down sGC at 16 Hz as arrows for V1/​V2-​
extrastriate pairs. Bottom: corresponding maps of coherence for the same site pairs. Thickness of
the top-​down sGC arrows and coherence bars is proportional to the magnitude of sGC or coher-
ence at 16 Hz.

before the actual onset of the visual stimulus. This result validates previous proposals
that top-​down visual processing depends on interareal synchronization in visual neo-
cortex (von Stein et al., 2000), and suggests that it acts to “prime” visual cortex to pre-
pare it for receiving the visual stimulus.
The same basic methodology, namely conditional spectral WG causality analysis, has
subsequently been applied to visual neocortical LFPs in macaque monkeys performing
a visuospatial attention task (Bastos et al., 2015). In the visual system, neocortical areas
are seen to interact in both bottom-​up and top-​down directions, with bottom-​up
gamma-​band influences conveying sensory signals, and top-​down beta-​band influences
modulating those bottom-​up influences according to behavioral context. In the ma-
caque monkey visual neocortex, bottom-​up influences are carried by theta-​band (~4
Hz) and gamma-​band (~60–​80 Hz) synchronization, and top-​down influences by
beta-​band (~14–​18 Hz) synchronization (Bastos et al. 2015). Furthermore, neocor-
tical hierarchies (Felleman & Van Essen, 1991; Hilgetag et al., 1996) created based on
138   STEVEN L. BRESSLER

asymmetries in these directional influences are similar to those based on asymmetries

in neuroanatomical connections (Markov et al., 2014).
Effective interareal interaction in the visual system depends on local (within-​area)
synchronization of oscillations that are layer specific. Supragranular layers show
local gamma-​band synchronization, whereas infragranular layers show local alpha-​/​
beta-​band synchronization (Buffalo et al., 2011; Xing et al., 2012; Roberts et al., 2013).
Since supragranular layers primarily send bottom-​up projections, and infragranular
layers primarily send top-​down projections, it is proposed that interareal syn-
chronization in the gamma band mediates bottom-​up influences and that the beta
band mediates top-​down influences (Wang, 2010; Bastos et al., 2012; van Kerkoerle
et al., 2014).
Metrics of the bottom-​up or top-​down character of interareal connections have
been used to create neocortical hierarchies. A functional metric of directed influence is
computed as the directed influence asymmetry index (DAI), based on the conditional
spectral WG causality in bottom-​up and top-​down directions. A neuroanatomical
metric of directional influence is computed as the proportion of supragranular labeled
neurons to the sum of supragranular and infragranular labeled neurons (SLN). The DAI
and SLN metrics quantify the degree to which an interareal projection is top-​down or
bottom-​up. These hierarchies are generally similar whether created from conditional
spectral WG causality or from neuroanatomical metrics. The functional hierarchies fur-
ther demonstrate that bottom-​up influences utilize theta and gamma bands, whereas
top-​down influences utilize the beta band. If directional influences represent interareal
communication, and, as has been speculated (Bastos et al., 2015), increasing oscillation
frequency entails increasing communication throughput, then gamma-​band commu-
nication might be expected for bottom-​up influences, since they are expected to require
higher-​throughput communication.
The finding of top-​ down beta influences in the visual system (Bastos
et al., 2015) is consistent with Richter and colleagues’ (2018) results that top-​down
beta signaling conveys behavioral context to the visual cortex, and with the general
conclusion that beta-​band synchrony signals the “status-​quo” in neocortex (Engel &
Fries, 2010). In fact, a distributed network of phase-​coupled beta-​band oscillations
might easily signal predicted sensory and motor events (Bastos et al., 2012; Bressler &
Richter, 2015).

7.5 Oscillations
in Prefrontal Neocortex

Monkey LFP oscillations have been reported during working memory in the theta,
alpha, beta, and gamma bands. The gamma band is associated with sensory information,
 FREQUENCY ANALYSIS OF THE MONKEY    139

and gamma-​band power correlates with the number of objects held in working
memory, whereas the beta band is associated with top-​down information, and beta-​
band synchrony correlates with task rules (Liang et al., 2002; Miller et al., 2018; Richter
et al., 2018). Gamma bursting is anti-​correlated with alpha-​beta bursting (Lundqvist
et al., 2016).
Information in prefrontal neuronal spiking has been linked to brief bursts in the
gamma band in monkeys performing a working memory task (Lundqvist et al., 2016).
Prefrontal laminar LFP data has been obtained from monkeys using prefrontal laminar
probes (Bastos et al., 2018). Gamma-​band activity is strongest in the superficial layers,
and beta and alpha LFP power is strongest in the deep layers. In keeping with pre-
vious studies (Lundqvist et al., 2016), gamma-​band bursting is most informative about
working memory in the superficial layers.
Gamma-​band bursts, varying in time and frequency, were reported to accompany
both the encoding and re-​activation of sensory information (Bastos et al., 2015). The
conclusion is that gamma bursts could gate access to, and prevent sensory interfer-
ence with, working memory, since only the neuronal activity that was associated with
working memory encoding and decoding was correlated with gamma-​band burst rate
changes. Bursts in the beta band were also brief and variable, but they reflected a “default
state” that was interrupted by encoding and decoding.

7.6  Phase Coupling and Causality

in the Fronto-​Parietal Network

The prefrontal cortex is not the only region of neocortex involved in working
memory. To test the involvement of posterior parietal cortex in working memory,
LFPs were recorded from distributed sites in the prefrontal cortex and in the pos-
terior parietal cortex of macaque monkeys performing a working memory delayed-​
match-​to-​sample visual identity task (Salazar et al., 2012). Phase coupling between
prefrontal and posterior parietal cortices, examined by computing spectral coher-
ence between prefrontal-​posterior parietal LFP pairs, was found in the beta frequency
band. Analysis of prefrontal-​posterior parietal interactions in working memory by
conditional spectral WG causality applied to the delay period of the delayed match-​
to-​sample visual identity task showed that the beta frequency band was dominant.
Causal influences in the beta band were roughly balanced between the two directions,
that is, beta causal influences in the prefrontal-​to-​posterior parietal and posterior
parietal-​to-​prefrontal directions were roughly the same (slightly greater from pos-
terior parietal cortex to prefrontal cortex). This finding indicates that prefrontal
and posterior parietal cortices are roughly in balance during working memory task
performance.
140   STEVEN L. BRESSLER

7.7  Conclusions

This chapter focused on neocortical oscillations in the macaque monkey related to

cognitive processes in visual pattern discrimination, visuospatial attention, and visual
working memory tasks. In visual processing, beta-​frequency oscillatory influences pre-
dominate in the top-​down direction prior to arrival of the visual stimulus, suggesting
that beta-​frequency oscillations convey task rule-​related information from higher to
lower areas of visual neocortex for visual processing during vision.
In visual working memory, the prefrontal cortex and posterior parietal cortex in both
monkeys and humans are expected to be linked together as parts of the fronto-​parietal
network (Salazar et al., 2012; Alekseichuk et al., 2016). Beta-​frequency oscillations are
found to link posterior parietal and prefrontal cortex, with slightly greater causal in-
fluence from the posterior parietal cortex to the prefrontal cortex. Oscillations in the
gamma and theta frequency bands are also prominent in neocortex in working memory.
The gamma band is associated with sensory information in monkey working memory.
The theta band is associated with human working memory (Raghavachari et al., 2001).
Potential topics for future investigation are the presence of gamma oscillations in the
human prefrontal cortex during working memory (Howard et al., 2003), and their rela-
tion to theta oscillations (Jokisch & Jensen, 2007).
Oscillations in different frequency bands are exhibited in the monkey neocortex in
relation to cognitive function. These oscillations are similar to those in humans, and
therefore should be considered when trying to understand the role of oscillations in
human cognition. Prominent among the frequency bands at play in cognition involving
visual and prefrontal systems are theta, alpha-​beta, and gamma. These bands are fore-
most among those found in visual cortex, prefrontal cortex, and posterior parietal
cortex in relation to visual pattern discrimination and visual working memory.

References
Alekseichuk, I., Turi, Z., Amador de Lara, G., Antal, A., & Paulus, W. (2016). Spatial working
memory in humans depends on theta and high gamma synchronization in the prefrontal
cortex. Current Biology, 26, 1513–​1521.
Antzoulatos, E. & Miller, E. (2016). Synchronous beta rhythms of frontoparietal networks
support only behaviorally relevant representations. eLife, 5, e17822.doi: 10.7554/​eLife.17822
Bastos, A., Litvak, V., Moran, R., Bosman, C., Fries, P., & Friston, K. (2015). A DCM study of
spectral asymmetries in feedforward and feedback connections between visual areas V1 and
V4 in the monkey. Neuroimage, 108, 460–​475.
Bastos, A., Loonis, R., Kornblith, S., Lundqvist, M., & Miller, E. (2018). Laminar recordings
in frontal cortex suggest distinct layers for maintenance and control of working memory.
Proceedings of the National Academy of Sciences of the United States of America, 115, 1117–​1122.
Bastos, A., Usrey, W., Adams, R., Mangun, G., Fries, P., & Friston, K. (2012). Canonical
microcircuits for predictive coding. Neuron, 76, 695–​7 11.
 FREQUENCY ANALYSIS OF THE MONKEY    141

Bressler, S., Coppola, R., & Nakamura, R. (1993). Episodic multiregional cortical coherence at
multiple frequencies during visual task performance. Nature, 366, 153–​156.
Bressler, S., Richter, C., Chen, Y., & Ding, M. (2007). Cortical functional network organization
from autoregressive modeling of local field potential oscillations. Statistics in Medicine, 26,
3875–​3885.
Bressler, S. & Richter, C. (2015). Interareal oscillatory synchronization in top-​down neocortical
processing. Current Opinion in Neurobiology, 31C, 62–​66.
Brovelli, A., Ding, M., Ledberg, A., Chen, Y., Nakamura, R., & Bressler, S. (2004). Beta
oscillations in a large-​scale cortical network: Directional influences revealed by Granger
causality. Proceedings of the National Academy of Sciences of the United States of America, 101,
9849–​9854.
Buffalo, E., Fries, P., Landman, R., Buschman, T., & Desimone, R. (2011). Laminar differences
in gamma and alpha coherence in the ventral stream. Proceedings of the National Academy of
Sciences of the United States of America, 108, 11262–​11267.
Buzsaki, G., Anastassiou, C., & Koch, C. (2012). The origin of extracellular fields and currents—​
EEG, ECoG, LFP and spikes. Nature Reviews Neuroscience, 13, 407–​420.
Crone, N., Sinai, A., & Korzeniewska, A. (2006). High-​frequency gamma oscillations
and human brain mapping with electrocorticography. Progress in Brain Research, 159,
275–​295.
D’Esposito M, Detre J, Alsop D, Shin R, Atlas S, Grossman M (1995) The neural basis of the cen-
tral executive system in working memory. Nature, 378, 279–​281.
Ding, M., Chen, Y., & Bressler, S. (2006). Granger causality: Basic theory and application to
neuroscience. In B. Schelter, M. Winterhalder, & J. Timmer (Eds.), Handbook of time series
analysis: Recent theoretical developments and applications, (pp. 437–​460). Wiley.
Donner, T. & Siegal, M. (2011). A framework for local cortical oscillation patterns. Trends in
Cognitive Science, 15, 191–​199.
Engel, A. & Fries, P. (2010). Beta-​band oscillations –​signaling the status quo? Current Opinion
in Neurobiology, 20, 156–​165.
Felleman, D. & Van Essen, D. (1991). Distributed hierarchical processing in the primate cere-
bral cortex. Cerebral Cortex, 1, 1–​47.
Freeman, W. (1975). Mass action in the nervous system. Academic.
Hilgetag, C., O’Neill, M., & Young, M. (1996). Indeterminate organization of the visual system.
Science, 271, 776–​777.
Howard, M., Rizzuto, D., Caplan, J., Madsen, J., Lisman, J., Aschenbrenner-​Scheibe, R.,
Schulze-​Bonhage, A., & Kahana, M. (2003). Gamma oscillations correlate with working
memory load in humans. Cerebral Cortex, 13, 1369–​1374.
Jensen, O., Kaiser, J., & Lachaux, J. (2007). Human gamma-​frequency oscillations associated
with attention and memory. Trends in Neuroscience, 30, 317–​324.
Jokisch, D. & Jensen, O. (2007). Modulation of gamma and alpha activity during a working
memory task engaging the dorsal or ventral stream. Journal of Neuroscience, 27, 3244–​3251.
Kopell, N. (2000). We got rhythm: Dynamical systems of the nervous system. Notices of the
American Mathematical Society, 47, 6–​16.
Liang, H., Bressler, S., Ding, M., Truccolo, W., & Nakamura, R. (2002). Synchronized activity in
prefrontal cortex during anticipation of visuomotor processing. Neuroreports, 13, 2011–​2015.
Lundqvist, M., Rose, J., Herman, P., Brincat, S., Buschman, T., & Miller, E. (2016). Gamma and
beta bursts underlie working memory. Neuron, 90, 152–​164.
Lundqvist, M., Herman, P., Warden, M., Brincat, S., & Miller, E. (2018). Gamma and beta
bursts during working memory readout suggest roles in its volitional control. Nature
Communications, 9, 394.
142   STEVEN L. BRESSLER

Markov, N., Ercsey-​Ravasz, M., Van Essen, D., Knoblauch, K., Toroczkai, Z., & Kennedy, H.
(2013). Cortical high-​density counterstream architectures. Science, 342, 1238406.
Markov, N., Vezoli, J., Chameau, P., Falchier, A., Quilodran, R., Huissod, C., Lamy, C., Misery,
P., . . . Kennedy, H. (2014). Anatomy of hierarchy: Feedforward and feedback pathways in
macaque visual cortex. Journal of Comparative Neurology, 522, 225–​229.
Michalareas, G., Vezoli, J., Van Pelt, S., Schoffelen, J-​M., Kennedy, H., & Fries, P. (2016). Alpha-​
beta and gamma rhythms subserve feedback and feedforward influences among human
visual cortical areas. Neuron, 46, 60528.
Miller, E., Lundqvist, M., & Bastos, A. (2018). Working memory 2.0. Neuron, 100, 463–​475.
Murakami, S. & Okada, Y. (2006). Contributions of principal neocortical neurons to
magnetoencephalography and electroencephalography signals. Journal of Physiology, 575,
925–​936.
Murthy, V. & Fetz, E. (1996). Synchronization of neurons during local field potential oscillations
in sensorimotor cortex of awake monkeys. Journal of Neurophysiology, 76, 3968–​3982.
Perelman, Y. & Ginosar, R. (2007). An integrated system for multichannel recording with spike/​
LFP separation, integrated A/​D conversion, and threshold detection. IEEE Transactions on
Biomedical Engineering, 54, 130–​137.
Pesaran, B., Pezaris, J., Sahani, M., Mitra, P., & Anderson, R. (2002). Temporal structure in neuronal
activity during working memory in macaque parietal cortex. Nature Neuroscience, 5, 805–​81.
Raghavachari, S., Kahana, M., Rizzuto, D., Caplan, J., Kirschen, M., Bourgeois, B., Madsen, J.,
& Lisman, J. (2001). Gating of human theta oscillations by a working memory task. Journal
of Neuroscience, 21, 3175–​3183.
Richter, C., Copolla, R., & Bressler, S. (2018). Top-​down beta oscillatory signaling conveys be-
havioral context in early visual cortex. Scientific Reports, 8, 6991.
Roberts, M., Lowet, E., Brunet, N., Ter Wal, M., Tiesinga, P., Fries, P., & De Weerd, P. (2013).
Robust gamma coherence between macaque V1 and V2 by dynamic frequency matching.
Neuron, 78, 523–​536
Salazar, R., Dotson, N., Bressler, S., & Gray, C. (2012). Content-​specific fronto-​parietal syn-
chronization during visual working memory. Science, 338, 1097–​1100
Siegel, M., Warden, M., & Miller, E. (2009). Phase-​dependent neuronal coding of objects in
short-​term memory. Proceedings of the National Academy of Sciences of the United States of
America, 106, 21341–​21346
Van Kerkoerle, T., Self, M., Dagnino, B., Gariel-​Mathis, M-​A., Poort, J., van der Togt, C., &
Roelfsema, P. (2014). Alpha and gamma oscillations characterize feedback and feedforward
processing in monkey visual cortex. Proceedings of the National Academy of Sciences of the
United States of America, 111, 14332–​14341.
von Stein, A., Chiang, C., & Konig, P. (2000). Top-​down processing mediated by interareal syn-
chronization. Proceedings of the National Academy of Sciences of the United States of America,
97, 14748–​14753.
Voytek, B. & Knight, R. (2015). Dynamic network communication as a unifying neural basis for
cognition, development, aging, and disease. Biol Psych 77, 1089–​1097.
Wang, X-​J. (2010). Neurophysiological and computational principles of cortical rhythms in
cognition. Physiological Reviews, 90, 1195–​1268.
Xing, B., Guo, J., Meng, X., Wei, S-​G., & Li, S-​B. (2012). The dopamine D1 but not D3 receptor
plays a fundamental role in spatial working memory and BDNF expression in prefrontal
cortex of mice. Behavioral Brain Research, 235, 36–​41.
Pa rt I I
 CHAPTER 8

GAMM A ACT I V I T Y I N
SE NSORY AND C O G NI T I V E
PRO CES SI NG

DANIEL STRÜBER AND CHRISTOPH S. HERRMANN

8.1  Introduction and history of

research on gamma oscillations

When the German psychiatrist Hans Berger reported his discovery of the human EEG
in 1929, he described two types of waves with the larger ones oscillating at 10–​11 Hz and
the smaller ones at 20–​30 Hz (Berger, 1929)—​the well-​known alpha-​and beta-​waves,
respectively. However, in view of the results from the first Fourier analysis carried out
on the human EEG by his physicist co-​worker Dietsch (1932), Berger had to acknow-
ledge that his beta-​waves contained a lot more components than originally thought with
frequencies up to 125 Hz (Berger, 1934;1936). By comparing spontaneous EEG recordings
with recordings during mental calculation, Berger (1937) observed effects predomin-
antly in the 40–​90 Hz range which led him to conclude that beta-​waves of this specific
(high-​)frequency band “are the physical effects that accompany mental processes”. One
year later, the term “gamma waves” was proposed for higher frequencies at 35–​45 Hz,
that is, beyond the traditional beta-​band (Jasper & Andrews, 1938). However, this first-​
time labeling went mostly unnoticed at that time and “gamma” was later reintroduced
by other authors (e.g., Başar & Özesmi, 1972; Bressler & Freeman, 1980). Instead of
“gamma”, the term “40-​Hz oscillation” is also widely used.
The first experimental evidence for a possible role of gamma oscillations in early
sensory processing in the mammalian brain was provided by Adrian (1942; 1950), who
recorded oscillatory responses of the olfactory bulb of hedgehogs, cats, and rabbits
to odorous substances. He obtained oscillatory responses in the 30–​60 Hz frequency
range which he termed “induced waves” to differentiate these events from “intrinsic
146    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

waves”, signaling spontaneous activity (Adrian, 1950). Inspired by Adrian’s suggestion

that neurons responding preferentially to certain odors might be spatially organized,
Freeman collected multi-​channel EEG recordings from the surface of the olfactory bulb
of rabbits trained to respond to different odorants (Freeman & Skarda, 1985; Freeman,
1975). These analyses revealed odor-​specific spatial amplitude patterns of transient
gamma bursts at 40–​80 Hz occurring between inhalation and response, reflecting a spa-
tial code of Adrian’s induced waves that seemed to underlie the discrimination of odors.
In addition to the pioneering studies of Freeman on the olfactory bulb of the rabbit,
Başar and colleagues observed “gamma resonance” phenomena in the hippocampus and
other structures of the cat brain in response to auditory stimulation (Başar et al., 1975;
Başar et al., 1976; Başar & Özesmi, 1972), that is, an amplification of the gamma frequency
component of the evoked potential in relation to the spontaneous gamma activity just
before stimulation. Resonance phenomena have also been studied by recording the
evoked potential in response to repetitive stimulation at different frequencies (so-​called
steady-​state evoked potentials, Regan & Spekreijse, 1986). If the amplitude of the steady-​
state response peaks at a certain frequency, this component is interpreted as the reson-
ance frequency of the underlying oscillator. For gamma oscillations in the human visual
cortex, Regan (1968) first demonstrated a peak frequency of 45–​55 Hz by using photic
stimulation flickering between 5 and 60 Hz. Later on, Herrmann (2001) applied flick-
ering light at frequencies from 1 to 100 Hz and found clear resonance phenomena in
the gamma range. For the auditory modality, Galambos and colleagues (1981) reported
a comparable phenomenon at 40 Hz in response to tone bursts at different rates, which
the authors termed the auditory “40-​Hz event-​related potential”.
Whereas most of the early studies on gamma activity were concerned with its role
in sensory processing, the first attempts to relate gamma to more cognitive processes
lacking a strict relation to stimulation were in the late 1970’s and early 1980’s. One prom-
inent example is the work of Sheer (1984), who used 40 Hz EEG as a measure for chan-
ging states of focused arousal during cognitive tasks in humans (e.g., Spydell et al., 1979).
Similarly in the cat neocortex, fronto-​parietal gamma band coherence was shown to
increase during states of expectancy and focused attention (Bouyer et al., 1981). These
studies pioneered the current notion of a role for gamma oscillations in top-​down atten-
tional networks (Engel et al., 2001).
In the late 1980’s, Gray & Singer (1989) revolutionized the research on gamma ac-
tivity by observing synchronous gamma oscillations in spiking activity of the cat visual
cortex in response to light stimuli. Gray and collaborators (1989) extended their ini-
tial finding of short-​range gamma synchronization to spatially more segregated cells.
They demonstrated that neurons from distant parts of the visual cortex oscillate syn-
chronously if presented with a coherent stimulus like a single long bar (or two shorter
bars moving in the same direction), but not in case of two independent stimuli like
two bars moving in opposite directions. This finding was highly influential because
it suggested that gamma synchrony could serve as a mechanism for binding together
different features to form a coherent object (see, for reviews, Engel et al., 1997; Singer &
Gray, 1995).
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    147

Such binding-​ related synchronization of oscillatory gamma responses between

neural assemblies has not only been observed in the visual cortex of the anaesthetized
cats (Eckhorn et al., 1988; Engel et al., 1991; Gray et al., 1989), but also in awake monkeys
(Frien et al., 1994; Kreiter & Singer, 1996). This work stimulated a wealth of human
EEG studies on gamma oscillations and their possible role in visual feature-​binding
and object representation (see, for review, Tallon-​Baudry & Bertrand, 1999). However,
it soon turned out that gamma oscillations are not related to a single function like
visual grouping but that they subserve a multiplicity of cognitive functions, including
attention, learning, memory, and language processing, to name just a few (for reviews,
see Herrmann et al., 2010; Jensen et al., 2007; Pulvermüller et al., 1997; Tallon-​
Baudry, 2009).
Given this large variety of cognitive gamma correlates, the question arose whether
there might be a common fundamental process to which the many functions can be
reduced to. In this context, it has been proposed that basic memory mechanisms could
underlie functions like attention, object representation, and language (Herrmann et al.,
2004). Going further by including “non-​cognitive” functions of gamma oscillations
recorded from subcortical areas of the mammalian brain and even from invertebrate
ganglia, it has been argued that gamma oscillations represent a universal operator acting
in concert with other oscillatory systems to control the integrative brain functions at all
sensory and cognitive levels (Başar, 2013; Başar-​Eroǧlu, Strüber, Schürmann et al. 1996).
However, Whitham and colleagues (2007) challenged research on EEG gamma ac-
tivity by demonstrating that most of the EEG gamma activity disappeared from the
spectrum as a result of total neuromuscular blockade. In the following year, Yuval-​
Greenberg and colleagues’ (2008) work questioned the widely held assumption that
scalp-​recorded induced gamma activity is of cortical origin. They demonstrated that
this type of gamma activity coincides with the occurrence of miniature eye movement.
The possibility that large parts of the EEG gamma activity were artefactual rather than
neural activity had presented a major challenge to the EEG gamma community, and
it is likely that many earlier reports on the role of induced gamma activity are heavily
contaminated by muscular activity. Nevertheless, this does not mean that all previous
research is invalidated because there are several methodological issues that need to be
considered when evaluating how severe specific data sets are affected. There is clear evi-
dence in the literature that neural gamma activity can, and has been, detected by means
of EEG (Schwartzman & Kranczioch, 2011). Since then, research aims to develop arte-
fact removal techniques in order to regain confidence into the functional role of EEG
gamma activity (see Sections 8.8, 8.9).

8.2  Types of gamma activity

Gamma oscillations are part of the total EEG energy to a varying degree at any moment
in time. Such spontaneous or ongoing activity occurs independently of any external
148    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

stimulation and may signal alterations of internal states like arousal or alertness (Strüber
et al., 2001). If gamma oscillations are related to the processing of external stimuli, a
distinction is made between “evoked” and “induced” activity (Başar-​Eroǧlu, Strüber,
Schürmann, et al., 1996). Evoked gamma responses are strictly time-​and phase-​locked
to stimulus onset, that is, each single trial occurs at the same latency with zero phase
lag across trials, therefore summing up after averaging. Thus, evoked activity can be
analyzed by transforming the averaged single-​trials (i.e., the averaged evoked potential,
ERP) into the frequency domain (see Figure 8.1, left panel). This type of gamma activity
is typically observed within an early time window of ~50–​150 ms following stimula-
tion onset. In contrast, induced activity occurs later, following stimulation by at least
200–​300 ms, and it cancels out almost completely if averaged due to its inter-​trial vari-
ation of phase and latency. Therefore, to detect induced gamma oscillations, each single
trial needs to be subjected to a wavelet transform, and then the resulting absolute power

Evoked Induced Evoked Induced

amplitude
[a.u.]

2
transform
wavelet

...

averaging averaging

Total Activity
frequency

100
[Hz]

ERP
50
0 100 300
time [ms]

Evoked Activity
frequency

100 0 0.5 1
[Hz]

50
0 100 300 amplitude [a.u.]
time [ms]

Figure 8.1  Analysis of evoked and induced gamma activity. Left: Averaging all single trials
containing evoked and induced gamma oscillations yields the ERP. Transforming the ERP into
the time-​frequency domain (wavelet transform) leaves only the evoked gamma activity, because
the induced gamma activity cancels out in the ERP due to phase jitter. Right: Averaging the ab-
solute values of each single trial’s wavelet transform yields both evoked and induced activity (i.e.,
the total activity). Thus, evoked activity is obtained with both types of analyses, whereas induced
gamma activity appears only in the average of the single trial wavelet transforms.
Adapted from Herrmann et al., 2014.
NB: The latency jitter of the induced activity induces temporal smearing in the total activity. a.u., arbitrary units.
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    149

values are averaged across trials without cancellation (see Figure 8.1, right panel). Note,
however, that this average contains not only the induced but also the evoked activity and
has, therefore, been termed “total activity” (Herrmann et al., 2014). Within this plot of
total activity, all activity that is not also present in the evoked plot, can be referred to as
induced activity. While Figure 8.1 depicts the differences between the different types of
gamma activity in principle, Figure 8.2 represents real data from human experiments.
In traditional EEG research, the range of gamma frequencies is given as 30–​80 Hz
with evoked activity often oscillating nearby 40 Hz, whereas induced responses can
also reach higher frequencies (Herrmann, Munk, et al., 2004). However, in the con-
text of subdural electrocorticography (ECoG) in epilepsy patients, a broad range of
very high gamma frequencies (around 80–​200 Hz) was discovered unexpectedly and
called “high gamma” to distinguish this broadband response from the traditional “low
gamma” oscillations in narrower bands (for a review, see Crone et al., 2011). Although

(a) evoked total

80
frequency [Hz]

60
Reversal
Pattern

40

(b)
80
frequency [Hz]

60
Motion

40

–0.2 00 0.2 0.4 0 0.2 0.4 0.6 0.8

time [s] time [s]
[a.u.]
0 1
(c)
graphies
Topo-

[a.u.]
0 1

Figure 8.2  Time-​frequency plots and topographies of evoked and induced gamma activity.
White box: Evoked gamma activity for pattern reversal (A) and motion (B). Yellow box: Induced
gamma activity for pattern reversal (A) and motion (B) within the plot of total activity. Red
box: Steady-​state visual evoked potential (SSVEP) in the motion condition as a response to the
single images representing the motion of the gratings. The green line represent stimulus onset.
C: Topographic maps of evoked (left) and induced (right) gamma activity during an object recog-
nition task. a.u.: arbitrary units.
(A, B) Adapted from Naue et al., 2011; (C) Adapted from Busch, Herrmann, et al., 2006.
150    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

this broadband activity often overlaps with the band-​limited (low) gamma oscillations,
it is possible that such broadband responses reflect mere increases of (non-​oscillatory)
gamma power and/​or spiking activity rather than a true oscillation (Buzsáki & Wang,
2012; Ray & Maunsell, 2011), since the latter would be indicated as a clear peak in the
power spectrum. There is a recent debate about how to assess and interpret high gamma
activity in the absence of a spectral peak (Brunet et al., 2014; Hermes et al., 2015). Further
research is needed to elucidate the distinction between “low and high” or “narrow-​and
broadband” gamma activity in terms of their neurophysiological underpinnings and
functional roles. In this context, note that the observation of high gamma responses is
not bound by its superior signal-​to-​noise ratio to invasive depth recordings and ECoG
in patients, as gamma responses in the 90-​250 Hz range have also been recorded from
conventional scalp EEGs of healthy volunteers (Darvas et al., 2010; Lenz, Jeschke,
et al., 2008).

8.3  Evoked gamma activity

In light of the latency difference between evoked (~50–​150 ms) and induced gamma ac-
tivity (~200–​300 ms), it has been suggested that evoked activity reflects an early pro-
cessing stage at the level of primary visual cortices (Zaehle et al., 2009), whereas induced
activities occur at later stages (Herrmann et al., 2010). Findings of evoked gamma ac-
tivity modulated by low-​level physical features of visual stimuli support this view (for
the sake of brevity, we focus on the visual domain in the remainder of this chapter).
However, there is a remarkable overlap between evoked and induced gamma activity in
reflecting sensory vs. cognitive effects, as demonstrated in the sequel.
Regarding stimulus-​driven effects, early evoked gamma activity has been observed
to increase with stimulus size and with central as compared to peripheral stimulation
(Busch et al., 2004). Also high visual contrast (Schadow et al., 2007) and low spatial
frequencies (Fründ et al., 2007) of simple grating stimuli increased the power of evoked
gamma activity. With regard to motion, evoked gamma power did not differ between
stationary and moving gratings (Naue et al., 2011; Swettenham et al., 2009). However,
inverting the black and white stripes of a stationary grating (pattern reversal) led to a
threefold increase of the evoked gamma amplitude compared to stationary and moving
gratings, probably due to related contrast effects (Naue et al., 2011, see Figure 8.2).
These exemplary findings not only indicate an early processing stage of evoked
gamma responses but also implicate that finding evoked gamma activity requires a
corresponding design of physical stimulus parameters. Relatedly, before a cognitive
effect on evoked gamma activity can be inferred from two experimental conditions, care
must be taken that physically identical stimuli were used. Otherwise, differences of the
evoked gamma response cannot unequivocally be attributed to the cognitive process
under study.
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    151

Cognitive effects on the evoked gamma activity have been observed in visual discrim-
ination tasks where participants had to attend to a target and to ignore distractor stimuli
that were physically more or less similar to the target (Herrmann & Mecklinger, 2001;
Herrmann et al., 1999). The results not only demonstrated a target-​effect (i.e., higher
evoked gamma activity to attended stimuli), but also a graded effect of similarity be-
tween target and distractor stimuli (i.e., the more features a distractor shared with the
target the stronger was the evoked gamma activity). This led to the suggestion that each
stimulus is compared to a short-​term memory template of the target and that the de-
gree of matching between stimulus and template determines the strength of the evoked
gamma activity. Similarly for long-​term memory (LTM), a match between line drawings
of real-​ world objects and their well-​ consolidated memory representation evoked
stronger gamma responses than the perception of unfamiliar (non-​)objects without an
LTM representation (Herrmann et al., 2004).
Modulations of evoked gamma activity have also been reported in the context of
visual semantic memory (Oppermann et al., 2012). Simultaneously presented pairs
of conceptually coherent scenes (e.g., mouse–​cheese) evoked stronger gamma-​band
responses than semantically unrelated object pairs (e.g., camel–​magnet). This effect
occurred within a widespread network of bilateral occipital as well as right temporal and
frontal regions in a time window between 70–​130 ms after stimulus onset, indicating a
role of early gamma activity for a rapid memory-​based extraction of the gist of a scene.
Together, studies on early evoked gamma oscillations demonstrate not only their sen-
sitivity to low-​level stimulus features but also an influence of cognitive effects occurring
as early as 50–​150 ms after stimulus onset, thereby revealing an early interaction between
bottom-​up and top-​down processes in the gamma band (Busch et al., 2006).

8.4  Induced (total) gamma activity

Especially the induced type of gamma activity has been consistently related to higher
cognitive processes (Kaiser & Lutzenberger, 2005), motivated by the initial findings
in animals suggesting a possible role of induced synchronous neural discharges in
bottom-​up feature binding (see Section 8.1; Eckhorn et al., 1988; Gray et al., 1989). By
using protocols very similar to these animal studies, their main finding of an increase in
the strength of induced gamma synchrony during passive viewing of coherent moving
bars could be replicated in the human scalp EEG (Lutzenberger et al., 1995; Müller et al.,
1996). Increases of induced gamma activity have also been reported in response to co-
herent versus incoherent static stimuli during a visual discrimination task. In a classical
study, presenting an illusory Kanizsa triangle, a real triangle, and a no-​triangle stimulus
with the black inducer disks rotated outwards, resulted in specific enhancements of the
induced gamma activity for the coherent triangles (illusory and real) as compared to the
no-​triangle stimuli (Tallon-​Baudry et al., 1996).
152    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

In addition to these relatively low-​level feature binding processes originating from

visual cortices, induced gamma activity has been observed also in higher stages of
perceptual processing. For instance, at occipito-​temporal and frontal areas during
rehearsal of an object representation in short-​term memory (Tallon-​Baudry et al.,
1998), and at occipito-​parietal areas during the top-​down activation of internal object
representations (Tallon-​Baudry et al., 1997), as well as during selective spatial attention
to moving stimuli (Gruber et al., 1999). Together, those findings are in line with the
interpretation of induced gamma activity as a signature of both bottom-​up and top-​
down related binding processes involved in object representation (Tallon-​Baudry &
Bertrand, 1999).
Consistent with this “representational hypothesis” of induced gamma activity are
studies demonstrating augmented gamma power and phase coupling during retrieval
from LTM for familiar objects compared to unfamiliar ones (e.g., Busch et al., 2006;
Gruber et al., 2006). Furthermore, in a recognition memory task, Gruber and colleagues
(2004) showed that induced gamma activity during the encoding phase was higher for
subsequently recognized words as compared to forgotten words.
Summerfield and Mangels (2006) describe similar enhancements of induced gamma
activity during successful encoding, although they compared later memory perform-
ance between predictable items that were encoded under top-​down attentional con-
trol and unpredictable items to which attention could not be oriented in a top-​down
manner during encoding. Enhanced gamma activity over frontal regions predicted
successful memory formation for the predictable items only, indicating a role of frontal
gamma activity in attentional top-​down mechanisms facilitating memory formation
(Summerfield & Mangels, 2006).
Interestingly, a frontal gamma-​band enhancement was also reported during multi-​
stable visual perception (Başar-​Eroǧlu, Strüber, Kruse, et al., 1996), that is, spontan-
eously switching between different interpretations of an invariant stimulus pattern
like the famous Necker cube. This frontal gamma activity was stronger for observers
experiencing more figure reversals compared to those with a lower reversal rate (Strüber
et al., 2000; Strüber et al., 2001), and when observers were required to control their re-
versal rate intentionally (Mathes et al., 2006). Together, these findings might indicate
that frontal gamma band activity represents top-​down influences of attentional selec-
tion on feature binding of relevant object representations during perceptual reversals
(Engel et al., 2001).
Overall, these example studies on induced gamma activity demonstrate a variety
of gamma-​related functions ranging from basic perceptual to high-​level cognitive
processes like learning, memory, and attention. On the one hand, such a diversity of
functional correlates speaks against a role of induced gamma activity for a single specific
cognitive function. On the other hand, the processes of perception, recognition, and
attention are closely intertwined and, therefore, might rely on the same neurophysio-
logical mechanisms inherent in gamma oscillations that subserve these functions in a
dynamic task-​dependent manner (Fries, 2009; Tallon-​Baudry, 2009; Varela et al., 2001).
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    153

8.5  Neurophysiological mechanisms

How do gamma oscillations exert their functions in basic sensory and higher cogni-
tive functions and what are the neurophysiological mechanisms underlying oscillatory
gamma activity?
The central concept which is thought to underlie the functional relevance of gamma
activity is referred to as “oscillatory synchrony”, that is, the periodic co-​occurrence
of electrical impulses from a group of neurons on a fine temporal scale. In the con-
text of EEG scalp recordings, the obtained electrophysiological data inevitably reflect
synchronized activity from large neuronal populations, because otherwise the weak
synaptic currents would not be measurable at the scalp level. Local oscillatory syn-
chrony resulting from within-​area interactions would then appear as increased power
at individual electrodes, whereas oscillatory synchrony related to large-​scale integration
is best characterized by phase coherence between two distant sources (Siegel et al., 2012;
Varela et al., 2001).
Oscillatory synchrony is thought to temporally structure the occurrence of spike
trains without changing the mean firing rates of neurons and, thereby, to have a func-
tional role in the processing of incoming inputs and the emergence of functional
networks by gating the information flow (Salinas & Sejnowski, 2001). Converging
evidence from experimental work in animals (in vivo and in vitro) and modeling
approaches suggests that cortical gamma oscillations and their local synchronization
result from interactions of reciprocally connected excitatory pyramidal cells and in-
hibitory gamma-​aminobutyric acid (GABA)-​ergic interneurons (Bartos et al., 2007;
Buzsáki & Wang, 2012; Wang, 2010; Whittington et al., 2011; Whittington et al., 2000).
In such a network, the pyramidal cells activate the interneurons, which self-​
generate synchronized gamma oscillations. This gamma-​synchronized activity of the
interneurons is then imposed onto the pyramidal cells, resulting in rhythmic inhib-
ition of the pyramidal cells, which in turn leads to a rhythmic synchronization of their
discharges. Thus, during each cycle of these excitatory-​inhibitory feedback loops, the
time window during which the pyramidal cells are able to discharge is restricted by the
decay time of their inhibitory input from the fast-​spiking interneurons, introducing a
phase delay of a few milliseconds between pyramidal and interneuron discharges (Fries
et al, 2007). From this basic mechanism of gamma synchronization several mechanistic
consequences arise that are thought to be instrumental for the formation of neuronal
cell assemblies, cortical signal transmission, and, thereby, the implementation of cogni-
tive functions (Bosman et al., 2014; Cannon et al., 2014; Vinck & Bosman, 2016).
One consequence of gamma synchronization that relates to assembly formation is
its involvement in the regulation of synaptic plasticity. The precise timing of pre-​and
post-​synaptic processes emerging from gamma synchronization acts on a time scale
of a few tens of milliseconds, which is relevant for spike-​timing-​dependent plasticity
and, thus, for the induction of long-​term potentiation or depression (Fell & Axmacher,
154    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

2011; Paulsen & Sejnowski, 2000; Sejnowski & Paulsen, 2006) and associative learning
(Miltner et al., 1999). It has been proposed that the period of gamma oscillations (~25
msec) is “designed” to match the time course of calcium fluctuations in dendrites and,
therefore, to facilitate learning (Bibbig et al., 2001).
With regard to local within-​area interactions, synchronization in the gamma-​band
with its high temporal precision in the millisecond range is hypothesized to increase the
impact of presynaptic neurons on their target cells because the gamma-​synchronized
spike packages arrive close together, thus summing up more effectively to initiate
postsynaptic discharges. This effect of precise spike timing is referred to as feedforward
coincidence detection (Fries, 2009; Salinas & Sejnowski, 2001), which has been linked
to the integration (binding) of different stimulus features during object recognition
(Bosman et al., 2014).
This concept has also been transferred to inter-​areal communication between mul-
tiple groups of neurons, each oscillating in the gamma frequency range. In this context,
the “communication through coherence” (CTC) hypothesis (Fries, 2005; 2015) claims
that the communication between two groups of neurons can be facilitated by gamma
synchronization in the two groups, if the spikes from the presynaptic group (sender)
arrive at the postsynaptic group (receiver) at the appropriate phase, that is, during a min-
imal amount of GABAergic inhibition. This phase-​coupling of oscillations constitutes a
window of “opportunity” in which neural networks jointly involved in signal processing
can communicate. This mechanism allows for gain modulation of pre-​synaptic inputs
that compete for activating higher-​level post-​synaptic targets as is the case with se-
lective attention. In this scenario, visual attention might selectively increase the effective
strength of those synaptic inputs from lower level neurons that process attended stimuli
at the expense of inputs from the non-​attended stimuli (Bosman et al., 2014; Fries, 2015).
In this way, gamma synchronization might dynamically route the information flow be-
tween higher and lower level areas within the visual hierarchy as has been observed lo-
cally between multiple visual areas (see, for review, Bosman et al., 2014).
However, it is less clear whether gamma synchronization also serves as a mech-
anism for large-​scale integration across distant brain regions that also include, for ex-
ample, frontal or parietal areas. It has been suggested that the spatial distance between
interacting brain areas and, hence, the conduction delay may define the communication
frequency, with gamma oscillations acting more locally and lower frequencies more glo-
bally (Kopell et al., 2000; von Stein & Sarnthein, 2000). A reason for this may be that, in
contrast to the millisecond precision of gamma oscillations, lower-​frequency bands are
more robust to spike timing delays (Buschman & Miller, 2007). Indeed, several findings
in monkeys have shown that long-​distance top-​down processes are carried by inter-​
areal synchrony in the alpha and low-​beta frequency range, whereas gamma oscillations
index a local encoding of information and the bottom-​up transfer of low-​level sensory
information to higher-​level areas (for reviews, see, Bressler & Richter, 2015; Gregoriou
et al., 2015; Siegel et al., 2012; Wang, 2010).
On the other hand, there is also increasing evidence for a role of gamma synchrony
in large-​scale interaction during various perceptual and attentional processes (see
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    155

for a review, Gregoriou et al., 2015), indicating that physical distance might not be the
only factor that determines the frequency band used for inter-​areal synchronization.
Moreover, gamma-​synchronized long-​range signal transmission seems to work both
upstream (i.e., bottom-​up) and downstream (i.e., top-​down) within the cortical hier-
archy. For example, long-​range gamma coupling between prefrontal and visual areas
during directed attention was found to be initiated frontally, thereby signaling top-​
down attentional influences on the visual cortex (Gregoriou et al., 2009). Another study
reported long-​range bottom-​up directed gamma synchrony between posterior parietal
and prefrontal regions during automatic attention driven by salient stimuli (Buschman
& Miller, 2007). Intriguingly, the same areas synchronized in top-​down direction if
attention was focused volitionally, but in this case in the beta-​range (Buschman &
Miller, 2007), indicating that different frequencies are used for feedforward and feed-
back signaling.
Such frequency-​specific differences in the direction of inter-​areal interaction (i.e.,
bottom-​up vs. top-​down) have been related to the different directions of information
flow in the cortical layers with feedforward and feedback connections originating pri-
marily in superficial and deep layers, respectively (Felleman & Van Essen, 1991; Markov
et al., 2014). Accumulating evidence suggests that alpha/​beta oscillations originate
in deeper layers of the visual cortex and support feedback signaling, whereas gamma
synchrony emerges from superficial layers and signals feedforward information flow
(Buffalo et al., 2011; Michalareas et al., 2016; van Kerkoerle et al., 2014; von Stein et al.,
2000). Together, these findings clearly suggest a role for gamma synchrony in local
bottom-​up interaction between visual cortices (Siegel et al., 2012). However, it remains
an open question how this function can be reconciled with the documented long-​range
gamma synchrony during top-​down attention (Gregoriou et al., 2015).
Overall, the recurrent excitatory-​inhibitory network interactions underlying local
gamma synchronization are thought to establish low-​level circuit functions (e.g.,
synaptic plasticity, coincidence detection, gain modulation, phase coding, dynamic
routing) that may act as elementary building blocks of cognitive functions (e.g., visual
feature integration, selective attention, learning, and memory) in a task-​specific com-
bination (Bosman et al., 2014; Siegel et al., 2012). Nevertheless, there are multiple meth-
odological concerns that need to be considered to reliably assess EEG gamma activity as
outlined in the next section.

8.6  Methodological aspects

Scalp recorded gamma activity is subject to a variety of high-​frequency artefacts which

might seriously affect recording, analysis, and interpretation of the data. Therefore,
these artefacts need to be either prevented by appropriate recording conditions or to be
removed by post hoc analysis techniques. There are two main sources of artefacts. First,
technical artefacts like power line noise, the screen refresh rate, or the rate at which
156    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

single images are presented in order to show a movie (cf. Figure 8.2 right panel, SSVEP).
Second, physiological artefacts like eye movements and electromyogenic (EMG) ac-
tivity generated by muscles from the scalp, face, and neck (see, for review, Nottage &
Horder, 2016).

8.7  Technical artefacts

Power line noise occurs at a frequency of 50 Hz in Europe and 60 Hz in the US; both
frequencies are in the gamma range. Therefore, any power supply like electric cables,
wall sockets, or electrically operated equipment inside the recording cabin (lamps)
results in a 50-​or 60-​Hz peak in the EEG power spectrum. To effectively avoid frequency
interference, experiments should be conducted in an electrically shielded room with all
devices inside the cabin operated on batteries. The stimulation monitor can be placed
outside the cabin behind an electrically shielded window and a fiberoptic cable can be
used to transfer the EEG data to a computer outside the recording cabin. If it is not pos-
sible to prevent power line noise from being recorded, a low-​pass or “notch” filter at
50 or 60 Hz might be applied to the data. However, the use of such filters is problem-
atic because they might induce “ringing” (i.e., the induction of spurious oscillations by
transients in the EEG) and distort the phase of neural oscillations. Alternative strategies
have been developed on the basis of noise cancellation (see Nottage, 2010 for details).
In addition to power line noise, every screen refresh generates an electromagnetic
signal which might be seen as a narrow band in the EEG gamma range, typically at
anterior electrodes. The exact frequency depends on the primary refresh rate and its
harmonics. Nottage & Horder (2016) explore possible ways to remove this type of
artefact.

8.8  Physiological artefacts

The difficulty of properly removing EMG artifacts is particularly important for studies
on gamma activity, given the fact that the broad frequency spectrum of EMG activity
substantially overlaps with the gamma frequency range. An amplitude maximum
of EMG contamination in the gamma range (40–​80 Hz) was found at temporal sites
during phasic contraction of facial muscles (Goncharova et al., 2003). Because of their
high amplitude, occasionally occurring phasic muscle contractions (e.g., chewing
or jaw clenching) can be detected relatively easily by visual inspection or mathemat-
ical algorithms and then be omitted from further analysis (e.g., Fitzgibbon et al., 2015).
However, in addition to large phasic contractions, the head and neck muscles are con-
stantly active to maintain posture, which might result in tonic EMG activity throughout
an EEG session.
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    157

Critically, low-​amplitude tonic muscle activity occurs even in “relaxed” states and
is, thus, difficult to detect in scalp recordings but still contributes significantly to EMG
contamination in the gamma range, as has been shown in pharmacologically paralyzed
human volunteers (Whitham et al., 2007). Paralysis compared to pre-​paralyzed states
of the same participants was found to result in a marked reduction of spectral power in
the gamma range, with 84% of the power derived from EMG, mostly over peripheral
scalp regions. Moreover, the execution of different cognitive tasks induced a broadband
increase in the gamma frequency range in unparalyzed but not paralyzed participants,
indicating that EMG activity was responsible for the task-​related spectral power
increases (Whitham et al., 2008). However, when employing a standard oddball task
that allows for stimulus-​locked data analysis, significant gamma activity was identified
in both the pre-​paralyzed and the paralyzed condition, with stronger activity for rare
target than for more frequent standard stimuli (Pope et al., 2009).
While these studies clearly demonstrate a large contribution of EMG activity to the
overall EEG spectral power, they also show that (at least under experimental conditions
where time-​and stimulus-​locked analysis is possible, and in contrast to, for example,
analyzing states of varying cognitive load during mental arithmetic) neuronal gamma
activity can still be measured at the scalp EEG. Thus, it seems possible to extract neural
gamma activity from EMG noise if it is analyzed in response to discrete stimuli (e.g., co-
herent stimuli vs. incoherent visual objects). For this, however, methods for the effective
removal of EMG artefacts are required.
There is a multitude of methods for dealing with scalp EMG (see, for review, Nottage
& Horder, 2016). One novel approach that specifically addresses the tonic nature of scalp
and neck muscle artefacts uses mathematical modeling to fit individual muscle spikes
and subtract these from the signal, resulting in an effective correction of the gamma ac-
tivity associated with a self-​paced motor task (Nottage et al., 2013). Recently, Janani and
colleagues (2018) used datasets that are free of muscle activity due to paralysis (taken
from Whitham et al., 2007, 2008) to identify limitations of traditional approaches and,
then, to evaluate the improvements of a newly developed algorithm for tonic muscle
artefact removal. With this method, high-​frequency EMG artefacts were reduced con-
siderably, although a residual artefact still remains (compared to paralysis). Given the
variety of techniques that are based on different mathematical concepts, the authors
suggested using a combination of complementary algorithms for a further improve-
ment of EMG artefact removal (Janani et al., 2018).
Ocular activity also generates muscle-​related artefacts. The main sources of eye
movement artefacts are blinks and saccades. It is standard practice to measure the
electro-​oculogram (EOG) from two channels of the left and right eye. For rejecting eye
blinks and large saccades, an amplitude threshold is usually set (e.g., 50 µV), which is
then used by an algorithm to exclude contaminated EEG trials in any channel from fur-
ther analysis. This automatic amplitude threshold procedure is then complemented by
visual inspection of all epochs. For algorithms based on eye tracking data that detect
and correct eye blinks and other ocular artifacts in a fully automated fashion, see Plöchl
et al., 2012.
158    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

Blink artefacts elicit a large potential with a predominantly frontal topography and are
easy to identify in the vertical electro-​oculogram (VEOG). Saccades are generated by a
pair of extra-​ocular muscles which contract to move the eyeball, thereby inducing a sac-
cadic spike potential in the EEG at the onset of each saccade (Thickbroom & Mastaglia,
1985). Saccadic spike potentials are too small to be detected by standard amplitude
thresholds for automatic EOG-​artefact removal, especially in case of microsaccades
which are produced during attempted fixation (Martinez-​Conde et al., 2013). In their
seminal paper, Yuval-​Greenberg and colleagues (2008) suspected that high-​frequency
EEG activity that had been regarded as induced gamma activity in fact reflects
microsaccade-​induced muscle artefacts. Naturally, this report triggered an intense de-
bate within the field of induced gamma activity research (Schwartzman & Kranczioch,
2011). Section 8.9 summarizes the main points.

8.9  Microsaccades and induced

gamma activity

Microsaccades are small (up to 1 degree), jerk-​like saccades with a duration of about
25 ms and an average rate of 1–​2 per second (Martinez-​Conde et al., 2013). There are at
least three important similarities between microsaccades and induced gamma activity
that need to be considered. First, in response to a sudden change in stimulus input, the
microsaccade rate shows a characteristic biphasic time course, with an early inhibition
phase peaking at 100–​150 ms after stimulus onset, followed by a rebound phase peaking
between 200 and 400 ms after stimulus onset (Engbert, 2006). Thus, the rebound phase
of microsaccades corresponds to the time window where induced gamma activity typ-
ically appears.
Second, the rate of microsaccades is modulated by perceptual and cognitive factors
that have also been linked to induced gamma activity, including attention and memory-​
related processes (Engbert & Kliegl, 2003; Valsecchi et al., 2007; Valsecchi et al., 2009),
physical stimulus features like color and luminance contrast (Rolfs et al., 2008), and the
coherence of objects (Yuval-​Greenberg et al., 2008). Thus, microsaccade rate represents
a true confound in experiments on gamma activity since modulations of microsaccade
rate and gamma activity might generate an identical pattern of results across experi-
mental conditions. For example, both microsaccade rate and induced gamma power
show increased responses to a coherent object in comparison to an incoherent object.
Third, depending on the location of the reference electrode, the frontally occurring
microsaccade-​induced saccadic spike potential translates into a broadband (~20–​90
Hz) gamma power increase with a maximum at centro-​parietal and occipital electrodes,
that is, regions where it strongly coincides with induced gamma activity (Reva &
Aftanas, 2004; Yuval-​Greenberg et al., 2008). Thus, saccadic spike potentials mimic not
only the frequency content of induced gamma activity but also its typical topography.
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    159

Notably, this can be avoided by using MEG, since it does not require a reference (Gruber
et al., 2008).
These similarities between microsaccades and induced gamma activity regarding
their sensitivity to cognitive effects as well as their temporal, topographical and spec-
tral properties have been convincingly demonstrated and have led to the suggestion
that—​at least in some cases—​induced gamma activity reflect saccadic spike potentials
rather than a neural response (Yuval-​Greenberg et al., 2008). This also concerns earlier
EEG findings that might have been erroneously interpreted as neuronal gamma activity,
when in fact they reflected microsaccade-​induced spike potential artefacts (Keren et al.,
2010). How strong previous EEG findings might be affected by microsaccades depends
on several aspects, for example, the exact time window of the effects (in relation to the
saccadic rebound), the broadness of the gamma response (in relation to the 20–​90 Hz
spike potential), and the choice of the reference electrode, given its influence on the top-
ography, to name but a few ( for further details, see Schwartzman & Kranczioch, 2011).
Notably, evoked gamma activity is not affected by microsaccade-​induced spike po-
tential artefacts. One reason is that evoked gamma activity occurs much earlier than
the microsaccade rebound after sensory stimulation. Another reason is that spike
potentials, in contrast to the evoked gamma activity, are not tightly time-​locked to
the stimulus and, thus, cancel out during averaging of the evoked potential (Yuval-​
Greenberg & Deouell, 2009).
Although Yuval-​Greenberg and colleagues (2008) did not deny the existence of
induced gamma activity and its role in perception and cognition in general, their findings
posed a challenge to develop methods for separating the effects of microsaccades and
induced gamma responses in EEG scalp recordings. One immediate consequence of
this study was the necessity to use eye tracking with sufficient spatial and temporal reso-
lution for detecting microsaccades as small as 0.15° visual angle, given that even precise
fixation of a continuously present fixation point does not preclude microsaccade-​related
brain activity (Dimigen et al., 2009). The rationale behind a combined recording of EEG
and eye tracking data is to demonstrate that differences of induced gamma activity and
microsaccade rate do not covary across conditions and, thus, effects of induced gamma
activity cannot easily be explained by microsaccadic muscle potentials. Indeed, such
differential modulations of gamma activity and microsaccades time courses have been
reported, for example, during object motion (Naue et al., 2011) and memory-​based ob-
ject recognition (Hassler et al., 2013).
However, high-​ resolution eye trackers are expensive and not always available.
Alternatively, there are methods available allowing for offline artefact correction
that identify saccadic spike potentials via EOG sensors, that is, without the need of
an eye tracker (Hassler et al., 2011; Keren et al., 2010; Nottage, 2010). However, Keren
and colleagues (2010) used eye tracking in addition to EOG-​based detection of
microsaccades to evaluate the hit and false alarm rates of several spatiotemporal filters
that were applied to the EOG data to identify the sharp amplitude increase at the onset
of saccadic spike potentials. With this method, detection rates of 80% on average could
be achieved for microsaccades of at least 0.2°, which were then efficiently attenuated by
means of mathematical algorithms. For artifact correction methods based on combined
160    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

EEG and eye tracking recordings, see also Plöchl et al. (2012). Nottage (2010) and
Hassler and colleagues (2011) used different mathematical approaches but both have
been demonstrated to effectively remove microsaccadic muscle artefacts, resulting in a
more sustained and narrow-​band gamma signal of the residual activity compared to the
frequency plot of the saccadic spike potential (see, for review, Nottage & Horder, 2016).
Although the available methods are relatively easy to apply and effective in reducing
saccadic spike potentials, they do not remove the artefact completely and they do not
attenuate saccade-​related visual brain activity (Dimigen et al., 2009; Plöchl et al., 2012).
Also, the fundamental problem of the confounding co-​modulation of induced gamma
activity and microsaccade rate cannot be solved by artefact correction techniques.
Therefore, it has been suggested recently to reduce the occurrence of microsaccades and
related confounds in the EEG at the level of experimental design instead of applying off-
line correction methods (Tal & Yuval-​Greenberg, 2018). Considerably reducing the in-
cidence of microsaccades during experimentation would allow rejecting microsaccades
rather than just correcting artefactual trials and still leaving enough (then artefact-​free)
trials for analysis. As a first step, Tal and Yuval-​Greenberg (2018) were able to reduce the
average number of saccades (including microsaccades) by 10–​25% through manipula-
tion of different task characteristics (e.g., by adding a foveal task, whereas the stimulus
of interest was parafoveal). However, it remains to be seen how this approach can be
applied to the diverse experimental setups covering the full range of induced gamma ac-
tivity related cognitive processes.
In summary, together with other muscle artefacts, microsaccades impose a serious
difficulty on the analysis and interpretation of induced gamma activity in human EEG.
To separate activity related to saccadic spike potentials from induced gamma activity,
using high-​resolution eye tracking is recommended as the most reliable way to iden-
tify microsaccades. However, there are also techniques available to use EOG data for
saccadic spike potential detection. In a second step, off-​line artefact removal methods
should be used to correct artefactual trials. Rejecting all artefactual trials is currently
not possible due to the high prevalence of microsaccades in typical visual experiments,
but there are suggestions how to reduce the number of microsaccades through experi-
mental design. Current evidence from artefact-​corrected data confirms the influence of
microsaccades on induced gamma activity, but also indicates the existence of induced
gamma activity that survived artifact suppression, thereby replicating earlier findings
on the functional roles of induced gamma activity in, for instance, object representation
(Hassler et al., 2013; 2011). Finally, depending on the research question at hand, a further
option to prevent microsaccadic contamination of gamma activity might be to restrict
the analyses to the evoked gamma activity, which is not affected (e.g., Lally et al., 2014).

8.10  Clinical relevance

Given its role in multiple cognitive processes and neural information integration,
disturbed gamma activity might reflect an important pathophysiological mechanism
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    161

underlying the mental deficits of patients suffering from diverse neuropsychiatric

disorders (Başar, 2013; Herrmann & Demiralp, 2005; Uhlhaas & Singer, 2006). One of
the most extensively studied disorders in relation to gamma activity is schizophrenia
(Uhlhaas & Singer, 2010) (see also Chapter 18), which is characterized by positive
symptoms like hallucinations, delusions, and thought disorders, as well as negative
symptoms like reduced affect, motivation, and behavior. Positive symptoms have been
generally linked to increased gamma activity, whereas negative symptoms correlate with
a decrease of gamma activity compared to healthy controls (Herrmann & Demiralp,
2005). Moreover, as a group, schizophrenic patients have deficits in both basic sen-
sory and cognitive functions, which have been related to evoked and induced gamma
activity.
For instance, early evoked gamma activity in response to auditory stimulation was
found to be reduced in schizophrenic patients receiving medication (Leicht et al., 2010;
Lenz et al., 2011), but not in unmedicated patients (Gallinat et al., 2004). Başar-​Eroǧlu
and colleagues (2011) reported that auditorily evoked gamma responses did not differ
between schizophrenic patients and healthy controls, but on the single-​trial level,
gamma responses were higher in patients compared to controls. Modality-​specific
effects were found for chronic medicated patients, demonstrating reduced early evoked
gamma activity for visual but not auditory stimulation (Spencer et al., 2008). Seemingly,
more research is needed to get a clearer picture regarding the role of early evoked gamma
activity in sensory processing of schizophrenic patients.
With regard to induced gamma activity in schizophrenic patients, most of the evi-
dence points to impaired gamma activity related to higher perceptual and cognitive
functions (see, for review, Uhlhaas & Singer, 2010; 2012). This includes, for example,
cognitive control in first-​episode schizophrenia patients with and without medication
(Minzenberg et al., 2010), and working memory (Haenschel et al., 2009), although one
study found working memory-​related gamma amplitudes to be preserved in patients
but lacking any relation to task difficulty, as present in normal controls (Basar-​Eroǧlu
et al., 2007). Reduced amplitudes or reduced phase locking of gamma oscillations
during working memory and other cognitive tasks have been found predominantly in
frontal areas which corresponds to the frequently reported hypo-​frontality in schizo-
phrenia (see, for review, Senkowski & Gallinat, 2015).
Interestingly, a recent review on gamma activity in first episode psychosis patients
and people at high risk for psychosis found a similar decrease of evoked and induced
gamma activity as has been reported for chronic schizophrenia (Reilly et al., 2018),
indicating that reduced gamma activity in the early phase of psychosis might serve as a
biomarker or endophenotype allowing for an early intervention before the disorder has
fully developed. This, however, would require a more standardized procedure regarding
the employed experimental paradigms and measures of gamma activity.
Alternatively, spontaneous or resting-​state gamma activity might be used as a bio-
marker of schizophrenia, which would bear the advantage that it can be recorded
without engagement in a task (i.e., spontaneous activity) or as pre-​stimulus baseline
activity (i.e., resting-​state). Indeed, there is evidence for altered spontaneous/​resting
162    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

gamma activity in schizophrenia. But in contrast to the reported reduction of evoked

and induced gamma activity, this type of gamma activity has been found to be pre-
dominantly increased in chronic schizophrenic patients (Spencer, 2012; see, for review,
White & Siegel, 2016) as well as in first episode patients and high-​risk populations (Reilly
et al., 2018). While it has been proposed that increased spontaneous/​resting gamma ac-
tivity contributes to positive symptoms like hallucinations (White & Siegel, 2016), its
relation to negative symptoms and reduced gamma activity during stimulus processing
is less clear. Thus, different computational models have been discussed regarding the
neurophysiological mechanisms underlying gamma activity increases during resting
state and gamma decreases during stimulus processing in schizophrenia (Jadi et al.,
2016). In general, abnormal gamma activity in schizophrenia has been related to dys-
functional circuit mechanisms responsible for generating gamma oscillations, that is, a
reduced input from inhibitory GABAergic interneurons to pyramidal cells and/​or ab-
normal glutamatergic input from the pyramidal cells to the interneurons (see, for re-
view, McNally & McCarley, 2016), resulting in a disturbed balance between excitatory
and inhibitory mechanisms (E/​I balance).
Also in autism spectrum disorders (ASD), abnormal gamma oscillations have been
suggested as a potential biomarker for a dysfunctional E/​I balance in children with
ASD (Stroganova et al., 2015; Uhlhaas & Singer, 2012). Similar to patients with schizo-
phrenia, children with ASD have been consistently characterized by reduced gamma
activity during sensory stimulation with overlapping perceptual deficits (see, for re-
view, Uhlhaas & Singer, 2012). Interestingly, children with ASD also show an increase
in resting-​state gamma activity (van Diessen et al., 2015; Wang et al., 2013) but, unlike
schizophrenic patients, do not experience hallucinations. However, despite the substan-
tial overlap between schizophrenia and ASD regarding the dysfunctional E/​I balance
and the resulting impairments in cognitive integration, there are important differences
with regard to the developmental timing of the changing E/​I balance, which might ex-
plain some of the unique features of each disorder (Uhlhaas & Singer, 2012; White &
Siegel, 2016).
Another neurodevelopmental disorder that is predominantly diagnosed in childhood
and adolescence is attention-​deficit/​hyperactivity disorder (ADHD). According to its
core symptoms (inattention, hyperactivity, impulsivity), one might expect a reduction
of gamma activity due to the attention deficit and/​or a gamma increase due to the hyper-
activity component. In one of the first studies on evoked gamma activity in ADHD
children, Yordanova and colleagues (2001) reported larger and more strongly phase-​
locked early evoked gamma activity in ADHD children during an auditory detection
task involving a motor response. Gamma augmentations did not differentiate between
attended and ignored stimuli. This finding was interpreted as reflecting impaired early
auditory processing due to deficient motor inhibition in ADHD children (Yordanova
et al., 2001).
Enhanced evoked gamma activity in children with ADHD was also found during
stimulus encoding of a visual memory task (Lenz, Krauel, et al., 2008). However, in
contrast to healthy children, the encoding-​related gamma activity was enhanced
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    163

unspecifically, that is, it was unrelated to subsequent recognition performance. Similarly,

early evoked gamma activity did not reflect the difference in long-​term memory repre-
sentation between familiar and unfamiliar objects in a simple forced-​choice reaction
task (Lenz et al., 2010).
In a study by Prehn-​Kristensen and colleagues (2015), the distractibility of ADHD
patients was assessed in a delayed-​match-​to-​sample paradigm by presenting a distractor
stimulus during the delay period, which should be ignored. Children with ADHD but
not healthy controls exhibited an increase of occipital early evoked gamma activity
in response to the distractor, indicating a higher distractibility resulting in disturbed
working memory maintenance already on a very early level of interference processing
(Prehn-​Kristensen et al., 2015).
Together, these findings might indicate that attentional problems in ADHD are
related to early sensory processing deficits as reflected by unspecific evoked gamma
increases that might be interpreted as an increase of noise. This may be partially caused
by the fact that the same genetic variations within the dopaminergic pathway that have
been associated with ADHD, also contribute to enhancements of gamma activity in
healthy volunteers (Demiralp et al., 2007; Herrmann & Demiralp, 2005). However,
this hyperactivity-​based interpretation might be restricted to gamma activity during
stimulus or cognitive processing since spontaneous gamma activity was shown to be
diminished in children (Barry et al., 2010) and adults (Tombor et al., 2019) with ADHD.
Gamma oscillations have also been associated with neurodegenerative diseases
like Parkinson’s disease (PD) and Alzheimer’s dementia (AD) (Nimmrich et al., 2015).
For PD, however, oscillations in the beta range are more directly related to the clinical
symptoms than gamma activity and might serve as a biomarker, whereas studies on
gamma oscillations in AD yielded divergent findings of reduced as well as enhanced
amplitudes, indicating the need for further research before clear statements about the
usefulness of gamma oscillations as a biomarker for AD can be made (see, for review,
Nimmrich et al., 2015). In two recent studies on AD, Başar and colleagues employed a
target detection task and simple visual stimulation to analyze gamma activity within
three sub-​bands over four time windows and found a decreased response to visual
stimuli and a delayed gamma response to target stimuli compared to healthy controls
(Başar et al., 2016), as well as an abnormal increase of gamma coherence for AD patients
in both conditions (Başar et al., 2017).
Overall, AD and many other neuropsychiatric disorders are characterized by aber-
rant gamma activity pointing to dysfunctional oscillatory network activities that are
regulated by inhibitory interneurons (see, for reviews, Palop & Mucke, 2016; Ruden et al.,
2021). While such an interneuron impairment might indeed represent a common mech-
anism of cognitive dysfunction in diverse neuropsychiatric disorders, the use of gamma
oscillations as a single oscillatory biomarker is limited due to its lack of specificity (see,
however, Lenz et al., 2011 for a study on the specificity of gamma activity in neuropsychi-
atric disorders). Therefore, it might be important to look for interactions with other fre-
quency bands to create oscillatory biomarkers that are more specific for each disorder
(Başar et al., 2013; Başar, Schmiedt-​Fehr, et al., 2016; Uhlhaas & Singer, 2012).
164    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

Notably, however, there is recent evidence from a mouse model of AD that impaired
gamma oscillations are specifically related to a hallmark of AD, that is, the abnormal
aggregation of plaque-​forming proteins (amyloid-​beta protein) in the brain (Iaccarino
et al., 2016). The authors found that inducing gamma oscillations by a 40-​Hz flickering
light led to a major reduction of plaques in the visual cortex of the exposed mice and
to an activation of microglia (i.e., immune cells in the brain) that degrade the plaques
(Iaccarino et al., 2016). Crucially, later studies using different forms of sensory gamma
stimulation in multiple AD mouse models could not only demonstrate a clear link be-
tween gamma activity and cellular metabolism but also improvements of cognitive
functions like learning and memory, suggesting a therapeutic role of gamma entrain-
ment in AD (see, for review, Adaikkan & Tsai, 2020). There is emerging evidence that
similar cognitive effects can be achieved in humans by employing non-​invasive brain
stimulation techniques that could, in contrast to rhythmic sensory stimulation, target
higher-​order cognitive brain areas linked more directly to core symptoms of the dis-
order than sensory cortices (Benussi et al., 2021; see, for reviews, Bréchet et al., 2021, and
Strüber & Herrmann, 2020).

8.11  Challenges and future directions

There are a number of challenges in relation to the ubiquitous role of gamma oscillations
for cognitive functions. For instance, it has been criticized that the power of gamma
oscillations is low and inconsistent and that its frequency and power depend on low-​
level stimulus features like size or contrast, which seems to be incompatible with the
proposed role of gamma synchronization in cortical processing (Ray & Maunsell, 2015).
However, there is also recent reconciling evidence in support of a functional role for
gamma synchronization (Singer, 2018).
One related issue regarding the functions of gamma activity in sensory and cogni-
tive processing as well as in clinical contexts is that most of the evidence is correlative
in nature. Therefore, it remains unclear whether gamma oscillations and their syn-
chronization are truly relevant for information processing in the brain or whether they
merely reflect a by-​product of brain organization. It has been argued that even gamma
oscillations as such may be a functional epiphenomenon arising from network activities
supporting the excitatory-​inhibitory balance necessary for normal brain functioning
(Merker, 2013). Although this argumentation might reflect a “category mistake” since
gamma oscillations cannot be functionally separated from the circuit mechanisms that
generate them (Bosman et al., 2014), the necessity remains to go beyond correlations
and to demonstrate that gamma activity is causally involved in cortical information pro-
cessing and cognitive functions.
Causal evidence for a role of gamma oscillation in cognitive processes can be
provided by demonstrating that modulating gamma power or coherence improves cog-
nitive outcomes. There are several established methods to modulate brain oscillations,
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    165

including rhythmic sensory (steady-​state) stimulation, EEG neurofeedback, and non-​

invasive brain stimulation like repetitive transcranial magnetic stimulation (rTMS;
see, for a methods overview, Herrmann et al., 2016). Whereas rTMS is not considered
safe for stimulation in the gamma frequency range due to its risk of inducing epi-
leptic seizure (Rossi et al., 2009), steady-​state visual stimulation has been successful in
entraining gamma oscillations (Herrmann, 2001; Regan, 1968) and improving binding-​
related perceptual performance (Elliott et al., 2000). However, whereas most human
EEG studies using rhythmic visual stimulation obtained effects restricted to early visual
cortex, EEG-​based neurofeedback allows for direct neurocognitive modulation of those
brain regions that are crucially involved in specific tasks (see, for review, Enriquez-​
Geppert et al., 2013).
Neurofeedback training to increase EEG gamma oscillations has been shown to im-
prove perceptual processing (Salari et al., 2014), cognitive control and intelligence
measures (Keizer et al., 2010; Keizer, Verschoor, et al., 2010), indicating a functional role
of gamma activity for these cognitive processes. However, gamma neurofeedback is tech-
nically challenging due to its susceptibility to muscle and ocular artefacts (see Section
8.8). Indeed, there are reports that participants of a neurofeedback training were able
to control the feedback signal by activating their head and neck muscles, which might
serve as a caveat when designing neurofeedback studies, especially if EEG recordings are
used (Merkel et al., 2018). Furthermore, neurofeedback is an endogenous technique that
needs to be learned and not all participants might be able to do this, especially patients.
A recent method of non-​invasive brain stimulation, called transcranial alternating
current stimulation (tACS) avoids these problems by applying sinusoidal currents to
stimulate the brain exogenously (see Chapter 22). Its effectiveness in modulating gamma
oscillations during motor, sensory and a wide range of high-​level cognitive processes
has been demonstrated recently (see, for a review, Strüber & Herrmann, 2020). Thus, we
propose that tACS might be the appropriate method not only to provide causal evidence
for a role of gamma oscillations in brain processing but also to improve gamma activity-​
related sensory and cognitive functioning in healthy volunteers and clinical populations
(Herrmann & Strüber, 2017; Strüber & Herrmann, 2020).

REFERENCES
Adaikkan, C. & Tsai, L.-​H. (2020). Gamma entrainment: Impact on neurocircuits, glia, and
therapeutic opportunities. Trends in Neurosciences, 43(1), 24–​41. https://​doi.org/​10.1016/​
j.tins.2019.11.001
Adrian, E. D. (1942). Olfactory reactions in the brain of the hedgehog. Journal of Physiology,
100(4), 459–​473.
Adrian, E. D. (1950). The electrical activity of the mammalian olfactory bulb.
Electroencephalography and Clinical Neurophysiology, 2, 377–​388.
Barry, R. J., Clarke, A. R., Hajos, M., McCarthy, R., Selikowitz, M., & Dupuy, F. E. (2010).
Resting-​state EEG gamma activity in children with attention-​deficit/​hyperactivity disorder.
Clinical Neurophysiology, 121(11), 1871–​1877. http://​doi.org/​10.1016/​j.cli​nph.2010.04.022
166    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

Bartos, M., Vida, I., & Jonas, P. (2007). Synaptic mechanisms of synchronized gamma
oscillations in inhibitory interneuron networks. Nature Reviews Neuroscience, 8(1), 45–​56.
http://​doi.org/​10.1038/​nrn2​044
Başar, E. (2013). A review of gamma oscillations in healthy subjects and in cognitive impair-
ment. International Journal of Psychophysiology, 90(2), 99–​117. http://​doi.org/​10.1016/​j.ijpsy​
cho.2013.07.005
Başar, E., Başar-​Eroǧlu, C., Güntekin, B., & Yener, G. G. (2013). Brain’s alpha, beta, gamma,
delta, and theta oscillations in neuropsychiatric diseases: Proposal for biomarker
strategies. Supplements to Clinical Neurophysiology, 62, 19–​54. http://​doi.org/​10.1016/​
B978-​0-​7020-​5307-​8.00002-​8
Başar, E., Emek-​Savaş, D. D., Güntekin, B., & Yener, G. G. (2016). Delay of cognitive gamma
responses in Alzheimer’s disease. NeuroImage: Clinical, 11, 106–​115. http://​doi.org/​10.1016/​
j.nicl.2016.01.015
Başar, E., Femir, B., Emek-​Savaş, D. D., Güntekin, B., & Yener, G. G. (2017). Increased long dis-
tance event-​related gamma band connectivity in Alzheimer’s disease. NeuroImage: Clinical,
14, 580–​590. http://​doi.org/​10.1016/​j.nicl.2017.02.021
Başar, E., Gönder, A., Özesmi, C., & Ungan, P. (1975). Dynamics of brain rhythmic and evoked
potentials. II. Studies in the auditory pathway, reticular formation and hippocampus during
the waking stage. Biological Cybernetics, 20(3-​4), 145–​160.
Başar, E., Gönder, A., & Ungan, P. (1976). Important relation between EEG and brain evoked
potentials. I. Resonance phenomena in subdural structures of the cat. Biological Cybernetics,
25(1), 27–​40.
Başar, E. & Özesmi, C. (1972). The hippocampal EEG-​activity and a systems analytical inter-
pretation of averaged evoked potentials of the brain. Kybernetik, 12, 45–​54.
Başar, E., Schmiedt-​Fehr, C., Mathes, B., Femir, B., Emek-​Savaş, D. D., Tülay, E., Tan, D.,
Düzgün, A., . . . Başar-​Eroǧlu, C. (2016). What does the broken brain say to the neuroscien-
tist? Oscillations and connectivity in schizophrenia, Alzheimer’s disease, and bipolar dis-
order. International Journal of Psychophysiology, 103, 135–​148. http://​doi.org/​10.1016/​j.ijpsy​
cho.2015.02.004
Başar-​Eroǧlu, C., Brand, A., Hildebrandt, H., Karolina Kedzior, K., Mathes, B., & Schmiedt,
C. (2007). Working memory related gamma oscillations in schizophrenia patients.
International Journal of Psychophysiology, 64(1), 39–​45. http://​doi.org/​10.1016/​j.ijpsy​
cho.2006.07.007
Başar-​Eroǧlu, C., Mathes, B., Brand, A., & Schmiedt-​ Fehr, C. (2011). Occipital γ re-
sponse to auditory stimulation in patients with schizophrenia. International Journal of
Psychophysiology, 79, 3–​8.
Başar-​Eroǧlu, C., Strüber, D., Kruse, P., Başar, E., & Stadler, M. (1996). Frontal gamma-​band en-
hancement during multistable visual perception. International Journal of Psychophysiology,
24(1-​2), 113–​125. http://​doi.org/​10.1016/​S0167-​8760(96)00055-​4
Başar-​Eroǧlu, C., Strüber, D., Schürmann, M., Stadler, M., & Başar, E. (1996). Gamma-​band
responses in the brain: A short review of psychophysiological correlates and functional sig-
nificance. International Journal of Psychophysiology, 24(1-​2), 101–​112. http://​doi.org/​10.1016/​
S0167-​8760(96)00051-​7
Benussi, A., Cantoni, V, Cotelli, M. S., Cotelli, M., Brattini, C., Datta, A., Thomas, C.,
Santarnecchi, E., Pascual-​Leone, A., & Borroni, B. (2021). Exposure to gamma tACS in
Alzheimer's disease: A randomized, double-​blind, sham-​controlled, crossover, pilot study.
Brain Stimulation, 14, 531–​540. https://​doi.org/​10.1016/​j.brs.2021.03.007
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    167

Berger, H. (1929). Über das Elektrenkephalogramm des Menschen, I. Mitteilung. Archiv Für
Psychiatrie Und Nervenkrankheiten, 87(4), 527–​570.
Berger, H. (1934). Über das Elektrenkephalogramm des Menschen, IX. Mitteilung. Archiv Für
Psychiatrie Und Nervenkrankheiten, 102, 538–​557. http://​doi.org/​10.1007/​BF0​1797​193
Berger, H. (1936). Über das Elektrenkephalogramm des Menschen, XI. Mitteilung. Archiv Für
Psychiatrie Und Nervenkrankheiten, 104, 678–​689. http://​doi.org/​10.1007/​BF0​1797​193
Berger, H. (1937). Über das Elektrenkephalogramm des Menschen, XII. Mitteilung. Archiv Für
Psychiatrie Und Nervenkrankheiten, 106, 165–​187. http://​doi.org/​10.1007/​BF0​1797​193
Bibbig, A., Faulkner, H. J., Whittington, M. A., & Traub, R. D. (2001). Self-​organized synaptic
plasticity contributes to the shaping of gamma and beta oscillations in vitro. Journal of
Neuroscience, 21(22), 9053–​9067. http://​doi.org/​21/​22/​9053 [pii]
Bosman, C. A., Lansink, C. S., & Pennartz, C. M. A. (2014). Functions of gamma-​band syn-
chronization in cognition: From single circuits to functional diversity across cortical and
subcortical systems. European Journal of Neuroscience, 39(11), 1982–​1999. http://​doi.org/​
10.1111/​ejn.12606
Bouyer, J. J., Montaron, M. F., & Rougeul, A. (1981). Fast fronto-​parietal rhythms during
combined focused attentive behaviour and immobility in cat: Cortical and thalamic
localizations. Electroencephalography and Clinical Neurophysiology, 51(3), 244–​252. http://​
doi.org/​10.1016/​0013-​4694(81)90138-​3
Bréchet, L., Michel, C. M., Schacter, D. L., & Pascual-​Leone, A. (2021). Improving auto-
biographical memory in Alzheimer's disease by transcranial alternating current stimu-
lation. Current Opinion in Behavioral Sciences, 40, 64–​71. https://​doi.org/​10.1016/​j.cob​
eha.2021.01.003
Bressler, S. L. & Freeman, W. J. (1980). Frequency analysis of olfactory system EEG in cat,
rabbit, and rat. Electroencephalography and Clinical Neurophysiology, 50(1-​2), 19–​24. http://​
doi.org/​10.1016/​0013-​4694(80)90319-​3
Bressler, S. L. & Richter, C. G. (2015). Interareal oscillatory synchronization in top-​down neo-
cortical processing. Current Opinion in Neurobiology, 31, 62–​66. http://​doi.org/​10.1016/​
j.conb.2014.08.010
Brunet, N., Vinck, M., Bosman, C. A., Singer, W., & Fries, P. (2014). Gamma or no gamma,
that is the question. Trends in Cognitive Sciences, 18(10), 507–​509. http://​doi.org/​10.1016/​
j.tics.2014.08.006
Buffalo, E. A., Fries, P., Landman, R., Buschman, T. J., & Desimone, R. (2011). Laminar
differences in gamma and alpha coherence in the ventral stream. Proceedings of the National
Academy of Sciences of the United States of America, 108(27), 11262–​11267.
Busch, N. A., Debener, S., Kranczioch, C., Engel, A. K., & Herrmann, C. S. (2004). Size
matters: Effects of stimulus size, duration and eccentricity on the visual gamma-​
band response. Clinical Neurophysiology, 115(8), 1810–​1820. http://​doi.org/​10.1016/​j.cli​
nph.2004.03.015
Busch, N. A., Herrmann, C. S., Müller, M. M., Lenz, D., & Gruber, T. (2006). A cross-​
laboratory study of event-​related gamma activity in a standard object recognition paradigm.
NeuroImage, 33(4), 1169–​1177. http://​doi.org/​10.1016/​j.neu​roim​age.2006.07.034
Busch, N. A., Schadow, J., Fründ, I., & Herrmann, C. S. (2006). Time-​frequency analysis of
target detection reveals an early interface between bottom-​up and top-​down processes
in the gamma-​ band. NeuroImage, 29(4), 1106–​1116. http://​doi.org/​10.1016/​j.neu​roim​
age.2005.09.009
168    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

Buschman, T. J. & Miller, E. K. (2007). Top-​down versus bottom-​up control of attention in

the prefrontal and posterior parietal cortices. Science, 315(5820), 1860–​1862. http://​doi.org/​
10.1126/​scie​nce.1138​071
Buzsáki, G. & Wang, X.-​J. (2012). Mechanisms of gamma oscillations. Annual Review of
Neuroscience, 35(1), 203–​225. http://​doi.org/​10.1146/​annu​rev-​neuro-​062​111-​150​444
Cannon, J., McCarthy, M. M., Lee, S., Lee, J., Börgers, C., Whittington, M. A., & Kopell, N.
(2014). Neurosystems: Brain rhythms and cognitive processing. European Journal of
Neuroscience, 39(5), 705–​7 19. http://​doi.org/​10.1111/​ejn.12453
Crone, N. E., Korzeniewska, A., & Franaszczuk, P. J. (2011). Cortical gamma
responses: Searching high and low. International Journal of Psychophysiology, 79(1), 9–​15.
http://​doi.org/​10.1016/​j.ijpsy​cho.2010.10.013
Darvas, F., Scherer, R., Ojemann, J. G., Rao, R. P., Miller, K. J., & Sorensen, L. B. (2010). High
gamma mapping using EEG. NeuroImage, 49(1), 930–​938. http://​doi.org/​10.1016/​j.neu​roim​
age.2009.08.041
Demiralp, T., Herrmann, C. S., Erdal, M. E., Ergenoglu, T., Keskin, Y. H., Ergen, M., & Beydagi,
H. (2007). DRD4 and DAT1 polymorphisms modulate human gamma band responses.
Cerebral Cortex, 17(5), 1007–​1019. http://​doi.org/​10.1093/​cer​cor/​bhl​011
Dietsch, G. (1932). Fourier-​Analyse von Elektrencephalogrammen des Menschen. Pflügers
Archiv für die gesamte Physiologie des Menschen und der Tiere, 230, 106–​112. http://​doi.org/​
10.1007/​BF0​1751​972
Dimigen, O., Valsecchi, M., Sommer, W., & Kliegl, R. (2009). Human microsaccade-​related
visual brain responses. Journal of Neuroscience, 29(39), 12321–​12331. http://​doi.org/​10.1523/​
JNEURO​SCI.0911-​09.2009
Eckhorn, R., Bauer, R., Jordan, W., Brosch, M., Kruse, W., Munk, M., & Reitboeck, H. J. (1988).
Coherent oscillations: A mechanism of feature linking in the visual cortex? Biological
Cybernetics, 60, 121–​130.
Elliott, M. A., Herrmann, C. S., Mecklinger, A., & Müller, H. J. (2000). The loci of oscilla-
tory visual-​ object priming: A combined electroencephalographic and reaction-​ time
study. International Journal of Psychophysiology, 38(3), 225–​241. http://​doi.org/​10.1016/​
S0167-​8760(0  0)00167-​7
Engbert, R. (2006). Microsaccades: A microcosm for research on oculomotor control,
attention, and visual perception. Progress in Brain Research, 154, 177–​192. http://​doi.org/​
10.1016/​S0079-​6123(06)54009-​9
Engbert, R. & Kliegl, R. (2003). Microsaccades uncover the orientation of covert attention.
Vision Research, 43(9), 1035–​1045. http://​doi.org/​10.1016/​S0042-​6989(03)00084-​1
Engel, A. K., Fries, P., & Singer, W. (2001). Dynamic predictions: oscillations and synchrony in
top-​down processing. Nature Reviews Neuroscience, 2(10), 704–​7 16. http://​doi.org/​10.1038/​
35094​565
Engel, A. K., Roelfsema, P. R., Fries, P., Brecht, M., & Singer, W. (1997). Role of the temporal do-
main for response selection and perceptual binding. Cerebral Cortex, 7(6), 571–​582. http://​
doi.org/​10.1093/​cer​cor/​7.6.571
Engel, A., König, P., Kreiter, A. K., & Singer, W. (1991). Interhemispheric synchronization of
oscillatory neuronal responses in cat visual cortex. Science, 252(5009), 1177–​1179. http://​doi.
org/​10.1126/​scie​nce.252.5009.1177
Enriquez-​ Geppert, S., Huster, R. J., & Herrmann, C. S. (2013). Boosting brain
functions: Improving executive functions with behavioral training, neurostimulation, and
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    169

neurofeedback. International Journal of Psychophysiology, 88(1), 1–​16. http://​doi.org/​10.1016/​

j.ijpsy​cho.2013.02.001
Fell, J. & Axmacher, N. (2011). The role of phase synchronization in memory processes. Nature
Reviews Neuroscience, 12(2), 105–​118. http://​doi.org/​10.1038/​nrn2​979
Felleman, D. J. & Van Essen, D. C. (1991). Distributed hierarchical processing in the primate
cerebral cortex. Cerebral Cortex, 1, 1–​47.
Fitzgibbon, S. P., DeLosAngeles, D., Lewis, T. W., Powers, D. M., Whitham, E. M., Willoughby,
J. O., & Pope, K. J. (2015). Surface Laplacian of scalp electrical signals and independent
component analysis resolve EMG contamination of electroencephalogram. International
Journal of Psychophysiology, 97(3), 277–​284.
Freeman, W. J. (1975). Mass action in the nervous system. Academic Press.
Freeman, W. J. & Skarda, C. A. (1985). Spatial EEG patterns, non-​linear dynamics and percep-
tion: the neo-​Sherringtonian view. Brain Research Reviews, 10, 147–​175.
Frien, A., Eckhorn, R., Bauer, R., Woelbern, T., & Kehr, H. (1994). Stimulus-​specific fast
oscillations at zero phase between visual areas V1 and V2 of awake monkey. Neuroreport,
5(17), 2273–​2277.
Fries, P. (2005). A mechanism for cognitive dynamics: Neuronal communication through
neuronal coherence. Trends in Cognitive Sciences, 9(10), 474–​480. http://​doi.org/​10.1016/​
j.tics.2005.08.011
Fries, P. (2009). Neuronal gamma-​band synchronization as a fundamental process in cortical
computation. Annual Review of Neuroscience, 32(1), 209–​224. http://​doi.org/​10.1146/​annu​
rev.neuro.051​508.135​603
Fries, P. (2015). Rhythms for cognition: Communication through coherence. Neuron, 88(1),
220–​235. http://​doi.org/​10.1016/​j.neu​ron.2015.09.034
Fries, P., Nikolić, D., & Singer, W. (2007). The gamma cycle. Trends in Neurosciences, 30(7),
309–​316. http://​doi.org/​10.1016/​j.tins.2007.05.005
Fründ, I., Busch, N. A., Körner, U., Schadow, J., & Herrmann, C. S. (2007). EEG oscillations in
the gamma and alpha range respond differently to spatial frequency. Vision Research, 47(15),
2086–​2098. http://​doi.org/​10.1016/​j.vis​res.2007.03.022
Galambos, R., Makeig, S., & Talmachoff, P. J. (1981). A 40-​Hz auditory potential recorded from
the human scalp. Proceedings of the National Academy of Sciences of the United States of
America, 78(4), 2643–​2647. http://​doi.org/​10.1073/​pnas.78.4.2643
Gallinat, J., Winterer, G., Herrmann, C. S., & Senkowski, D. (2004). Reduced oscillatory
gamma-​band responses in unmedicated schizophrenic patients indicate impaired frontal
network processing. Clinical Neurophysiology, 115(8), 1863–​1874. http://​doi.org/​10.1016/​j.cli​
nph.2004.03.013
Goncharova, I. I., McFarland, D. J., Vaughan, T. M., & Wolpaw, J. R. (2003). EMG contamination
of EEG: Spectral and topographical characteristics. Clinical Neurophysiology, 114(9), 1580–​1593.
Gray, C. M., König, P., Engel, A. K., & Singer, W. (1989). Oscillatory responses in cat visual
cortex exhibit inter-​columnar synchronization which reflects global stimulus properties.
Nature, 338, 334–​337.
Gray, C. M. & Singer, W. (1989). Stimulus-​specific neuronal oscillations in orientation columns
of cat visual cortex. Proceedings of the National Academy of Sciences of the United States of
America, 86(5), 1698–​1702. http://​doi.org/​10.1073/​pnas.86.5.1698
Gregoriou, G. G., Gotts, S. J., Zhou, H., & Desimone, R. (2009). High-​frequency, long-​range
coupling between prefrontal and visual cortex during attention. Science, 324(5931), 1207–​
1210. http://​doi.org/​10.1126/​scie​nce.1171​402
170    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

Gregoriou, G. G., Paneri, S., & Sapountzis, P. (2015). Oscillatory synchrony as a mechanism
of attentional processing. Brain Research, 1626, 165–​182. http://​doi.org/​10.1016/​j.brain​
res.2015.02.004
Gruber, T., Maess, B., Trujillo-​Barreto, N. J., & Müller, M. M. (2008). Sources of synchronized
induced gamma-​band responses during a simple object recognition task: A replica-
tion study in human MEG. Brain Research, 1196, 74–​84. http://​doi.org/​10.1016/​j.brain​
res.2007.12.037
Gruber, T., Müller, M. M., Keil, A., & Elbert, T. (1999). Selective visual-​spatial attention induced
gamma band responses in the human EEG. Clinical Neurophysiology, 110(1999), 2074–​2085.
Gruber, T., Trujillo-​Barreto, N. J., Giabbiconi, C. M., Valdés-​Sosa, P. A., & Müller, M. M.
(2006). Brain electrical tomography (BET) analysis of induced gamma band responses
during a simple object recognition task. NeuroImage, 29(3), 888–​900. http://​doi.org/​10.1016/​
j.neu​roim​age.2005.09.004
Gruber, T., Tsivilis, D., Montaldi, D., & Müller, M. M. (2004). Induced gamma band
responses: An early marker of memory encoding and retrieval. NeuroReport, 15(11), 1837–​
1841. http://​doi.org/​10.1097/​01.wnr.000​0137​077.26010.12
Haenschel, C., Bittner, R. A., Waltz, J., Haertling, F., Wibral, M., Singer, W., . . . Rodriguez, E.
(2009). Cortical oscillatory activity is critical for working memory as revealed by deficits
in early-​onset schizophrenia. Journal of Neuroscience, 29(30), 9481–​9489. http://​doi.org/​
10.1523/​JNEURO​SCI.1428-​09.2009
Hassler, U., Friese, U., Martens, U., Trujillo-​Barreto, N., & Gruber, T. (2013). Repetition priming
effects dissociate between miniature eye movements and induced gamma-​band responses
in the human electroencephalogram. European Journal of Neuroscience, 38(3), 2425–​2433.
http://​doi.org/​10.1111/​ejn.12244
Hassler, U., Trujillo Barreto, N., & Gruber, T. (2011). Induced gamma band responses in human
EEG after the control of miniature saccadic artifacts. NeuroImage, 57(4), 1411–​1421. http://​
doi.org/​10.1016/​j.neu​roim​age.2011.05.062
Hermes, D., Miller, K. J., Wandell, B. A., & Winawer, J. (2015). Gamma oscillations in visual
cortex: The stimulus matters. Trends in Cognitive Sciences, 19(2), 57–​58. http://​doi.org/​
10.1016/​j.tics.2014.12.009
Herrmann, C. S. (2001). Human EEG responses to 1-​100 Hz flicker: Resonance phenomena in
visual cortex and their potential correlation to cognitive phenomena. Experimental Brain
Research, 137(3-​4), 346–​353. http://​doi.org/​10.1007/​s00221​0100​682
Herrmann, C. S. & Demiralp, T. (2005). Human EEG gamma oscillations in neuropsychi-
atric disorders. Clinical Neurophysiology, 116(12), 2719–​2733. http://​doi.org/​10.1016/​j.cli​
nph.2005.07.007
Herrmann, C. S., Fründ, I., & Lenz, D. (2010). Human gamma-​band activity: A review on
cognitive and behavioral correlates and network models. Neuroscience and Biobehavioral
Reviews, 34(7), 981–​992. http://​doi.org/​10.1016/​j.neubio​rev.2009.09.001
Herrmann, C. S., Lenz, D., Junge, S., Busch, N. A., & Maess, B. (2004). Memory-​matches evoke
human gamma-​responses. BMC Neuroscience, 5, 13.
Herrmann, C. S. & Mecklinger, A. (2001). Gamma activity in human EEG is related to
highspeed memory comparisons during object selective attention. Visual Cognition, 8(3-​5),
593–​608. http://​doi.org/​10.1080/​135062​8014​3000​142
Herrmann, C. S., Mecklinger, A., & Pfeifer, E. (1999). Gamma responses and ERPs in a visual
classification task. Clinical Neurophysiology, 110(4), 636–​642. http://​doi.org/​10.1016/​
S1388-​2457(99)00002-​4
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    171

Herrmann, C. S., Munk, M. H. J., & Engel, A. K. (2004). Cognitive functions of gamma-​band
activity: Memory match and utilization. Trends in Cognitive Sciences, 8(8), 347–​355. http://​
doi.org/​10.1016/​j.tics.2004.06.006
Herrmann, C. S., Rach, S., Vosskuhl, J., & Strüber, D. (2014). Time-​frequency analysis of event-​
related potentials: A brief tutorial. Brain Topography, 27(4), 438–​450. http://​doi.org/​10.1007/​
s10​548-​013-​0327-​5
Herrmann, C. S. & Strüber, D. (2017). What can transcranial alternating current stimulation
tell us about brain oscillations? Current Behavioral Neuroscience Reports, 4(2), 128–​137.
http://​doi.org/​10.1007/​s40​473-​017-​0114-​9
Herrmann, C. S., Strüber, D., Helfrich, R. F., & Engel, A. K. (2016). EEG oscillations: From
correlation to causality. International Journal of Psychophysiology, 103, 12–​21. http://​doi.org/​
10.1016/​j.ijpsy​cho.2015.02.003
Iaccarino, H. F., Singer, A. C., Martorell, A. J., Rudenko, A., Gao, F., Gillingham, T. Z., . . . Tsai, L.
H. (2016). Gamma frequency entrainment attenuates amyloid load and modifies microglia.
Nature, 540(7632), 230–​235. http://​doi.org/​10.1038/​natu​re20​587
Jadi, M. P., Behrens, M. M., & Sejnowski, T. J. (2016). Abnormal gamma oscillations in N-​
Methyl-​D-​Aspartate receptor hypofunction models of schizophrenia. Biological Psychiatry,
79(9), 716–​726. http://​doi.org/​10.1016/​j.biops​ych.2015.07.005
Janani, A. S., Grummett, T. S., Lewis, T. W., Fitzgibbon, S. P., Whitham, E. M., DelosAngeles,
D., . . . Pope, K. J. (2018). Improved artefact removal from EEG using canonical correl-
ation analysis and spectral slope. Journal of Neuroscience Methods, 298, 1–​15. http://​doi.org/​
10.1016/​j.jneum​eth.2018.01.004
Jasper, H. H. & Andrews, H. L. (1938). Electro-​encephalography III. Normal differentiation of
occipital and precentral regions in man. Archives of Neurology & Psychiatry, 39(1), 96–​115.
Jensen, O., Kaiser, J., & Lachaux, J. P. (2007). Human gamma-​frequency oscillations associated
with attention and memory. Trends in Neurosciences, 30(7), 317–​324. http://​doi.org/​10.1016/​
j.tins.2007.05.001
Kaiser, J. & Lutzenberger, W. (2005). Human gamma-​band activity: A window to cognitive pro-
cessing. NeuroReport, 16(3), 207–​211. http://​doi.org/​10.1097/​00001​756-​200502​280-​00001
Keizer, A. W., Verment, R. S., & Hommel, B. (2010). Enhancing cognitive control through
neurofeedback: A role of gamma-​band activity in managing episodic retrieval. NeuroImage,
49(4), 3404–​3413. http://​doi.org/​10.1016/​j.neu​roim​age.2009.11.023
Keizer, A. W., Verschoor, M., Verment, R. S., & Hommel, B. (2010). The effect of gamma
enhancing neurofeedback on the control of feature bindings and intelligence measures.
International Journal of Psychophysiology, 75(1), 25–​32. http://​doi.org/​10.1016/​j.ijpsy​
cho.2009.10.011
Keren, A. S., Yuval-​Greenberg, S., & Deouell, L. Y. (2010). Saccadic spike potentials in gamma-​
band EEG: Characterization, detection and suppression. NeuroImage, 49(3), 2248–​2263.
http://​doi.org/​10.1016/​j.neu​roim​age.2009.10.057
Kopell, N., Ermentrout, G. B., Whittington, M. A., & Traub, R. D. (2000). Gamma rhythms
and beta rhythms have different synchronization properties. Proceedings of the National
Academy of Sciences of the United States of America, 97(4), 1867–​1872. http://​doi.org/​10.1073/​
pnas.97.4.1867
Kreiter, A. K. & Singer, W. (1996). Stimulus-​dependent synchronization of neuronal responses
in the visual cortex of the awake macaque monkey. Journal of Neuroscience, 16(7), 2381–​2396.
Lally, N., Mullins, P. G., Roberts, M. V., Price, D., Gruber, T., & Haenschel, C. (2014).
Glutamatergic correlates of gamma-​ band oscillatory activity during cognition: A
172    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

concurrent ER-​MRS and EEG study. NeuroImage, 85, 823–​833. http://​doi.org/​10.1016/​j.neu​

roim​age.2013.07.049
Leicht, G., Kirsch, V., Giegling, I., Karch, S., Hantschk, I., Möller, H. J., . . . Mulert, C. (2010).
Reduced early auditory evoked gamma-​band response in patients with schizophrenia.
Biological Psychiatry, 67(3), 224–​231. http://​doi.org/​10.1016/​j.biops​ych.2009.07.033
Lenz, D., Fischer, S., Schadow, J., Bogerts, B., & Herrmann, C. S. (2011). Altered evoked gamma-​
band responses as a neurophysiological marker of schizophrenia? International Journal of
Psychophysiology, 79(1), 25–​31. http://​doi.org/​10.1016/​j.ijpsy​cho.2010.08.002
Lenz, D., Jeschke, M., Schadow, J., Naue, N., Ohl, F. W., & Herrmann, C. S. (2008). Human
EEG very high frequency oscillations reflect the number of matches with a template in
auditory short-​term memory. Brain Research, 1220, 81–​92. http://​doi.org/​10.1016/​j.brain​
res.2007.10.053
Lenz, D., Krauel, K., Flechtner, H. H., Schadow, J., Hinrichs, H., & Herrmann, C. S. (2010).
Altered evoked gamma-​band responses reveal impaired early visual processing in ADHD
children. Neuropsychologia, 48(7), 1985–​1993. http://​doi.org/​10.1016/​j.neuro​psyc​holo​
gia.2010.03.019
Lenz, D., Krauel, K., Schadow, J., Baving, L., Duzel, E., & Herrmann, C. S. (2008). Enhanced
gamma-​band activity in ADHD patients lacks correlation with memory performance
found in healthy children. Brain Research, 1235, 117–​132. http://​doi.org/​10.1016/​j.brain​
res.2008.06.023
Lutzenberger, W., Pulvermüller, F., Elbert, T., & Birbaumer, N. (1995). Visual stimulation alters
local 40-​Hz responses in humans: an EEG-​study. Neuroscience Letters, 183(1–​2), 39–​42.
http://​doi.org/​10.1016/​0304-​3940(94)11109-​V
Markov, N. T., Vezoli, J., Chameau, P., Falchier, A., Quilodran, R., Huissoud, C., . . . Kennedy,
H. (2014). Anatomy of hierarchy: Feedforward and feedback pathways in macaque visual
cortex. Journal of Comparative Neurology, 522(1), 225–​259. http://​doi.org/​10.1002/​cne.23458
Martinez-​Conde, S., Otero-​Millan, J., & Macknik, S. L. (2013). The impact of microsaccades on
vision: Towards a unified theory of saccadic function. Nature Reviews Neuroscience, 14(2),
83–​96. http://​doi.org/​10.1038/​nrn3​405
Mathes, B., Strüber, D., Stadler, M. A., & Başar-​Eroǧlu, C. (2006). Voluntary control of Necker
cube reversals modulates the EEG delta-​and gamma-​band response. Neuroscience Letters,
402(1-​2), 145–​149. http://​doi.org/​10.1016/​j.neu​let.2006.03.063
McNally, J. M. & McCarley, R. W. (2016). Gamma band oscillations: A key to understanding
schizophrenia symptoms and neural circuit abnormalities. Current Opinion in Psychiatry,
29(3), 202–​210. http://​doi.org/​10.1097/​YCO.00000​0000​0000​244.Gamma
Merkel, N., Wibral, M., Bland, G., & Singer, W. (2018). Endogenously generated gamma-​band
oscillations in early visual cortex: A neurofeedback study. Human Brain Mapping, 39(9),
3487–​3502. http://​doi.org/​10.1002/​hbm.24189
Merker, B. (2013). Cortical gamma oscillations: The functional key is activation, not cogni-
tion. Neuroscience and Biobehavioral Reviews, 37(3), 401–​417. http://​doi.org/​10.1016/​j.neubio​
rev.2013.01.013
Michalareas, G., Vezoli, J., van Pelt, S., Schoffelen, J. M., Kennedy, H., & Fries, P. (2016). Alpha-​
beta and gamma rhythms subserve feedback and feedforward influences among human
visual cortical areas. Neuron, 89(2), 384–​397. http://​doi.org/​10.1016/​j.neu​ron.2015.12.018
Miltner, W. H. R., Braun, C., Arnold, M., Witte, H., & Taub, E. (1999). Coherence of gamma-​
band EEG activity as a basis for associative learning. Nature, 397(6718), 434–​436. http://​doi.
org/​10.1038/​17126
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    173

Minzenberg, M. J., Firl, A. J., Yoon, J. H., Gomes, G. C., Reinking, C., & Carter, C. S. (2010).
Gamma oscillatory power is impaired during cognitive control independent of medication
status in first-​episode schizophrenia. Neuropsychopharmacology, 35(13), 2590–​2599. http://​
doi.org/​10.1038/​npp.2010.150
Müller, M. M., Bosch, J., Elbert, T., Kreiter, A., Sosa, M., Sosa, P., & Rockstroh, B. (1996).
Visually induced gamma-​band responses in human electroencephalographic activity: A
link to animal studies. Experimental Brain Research, 112(1), 96–​102. http://​doi.org/​10.1007/​
BF0​0227​182
Naue, N., Strüber, D., Fründ, I., Schadow, J., Lenz, D., Rach, S., Körner, U., & Herrmann, C.
S. (2011). Gamma in motion: Pattern reversal elicits stronger gamma-​band responses than
motion. NeuroImage, 55(2), 808–​817. http://​doi.org/​10.1016/​j.neu​roim​age.2010.11.053
Nimmrich, V., Draguhn, A., & Axmacher, N. (2015). Neuronal network oscillations in
neurodegenerative diseases. Neuromolecular Medicine, 17(3), 270–​284. http://​doi.org/​
10.1007/​s12​017-​015-​8355-​9
Nottage, J. F. (2010). Uncovering gamma in visual tasks. Brain Topography, 23(1), 58–​7 1. http://​
doi.org/​10.1007/​s10​548-​009-​0129-​y
Nottage, J. F. & Horder, J. (2016). State-​of-​the-​art analysis of high-​frequency (gamma range)
electroencephalography in humans. Neuropsychobiology, 72(3-​4), 219–​228. http://​doi.org/​
10.1159/​000382​023
Nottage, J. F., Morrison, P. D., Williams, S. C. R., & Ffytche, D. H. (2013). A novel method for
reducing the effect of tonic muscle activity on the gamma band of the scalp EEG. Brain
Topography, 26(1), 50–​61. http://​doi.org/​10.1007/​s10​548-​012-​0255-​9
Oppermann, F., Hassler, U., Jescheniak, J. D., & Gruber, T. (2012). The rapid extraction of gist—​
early neural correlates of high-​level visual processing. Journal of Cognitive Neuroscience,
24(2), 521–​529.
Palop, J. J. & Mucke, L. (2016). Network abnormalities and interneuron dysfunction in
Alzheimer disease. Nature Reviews Neuroscience, 17(12), 777–​792. http://​doi.org/​10.1038/​
nrn.2016.141
Paulsen, O. & Sejnowski, T. J. (2000). Natural patterns of activity and long-​term syn-
aptic plasticity. Current Opinion in Neurobiology, 10(2), 172–​179. http://​doi.org/​10.1016/​
S0959-​4388(0  0)00076-​3
Plöchl, M., Ossandón, J. P., & König, P. (2012). Combining EEG and eye
tracking: Identification, characterization, and correction of eye movement artifacts in
electroencephalographic data. Frontiers in Human Neuroscience, 6, 278. http://​doi.org/​
10.3389/​fnhum.2012.00278
Pope, K. J., Fitzgibbon, S. P., Lewis, T. W., Whitham, E. M., & Willoughby, J. O. (2009). Relation
of gamma oscillations in scalp recordings to muscular activity. Brain Topography, 22(1), 13–​
17. http://​doi.org/​10.1007/​s10​548-​009-​0081-​x
Prehn-​Kristensen, A., Wiesner, C. D., & Baving, L. (2015). Early gamma-​band activity during
interference predicts working memory distractibility in ADHD. Journal of Attention
Disorders, 19(11), 971–​976. http://​doi.org/​10.1177/​10870​5471​2459​887
Pulvermüller, F., Birbaumer, N., Lutzenberger, W., & Mohr, B. (1997). High-​frequency brain
activity: Its possible role in attention, perception and language processing. Progress in
Neurobiology, 52(5), 427–​445.
Ray, S. & Maunsell, J. H. R. (2011). Different origins of gamma rhythm and high-​gamma ac-
tivity in macaque visual cortex. PLoS Biology, 9(4), e1000610. http://​doi.org/​10.1371/​jour​nal.
pbio.1000​610
174    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

Ray, S. & Maunsell, J. H. R. (2015). Do gamma oscillations play a role in cerebral cortex? Trends
in Cognitive Sciences, 19(2), 78–​85. http://​doi.org/​10.1016/​j.tics.2014.12.002
Regan, D. (1968). A high frequency mechanism which underlies visual evoked potentials.
Electroencephalography and Clinical Neurophysiology, 25, 231–​237.
Regan, D. & Spekreijse, H. (1986). Evoked potentials in vision research 1961–​86. Vision
Research, 26(9), 1461–​1480. http://​doi.org/​10.1016/​B978-​0-​12-​385​157-​4.00529-​7
Reilly, T. J., Nottage, J. F., Studerus, E., Rutigliano, G., De Micheli, A. I., Fusar-​Poli, P., &
McGuire, P. (2018). Gamma band oscillations in the early phase of psychosis: A systematic
review. Neuroscience & Biobehavioral Reviews, 90, 381–​399. http://​doi.org/​10.1016/​j.neubio​
rev.2018.04.006
Reva, N. V. & Aftanas, L. I. (2004). The coincidence between late non-​ phase-​ locked
gamma synchronization response and saccadic eye movements. International Journal of
Psychophysiology, 51(3), 215–​222. http://​doi.org/​10.1016/​j.ijpsy​cho.2003.09.005
Rolfs, M., Kliegl, R., & Engbert, R. (2008). Toward a model of microsaccade generation: The
case of microsaccadic inhibition. Journal of Vision, 8(5), 1–​23.
Rossi, S., Hallett, M., Rossini, P. M., Pascual-​Leone, A., Avanzini, G., Bestmann, S., . . . Ziemann,
U. (2009). Safety, ethical considerations, and application guidelines for the use of transcranial
magnetic stimulation in clinical practice and research. Clinical Neurophysiology, 120(12),
2008–​2039. http://​doi.org/​10.1016/​j.cli​nph.2009.08.016
Ruden, J. B., Dugan, L. L., Konradi, C. (2021). Parvalbumin interneuron vulnerability and
brain disorders. Neuropsychopharmacology, 46, 279–​ 287. https://​doi.org/​10.1038/​s41​
386-​020-​0778-​9
Salari, N., Büchel, C., & Rose, M. (2014). Neurofeedback training of gamma band oscillations
improves perceptual processing. Experimental Brain Research, 232(10), 3353–​3361. http://​doi.
org/​10.1007/​s00​221-​014-​4023-​9
Salinas, E. & Sejnowski, T. J. (2001). Correlated neuronal activity and the flow of neural infor-
mation. Nature Reviews Neuroscience, 2, 539–​550. http://​doi.org/​10.1038/​35086​012
Schadow, J., Lenz, D., Thaerig, S., Busch, N. A., Fründ, I., Rieger, J. W., & Herrmann, C. S.
(2007). Stimulus intensity affects early sensory processing: Visual contrast modulates
evoked gamma-​band activity in human EEG. International Journal of Psychophysiology,
66(1), 28–​36. http://​doi.org/​10.1016/​j.ijpsy​cho.2007.05.010
Schwartzman, D. J. & Kranczioch, C. (2011). In the blink of an eye: The contribution of
microsaccadic activity to the induced gamma band response. International Journal of
Psychophysiology, 79(1), 73–​82. http://​doi.org/​10.1016/​j.ijpsy​cho.2010.10.006
Sejnowski, T. J. & Paulsen, O. (2006). Network oscillations: Emerging computational
principles. Journal of Neuroscience, 26(6), 1673–​1676. http://​doi.org/​10.1523/​JNEURO​
SCI.3737-​05d.2006
Senkowski, D. & Gallinat, J. (2015). Dysfunctional prefrontal gamma-​band oscillations reflect
working memory and other cognitive deficits in schizophrenia. Biological Psychiatry, 77(12),
1010–​1019.
Sheer, D. E. (1984). Focused arousal, 40-​Hz EEG, and dysfunction. In T. Elbert, B. Rockstroh,
W. Lutzenberger, & N. Birbaumer (Eds.), Self-​regulation of the brain and behavior (pp. 64–​
84). Springer.
Siegel, M., Donner, T. H., & Engel, A. K. (2012). Spectral fingerprints of large-​scale neuronal
interactions. Nature Reviews Neuroscience, 13(2), 121–​134. http://​doi.org/​10.1038/​nrn3​137
Singer, W. (2018). Neuronal oscillations: Unavoidable and useful? European Journal of
Neuroscience, 48(7), 2389–​2398. http://​doi.org/​10.1111/​ejn.13796
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    175

Singer, W. & Gray, C. M. (1995). Visual feature integration and the temporal correlation hy-
pothesis. Annual Review of Neuroscience, 18, 555–​586. http://​doi.org/​10.1146/​annu​rev.
ne.18.030​195.003​011
Spencer, K. M. (2012). Baseline gamma power during auditory steady-​ state stimula-
tion in schizophrenia. Frontiers in Human Neuroscience, 5, 190. http://​doi.org/​10.3389/​
fnhum.2011.00190
Spencer, K. M., Niznikiewicz, M. A., Shenton, M. E., & McCarley, R. W. (2008). Sensory-​
evoked gamma oscillations in chronic schizophrenia. Biological Psychiatry, 63(8), 744–​747.
Spydell, J. D., Ford, J. D., & Sheer, D. E. (1979). Task dependent cerebral lateralization of the 40
Hertz EEG rhythm. Psychophysiology, 16(4), 347–​350.
Stroganova, T. A., Butorina, A. V., Sysoeva, O. V., Prokofyev, A. O., Nikolaeva, A. Y., Tsetlin, M.
M., & Orekhova, E. V. (2015). Altered modulation of gamma oscillation frequency by speed
of visual motion in children with autism spectrum disorders. Journal of Neurodevelopmental
Disorders, 7(1), 1–​17. http://​doi.org/​10.1186/​s11​689-​015-​9121-​x
Strüber, D., Başar-​Eroǧlu, C., Hoff, E., & Stadler, M. A. (2000). Reversal-​rate dependent
differences in the EEG gamma-​band during multistable visual perception. International
Journal of Psychophysiology, 38(3), 243–​252.
Strüber, D., Başar-​Eroǧlu, C., Miener, M., & Stadler, M. A. (2001). EEG gamma-​band response
during the perception of Necker cube reversals. Visual Cognition, 8(3), 609–​621. http://​doi.
org/​10.1080/​135062​8014​3000​151
Strüber, D. & Herrmann, C. S. (2020). Modulation of gamma oscillations as a possible thera-
peutic tool for neuropsychiatric diseases: A review and perspective. International Journal of
Psychophysiology, 152, 15–​25. https://​doi.org/​10.1016/​j.ijpsy​cho.2020.03.003
Summerfield, C. & Mangels, J. A. (2006). Dissociable neural mechanisms for encoding pre-
dictable and unpredictable events. Journal of Cognitive Neuroscience, 18(7), 1120–​1132.
Swettenham, J. B., Muthukumaraswamy, S. D., & Singh, K. D. (2009). Spectral properties of
induced and evoked gamma oscillations in human early visual cortex to moving and sta-
tionary stimuli. Journal of Neurophysiology, 102(2), 1241–​1253. http://​doi.org/​10.1152/​
jn.91044.2008
Tal, N. & Yuval-​Greenberg, S. (2018). Reducing saccadic artifacts and confounds in brain im-
aging studies through experimental design. Psychophysiology, 55(11), 1–​20. http://​doi.org/​
10.1111/​psyp.13215
Tallon-​Baudry, C. (2009). The roles of gamma-​band oscillatory synchrony in human visual
cognition. Frontiers in Bioscience, 14, 321–​332.
Tallon-​Baudry, C. & Bertrand, O. (1999). Oscillatory gamma activity in humans and its role in
object representation. Trends in Cognitive Sciences, 3(4), 151–​162.
Tallon-​Baudry, C., Bertrand, O., Delpuech, C., & Pernier, J. (1997). Oscillatory γ-​band (30–​70
Hz) activity induced by a visual search task in humans. The Journal of Neuroscience, 17(2),
722–​734. https://​doi.org/​10.1523/​JNEURO​SCI.17-​02-​00722.1997
Tallon-​Baudry, C., Bertrand, O., Delpuech, C., & Pernier, J. (1996). Stimulus specificity of
phase-​locked and non-​phase-​locked 40 Hz visual responses in human. The Journal of
Neuroscience, 16(13), 4240–​4249. http://​doi.org/​10.1016/​j.neuro​psyc​holo​gia.2011.02.038
Tallon-​Baudry, C., Bertrand, O., Peronnet, F., & Pernier, J. (1998). Induced gamma-​band ac-
tivity during the delay of a visual short-​term memory task in humans. The Journal of
Neuroscience, 18(11), 4244–​4254. http://​doi.org/​20026​318
Thickbroom, G. W. & Mastaglia, L. (1985). Presaccadic “spike” potential: Investigation of top-
ography and source. Brain Research, 339, 271–​280.
176    DANIEL STRÜBER and CHRISTOPH S. HERRMANN

Tombor, L., Kakuszi, B., Papp, S., Réthelyi, J., Bitter, I., & Czobor, P. (2019). Decreased resting
gamma activity in adult attention deficit/​hyperactivity disorder. The World Journal of
Biological Psychiatry, 20(9), 691-​702. http://​doi.org/​10.1080/​15622​975.2018.1441​547
Uhlhaas, P. J. & Singer, W. (2006). Neural synchrony in brain disorders: Relevance for cogni-
tive dysfunctions and pathophysiology. Neuron, 52(1), 155–​168. http://​doi.org/​10.1016/​j.neu​
ron.2006.09.020
Uhlhaas, P. J. & Singer, W. (2010). Abnormal neural oscillations and synchrony in schizo-
phrenia. Nature Reviews Neuroscience, 11(2), 100–​113. http://​doi.org/​10.1038/​nrn2​774
Uhlhaas, P. J. & Singer, W. (2012). Neuronal dynamics and neuropsychiatric disorders: Toward
a translational paradigm for dysfunctional large-​scale networks. Neuron, 75(6), 963–​980.
http://​doi.org/​10.1016/​j.neu​ron.2012.09.004
Valsecchi, M., Betta, E., & Turatto, M. (2007). Visual oddballs induce prolonged microsaccadic
inhibition. Experimental Brain Research, 177(2), 196–​208. http://​doi.org/​10.1007/​s00​
221-​006-​0665-​6
Valsecchi, M., Dimigen, O., Kliegl, R., Sommer, W., & Turatto, M. (2009). Microsaccadic in-
hibition and P300 enhancement in a visual oddball task. Psychophysiology, 46(3), 635–​644.
http://​doi.org/​10.1111/​j.1469-​8986.2009.00791.x
Van Diessen, E., Senders, J., Jansen, F. E., Boersma, M., & Bruining, H. (2015). Increased power
of resting-​state gamma oscillations in autism spectrum disorder detected by routine elec-
troencephalography. European Archives of Psychiatry and Clinical Neuroscience, 265(6), 537–​
540. http://​doi.org/​10.1007/​s00​406-​014-​0527-​3
Van Kerkoerle, T., Self, M. W., Dagnino, B., Gariel-​Mathis, M.-​A., Poort, J., van der Togt, C.,
& Roelfsema, P. R. (2014). Alpha and gamma oscillations characterize feedback and feed-
forward processing in monkey visual cortex. Proceedings of the National Academy of Sciences
of the United States of America, 111(40), 14332–​14341.
Varela, F., Lachaux, J. P., Rodriguez, E., & Martinerie, J. (2001). The brainweb: Phase synchron-
ization and large-​scale integration. Nature Reviews Neuroscience, 2(4), 229–​239. http://​doi.
org/​10.1038/​35067​550
Vinck, M. & Bosman, C. A. (2016). More gamma more predictions: Gamma-​synchronization
as a key mechanism for efficient integration of classical receptive field inputs with surround
predictions. Frontiers in Systems Neuroscience, 10, 35. http://​doi.org/​10.3389/​fnsys.2016.00035
Von Stein, A., Chiang, C., & König, P. (2000). Top-​down processing mediated by interareal
synchronization. Proceedings of the National Academy of Sciences of the United States of
America, 97(26), 14748–​14753. http://​doi.org/​10.1073/​pnas.97.26.14748
Von Stein, A. & Sarnthein, J. (2000). Different frequencies for different scales of cortical inte-
gration: From local gamma to long range alpha/​theta synchronization. International Journal
of Psychophysiology, 38(3), 301–​313. http://​doi.org/​10.1016/​S0167-​8760(0  0)00172-​0
Wang, J., Barstein, J., Ethridge, L. E., Mosconi, M. W., Takarae, Y., & Sweeney, J. A. (2013). Resting
state EEG abnormalities in autism spectrum disorders. Journal of Neurodevelopmental
Disorders, 5(1), 24. http://​doi.org/​10.1186/​1866-​1955-​5-​24
Wang, X.-​J. (2010). Neurophysiological and computational principles of cortical rhythms in
cognition. Physiological Reviews, 90(3), 1195–​1268. http://​doi.org/​10.1152/​phys​rev.00035.2008
White, R. S. & Siegel, S. J. (2016). Cellular and circuit models of increased resting-​state network
gamma activity in schizophrenia. Neuroscience, 321, 66–​76.
Whitham, E. M., Lewis, T., Pope, K. J., Fitzgibbon, S. P., Clark, C. R., Loveless, S., . . . Willoughby,
J. O. (2008). Thinking activates EMG in scalp electrical recordings. Clinical Neurophysiology,
119(5), 1166–​1175. http://​doi.org/​10.1016/​j.cli​nph.2008.01.024
 GAMMA ACTIVITY IN SENSORY AND COGNITIVE PROCESSING    177

Whitham, E. M., Pope, K. J., Fitzgibbon, S. P., Lewis, T., Clark, C. R., Loveless, S., . . . Willoughby,
J. O. (2007). Scalp electrical recording during paralysis: Quantitative evidence that EEG
frequencies above 20 Hz are contaminated by EMG. Clinical Neurophysiology, 118(8), 1877–​
1888. http://​doi.org/​10.1016/​j.cli​nph.2007.04.027
Whittington, M. A., Cunningham, M. O., LeBeau, F. E. N., Racca, C., & Traub, R. D. (2011).
Multiple origins of the cortical gamma rhythm. Developmental Neurobiology, 71(1), 92–​106.
http://​doi.org/​10.1002/​dneu.20814
Whittington, M. A., Traub, R. D., Kopell, N., Ermentrout, B., & Buhl, E. H. (2000). Inhibition-​
based rhythms: Experimental and mathematical observations on network dynamics.
International Journal of Psychophysiology, 38(3), 315–​336.
Yordanova, J., Banaschewski, T., Kolev, V., Woerner, W., & Rothenberger, A. (2001). Abnormal
early stages of task stimulus processing in children with attention-​deficit hyperactivity dis-
order: Evidence from event-​related gamma oscillations. Clinical Neurophysiology, 112(6),
1096–​1108. http://​doi.org/​10.1016/​S1388-​2457(01)00524-​7
Yuval-​Greenberg, S. & Deouell, L. Y. (2009). The broadband-​transient induced gamma-​band
response in scalp EEG reflects the execution of saccades. Brain Topography, 22(1), 3–​6. http://​
doi.org/​10.1007/​s10​548-​009-​0077-​6
Yuval-​Greenberg, S., Tomer, O., Keren, A. S., Nelken, I., & Deouell, L. Y. (2008). Transient
induced gamma-​band response in EEG as a manifestation of miniature saccades. Neuron,
58(3), 429–​441. http://​doi.org/​10.1016/​j.neu​ron.2008.03.027
Zaehle, T., Fründ, I., Schadow, J., Thärig, S., Schoenfeld, M. A., & Herrmann, C. S. (2009).
Inter-​and intra-​individual covariations of hemodynamic and oscillatory gamma responses
in the human cortex. Frontiers in Human Neuroscience, 3, 8. http://​doi.org/​10.3389/​
neuro.09.008.2009
 CHAPTER 9

F RONTAL MIDL I NE T H ETA

AS A MODEL SPE C I ME N OF
C ORTICAL T H ETA

JAMES F. CAVANAGH AND MICHAEL X COHEN

9.1  History

Multiple distinct rhythmic processes in the approximate 4–​8 Hz theta-​band range

have been historically observed in the continuous EEG. Widely distributed theta-​
band rhythmicity is commonly observed during stage 1 sleep. Abnormal background
presence or hemispheric asymmetries in this rhythm are used to infer neural dysfunc-
tion in clinical practice. Yet nearly 70 years of observation have also detailed a task-​
related increase in frontal midline theta (FMT), usually observed over electrode Fz or its
nearest 10/​20 system neighbors during effortful mental processes (Arellano & Schwab,
1950; Brazier & Casby, 1952; Inouye, Shinosaki, Iyama, Matsumoto, Toi, et al., 1994; Sato,
1952). Since this FMT feature is cognitively induced, it has been considered distinct from
arousal-​or clinically related theta rhythms. These spatially specified and elicitation-​
dependent distinctions are critical to make when describing any frequency-​based EEG
activity: manifest characteristics like a common frequency range can be shared between
different latent processes.
Towards the end of the twentieth century, a growing quantitative approach to EEG
was facilitated by advancements in signal processing methods, including event-​related
potentials (ERPs) and Fourier-​based analyses, improvements in computational power
to implement those analyses, and increased data quality through better scalp EEG
equipment and direct intracranial human recordings during cognitive performance.
Following these technical revolutions, an emerging consensus deduced that cortically
generated theta-​band activities are reliably associated with general cognitive perform-
ance (Başar, 1998b), including specific processes like working memory (Asada et al.,
1999; Gevins et al., 1997; Ishii et al., 1999), spatial navigation (Kahana et al., 1999), or
 FRONTAL MIDLINE THETA AS A MODEL SPECIMEN OF CORTICAL THETA    179

episodic memory encoding and retrieval (Jacobs et al., 2006; Kahana et al., 1999;
Klimesch, 1999; Klimesch et al., 2000; Nyhus & Curran, 2010; Rizzuto et al., 2006;
Sauseng et al., 2004). These findings indicated that theta is generated across human neo-
cortical areas (Caplan et al., 2003; Jacobs et al., 2006; Raghavachari et al., 2006) and
that it reflects a multitude of active cortical processes. Here we reiterate our caveat for
determining the relationship between a brain rhythm and a specific cognitive pro-
cess: rhythmic processes reflect common neural operations that have distinct repre-
sentational content depending on the generative neural system. Theta-​band dynamics
reflect a non-​specific marker of active cortical operation. The frontal midline variant of
theta is particularly prevalent in the human EEG, making it a good example for under-
standing broader cortical theta activities.
Experimental findings have accumulated an increasingly well-​ defined set of
processes associated with FMT. Talairach and colleagues (1973) described how electrical
stimulation of the human anterior cingulate cortex (ACC) elicited motor actions that
were integrated with environmental context, sometimes accompanied by FMT oscilla-
tory activities. Throughout the 1990s, the qualitative appearance of scalp-​recorded FMT
during cognitive effort could be reliably evoked (Asada et al., 1999; Inouye et al., 1994;
Inouye, Shinosaki, Iyama, Matsumoto, Toi, et al., 1994) and a corresponding relation-
ship with anxiety was often observed (Mizuki et al., 1997; Mizuki et al., 1992; Mizuki
et al., 1996). These two effective and affective facets of vigilance have been increas-
ingly associated with FMT throughout the past few decades. Paralleling the evolving
capabilities of experimental neurophysiology, a growing area of research has moved be-
yond qualitative assessment towards a detailed quantification of the generators, elicitors,
and moderators involved in the genesis of the FMT rhythm.

9.2  Characteristics

Mental effort is a reliable elicitor of FMT (Smit et al., 2004; Smit et al., 2005). FMT
increases during perseverance and decreases during fatigue (Wascher et al., 2014).
Working memory load scales with FMT power (Gevins & Smith, 2000; Ishii et al., 1999;
Itthipuripat et al., 2013; Onton et al., 2005; Sauseng et al., 2010), although it should be
examined if this relationship is simply due to increased effort or if it represents specific
information content (see Hsieh et al., 2011; Roberts et al., 2013). Memory encoding and
retrieval are associated with broad cortical theta, including FMT (Hsieh & Ranganath,
2014; Jacobs et al., 2006; Kahana et al., 1999; Klimesch, 1999; Klimesch et al., 2000; Nyhus
& Curran, 2010; Rizzuto et al., 2003, 2006; Sauseng et al., 2004). It remains unknown if
the role of FMT is specific to control processes in memory rather than encoding per se
(see Hanslmayr et al., 2010; Staudigl et al., 2010), particularly since other cortical theta is
specifically associated with encoding (see Rizzuto et al., 2006; Wang et al., 2018).
FMT has been localized to broad medial frontal cortical areas, including the ACC and
the midcingulate cortex (MCC) using MEG (Beaton et al., 2018; Ishii et al., 1999; Jensen
180    JAMES F. CAVANAGH and MICHAEL X COHEN

& Tesche, 2002) and EEG (Cohen & Ridderinkhof, 2013; Gevins & Smith, 2000; Gevins
et al., 1999; Gevins et al., 1997; Onton et al., 2005). The MCC generates oscillations in the
theta band in human intracranial recording (Cohen et al., 2008; Wang et al., 2005) as well
as in non-​human primates (Tsujimoto et al., 2010; Tsujimoto et al., 2006; Womelsdorf,
Johnston, et al., 2010; Womelsdorf, Vinck, et al., 2010). Recent reviews have summarized
distinct functional aspects of FMT, including its modulators (Mitchell, McNaughton,
Flanagan, & Kirk, 2008), its role in memory (Hsieh & Ranganath, 2014), and its broader
role in cognitive control (Cavanagh & Frank, 2014). We turn now to this defining area
of cognitive control and the history of linking FMT processes to frontal midline ERP
components intricately related to the need for control.

9.2.1 ERP Findings Linked to the FMT Response

Figure 9.1 shows frontal midline ERPs associated with a common theta-​band substrate.
The discovery of the response-​locked frontal midline ERP feature known as the error-​
related negativity (ERN) indirectly motivated a renewed interest in FMT dynamics
(Falkenstein et al., 1991; Gehring et al., 1993). Not long after its discovery, the ERN was
characterized as being particularly sensitive to anxiety (Gehring et al., 2000) with a
presumed generative source in ACC (Dehaene et al., 1994; Ishii et al., 1999; Van Veen &
Carter, 2002). Importantly, the ERN was shown to have a spectral response in the theta
band (Luu & Tucker, 2001; Luu et al., 2004), although concurrent delta-​band activities
have also been noted (Yordanova et al., 2004) and recently highlighted as functionally
distinct processes (Cohen & Donner, 2013).
A smaller voltage negativity was also observed on non-​error trials (Coles et al., 2001;
Vidal et al., 2003; Vidal et al., 2000), which is sometimes called the correct-​related nega-
tivity (CRN). While this EEG feature was sometimes interpreted as an artifact (Coles
et al., 2001), it is now known to be reliably observed during action commission, even in
the absence of task demands (Cavanagh et al., 2012). CRN amplitudes mirror variations
in performance monitoring during manual responses, as they are larger under
conditions of increased task difficulty (Hajcak et al., 2005) and uncertainty (Pailing
& Segalowitz, 2004) and they are diminished on correct trials immediately preceding
errors (Allain et al., 2004; Cavanagh et al., 2009).
A stimulus-​ locked error signal following punishing or error feedback was
characterized soon after the discovery of the ERN (Miltner et al., 1997), with varied
theoretical accounts arguing for a common process with the response-​locked ERN
(Holroyd & Coles, 2002; Holroyd et al., 2002) or a similar but distinct comparator pro-
cess (Gehring & Willoughby, 2002). This component developed many different names,
including the feedback-​related negativity (FRN), the feedback error-​related negativity
(fERN), or the mediofrontal negativity (MFN). However, the process reflected by these
terms all share common features with the well-​known frontal midline N2 component
(Folstein & Van Petten, 2008; Holroyd, 2002), arguing against any specificity of infor-
mation content in these processes. Indeed, the N2 component was already known to
 FRONTAL MIDLINE THETA AS A MODEL SPECIMEN OF CORTICAL THETA    181

Stimulus-Locked Response-Locked
Novelty Conflict Punishment Conflict Errors
(a)
Event-Related
Potentital

μV

N2 N2 N2/FRN CRN ERN

(b) 47
Novel - Standard
47
Hi Conflict - Lo Conflict
47
Incorrect - Correct
47
Hi Conflict - Lo Conflict
47
Error - Correct
dB
Time-Frequency

26 26 26 26 26
15 15 15 15 15
Hz 8
Power

8 8 8 8
5 5 5 5 5
3 3 3 3 3 +/–4
1 +/–2 1 +/–1 1 +/–2 1 +/–1 1
–250 0 250 500 750 –250 0 250 500 750 –250 0 250 500 750 –500 –250 0 250 750 –500 –250 0 250 750
ms peri-stimulus ms peri-stimulus ms peri-stimulus ms peri-stimulus ms peri-stimulus
(c)
Theta Increase
Topography of

+/–8 +/–4 +/–12 +/–4 +/–12

Figure 9.1  The need for cognitive control is associated with a similar frontal midline theta
signature across a variety of eliciting events. (A) Phase-​locked EEG activities (ERPs). While
these ERP components (i.e., peaks and troughs in the signal locked to particular external events
and averaged across trials) are related to learning and adaptive control, they represent a small
fraction of ongoing neural dynamics. (B) Time-​frequency plots show richer spectral dynamics of
event-​related neuro-​electrical activity by averaging activities regardless of phase-​locking. Here,
significant increases in power to novelty, conflict, punishment, and error are outlined in black,
revealing a common frontal midline theta band feature during events that signal a need for con-
trol. (C) Scalp topography of event-​related frontal midline theta activity. The distribution of theta
power bursts is consistently maximal over the frontal midline.
N2, a component elicited by novelty or stimulus/​response conflict; Feedback related negativity
(FRN), A similar N2-​like component elicited by external feedback signaling that one’s actions were
incorrect or yielded a loss; Correct-​related negativity (CRN), a small, obligatory component evoked
by motor responses even when these are correct according to the task and enhanced by response
conflict; Error related negativity (ERN), A component evoked by motor commission errors.

have a spectral representation in the theta band (Başar-​Eroğlu et al., 1992; Başar, 1998a;
Yordanova et al., 2002). The ERN and the FRN/​N2 are estimated to have MCC sources
via EEG source estimation (Gehring et al., 2012; Gruendler et al., 2011; van Noordt &
Segalowitz, 2012; Walsh & Anderson, 2012) and EEG-​informed fMRI (Becker et al.,
2014; Debener et al., 2005; Edwards et al., 2012; Hauser et al., 2014; Huster et al., 2011),
suggesting at least some common processes linking the two.
A parsimonious summary could propose that both the stimulus-​and response-​
related fronto-​central negativities reflect common features of the processing demands
of the MCC. These features are varied across systems related to cognitive and motor
control, attention, and reinforcement learning, but are especially sensitive to mismatch
signals of conflict, punishment, and error in the service of behavioral adaptation. The
commonality of these theta-​band processes led to an integrative theory of a common
182    JAMES F. CAVANAGH and MICHAEL X COHEN

language, a theta lingua franca, for the realization of the need for control (Cavanagh
et al., 2009; 2012). Stimulus-​and response-​locked obligatory theta-​band phase dy-
namics were proposed to represent a biophysical mechanism for the common tem-
poral organization of neural processes during stimulus or response processes. Variation
on this theme, such as power enhancement, reflects the realization of these reactive
responses (Figure 9.1). These computations appear to be used to merge attentive, af-
fective, and cognitive functions with motor selection in order to utilize environmental
context during action monitoring. FMT therefore appears to reflect general operations
of the MCC during action monitoring, particularly as an initial orienting response to a
novel or surprising event (Wessel, 2018).

9.2.2 Do ERP Theta and FMT Reflect the Same Process?

Recent findings have begun to parse some of the overlapping constructs in the broad
theta lingua franca perspective. FMT dynamics occur in the “background” during cog-
nitive performance, emerging in a scale-​free manner over varied time scales and thus
not only to punctate evoked orienting responses (Cohen, 2016). Conflict appears to be
specifically represented in the theta band, whereas error-​specific features are associated
with an additional delta-​band response (Cohen & Donner, 2013; Cohen & van Gaal,
2014; Yordanova et al., 2004). Conflict can have many different definitions, with formal
mathematical models equating to a type of surprise (Berlyne, 1957; Botvinick et al., 2001;
Wiecki & Frank, 2013) and informal definitions comprising a homology of difficulty or
effort.
In line with Shackman and colleagues’ (2011) adaptive control hypothesis, FMT
closely aligns with the proposed domain-​general (effective and affective) role of the
MCC for selecting actions under uncertainty (Cavanagh & Shackman, 2014). Meta-​
analytic evidence supports the hypothesis that cognitive effort and anxiety are both
related to FMT and associated ERP features (Cavanagh & Shackman, 2014; Moser et al.,
2013). Highly anxious individuals appear to utilize punishment and error information
more effectively than a control sample. Enhanced FMT mediates the relationship be-
tween anxiety and risky decision making (Schmidt et al., 2018), and it correlates with an
enhanced ability to learn from punishment (Cavanagh et al., 2018) and adjust behavior
following errors (Cavanagh, Meyer, Hajcak, et al., 2017).
In sum, definitions of conflict, difficulty, and effort can all be equivalently applied to
situations that elicit FMT as well as ERP components with theta-​dominant substrates.
In line with the adaptive control hypothesis, FMT appears to mediate the increased af-
fective and effective vigilance leading to more avoidant behaviors, particularly in highly
anxious individuals. However, our overarching caveat should be noted again: there are a
multitude of theta band responses, even over the frontal midline, and each can reflect a
variety of processes (Töllner et al., 2017). For example, Cohen and Donner (2013) found
that the response-​conflict-​related N2 ERP component was uncorrelated with conflict-​
related FMT, and that removing the phase-​locked (ERP) component of the signal
 FRONTAL MIDLINE THETA AS A MODEL SPECIMEN OF CORTICAL THETA    183

did not affect the conflict-​related FMT. This is consistent with other reports that have
reported a qualitative absence of phase-​locking associated with response-​conflict FMT
(Nigbur et al., 2012; Pastötter et al., 2010). These findings can be contrasted with similar
analyses of the FMT response to erroneous button presses, which contains theta-​band
phase-​locking (Trujillo & Allen, 2007) that is significantly affected by removing the ERP
(Munneke et al., 2015).

9.3  Translational Underpinnings

In some fields of neuroscience research, the term “theta” implicitly implies rodent
hippocampal activity (~4–​12 Hz) that has been associated with learning, memory, and
spatial navigation (Buzsáki, 2006). Rodent hippocampal theta is not a unitary construct
(Colgin, 2013; Pignatelli et al., 2012), with separate theta rhythms occurring due to septal
drive as well as an intrinsic generative process that seems to be common to many types
of cortical and sub-​cortical excitatory-​inhibitory networks (Womelsdorf et al., 2014).
Mediofrontal spikes are phase-​ locked to both mediofrontal theta as well as
hippocampal theta (Benchenane et al., 2010; Hyman et al., 2011; Jones & Wilson, 2005b;
2005a; Paz et al., 2008; Pignatelli et al., 2012; Siapas et al., 2005). However, this evidence
of hippocampal interaction with frontal theta processes could reflect a generic phenom-
enon whereby cortical theta synchronizes disparate neural areas in a global workspace,
possibly via travelling waves (Lubenov & Siapas, 2009; Zhang et al., 2018). Many cortical
areas have shown phase-​synchronous relationships with frontal theta, including visual
cortex (Lee et al., 2005; Liebe et al., 2012; Phillips et al., 2013), amygdala (Taub et al.,
2018), and ventral tegmental areas (Fujisawa & Buzsáki, 2011). The ubiquity of theta-​
band findings across species has led to the suggestion that FMT reflects a non-​specific
mechanism for organizing neural processes around “decision points”, such as action se-
lection (Womelsdorf, Vinck, et al., 2010).
The translational potential for using theta to infer similar cognitive processes between
species is promising but needs additional clarification. Some studies show that non-​
human primates have similar error, conflict, and feedback ERPs at the skull (Phillips &
Everling, 2014), the scalp (Godlove et al., 2011), the dura (Vezoli & Procyk, 2009), and
within the cingulate cortex (Emeric et al., 2010), although the spectral representation
of these signals has not been defined. Rats have a FMT-​dominant control network that
is transiently instantiated following an imperative tone, affording a chance to causally
manipulate this network and draw parallel conclusions to humans (Narayanan et al.,
2013) although this is non-​specifically spectrally localized to the theta band compared
to typical human EEG findings. This common FMT electrophysiological response is
diminished in Parkinson’s patients as well as in a dopamine depletion rodent model
(Parker et al., 2015), suggesting a novel model of cognitive dysfunction in Parkinsonism.
Ample evidence suggests that FMT is sensitive to dopamine in humans, but it appears
to also be sensitive to other monoamines like norepinephrine and acetylcholine (see
184    JAMES F. CAVANAGH and MICHAEL X COHEN

review by Jocham & Ullsperger, 2009) so the specificity of neuromodulator influence is

likely to be low.
Given this pervasive dominance of theta-​band activities across mammalian cognitive
processes, one may wonder if there is something special about this frequency. Indeed,
many mammalian motor activities occur within a broadly-​defined theta frequency
(Cohen, 2014; Colgin, 2013). Reflexive movements like sniffing (Macrides et al., 1982),
whisking (Berg & Kleinfeld, 2002), licking (Amarante et al., 2017), giggling (Luschei,
2006), and shivering (Petajan & Williams, 1972), as well as controlled processes like
saccade initiation (Jutras et al., 2013), typing (Yamaguchi et al., 2013), and speaking
(Pellegrino et al., 2011), all occur with theta rhythmicity. This theta dominance of
the speech rate may have emerged as a consequence of motor properties of mouth
movements, which themselves emerged from reflexive sucking, chewing, and licking
patterns (MacNeilage & Davis, 2001). Yet there are theta rhythms in attentive processes
as well. Saccades reset hippocampal theta rhythms in monkeys (Jutras et al., 2013),
which appear to facilitate the creation of grid-​based representations of space (Killian
et al., 2012). Sustained attention has rhythmic fluctuations at an approximate theta fre-
quency (Helfrich et al., 2018; Huang et al., 2015), although this may be a general low-​
frequency phenomenon and may not be specific to theta (VanRullen, 2016).
In sum, cognitive processes and controlled motor activities appear to emerge from
existing phylogenetic scaffolds that use a basic pattern generator for action initiation.
For whatever reason, theta rhythmicity may have first been leveraged to optimize
skeleto-​motor action integration. The common occurrence of theta across arousal,
motor, cognitive, and attentive processes suggests a degeneracy of function: many
different processes evoke a theta band correlate. Still, there might be a common compu-
tational advantage of particular temporal pattern.

9.3.1 Theta Phase Dynamics and Decision Integration

Theta oscillatory dynamics are a possible computational mechanism by which
expectations and outcomes can be compared. Oscillations alter the membrane poten-
tial of neurons “tuned” to the oscillation frequency, forcing windows of time where
any given neuron is either more (trough) or less (peak) likely to be excited. Neurons
participating in this given frequency perturbation are more likely to interact, exchange
information, and modulate synaptic plasticity together (Fries, 2015). Since oscillations
reflect the action of a fundamental, energy-​efficient physical principle, functional dy-
namics of information processing may be inferred from the qualities inherent to
oscillations: timing, prediction, storage, and communication.
The 1/​f characteristic of brain oscillations suggests that small-​ amplitude fast-​
oscillating networks are a characteristic of more local operations, whereas slow, large
rhythms link areas over a greater spatial distance. Sinusoidal (harmonic) oscillators,
such as the theta rhythm, are good time keepers due to the ability to predict future
states based on knowledge of the oscillation period and the phase at any given moment
 FRONTAL MIDLINE THETA AS A MODEL SPECIMEN OF CORTICAL THETA    185

(Buzsáki, 2006). Pulsatile (non-​harmonic, or relaxation) oscillators, such as the neur-

onal membrane potential, may be synchronized easily by harmonic oscillators which
can act to separate information transfer and information intake (Buzsáki & Draguhn,
2004). These characteristics of timing and selective entrainment make oscillations a
substrate for ongoing processing (storage) and phase reset (input enhancement), two
necessary components of expectation and prediction (Buzsáki, 2006).
Across networks, oscillations within one network may entrain other neurons by
locking them into the same oscillatory phase (Fries, 2005; Womelsdorf et al., 2007), to
a harmonic oscillatory phase (Gruber et al., 2005), or by coupling a higher frequency
power increase to lower frequency phase (Canolty et al., 2006; Jensen & Lisman, 2005).
Coherent oscillations between distal areas are thought to reflect entrained inter-​regional
activity, which serves to increase the coordination of spike timing across spatially sep-
arate neural networks (Fries, 2005). Thus, slower oscillations like theta can act as a
reader of fast activities (Buzsáki, 2010; Jensen & Colgin, 2007; Womelsdorf, Vinck, et al.,
2010), for example integrating phonemes into words during speech processing (Giraud
et al., 2007; Giraud & Poeppel, 2012). Theta phase thus appears to be a general neural
mechanism for coupling disparate local gamma band sequences (Canolty & Knight,
2010; Fukai, 1999; Jensen & Lisman, 2005; Solomon et al., 2017; Tang et al., 2016; White
et al., 2000). This pattern of theta-​gamma coupling even forms the basis of some current
network-​level models of cognitive control (Gratton, 2018; Verguts, 2017).

9.3.2   Theta phase dynamics and cognitive control

If FMT power bursts signal a generic need for control (Figure 9.1), theta-​band phase
synchrony between frontal midline and distal sites may communicate how to imple-
ment that control (Figure 9.2a). In the more than ten years since the initial publication of
this simultaneous discovery by two separate groups (Cavanagh et al., 2009; Hanslmayr
et al., 2008), there have been over 20 replications of this effect of transient similarity in
theta-​specific phase angle following a variety of events indicating a need for control.
This finding further validates a theta-​based similarity between conflict, punishment,
error, and working-​memory evoked FMT as a common lingua franca for implementing
control.
Other types of statistical interaction have also been shown in theta-​band networks,
primarily using Granger prediction where midline areas lead distal areas (Cohen &
van Gaal, 2013; Popov et al., 2018; Rajan et al., 2018; Zavala et al., 2016; Zavala et al.,
2014). Intracranial recordings in humans have validated the hypothesis that cingulate
theta couples with gamma, and that this process leads dlPFC, MFC, and OFC during
the need for cognitive control (Bartoli et al., 2017; Oehrn et al., 2014; Rothé et al., 2011;
Smith et al., 2015; Tang et al., 2016). Similar medio-​occipital phase synchrony has been
observed in monkeys (Phillips et al., 2013) and medio-​motor synchrony has been
observed in rats (Narayanan et al., 2013). These theta-​phase networks can be boosted by
transcranial stimulation (Reinhart & Woodman, 2014; Reinhart, 2017), and diminished
186    JAMES F. CAVANAGH and MICHAEL X COHEN

(a)

Motor
IPFC

MCC

Sensory

BG
WM
Conflict
Error
(b) e e
Cu ons back
IPFC sp ed
Re Fe
age schizophrenia
tDCS age
in-phase tACS out-phase tACS
anxiety mild TBI

(c)
IPFC: L>R IPFC: R>L

Figure 9.2  Theta band phase consistency between mid-​frontal and distal sites is transiently
increased following events that indicate a need for control. (A) Twenty five separate studies (A
through Y) have replicated the finding of theta-​band phase synchrony between the frontal mid-
line (presumably MCC) and varied cortical areas, including lateral prefrontal cortex (lPFC),
motor cortex, sensory cortices, and basal ganglia (BG). WM =​working memory. (B) A var-
iety of moderators affect medio-​lateral phase synchrony, with increases due to age, anxiety and
transcranial direct or alternating current stimulation (tD/​ACS), and decreases due to schizo-
phrenia, age, anti-​phase tACS, and mild traumatic brain injury (TBI). (C) Studies often-
times report a nominal pattern of hemisphericity in medio-​lateral phase synchrony. Errors
and punishments consistently evoked a right>left pattern, whereas conflict tended towards a
left>right pattern. However, the studies contributing to the left>right pattern were more com-
plex and involved proactive and reactive processes compared to error realization, which is ra-
ther straightforward and reactive. Future studies should formally investigate the moderators of
hemisphericity in medio-​lateral phase synchrony.
Citations for fi
­ gure 9.2:
A: Hanslmayr et al., 2008; B: Cavanagh et al., 2009; C: Cohen et al., 2009; D: Cavanagh et al., 2010; E: Cohen & Cavanagh,
2011; F: Cohen & van Gaal, 2013; G: Nigbur et al., 2012; H: van de Vijver et al., 2011; I: van Driel et al., 2012; J: Narayanan et
al., 2013; K: Anguera et al., 2013; L: Cohen & van Gaal, 2014; M: Tóth et al., 2014; N: Van de Vijver et al., 2014; O: Moran et
al., 2014; P: Reinhart et al., 2015; Q: Zavala et al., 2013; R: Cavanagh et al., 2017; S: Reinhart, 2017; T: Vissers et al., 2018: U:
Ryman et al., 2018; V: Swart et al., 2018; W: Buzzell et al., 2018; X: Oehrn et al., 2014; Y: Cavanagh et al., 2020.
 FRONTAL MIDLINE THETA AS A MODEL SPECIMEN OF CORTICAL THETA    187

by out-​of-​phase alternating current (Reinhart, 2017). These networks are also altered in
psychiatric distress, being increased in anxiety (Cavanagh et al., 2017) and diminished
in schizophrenia (Ryman et al., 2018), see Figure 9.2b. Many questions remain to be
addressed about the function of this theta-​band phase synchrony, but there is correlative
(Anguera et al., 2013; Cavanagh et al., 2009; Cavanagh et al., 2017; Swart et al., 2018) and
causal evidence (Narayanan et al., 2013; Reinhart, 2017; Reinhart et al., 2015) that this
network directly affects behaviors related to the ability to learn from and adapt to the
need for control.
Many studies have observed a right-​sided dominance of medio-​lateral phase syn-
chrony, but this issue of hemisphericity requires further rigorous testing. Figure 9.2c
sorts studies that reported even a nominal pattern of hemisphericity, and it can be
seen that errors and punishments consistently evoked a right>left bias, whereas con-
flict tended towards a left>right bias. Although this distinction appears straightfor-
ward, it is likely overly simplistic to suggest a simple conflict vs. error dissociation on
hemisphericity. The studies contributing to the left>right pattern were more complex
and involved both proactive and reactive processes whereas error realization is rather
straightforward and reactive. Future studies should be formally test for hemispheric
bias in medio-​lateral phase synchrony to better address questions about the functional
role of this signal.

9.4  Clinical applications

FMT and related ERP features have compelling characteristics for clinical advance-
ment. The majority of the units of analysis in the National Institute of Mental Health
(NIMH) Research Domain Criteria (Insel et al., 2010) are EEG-​based, and many of
these are FMT-​family responses. Lower FMT appears to be a reliable endophenotype
for substance abuse and externalizing disorders (Gilmore et al., 2010; Kamarajan et al.,
2015; Kang et al., 2012; Rangaswamy et al., 2007; Zlojutro et al., 2011). Higher FMT is
reliably associated with anxious temperament (Cavanagh & Shackman, 2014; Moser
et al., 2013; Riesel et al., 2017), and ERN amplitude can even predict treatment response
in anxiety disorder patients (Gorka et al., 2018) . Future studies should derive the sen-
sitivity and specificity of FMT to determine the biomarker potential in select clinical
applications.
FMT can be elicited in simple tasks that are viable within a clinical environment.
Aberrant auditory orienting responses have already been advanced as candidate
biomarkers, like diminished mismatch negativity (MMN) in schizophrenia (Javitt
et al., 2018; Light et al., 2015) or diminished novelty habituation in Parkinson’s disease
(Cavanagh, Kumar, et al., 2018). The MMN is a theta-​dominant response with sep-
arable frontal and temporal processes (Fuentemilla et al., 2008; Ko et al., 2012) that
may interact via theta-​band phase synchrony (Choi et al., 2013). The neural systems
underlying auditory novelty detection are well detailed in rodent models (Escera &
188    JAMES F. CAVANAGH and MICHAEL X COHEN

Malmierca, 2014; Featherstone et al., 2018; Lee et al., 2018), facilitating cross-​species
translation. Auditory-​evoked responses are already routinely used in brainstem audi-
tory testing for hearing acuity in newborns, demonstrating that clinical infrastructure
and expertise exists for applying relevant tasks to patient groups when using EEG as a
diagnostic tool.

9.5  Broader impact and

future directions

FMT is a well-​characterized candidate mechanism underlying the ability to realize and

communicate the need for cognitive control. Further tests of this theory will need to
integrate findings from preclinical animal models, computational accounts of informa-
tion representation, broader human imaging literature, and the sensitivity and specifi-
city diagnostics for human patient groups. Fortunately, electrophysiology is routinely
utilized in vitro, in vivo, and in outpatient neurological clinics, making it uniquely
positioned at the crossroads of many sub-​fields of neuroscience.

References
Allain, S., Carbonnell, L., Falkenstein, M., Burle, B., & Vidal, F. (2004). The modulation of the
Ne-​like wave on correct responses foreshadows errors. Neuroscience Letters, 372(1–​2), 161–​
166. https://​doi.org/​S0304-​3940(04)01171-​1 [pii]10.1016/​j.neulet.2004.09.036
Amarante, L. M., Caetano, M. S., & Laubach, M. (2017). Medial frontal theta is entrained to
rewarded actions. The Journal of Neuroscience, 37(44), 1965–​1917. https://​doi.org/​10.1523/​
JNEURO​SCI.1965-​17.2017
Anguera, J. A., Boccanfuso, J., Rintoul, J. L., Al-​Hashimi, O., Faraji, F., Janowich, J., . . . Gazzaley,
A. (2013). Video game training enhances cognitive control in older adults. Nature, 501(7465),
97–​101. https://​doi.org/​10.1038/​natu​re12​486
Arellano, A. P. & Schwab, R. S. (1950). Scalp and basal recording during mental activity.
Proceedings of the 1st International Congress of Psychiatry, September 18–​27, Paris.
Asada, H., Fukuda, Y., Tsunoda, S., Yamaguchi, M., & Tonoike, M. (1999). Frontal midline
theta rhythms reflect alternative activation of prefrontal cortex and anterior cingulate cortex
in humans. Neuroscience Letters, 274(1), 29–​32. https://​doi.org/​S0304-​3940(99)00679-​5
Bartoli, E., Conner, C. R., Kadipasaoglu, C. M., Yellapantula, S., Rollo, M. J., Carter, C. S., &
Tandon, N. (2017). Temporal dynamics of human frontal and cingulate neural activity
during conflict and cognitive control. Cerebral Cortex, 28(11), 3842–​3856. https://​doi.org/​
10.1093/​cer​cor/​bhx​245
Başar-​Eroğlu, C., Başar, E., Demiralp, T., & Schurmann, M. (1992). P300-​response: Possible
psychophysiological correlates in delta and theta frequency channels. A review. International
Journal of Psychophysiology, 13, 161–​179.
Başar, E. (1998a). Brain function and oscillations: Brain oscillations–​principles and approaches.
Springer-​Verlag. https://​doi.org/​10.1007/​978-​3-​642-​72192-​2
 FRONTAL MIDLINE THETA AS A MODEL SPECIMEN OF CORTICAL THETA    189

Başar, E. (1998b). Brain function and oscillations: Integrative brain function–​neurophysiology

and cognitive processes. Springer-​Verlag. https://​doi.org/​10.1007/​978-​3-​642-​59893-​7
Beaton, L. E., Azma, S., & Marinkovic, K. (2018). When the brain changes its mind: Oscillatory
dynamics of conflict processing and response switching in a flanker task during alcohol
challenge. PLoS One, 13(1), 1–​24. https://​doi.org/​10.1371/​jour​nal.pone.0191​200
Becker, M. P. I., Nitsch, A. M., Miltner, W. H. R., & Straube, T. (2014). A single-​trial estimation
of the feedback-​related negativity and its relation to BOLD responses in a time-​estimation
task. The Journal of Neuroscience, 34(8), 3005–​3012. https://​doi.org/​10.1523/​JNEURO​
SCI.3684-​13.2014
Benchenane, K., Peyrache, A., Khamassi, M., Tierney, P. L., Gioanni, Y., Battaglia, F. P., &
Wiener, S. I. (2010). Coherent theta oscillations and reorganization of spike timing in the
hippocampal-​prefrontal network upon learning. Neuron, 66(6), 921–​936. https://​doi.org/​
10.1016/​j.neu​ron.2010.05.013
Berg, R. W. & Kleinfeld, D. (2002). Rhythmic whisking by rat: Retraction as well as protraction
of the vibrissae is under active muscular control. Journal of Neurophysiology, 89(1), 104–​117.
https://​doi.org/​10.1152/​jn.00600.2002
Berlyne, D. E. (1957). Uncertainty and conflict: A point of contact between information-​theory
and behavior-​theory concepts. Psychological Review, 64(6), 329–​339.
Botvinick, M. M., Braver, T. S., Barch, D. M., Carter, C. S., & Cohen, J. D. (2001). Conflict
monitoring and cognitive control. Psychological Review, 108(3), 624–​652. https://​pub​med.
ncbi.nlm.nih.gov/​11488​380/​
Brazier, M. A. B. & Casby, J. U. (1952). Cross-​correlation and autocorrelation studies of
electroencephalographic potentials. Electroencephalography and Clinical Neurophysiology,
4, 201–​211.
Buzsáki, G. (2006). Rhythms of the brain. Oxford University Press.
Buzsáki, G. (2010). Neural syntax: Cell assemblies, synapsembles, and readers. Neuron, 68(3),
362–​385. https://​doi.org/​10.1016/​j.neu​ron.2010.09.023
Buzsáki, G. & Draguhn, A. (2004). Neuronal oscillations in cortical networks. Science,
304(5679), 1926–​1929. https://​doi.org/​10.1126/​scie​nce.1099​745 304/​5679/​1926
Buzzell, G. A., Barker, T. V, Troller-​Renfree, S. V, Bernat, E. M., Bowers, M. E., Morales,
S., . . . Fox, N. A. (2018). Adolescent cognitive control, theta oscillations, and social motiv-
ation. BioRxiv [online], 366831. https://​doi.org/​10.1101/​366​831
Canolty, R. T., Edwards, E., Dalal, S. S., Soltani, M., Nagarajan, S. S., Kirsch, H. E., . . . Knight,
R. T. (2006). High gamma power is phase-​locked to theta oscillations in human neocortex.
Science, 313(5793), 1626–​1628. https://​doi.org/​10.1126/​scie​nce.1128​115
Canolty, R. T. & Knight, R. T. (2010). The functional role of cross-​frequency coupling. Trends in
Cognitive Sciences, 14(11), 506–​515. https://​doi.org/​10.1016/​j.tics.2010.09.001
Caplan, J. B., Madsen, J. R., Schulze-​Bonhage, A., Aschenbrenner-​Scheibe, R., Newman, E. L.,
& Kahana, M. J. (2003). Human theta oscillations related to sensorimotor integration and
spatial learning. Journal of Neuroscience, 23(11), 4726–​4736. https://​doi.org/​23/​11/​4726
Cavanagh, J. F., Bismark, A. W., Frank, M. J., & Allen, J. J. B. (2018). Multiple dissociations between
comorbid depression and anxiety on reward and punishment processing: Evidence from com-
putationally informed EEG. Computational Psychiatry, 3, 1–​17. doi: 10.1162/​cpsy_​a_​00024.
Cavanagh, J. F., Cohen, M. X., & Allen, J. J. B. (2009). Prelude to and resolution of an error: EEG
phase synchrony reveals cognitive control dynamics during action monitoring. The Journal
of Neuroscience, 29(1), 98–​105. https://​doi.org/​10.1523/​JNEURO​SCI.4137-​08.2009
190    JAMES F. CAVANAGH and MICHAEL X COHEN

Cavanagh, J. F. & Frank, M. J. (2014). Frontal theta as a mechanism for cognitive control. Trends
in Cognitive Sciences, 18(8), 1–​8. https://​doi.org/​10.1016/​j.tics.2014.04.012
Cavanagh, J. F., Frank, M. J., Klein, T. J., & Allen, J. J. B. (2010). Frontal theta links prediction
errors to behavioral adaptation in reinforcement learning. NeuroImage, 49(4), 3198–​3209.
https://​doi.org/​10.1016/​j.neu​roim​age.2009.11.080
Cavanagh, J. F., Kumar, P., Mueller, A. A., Pirio Richardson, S., Mueen, A., & Richardson, S. P.
(2018). Diminished EEG habituation to novel events effectively classifies Parkinson’s patients.
Clinical Neurophysiology, 129(2), 409–​418. https://​doi.org/​10.1016/​j.cli​nph.2017.11.023
Cavanagh, J. F., Meyer, A., & Hajcak, G. (2017). Error-​specific cognitive control alterations
in generalized anxiety disorder. Biological Psychiatry: Cognitive Neuroscience and
Neuroimaging, 2(5), 413–​420. https://​doi.org/​10.1016/​j.bpsc.2017.01.004
Cavanagh, J. F., Rieger, R. E., Wilson, J. K., Gill, D., Fullerton, L., Brandt, E., & Mayer, A. R.
(2020). Joint analysis of frontal theta synchrony and white matter following mild traumatic
brain injury. Brain Imaging and Behavior, 14(6), 2210–​2223.
Cavanagh, J. F., & Shackman, A. J. (2014). Frontal midline theta reflects anxiety and cogni-
tive control: Meta-​analytic evidence. Journal of Physiology, 109(1–​3), 3–​15. https://​doi.org/​
10.1016/​j.jph​yspa​ris.2014.04.003
Cavanagh, J. F., Zambrano-​Vazquez, L., & Allen, J. J. B. (2012). Theta lingua franca: A common
mid-​frontal substrate for action monitoring processes. Psychophysiology, 49(2), 220–​238.
https://​doi.org/​10.1111/​j.1469-​8986.2011.01293.x
Choi, J. W., Lee, J. K., Ko, D., Lee, G. T., Jung, K. Y., & Kim, K. H. (2013). Fronto-​temporal
interactions in the theta-​band during auditory deviant processing. Neuroscience Letters, 548,
120–​125. https://​doi.org/​10.1016/​j.neu​let.2013.05.079
Cohen, M. X. (2014). A neural microcircuit for cognitive conflict detection and signaling.
Trends in Neurosciences, 37(9), 480–​490. https://​doi.org/​10.1016/​j.tins.2014.06.004
Cohen, M. X. (2016). Midfrontal theta tracks action monitoring over multiple interactive time
scales. NeuroImage, 141, 262–​272. https://​doi.org/​10.1016/​J.NEU​ROIM​AGE.2016.07.054
Cohen, M. X. & Cavanagh, J. F. (2011). Single-​trial regression elucidates the role of prefrontal
theta oscillations in response conflict. Frontiers in Psychology [online], 2, 30. https://​doi.org/​
10.3389/​fpsyg.2011.00030
Cohen, M. X. & Donner, T. H. (2013). Midfrontal conflict-​related theta-​band power reflects
neural oscillations that predict behavior. Journal of Neurophysiology, 110(12), 2752–​2763.
https://​doi.org/​10.1152/​jn.00479.2013
Cohen, M. X. & Ridderinkhof, K. R. (2013). EEG source reconstruction reveals frontal-​parietal
dynamics of spatial conflict processing. PLoS One, 8(2), e57293. https://​doi.org/​10.1371/​jour​
nal.pone.0057​293
Cohen, M. X., Ridderinkhof, K. R., Haupt, S., Elger, C. E., & Fell, J. (2008). Medial frontal cortex
and response conflict: Evidence from human intracranial EEG and medial frontal cortex
lesion. Brain Research, 1238, 127–​142. https://​doi.org/​S0006-​8993(08)01872-​6 [pii]10.1016/​
j.brainres.2008.07.114
Cohen, M. X, & van Gaal, S. (2013). Dynamic interactions between large-​scale brain networks
predict behavioral adaptation after perceptual errors. Cerebral Cortex (New York, N.Y.: 1991),
23(5), 1061–​1072. https://​doi.org/​10.1093/​cer​cor/​bhs​069
Cohen, M. X, & van Gaal, S. (2014). Subthreshold muscle twitches dissociate oscillatory neural
signatures of conflicts from errors. NeuroImage, 86, 503–​513. https://​doi.org/​10.1016/​J.NEU​
ROIM​AGE.2013.10.033
 FRONTAL MIDLINE THETA AS A MODEL SPECIMEN OF CORTICAL THETA    191

Cohen, M. X, van Gaal, S., Ridderinkhof, K. R., & Lamme, V. A. F. (2009). Unconscious errors
enhance prefrontal-​occipital oscillatory synchrony. Frontiers in Human Neuroscience, 3, 54.
https://​doi.org/​10.3389/​neuro.09.054.2009
Coles, M. G., Scheffers, M. K., & Holroyd, C. B. (2001). Why is there an ERN/​Ne on correct trials?
Response representations, stimulus-​related components, and the theory of error-​processing.
Biological Psychology, 56(3), 173–​189. https://​doi.org/​10.1016/​S0301-​0511(01)00076-​X
Colgin, L. L. (2013). Mechanisms and functions of theta rhythms. Annual Review of
Neuroscience, 36(1), 295–​312. https://​doi.org/​10.1146/​annu​rev-​neuro-​062​012-​170​330
Debener, S., Ullsperger, M., Siegel, M., Fiehler, K., von Cramon, D. Y., & Engel, A. K. (2005).
Trial-​by-​trial coupling of concurrent electroencephalogram and functional magnetic reson-
ance imaging identifies the dynamics of performance monitoring. Journal of Neuroscience,
25(50), 11730–​11737. https://​doi.org/​25/​50/​11730 [pii]10.1523/​JNEUROSCI.3286-​05.2005
Dehaene, S., Posner, M. I., & Tucker, D. M. (1994). Localization of a neural system for error de-
tection and compensation. Psychological Science, 5(5),303–​305.
Edwards, B. G., Calhoun, V. D., & Kiehl, K. A. (2012). Joint ICA of ERP and fMRI during
error-​monitoring. NeuroImage, 59(2), 1896–​1903. https://​doi.org/​10.1016/​j.neu​roim​
age.2011.08.088
Emeric, E. E., Leslie, M. W., Pouget, P., & Schall, J. D. (2010). Performance monitoring local
field potentials in the medial frontal cortex of primates: Supplementary eye field. Journal of
Neurophysiology, 104, 1523–​1537. https://​doi.org/​jn.01001.2009
Escera, C. & Malmierca, M. S. (2014). The auditory novelty system: An attempt to integrate
human and animal research. Psychophysiology, 51(2), 111–​123. https://​doi.org/​10.1111/​
psyp.12156
Falkenstein, M., Hohnsbein, J., Hoormann, J., & Blanke, L. (1991). Effects of crossmodal
divided attention on late ERP components. II. Error processing in choice reaction tasks.
Electroencephalography and Clinical Neurophysiology, 78(6), 447–​455. https://​pub​med.ncbi.
nlm.nih.gov/​1712​280/​
Featherstone, R. E., Melnychenko, O., & Siegel, S. J. (2018). Mismatch negativity in preclinical
models of schizophrenia. Schizophrenia Research, 191, 35–​42. https://​doi.org/​10.1016/​j.sch​
res.2017.07.039
Folstein, J. R. & Van Petten, C. (2008). Influence of cognitive control and mismatch on the N2
component of the ERP: a review. Psychophysiology, 45(1), 152–​170. https://​doi.org/​PSYP​602
[pii]10.1111/​j.1469-​8986.2007.00602.x
Fries, P. (2005). A mechanism for cognitive dynamics: neuronal communication through
neuronal coherence. Trends in Cognitive Science, 9(10), 474–​480. https://​doi.org/​S1364-​
6613(05)00242-​1 [pii]10.1016/​j.tics.2005.08.011
Fries, P. (2015). Rhythms for cognition: Communication through coherence. Neuron, 88(1),
220–​235. https://​doi.org/​10.1016/​j.neu​ron.2015.09.034
Fuentemilla, L., Marco-​Pallarés, J., Münte, T. F., & Grau, C. (2008). Theta EEG oscillatory ac-
tivity and auditory change detection. Brain Research, 1220, 93–​101. https://​doi.org/​10.1016/​
j.brain​res.2007.07.079
Fujisawa, S. & Buzsáki, G. (2011). A 4 Hz oscillation adaptively synchronizes prefrontal,
VTA, and hippocampal activities. Neuron, 72(1), 153–​165. https://​doi.org/​10.1016/​j.neu​
ron.2011.08.018
Fukai, T. (1999). Sequence generation in arbitrary temporal patterns from theta-​nested gamma
oscillations: A model of the basal ganglia-​thalamo-​cortical loops. Neural Networks, 12(7–​8),
975–​987. https://​pub​med.ncbi.nlm.nih.gov/​12662​640/​
192    JAMES F. CAVANAGH and MICHAEL X COHEN

Gehring, W. J., Goss, B., Coles, M. G. H., Meyer, D. E., & Donchin, E. (1993). A neural system
for error-​detection and compensation. Psychological Science, 4(6), 385–​390.
Gehring, W. J., Himle, J., & Nisenson, L. G. (2000). Action-​monitoring dysfunction in
obsessive-​compulsive disorder. Psychological Science, 11(1), 1–​6. https://​pub​med.ncbi.nlm.
nih.gov/​11228​836/​
Gehring, W. J., Liu, Y., Orr, J. M., & Carp, J. (2012). The error-​related negativity (ERN/​Ne). In S.
J. Luck & E. Kappenman (Eds.), Oxford handbook of event-​related potential components (pp.
231–​291). Oxford University Press.
Gehring, W. J. & Willoughby, A. R. (2002). The medial frontal cortex and the rapid processing
of monetary gains and losses. Science, 295(5563), 2279–​2282. https://​doi.org/​10.1126/​scie​
nce.106​6893​295/​5563/​2279
Gemba, H., Sasaki, K., & Brooks, V. B. (1986). “Error” potentials in limbic cortex (anterior
cingulate area 24) of monkeys during motor learning. Neuroscience Letters, 70(2), 223–​227.
https://​doi.org/​0304-​3940(86)90467-​2
Gevins, A. & Smith, M. E. (2000). Neurophysiological measures of working memory and in-
dividual differences in cognitive ability and cognitive style. Cerebral Cortex, 10(9), 829–​839.
https://​pub​med.ncbi.nlm.nih.gov/​10982​744/​
Gevins, A., Smith, M. E., McEvoy, L. K., Leong, H., & Le, J. (1999). Electroencephalographic
imaging of higher brain function. Philosophical Transactions of the Royal Society of London
Series B: Biological Sciences, 354(1387), 1125–​1133. https://​doi.org/​10.1098/​rstb.1999.0468
Gevins, A., Smith, M. E., McEvoy, L., & Yu, D. (1997). High-​resolution EEG mapping of cor-
tical activation related to working memory: Effects of task difficulty, type of processing, and
practice. Cerebral Cortex, 7(4), 374–​385. https://​pub​med.ncbi.nlm.nih.gov/​9177​767/​
Gilmore, C. S., Malone, S. M., & Iacono, W. G. (2010). Brain electrophysiological
endophenotypes for externalizing psychopathology: A multivariate approach. Behavior
Genetics, 40(2), 186–​200. https://​doi.org/​10.1007/​s10​519-​010-​9343-​3
Giraud, A.-​L. L., Kleinschmidt, A., Poeppel, D., Lund, T. E., Frackowiak, R. S. J. J., & Laufs,
H. (2007). Endogenous cortical rhythms determine cerebral specialization for speech
perception and production. Neuron, 56(6), 1127–​1134. https://​doi.org/​10.1016/​j.neu​
ron.2007.09.038
Giraud, A.-​L. L., & Poeppel, D. (2012). Cortical oscillations and speech processing: emerging
computational principles and operations. Nature Neuroscience, 15(4), 511–​517. https://​doi.
org/​10.1038/​nn.3063
Godlove, D. C., Emeric, E. E., Segovis, C. M., Young, M. S., Schall, J. D., & Woodman, G. F.
(2011). Event-​related potentials elicited by errors during the stop-​signal task. I. Macaque
monkeys. The Journal of Neuroscience, 31(44), 15640–​15649. https://​doi.org/​10.1523/​JNEURO​
SCI.3349-​11.2011
Gorka, S. M., Burkhouse, K. L., Klumpp, H., Kennedy, A. E., Afshar, K., Francis, J., . . . Phan,
K. L. (2018). Error-​related brain activity as a treatment moderator and index of symptom
change during cognitive-​behavioral therapy or selective serotonin reuptake inhibitors.
Neuropsychopharmacology, 43(6), 1355–​1363. https://​doi.org/​10.1038/​npp.2017.289
Gratton, G. (2018). Brain reflections: A circuit-​based framework for understanding informa-
tion processing and cognitive control. Psychophysiology, 55(3), 1–​26. https://​doi.org/​10.1111/​
psyp.13038
Gruber, W. R., Klimesch, W., Sauseng, P., & Doppelmayr, M. (2005). Alpha phase synchroniza-
tion predicts P1 and N1 latency and amplitude size. Cerebral Cortex, 15(4), 371–​377. https://​
doi.org/​10.1093/​cer​cor/​bhh​139
 FRONTAL MIDLINE THETA AS A MODEL SPECIMEN OF CORTICAL THETA    193

Gruendler, T. O. J., Ullsperger, M., & Huster, R. J. (2011). Event-​related potential correlates
of performance-​monitoring in a lateralized time-​estimation task. PloS One, 6(10), e25591.
https://​doi.org/​10.1371/​jour​nal.pone.0025​591
Hajcak, G., Moser, J. S., Yeung, N., & Simons, R. F. (2005). On the ERN and the significance of
errors. Psychophysiology, 42(2), 151–​160.
Hanslmayr, S., Pastotter, B., Bauml, K. H., Gruber, S., Wimber, M., & Klimesch, W. (2008). The
electrophysiological dynamics of interference during the Stroop task. Journal of Cognitive
Neuroscience, 20(2), 215–​225. https://​doi.org/​10.1162/​jocn.2008.20020
Hanslmayr, S., Staudigl, T., Aslan, A., & Bauml, K. H. (2010). Theta oscillations predict the
detrimental effects of memory retrieval. Cognitive, Affective, and Behavioral Neuroscience,
10(3), 329–​338. doi: 10.3758/​cabn.10.3.329
Hauser, T. U., Iannaccone, R., Stämpfli, P., Drechsler, R., Brandeis, D., Walitza, S., & Brem, S.
(2014). The feedback-​related negativity (FRN) revisited: New insights into the localization,
meaning and network organization. NeuroImage, 84, 159–​168. https://​doi.org/​10.1016/​j.neu​
roim​age.2013.08.028
Helfrich, R. F., Fiebelkorn, I. C., Szczepanski, S. M., Lin, J. J., Parvizi, J., Knight, R. T., & Kastner,
S. (2018). Neural mechanisms of sustained attention are rhythmic. Neuron, 99(4), 854–​865.
e5. https://​doi.org/​10.1016/​j.neu​ron.2018.07.032
Holroyd, C. B. (2002). A note on the oddball N200 and the feedback ERN. In M. Ullsperger
& M. Falkenstein (Eds.), Errors, conflicts and the brain. Current opinions on performance
monitoring (pp. 211–​218). Max Planck Institute for Human Cognitive and Brain Sciences.
Holroyd, C. B. & Coles, M. G. (2002). The neural basis of human error processing: reinforce-
ment learning, dopamine, and the error-​related negativity. Psychological Review, 109(4),
679–​709. https://​pub​med.ncbi.nlm.nih.gov/​12374​324/​
Holroyd, C. B., Coles, M. G. H., Nieuwenhuis, S., Gehring, W. J., & Willoughby, A. R. (2002).
Medial prefrontal cortex and error potentials. Science, 296(5573), 1610–​1611.
Hsieh, L.-​T., Ekstrom, A. D., & Ranganath, C. (2011). Neural oscillations associated with item
and temporal order maintenance in working memory. The Journal of Neuroscience, 31(30),
10803–​10810. https://​doi.org/​10.1523/​JNEURO​SCI.0828-​11.2011
Hsieh, L. T. & Ranganath, C. (2014). Frontal midline theta oscillations during working memory
maintenance and episodic encoding and retrieval. NeuroImage, 85, 721–​729. https://​doi.org/​
10.1016/​j.neu​roim​age.2013.08.003
Huang, Y., Chen, L., & Luo, H. (2015). Behavioral oscillation in priming: Competing percep-
tual predictions conveyed in alternating theta-​band rhythms. Journal of Neuroscience, 35(6),
2830–​2837. https://​doi.org/​10.1523/​JNEURO​SCI.4294-​14.2015
Huster, R. J., Eichele, T., Enriquez-​Geppert, S., Wollbrink, A, Kugel, H., Konrad, C., & Pantev, C.
(2011). Multimodal imaging of functional networks and event-​related potentials in performance
monitoring. NeuroImage, 56(3), 1588–​1597. https://​doi.org/​10.1016/​j.neu​roim​age.2011.03.039
Hyman, J. M., Hasselmo, M. E., & Seamans, J. K. (2011). What is the functional relevance of pre-
frontal cortex entrainment to hippocampal theta rhythms? Frontiers in Neuroscience, 5, 1–​13.
https://​doi.org/​10.3389/​fnins.2011.00024
Inouye, T., Shinosaki, K., Iyama, A., Matsumoto, Y., & Toi, S. (1994). Moving potential field of
frontal midline theta activity during a mental task. Cognitive Brain Research, 2, 87–​92.
Inouye, T., Shinosaki, K., Iyama, A., Matsumoto, Y., Toi, S., & Ishihar, T. (1994). Potential flow
of frontal midline theta activity during a mental task in the human electroencephalogram.
Neuroscience Letters, 169, 145–​148.
194    JAMES F. CAVANAGH and MICHAEL X COHEN

Insel, T., Cuthbert, B., Garvey, M., Heinssen, R., Pine, D. S., Quinn, K., . . . Wang, P. (2010).
Research domain criteria (RDoC): Toward a new classification framework for research on
mental disorders. American Journal of Psychiatry, 167(7), 748–​751. https://​doi.org/​167/​7/​748
[pii]10.1176/​appi.ajp.2010.09091379
Ishii, R., Shinosaki, K., Ukai, S., Inouye, T., Ishihara, T., Yoshimine, T., . . . Takeda, M. (1999).
Medial prefrontal cortex generates frontal midline theta rhythm. Neuroreport, 10(4), 675–​
679. https://​pub​med.ncbi.nlm.nih.gov/​10208​529/​
Itthipuripat, S., Wessel, J. R., & Aron, A. R. (2013). Frontal theta is a signature of successful
working memory manipulation. Experimental Brain Research, 224(2), 255–​262. https://​doi.
org/​10.1007/​s00​221-​012-​3305-​3
Jacobs, J., Hwang, G., Curran, T., & Kahana, M. J. (2006). EEG oscillations and recognition
memory: Theta correlates of memory retrieval and decision making. NeuroImage, 32(2),
978–​987. https://​pub​med.ncbi.nlm.nih.gov/​16843​012/​
Javitt, D. C., Lee, M., Kantrowitz, J. T., & Martinez, A. (2018). Mismatch negativity as a bio-
marker of theta band oscillatory dysfunction in schizophrenia. Schizophrenia Research, 191,
51–​60. https://​doi.org/​10.1016/​j.sch​res.2017.06.023
Jensen, O. & Tesche, C. D. (2002). Frontal theta activity in humans increases with memory load
in a working memory task. European Journal of Neuroscience, 15(8), 1395–​1399. https://​pub​
med.ncbi.nlm.nih.gov/​11994​134/​
Jensen, O. & Colgin, L. L. (2007). Cross-​frequency coupling between neuronal oscillations.
Trends in Cognitive Sciences, 11(7), 267–​269. https://​doi.org/​10.1016/​j.tics.2007.05.003
Jensen, O. & Lisman, J. E. (2005). Hippocampal sequence-​encoding driven by a cortical multi-​
item working memory buffer. Trends in Neurosciences, 28(2), 67–​72. https://​doi.org/​10.1016/​
j.tins.2004.12.001
Jocham, G. & Ullsperger, M. (2009). Neuropharmacology of performance monitoring. Neuroscience
and Biobehavioral Reviews, 33(1), 48–​60. https://​pub​med.ncbi.nlm.nih.gov/​18789​964/​
Jones, M. W. & Wilson, M. A. (2005a). Phase precession of medial prefrontal cortical activity
relative to the hippocampal theta rhythm. Hippocampus, 15(7), 867–​873. https://​doi.org/​
10.1002/​hipo.20119
Jones, M. W. & Wilson, M. A. (2005b). Theta rhythms coordinate hippocampal-​prefrontal
interactions in a spatial memory task. PLoS Biology, 3(12), e402. https://​doi.org/​10.1371/​jour​
nal.pbio.0030​402
Jutras, M. J., Fries, P., & Buffalo, E. A. (2013). Oscillatory activity in the monkey hippocampus
during visual exploration and memory formation. Proceedings of the National Academy of
Sciences of the United States of America, 110(32), 13144–​13149.
Kahana, M. J., Sekuler, R., Caplan, J. B., Kirschen, M., & Madsen, J. R. (1999). Human theta
oscillations exhibit task dependence during virtual maze navigation. Nature, 399(6738), 781–​
784. https://​doi.org/​10.1038/​21645
Kamarajan, C., Pandey, A. K., Chorlian, D. B., Manz, N., Stimus, A. T., Anokhin, A.
P., . . . Porjesz, B. (2015). Deficient event-​related theta oscillations in individuals at risk for
alcoholism: A study of reward processing and impulsivity features. PLoS One, 10(11), 1–​32.
https://​doi.org/​10.1371/​jour​nal.pone.0142​659
Kang, S. J., Rangaswamy, M., Manz, N., Wang, J. C., Wetherill, L., Hinrichs, T., . . . Porjesz, B.
(2012). Family-​based genome-​wide association study of frontal theta oscillations identifies
potassium channel gene KCNJ6. Genes, Brain and Behavior, 11(6), 712–​7 19. https://​doi.org/​
10.1111/​j.1601-​183X.2012.00803.x
 FRONTAL MIDLINE THETA AS A MODEL SPECIMEN OF CORTICAL THETA    195

Killian, N. J., Jutras, M. J., & Buffalo, E. A. (2012). A map of visual space in the primate
entorhinal cortex. Nature, 491(7426), 761–​764. https://​doi.org/​10.1038/​natu​re11​587
Klimesch, W. (1999). EEG alpha and theta oscillations reflect cognitive and memory per-
formance: a review and analysis. Brain Research: Brain Research Reviews, 29(2–​3), 169–​195.
https://​pub​med.ncbi.nlm.nih.gov/​10209​231/​
Klimesch, W., Doppelmayr, M., Schwaiger, J., Winkler, T., & Gruber, W. (2000). Theta
oscillations and the ERP old/​new effect: Independent phenomena? Clinical Neurophysiology,
111(5), 781–​793.
Ko, D., Kwon, S., Lee, G. T., Im, C. H., Kim, K. H., & Jung, K. Y. (2012). Theta oscillation related
to the auditory discrimination process in mismatch negativity: Oddball versus control para-
digm. Journal of Clinical Neurology (Korea), 8(1), 35–​42. https://​doi.org/​10.3988/​jcn.2012.8.1.35
Lee, H., Simpson, G. V., Logothetis, N. K., & Rainer, G. (2005). Phase locking of single neuron
activity to theta oscillations during working memory in monkey extrastriate visual cortex.
Neuron, 45(1), 147–​156. https://​doi.org/​10.1016/​j.neu​ron.2004.12.025
Lee, M., Balla, A., Sershen, H., Sehatpour, P., Lakatos, P., & Javitt, D. C. (2018). Rodent
mismatch negativity/​theta neuro-​oscillatory response as a translational neurophysio-
logical biomarker for N-​methyl-​D-​aspartate receptor-​based new treatment development
in schizophrenia. Neuropsychopharmacology, 43(3), 571–​582. https://​doi.org/​10.1038/​
npp.2017.176
Liebe, S., Hoerzer, G. M., Logothetis, N. K., & Rainer, G. (2012). Theta coupling between V4 and
prefrontal cortex predicts visual short-​term memory performance. Nature Neuroscience,
15(3), 456–​462, S1-​2. https://​doi.org/​10.1038/​nn.3038
Light, G. A., Swerdlow, N. R., Thomas, M. L., Calkins, M. E., Green, M. F., Greenwood, T.
A., . . . Turetsky, B. I. (2015). Validation of mismatch negativity and P3a for use in multi-​
site studies of schizophrenia: Characterization of demographic, clinical, cognitive, and
functional correlates in COGS-​2. Schizophrenia Research, 163(1–​3), 63–​72. https://​doi.org/​
10.1016/​j.sch​res.2014.09.042
Lubenov, E. V. & Siapas, A. G. (2009). Hippocampal theta oscillations are travelling waves.
Nature, 459(7246), 534–​539. https://​doi.org/​10.1038/​natu​re08​010
Luschei, E. S. (2006). Patterns of laryngeal electromyography and the activity of the respiratory
system during spontaneous laughter. Journal of Neurophysiology, 96(1), 442–​450. https://​doi.
org/​10.1152/​jn.00102.2006
Luu, P. & Tucker, D. M. (2001). Regulating action: Alternating activation of midline frontal and
motor cortical networks. Clinical Neurophysiology, 112(7), 1295–​1306. https://​doi.org/​S1388-​
2457(01)00559-​4 [pii]
Luu, P., Tucker, D. M., & Makeig, S. (2004). Frontal midline theta and the error-​related nega-
tivity: Neurophysiological mechanisms of action regulation. Clinical Neurophysiology,
115(8), 1821–​1835. https://​doi.org/​10.1016/​j.cli​nph.2004.03.031S1​3882​4570​4001​294 [pii]
MacNeilage, P. F. & Davis, B. L. (2001). Motor mechanisms in speech ontogeny: Phylogenetic,
neurobiological and linguistic implications. Current Opinion in Neurobiology, 11(6), 696–​
700. https://​doi.org/​10.1016/​S0959-​4388(01)00271-​9
Macrides, F., Eichenbaum, H., & Forbes, W. B. (1982). Temporal relationship between sniffing
and the limbic theta rhythm during odor discrimination reversal learning. Journal of
Neuroscience, 2(12), 1705–​1717.
Miltner, W. H. R., Braun, C. H., & Coles, M. G. H. (1997). Event-​related brain potentials
following incorrect feedback in a time-​estimation task: Evidence for a “generic” neural
system for error detection. Journal of Cognitive Neuroscience, 9(6), 788–​798.
196    JAMES F. CAVANAGH and MICHAEL X COHEN

Mitchell, D. J., McNaughton, N., Flanagan, D., & Kirk, I. J. (2008). Frontal-​midline theta from
the perspective of hippocampal “theta”. Progress in Neurobiology, 86(3), 156–​185. https://​doi.
org/​10.1016/​j.pneuro​bio.2008.09.005
Mizuki, Y., Kajimura, N., Kai, S., Suetsugi, M., Ushijima, I., & Yamada, M. (1992). Differential
responses to mental stress in high and low anxious normal humans assessed by frontal mid-
line theta activity. International Journal of Psychophysiology, 12, 169–​178.
Mizuki, Y., Suetsugi, M., Ushijima, I., & Yamada, M. (1996). Differential effects of noradrenergic
drugs on anxiety and arousal in healthy volunteers with high and low anxiety. Progress in
Neuro-​Psychopharmacology & Biological Psychiatry, 20(8), 1353–​1367.
Mizuki, Y, Suetsugi, M., Ushijima, I., & Yamada, M. (1997). Differential effects of dopamin-
ergic drugs on anxiety and arousal in healthy volunteers with high and low anxiety. Progress
in Neuro-​Psychopharmacology & Biological Psychiatry, 21(4), 573–​590. http://​www.ncbi.nlm.
nih.gov/​pub​med/​9194​141
Moran, T. P., Bernat, E. M., Aviyente, S., Schroder, H. S., & Moser, J. S. (2014). Sending mixed
signals: Worry is associated with enhanced initial error processing but reduced call for sub-
sequent cognitive control. Social Cognitive and Affective Neuroscience, 10(11), 1548–​1556.
https://​doi.org/​10.1093/​scan/​nsv​046
Moser, J. S., Moran, T. P., Schroder, H. S., Donnellan, M. B., & Yeung, N. (2013). On the relation-
ship between anxiety and error monitoring: A meta-​analysis and conceptual framework.
Frontiers in Human Neuroscience, 7, 466. https://​doi.org/​10.3389/​fnhum.2013.00466
Munneke, G.-​J., Nap, T. S., Schippers, E. E., & Cohen, M. X. (2015). A statistical comparison of
EEG time-​and time–​frequency domain representations of error processing. Brain Research,
1618, 222–​230. https://​doi.org/​10.1016/​j.brain​res.2015.05.030
Narayanan, N. S., Cavanagh, J. F., Frank, M. J., & Laubach, M. (2013). Common medial frontal
mechanisms of adaptive control in humans and rodents. Nature Neuroscience, 16, 1–​10.
https://​doi.org/​10.1038/​nn.3549
Nigbur, R., Cohen, M. X., Ridderinkhof, K. R., & Stürmer, B. (2012). Theta dynamics re-
veal domain-​specific control over stimulus and response conflict. Journal of Cognitive
Neuroscience, 24(5), 1264–​1274.
Nyhus, E., & Curran, T. (2010). Functional role of gamma and theta oscillations in episodic
memory. Neuroscience and Biobehavioral Reviews, 34(7), 1023–​1035. https://​doi.org/​10.1016/​
j.neubio​rev.2009.12.014
Oehrn, C. R., Hanslmayr, S., Fell, J., Deuker, L., Kremers, N. A., Do Lam, A. T., . . . Axmacher,
N. (2014). Neural communication patterns underlying conflict detection, resolution, and
adaptation. Journal of Neuroscience, 34(31), 10438–​10452. https://​doi.org/​10.1523/​JNEURO​
SCI.3099-​13.2014
Onton, J., Delorme, A., & Makeig, S. (2005). Frontal midline EEG dynamics during working
memory. NeuroImage, 27(2), 341–​356. https://​pub​med.ncbi.nlm.nih.gov/​15927​487/​
Pailing, P. E. & Segalowitz, S. J. (2004). The effects of uncertainty in error monitoring on
associated ERPs. Brain and Cognition, 56(2), 215–​233.
Parker, K. L., Chen, K.-​H., Kingyon, J. R., Cavanagh, J. F., & Narayanan, N. S. (2015). Medial
frontal ~4-​Hz activity in humans and rodents is attenuated in PD patients and in rodents
with cortical dopamine depletion. Journal of Neurophysiology, 114(2), 1310–​1320. https://​doi.
org/​10.1152/​jn.00412.2015
Pastötter, B., Hanslmayr, S., & Bauml, K.-​H. T. (2010). Conflict processing in the anterior cin-
gulate cortex constrains response priming. NeuroImage, 50(4), 1599–​1605. https://​doi.org/​
10.1016/​j.neu​roim​age.2010.01.095
 FRONTAL MIDLINE THETA AS A MODEL SPECIMEN OF CORTICAL THETA    197

Paz, R., Bauer, E. P., & Pare, D. (2008). Theta synchronizes the activity of medial prefrontal
neurons during learning. Learning & Memory, 15(7), 524–​531. https://​doi.org/​10.1101/​
lm.932​408
Pellegrino, F., Coupé, C., & Marsico, E. (2011). Across-​language perspective on speech infor-
mation rate. Language, 87(3), 539–​558. https://​doi.org/​10.1353/​lan.2011.0057
Petajan, J. H. & Williams, D. D. (1972). Behavior of single motor units during pre-​shivering
tone and shivering tremor. American Journal of Physical Medicine, 51(1), 16–​22.
Phillips, J. M. & Everling, S. (2014). Event-​related potentials associated with performance
monitoring in non-​human primates. NeuroImage, 97, 308–​320. https://​doi.org/​10.1016/​j.neu​
roim​age.2014.04.028
Phillips, J. M., Vinck, M., Everling, S., & Womelsdorf, T. (2013). A long-​range fronto-​parietal
5-​to 10-​Hz network predicts “top-​down” controlled guidance in a task-​switch paradigm.
Cerebral Cortex, 24(8), 1996–​2008. https://​doi.org/​10.1093/​cer​cor/​bht​050
Pignatelli, M., Beyeler, A., & Leinekugel, X. (2012). Neural circuits underlying the generation
of theta oscillations. Journal of Physiology, 106(3–​4), 81–​92. https://​doi.org/​10.1016/​j.jph​yspa​
ris.2011.09.007
Popov, T., Westner, B. U., Silton, R. L., Sass, S. M., Spielberg, J. M., Rockstroh, B., . . . Miller, G.
A. (2018). Time course of brain network reconfiguration supporting inhibitory control. The
Journal of Neuroscience, 38(18), 2639–​17. https://​doi.org/​10.1523/​JNEURO​SCI.2639-​17.2018
Raghavachari, S., Lisman, J. E., Tully, M., Madsen, J. R., Bromfield, E. B., & Kahana, M. J.
(2006). Theta oscillations in human cortex during a working-​memory task: Evidence
for local generators. Journal of Neurophysiology, 95(3), 1630–​1638. doi: 10.1152/​
jn.00409.2005
Rajan, A., Siegel, S. N., Liu, Y., Bengson, J., Mangun, G. R., & Ding, M. (2018). Theta oscillations
index frontal decision-​making and mediate reciprocal frontal–​parietal interactions in
willed attention. Cerebral Cortex, 29(7), 2832–​2843 . https://​doi.org/​10.1093/​cer​cor/​bhy​149
Rangaswamy, M., Jones, K. A., Porjesz, B., Chorlian, D. B., Padmanabhapillai, A., Kamarajan,
C., . . . Begleiter, H. (2007). Delta and theta oscillations as risk markers in adolescent off-
spring of alcoholics. International Journal of Psychophysiology, 63(1), 3–​15. https://​doi.org/​
10.1016/​j.ijpsy​cho.2006.10.003
Reinhart, R. M. G. & Woodman, G. F. (2014). Causal control of medial-​frontal cortex governs
electrophysiological and behavioral indices of performance monitoring and learning.
Journal of Neuroscience, 34(12), 4214–​4227. https://​doi.org/​10.1523/​JNEURO​SCI.5421-​13.2014
Reinhart, R. M. G. (2017). Disruption and rescue of interareal theta phase coupling and
adaptive behavior. Proceedings of the National Academy of Sciences of the United States of
America, 114(43), 11542–​11547. https://​doi.org/​10.1073/​pnas.171​0257​114
Reinhart, R. M. G., Zhu, J., Park, S., & Woodman, G. F. (2015). Synchronizing theta oscillations
with direct-​ current stimulation strengthens adaptive control in the human brain.
Proceedings of the National Academy of Sciences of the United States of America, 112(30),
9448–​9453. https://​doi.org/​10.1073/​pnas.150​4196​112
Riesel, A., Goldhahn, S., & Kathmann, N. (2017). Hyperactive performance monitoring
as a transdiagnostic marker: Results from health anxiety in comparison to obsessive–​
compulsive disorder. Neuropsychologia, 96, 1–​8. https://​doi.org/​10.1016/​j.neuro​psyc​holo​
gia.2016.12.029
Rizzuto, D. S., Madsen, J. R., Bromfield, E. B., Schulze-​Bonhage, A., & Kahana, M. J. (2006).
Human neocortical oscillations exhibit theta phase differences between encoding and re-
trieval. NeuroImage, 31(3), 1352–​1358. doi: 10.1016/​j.neuroimage.2006.01.009
198    JAMES F. CAVANAGH and MICHAEL X COHEN

Rizzuto, D. S., Madsen, J. R., Bromfield, E. B., Schulze-​Bonhage, A., Seelig, D., Aschenbrenner-​
Scheibe, R., & Kahana, M. J. (2003). Reset of human neocortical oscillations during a
working memory task. Proceedings of the National Academy of Sciences of the United States of
America, 100(13), 7931–​7936. https://​doi.org/​10.1073/​pnas.07320​6110​0073​2061​100 [pii]
Roberts, B. M., Hsieh, L. T., & Ranganath, C. (2013). Oscillatory activity during maintenance
of spatial and temporal information in working memory. Neuropsychologia, 51(2), 349–​357.
https://​doi.org/​10.1016/​j.neuro​psyc​holo​gia.2012.10.009
Rothé, M., Quilodran, R., Sallet, J., & Procyk, E. (2011). Coordination of high gamma activity
in anterior cingulate and lateral prefrontal cortical areas during adaptation. The Journal of
Neuroscience, 31(31), 11110–​11117. https://​doi.org/​10.1523/​JNEURO​SCI.1016-​11.2011
Ryman, S. G., Cavanagh, J. F., Wertz, C. J., Shaff, N. A., Dodd, A. B., Stevens, B., . . . Mayer, A.
R. (2018). Impaired midline theta power and connectivity during proactive cognitive con-
trol in schizophrenia. Biological Psychiatry, 84(9), 675–​683. https://​doi.org/​10.1016/​j.biops​
ych.2018.04.021
Sato, K. (1952). On the theta rhythms in healthy human EEG. Folia Psychiatrica et Neurologica,
5(4), 283–​297.
Sauseng, P., Griesmayr, B., Freunberger, R., & Klimesch, W. (2010). Control mechanisms
in working memory: A possible function of EEG theta oscillations. Neuroscience and
Biobehavioral Reviews, 34(7), 1015–​1022. doi: 10.1016/​j.neubiorev.2009.12.006
Sauseng, P., Klimesch, W., Doppelmayr, M., Hanslmayr, S., Schabus, M., & Gruber, W. R.
(2004). Theta coupling in the human electroencephalogram during a working memory task.
Neuroscience Letters, 354(2), 123–​126. doi: 10.1016/​j.neulet.2003.10.002
Schmidt, B., Kanis, H., Holroyd, C. B., Miltner, W. H. R., & Hewig, J. (2018). Anxious
gambling: Anxiety is associated with higher frontal midline theta predicting less risky
decisions. Psychophysiology, 55(10), 1–​9. https://​doi.org/​10.1111/​psyp.13210
Shackman, A. J., Salomons, T. V, Slagter, H. A, Fox, A. S., Winter, J. J., & Davidson, R. J. (2011).
The integration of negative affect, pain and cognitive control in the cingulate cortex. Nature
Reviews. Neuroscience, 12(3), 154–​167. https://​doi.org/​10.1038/​nrn2​994
Siapas, A. G., Lubenov, E. V, & Wilson, M. A. (2005). Prefrontal phase locking to hippocampal
theta oscillations. Neuron, 46(1), 141–​151. https://​doi.org/​10.1016/​j.neu​ron.2005.02.028
Smit, A. S., Eling, P. A T. M., & Coenen, A. M. L. (2004). Mental effort affects vigilance en-
duringly: after-​effects in EEG and behavior. International Journal of Psychophysiology, 53(3),
239–​243. https://​doi.org/​10.1016/​j.ijpsy​cho.2004.04.005
Smit, A. S., Eling, P. A T. M., Hopman, M. T., & Coenen, A. M. L. (2005). Mental and physical
effort affect vigilance differently. International Journal of Psychophysiology, 57(3), 211–​217.
https://​doi.org/​10.1016/​j.ijpsy​cho.2005.02.001
Smith, E. H., Banks, G. P., Mikell, C. B., Cash, S. S., Patel, S. R., Eskandar, E. N., & Sheth, S. A.
(2015). Frequency-​dependent representation of reinforcement-​related information in the
human medial and lateral prefrontal cortex. Journal of Neuroscience, 35(48), 15827–​15836.
https://​doi.org/​10.1523/​JNEURO​SCI.1864-​15.2015
Solomon, E. A., Kragel, J. E., Sperling, M. R., Sharan, A., Worrell, G., Kucewicz, M., . . . Kahana,
M. J. (2017). Widespread theta synchrony and high-​frequency desynchronization underlies
enhanced cognition. Nature Communications, 8, 1704. https://​doi.org/​10.1038/​s41​
467-​017-​01763-​2
Staudigl, T., Hanslmayr, S., & Bauml, K. H. (2010). Theta oscillations reflect the dynamics of
interference in episodic memory retrieval. Journal of Neuroscience, 30(34), 11356–​11362.
doi:10.1523/​JNEUROSCI.0637-​10.2010
 FRONTAL MIDLINE THETA AS A MODEL SPECIMEN OF CORTICAL THETA    199

Swart, J. C., Frank, M. J., Määttä, J. I., Jensen, O., Cools, R., & den Ouden, H. E. M. (2018).
Frontal network dynamics reflect neurocomputational mechanisms for reducing maladap-
tive biases in motivated action. PLoS Biology [online], 1–​25. https://​doi.org/​10.1371/​jour​nal.
pbio.2005​979
Talairach, J., Bancaud, J., Geier, S., Bordas-​Ferrer, M., Bonis, A., Szikla, G., & Rusu, M.
(1973). The cingulate gyrus and human behaviour. Electroencephalography and Clinical
Neurophysiology, 34(1), 45–​52. doi: 10.1016/​0013-​4694(73)90149-​1
Tang, H., Yu, H. Y., Chou, C. C., Crone, N. E., Madsen, J. R., Anderson, W. S., & Kreiman, G.
(2016). Cascade of neural processing orchestrates cognitive control in human frontal cortex.
ELife, 5, e12352. https://​doi.org/​10.7554/​eLife.12352
Taub, A. H., Perets, R., Kahana, E., & Paz, R. (2018). Oscillations synchronize amygdala-​to-​pre-
frontal primate circuits during aversive learning. Neuron, 97(2), 291–​298.e3. https://​doi.org/​
10.1016/​j.neu​ron.2017.11.042
Töllner, T., Wang, Y., Makeig, S., Müller, H. J., Jung, T.-​P., & Gramann, K. (2017). Two inde-
pendent frontal midline theta oscillations during conflict detection and adaptation in a
Simon-​type manual reaching task. The Journal of Neuroscience, 37(9), 2504–​2515. https://​doi.
org/​10.1523/​JNEURO​SCI.1752-​16.2017
Tóth, B., Kardos, Z., File, B., Boha, R., Stam, C. J., & Molnár, M. (2014). Frontal midline
theta connectivity is related to efficiency of WM maintenance and is affected by aging.
Neurobiology of Learning and Memory, 114, 58–​69. https://​doi.org/​10.1016/​j.nlm.2014.04.009
Trujillo, L. T. & Allen, J. J. (2007). Theta EEG dynamics of the error-​related negativity. Clinical
Neurophysiology, 118(3), 645–​668. doi: 10.1016/​j.clinph.2006.11.009
Tsujimoto, S., Genovesio, A., & Wise, S. P. (2010). Evaluating self-​generated decisions in frontal
pole cortex of monkeys. Nature Neuroscience, 13(1), 120–​126. https://​doi.org/​10.1038/​nn.2453
Tsujimoto, T., Shimazu, H., & Isomura, Y. (2006). Direct recording of theta oscillations in pri-
mate prefrontal and anterior cingulate cortices. Journal of Neurophysiology, 95(5), 2987–​
3000. doi:10.1152/​jn.00730.2005
van de Vijver, I., Cohen, M. X., & Ridderinkhof, K. R. (2014). Aging affects medial but not
anterior frontal learning-​related theta oscillations. Neurobiology of Aging, 35(3), 692–​704.
https://​doi.org/​10.1016/​j.neu​robi​olag​ing.2013.09.006
van de Vijver, I., Ridderinkhof, K. R., & Cohen, M. X. (2011). Frontal oscillatory dynamics
predict feedback learning and action adjustment. Journal of Cognitive Neuroscience, 23(12),
4106–​4121. https://​doi.org/​10.1162/​jocn_​a_​00​110
van Driel, J., Ridderinkhof, K. R., & Cohen, M. X. (2012). Not all errors are alike: Theta and
alpha EEG dynamics relate to differences in error-​processing dynamics. The Journal of
Neuroscience, 32(47), 16795–​16806. https://​doi.org/​10.1523/​JNEURO​SCI.0802-​12.2012
van Noordt, S. J. R. & Segalowitz, S. J. (2012). Performance monitoring and the medial
prefrontal cortex: A review of individual differences and context effects as a window
on self-​regulation. Frontiers in Human Neuroscience, 6, 197. https://​doi.org/​10.3389/​
fnhum.2012.00197
Van Veen, V. & Carter, C. S. (2002). The timing of action-​monitoring processes in the anterior
cingulate cortex. Journal of Cognitive Neuroscience, 14(4), 593–​602. https://​doi.org/​10.1162/​
089892​9026​0045​837
VanRullen, R. (2016). Perceptual cycles. Trends in Cognitive Sciences, 20(10), 723–​735. https://​
doi.org/​10.1016/​j.tics.2016.07.006
Verguts, T. (2017). Binding by random bursts: A computational model of cognitive control.
Journal of Cognitive Neuroscience, 29(6), 1103–​1118. https://​doi.org/​10.1162/​jocn_​a_​01​117
200    JAMES F. CAVANAGH and MICHAEL X COHEN

Vezoli, J. & Procyk, E. (2009). Frontal feedback-​ related potentials in nonhuman pri-
mates: modulation during learning and under haloperidol. Journal of Neuroscience, 29(50),
15675–​15683. doi:10.1523/​JNEUROSCI.4943-​09.2009
Vidal, F., Burle, B., Bonnet, M., Grapperon, J., & Hasbroucq, T. (2003). Error negativity on
correct trials: a reexamination of available data. Biological Psychology, 64(3), 265–​282.
https://​doi.org/​S03010​5110​3000​978
Vidal, F., Hasbroucq, T., Grapperon, J., & Bonnet, M. (2000). Is the “error negativity”
specific to errors? Biological Psychology, 51(2–​3), 109–​128. https://​doi.org/​10.1016/​
S0301-​0511(99)00032-​0
Vissers, M. E., Ridderinkhof, K. R., Cohen, M. X., & Slagter, H. A. (2018). Oscillatory
mechanisms of response conflict elicited by color and motion direction: An individual
differences approach. Journal of Cognitive Neuroscience, 30(4), 468–​481. https://​doi.org/​
10.1162/​jocn_​a_​01​222
Walsh, M. M. & Anderson, J. R. (2012). Learning from experience: Event-​related potential
correlates of reward processing, neural adaptation, and behavioral choice. Neuroscience and
Biobehavioral Reviews, 36(8), 1870–​1884. https://​doi.org/​10.1016/​j.neubio​rev.2012.05.008
Wang, C., Ulbert, I., Schomer, D. L., Marinkovic, K., & Halgren, E. (2005). Responses of human
anterior cingulate cortex microdomains to error detection, conflict monitoring, stimulus-​
response mapping, familiarity, and orienting. Journal of Neuroscience, 25(3), 604–​613.
doi:10.1523/​JNEUROSCI.4151-​04.2005
Wang, D., Clouter, A., Chen, Q., Shapiro, K. L., & Hanslmayr, S. (2018). Single-​trial phase entrain-
ment of theta oscillations in sensory regions predicts human associative memory performance.
The Journal of Neuroscience, 38(28), 0349–​18. https://​doi.org/​10.1523/​JNEURO​SCI.0349-​18.2018
Wascher, E., Rasch, B., Sänger, J., Hoffmann, S., Schneider, D., Rinkenauer, G., . . . Gutberlet, I.
(2014). Frontal theta activity reflects distinct aspects of mental fatigue. Biological Psychology,
96, 57–​65. https://​doi.org/​10.1016/​j.biopsy​cho.2013.11.010
Wessel, J. R. (2018). An adaptive orienting theory of error processing. Psychophysiology, 55(3),
1–​21. https://​doi.org/​10.1111/​psyp.13041
White, J. A., Banks, M. I., Pearce, R. A., & Kopell, N. J. (2000). Networks of interneurons with
fast and slow gamma-​aminobutyric acid type A (GABAA) kinetics provide substrate for
mixed gamma–​theta rhythm. Proceedings of the National Academy of Sciences of the United
States of America, 97(14), 8128–​8133.
Wiecki, T. V. & Frank, M. J. (2013). A computational model of inhibitory control in frontal
cortex and basal ganglia. Psychological Review, 120(2), 329–​355.
Womelsdorf, T., Johnston, K., Vinck, M., & Everling, S. (2010). Theta-​activity in anterior cin-
gulate cortex predicts task rules and their adjustments following errors. Proceedings of the
National Academy of Sciences of the United States of America, 107(11), 5248–​5253. doi: 10.1073/​
pnas.0906194107
Womelsdorf, T., Schoffelen, J. M., Oostenveld, R., Singer, W., Desimone, R., Engel, A. K., &
Fries, P. (2007). Modulation of neuronal interactions through neuronal synchronization.
Science, 316(5831), 1609–​1612. doi:10.1126/​science.1139597
Womelsdorf, T., Valiante, T. A., Sahin, N. T., Miller, K. J., & Tiesinga, P. (2014). Dynamic circuit
motifs underlying rhythmic gain control, gating and integration. Nature Neuroscience, 17(8),
1031–​1039. https://​doi.org/​10.1038/​nn.3764
Womelsdorf, T., Vinck, M., Leung, L. S., & Everling, S. (2010). Selective theta-​synchronization
of choice-​ relevant information subserves goal-​ directed behavior. Frontiers in Human
Neuroscience, 4, 210. https://​doi.org/​10.3389/​fnhum.2010.00210
 FRONTAL MIDLINE THETA AS A MODEL SPECIMEN OF CORTICAL THETA    201

Yamaguchi, M., Crump, M. J. C., & Logan, G. D. (2013). Speed-​accuracy trade-​off in skilled
typewriting: Decomposing the contributions of hierarchical control loops. Journal of
Experimental Psychology: Human Perception and Performance, 39(3), 678–​699.
Yordanova, J, Falkenstein, M., Hohnsbein, J., & Kolev, V. (2004). Parallel systems of error
processing in the brain. NeuroImage, 22(2), 590–​602. https://​doi.org/​10.1016/​j.neu​roim​
age.2004.01.040S1​0538​1190​4000​850 [pii]
Yordanova, Juliana, Kolev, V., Rosso, O. A., Schürmann, M., Sakowitz, O. W., Özgören, M., &
Basar, E. (2002). Wavelet entropy analysis of event-​related potentials indicates modality-​
independent theta dominance. Journal of Neuroscience Methods, 117(1), 99–​109. https://​doi.
org/​10.1016/​S0165-​0270(02)00095-​X
Zavala, B. A., Tan, H., Little, S., Ashkan, K., Hariz, M., Foltynie, T., . . . Brown, P. (2014). Midline
frontal cortex low-​frequency activity drives subthalamic nucleus oscillations during conflict.
Journal of Neuroscience, 34(21), 7322–​7333. https://​doi.org/​10.1523/​JNEURO​SCI.1169-​14.2014
Zavala, B., Brittain, J.-​S., Jenkinson, N., Ashkan, K., Foltynie, T., Limousin, P., . . . Brown, P.
(2013). Subthalamic nucleus local field potential activity during the Eriksen Flanker task
reveals a novel role for theta phase during conflict monitoring. The Journal of Neuroscience,
33(37), 14758–​14766. https://​doi.org/​10.1523/​JNEURO​SCI.1036-​13.2013
Zavala, B., Tan, H., Little, S., Ashkan, K., Green, A. L., Aziz, T., . . . Brown, P. (2016). Decisions
made with less evidence involve higher levels of corticosubthalamic nucleus theta band
synchrony. Journal of Cognitive Neuroscience, 28(6), 811–​825. https://​doi.org/​10.1162/​jocn_​
a_​00​934
Zhang, H., Watrous, A. J., Patel, A., & Jacobs, J. (2018). Theta and alpha oscillations are traveling
waves in the human neocortex. Neuron, 98(6), 1269–​1281.e4. https://​doi.org/​10.1016/​j.neu​
ron.2018.05.019
Zlojutro, M., Manz, N., Rangaswamy, M., Xuei, X., Flury-​Wetherill, L., Koller, D., . . . Almasy,
L. (2011). Genome-​wide association study of theta band event-​related oscillations identifies
serotonin receptor gene HTR7 influencing risk of alcohol dependence. American Journal of
Medical Genetics, Part B: Neuropsychiatric Genetics, 156(1), 44–​58. https://​doi.org/​10.1002/​
ajmg.b.31136
 CHAPTER 10

THE ROLE OF A L PHA A ND

B ETA OSCILL AT I ONS I N
T HE HUM AN EE G DU RI NG
PERCEP TION A ND ME MORY
PRO CE S SE S

SEBASTIAN MICHELMANN, BENJAMIN GRIFFITHS,

AND SIMON HANSLMAYR

10.1  Alpha oscillations and their

relation to cognition

In 1929 a German physician named Hans Berger recorded the first human EEG. The
first thing he noticed was a regular oscillation with a frequency of 10 Hz (Berger, 1929),
which he termed alpha oscillations. Many decades after Berger discovered these alpha
oscillations researchers use them as a first quality check of their EEG signal. After
attaching electrodes to the subject’s head, the researcher typically asks the subject to
close their eyes and relax; the researcher then sees beautiful alpha waves with a fre-
quency of around 10 Hz being maximal over posterior channels. When the subject then
opened their eyes, alpha oscillations largely reduce. This phenomenon is extremely re-
liable, such that not seeing the reduction in alpha amplitude when subjects open their
eyes would typically indicate that something went wrong. Reductions in alpha amp-
litude occur in all ranges of cognitive tasks such as visual processing (Adrian, 1944),
auditory processing (Krause et al., 1994; Obleser & Weisz, 2012), somatosensory pro-
cessing (Crone et al., 1998), memory encoding (Hanslmayr et al., 2009; Klimesch et al.,
1996), memory retrieval (Burgess & Gruzelier, 2000; Waldhauser et al., 2016), working
memory maintenance (Sauseng et al., 2009), decision making (Pornpattananangkul
 THE ROLE OF ALPHA AND BETA OSCILLATIONS IN THE HUMAN EEG     203

et al., 2019), and motor preparation and execution (Pfurtscheller et al., 1997). The exact
frequency at which power reductions are maximal varies between tasks and often
involves the faster beta oscillation around 15 Hz, which can be considered the “fast” sib-
ling of alpha. In this chapter we therefore do not distinguish between alpha and beta
oscillations and refer to these oscillations as alpha/​beta. Suppression of alpha/​beta
oscillations is not only observed in humans, but also in a wide range of animals, for ex-
ample, non-​human primates (Haegens et al., 2011), dogs (Lopes da Silva et al., 1980), cats
(von Stein et al., 2000), rodents (Wiest & Nicolelis, 2003), and even insects (Popov &
Szyszka, 2019). This ubiquity of alpha/​beta power suppression across cognitive domains
and across the animal kingdom indicates that alpha/​beta power reductions are a signa-
ture of an extremely general mechanism, which is called upon in almost any cognitive
task and has been retained over millions of years of evolution. What could this mech-
anism be? This chapter attempts to answer this question.
Before delving into the different physiological interpretations of alpha oscillations
it is worth pointing out a theoretical caveat that has become evident in cognitive
neuroscience and the way we can avoid these problems. Historically the job descrip-
tion for a cognitive neuroscientist was to pick a cognitive phenomenon (i.e., attention,
memory) and then find the “neural correlate” of that phenomenon. To demonstrate
this approach let us consider a short thought experiment involving two hypothetical
cognitive neuroscientists: AC and BD. Researcher AC is interested in attention. She
runs several meticulously controlled experiments that all manipulate certain aspects
of attention while she records EEG. Across this series of experiments, she finds that
alpha oscillations are very consistently modulated by attention. She goes to a confer-
ence, presents her results, and concludes that alpha oscillations are the neural correlate
of attention. At that same conference, researcher BD, who is interested in memory, also
presents his results. In a series of carefully controlled experiments he shows that alpha
oscillations are reliably modulated by various memory processes. He concludes his talk
with saying that alpha oscillations are the neural correlate of memory.
So, who is right? What cognitive function do alpha oscillations represent: memory
or attention? The answer is both are wrong. The error that both scientists make is to
assume that there is a one-​to-​one mapping between neural phenomena and cognitive
functions. This error has become known under the term “reverse inference error”, that
is, observing neural signature X has no predictive value for cognitive process Y to occur
(Poldrack, 2011). With respect to alpha oscillations, given their ubiquity in terms of cog-
nitive tasks (from attention to decision making) and species (from human to honeybees)
it is evident that the task of trying to attach one particular label from cognitive psych-
ology (attention vs. memory) to them is bound to fail. An alternative approach is
needed if we want to truly understand the function of alpha oscillations. This alternative
approach needs to avoid limiting itself by definitions of cognitive processes. Instead, this
approach needs to embrace the fact that a given neural phenomenon can be of service
to many different cognitive processes in many different species. One such alternative is
to assume that different oscillations implement canonical computations (Siegel et al.,
2012; Womelsdorf et al., 2014), which are basic neural operations that are called upon by
204    SEBASTIAN MICHELMANN et al.

different cognitive processes. Regulating the balance between excitation and inhibition,
for instance, would be one such basic operation. Another basic operation is to enable
the neural representation of information rich content. These operations arguably are
required by almost any cognitive task and species. The difference from this approach to
the traditional cognitive neuroscience approach is not in using different labels, but to try
to understand the computational utility of a neural operation for a given cognitive pro-
cess (see Buzsaki, 2019 for a similar line of argument). Instead of asking what the neural
correlate of attention is, we ask how a decrease in alpha oscillations can be of service for
attention, memory, decision making, etc. Section 10.2 provides a brief overview of the
behaviour of alpha oscillations in terms of frequency, power, and phase. It is critical to
understand these terms first before we can consider the physiological interpretations of
alpha oscillations.

10.2  Signal properties of alpha:

Frequency, Power, and Phase

10.2.1  Frequency
Analyzing alpha oscillations typically involves transforming an EEG signal into time-​
frequency space (see Cohen, 2014 for an excellent overview of the different methods
and hands-​on tutorials). Figure 10.1A shows a typical example of a raw EEG trace in a
healthy human subject. It is easy to spot the decrease in alpha amplitudes at time 0 (when
a stimulus was presented). Brain oscillations are defined by three physical properties: (i)
frequency (Figure 10.1B), (ii) amplitude (Figure 10.1C), and (iii) phase (Figure 10.1D).
Different brain networks are hypothesized to oscillate at different frequencies (Keitel
& Gross, 2016), with small networks oscillating at fast frequencies (>40 Hz) and large
networks oscillating at slower frequencies (<20 Hz) (von Stein & Sarnthein, 2000). Small
and large here refers to the number of neurons involved in generating the signal. This ana-
tomical property is reflected in the 1/​F power ratio of EEG signals, which refers to the drop
in signal power with increasing frequency. Alpha oscillations are remarkable because
they stand out from the 1/​F pattern (Figure 10.1B), which shows that they are a particu-
larly strong oscillation recruiting large pools of neurons. Frequencies are typically used
to distinguish between different types of oscillations, that is, theta ~ 4 Hz, beta ~15 Hz,
gamma ~ 40 Hz, etc. The frequency within an oscillation has been shown to be linked to
interindividual variability in memory processes (Cohen, 2011) or intelligence (Anokhin
& Vogel, 1996). Recent work demonstrates that the frequency of alpha can also change
within a subject, from trial-​to-​trial (Haegens et al., 2014) and may reflect cortical excit-
ability ( Cohen, 2014). Therefore, it is important to consider that the frequency of alpha
may vary from individual to individual and even from trial to trial within a participant.
Sometimes it can even be challenging to distinguish a “fast theta” from a “slow alpha”.
 THE ROLE OF ALPHA AND BETA OSCILLATIONS IN THE HUMAN EEG     205

(a) Raw Signal

20 20
15 2

Absolute Power [a.u.]

10

Frequency (Hz)
Amplitude (μV)

5 T.F. -
0 10 1
Analysis
–10
–15 0
2
–20 –1 –0.5 0 0.5 1 1.5
–1 –0.5 0 0.5 1 1.5 Time (sec)
Time (sec.)

(b) (c) (d)

Frequency Power Phase
100 π/2
40
30 π
–π 0
recruited assemblies 20

Relative Power [%]

Frequency [Hz]

10 –π/2
Alpha 4.4 Hz
(~10 Hz) 0
Power

35 –10
–20
13 –30
7
3 –0.2 0 –40
0.2 0.4 0.6 0.8 1 1.2 1.4
Time [sec]
Frequency

Figure 10.1  Alpha oscillations and their parameters. (A) An example of a raw signal as
recorded with a parietal EEG electrode is shown on the left. A stimulus was presented at time
0. The plot on the right shows the results of a time-​frequency analysis in which power is depicted
for each time-​point (x-​axis) and frequency band (y-​axis; a.u. =​arbitrary units). (B) A sche-
matic of a typical EEG power spectrum is shown, with frequency on the x-​axis and power on
the y-​axis. The inverse relationship between the size of neural assemblies and power is depicted.
Note the peak at the alpha frequency which violates the 1/​F relation between power and fre-
quency. (C) A typical time-​frequency plot showing event related power increases (hot colors)
and decreases (cold colors) during processing of verbal information. Note the power increases
in theta (3–​7 Hz) and gamma (35–​100 Hz) and the power decreases in alpha (8–​12 Hz) and beta
(13–​35 Hz). (D) The relationship between EEG phase (top) and firing rates (bottom) is shown.
The differently colored lines show phase modulations in trials with high (red), medium (purple)
or low (blue) power.
(A) Reprinted with permission from Hanslmayr et al., 2011. (C) is modified and reprinted with permission from
Hanslmayr et al., 2012. (D) modified and reprinted with permission from Jacobs et al., 2007.

10.2.2  Power
The power of an oscillation refers to its signal strength. It is usually calculated by taking
the square of the signal. In human EEG, a signal is generated by the summation of several
millions of postsynaptic potentials (inhibitory and excitatory) over an area of some cm2
(Pfurtscheller et al., 1996). Importantly, the current changes induced by postsynaptic
potentials are tiny and we record these potentials with an electrode that is attached to
the scalp, separated by various layers of bone, cerebrospinal fluid, skin, etc., from the
brain. Therefore, in order to detect a signal that is large enough to be visible in the EEG,
tens of thousands of post-​synaptic potentials must come together in time. To give an
analogy, recording EEG is a bit like recording the noise in a football stadium with one
206    SEBASTIAN MICHELMANN et al.

big microphone hanging from the ceiling. Using this coarse signal we cannot stand the
chance to tune in onto an individual conversation between two fans, but we can use the
signal to tell whether a goal was scored (because thousands of fans start shouting at the
same time). Accordingly, the strength of an oscillation is assumed to reflect the degree
of synchrony between inhibitory or excitatory postsynaptic potentials to an underlying
neural assembly. Power increases indicate increased local synchrony whereas power
decreases indicate de-​synchronized local activity. This idea is reflected in the classic work
of Pfurtscheller & Aranibar (1977), who coined the terms event-​related synchroniza-
tion and de-​synchronization (ERS/​ERD), which denotes power increases and decreases
in response to an event or stimulus, respectively. In EEG experiments absolute power
is usually transformed into power changes in response to a baseline (e.g., prestimulus
interval). Figure 10.1C shows a typical example of such data with stimulus driven power
increases in the lower (1–​8 Hz: delta/​theta) and higher (40–​100 Hz; gamma) frequency
ranges, and power decreases in the middle frequency ranges (8–​35 Hz; alpha/​beta).

10.2.3  Phase
The phase of an oscillation specifies the current position in a given cycle (Figure 10.1D),
that is whether the oscillation exhibits a peak, trough, or zero crossing. Because the EEG
reflects the sum of postsynaptic input to a given neuron, we can assume that it impinges
on the neuron’s probability to fire an action potential. Figure 10.1D shows a single neuron
recorded in the human brain, and that the neuron is more likely to fire in the trough of
the oscillation, which indeed resembles the time point of maximally coinciding excita-
tory input (note that the LFP in this case is measured in the extracellular space; there-
fore, negativity indexes excitation). This same figure also shows that the modulation of
firing rate is stronger for trials of high power (red) and lower for trials of low power
(blue). We can therefore assume that the phase of alpha oscillations (or any other oscil-
lation for that matter) represent discrete time windows for neural firing, and that this
synchronizing effect scales with power. This is a very useful computational property as it
gives alpha oscillations the power to control the timing of neural firing in large groups of
neurons. Like the conductor of an orchestra, who tells individual instruments when to
play a particular note (and when to not play a note), alpha oscillations can synchronize
large groups of neurons to temporally structure neural processing. This aspect becomes
particularly important in Section 10.5, which covers the role of alpha phase for sampling
information and replaying this information from memory.

10.3  Alpha Oscillations: Passive idling

versus active inhibition

Alpha oscillations decrease in amplitude when a subject is engaged in a task as opposed

to when a subject is resting (especially with eyes closed). This goes against intuition
 THE ROLE OF ALPHA AND BETA OSCILLATIONS IN THE HUMAN EEG     207

as one would usually expect to see an increase in brain signal strength when a subject
performs a challenging task, not a decrease. How can we functionally interpret this
negative relationship between alpha power and cognitive processing? Up until the early
2000s the prevailing view was that alpha oscillations reflect a state of “idling” or rest. In
their article, Pfurtscheller and colleagues (1996) give the example of the motor cortex,
in particular the visual cortex and the hand area during a reading task or a motor task
requiring finger movements, respectively. During reading, the visual cortex displays
profound alpha-​power decreases, whereas the hand motor area shows an increase in
alpha power. This picture switches when the subject engages in a motor task requiring
finger movement. Within the idling hypothesis, one would interpret the increased alpha
power over areas that are not required by the task as “nil work”, that is, a passive res-
onance phenomenon of a part of cortex that has “nothing to do” (Adrian & Matthews,
1934). Since almost any cognitive task always involves specific activation of some regions
and de-​activation of other regions (Fox et al., 2005) the EEG would always reflect some
areas that show alpha power decreases (or desynchronization) and some areas that show
alpha-​power increases (or synchronization). The important emphasis of the idling hy-
pothesis is on the passive aspect of alpha synchronization which has no functional role
per se.
Klimesch and colleagues (2007) and Jensen and Mazaheri (2010) presented a
contrasting view to the idling hypothesis and suggested that alpha oscillations play
a critical role in cognitive processing. The seminal findings that led to this interpret-
ation were studies showing that alpha power increased with increasing cognitive load
in a working memory task (Jensen et al., 2002; Klimesch et al., 1999). This alpha-​power
increase with cognitive load is difficult to reconcile with the idling hypothesis, which
led to the active inhibition hypothesis (Jensen & Mazaheri, 2010; Klimesch et al., 2007).
Within the active inhibition hypothesis an increase in alpha power reflects an active
inhibition process that serves to silence a particular region that is task irrelevant. This
silencing of task-​irrelevant areas ensures that information is processed selectively in
task-​relevant areas and protects the processing of this information from interference
or noise. A critical prediction that the inhibition account made was that an increase in
alpha oscillations narrows the time windows for neurons to fire (see red vs. blue lines
in Figure 10.1D) and therefore reduces neural firing. Thus, periods of high alpha power
should coincide with low neural firing, whereas periods of low alpha power should co-
incide with high neural firing. This prediction was confirmed in a non-​human primate
study (Haegens et al., 2011), which suggests that an increase in alpha power in a given
area acts as a “silencing mechanism” which muffles neural assemblies that otherwise
might interfere.
Coming back to our example, alpha synchronization of the hand area while reading
this chapter ensures that you can focus on the text instead of moving around (or
thinking about movements). The more challenging a task, the more we need to tune out
task-​irrelevant activity. The inhibition account has gained considerable support over the
last decades because it can accommodate the findings in the literature better than the
idling hypothesis. To give two examples, if subjects maintain visual content in working
208    SEBASTIAN MICHELMANN et al.

memory that was presented in the left hemifield, therefore being processed in the right
occipital cortex, alpha power increases over the left occipital cortex (Sauseng et al.,
2009). Externally enhancing alpha power with repetitive transcranial magnetic stimu-
lation over the irrelevant hemisphere then increases working memory performance.
Similar evidence comes from Bonnefond and Jensen (2012), who demonstrated that
subjects actively increase their alpha power in anticipation of a task-​irrelevant distractor
presented during working memory maintenance. The more the subjects upregulated
alpha power the better the performance on the working memory task. These results rule
out a passive perspective of alpha oscillations and instead suggest that alpha oscillations
are very much an active process that regulates neural activity to ensure selective infor-
mation processing. Within this perspective, alpha oscillations serve the function of a
filter that tunes out task-​irrelevant information to render the task-​relevant signal more
salient.

10.4  Alpha Power Decreases and

the Representation of Information

The active inhibition account has been extremely useful in interpreting the role of alpha
power increases, or alpha synchronization during cognitive processing. This is because
any cognitive process requires selective information processing; alpha oscillations, by
inhibiting task irrelevant neural assemblies, ensure such selective information pro-
cessing. This functional interpretation of alpha oscillations is broad enough to ac-
commodate the fact that modulations of alpha oscillations are observed in a variety
of cognitive tasks and species. Returning to the thought experiment from earlier, the
attention scientist AC and memory scientist BD would interpret their findings to show
that both memory and attention crucially rely on an active filtering mechanism. Indeed,
alpha power increases over areas that hold the representation of task-​irrelevant infor-
mation, regardless of whether this information is currently perceived (Thut et al., 2006;
Worden et al., 2000), held in working memory (Sauseng et al., 2009), or stored in long-​
term memory (Waldhauser et al., 2012). The emphasis of the active inhibition hypoth-
esis is on alpha synchronization and its computational utility in terms of providing a
filter mechanism for selective information processing. What is less clear from this per-
spective, however, is what the computational utility of alpha power decreases are for
information processing (other than allowing for increased neural spike rates through
less inhibition). We therefore proposed an additional theory, which is complemen-
tary to the inhibition account. Within this framework we emphasized the role of alpha
power decreases in allowing for high-​fidelity information to be represented in neural
assemblies. A key assumption of this account rests on the fact the alpha/​beta power
decreases represent periods of de-​correlated neural firing (see Murthy & Fetz, 1996 for
such a demonstration for beta oscillations in the motor cortex).
 THE ROLE OF ALPHA AND BETA OSCILLATIONS IN THE HUMAN EEG     209

One way of interpreting the functional utility of de-​correlated firing in alpha for cogni-
tive processing applies tenets of information theory (Shannon & Weaver, 1949) to neural
oscillations. This framework is known as the “information-​via-​desynchronization hy-
pothesis” (Hanslmayr et al., 2012), which proposes that synchronized alpha/​beta states
are inherently bad for information representation as neuronal activity is highly redun-
dant. Take the simplified instance of two presynaptic neurons that act upon the same
postsynaptic neuron: if one presynaptic neuron fires in perfect synchrony with another,
what can this neuron add to the neuronal code that its synchronous partner does not
already (Schneidman et al., 2011)? If we expand this principle to networks of neurons,
we can postulate that highly synchronous networks are detrimental to information pro-
cessing, because they only represent redundancies. To overcome this limitation there-
fore, the networks must desynchronize. Through desynchronization, the underlying
neural code can be more complex and hence convey a more detailed representation of
information. The event-​related desynchronization so commonly seen in alpha oscilla-
tion may be a prime example of this phenomenon.
Numerous studies support the idea that alpha/​beta power decreases reflect the rep-
resentation of information within the cortex. One of the most direct lines of support
comes from a recent simultaneous EEG-​fMRI experiment by Griffiths and colleagues
(2019), who asked participants to associate video clips with words, and to later recall
the clips using the words as a cue (Figure 10.2). For each trial, the researchers quantified
the amount of visual information present in the cortex by conducting representa-
tional similarity analysis (RSA) on the fMRI data (Kriegeskorte et al., 2008). RSA is
based on correlations of neural patterns and reasons that representations of the same
content should elicit neural patterns that are more alike than the patterns elicited by
representations of different content (Kriegeskorte et al., 2008). The researchers then
asked whether the power of the alpha and beta frequencies (8–​30Hz) correlated with
the quantity of information (calculated via RSA) represented on a given trial. Indeed,
they found evidence to suggest a parametric link between alpha/​beta power and infor-
mation: as power decreased, information increased (Figure 10.2b). Similarly, Hanslmayr
and colleagues (2009) presented participants with words and asked them to engage in
semantic processing (i.e., does this word represent a living entity or a non-​living en-
tity?) or shallow processing (i.e., does the first letter of the word precede the last in the
alphabet?). As semantic processing involves much greater levels of information pro-
cessing (you must not only process the letters, but also what those letters mean), the
researchers hypothesized that alpha/​beta power decreases would be greater during
this type of processing. Their results revealed just that—​suggesting that alpha/​beta
power decreases scale with the depth of information processing (see Fellner et al., 2018
for similar results contrasting familiar and unfamiliar stimuli). In conjunction with a
number of other studies, these results strongly implicate alpha/​beta power reductions in
information processing (Hanslmayr et al., 2012).
While the alpha idling theory assumes that synchronous alpha oscillations mark a
default state in which the cortex does nothing (Pfurtscheller et al., 1996), the alpha in-
hibition theory highlights the active role of alpha synchronization in the suppression of
210    SEBASTIAN MICHELMANN et al.

(a) Perception Interval Retrieval (b) 0.4

Power Similarity Correlation (z)

0.2

Noise correlations
0

Info-via-desync
–0.2

–0.4
Perception Retrieval
Low Sync/High Info. High Sync/Low Info. Low Sync/High Info.

Figure 10.2  Alpha power and information processing. (A) Infographic depicting theories be-
hind alpha and information processing. Perception and memory retrieval involve the processing
of large quantities of information. The noise correlation account proposes that when task irrele-
vant neurons (in blue) synchronize (e.g., during the interval), they mask the signal generated
by task-​relevant neurons (in red). When the task-​irrelevant neurons desynchronize however
(i.e., during perception/​retrieval), the signal can be detected above the background noise. The
information-​via-​desynchronization account proposes that oscillatory desynchronization allows
a more complex neural code to be generated. Such a complex code is necessary to process the
highly complex information encountered in daily life. In both instances, oscillatory desyn-
chronization benefits information processing (B) Reproduction of the results by Griffiths and
colleagues. Power decreases during both perception and retrieval negatively correlate with the
amount of stimulus specific information present on that trial.

task irrelevant information (Jensen & Mazaheri, 2010; Klimesch et al., 2007). It therefore
attributes an operative function to alpha synchrony. The information via desynchron-
ization hypothesis goes beyond the inhibition theory, in that it highlights the active role
of power decreases for the processing of information. Therein, power decreases are not
a mere absence of inhibition, but rather functionally involved in neural computations.
The crucial insight is that in order to process complex information or represent informa-
tion rich content, synchronous neural activity does not provide enough coding space.
Desynchronous neural activity on the other hand, which is marked by power decreases
in the alpha/​beta band, provides the required coding space through locally decoupled
neural assemblies. The information via desynchronization theory therefore stresses
that, in order to perform cognitive operations that work on complex and information-​
rich content, alpha/​beta power must decrease.
Another way to interpret the inverse relation between alpha power and information
representation is offered by studies investigating “noise-​correlations”, which refers to
correlated firing of task-​irrelevant neurons—​a process that can be detrimental to in-
formation representation (Mitchell et al., 2009). If two task-​irrelevant neurons fire
together, their noise is amplified. Expand this principle to hundreds or thousands of
neurons and their noise becomes deafening. In such quantities, these noise correlations
 THE ROLE OF ALPHA AND BETA OSCILLATIONS IN THE HUMAN EEG     211

mask the signal generated by neurons critical to the task at hand (Averbeck et al., 2006;
see also Figure 10.2a), leading to an impaired ability in processing and representing
information. To rectify this situation, the magnitude of noise correlations needs to be
attenuated. How, though, do noise correlations relate to alpha oscillations? Given that
the summed electric potential of the correlated neurons creates a spike in the amplitude
of local field potential (Averbeck et al., 2006), repeated and rhythmic patterns of noise
correlations would create repeated and rhythmic increases in the amplitude of local field
potential (LFP). As alpha oscillations dominate the neocortex, one may speculate that
the rhythmic noise correlations may resonate within this frequency band. Under this
assumption, periods of high-​amplitude alpha oscillations would reflect periods of nu-
merous noise correlations where information processing is inhibited. This interpret-
ation conforms with the active inhibition account because it would allow alpha power
increases to suppress task-​irrelevant information. Periods of alpha desynchrony, in con-
trast, would reflect periods of limited noise correlations, where there is a greatest poten-
tial for information representation.
In summary, there are two theoretical arguments that implicate alpha power
decreases in the representation of stimulus-​specific information. The information-​
via-​desynchronization account suggests that alpha power reductions facilitate the
evolution of more complex neural codes, which then allows for the representation of
high-​fidelity information in the cortex. The noise correlation account suggests that
alpha power decreases reduce the background noise in the cortex, allowing for key
signals to be more clearly communicated. Currently, empirical evidence supports both
ideas by demonstrating that alpha power decreases scale with the quantity of informa-
tion present in the cortex.

10.5 Alpha Phase: Information Sampling

and Replay

Recent evidence suggests that the continuous input that our brain receives from the
outside world is not sampled continuously, but in discrete rhythmic steps around the
alpha frequency (VanRullen, 2016). These studies show that the probability of detecting
a briefly presented visual stimulus fluctuates rhythmically (VanRullen et al., 2007).
This attentional sampling process has been suggested to operate at a frequency of
roughly 8 Hz (Landau & Fries, 2012), even when sustained attention to the same ob-
ject is maintained (Fiebelkorn & Kastner, 2019; Fiebelkorn et al., 2013). Overall, there
appears to be a close correlation between the phase of an oscillation in the lower alpha
band (around 8 Hz) and the perception of an incoming stimulus. In the perception of
continuous and dynamic stimuli, the stimulus identity can be reliably decoded from
the ongoing phase of neural oscillations. Therein, an individual continuous stimulus
is associated with a unique time course of neural activity. Specifically, the stimulus
212    SEBASTIAN MICHELMANN et al.

entrains the cortical rhythm in a content-specific way that organizes neural firing (Ng
et al., 2013). Interestingly, the phase of the ongoing oscillation contains more informa-
tion about stimulus identity than its power (Schyns et al., 2011).
Considering this information sampling role of alpha phase in perception, an immi-
nent question is whether or not the reinstatement of information from memory relies
on the replay of that information sampled in the alpha frequency. To this end, alpha
phase could index similar mechanisms during attention and memory, just like alpha
power decreases. But how can we measure the information sampling and the replay
thereof in the phase of a recorded EEG?
Similar to assessing the similarity of neural patterns in space, as is usually done in
fMRI, one can assess the similarity of neural patterns in phase (over time) via the use
of RSA methods (discussed earlier). Established measures of connectivity can help
quantify the similarity of neural patterns in the phase of the alpha-​frequency band
(Greenblatt et al., 2012). Connectivity measures usually assess the similarity between
different channels in their time course of activity. This typically measures shared infor-
mation between regions. Yet, measures of connectivity will lend themselves perfectly to
quantify representational similarity between encoding and retrieval (Figure 10.3a).
In a first study, we applied such similarity measures of phase in a human EEG experi-
ment where subjects were instructed to encode and replay dynamic visual (short movie
clips) or auditory stimuli (short melodies played by different instruments). Indeed,
content-​specific patterns of oscillatory phase in the lower alpha band during percep-
tion represent the identity of the visual or auditory stimuli in the visual and auditory
cortex, respectively. Strikingly, these phase patterns reappear when representations of
short video clips and short sound clips are replayed from memory (Michelmann et al.,
2016). Importantly, this replay takes place in the absence of the dynamic stimulus itself
and can be localized in sensory specific areas (Figure 10.3c). A recent study replicated
this effect in the visual domain and demonstrated that the reinstatement of temporal
patterns is only observed when content is successfully recalled, that is, temporal pattern
reinstatement is implicated in successful memory (Michelmann et al., 2019). Another
study replicated this effect during sleep, indicating that replay of stimulus-​specific phase
patterns supports memory consolidation (Schreiner et al., 2018). Further evidence
documents that such content-​specific phase patterns are also replayed when an asso-
ciation with a previously shown dynamic stimulus is formed (Michelmann et al., 2018).
Interestingly, the reinstatement of temporal patterns is not always beneficial for
memory but can in some cases interfere with memory as demonstrated by studies
which manipulated the contextual overlap between encoding and retrieval. For in-
stance, (Staudigl et al., 2015) manipulated the context in which a word is learned and
remembered by playing the same video clip in the background behind the word at
encoding and at retrieval (context match); or playing a different video clip in the back-
ground behind the word at encoding and at retrieval (context mismatch). The import-
ance of reinstatement of contextual information was observed via temporal and spatial
pattern similarity in the beta frequency band. Specifically, higher pattern similarity was
associated with better memory performance when contexts where matching. On the
 THE ROLE OF ALPHA AND BETA OSCILLATIONS IN THE HUMAN EEG     213

(a)

μV

μV
stimulus onset cue onset cue onset response
time (t) time (t)

PI PI
phase

phase
angle

angle
0 0
–PI –PI
stimulus onset cue onset cue onset response
time (t) time (t)
sliding window
Phase similarity
(b) (c)
40
2
30
frequency [Hz]

T-values
20 0
0 –1 –2 –3 –4 –5
10 –2
t-values

0 1 2 3 4
time [seconds]

Figure 10.3  Alpha power decreases during memory retrieval code stimulus-​specific infor-
mation. (A) Subjects first encoded a video (left). They later retrieved a vivid representation of
that video from memory (right). The phase time course was extracted from the EEG during
encoding and retrieval in order to calculate a similarity measure between encoding and retrieval.
(B) During retrieval, strong and sustained alpha power decreases were observed. (C) Reactivation
of stimulus-​specific information, as measured with phase similarity, could be detected in the
alpha frequency band with a maximum in parietal regions. This reactivation was localized in par-
ietal cortex (C, left).
Reproduced from Michelmann et al., 2016.

other hand, non-​overlapping contexts were characterized by more dissimilar patterns

for remembered vs. forgotten words. These findings were recently replicated in a study
using sensory modality (i.e., presenting a word visually or aurally) as a context match/​
mismatch manipulation (Staudigl & Hanslmayr, 2019). The results of these studies
are in line with the notion that context reinstatement is only helpful when the con-
text has not changed and substantiate the importance of temporal patterns for content
representation.
Most of the studies referenced earlier found that stimulus-​specific information was
coded in the phase of the lower alpha band, around 8 Hz (Michelmann et al., 2016, 2018;
Michelmann et al., 2019; Staudigl & Hanslmayr, 2019). Corroborating evidence for a
special role of 8 Hz in the sampling of memories comes from Kerren and colleagues
(2018), who showed decoded content-​specific representations in memory from spatial
patterns of activity, and that these patterns fluctuate at a frequency of 8 Hz. The sampling
of information at an 8 Hz rhythm therefore seems to underlie both, rhythmic sampling
214    SEBASTIAN MICHELMANN et al.

of information during perception (VanRullen et al., 2007) and the replay of that infor-
mation during memory reinstatement.

10.6 Linking alpha phase and power

Michelmann and colleagues (2016) showed that the frequency band that contains
content-specific temporal patterns is also the one that displays the most prominent
power decreases during retrieval (Figure 10.3b), and furthermore, they observed an
interaction such that sensory areas that were involved in the reinstatement of auditory
and visual temporal patterns also expressed stronger power decreases in the respective
condition. This suggests that power decreases and the representation of information in
oscillatory phase are not two separate processes but rather are intertwined. This raises
the question as to how the two signal properties of alpha—​power and phase—​interact in
the service of information representation.
We suggest that a decrease of power in an ongoing oscillation renders a signal less
stationary (and therefore also less predictable) and thereby allows for a flexible adjust-
ment of phase (Hanslmayr et al., 2016). These phase adjustments, or deviations from
stationarity, make it possible that time courses in phase can represent stimulus spe-
cific patterns, and to replay these patterns from memory (Figure 10.4C). From an in-
formation theoretic view, a stationary oscillation without phase adjustments wouldn’t

(a) Predictable Signal (High Power) (b) Phase per Period (c)
(every 100 ms)
Stimulus A

Stimulus B

Complex Signal (Low Power)

Phase per Period
(every 100 ms) Stimulus C

Stimulus D

0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 6

Time [s] Time [s]

Figure 10.4 Information coding properties for stationary and non-​ stationary signals is
illustrated. (A) A stationary (high power) signal (orange) is shown together with its phase (blue)
in the upper row. The lower row shows a less stationary signal. (B) Phases for each signal are
shown every 100 ms (indicated by ticks in A). (C) Non-​stationary signals allow for stimulus spe-
cific coding by assigning a different time course to each stimulus.
 THE ROLE OF ALPHA AND BETA OSCILLATIONS IN THE HUMAN EEG     215

be able to represent much information in its phase because the time course of a sta-
tionary signal is perfectly predictable once the phase at one time point is known. For
example, the signal in the top row of Figure 10.4A visits the same phase every 100 ms
(top row in Figure 10.4B). Since information theory quantifies information as the in-
verse of the predictability (i.e., negative logarithm in the case of Shannon’s Entropy, see
Shannon & Weaver, 1949) we can infer that this signal has little potential to carry infor-
mation. Indeed, if we were to code the identity of a stimulus in such a perfectly predict-
able signal, we would not be able to distinguish between different stimuli. In contrast,
a non-​stationary signal (lower row of Figure 10.4A), which has phase modulations, can
carry much more information. In this case, the phase cannot be predicted from pre-
vious time points (lower panel in Figure 10.4B). This allows us to code different stimuli
by assigning a phase time course to each stimulus (Figure 10.4C). This simple relation-
ship between the power of a signal and predictability of phase time courses elegantly
unifies the findings described in this chapter. To this end, a signal with high alpha power
leads to a more stationary time course and thus inhibits information coding. In con-
trast, a signal with lower alpha power allows for a less stationary time course and there-
fore the coding of information. Importantly, this idea is in line with the general notion
of an inhibitory role of alpha power increases but goes beyond the previous work in
ascribing specific computational roles to power and phase in the service of representing
information.

10.7  Concluding Remarks

This chapter showed that alpha oscillations are ubiquitous as they are modulated by al-
most any task and can be observed in almost any animal. It therefore follows that alpha
oscillations must perform a basic neural operation, which is of service for many cognitive
operations. After an overview of the idling vs. inhibition hypothesis we then discussed
the computational utility of alpha power reductions for information representation. We
reviewed studies that demonstrated that alpha power reductions are intimately linked to
information coding—​specifically, these studies showed that stimulus-​specific informa-
tion is coded in the phase of alpha. Importantly, several studies demonstrated that this
phase information is replayed when a reminder to that stimulus is presented. Finally,
we illustrated how power decreases allow for less stationary phase time courses and
consequently for information representation. Together, we conclude that alpha power
decreases do play an important role for information representation—​a neural operation
needed in almost any task and in almost any animal.
An important crucial future question refers to the nature of the relationship between
alpha power decreases and its role for coding information. If indeed, as we here suggest,
alpha power decreases are mechanisms for representing information we should be
able to manipulate perception, maintenance, and retrieval of information by directly
manipulating alpha oscillations via brain stimulation techniques (Hanslmayr et al.,
216    SEBASTIAN MICHELMANN et al.

2019). Such a demonstration of a causal relationship between alpha power decreases and
the representation of information is crucial in order to show that alpha oscillations are
indeed a mechanism for information representation, instead of a mere epiphenomenon.

References
Adrian, E. D. (1944). Brain rhythms. Nature, 153, 360–​362.
Adrian, E. D. & Matthews, B. H. (1934). The interpretation of potential waves in the cortex.
Journal of Physiology, 81(4), 440–​471.
Anokhin, A. & Vogel, F. (1996). EEG alpha rhythm frequency and intelligence in normal adults.
Intelligence, 23(1), 1–​14. doi:10.1016/​S0160-​2896(96)80002-​X
Averbeck, B. B., Latham, P. E., & Pouget, A. (2006). Neural correlations, population coding and
computation. Nature Reviews Neuroscience, 7(5), 358–​366. doi:10.1038/​nrn1888
Berger, H. (1929). Über das Elektrenkephalogramm des Menschen. Archiv für Psychiatrie und
Nervenkrankheiten, 87, 527–​570.
Bonnefond, M. & Jensen, O. (2012). Alpha oscillations serve to protect working memory main-
tenance against anticipated distracters. Current Biology, 22(20), 1969–​1974. doi:10.1016/​
j.cub.2012.08.029
Burgess, A. P. & Gruzelier, J. H. (2000). Short duration power changes in the EEG during rec-
ognition memory for words and faces. Psychophysiology, 37(5), 596–​606.
Buzsaki, G. (2019). The Brain from inside out. Oxford University Press.
Cohen, M. X. (2011). Hippocampal-​prefrontal connectivity predicts midfrontal oscillations
and long-​term memory performance. Current Biology, 21(22), 1900–​1905. doi:10.1016/​
j.cub.2011.09.036
Cohen, M. X. (2014). Analyzing neural time series data: Theory and practice. MIT Press.
Cohen, M. X. (2014). Fluctuations in oscillation frequency control spike timing and co-
ordinate neural networks. Journal of Neuroscience, 34(27), 8988–​ 8998. doi:10.1523/​
JNEUROSCI.0261-​14.2014
Crone, N. E., Miglioretti, D. L., Gordon, B., Sieracki, J. M., Wilson, M. T., Uematsu, S., & Lesser, R.
P. (1998). Functional mapping of human sensorimotor cortex with electrocorticographic spec-
tral analysis. I. Alpha and beta event-​related desynchronization. Brain, 121 (Pt 12), 2271–​2299.
Fellner, M. C., Gollwitzer, S., Rampp, S., Kreiselmeyr, G., Bush, D., Diehl, B., . . . Hanslmayr,
S. (2018). Spectral fingerprints or spectral tilt? Evidence for distinct oscillatory signatures
of memory formation. https://journals.plos.org/plosbiology/article?id=10.1371/journal.
pbio.3000403
Fiebelkorn, I. C. & Kastner, S. (2019). A rhythmic theory of attention. Trends in Cognitive
Sciences, 23(2), 87–​101. doi:10.1016/​j.tics.2018.11.009
Fiebelkorn, I. C., Saalmann, Y. B., & Kastner, S. (2013). Rhythmic sampling within and between
objects despite sustained attention at a cued location. Current Biology, 23(24), 2553–​2558.
doi:10.1016/​j.cub.2013.10.063
Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., & Raichle, M. E.
(2005). The human brain is intrinsically organized into dynamic, anticorrelated functional
networks. Proceedings of the National Academy of Sciences of the United States of America,
102(27), 9673–​9678. doi:10.1073/​pnas.0504136102
Greenblatt, R. E., Pflieger, M. E., & Ossadtchi, A. E. (2012). Connectivity measures applied
to human brain electrophysiological data. Journal of Neuroscience Methods, 207(1), 1–​16.
doi:10.1016/​j.jneumeth.2012.02.025
 THE ROLE OF ALPHA AND BETA OSCILLATIONS IN THE HUMAN EEG     217

Griffiths, B. J., Mayhew, S. D., Mullinger, K. J., Jorge, J., Charest, I., Wimber, M., & Hanslmayr,
S. (2019). Alpha/​beta power decreases track the fidelity of stimulus-​specific information.
https://elifesciences.org/articles/49562
Haegens, S., Cousijn, H., Wallis, G., Harrison, P. J., & Nobre, A. C. (2014). Inter-​and intra-​
individual variability in alpha peak frequency. NeuroImage, 92, 46–​ 55. doi:10.1016/​
j.neuroimage.2014.01.049
Haegens, S., Nacher, V., Luna, R., Romo, R., & Jensen, O. (2011). alpha-​Oscillations in the
monkey sensorimotor network influence discrimination performance by rhythmical inhib-
ition of neuronal spiking. Proceedings of the National Academy of Sciences of the United States
of America, 108(48), 19377–​19382. doi:10.1073/​pnas.1117190108
Hanslmayr, S., Axmacher, N., & Inman, C. S. (2019). Modulating human memory via entrain-
ment of brain oscillations. Trends in Neuroscience, 42(7), 485–​499.
Hanslmayr, S., Gross, J., Klimesch, W., & Shapiro, K. L. (2011). The role of α oscillations in tem-
poral attention. Brain Research Reviews, 67(1–​2), 331–​343.
Hanslmayr, S., Spitzer, B., & Bauml, K. H. (2009). Brain oscillations dissociate between se-
mantic and nonsemantic encoding of episodic memories. Cerebral Cortex, 19(7), 1631–​1640.
doi:10.1093/​cercor/​bhn197
Hanslmayr, S., Staresina, B. P., & Bowman, H. (2016). Oscillations and episodic
memory: Addressing the synchronization/​ desynchronization conundrum. Trends in
Neuroscience, 39(1), 16–​25. doi:10.1016/​j.tins.2015.11.004
Hanslmayr, S., Staudigl, T., & Fellner, M. C. (2012). Oscillatory power decreases and long-​
term memory: The information via desynchronization hypothesis. Frontiers in Human
Neuroscience, 6, 74. doi:10.3389/​fnhum.2012.00074
Jacobs, J., Kahana, M. J., Ekstrom, A. D., & Fried, I. (2007). Brain oscillations control timing of
single-​neuron activity in humans. Journal of Neuroscience, 27(14), 3839–​3844.
Jensen, O., Gelfand, J., Kounios, J., & Lisman, J. E. (2002). Oscillations in the alpha band (9-​
12 Hz) increase with memory load during retention in a short-​term memory task. Cerebral
Cortex, 12(8), 877–​882.
Jensen, O. & Mazaheri, A. (2010). Shaping functional architecture by oscillatory alpha
activity: gating by inhibition. Frontiers in Human Neuroscience, 4, 186. doi:10.3389/​
fnhum.2010.00186
Keitel, A. & Gross, J. (2016). Individual human brain areas can be identified from their charac-
teristic spectral activation fingerprints. PLoS Biology, 14(6), e1002498. doi:10.1371/​journal.
pbio.1002498
Kerren, C., Linde-​Domingo, J., Hanslmayr, S., & Wimber, M. (2018). An optimal oscillatory
phase for pattern reactivation during memory retrieval. Current Biology, 28(21), 3383–​3392
e3386. doi:10.1016/​j.cub.2018.08.065
Klimesch, W., Doppelmayr, M., Schwaiger, J., Auinger, P., & Winkler, T. (1999). ‘Paradoxical’
alpha synchronization in a memory task. Brain Research: Cognitive Brain Research, 7(4),
493–​501.
Klimesch, W., Sauseng, P., & Hanslmayr, S. (2007). EEG alpha oscillations: the inhibition-​timing
hypothesis. Brain Research Reviews, 53(1), 63–​88. doi:10.1016/​j.brainresrev.2006.06.003
Klimesch, W., Schimke, H., Doppelmayr, M., Ripper, B., Schwaiger, J., & Pfurtscheller, G.
(1996). Event-​related desynchronization (ERD) and the Dm effect: Does alpha desyn-
chronization during encoding predict later recall performance? International Journal of
Psychophysiology, 24(1-​2), 47–​60.
Krause, C. M., Lang, H. A., Laine, M., Helle, S. I., Kuusisto, M. J., & Porn, B. (1994). Event-​
related desynchronization evoked by auditory stimuli. Brain Topography, 7(2), 107–​112.
218    SEBASTIAN MICHELMANN et al.

Kriegeskorte, N., Mur, M., & Bandettini, P. (2008). Representational similarity analysis -​
connecting the branches of systems neuroscience. Frontiers in Systems Neuroscience, 2, 4.
doi:10.3389/​neuro.06.004.2008
Landau, A. N. & Fries, P. (2012). Attention samples stimuli rhythmically. Current Biology,
22(11), 1000–​1004. doi:10.1016/​j.cub.2012.03.054
Lopes da Silva, F. H., Vos, J. E., Mooibroek, J., & Van Rotterdam, A. (1980). Relative
contributions of intracortical and thalamo-​cortical processes in the generation of alpha
rhythms, revealed by partial coherence analysis. Electroencephalography and Clinical
Neurophysiology, 50(5-​6), 449–​456.
Michelmann, S., Bowman, H., & Hanslmayr, S. (2016). The temporal signature of
memories: Identification of a general mechanism for dynamic memory replay in humans.
PLoS Biology, 14(8), e1002528. doi:10.1371/​journal.pbio.1002528
Michelmann, S., Bowman, H., & Hanslmayr, S. (2018). Replay of stimulus-​specific temporal
patterns during associative memory formation. Journal of Cognitive Neuroscience, 30(11),
1577–​1589. doi:10.1162/​jocn_​a_​01304
Michelmann, S., Staresina, B. P., Bowman, H., & Hanslmayr, S. (2019). Speed of time-​
compressed forward replay flexibly changes in human episodic memory. Nature Human
Behaviour, 3(2), 143–​154. doi:10.1038/​s41562-​018-​0491-​4
Mitchell, J. F., Sundberg, K. A., & Reynolds, J. H. (2009). Spatial attention decorrelates intrinsic ac-
tivity fluctuations in macaque area V4. Neuron, 63(6), 879–​888. doi:10.1016/​j.neuron.2009.09.013
Murthy, V. N. & Fetz, E. E. (1996). Synchronization of neurons during local field potential
oscillations in sensorimotor cortex of awake monkeys. Journal of Neurophysiology, 76(6),
3968–​3982. doi:10.1152/​jn.1996.76.6.3968
Ng, B. S., Logothetis, N. K., & Kayser, C. (2013). EEG phase patterns reflect the selectivity of
neural firing. Cerebral Cortex, 23(2), 389–​398. doi:10.1093/​cercor/​bhs031
Obleser, J. & Weisz, N. (2012). Suppressed alpha oscillations predict intelligibility of speech and
its acoustic details. Cerebral Cortex, 22(11), 2466–​2477. doi:10.1093/​cercor/​bhr325
Pfurtscheller, G. & Aranibar, A. (1977). Event-​related cortical desynchronization detected by
power measurements of scalp EEG. Electroencephalography and Clinical Neurophysiology,
42(6), 817–​826.
Pfurtscheller, G., Neuper, C., Andrew, C., & Edlinger, G. (1997). Foot and hand area mu
rhythms. International Journal of Psychophysiology, 26(1–​3), 121–​135.
Pfurtscheller, G., Stancak, A., Jr., & Neuper, C. (1996). Event-​related synchronization (ERS) in
the alpha band-​-​an electrophysiological correlate of cortical idling: a review. International
Journal of Psychophysiology, 24(1-​2), 39–​46.
Poldrack, R. A. (2011). Inferring mental states from neuroimaging data: from reverse inference
to large-​scale decoding. Neuron, 72(5), 692–​697. doi:10.1016/​j.neuron.2011.11.001
Popov, T., & Szyszka, P. (2019). Alpha oscillations govern interhemispheric spike timing
coordination in the honeybee brain. https://royalsocietypublishing.org/doi/10.1098/
rspb.2020.0115#:~:text=What%20is%20the%20function%20of,information%20
flow%20during%20spontaneous%20activity.
Pornpattananangkul, N., Grogans, S., Yu, R., & Nusslock, R. (2019). Single-​trial EEG dissociates
motivation and conflict processes during decision-​making under risk. NeuroImage, 188,
483–​501. doi:10.1016/​j.neuroimage.2018.12.029
Sauseng, P., Klimesch, W., Heise, K. F., Gruber, W. R., Holz, E., Karim, A. A., . . . Hummel, F. C.
(2009). Brain oscillatory substrates of visual short-​term memory capacity. Current Biology,
19(21), 1846–​1852. doi:10.1016/​j.cub.2009.08.062
 THE ROLE OF ALPHA AND BETA OSCILLATIONS IN THE HUMAN EEG     219

Schneidman, E., Puchalla, J. L., Segev, R., Harris, R. A., Bialek, W., & Berry, M. J., 2nd. (2011).
Synergy from silence in a combinatorial neural code. Journal of Neuroscience, 31(44), 15732–​
15741. doi:10.1523/​JNEUROSCI.0301-​09.2011
Schreiner, T., Doeller, C. F., Jensen, O., Rasch, B., & Staudigl, T. (2018). Theta phase-​coordinated
memory reactivation reoccurs in a slow-​oscillatory rhythm during NREM sleep. Cell
Reports, 25(2), 296–​301. doi:10.1016/​j.celrep.2018.09.037
Schyns, P. G., Thut, G., & Gross, J. (2011). Cracking the code of oscillatory activity. PLoS Biology,
9(5), e1001064. doi:10.1371/​journal.pbio.1001064
Shannon, C. E. & Weaver, W. (1949). A mathematical theory of communication. University of
Illinois Press.
Siegel, M., Donner, T. H., & Engel, A. K. (2012). Spectral fingerprints of large-​scale neuronal
interactions. Nature Reviews Neuroscience, 13(2), 121–​134. doi:10.1038/​nrn3137
Staudigl, T. & Hanslmayr, S. (2019). Reactivation of neural patterns during memory reinstate-
ment supports encoding specificity. Cognitive Neuroscience, 10(4), 175–​185.
Staudigl, T., Vollmar, C., Noachtar, S., & Hanslmayr, S. (2015). Temporal-​pattern similarity
analysis reveals the beneficial and detrimental effects of context reinstatement on human
memory. Journal of Neuroscience, 35(13), 5373–​5384. doi:10.1523/​JNEUROSCI.4198-​14.2015
Thut, G., Nietzel, A., Brandt, S. A., & Pascual-​ Leone, A. (2006). Alpha-​ band
electroencephalographic activity over occipital cortex indexes visuospatial attention bias
and predicts visual target detection. Journal of Neuroscience, 26(37), 9494–​9502. doi:10.1523/​
JNEUROSCI.0875-​06.2006
VanRullen, R. (2016). Perceptual cycles. Trends in Cognitive Sciences, 20(10), 723–​735.
doi:10.1016/​j.tics.2016.07.006
VanRullen, R., Carlson, T., & Cavanagh, P. (2007). The blinking spotlight of attention.
Proceedings of the National Academy of Sciences of the United States of America, 104(49),
19204–​19209. doi:10.1073/​pnas.0707316104
von Stein, A., Chiang, C., & Konig, P. (2000). Top-​down processing mediated by interareal syn-
chronization. Proceedings of the National Academy of Sciences of the United States of America,
97(26), 14748–​14753. doi:10.1073/​pnas.97.26.14748
von Stein, A. & Sarnthein, J. (2000). Different frequencies for different scales of cortical inte-
gration: from local gamma to long range alpha/​theta synchronization. International Journal
of Psychophysiology, 38(3), 301–​313.
Waldhauser, G. T., Braun, V., & Hanslmayr, S. (2016). Episodic memory retrieval functionally
relies on very rapid reactivation of sensory information. Journal of Neuroscience, 36(1), 251–​
260. doi:10.1523/​JNEUROSCI.2101-​15.2016
Waldhauser, G. T., Johansson, M., & Hanslmayr, S. (2012). alpha/​beta oscillations indi-
cate inhibition of interfering visual memories. Journal of Neuroscience, 32(6), 1953–​1961.
doi:10.1523/​JNEUROSCI.4201-​11.2012
Wiest, M. C. & Nicolelis, M. A. (2003). Behavioral detection of tactile stimuli during 7-​12 Hz
cortical oscillations in awake rats. Nature Neuroscience, 6(9), 913–​914. doi:10.1038/​nn1107
Womelsdorf, T., Valiante, T. A., Sahin, N. T., Miller, K. J., & Tiesinga, P. (2014). Dynamic circuit
motifs underlying rhythmic gain control, gating and integration. Nature Neuroscience, 17(8),
1031–​1039. doi:10.1038/​nn.3764
Worden, M. S., Foxe, J. J., Wang, N., & Simpson, G. V. (2000). Anticipatory biasing of visuo-
spatial attention indexed by retinotopically specific alpha-​band electroencephalography
increases over occipital cortex. Journal of Neuroscience, 20(6), RC63.
 CHAPTER 11

T heory and Re se a rc h
on Asymm etri c Fronta l
C ortical Ac t i v i t y
as Assesse d by E E G
F requ ency A na lyse s

EDDIE HARMON-​J ONES, TAYLOR POPP,

AND PHILIP A. GABLE

Frequency analyses of electroencephalographic (EEG) activity have played a major

role in research and theory concerning the role of left versus right frontal cortical ac-
tivity in emotion-​and motivation-​related phenomena. In this work, researchers have
focused primarily on alpha power (8–​13 Hz) activity in the left versus right frontal
regions. This focus on alpha power was based on other research suggesting that alpha
power is inversely related to cortical activity (Cook et al., 1998; Davidson et al., 1990).
Much of this research has used the difference between the left and right frontal re-
gion as the variable of interest. The use of difference scores is based on past research
using a variety of methods that suggest with regard to emotion-​and motivation-​related
variables, one frontal hemispheric region may be inhibiting the opposite frontal hemi-
spheric region (Schutter, 2009; Schutter et al., 2001). The corpus callosum, the largest
white matter bundle connecting the left and right hemispheres, likely plays a critical role
in this asymmetric functioning of the frontal cortices (Schutter & Harmon-​Jones, 2013).
Given this, researchers typically subtract left frontal alpha power from right frontal
alpha power (after the values are log transformed to normalize the distributions, e.g., log
F4 minus log F3). The resulting metric is then referred to as relative left or relative right
frontal activity, depending on whether the difference score is a more positive (relative
left) or a more negative (relative right) numeric value.
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    221

11.1  Definitions of Psychological

Concepts: Affective Valence and
Motivational Direction

We begin by providing our definitions of the psychological concepts of affective valence

and motivational direction. Affective valence denotes whether an affective trait or state
is positive or negative. Although affective valence can be defined in a number of ways
(Harmon-​Jones & Gable, 2018; Lazarus, 1991), we define it as the subjective feel of the
affect (emotion or mood; affect encompasses both of these latter concepts). Affective
experiences that organisms like feeling are positive, and affective experiences that
organisms dislike feeling are negative (Harmon-​Jones et al., 2011).
Motivational direction refers to the urge to move toward (approach) or away (with-
drawal) from something (Harmon-​Jones et al., 2013; Gable & Dreisbach, 2021). Many
theories suggest that approach motivation is triggered by rewards, desired outcomes, or
positive goals, and that withdrawal (avoidance) motivation is triggered by punishments,
undesired outcomes, or negative goals. The anticipations of these end-​products may
inspire much approach and withdrawal motivation, but these anticipations are not the
only causes of approach and withdrawal motivation and they should therefore not be
part of the definition. That is, approach and withdrawal motivation can occur without
being prompted by these anticipations (for an extended discussion, see Harmon-​Jones
et al., 2013).

11.2  Affective Valence and Asymmetric

Frontal Cortical Activity

Beginning in the 1930s, research using a variety of methods suggested that the left and
right frontal cortices are involved in different emotional (affective) responses. For ex-
ample, lesion studies as well as experiments that injected a barbiturate derivative
(amytal) into one of the internal carotid arteries (to suppress the activity of one hemi-
sphere) showed that the loss of activity in the left frontal cortex was associated with
depressed affect, whereas loss of activity in the right frontal cortex was associated with
manic affect and euphoria (Alema et al., 1961; Black, 1975; Gainotti, 1972; Gasparrini
et al., 1978; Goldstein, 1939; Perria et al., 1961; Robinson & Price, 1982; Rossi & Rosadini,
1967; Sackeim et al., 1982; Terzian & Cecotto, 1959). These outcomes are likely due to
the release of one hemisphere from contralateral inhibitory forces (Schutter & Harmon-​
Jones, 2013). For example, when the right hemisphere was deactivated by damage or
amytal, the left hemisphere became more uninhibited and more active, which caused
manic affect.
222    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

These results can be interpreted in one of two ways. According to the affective va-
lence model of frontal asymmetry, the left frontal cortical region is involved in the ex-
perience and expression of positive affect, whereas the right frontal cortical region is
involved in the experience and expression of negative affect. According to the motiv-
ational direction model of frontal asymmetry, the left frontal cortical region is involved
in the experience and expression of approach motivation, whereas the right frontal cor-
tical region is involved in the experience and expression of withdrawal motivation. Until
the 1990s, the two conceptual models were considered to yield the same predictions be-
cause approach motivation was conceived of as being associated with positive affect and
withdrawal motivation was conceived of as being associated with negative affect. In the
late 1990s, researchers began using anger to tease predictions from these two conceptual
models apart, because anger is an approach-​motivated but negative affect (Harmon-​
Jones, 2003a). The following sections briefly review the research on the two models
along with research on anger and frontal asymmetry.

11.3  Resting Asymmetric Frontal

Activity and Trait Affective Valence

These early results inspired EEG researchers to examine EEG alpha power over the
frontal cortex and test whether it was associated with affective variables. Most of the first
EEG studies on asymmetric frontal asymmetry tested individuals in a resting, baseline
state (i.e., sitting quietly in the lab for four to eight minutes). Researchers assumed that
this resting, baseline EEG would tap into a personality trait, and they then related EEG
frontal asymmetry with other personality or individual difference measures.
Several studies found that depression was correlated with less relative left frontal
cortical activity (e.g., Allen et al., 1993; Henriques & Davidson, 1990; Jacobs & Snyder,
1996; Schaffer et al., 1983; see meta-​analysis by Thibodeau et al., 2006). Other studies
suggested that trait negative affect was correlated with greater relative right frontal ac-
tivity, whereas trait positive affect was correlated with greater relative left frontal activity
(Tomarken et al., 1992).

11.4  Manipulations of Asymmetric

Frontal Cortical Activity and
Affective Reactions

The studies assessing resting baseline asymmetric frontal cortical activity were correl-
ational; therefore, it is impossible to infer that the differences in asymmetric frontal
cortical activity were causally involved in the observed affective processes. In an effort
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    223

to provide evidence that would allow causal inferences, some researchers manipulated
asymmetric frontal cortical activity and tested whether manipulation influenced other
affective variables.

11.4.1  Neurofeedback
Studies have used neurofeedback training to manipulate asymmetric frontal cortical ac-
tivity (e.g., Allen et al., 2001; Harmon-​Jones et al., 2008). In this research, operant con-
ditioning is used to produce certain patterns of brainwaves. Reward feedback (e.g., a
simple tone) corresponding to “desired” patterns of brainwave activity is presented to
participants. Over numerous presentations of this reward feedback, the brain learns
to produce the desired brainwave activity, such as greater relative left frontal cortical
activity. These neurofeedback-​induced changes in brainwaves occur via nonconscious
learning processes (Kamiya, 1979; Siniatchkin et al., 2000).
In one example experiment, relative right versus relative left frontal activity was
manipulated using neurofeedback (Allen et al., 2001). In the experiment, participants
were instructed to attempt to make a particular tone play as much as possible.
Asymmetric frontal cortical activity (i.e., alpha power at F4 minus alpha power at F3)
was calculated during the first second of each two-​second time period. This calculated
value was then compared against a criterion value that had been set for that session
(based on the individual’s previous asymmetry index). If the calculated value was larger
than the criterion value in the desired direction, a “reward” tone was played; if it was
not, a “non-​reward” tone was played. After several days of neurofeedback training,
participants then viewed emotionally evocative film clips as zygomatic and corrugator
muscle region activity was recorded. Results revealed that the neurofeedback training
influenced asymmetric frontal cortical activity in the predicted direction (for a repli-
cation, see Quaedflieg et al., 2016). Moreover, the manipulated increase in relative right
frontal cortical activity, as compared to relative left frontal cortical activity, caused less
zygomatic and more corrugator muscle region activity in response to all film clips. These
results suggest that asymmetric frontal cortical activity is causally involved in emotional
responses.

11.4.2 Unilateral hand contractions

Asymmetric frontal cortical activity has also been manipulated using unilateral hand
contractions. Because unilateral hand contractions cause increased activation of the
contralateral motor region (Hellige, 1993), whose activation may spread to frontal
regions, unilateral hand contractions may influence emotional responses (Schiff &
Lamon, 1989; 1994). Indeed, research revealed that contractions of the left hand cause
increased feelings of sadness and more negative perceptions and judgments, whereas
224    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

contractions of the right hand cause increased feelings of positive affect and more posi-
tive perceptions and judgments (Schiff & Lamon, 1989, 1994).
Based on this research, experiments have tested whether unilateral hand contractions
would influence EEG and other emotional responses. In one experiment, participants
were instructed to squeeze a ball in their left or right hand for several minutes (Harmon-​
Jones, 2006). Then, their self-​reported affective responses were measured in response
to a radio editorial designed to evoke a moderate amount of positive affect. Results
revealed that the contraction of one hand increased cortical activity over the central and
frontal regions of the contralateral hemisphere (as measured by EEG alpha suppression;
see Gable et al., 2013 for replication). Moreover, this manipulation influenced positive
affect, such that right-​hand contractions caused more positive affect than the left-​hand
contractions.

11.4.3 Situational Manipulations of Positive and Negative

Affect and Asymmetric Frontal Cortical Responses
Additional research has measured asymmetric frontal cortical activity in response to
manipulations of positive and negative affect. For example, Davidson and Fox (1982)
found that 10-​month-​old infants evidenced greater relative left frontal cortical activity
to film clips of an actress displaying happy facial expressions as compared to sad facial
expressions. Ekman and Davidson (1993) found that adults evidenced greater relative
left frontal activity when they were induced to make facial expressions of genuine smiles
of joy as compared to facial expressions of non-​genuine smiles of joy. Coan, Allen, and
Harmon-​Jones (2001) found that adults evidenced less relative left frontal activity when
they were induced to make facial expressions of fear as compared to several other types
of emotional facial expressions.

11.5  Asymmetric Frontal Cortical

Activity and Motivational Direction

Several studies suggest that the left frontal cortical region is involved in the experience
and expression of positive affect, whereas the right frontal cortical region is involved
in the experience and expression of negative affect. This research suggested that asym-
metric frontal cortical activity reflected positive or negative affect, or affective valence.
Research testing this affective valence model happened concurrently with other re-
search testing a motivational direction model, which posits that relative left frontal
cortical activity is associated with approach motivation and that relative right frontal
cortical activity is associated with withdrawal motivation. For several years, the affective
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    225

valence and motivational direction models were viewed as compatible models that
made identical predictions. This compatibility resulted from viewing positive affect as
being always associated with approach motivation and negative affect as being always
associated with withdrawal motivation.

11.5.1 Resting Asymmetric Frontal Activity and Trait

Motivational Direction
Many studies measured trait approach and withdrawal motivation with Carver
and White’s (1994) behavioral inhibition/​ behavioral activation system (BIS/​ BAS)
questionnaires. The approach motivation (BAS) questionnaire has items such as “I go
out of my way to get things I want” and “I crave excitement and new sensations”. The
withdrawal motivation (BIS) questionnaire has items such as “I worry about making
mistakes” and “I have very few fears compared to my friends (reverse scored).”
The first two studies found that individual differences in self-​reported trait approach
motivation were correlated with greater relative left frontal cortical activity during
resting baseline sessions (Harmon-​Jones & Allen, 1997; Sutton & Davidson, 1997). One
of these studies also found that trait “withdrawal” motivation correlated with greater
relative right frontal activity during resting baseline (Sutton & Davidson, 1997), whereas
the other study found no significant correlation between trait withdrawal motivation
and relative right frontal activity (Harmon-​Jones & Allen, 1997).
Additional studies replicated this latter pattern of results (Amodio et al., 2008;
Amodio et al., 2004; Coan & Allen, 2003), and an EEG source localization study
suggested that this trait approach/​relative left frontal cortical activity correlation was
due to activation in the middle frontal gyrus (BA11; De Pascalis et al., 2013).

11.5.2 Situational Manipulations of Motivation and

Asymmetric Frontal Cortical Responses
11.5.2.1 Pictures of Motivationally Significant Stimuli
To test whether approach motivational intensity would predict relative left frontal cor-
tical activity to appetitive stimuli, studies have been conducted that first measured
individuals’ self-​reported liking for dessert and the time since they had last eaten. These
measures were included to assess individual differences in approach motivation rele-
vant to the stimuli to be presented. Next, participants viewed pictures of desserts and
neutral objects while EEG was recorded. Results revealed that individuals with more
intense approach motivation (i.e., longer time since eating, more liking for dessert) to-
ward pictures of desserts evidenced more relative left frontal activity to dessert stimuli
but not to neutral stimuli (Gable & Harmon-​Jones, 2008; Harmon-​Jones & Gable,
2009). In these studies, the appetitive pictures alone did not cause a significant increase
226    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

in relative left frontal cortical activity. This lack of a main effect of picture type on asym-
metric frontal activity is consistent with some other research (Elgavish et al., 2003;
Hagemann et al., 1998; see also reviews by Murphy et al., 2003 and Pizzagalli et al.,
2003). The lack of a main effect may have occurred because pictures evoke different
amounts of approach (withdrawal) motivation across participants. Some individuals
may respond with no motivation, and others may respond with much motivation
(Harmon-​Jones, 2007).
Other research has suggested that some pictorial stimuli may evoke intense approach
(or withdrawal) motivation in all participants. For example, Schöne and colleagues
(2016) found that erotic stimuli caused greater relative left frontal activity than com-
parison stimuli of extreme sports, dressed women, and daily activities. The observed
difference in relative left frontal activity between erotic and extreme sports stimuli is
particularly interesting because both sets of stimuli evoked high and equal levels of self-​
reported positive affect and arousal.

11.5.2.2 Positive Affects Varying in Approach and Asymmetric

Frontal Cortical Activity
This research suggests that relative left frontal cortical activity reflects the intensity of
approach motivation. However, most of this research could be interpreted by the va-
lence model as well, which would simply posit that the results are due to positive affect
instead of approach motivation. One way to tease these two conceptual models apart
is to manipulate the intensity of approach motivation while holding positive affect
constant. The motivational direction model would predict that positive affects high in
approach motivation should evoke greater relative left frontal cortical activity than posi-
tive affects low in approach motivation. The affective valence model would instead pre-
dict that both types of positive affect should evoke equal levels of relative left frontal
cortical activity.
One experiment tested these competing predictions by having individuals write
about: 1) the steps needed to obtain a desired goal (positive action-​oriented); 2) a normal
day (neutral); or 3) a past event that made them feel good without personal action (posi-
tive inaction-​oriented; Harmon-​Jones et al., 2008, Experiment 2). The two positive
conditions evoked greater levels of self-​reported general positive affect than the neutral
condition. However, the positive action-​oriented condition caused greater relative left
frontal cortical activity than the other two conditions did. Thus, these results suggest
that high approach-​motivated positive affect caused greater relative left frontal cortical
activity than low approach-​motivated positive affect.

11.5.2.3 Facial Expressions of Approach-​Motivated Positive Affect

Based on research that had revealed that facial expressions of determination were
identified as being high in positive approach motivation (Harmon-​Jones et al., 2011),
subsequent research instructed individuals to make a facial expression that expressed
“determination” or a low approach-​motivated positive expression of “satisfaction”
or a neutral expression (Price et al., 2013). Then, individuals performed a task that
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    227

assessed behavioral persistence. As predicted by the motivational model (but not the
affective valence model), individuals who made the determination facial expression
(high approach-​motivated positive affect) had greater relative left frontal activity than
individuals in the other two conditions. In addition, within the determination condi-
tion, greater relative left frontal cortical activity was associated with greater behavioral
persistence.

11.5.2.4 Using Whole Body Posture to Manipulate Approach Motivation

Based on previous research that had shown that whole body posture can manipu-
late levels of approach motivation (e.g., Harmon-​Jones & Peterson, 2009; Price &
Harmon-​Jones, 2011), research was conducted to test whether this manipulation
would influence relative left frontal cortical activity. In this study, seated individuals
were instructed to either lean forward as one might do while reaching for a desired
object (high approach) or to recline fully in a reclining chair (low approach; Harmon-​
Jones et al., 2011). Then, while in one of these two positions, the individuals viewed
approach-​oriented (dessert) and neutral (rock) pictures using virtual reality glasses,
so that the viewing distance was held constant. As predicted, individuals in the high
approach leaning forward posture evidenced greater relative left frontal activity to the
approach-​oriented stimuli as compared to the neutral stimuli. Individuals in the low
approach reclining posture did not evidence a difference in relative left frontal activity
to the two picture types.

11.5.2.5 Final Thoughts
The reviewed evidence suggests that relative left frontal cortical activity is associated
with approach motivation. This association occurs even when approach motivation
is not confounded with positive affect. That is, in approach motivation, some positive
affects are low and some are high, but the research has revealed that it is primarily the
high approach-​motivated positive affects that are associated with greater relative left
frontal activity.

11.6  Anger and Asymmetric Frontal

Cortical Activity

To better understand the emotive functions of asymmetric frontal cortical activity,

anger has been examined, as anger provides a way of removing the “natural” confound
between affective valence and motivational direction. That is, anger is often posited to
be a negative affect (Harmon-​Jones, 2004; Harmon-​Jones et al., 2011) associated with
approach motivation, as recognized in classic work (e.g., Darwin, 1872; Blanchard
& Blanchard, 1984; Ekman & Friesen, 1975; Lagerspetz, 1969; Plutchik, 1980; Young,
1943) as well as more contemporary work (e.g., Berkowitz & Harmon-​Jones, 2004;
228    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

Carver & Harmon-​Jones, 2009; Harmon-​Jones et al., 2009; Harmon-​Jones et al., 2013).
To give just a few examples, research has revealed that individual differences in BAS
(Carver & White, 1994) are positively correlated with individual differences in anger
(Harmon-​Jones, 2003b; Smits & Kuppens, 2005), greater anger responses to situational
anger manipulations (Carver, 2004), greater aggressive inclinations especially when
approach motivation is activated (Harmon-​Jones & Peterson, 2008), and more atten-
tional engagement to angry faces, as in approach-​based dominance confrontations
(Putman et al., 2004).
If asymmetric frontal cortical activity reflects affective valence, then anger should
be associated with relative right frontal activity because anger is a negative affect. In
contrast, if asymmetric frontal cortical activity reflects motivational direction, then
anger should be associated with relative left frontal activity because anger is approach
motivated. Research has tested these competing predictions.

11.6.1 Resting Asymmetric Frontal Cortical Activity and

Trait Anger
Studies with adolescents (Harmon-​Jones & Allen, 1998) and young adults (Harmon-​
Jones, 2004) have found that individual differences in anger relate positively with rela-
tive left frontal cortical activity, assessed during resting baseline. This latter study also
measured attitudes toward anger and revealed that anger was regarded as a negative
affect and that these negative attitudes toward anger did not correlate with asymmetric
frontal activity. Other studies have revealed that trait anger correlates positively with
relative left frontal activity in incarcerated violent offenders (Keune et al., 2012), and
that trait aggression correlates positively with relative left frontal activity in adults with
ADHD (Keune et al., 2011). Following from research showing that anger and jealousy
are positively correlated in some circumstances, research has revealed that one-​year-​old
infants with greater relative left frontal activity during a resting baseline display more
jealous responses when their mothers attend to a social rival (Mize & Jones, 2012).

11.6.2 Manipulation of Asymmetric Frontal Cortical

Activity and Anger Reactions
Other research has tested whether the manipulation of asymmetric frontal cortical
activity via unilateral hand contractions will influence anger-​related responses. In
one experiment, participants contracted their right or left hand using the methods
described earlier (Harmon-​Jones, 2006). Then, they received insulting interpersonal
feedback and then played a reaction time game against the person who had osten-
sibly insulted them. The reaction time game provided an assessment of behavioral
aggression, as participants could select the volume and duration of noise blast to give
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    229

to the other participants on trials they won. Replicating previous research, the con-
traction of the right hand led to greater relative left central and frontal cortical activity
than the contraction of left hand. More importantly, as compared to the left hand
contractions, the right hand contractions led to more aggression behavior (Peterson
et al., 2008).
Additional research revealed that compared to left-​ hand contractions, right-​
hand contractions led to greater self-​reported anger to being socially ostracized in
a Cyberball game (Peterson et al., 2011). These results suggest that manipulated
increases in relative left frontal cortical activity lead to increased anger-​related
responses.

11.6.3 State Anger and Relative Left Frontal Cortical Activity

Other research has tested whether situationally manipulated anger influences relative
left frontal cortical activity. In one experiment, participants who were insulted (i.e.,
received insulting feedback on an essay they had written) responded with greater rela-
tive left frontal activity than individuals who were not insulted (i.e., received mildly
positive feedback; Harmon-​Jones & Sigelman, 2001). Moreover, within the insult con-
dition, self-​reported anger to the feedback and behavioral aggression toward the person
who provided the feedback were both positively correlated with relative left frontal ac-
tivity. Other experiments have conceptually replicated these results (e.g., Harmon-​Jones
et al., 2004; Jensen-​Campbell et al., 2007; Verona et al., 2009). Research has extended
these early results by showing that lab-​induced social rejections can induce feelings of
jealousy and anger as well as increased relative left frontal cortical activity (Harmon-​
Jones et al., 2009).
Individual differences have also been found to moderate these anger-​related relative
left frontal cortical activity responses. For instance, one study found that, as compared to
individuals with no affective disorders, individuals with borderline personality disorder
had greater relative left frontal activity to social rejection, whereas individuals with
major depression had greater relative right frontal activity to social rejection (Beeney
et al., 2014). In addition, individual differences in BAS positively correlated with greater
relative left frontal cortical activity to anger induced via pictures offensive to the sample
of individuals (Americans viewing anti-​American images such as flag burning; Gable &
Poole, 2014).

11.6.4 Manipulating Approach Motivation Independently

of Anger
Anger is presumably related to relative left frontal cortical activity because anger
is associated with approach motivation. Even more compelling evidence for the
230    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

association between approach motivation and relative left frontal cortical activity
could be provided by manipulating approach motivation independent of anger. That is,
even though anger is often approach motivated, anger is not perfectly associated with
approach motivation and thus it should be possible to manipulate the two constructs
separately.
For example, one variable that should influence (approach) motivational intensity is
coping potential or the difficulty of engaging in behavior. That is, motivational intensity
increases with perceived task difficulty up to the point where the task is perceived as im-
possible, and then motivational intensity drops. So, when a task is perceived as impos-
sible, or coping potential is very low, motivational intensity should be low (Brehm, 1999;
Brehm & Self, 1989).
In one experiment testing these hypotheses, individuals were induced to believe
that they would or would not be able to engage in action that might resolve the anger-​
evoking event (i.e., sign petitions to halt a university tuition increase; Harmon-​Jones
et al., 2003). Results revealed that individuals who were angered and believed they could
engage in action had greater relative left frontal activity than individuals who were
angered and believed they could not engage in action (the tuition increase had already
been approved). Moreover, in the action-​possible condition, greater relative left frontal
activity in response to the angering event correlated with more approach-​related be-
havior (i.e., signing the petition and taking more petitions to have others sign). Other
studies have conceptually replicated this effect of anger and approach action possibility
on relative left frontal activity using pictorial stimuli to evoke anger (Harmon-​Jones
et al., 2006).
These results could be interpreted to indicate that greater relative left frontal cor-
tical activity only occurs to anger evocations when individuals are given explicit
approach motivational opportunities. Other research suggests, however, that these
explicit approach motivational opportunities increase relative left frontal activity but
are not necessary for it to occur. That is, individuals who were exposed to pictures
that evoked anger and were given no explicit approach opportunities had increased
relative left frontal cortical activity if they were high in trait anger (Harmon-​Jones,
2007). Thus, explicit opportunities for approach-​motivated behavior are not neces-
sary to cause relative left frontal activity during anger. Anger can evoke approach
motivation without explicit approach motivational opportunities being immediately
present.
Other experiments have manipulated approach motivation independently of anger
and found that the approach motivation drives the increase in relative left frontal ac-
tivity. For example, one experiment used a manipulation of whole-​body posture to ma-
nipulate approach motivation. When individuals are in a supine body position (lying flat
on their backs), they are likely to be less approach motivated. In this anger experiment,
individuals were interpersonally insulted while sitting upright or while in a supine pos-
ture. Results revealed that individuals who were insulted while in the supine posture
had lower relative left frontal cortical activity than individuals who were insulted while
sitting upright (and the latter condition had greater relative left frontal activity than an
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    231

upright-​neutral-​no-​insult comparison condition; Harmon-​Jones & Peterson, 2009).

Interestingly, the results also revealed that both the supine and upright insult conditions
reported feeling angrier than the neutral comparison condition, and these two insult
conditions did not differ from each other. Thus, this research suggests that anger relates
to relative left frontal cortical activity because of approach motivation; when approach
motivation was decreased with a supine body posture, individuals who were angered
did not have the typical increase in relative left frontal activity. However, they did have
the same level of angry feelings as those who were in the standard upright insult condi-
tion, suggesting that angry feelings are not inevitably associated with relative left frontal
activity or approach motivation.

11.6.5 Anger and Avoidance Motivation

A correlational study (Hewig et al., 2004) measured trait anger-​out, trait anger-​in, and
trait anger-​control using the State-​Trait Anger Expression Questionnaire (Spielberger,
1988). Resting baseline asymmetric frontal cortical activity was also assessed. Trait
anger-​out likely measures approach-​motivated anger (e.g., “When angry or furious,
I lose my temper”; Spielberger et al., 1995, p. 57). Trait anger-​in measures the extent
to which individuals hold anger in (e.g., “When angry or furious, I keep things in”).
Trait anger-​control measures the extent to which individuals control their anger (e.g.,
“When angry or furious, I control my angry feelings.”). Trait anger-​out correlated with
greater relative left frontal activity. Trait anger-​control correlated with greater relative
right frontal activity. Trait anger-​in was not significantly correlated with asymmetric
frontal cortical activity. The researchers suggested that anger-​control was associated
with relative right frontal activity because anger-​control was associated with anger
withdrawal.
Anger may evoke withdrawal when anger is mixed with concerns about being
punished. For example, some individuals may become angry over social policies
that pressure one to behave less racially prejudiced. At the same time, however,
they may experience anxiety about expressing anger in these situations because
they fear social censure. A study designed such a situation in the lab and found that
anger in this situation was associated with greater relative right frontal cortical ac-
tivity (Zinner et al., 2008). In this study, anger in response to the situation correlated
with more spontaneous eye blinking, suggesting that anger was also associated with
suppressing emotions (Gross & Levenson, 1993). Moreover, self-​reported anger was
associated with self-​reported anxiety. These latter results support the idea that the
social situation had also evoked concerns about being socially censured for feeling
angry. Although these results are correlational, the authors suggest that anger may
be associated with relative right frontal cortical activity when the motivation to with-
draw is also high.
232    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

11.7  Effortful Control and Relative

Right Frontal Activity

As noted, models of frontal asymmetry link approach motivation with greater relative
left frontal activity. Both the affective valence model and the motivational direction
model of frontal asymmetry associate withdrawal motivation with greater relative right
frontal activity. Despite evidence supporting this model, many studies have failed to
replicate the relationship between right frontal activity and withdrawal motivated traits
and states (Amodio et al., 2008; Berkman & Lieberman, 2010; Coan & Allen, 2003; Coan
et al., 2001; De Pascalis et al., 2013; Henriques & Davidson, 2000; Hewig et al., 2004,
2006; Jackson et al., 2003; Keune et al., 2012; Kline et al., 2000; Pizzagalli et al., 2005;
Quirin et al., 2013; Wacker et al., 2008; Wacker et al., 2010). This has led researchers to
question what could be causing the inconsistencies in the literature. Some suggest that
withdrawal motivation is a complex system that is difficult to accurately measure inde-
pendently of confounding variables (Amodio et al., 2008; Coan & Allen, 2004). Others
suggest that another system entirely accounts for greater right frontal asymmetry.
A model presented by Gable and colleagues (2018) suggested that right frontal activity
is more related to regulatory control than to withdrawal motivation. Regulatory con-
trol is thought to be carried out by the revised BIS (r-​BIS; Gray & McNaughton, 2000),
which may act as a governing body over conflicts between the approach and withdrawal
systems. Activation of r-​BIS leads to enhanced attention to, memory for, and detec-
tion of negatively valenced information, allowing it to manage conflicts by enhancing
aversion to one motivated behavior over the other (Heym et al., 2008). This can occur as
either the suppression of a behavioral response or an override of motivational impulses
(Aron et al., 2004, 2014; Carver & Connor-​Smith, 2010; Hester & Garavan, 2004, 2009).
As such, r-​BIS is related to effortful control, constraint, self-​control, inhibition, conflict
monitoring, and error detection (Carver & Connor-​Smith, 2010; Carver et al., 2008;
Derryberry & Rothbart, 1997; Gray & McNaughton, 2000; Kochanska & Knaack, 2003;
Nigg, 2006; Rothbart & Rueda, 2005). Low functioning r-​BIS is thought to be related to
impulsive behavior, deficits in inhibitory control, and externalizing disorders such as
substance abuse (Enticott et al., 2006; Logan et al., 1997). Unusually high functioning
of r-​BIS, on the other hand, may be related to passive avoidance, anxious inaction,
and internalizing disorders such as generalized anxiety disorder (Carver et al., 2008;
DeYoung, 2015; Eisenberg et al., 2004; Rothbart et al., 2004; Strack & Deutsch, 2004;
Valiente et al., 2003).
While much research has examined the relationship between asymmetric frontal cor-
tical activity and motivational systems, few studies have investigated the connections
between regulatory control (r-​BIS) and asymmetric frontal activity (Gable et al., 2015;
Grimshaw & Carmel, 2014; Neal & Gable, 2016; Wacker et al., 2003). R-​BIS acts as a
controlling agent over approach and withdrawal behaviors. The present model suggests
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    233

that greater relative right frontal activity is indicative of greater r-​BIS functioning
whereas reduced relative right frontal activity suggests reduced r-​BIS functioning.

11.7.1 Trait r-​BIS and Frontal EEG Activity

R-​BIS functioning is a stable individual difference measured via personality
questionnaires targeting traits such as impulsivity, sensation seeking, and inhib-
ition. When r-​BIS is hyperactive, traits such as neuroticism and anxiety caused by
passive avoidance become prevalent, often resulting from approach-​avoidant conflicts
(DeYoung, 2015). When r-​BIS is hypoactive, on the other hand, approach and with-
drawal may be unregulated and individuals may be less able to inhibit motivational
tendencies. Impulsivity is thought to index inverse functioning of r-​BIS because r-​BIS is
strongly related to inhibition, effortful control, and overall executive functioning (Bari
& Robbins, 2013; Bickel et al., 2012; Eisenberg et al., 2004).
Impulsivity can be measured with a number of personality traits. For instance, posi-
tive urgency measures impulsivity through the failure of r-​BIS to inhibit approach
tendencies, which ultimately leads to rash action during intense positive states (Cyders
et al., 2010; Zapolski et al., 2009). To examine relationships between impulsive per-
sonality traits and asymmetrical frontal cortical activity, Gable and colleagues (2015)
conducted a resting frontal EEG study investigating the association between positive
urgency and frontal activity. Results showed a relationship between positive urgency
and greater relative left frontal activity. This suggests that reduced relative right frontal
activity is associated with reduced r-​BIS function. Using standardized low-​resolution
brain electromagnetic tomography (SLORETA; Pascual-​Marqui, 2002), source localiza-
tion results indicated that lower relative right frontal activity was due to reduced activity
in the right inferior frontal gyrus (rIFG). This further suggests that it is reduced right
frontal activity, rather than increased left frontal activity, that was driving the observed
asymmetric activity.
Neal and Gable (2016) investigated the relationship between frontal activity and tenets
of impulsivity that are not related to positive affect or approach motivation. Participants
completed the UPPS-​P scale, which assesses negative urgency, lack of premeditation,
and lack of perseverance, along with positive urgency (Cyders & Smith, 2007; Whiteside
et al., 2005). Participants’ resting EEG activity was then assessed. Negative urgency (i.e.,
rash behavior in negative emotional contexts) was related to heightened left frontal
activity at rest, suggesting that the relationship between impulsivity and relative left
frontal activity was not driven by positive emotionality. Non-​emotional impulsive traits
(i.e., lack of premeditation and lack of perseverance) were also associated with reduced
right frontal activity. This relationship between impulsivity and right frontal activity
remained unchanged when controlling for trait approach motivation. Source localiza-
tion for the relationship between these tenets of impulsivity showed reduced activity
in the right cingulate gyrus and the right medial frontal gyrus. Taken together, these
234    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

results suggest that impulsivity is associated with reduced right frontal activity, inde-
pendent of affective valence.
This study did not find a relationship between trait sensation seeking and frontal
activity. However, the type of sensation seeking scale used (UPPS-​P measure of trait
sensation seeking) does not correlate well with other subscales of the UPPS-​P, and
some researchers have suggested that it may reflect a construct other than impulsivity
(Simons et al., 2010). Santesso et al. (2008), however, used the Zuckerman Sensation
Seeking Scale to measure trait sensation seeking and found that it was related to greater
left frontal (reduced right frontal) activity.
Overall, these findings suggest that deficits in persistence and inhibiting behavior are
associated with reduced right frontal activity. Source localization of the relationship be-
tween r-​BIS and frontal asymmetry suggests that the asymmetry is driven by reduced
activity in the right medial and lateral frontal areas, including areas of the right pre-
frontal cortex.

11.7.2 Evidence of r-​BIS Functioning in Frontal

EEG Activity
Source localization studies have also investigated the source of activity relating to be-
havioral measures of control. Gianotti and colleagues (2009) collected resting EEG data
before having participants engage in a behavioral risk task. When participants engaged
in greater risk-​taking behavior, activity was localized to diminished baseline activity in
the right lateral prefrontal cortex. Those whose resting activation of the right prefrontal
cortex was less stable demonstrated less supervisory control of risky behavior. In a later
study, resting EEG activity was compared to participants’ subsequent acceptance of un-
fair offers in the ultimatum game (Knoch et al., 2010). When presented with an unfair
offer, participants could either accept the offer or punish the opponent for giving them
the offer. Acceptance of unfair offers was assumed to reflect an ability to exercise con-
trol over the initial emotional response in order to maximize economic benefits. Results
showed a positive correlation between baseline right frontal activity and increased
acceptance of most unfair offers. This activity was also localized to the right lateral pre-
frontal cortex.
Studies investigating regulation of anger have demonstrated that effortful control
of anger relates to greater right frontal activity. Hewig and colleagues (2004) found
that the extent to which individuals control their anger (State-​Trait Anger Expression
Questionnaire; Spielberger, 1988) related to greater relative right frontal asymmetry
during resting baseline. The researchers suggested that anger-​control was associated
with relative right frontal activity because anger-​control was associated with anger with-
drawal, but based on the evidence, it seems likely that greater right frontal activity is
linked with greater anger-​control because it is associated with greater effortful control.
Other work has demonstrated that suppressing anger, when it is socially inappropriate
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    235

to express it, causes greater right frontal activity (Zinner et al., 2008). Although greater
right frontal activity may be associated with the motivation to withdraw in some anger
states, these results also support that greater right frontal activity is associated with ef-
fortful control stemming from emotional suppression of anger.
Functioning of r-​BIS can also be connected to drug and alcohol reactivity. Greater
relative left frontal (reduced right frontal) activity has been connected to drug-​cue
reactivity such as alcohol exposure (Myrick et al., 2004) and cocaine cravings (van
de Laar et al., 2004). These increases in left frontal activity in response to substance
cues are thought to be indicative of appetitive responses evoked from substance-​
related stimuli (Carter & Tiffany, 1999). Hypoactivation of rBIS, however, can also
cause increased responsiveness toward alcohol. Mechin and colleagues (2016)
investigated whether it is trait impulsivity or trait approach motivation that drives
the increase in relative left frontal activity in response to alcohol-​related cues. To
determine this, they had participants complete the UPPS-​P Behavioral Impulsivity
Scale (Cyders & Smith, 2007; Whiteside et al., 2005), the BIS/​BAS scales (Carver &
White, 1994), and questions about their drinking habits. They then collected EEG
data while participants viewed alcohol-​related and neutral picture cues. Results
suggested that the reduction in right frontal activity toward alcohol cues was due
to trait impulsivity rather than trait approach motivation. The relationship between
impulsivity and alcohol picture presentation remained constant when controlling for
drinking behaviors and asymmetric frontal activity in response to neutral pictures.
These results suggest that r-​BIS moderates asymmetric frontal activity to alcohol
cues while BAS does not.
Impulsivity is presumably related to relative right frontal cortical activity because im-
pulsivity is associated with reduced effortful control. Evidence demonstrating increases
in relative right frontal activity when individuals demonstrate greater effortful control
and increases in relative left frontal activity when individuals demonstrate greater im-
pulsivity could provide more compelling evidence for this model. Neal and Gable (2019)
used a Balloon Analogue Risk Task (BART) to test whether impulsive or controlled
behaviors influence asymmetric frontal activity. In this study, EEG recordings were
collected as participants performed the BART while simultaneously viewing alcohol
stimuli designed to enhance impulsive tendencies. Participants could win money by
successfully blowing up a virtual balloon. With each pump of the balloon, more money
could be won, but the likelihood of the balloon popping increased. Each trial ended with
either the participant cashing out on the balloon or the balloon popping.
EEG data collected during this task showed that asymmetry scores shifted throughout
alcohol trials. Frontal activity would shift to greater relative left frontal activity in the last
half of trials where the balloon popped (impulsive behavior) while activity would shift
to the right on the last half of trials where the participant cashed out (successful inhib-
ition). These shifts were localized to reduced activity in the rIFG and lIFG, respectively.
This suggests that increased right frontal activity is indicative of impulse control and
diminished right frontal activity leads to more impulsive behavior.
236    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

The right frontal cortex has also been found to play an important role in the r-​BIS
functions of error detection, emotion regulation, and self-​control. When an incor-
rect or inappropriate behavior is enacted, the error-​related negativity (ERN) is evoked
in response. Individuals with greater levels of behavioral inhibition, anxiety, and
emotion regulation tend to have increased ERN amplitudes, suggesting that those
with higher functioning r-​BIS show greater neural responses in response to conflict
monitoring (Amodio et al., 2008; Proudfit et al., 2013; Teper & Inzlicht, 2013). Greater
relative right frontal activity at baseline has been linked to increased ERN amplitudes,
while greater relative left frontal activity has been linked to reduced ERNs (Nash et al.,
2012). Taken together, these results suggest that greater relative right frontal activity
is related to greater r-​BIS functioning in terms of conflict detection in response to
errors.
Recently, Lacey and colleagues (2020) further connected emotion regulation to
right frontal activity. In one experiment, participants listened to anxiety-​inducing
and neutral sound clips and were told to either listen naturally or suppress their emo-
tional reactions to the clips. Participants recorded their level of effort when suppressing
their reactions and noted their affective experience on each trial. Results showed that,
when participants recorded higher levels of effortful control, right frontal activity was
increased. However, experience of negative emotion was not associated with this in-
crease in right frontal activity. In a second experiment, participants were shown nega-
tive and neutral pictures and told that looking at the images for a long time would earn
them money, while choosing to escape from looking at the pictures would earn them
no reward. In this study, right frontal activity was associated with looking at negative
pictures for a longer time during reward trials, but not during non-​reward trials. Both
studies indicate that it was not the negative affect associated with the aversive stimuli,
but rather the effort to engage the negative stimuli that was related to an increase in right
frontal activity.
Schmeichel and colleagues (2016) evaluated the relationship between self-​control
and asymmetrical frontal activity. In this study, participants either had their self-​
control depleted or not, and then underwent EEG recording while viewing posi-
tive pictures. Among individuals who were relatively higher in trait BAS than BIS,
those with depleted (vs. non-​depleted) self-​control showed increased left frontal ac-
tivity in response to positive pictures. Among those with no relative difference in
BIS and BAS scores, those with depleted self-​control showed decreased left frontal
activity in response to positive pictures. This suggests that when r-​BIS is depleted,
those who generally exhibit more approach motivation show greater left frontal ac-
tivity in response to rewarding stimuli. An enhanced r-​BIS, on the other hand, may
be able to lower approach motivation in those with generally hyperactive BAS and
hypoactive BIS.
Overall, these studies suggest that greater right frontal activity may be associated
with processes involving emotion regulation while lower right frontal activity may be
associated with reduced self-​control and hindered error monitoring. Additionally, both
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    237

situational contexts where control must be utilized and control-​related personality traits
have been related to right frontal activity as measured with EEG.

11.8  Additional Models of

Frontal Asymmetry

Researchers have presented additional models to explain frontal asymmetry and its re-
lationship to emotional and motivational variables. The Bilateral BAS Model (Hewig
et al, 2004) and the Activation vs. Inhibition Model (Wacker et al., 2003) each propose
variants of how approach, withdrawal, and inhibition influences frontal asymmetry.

11.8.1 Bilateral BAS Model

Hewig’s bilateral BAS model suggests that both the approach and withdrawal systems
encompass the basic mechanisms of active behavior and are therefore both subsystems
of the BAS. When active behavior is initiated, then, bilateral activation of the frontal
cortices is expected. Hewig and colleagues (2004) first addressed the model in their
study analyzing resting frontal alpha band asymmetry and its relationships with af-
fective valence, motivational direction, and behavioral activation. Resting state data
obtained from each participant was related to measures of trait anger and different anger
styles (STAXI, Spielberger, 1988), affective valence (PANAS), aggression (Aggression
Questionnaire), and behavioral activation (BIS/​BAS). Data analyses indicated that
while valence was not significantly related to frontal asymmetry, relative left frontal
cortical activity was positively correlated with outwardly expressed anger (“anger-​
out,” Spielberger, 1988), trait anger, and aggression, while relative right frontal cortical
activity was positively correlated with lowering arousal in anger-​inducing situations
(“anger-​control,” Spielberger, 1988). Additionally, greater bilateral frontal cortical ac-
tivity was associated specifically with higher BAS scores. These results together suggest
that greater levels of frontal asymmetry are driven by motivational tendencies and that
bilateral frontal activation is driven by the combination of the approach and withdrawal
subsystems of the BAS. A later study (Hewig et al., 2006) using similar methods found
comparable results. Those participants who showed greater bilateral activation while in
a resting state had higher BAS scores. The authors suggest that this result indicates that
BAS scores may encompass both approach-​and withdrawal-​motivated behaviors.
In 2006, Hewig and colleagues conducted a go/​no-​go experiment to discern the re-
lationship between positive and negative reinforcement and BAS scores. In this study,
participants were first shown a cue indicating whether success on the given trial could
add to the participant’s money (positive reinforcement) or stop money from being
subtracted (negative reinforcement). According to Gray’s model of BIS/​BAS (e.g., 1982),
238    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

both types of reinforcement should activate the BAS, as both are a form of reward or
non-​punishment. Participants then completed a go/​no-​go task in which no-​go trials
were considered to be a form of passive avoidance, therefore activating the BIS. After the
task, participants were shown monetary feedback based on their performance. Results
showed that all participants showed greater bilateral frontal activation in response to
reinforcement trials—​regardless of whether it was positive or negative reinforcement—​
and that this effect was strongest in those with higher trait BAS scores. When these
results are considered with prior research suggesting that approach motivation aligns
with greater relative left frontal activity and withdrawal motivation aligns with greater
relative right frontal activity, the suggestion is that the two are subsystems of the
overarching BAS, once again supporting Hewig and colleagues’ bilateral BAS model.
Rodrigues and colleagues (2018) found further support for the bilateral BAS model
using a virtual reality paradigm. In this study, participants navigated a virtual T maze
in which they were to respond to various events. These events could be positive, nega-
tive, or neutral in valence. Positive trials encouraged participants to move toward the
event while negative trials encouraged withdrawal from the event. Approach-​avoidance
conflict trials involved having a positive stimulus guarded by a negative stimulus and
approach-​approach conflict trials involved choosing between two positive stimuli.
There were also two control trial types. In each trial, participants chose in which dir-
ection they would like to move while EEG was recorded. Left frontal activity increased
when participants chose an approach direction while right frontal activity increased
when participants chose a withdrawal direction. Further, bilateral frontal activity
increased during any choice in behavior relative to the choice to not move in any dir-
ection. The authors argue that these results support the role of frontal asymmetry in
behavioral approach or avoidance motivation, as well as the role of bilateral frontal acti-
vation in active behavior.

11.8.2 Activation vs. Inhibition Model

Wacker and colleagues (Wacker et al., 2003; Wacker et al., 2008, 2010) suggest that the
driving force behind frontal asymmetry is whether any motivational system is being
activated or inhibited. Consistent with Gray’s revised behavioral inhibition system/​
behavioral activation system (BIS/​BAS) model (Gray & McNaughton, 2000), BAS
is activated in response to approach motivation and rewarding stimuli, whereas the
fight-​flight-​freeze system (FFFS) responds to withdrawal motivation and aversive
stimuli. BIS responds to conflict between these two systems, acting as conflict monitor,
shifting attention to allow for more efficient goal direction in conflicting situations (i.e.,
situations with more than one appetitive goal or a goal that requires combating aver-
sive obstacles). Wacker and colleagues argue that all forms of behavioral activation are
controlled by BAS and FFFS and are associated with greater relative left frontal activa-
tion, whereas behavioral inhibition and conflict monitoring are controlled by BIS and
are associated with greater relative right frontal activation.
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    239

In an early study, Wacker and colleagues (2003) compared the viability of the BIS/​
BAS, motivational direction, and valence models of frontal asymmetry. Participants
completed a mental image script task in which emotion (fear vs. anger) and motivation
(approach vs. withdrawal) were manipulated and the participants reported the degree
to which they agreed that the outcome of each task was the best option (degree of con-
flict). Results did not fall in line with the predictions of either the motivational direc-
tion or valence models of anterior asymmetry, but the degree of conflict experienced by
participants was positively correlated with relative right frontal activation. Assuming
that agreement ratings were a valid measure of BIS activation, these results support the
model of frontal asymmetry suggested by Wacker and colleagues.
Similar results were found in a later study by Wacker and colleagues (2008), which
directly compared the BIS/​BAS model of anterior activation (BBMAA) to the mo-
tivational direction model. During a mental image script task similar to that used by
Wacker and colleagues (2003), participants showed greater relative right frontal acti-
vation in response to scripts designed to target BIS than to those targeting FFFS. Self-​
reported measures of FFFS activation, conversely, were associated with greater relative
left frontal activation.
The relationship between trait BIS and frontal asymmetry was investigated by Wacker
and colleagues (2010) via a go/​no-​go task. Such a paradigm was used because no-​go
tasks have been suggested to be a viable measure of the conflict and behavioral inhibition
functions of Wacker’s revised BIS. Consistent with this assumption, those participants
who had greater trait BIS showed greater relative right frontal activation in response to
no-​go trials than to go trials.

11.9  Psychopathology and

Frontal Asymmetry

Because frontal alpha asymmetry plays a role in the experience of motivation and
emotion, it follows that it would also factor into the experience of mental illness, par-
ticularly mood disorders. The psychological conditions most frequently investigated in
relation to frontal asymmetry are depression, anxiety, and bipolar disorder.

11.9.1  Depression
Depression is one of the most commonly studied conditions in relation to frontal asym-
metry. Depressive symptomology includes experiences such as decreased response to
reward, lack of positive affect, and greater tendencies toward withdrawal from triggering
activities. Davidson and colleagues (2002) pointed out that these symptoms can often
be described as deficiencies in approach motivation and hyperactive withdrawal motiv-
ation, and these trends are associated with decreased relative left frontal cortical activity
240    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

(greater relative right frontal activity). A number of studies have found a relationship
between depressive symptoms and reduced left-​frontal activity during a resting state.
For instance, Schaffer and colleagues (1983) found a negative correlation between scores
on the Beck Depression Inventory (BDI) and relative left frontal activity. Subsequent
studies have found similar relationships between relative left frontal activity at rest
and self-​reported (Diego et al., 2001) or clinically diagnosed depression (Henriques &
Davidson, 1990; Smith et al., 2018; Stewart et al., 2010). Henriques and Davidson (1990)
even found that participants who had previously been depressed showed lower relative
left frontal activity at rest compared to those who had never been depressed, and that
these patterns of asymmetry were comparable to those in participants experiencing
acute depressive symptoms. These results suggest that frontal asymmetry may be a state-​
independent marker of depression.
It is of note that diminished relative left frontal activity in depressed individuals is
particularly robust in women compared to men (Stewart et al., 2010). Stewart and Allen
(2018) found evidence supporting this notion in a sample with no history of major de-
pressive disorder. Participants engaged in resting state EEG recordings before returning
one year later to report depressive symptomology during the worst two-​week period
experienced throughout the one-​year interim. It was found that women—​but not
men—​with lower relative left frontal activity at baseline reported greater degrees of de-
pressive symptomology during the interim period.
While resting data provides a means of studying the relationship between frontal
asymmetry and depression, some studies have found a null relationship between de-
pression and frontal asymmetry (Harmon-​Jones et al., 2002; Metzger et al., 2004;
Tomarken & Davidson, 1994; McFarland et al., 2006). These null results have led
some researchers to argue that state-​measures of frontal asymmetry may be more re-
liably associated with depression. For example, the capability model of frontal asym-
metry suggests that cortical activity measured during emotional challenges is more
indicative of predispositions toward psychopathology than cortical activity measured
at rest (Stewart et al., 2014). Lower relative left frontal activity during a facial emotion
task was found to be indicative of a history of major depressive disorder (Stewart et al.,
2011). Participants prone to depressive symptomology have also exhibited lower rela-
tive left frontal activity during tasks that evoke anger (Harmon-​Jones et al., 2002) and
sadness (Nitschke et al., 2004). Those with early-​onset depression also exhibited lower
relative left frontal activity during an approach-​related reward paradigm (Shankman
et al., 2007).
Frontal asymmetry may act as more of a risk factor than an indicator of current de-
pression. In one study, Possel and colleagues (2008) measured resting frontal asym-
metry in adolescent boys and related it to depressive symptoms experienced throughout
the year following the EEG recording. Results suggested that lower baseline left frontal
activity was predictive of melancholic depressive symptoms and increased right frontal
activity was predictive of non-​melancholic depressive symptoms one year later, but
depressive state was not predictive of baseline asymmetry. This suggests that frontal
asymmetry may be indicative of a predisposition to depression. Mitchell and Possel
(2012) conducted a similar study comparing depression and resting asymmetry in a
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    241

nonclinical population and found that individuals with lower baseline left frontal ac-
tivity were more likely to develop depressive symptoms over the next year. Nusslock and
colleagues’ (2011) results echoed these findings, suggesting that cognitive vulnerability
to depression was both associated with lower relative left frontal activity at baseline and
predicted onset of depressive symptoms one year later.
In addition, frontal asymmetry has been found to be a predictor of treatment re-
sponse in depressed individuals. Greater relative left frontal activity prior to treatment
predicted more successful response to fluoxetine (Bruder et al., 2001), as well as to
escitalopram and sertraline in women (Arns et al., 2015).

11.9.2  Anxiety
Anxiety symptoms also appear to be related to greater right frontal activity. In a sample
of participants consisting of healthy controls, those with major depression in remis-
sion, those with acute depression without comorbid anxiety disorder, and those with
acute depression with a comorbid anxiety disorder, the only group difference observed
was greater relative right frontal activity in the group with both major depression and a
comorbid anxiety disorder compared to healthy controls (Feldmann et al., 2018). Other
findings suggested that those with both anxiety and depression show frontal asym-
metry patterns similar to those with depression alone (Mathersul et al., 2008). Nusslock
and colleagues (2018) found asymmetry patterns to be most similar between healthy
controls and those with comorbid depression and anxiety. In this study, women with a
history of childhood onset depression without anxiety diagnoses showed reduced left
frontal activity, which is consistent with past research on depression. However, women
with a history of childhood onset depression and with pathological levels of anxious ap-
prehension (in the form of generalized anxiety disorder, obsessive compulsive disorder,
or separation anxiety disorder) showed resting asymmetry patterns statistically indis-
tinguishable from healthy controls. These results highlight the role of comorbid depres-
sion and anxiety in its complex relationship with frontal asymmetry.
Similar results have been found in individuals with clinical diagnoses of anxiety
disorders. Adults with panic disorder, for example, showed increased right frontal ac-
tivity in both resting and anxiety-​provoking contexts relative to controls (Wiedemann
et al., 1999). Individuals with social phobia also showed increased right frontal activity
compared to controls in response to anticipation of giving a speech (Davidson et al.,
2000). Additionally, participants with post-​traumatic stress disorder showed greater
state-​dependent right frontal activity when they were presented with trauma-​relevant
stimuli (Meyer et al., 2015). When participants engaged in an emotional Stroop task
consisting of human faces depicting various emotions, those participants with greater
levels of trait anxiety showed increased right frontal activity in response to fearful
faces than did those with lower levels of trait anxiety (Avram et al., 2010). Similarly,
participants who scored higher in trait anxiety showed greater right frontal activity
during anxiety-​provoking situations (Balconi & Pagani, 2014; Cole et al., 2012; Crost
et al., 2008).
242    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

Inconsistent patterns of frontal asymmetry have been found in children with anxiety
disorders. In a study comparing resting data of boys and girls aged 8 years and 11 years,
anxious girls aged 8 and 11 showed decreased relative left frontal activity at rest, while
their healthy control counterparts showed no significant frontal asymmetry at 8 years
and greater relative left frontal activity at 11 years. While these results are consistent with
research on adults with anxiety disorders, the young boys in the study showed incon-
sistent patterns. Anxious 8-​year-​old boys showed no significant frontal asymmetry and
anxious 11-​year-​old boys showed greater relative left frontal activity while healthy boys
showed greater relative right frontal activity (Baving et al.,, 2002). These results suggest
that patterns of frontal asymmetry in the context of anxiety are not consistent across
gender and age; further research is needed to better understand this relationship.
Inconsistent patterns have also been found when comparing various subtypes of
anxiety. For instance, at baseline, participants with generalized anxiety disorder and
increased worry show greater relative left frontal activity while those with high trait anx-
iety and low worry show lower relative left frontal activity (Smith et al., 2016). Crost and
colleagues (2008) also found that those with more anxiety show greater relative right
frontal activity in response to social threat while those higher in defensiveness show
greater relative left frontal activity in response to social threat. It has further been argued
that symptoms of anxious arousal (e.g., panic) are correlated with lower relative left
frontal activity and symptoms of anxious apprehension (e.g., worry) are correlated with
greater relative left frontal activity. As these results suggest, symptoms of anxiety have
complex relationships with patterns of frontal asymmetry.

11.9.3 Bipolar Disorder
Individuals with bipolar disorder experience heightened approach motivation and
hypersensitivity to goal-​and reward-​relevant cues during episodes of mania/​hypomania
(Alloy & Abramson, 2010; Johnson, 2005; Urosevic et al., 2010). This trend is indicative
of increased BAS sensitivity in individuals with bipolar disorder. Indeed, self-​reported
BAS sensitivity scores are higher in those with bipolar I disorder (Meyer et al., 2001;
Salavert et al., 2007), bipolar II disorder, and cyclothymia (Alloy et al., 2008), as well
as those prone to hypomanic symptomology (Meyer et al., 1999). Since increased BAS
sensitivity and approach motivation are positively correlated with relative left frontal
cortical activity, it is expected that this trend should be found in individuals with bipolar
disorder. Kano and colleagues (1992) collected resting EEG data from participants with
bipolar disorder and found greater left frontal cortical activation, suggesting that those
experiencing manic symptoms (as opposed to depressive symptoms) have greater rela-
tive left frontal activity at baseline.
Nusslock and colleagues (2012) also measured resting EEG frontal asymmetry in
individuals with cyclothymia and followed up approximately 5 years later to observe
changes in bipolar course. Those with greater levels of left frontal activity at base-
line had a greater likelihood of converting to more severe diagnoses over the interim
period (i.e., conversion from cyclothymia or bipolar II to bipolar I). Greater relative left
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    243

frontal activity at baseline was also predictive of earlier age-​of-​onset of a first bipolar
spectrum episode, an indicator of severity of bipolar disorder. This relationship was
observed even when controlling for mood state and medication status at the time of
EEG recording.
An early study by Harmon-​Jones and colleagues (2002) also found associations be-
tween bipolar disorder and frontal asymmetry in a task-​based paradigm. In this study,
participants completed the General Behavior Inventory (GBI; Depue et al., 1989) to
assess potential risk for developing bipolar or depressive disorders. Then, EEG data was
collected while participants engaged in an anger-​evoking task. The authors hypothesized
that individuals with hypomania/​mania symptoms would have greater relative left
frontal activity when angered, based on prior research (Depue & Iacono, 1989). They
also hypothesized that the opposite pattern (a decrease in left frontal activity) would be
seen in participants with depressive symptoms. As predicted, those with hypomanic/​
manic symptoms showed increased left frontal activity during the anger-​inducing situ-
ation while those with depressive symptoms showed decreased left frontal activity. These
results suggest that the greater approach tendencies experienced by those with hypo-
manic/​manic symptoms and the diminished approach tendencies experienced by those
with depressive symptoms manifest through variations in frontal asymmetry.
Harmon-​Jones and colleagues (2008) tested the BAS dysregulation theory of bipolar
disorder by measuring frontal asymmetry in response to tasks of varying difficulty.
Participants had either a bipolar spectrum diagnosis or no major psychopathology.
During EEG data collection, participants engaged in an anagram task during which
they were given cues indicating the difficulty (i.e., easy, medium, or hard) of the up-
coming trial. They were also told whether they could receive money (win) or avoid
losing money (loss) by successfully completing the upcoming trial. Results indicated
that those with bipolar disorder had greater relative left frontal activity in preparation
for hard/​win trials, while control participants showed a decrease in relative left frontal
activity in anticipation of the same trial type. Greater relative left frontal activity was
also correlated with self-​reported hypomanic/​manic experience during the task in
individuals with bipolar disorder. These results therefore provide evidence supporting
BAS dysregulation theory. They also suggest that increased relative left frontal ac-
tivity, which may be related to manic symptoms, can be triggered by more difficult and
rewarding stimuli.

11.10  Discussion of Reviewed Research

11.10.1 Non-​Significant Associations of Frontal

Asymmetry and Affect/​Motivation
Some studies have reported non-​significant correlations of resting baseline frontal
asymmetry with trait affective valence/​motivational direction measures (Reid et al.,
244    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

1998). A meta-​analysis of the association between affect-​related personality traits and

frontal asymmetry found that some associations were non-​existent, and some were stat-
istically significant in the predicted direction, but with small effect sizes (Kuper et al.,
2019). We believe it is important to consider the complexity of human traits and neuro-
physiology before drawing conclusions about the interpretation of null-​effects and small
effect sizes of psychological phenomena. Next, we discuss the concerns of interpreting
effect sizes and reasons some frontal asymmetry effects may be “small”.
As it stands, effect sizes are generally misrepresented and misunderstood by
researchers and readers alike. Funder and Ozer (2019) note that, even when effect sizes
are reported and, even more rarely, are interpreted, those interpretations are based on
fundamentally flawed standards. The two most common means of interpreting effect
sizes are via Cohen’s standards and squaring the correlation coefficient r. Funder and
Ozer (2019) argue that the former of these techniques is nonsensical and is used out
of context of any sort of comparison (Cohen agrees that these standards are not ideal;
Cohen, 1977, 1988), while the latter is misleading. Squaring the correlation coefficient
changes the scale upon which the effect size is measured, making the effect appear less
impactful than it may be in reality.
More foundational to the issue of effect sizes is the field’s tendency to dismiss small
effect sizes without proper consideration. As Funder and Ozer (2019) point out, the
reality is that small effect sizes are the most believable. The human experience is com-
plex, and it is ultimately unrealistic to expect that any one phenomenon being studied
(neural or behavioral) will explain the bulk of any human behavior. In addition, small
effect sizes are not necessarily associated with small consequences. Immediate but
frequent phenomena with seemingly small effect sizes can cumulate to have greater
implications in the long run of the individual or the population (Funder & Ozer, 2019).
“Small” effect sizes should not be dismissed; rather, they should be reported explicitly
in the context of their overall consequence. The results of Kuper and colleagues’ (2019)
meta-​analysis also revealed much heterogeneity in results from individual studies,
suggesting that situational variables may influence the relationship between resting,
baseline frontal asymmetry and self-​reported personality traits.
The inconsistency observed in the literature concerning frontal asymmetry could be
a result of several things that do not necessarily indicate a lack of relationship with mo-
tivation. Motivational tendencies can be sensitive to individual situations, and their re-
lationship to frontal asymmetry could be masked by situational variables. For instance,
some research suggests that in baseline EEG recording sessions, half of the variation in
the data is due to trait influences and half is due to state influences (Hagemann et al.,
2002; Hagemann et al., 2005).
The relationship between trait BAS and resting relative left frontal activity may be
influenced by the specific circumstances of an experiment’s procedure. Wacker and
colleagues (2013) demonstrated this by analyzing the effect of attractiveness of opposite-​
sex experimenter on the correlation between trait BAS and frontal asymmetry. Results
suggested that the correlation between BAS and greater relative left frontal activity was
present primarily in cases when male participants interacted with attractive female
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    245

experimenters. The attractiveness of the experimenter seems to have encouraged

approach motivation in the participants, thereby strengthening the relationship be-
tween trait BAS and resting relative left frontal activity.
A similar pattern can be seen when reward and effort are manipulated. Hughes
and colleagues (2015) conducted an experiment in which low-​effort trials elicited low
rewards while high-​effort trials elicited high rewards. Participants showed greater
left frontal activity during high-​effort high-​reward trials than during low-​effort low-​
rewards trials. These results suggest that the motivation and incentive anticipation
involved in a situation can impact measures of frontal asymmetry.
Situational variables outside of the lab space can also impact frontal asymmetry
measures. Peterson and Harmon-​Jones (2009) found that participants had greater right
frontal activity when they participated in the study during fall mornings. Because de-
pression may be experienced more during the fall months (King et al., 2000) and cortisol
levels are high in the mornings (King et al., 2000), the variation in frontal asymmetry
may have been due to reductions in approach motivation associated with depression
and increases in inhibition or withdrawal motivation associated with higher cortisol.
Despite some inconsistencies in the literature, there is sufficient evidence to suggest a
relationship between trait motivational tendencies and frontal asymmetry. There are at
least three possible explanations for this trend in resting frontal asymmetry data. First,
resting frontal asymmetry may reflect neural tendencies of the individual; when they
are not engaged in a specific task, their frontal asymmetry scores reflect their trait-​based
tendencies toward approach and effortful control. Second, resting frontal asymmetry
could reflect the individual’s response to being in a novel environment. If participants
feel curiosity (approach) when introduced to the lab space, they exhibit greater relative
left frontal activity; if participants feel discomfort while continuing to engage in the new
setting (and engage effortful control), they exhibit greater relative right frontal activity.
Third, participants’ thought processes during resting data collection could be driving
frontal asymmetry variability. When not given any instruction, if participants tend to
think about their goals and aspirations, they may exhibit greater relative left frontal ac-
tivity; if participants tend to think about anxiety evoking situations, they may exhibit
greater relative right frontal activity. The underlying mechanisms driving baseline
frontal asymmetry are not yet understood and require further research.

11.11  CONCLUSION

The motivational model of frontal asymmetry suggests that relative left frontal activity
is associated with approach motivation while right frontal activity is associated with
withdrawal motivation. The former assumption of this model is supported by the litera-
ture, both through possible motivation confounds associated with the affective valence
model and through more direct manipulations of motivation. Anger—​an emotion that
is both negative and approach motivated—​is associated with greater left frontal activity
246    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

at the state and trait level. Further support stems from research connecting higher BAS
scores with greater baseline left frontal activity. The connection between BIS scores and
baseline right frontal activity, however, has been widely contested.
This inconsistency in the literature concerning withdrawal motivation and right
frontal has led to the development of the effortful control model of right frontal asym-
metry. The effortful control model suggests that right frontal activity is associated with
control and regulatory processing. Research supporting the effortful control model has
linked right frontal activity with increased anxious inaction, error detection, and emo-
tional control-​related behaviors; right frontal activity is also negatively correlated with
state and trait impulsivity. Past work linking right frontal activity and withdrawal mo-
tivation may have activated effortful control, because withdrawal manipulations may
have co-​activated effortful control to stay engaged with the aversive stimuli, but also be-
cause activation of r-​BIS increases the cognitive load devoted to negative stimuli.
Psychopathologies influence patterns of frontal asymmetry. For instance, individuals
with depression show reduced levels of left frontal activity at rest and during emo-
tionally salient tasks. Reduced left frontal activity may be a risk factor for depression
in nonclinical populations. Those with anxiety generally show increased levels of right
frontal activity at rest and during tasks that elicit fear and/​or anxiety; however, this re-
lationship is more complicated in children and when comparing subtypes of anxiety.
Those with bipolar disorder who experience manic symptoms exhibit greater left frontal
activity at rest and during anger-​evoking or difficult rewarding tasks. These patterns
are consistent with the motivational direction and effortful control models of frontal
asymmetry.
While there have been failures to replicate some past frontal asymmetry findings,
these failures to replicate may be due to the complex nature of the systems underlying
frontal asymmetry. Phenomena such as affect and motivation change by the moment
and can be swayed by situational effects. Despite this, frontal asymmetry research has
a long and well-​established history in EEG frequency research and continues to spark
new predictions, models, and discoveries.

REFERENCES
Alema, G., Rosadini, G., & Rossi, G. F. (1961). Preliminary experiments on the effects of the
intracarotid introduction of sodium amytal in parkinsonian syndromes. Bollettino della
Società Italiana di Biologia Sperimentale, 37, 1036–​1037.
Allen, J. J. B., Harmon-​Jones, E., & Cavender, J. H. (2001). Manipulation of frontal EEG asym-
metry through biofeedback alters self-​reported emotional responses and facial EMG.
Psychophysiology, 38, 685–​693.
Allen, J. J. B., Iacono, W. G., Depue, R. A., & Arbisi, P. (1993). Regional electroencephalographic
asymmetries in bipolar seasonal affective disorder before and after exposure to bright light.
Biological Psychiatry, 33, 642–​646.
Alloy, L. B., Abramson, L. Y., Walshaw, P. D., Cogswell, A., Grandin, L. D., Hughes, M. E.,
... & Hogan, M. E. (2008). Behavioral approach system and behavioral inhibition system
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    247

sensitivities and bipolar spectrum disorders: Prospective prediction of bipolar mood

episodes. Bipolar Disorders, 10(2), 310–​322.
Alloy, L. B., & Abramson, L. Y. (2010). The role of the behavioral approach system (BAS) in bi-
polar spectrum disorders. Current Directions in Psychological Science, 19(3), 189–​194.
Amodio, D. M., Master, S. L. Yee, C. M., & Taylor, S. E. (2008). Neurocognitive components
of behavioral inhibition and activation systems: Implications for theories of self-​regulation.
Psychophysiology, 45, 11–​19.
Amodio, D. M., Shah, J. Y., Sigelman, J., Brazy, P. C., & Harmon-​Jones, E. (2004). Implicit regu-
latory focus associated with resting frontal cortical asymmetry. Journal of Experimental
Social Psychology, 40, 225–​232.
Arns, M., Bruder, G., Hegerl, U., Spooner, C., Palmer, D. M., Etkin, A., ... & Gordon, E. (2016).
EEG alpha asymmetry as a gender-​specific predictor of outcome to acute treatment
with different antidepressant medications in the randomized iSPOT-​D study. Clinical
Neurophysiology, 127(1), 509–​519.
Aron, A. R., Robbins, T. W., & Poldrack, R. A. (2004). Inhibition and the right inferior frontal
cortex. Trends in Cognitive Sciences, 8(4), 170–​177. doi:10.1016/​j.tics.2004.02.010
Aron, A. R., Robbins, T. W., & Poldrack, R. A. (2014). Inhibition and the right inferior
frontal cortex: One decade on. Trends in Cognitive Sciences, 18(4), 177–​185. doi:10.1016/​
j.tics.2013.12.003
Avram, J., Balteş, F. R., Miclea, M., & Miu, A. C. (2010). Frontal EEG activation asymmetry
reflects cognitive biases in anxiety: Evidence from an emotional face Stroop task. Applied
Psychophysiology and Biofeedback, 35(4), 285–​292. doi:10.1007/​ s10484–​010-​9138–​6
Balconi, M. & Pagani, S. (2014). Personality correlates (BAS-​BIS), self-​perception of so-
cial ranking, and cortical (alpha frequency band) modulation in peer-​group comparison.
Physiology & Behavior, 133, 207–​215. doi:10.1016/​j.physbeh.2014.05.043
Bari, A. & Robbins, T. W. (2013). Inhibition and impulsivity: Behavioral and neural basis of
response control. Progress in Neurobiology, 108, 44–​79. doi:10.1016/​j.pneurobio.2013.06.005
Baving, L., Laucht, M., & Schmidt, M. H. (2002). Frontal brain activation in anxious school
children. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 43(2), 265–​274.
https://​doi.org/​10.1111/​1469-​7610.00019
Beeney, J. E., Levy, K. N., Gatzke-​Kopp, L. M., & Hallquist, M. N. (2014). EEG asym-
metry in borderline personality disorder and depression following rejection. Personality
Disorders: Theory, Research, and Treatment, 5, 178–​185.
Berkman, E. T. & Lieberman, M. D. (2010). Approaching the bad and avoiding the good: Lateral
prefrontal cortical asymmetry distinguishes between action and valence. Journal of
Cognitive Neuroscience, 22(9), 1970–​1979. doi:10.1162/​jocn.2009.21317
Berkowitz, L. & Harmon-​Jones, E. (2004). Toward an understanding of the determinants of
anger. Emotion, 4, 107–​130.
Bickel, W. K., Jarmolowicz, D. P., Mueller, E. T., Gatchalian, K. M., & McClure, S. M. (2012). Are
executive function and impulsivity antipodes? A conceptual reconstruction with special ref-
erence to addiction. Psychopharmacology, 221(3), 361–​387. doi:10.1007/​ s00213–​012-​2689-​x
Black, E W. (1975). Unilateral brain lesions and MMPI performance: A preliminary study.
Perceptual and Motor Skills, 40, 87–​93.
Blanchard R. J. & Blanchard D. C. (1984). Affect and aggression: An animal model applied
to human behavior. In R. J. Blanchard, & D. C. Blanchard (Eds.), Advances in the study of
aggression (pp. 1–​62). Academic Press.
Brehm, J. W. (1999). The intensity of emotion. Personality and Social Psychology Review, 3, 2–​22.
248    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

Brehm, J. W., & Self, E. A. (1989). The intensity of motivation. Annual Review of Psychology, 40,
109–​131.
Bruder, G. E., Stewart, J. W., Tenke, C. E., McGrath, P. J., Leite, P., Bhattacharya, N., & Quitkin,
F. M. (2001). Electroencephalographic and perceptual asymmetry differences between
responders and nonresponders to an SSRI antidepressant. Biological psychiatry, 49(5),
416–​425.
Carter, B. L. & Tiffany, S. T. (1999). Meta-​analysis of cue-​reactivity in addiction research.
Addiction, 94(3), 327–​340. doi:10.1046/​ j.1360-​0443.1999.9433273.x
Carver, C. S. (2004). Negative affects deriving from the behavioral approach system. Emotion,
4, 3–​22.
Carver, C. S. & Connor-​Smith, J. (2010). Personality and coping. Annual Review of Psychology,
61, 679–​704. doi:10.1146/​annurev.psych.093008.100352
Carver, C. S. & Harmon-​Jones, E. (2009). Anger is an approach-​related affect: Evidence and
implications. Psychological Bulletin, 135, 183–​204.
Carver, C. S. & White, T. L. (1994). Behavioral inhibition, behavioral activation, and affective
responses to impending reward and punishment: The BIS/​BAS scales. Journal of Personality
and Social Psychology, 67, 319–​333.
Carver, C. S., Johnson, S. L., & Joormann, J. (2008). Serotonergic function, two-​mode models
of self-​regulation, and vulnerability to depression: What depression has in common with
impulsive aggression. Psychological bulletin, 134(6), 912. doi:10.1037/​a0013740
Coan, J. A. & Allen, J. J. (2003). Frontal EEG asymmetry and the behavioral activation and in-
hibition systems. Psychophysiology, 40, 106–​114.
Coan, J. A. & Allen, J. J. (2004). Frontal EEG asymmetry as a moderator and mediator of
emotion. Biological Psychology, 67, 7–​50.
Coan, J. A., Allen, J. J. B., & Harmon-​Jones, E. (2001). Voluntary facial expression and hemi-
spheric asymmetry over the frontal cortex. Psychophysiology, 38, 912–​925.
Cohen, J. (1977). Statistical power analysis for the behavioral sciences (rev. ed.). Academic Press.
Cohen, J. (1988). Statistical power analysis for the behavioral sciences (2nd ed.). Erlbaum.
Cole, C., Zapp, D. J., Nelson, S. K., & Perez-​Edgar, K. (2012). Speech presentation cues mod-
erate frontal EEG asymmetry in socially withdrawn young adults. Brain and Cognition,
78(2), 156–​162. doi:10.1016/​j.bandc.2011.10.013
Cook, I. A., O’Hara, R., Uijtdehaage, S. H. J., Mandelkern, M., & Leuchter, A. F. (1998).
Assessing the accuracy of topographic EEG mapping for determining local brain function.
Electroencephalography and Clinical Neurophysiology, 107, 408–​414.
Crost, N. W., Pauls, C. A., & Wacker, J. (2008). Defensiveness and anxiety predict frontal
EEG asymmetry only in specific situational contexts. Biological Psychology, 78(1), 43–​52.
doi:10.1016/​j. biopsycho.2007.12.008
Cyders, M. A., & Smith, G. T. (2007). Mood-​based rash action and its components: Positive
and negative urgency. Personality and Individual Differences, 43(4), 839–​850. doi:10.1016/​
j.paid.2007. 02.008
Cyders, M. A., Zapolski, T. C., Combs, J. L., Settles, R. F., Fillmore, M. T., & Smith, G. T. (2010).
Experimental effect of positive urgency on negative outcomes from risk taking and on
increased alcohol consumption. Psychology of Addictive Behaviors, 24(3), 367–​375.
Darwin, C. (1872/​ 1965). The expressions of the emotions in man and animals. Oxford
University Press.
Davidson, R. J. & Fox, N. (1982). Asymmetric brain activity discriminates between positive and
negative affective stimuli in 10 month old infants. Science, 218, 1235–​1237.
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    249

Davidson, R. J., Chapman, J. P., Chapman, L. J., & Henriques, J. B. (1990). Asymmetric brain
electrical-​activity discriminates between psychometrically-​matched verbal and spatial cog-
nitive tasks. Psychophysiology, 27, 528–​543.
Davidson, R. J., Marshall, J. R., Tomarken, A. J., & Henriques, J. B. (2000). While a phobic
waits: Regional brain electrical and autonomic activity in social phobics during antici-
pation of public speaking. Biological Psychiatry, 47(2), 85–​95. https://​doi.org/​10.1016/​
s0006-​3223(99)00222-​x
Davidson, R. J., Pizzagalli, D., Nitschke, J. B., & Putnam, K. (2002). Depression: Perspectives
from affective neuroscience. Annual Review of Psychology, 53, 545–​574. doi:10.1146/​annurev.
psych.53.100901.135148
De Pascalis, V., Cozzuto, G., Caprara, G. V., & Alessandri, G. (2013). Relations among EEG-​
alpha asymmetry, BIS/​BAS, and dispositional optimism. Biological Psychology, 94, 198–​209.
Depue, R. A., Krauss, S., Spoont, M. R., & Arbisi, P. (1989). General Behavior Inventory identi-
fication of unipolar and bipolar affective conditions in a nonclinical university population.
Journal of Abnormal Psychology, 98(2), 117–​126.
Depue, R.A. & Iacono, W.G. (1989). Neurobehavioral aspects of affective disorders. Annual
Review of Psychology, 40, 457–​492.
Derryberry, D. & Rothbart, M. K. (1997). Reactive and effortful processes in the organ-
ization of temperament. Development and Psychopathology, 9(4), 633–​652. doi:10.1017/​
S095457949700 1375
DeYoung, C. G. (2015). Cybernetic big five theory. Journal of Research in Personality, 56, 33–​58.
doi:10.1016/​j.jrp.2014.07.004
Diego, M. A., Field, T., & Hernandez-​Reif, M. (2001). CES-​D depression scores are correlated
with frontal EEG alpha asymmetry. Depression and Anxiety, 13(1), 32–​37.
Eisenberg, N., Spinrad, T. L., Fabes, R. A., Reiser, M., Cumberland, A., Shepard, S. A., ...
Thompson, M. (2004). The relations of effortful control and impulsivity to children’s resili-
ency and adjustment. Child Development, 75(1), 25–​46. doi:10.1111/​j.1467-​ 8624.2004.00652.x
Ekman, P. & Davidson, R. J. (1993). Voluntary smiling changes regional brain activity.
Psychological Science, 4, 342–​345.
Ekman, P. & Friesen, W. V. (1975). Unmasking the face: A guide to recognizing emotions from fa-
cial clues. Prentice-​Hall.
Elgavish, E., Halpern, D., Dikman, Z., & Allen, J. J. B. (2003). Does frontal EEG asymmetry
moderate or mediate responses to the international affective picture system (IAPS)?
Psychophysiology, 40, S38.
Enticott, P. G., Ogloff, J. R., & Bradshaw, J. L. (2006). Associations between laboratory measures
of executive inhibitory control and self-​reported impulsivity. Personality and Individual
Differences, 41(2), 285–​294. doi:10.1016/​j.paid.2006.01.011
Feldmann, L., Piechaczek, C. E., Grünewald, B. D., Pehl, V., Bartling, J., Frey, M., ... &
Greimel, E. (2018). Resting frontal EEG asymmetry in adolescents with major depres-
sion: impact of disease state and comorbid anxiety disorder. Clinical Neurophysiology,
129(12), 2577–​2585.
Funder, D. C. & Ozer, D. J. (2019). Evaluating effect size in psychological research: Sense and
nonsense. Advances in Methods and Practices in Psychological Science, 2(2), 156–​168.
Gable, P. A. & Dreisbach, G. (2021). Approach motivation and positive affect. Current Opinion
in Behavioral Sciences, 39, 203–​208.
Gable, P. A. & Harmon-​ Jones, E. (2008). Relative left frontal activation to appetitive
stimuli: Considering the role of individual differences. Psychophysiology, 45, 275–​278.
250    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

Gable, P. A. & Poole, B. D. (2014). Influence of trait behavioral inhibition and behavioral
approach motivation systems on the LPP and frontal asymmetry to anger pictures. Social
Cognitive and Affective Neuroscience, 9, 182–​190.
Gable, P. A., Mechin, N. C., Hicks, J. A., & Adams, D. L. (2015). Supervisory control system
and frontal asymmetry: Neurophysiological traits of emotion-​based impulsivity. Social,
Cognitive, and Affective Neuroscience, 10(10), 1310–​315.
Gable, P. A., Mechin, N., Hicks, J.A., & Adams, D.A. (2015). Positive urgency and left-​frontal
asymmetry: Neurophysiological traits of emotion-​based impulsivity. Social Cognitive and
Affective Neuroscience, 10, 1310–​1315
Gable, P. A., Neal, L. B., & Threadgill, A. H. (2018). Regulatory behavior and frontal ac-
tivity: Considering the role of revised-​ BIS in relative right frontal asymmetry.
Psychophysiology, 55(1), e12910.
Gable, P. A., Poole, B. D., & Cook, M. S. (2013). Asymmetrical hemisphere activation enhances
global-​local processing. Brain and Cognition, 83, 337–​341.
Gainotti, G. (1972). Emotional behavior and hemispheric side of the lesion. Cortex, 8, 41–​55.
Gasparrini, W. G., Satz, P., Heilman, K., & Coolidge, F. L. (1978). Hemispheric asymmetries
of affective processing as determined by the Minnesota Multiphasic Personality Inventory.
Journal of Neurology, Neurosurgery and Psychiatry, 41, 470–​473.
Gianotti, L. R., Knoch, D., Faber, P. L., Lehmann, D., Pascual-​Marqui, R. D., Diezi, C., ... & Fehr,
E. (2009). Tonic activity level in the right prefrontal cortex predicts individuals’ risk taking.
Psychological Science, 20, 33–​38.
Goldstein, K. (1939). The organism: An holistic approach to biology, derived from pathological
data in man. American Books.
Gray, J. (1982). Précis of The neuropsychology of anxiety: An enquiry into the functions of the
septo-​hippocampal system. Behavioral and Brain Sciences, 5(3), 469–​ 484. doi:10.1017/​
S0140525X00013066
Gray, J. A. & McNaughton, N. (2000). The neuropsychology of anxiety: An enquiry into the
functions of the septo-​hippocampal system (2nd ed.). Oxford University Press.
Grimshaw, G. M. & Carmel, D. (2014). An asymmetric inhibition model of hemi-
spheric differences in emotional processing. Frontiers in Psychology, 5, 489. doi:10.3389/​
fpsyg.2014.00489
Gross, J. J. & Levenson, R. W. (1993). Emotional suppression: Physiology, self-​report, and ex-
pressive behavior. Journal of Personality and Social Psychology, 64, 970–​986. doi:10.1037/​
0022-​ 3514.64.6.970
Hagemann, D., Hewig, J., Seifert, J., Naumann, E., & Bartussek, D. (2005). The latent state-​
trait structure of resting EEG asymmetry: Replication and extension. Psychophysiology, 42,
740–​752.
Hagemann, D., Naumann, E., Becker, G., Maier, S., & Bartussek, D. (1998). Frontal brain asym-
metry and affective style: A conceptual replication. Psychophysiology, 35, 372–​388.
Hagemann, D., Naumann, E., Thayer, J. F., & Bartussek, D. (2002). Does resting EEG asym-
metry reflect a trait? An application of latent state-​trait theory. Journal of Personality and
Social Psychology, 82, 619–​641.
Harmon-​Jones, C., Schmeichel, B. J., Mennitt, E., & Harmon-​Jones, E. (2011). The expression
of determination: Similarities between anger and approach-​related positive affect. Journal of
Personality and Social Psychology, 100, 172–​181. doi:10.1037/​a0020966
Harmon-​Jones, E. (2003a). Clarifying the emotive functions of asymmetrical frontal cortical
activity. Psychophysiology, 40, 838–​848.
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    251

Harmon-​Jones, E. (2003b). Anger and the behavioural approach system. Personality and
Individual Differences, 35, 995–​1005.
Harmon-​Jones, E. (2004). On the relationship of anterior brain activity and anger: Examining
the role of attitude toward anger. Cognition and Emotion, 18, 337–​361.
Harmon-​Jones, E. (2006). Unilateral right-​hand contractions cause contralateral alpha power
suppression and approach motivational affective experience. Psychophysiology, 43, 598–​603.
Harmon-​Jones, E. (2007). Trait anger predicts relative left frontal cortical activation to anger-​
inducing stimuli. International Journal of Psychophysiology, 66, 154–​160.
Harmon-​Jones, E., Abramson, L. Y., Nusslock, R., Sigelman, J. D., Urosevic, S., Turonie, L. D.,
Alloy, L. B., & Fearn, M. (2008). Effect of bipolar disorder on left frontal cortical responses to
goals differing in valence and task difficulty. Biological Psychiatry, 63, 693–​698.
Harmon-​Jones, E., Abramson, L. Y., Sigelman, J., Bohlig, A., Hogan, M. E., & Harmon-​Jones,
C. (2002). Proneness to hypomania/​mania or depression and asymmetric frontal cor-
tical responses to an anger-​evoking event. Journal of Personality and Social Psychology, 82,
610–​618.
Harmon-​Jones, E. & Allen, J. J. B. (1997). Behavioral activation sensitivity and resting frontal
EEG asymmetry: Covariation of putative indicators related to risk for mood disorders.
Journal of Abnormal Psychology, 106, 159–​163.
Harmon-​Jones, E. & Allen, J. J. B. (1998). Anger and prefrontal brain activity: EEG asym-
metry consistent with approach motivation despite negative affective valence. Journal of
Personality and Social Psychology, 74, 1310–​1316.
Harmon-​Jones, E. & Gable, P. A. (2009). Neural activity underlying the effect of approach-​
motivated positive affect on narrowed attention. Psychological Science, 20, 406–​409.
Harmon-​Jones, E. & Gable, P. A. (2018). On the role of asymmetric frontal cortical activity in
approach and withdrawal motivation: An updated review of the evidence. Psychophysiology,
55(1), e12879.
Harmon-​Jones, E., Gable, P. A., & Price, T. F. (2011). Leaning embodies desire: Evidence that
leaning forward increases relative left frontal activation to appetitive stimuli. Biological
Psychology, 87, 311–​313.
Harmon-​Jones, E., Harmon-​Jones, C., Abramson, L. Y., & Peterson, C. K. (2009). PANAS posi-
tive activation is associated with anger. Emotion, 9, 183–​196.
Harmon-​Jones, E., Harmon-​Jones, C., Amodio, D. M., & Gable, P. A. (2011). Attitudes toward
emotions. Journal of Personality and Social Psychology, 101, 1332–​1350. doi:10.1037/​a0024951
Harmon-​Jones, E., Harmon-​Jones, C., Fearn, M., Sigelman, J. D., & Johnson, P. (2008).
Left frontal cortical activation and spreading of alternatives: Tests of the action-​based
model of dissonance. Journal of Personality and Social Psychology, 94, 1–​15. doi:10.1037/​
0022-​3514.94.1.1
Harmon-​Jones, E., Harmon-​Jones, C., & Price, T. F. (2013). What is approach motivation?
Emotion Review, 5, 291–​295. doi:10.1177/​1754073913477509
Harmon-​Jones, E., Lueck, L., Fearn, M., & Harmon-​Jones, C. (2006). The effect of personal
relevance and approach-​related action expectation on relative left frontal cortical activity.
Psychological Science, 17, 434–​440.
Harmon-​Jones, E. & Peterson, C. K. (2008). Effect of trait and state approach motivation on
aggressive inclinations. Journal of Research in Personality, 42, 1381–​1385.
Harmon-​Jones, E. & Peterson, C. K. (2009). Supine body position reduces neural response to
anger evocation. Psychological Science, 20, 1209–​1210. doi:10.1111/​j.1467-​9280.2009.02416.x
252    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

Harmon-​Jones, E., Peterson, C. K., & Harris, C. R. (2009). Jealousy: Novel methods and neural
correlates. Emotion, 9, 113–​117.
Harmon-​Jones, E. & Sigelman, J. D. (2001). State anger and prefrontal brain activity: Evidence
that insult-​related relative left-​prefrontal activation is associated with experienced anger
and aggression. Journal of Personality and Social Psychology, 80, 797–​803.
Harmon-​Jones, E., Sigelman, J. D., Bohlig, A., & Harmon-​Jones, C. (2003). Anger, coping, and
frontal cortical activity: The effect of coping potential on anger-​induced left frontal activity.
Cognition and Emotion, 17, 1–​24.
Harmon-​Jones, E., Vaughn-​Scott, K., Mohr, S., Sigelman, J., & Harmon-​Jones, C. (2004). The
effect of manipulated sympathy and anger on left and right frontal cortical activity. Emotion,
4, 95–​101.
Hellige, J. B. (1993). Hemispheric asymmetry: What’s right and what’s left. Harvard
University Press.
Henriques, J. B. & Davidson, R. J. (1990). Regional brain electrical asymmetries discriminate
between previously depressed and healthy control subjects. Journal of Abnormal Psychology,
99, 22–​31.
Henriques, J. B. & Davidson, R. J. (2000). Decreased responsiveness to reward in depression.
Cognition & Emotion, 14(5), 711–​724. doi:10.1080/​02699930050117684
Hester, R. & Garavan, H. (2004). Executive dysfunction in cocaine addiction: Evidence for dis-
cordant frontal, cingulate, and cerebellar activity. The Journal of Neuroscience, 24(49), 11017–​
11022. doi:10.1523/​JNEUROSCI.3321-​04.2004
Hester, R. & Garavan, H. (2009). Neural mechanisms underlying drug-​related cue distrac-
tion in active cocaine users. Pharmacology Biochemistry and Behavior, 93(3), 270–​277.
doi:10.1016/​j. pbb.2008.12.009
Hewig, J., Hagemann, D., Seifert, J., Naumann, E., & Bartussek, D. (2004). On the selective re-
lation of frontal cortical activity and anger-​out versus anger-​control. Journal of Personality
and Social Psychology, 87, 926–​939.
Hewig, J., Hagemann, D., Seifert, J., Naumann, E., & Bartussek, D. (2006). The relation of cor-
tical activity and BIS/​BAS on the trait level. Biological Psychology, 71(1), 42–​53. doi:10.1016/​j.
biopsycho.2005.01.006
Heym, N., Ferguson, E., & Lawrence, C. (2008). An evaluation of the relationship be-
tween Gray’s revised RST and Eysenck’s PEN: Distinguishing BIS and FFFS in Carver and
White’s BIS/​BAS scales. Personality and Individual Differences, 45(8), 709–​7 15. doi:10.1016/​
j.paid.2008.07.013
Hughes, D. M., Yates, M. J., Morton, E. E., & Smillie, L. D. (2015). Asymmetric frontal cortical
activity predicts effort expenditure for reward. Social Cognitive and Affective Neuroscience,
10, 1015–​1019.
Jackson, D. C., Mueller, C. J., Dolski, I., Dalton, K. M., Nitschke, J. B., Urry, H. L., ... & Davidson,
R. J. (2003). Now you feel it, now you don’t: Frontal brain electrical asymmetry and indi-
vidual differences in emotion regulation. Psychological Science, 14(6), 612–​617. doi:10.1046/​
j.0956-​7976.2003.psci_​1473.x
Jacobs, G. D. & Snyder, D. (1996). Frontal brain asymmetry predicts affective style in men.
Behavioral Neuroscience, 110, 3–​6.
Jensen-​Campbell, L. A., Knack, J. M., Waldrip, A. M., & Campbell, S. D. (2007). Do big five per-
sonality traits associated with self-​control influence the regulation of anger and aggression?
Journal of Research in Personality, 41, 403–​424.
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    253

Johnson, S. L. (2005). Mania and dysregulation in goal pursuit: A review. Clinical Psychology
Review, 25, 241–​262.
Kamiya, J. (1979). Autoregulation of the EEG alpha rhythm: A program for the study of con-
sciousness. In S. A. E. Peper & M. Quinn (Eds.), Mind/​body integration: Essential readings in
biofeedback (pp. 289–​297). Plenum Press.
Kano, K., Nakamura, M., Matsuoka, T., Iida, H., & Nakajima, T. (1992). The topographical
features of EEGs in patients with affective disorders. Electroencephalography and Clinical
Neurophysiology, 83, 124–​129.
Keune, P. M., Bostanov, V., Kotchoubey, B., & Hautzinger, M. (2012). Mindfulness versus ru-
mination and behavioral inhibition: A perspective from research on frontal brain asym-
metry. Personality and Individual Differences, 53(3), 323–​328. doi:10.1016/​j. paid.2012.03.034
Keune, P. M., Schönenberg, M., Wyckoff, S., Mayer, K., Riemann, S., Hautzinger, M., & Strehl,
U. (2011). Frontal alpha-​asymmetry in adults with attention deficit hyperactivity dis-
order: Replication and specification. Biological Psychology, 87, 306–​310.
Keune, P. M., van der Heiden, L., Várkuti, B., Konicar, L., Veit, R., & Birbaumer, N. (2012).
Prefrontal brain asymmetry and aggression in imprisoned violent offenders. Neuroscience
Letters, 515, 191–​195.
King, J. A., Rosal, M. C., Ma, Y., Reed, G., Kelly, T., Stanek, III, E.J., & Ockene, I. S. (2000).
Sequence and seasonal effects of salivary cortisol. Behavioral Medicine, 26, 67–​73.
Kline, J. P., Blackhart, G. C., Woodward, K. M., Williams, S. R., & Schwartz, G. E. (2000).
Anterior electroencephalographic asymmetry changes in elderly women in response
to a pleasant and an unpleasant odor. Biological Psychology, 52(3), 241–​250. doi:10.1016/​
S0301-​0511(99)00046-​0
Knoch, D., Gianotti, L. R., Baumgartner, T., & Fehr, E. (2010). A neural marker of costly pun-
ishment behavior. Psychological Science, 21(3), 337–​342. doi:10.1177/​0956797609360750
Kochanska, G. & Knaack, A. (2003). Effortful control as a personality characteristic of young
children: Antecedents, correlates, and consequences. Journal of Personality, 71(6), 1087–​1112.
doi:10.1111/​1467-​6494.7106008
Kuper, N., Käckenmester, W., & Wacker, J. (2019). Resting frontal EEG asymmetry and person-
ality traits: A meta-​analysis. European Journal of Personality, 33(2), 154–​175.
Lacey, M. F., Neal, L. B., & Gable, P. A. (2020). Effortful control of motivation, not with-
drawal motivation, relates to greater right frontal asymmetry. International Journal of
Psychophysiology, 147, 18–​25.
Lagerspetz, K. M. J. (1969). Aggression and aggressiveness in laboratory mice. In S. Garattini, &
E. B. Sigg (Eds.), Aggressive Behavior (pp. 77–​85). Wiley.
Lazarus, R. S. (1991). Emotion and adaptation. Oxford University Press.
Logan, G. D., Schachar, R. J., & Tannock, R. (1997). Impulsivity and inhibitory control.
Psychological Science, 8(1), 60–​64. doi:10.1111/​j.1467-​9280.1997.tb00545.x
Mathersul, D., Williams, L. M., Hopkinson, P. J., & Kemp, A. H. (2008). Investigating models of
affect: Relationships among EEG alpha asymmetry, depression, and anxiety. Emotion, 8(4),
560–​572
McFarland, B. R., Shankman, S. A., Tenke, C. E., Bruder, G. E., & Klein, D. N. (2006).
Behavioral activation system deficits predict the six-​month course of depression. Journal of
Affective Disorders, 91(2–​3), 229–​234.
Mechin, N., Gable, P. A., & Hicks, J. A. (2016). Frontal asymmetry and alcohol cue re-
activity: Influence of core personality systems. Psychophysiology, 53(8), 1224–​1231. doi:10.1111/​
psyp.12659
254    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

Metzger, L. J., Paige, S. R., Carson, M. A., Lasko, N. B., Paulus, L. A., Pitman, R. K., & Orr, S. P.
(2004). PTSD arousal and depression symptoms associated with increased right-​sided par-
ietal EEG asymmetry. Journal of Abnormal Psychology, 113(2), 324–​329.
Meyer, B., Johnson, S. L., & Carver, C. S. (1999). Exploring behavioral activation and inhibition
sensitivities among college students at risk for bipolar spectrum symptomatology. Journal of
Psychopathology and Behavioral Assessment, 21, 275–​292.
Meyer, B., Johnson, S.L., & Winters, R. (2001). Responsiveness to threat and incentive in bi-
polar disorder: Relations of the BIS/​BAS scales with symptoms. Journal of Psychopathology
and Behavioral Assessment, 23, 133–​143.
Meyer, T., Smeets, T., Giesbrecht, T., Quaedflieg, C. W., Smulders, F. T., Meijer, E. H., &
Merckelbach, H. L. (2015). The role of frontal EEG asymmetry in post-​traumatic stress dis-
order. Biological Psychology, 108, 62–​77. doi:10.1016/​j.biopsycho.2015.03.018
Mitchell, A. M. & Pössel, P. (2012). Frontal brain activity pattern predicts depression in adoles-
cent boys. Biological Psychology, 89(2), 525–​527.
Mize, K. D. & Jones, N. A. (2012). Infant physiological and behavioral responses to loss of ma-
ternal attention to a social-​rival. International Journal of Psychophysiology, 83(1), 16–​23.
doi:10.1016/​j.ijpsycho.2011.09.018
Murphy, F. C., Nimmo-​Smith, I., & Lawrence, A. D. (2003). Functional neuroanatomy of
emotion: A meta-​analysis. Cognitive, Affective, & Behavioral Neuroscience, 3, 207–​233.
Myrick, H., Anton, R. F., Li, X., Henderson, S., Drobes, D., Voronin, K., & George, M. S. (2004).
Differential brain activity in alcoholics and social drinkers to alcohol cues: Relationship to
craving. Neuropsychopharmacology, 29(2), 393–​402. doi:10.1038/​sj.npp.1300295
Nash, K., Inzlicht, M., & McGregor, I. (2012). Approach-​related left prefrontal EEG asymmetry
predicts muted error-​related negativity. Biological Psychology, 91, 96–​102.
Neal, L. B. & Gable, P. A. (2016). Neurophysiological markers of multiple facets of impulsivity.
Biological Psychology, 115, 64–​68. doi:10.1016/​j.biopsycho.2012.05.005
Neal, L. B. & Gable, P. A. (2019). Shifts in frontal asymmetry underlying impulsive and
controlled decision-​making. Biological Psychology, 140, 28–​34.
Nigg, J. T. (2006). Temperament and developmental psychopathology. Journal of Child
Psychology and Psychiatry, 47(3-​4), 395–​422. doi:10.1111/​j.1469-​7610.2006.01612.x
Nitschke, J. B., Heller, W., Etienne, M. A., & Miller, G. A. (2004). Prefrontal cortex activity
differentiates processes affecting memory in depression. Biological Psychology, 67(1–​2),
125–​143.
Nusslock, R., Harmon-​Jones, E., Alloy, L. B., Urosevic, S., Goldstein, K., & Abramson, L. Y.
(2012). Elevated left mid-​frontal cortical activity prospectively predicts conversion to bi-
polar I disorder. Journal of Abnormal Psychology, 121(3), 592–​601. doi:10.1037/​a0028973
Nusslock, R., Shackman, A. J., Harmon-​Jones, E., Alloy, L. B., Coan, J. A., & Abramson, L. Y.
(2011). Cognitive vulnerability and frontal brain asymmetry: Common predictors of first
prospective depressive episode. Journal of Abnormal Psychology, 120, 497–​503.
Nusslock, R., Shackman, A. J., McMenamin, B. W., Greischar, L. L., Davidson, R. J., & Kovacs,
M. (2018). Comorbid anxiety moderates the relationship between depression history and
prefrontal EEG asymmetry. Psychophysiology, 55(1), e12953.
Pascual-​Marqui, R. D. (2002). Standardized low-​resolution brain electromagnetic tomog-
raphy (sLORETA): Technical details. Methods and Findings in Experimental and Clinical
Pharmacology, 24 (Suppl D), 5–​12.
Perria, P., Rosadini, G., & Rossi, G. F. (1961). Determination of side of cerebral dominance with
Amobarbital. Archives of Neurology, 4, 175–​181.
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    255

Peterson, C. K. & Harmon-​Jones, E. (2009). Circadian and seasonal variability of resting

frontal EEG asymmetry. Biological Psychology, 80, 315–​320.
Peterson, C. K., Gravens, L., & Harmon-​Jones, E. (2011). Asymmetric frontal cortical activity
and negative affective responses to ostracism. Social Cognitive Affective Neuroscience, 6, 277–​
285. doi:10.1093/​scan/​nsq027
Peterson, C. K., Shackman, A. J., & Harmon-​Jones, E. (2008). The role of asymmetric frontal
cortical activity in aggression. Psychophysiology, 45, 86–​92.
Pizzagalli, D. A., Sherwood, R. J., Henriques, J. B., & Davidson, R. J. (2005). Frontal brain asym-
metry and reward responsiveness: A source-​localization study. Psychological Science, 16(10),
805–​813. doi:10.1111/​j.1467-​9280.2005.01618.x
Pizzagalli, D., Shackman, A. J., & Davidson, R. J. (2003). The functional neuroimaging of
human emotion: Asymmetric contributions of cortical and subcortical circuitry. In K.
Hugdahl & R. J. Davidson (Eds.), The asymmetric brain (pp. 511–​532). MIT Press.
Plutchik, R. (1980). Emotion: A psychoevolutionary synthesis. HarperCollins College Division.
Pössel, P., Lo, H., Fritz, A., & Seemann, S. (2008). A longitudinal study of cortical EEG activity
in adolescents. Biological Psychology, 78(2), 173–​178. https://​doi.org/​https://​doi.org/​10.1016/​
j.biopsy​cho.2008.02.004
Price, T. F. & Harmon-​Jones, E. (2011). Approach motivational body postures lean toward left
frontal brain activity. Psychophysiology, 48, 718–​722.
Price, T. F., Hortensius, R., & Harmon-​Jones, E. (2013). Neural and behavioral associations of
manipulated determination facial expressions. Biological Psychology, 94, 221–​227. http://​
dx.doi.org/​10.1016/​j.biopsy​cho.2013.06.001
Proudfit, G. H., Inzlicht, M., & Mennin, D. S. (2013). Anxiety and error monitoring: The im-
portance of motivation and emotion. Frontiers in Human Neuroscience, 7, 636. doi:10.3389/​
fnhum.2013.00636
Putman, P., Hermans, E., & van Honk, J. (2004). Emotional Stroop performance for masked
angry faces: It’s BAS, not BIS. Emotion, 4, 305–​311.
Quaedflieg, C. W. E. M., Smulders, F. T. Y., Meyer, T., Peeters, F. P. M. L., Merckelbach, H. L. G. J.,
& Smeets, T. (2016). The validity of individual frontal alpha asymmetry EEG neurofeedback.
Social Cognitive and Affective Neuroscience, 11, 33–​43. Doi: 10.1093/​scan/​nsv090
Quirin, M., Gruber, T., Kuhl, J., & Düsing, R. (2013). Is love right? Prefrontal resting brain
asymmetry is related to the affiliation motive. Frontiers in Human Neuroscience, 7, 902.
doi:10.3389/​ fnhum.2013.00902
Reid, S. A., Duke, L. M., & Allen, J. J. B. (1998). Resting frontal electroencephalographic
asymmetry in depression: Inconsistencies suggest the need to identify mediating factors.
Psychophysiology, 35, 389–​404.
Robinson, R. G. & Price, T. R. (1982). Post-​stroke depressive disorders: A follow-​up study of 103
patients. Stroke, 13, 635–​641.
Rodrigues, J., Müller, M., Mühlberger, A., & Hewig, J. (2018). Mind the movement: Frontal
asymmetry stands for behavioral motivation, bilateral frontal activation for behavior.
Psychophysiology, 55(1), e12908. https://​doi.org/​10.1111/​psyp.12908
Rossi, G. F. & Rosadini, G. R. (1967). Experimental analyses of cerebral dominance in man. In
D. H. Millikan & F. L. Darley (Eds.), Brain mechanisms underlying speech and language (pp.
167–​184). Grune & Stratton.
Rothbart, M. K. & Rueda, M. R. (2005). The development of effortful control. In U. Mayr, E.
Awh, & S. W. Keele (Eds.), Developing individuality in the human brain: A tribute to Michael
I. Posner (pp. 167–​188). American Psychological Association.
256    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

Rothbart, M. K., Ellis, L. K., & Posner, M. I. (2004). Temperament and self-​regulation. In
K. D. Vohs & R. F. Baumeister (Eds.), Handbook of self-​regulation: Research, theory, and
applications (pp. 284–​299). Guilford Press.
Sackeim, H., Greenberg, M. S., Weimen, A. L., Gur, R. C., Hungerbuhler, J. P., & Geschwind,
N. (1982). Hemispheric asymmetry in the expression of positive and negative
emotions: Neurologic evidence. Archives of Neurology, 39, 210–​218.
Salavert, J., Caseras, X., Torrubia, R., Furest, S., Arranz, B., Dueñas, R., & San, L. (2007). The
functioning of the Behavioral Activation and Inhibition Systems in bipolar I euthymic
patients and its influence in subsequent episodes over an eighteen-​month period. Personality
and Individual Differences, 42(7), 1323–​1331.
Santesso, D. L., Segalowitz, S. J., Ashbaugh, A. R., Antony, M. M., McCabe, R. E., & Schmidt,
L. A. (2008). Frontal EEG asymmetry and sensation seeking in young adults. Biological
Psychology, 78, 164–​172.
Schaffer, C. E., Davidson, R. J., & Saron, C. (1983). Frontal and parietal electroencephalogram
asymmetry in depressed and nondepressed subjects. Biological Psychiatry, 18, 753–​762.
Schiff, B. B. & Lamon, M. (1989). Inducing emotion by unilateral contraction of fa-
cial muscles: A new look at hemispheric specialization and the experience of emotion.
Neuropsychologia, 27, 923–​935.
Schiff, B. B. & Lamon, M. (1994). Inducing emotion by unilateral contraction of hand muscles.
Cortex, 30, 247–​254.
Schmeichel, B. J., Crowell, A., & Harmon-​Jones, E. (2016). Exercising self-​control increases rela-
tive left frontal cortical activation. Social Cognitive and Affective Neuroscience, 11, 282–​288.
Schöne, B., Schomberg, J., Gruber, T., & Quirin, M. (2016). Event-​related frontal alpha
asymmetries: Electrophysiological correlates of approach motivation. Experimental Brain
Research, 234(2), 559–​567. doi:10.1007/​s00221-​015-​4483-​6
Schutter, D. J. L. G. (2009). Transcranial magnetic stimulation. In E. Harmon-​Jones & J. S. Beer
(Eds.), Methods in social neuroscience (pp. 233–​258). Guilford Press.
Schutter, D. J. L. G. & Harmon-​Jones, E. (2013). The corpus callosum: A commissural road to
anger and aggression. Neuroscience & Biobehavioral Reviews, 37, 2481–​2488. http://​dx.doi.
org/​10.1016/​j.neubio​rev.2013.07.013
Schutter, D. J. L. G., van Honk, J., d’Alfonso, A. A. L., Postma, A., & de Haan, E.H.F. (2001).
Effects of slow rTMS at the right dorsolateral prefrontal cortex on EEG asymmetry and
mood. Neuroreport, 12, 445–​447.
Shankman, S. A., Klein, D. N., Tenke, C. E., & Bruder, G. E. (2007). Reward sensitivity in de-
pression: A biobehavioral study. Journal of Abnormal Psychology, 116(1), 95–​104
Simons, J. S., Dvorak, R. D., Batien, B. D., & Wray, T. B. (2010). Event-​level associations be-
tween affect, alcohol intoxication, and acute dependence symptoms: Effects of urgency,
self-​control, and drinking experience. Addictive Behaviors, 35(12), 1045–​1053. doi:10.1016/​
j.addbeh.2010.07.001
Siniatchkin, M., Kropp, P., & Gerber, W-​D. (2000). Neurofeedback—​The significance of re-
inforcement and the search for an appropriate strategy for the success of self-​regulation.
Applied Psychophysiology and Biofeedback, 25, 167–​175.
Smith E. E., Cavanagh, J. F., & Allen, J. J. B. (2018). Intracranial source activity (eLORETA)
related to scalp-​level asymmetry scores and depression status. Psychophysiology, 55(1), 119–​
134. https://​doi.org/​10.1111/​psyp.13019
Smith, E. E., Zambrano-​Vazquez, L., & Allen, J. J. B. (2016). Patterns of alpha asymmetry in
those with elevated worry, trait anxiety, and obsessive-​compulsive symptoms: A test of the
 ASYMMETRIC FRONTAL CORTICAL ACTIVITY    257

worry and avoidance models of alpha asymmetry. Neuropsychologia, 85, 118–​126. https://​doi.
org/​10.1016/​j.neuro​psyc​holo​gia.2016.03.010
Smits, D. J. M. & Kuppens, P. (2005). The relations between anger, coping with anger, and
aggression, and the BIS/​BAS system. Personality and Individual Differences, 39, 783–​793.
Spielberger, C. D. (1988). State–​trait anger expression inventory. Psychological Assessment
Resources.
Spielberger, C. D., Reheiser, E. C., & Sydeman, S. J. (1995). Measuring the experience, expres-
sion, and control of anger. In H. Kassinove (Ed.), Anger disorders: Definition, diagnosis, and
treatment (pp. 49–​67). Taylor & Francis.
Stewart, J. L. & Allen, J. J. (2018). Resting frontal brain asymmetry is linked to future depressive
symptoms in women. Biological Psychology, 136, 161–​167.
Stewart, J. L., Bismark, A. W., Towers, D. N., Coan, J. A., & Allen, J. J. B. (2010). Resting frontal
EEG asymmetry as an endophenotype for depression risk: Sex-​specific patterns of frontal
brain asymmetry. Journal of Abnormal Psychology, 119(3), 502–​512.
Stewart, J. L., Coan, J. A., Towers, D. N., & Allen, J. J. B. (2011). Frontal EEG asymmetry during
emotional challenge differentiates individuals with and without lifetime major depres-
sive disorder. Journal of Affective Disorders, 129(1), 167–​174. https://​doi.org/​https://​doi.org/​
10.1016/​j.jad.2010.08.029
Stewart, J. L., Coan, J. A., Towers, D. N., & Allen, J. J. B. (2014). Resting and task-​elicited
prefrontal EEG alpha asymmetry in depression: Support for the capability model.
Psychophysiology, 51(5), 446–​455. https://​doi.org/​10.1111/​psyp.12191
Strack, F. & Deutsch, R. (2004). Reflective and impulsive determinants of social behavior.
Personality and Social Psychology Review, 8(3), 220–​247. doi:10.1207/​s15327957pspr0803_​1
Sutton, S. K. & Davidson, R. J. (1997). Prefrontal brain asymmetry: A biological substrate of the
behavioral approach and inhibition systems. Psychological Science, 8, 204–​210.
Teper, R. & Inzlicht, M. (2013). Meditation, mindfulness and executive control: The import-
ance of emotional acceptance and brain-​based performance monitoring. Social, Cognitive,
and Affective Neuroscience, 8(1), 85–​92. doi:10.1093/​scan/​nss045
Terzian, H. & Cecotto, C. (1959). Determination and study of hemisphere dominance by
means of intracarotid sodium amytal injection in man: II. Electroencephalographic effects.
Bollettino della Societa Italiana Sperimentale, 35, 1626–​1630.
Thibodeau, R., Jorgensen, R. S., & Kim, S. (2006). Depression, anxiety, and resting frontal
EEG asymmetry: A meta-​analytic review. Journal of Abnormal Psychology, 115(4), 715–​729.
doi:10.1037/​ 0021-​843X.115.4.715.
Tomarken, A. J. & Davidson, R. J. (1994). Frontal brain activation in repressors and
nonrepressors. Journal of Abnormal Psychology, 103(2), 339–​ 349. doi:10.1037/​
0021-​843X.103.2.339
Tomarken, A. J., Davidson, R. J., Wheeler, R. E., & Doss, R. (1992). Individual differences in an-
terior brain asymmetry and fundamental dimensions of emotion. Journal of Personality and
Social Psychology, 62, 676–​687.
Urosevic, S., Abramson, L. Y., Alloy, L. B., Nusslock, R., Harmon-​Jones, E., Bender, R., &
Hogan, M. E. (2010). Increased rates of events that activate or deactivate the Behavioral
Approach System, but not events related to goal attainment, in bipolar spectrum disorders.
Journal of Abnormal Psychology, 119, 610–​615.
Valiente, C., Eisenberg, N., Smith, C. L., Reiser, M., Fabes, R. A., Losoya, S., ... Murphy, B. C.
(2003). The relations of effortful control and reactive control to children’s externalizing
258    EDDIE HARMON-JONES, TAYLOR POPP, AND PHILIP A. GABLE

problems: A longitudinal assessment. Journal of Personality, 71(6), 1171–​1196. doi:10.1111/​

1467-​6494.7106011
van de Laar, M. C., Licht, R., Franken, I. H. A., & Hendriks, V. M. (2004). Event-​related
potentials indicate motivational relevance of cocaine cues in abstinent cocaine addicts.
Psychopharmacology, 177, 121–​129.
Verona, E., Sadeh, N., & Curtin, J. J. (2009). Stress-​induced asymmetric frontal brain activity
and aggression risk. Journal of Abnormal Psychology, 118, 131–​145.
Wacker, J., Chavanon, M. L., Leue, A., & Stemmler, G. (2008). Is running away right? The be-
havioral activation-​behavioral inhibition model of anterior asymmetry. Emotion, 8(2), 232–​
249. doi:10.1037/​1528-​3542.8.2.232
Wacker, J., Chavanon, M. L., & Stemmler, G. (2010). Resting EEG signatures of agentic extra-
version: New results and meta-​analytic integration. Journal of Research in Personality, 44(2),
167–​179. doi:10.1016/​j.jrp.2009.12.004
Wacker, J., Heldmann, M., & Stemmler, G. (2003). Separating emotion and motivational direc-
tion in fear and anger: Effects on frontal asymmetry. Emotion, 3, 167–​193.
Wacker, J., Mueller, E. M., Pizzagalli, D. A., Hennig, J., & Stemmler, G. (2013). Dopamine-​D2-​
receptor blockade reverses the association between trait approach motivation and frontal
asymmetry in an approach-​motivation context. Psychological Science, 24, 489–​497.
Whiteside, S. P., Lynam, D. R., Miller, J. D., & Reynolds, S. K. (2005). Validation of the UPPS im-
pulsive behaviour scale: A four-​factor model of impulsivity. European Journal of Personality,
19(7), 559–​574. doi:10.1002/​per.556
Wiedemann, G., Pauli, P., Dengler, W., Lutzenberger, W., Birbaumer, N., & Buchkremer, G.
(1999). Frontal brain asymmetry as a biological substrate of emotions in patients with panic
disorders. Archives of GENERAL PSYCHIATRY, 56(1), 78–​84.
Young, P. T. (1943). Emotion in man and animal: Its nature and relation to attitude and motive.
John Wiley and Sons.
Zapolski, T. C., Cyders, M. A., & Smith, G. T. (2009). Positive urgency predicts illegal drug
use and risky sexual behavior. Psychology of Addictive Behaviors, 23(2), 348. doi:10.1037/​
a0014684
Zinner, L. R., Brodish, A. B., Devine, P. G., & Harmon-​Jones, E. (2008). Anger and asym-
metric frontal cortical activity: Evidence for an anger-​withdrawal relationship. Cognition &
Emotion, 22, 1081–​1093.
 CHAPTER 12

OSCI LL ATORY AC T I V I T Y I N
SENSORIMOTOR FU NC T I ON

Bernadette C. M. van WIJK

12.1 Understanding
the sensorimotor system

Movement is quintessential for most living organisms including humans. It is through

movement that we feed ourselves, reproduce, communicate, perceive, and affect the ex-
ternal world. Most of our daily movements are performed without giving them much
thought. We lift our arm to reach for a cup of coffee, grasp our fingers around it with
enough force to hold the cup, and bring it to our mouth in order to drink without
spilling—​all seemingly without any effort. Even this arguably simple action requires
transformation of an action goal into a movement trajectory, activation and deactiva-
tion of several muscle groups at appropriate moments in both space and time, and relies
on accurate integration of visual information on the shape and position of the cup, pro-
prioceptive input from muscles and joints on position and velocity of the limbs, and
haptic feedback from which we can infer the cup’s weight, to plan and adjust muscle
activations. Fortunately, we can acquire complex motor skills through practice. We can
learn how to coordinate our finger movements to efficiently type a text on a computer
keyboard, or even to play the most virtuoso piano pieces.
The sensorimotor system is the network of motor and sensory regions in the brain
and spinal cord thought to be involved in the planning, initiation, and execution of
movements. In humans, it comprises primary somatosensory cortex (S1), primary
motor cortex (M1), dorsal and ventral premotor cortex (PMd, PMv), (pre-​)supplemen-
tary motor area (SMA), cingulate motor areas (CMA), cerebellum, the basal ganglia,
several nuclei in brainstem and thalamus, motoneurons and interneurons in the spinal
cord, and muscle afferents (Figure 12.1). Roughly speaking, one can distinguish a medial
pathway of fiber tracts descending from cortex and brainstem nuclei down the spinal
260    Bernadette C. M. van Wijk

SMA
M1 S1

Striatum
PMC

GPe
VL/VA GPi
Thal.

STN
Thalamus
Brainstem
Cerebellum

Afferent
Efferent Pathways
Pathways
Spinal
Cord

Figure 12.1  Schematic overview of major cortical and subcortical pathways that comprise the
sensorimotor system. Left: primary and secondary motor cortex project directly to the spinal
cord and via brainstem nuclei. Afferent proprioceptive information travels to primary somato-
sensory cortex via thalamus and enters the cerebellum directly. Right: The basal ganglia con-
sist of the striatum, internal and external pallidum (GPi, GPe), and subthalamic nucleus (STN).
Together with the thalamus they form circuits with various cortical regions, of which the ventral
lateral and ventral anterior thalamus (VL, VA) project to primary and secondary motor cortex.

cord that innervate axial muscles for the regulation of posture and balance, and a lateral
tract innervating distal muscles. The sensorimotor system has a bilateral organization,
with most corticospinal tracts crossing at the level of the medulla. This suggests that
movements of the right arm and leg are primarily controlled by the left hemisphere, and
vice versa. Movements and actions are intricately linked with perception and cognition;
therefore, the sensorimotor system must uphold strong ties with other circuits. As such,
the distinction between systems is not always clear and some sensorimotor regions have
been ascribed more cognitive roles.
As much as one would like to understand how a gymnast performs a twisting
somersault, the study of (supraspinal) neural control of movement in laboratory
settings is typically restricted to what is often referred to as “simple” uni-​or bimanual
movements like finger tapping or isometric force generation. Electroencephalography
(EEG), magnetoencephalography (MEG), and electrocorticography (ECoG) are pre-
dominantly sensitive to synchronous synaptic transmission in cortical regions, while
electromyography (EMG) may provide insight into the activation of motoneurons
in the spinal cord via the spread of action potential currents that can be picked up
non-​invasively with electrodes placed on the skin over the muscle belly. Increasing
use of deep brain stimulation (DBS) for the treatment of movement disorders allows
for invasively recording local field potentials (LFPs) from basal ganglia and thalamic
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    261

structures in humans. It is even possible to combine recording techniques in a single

experiment to investigate distant interactions between different parts of the sensori-
motor system. For example, simultaneous use of EEG/​MEG and EMG allows for the
detection of functional interactions between cortex and spinal cord, and invasive LFP
recordings from DBS electrodes can be combined with non-​invasive EEG or MEG
to detect functional interactions between cortex and basal ganglia structures like the
subthalamic nucleus (STN) and internal pallidum (GPi). Performed movements can
be co-​registered via button-​presses, force sensors, trackpads, joy sticks, or motion-​
capturing systems. By investigating how recorded neural signals change during the
experimental task or due to pathology one could relate oscillatory activity to motor
function.
Movement-​related neural population activity appears in several frequency bands
(Figure 12.2). Many studies contributed to understanding the functional role of these
frequency bands in individual sensorimotor regions. Via measures of coupled oscil-
latory activity (e.g., coherence) one could get a sense of functional connectivity within
the system. This chapter highlights several research findings and (ongoing) debates
on which we build our current knowledge. While it covers many topics, it is meant as
introductory text rather than an exhaustive literature review. Although we have studied
oscillations in sensorimotor function for many decades, it is exciting to see that the field
is still evolving with new technologies, signal processing techniques, and novel experi-
mental paradigms.

M1 STN STN
Relative
90 90 350 log power
Frequency [Hz]

70 70 0.4
250
0.2
50 50
150 0
30 30
–0.2
10 10 50
–0.4
–2 0 2 4 6 –2 0 2 4 6 –2 0 2 4 6
Time from movement onset [s]
Figure 12.2  Movement-​related time-​frequency spectra for primary motor cortex (M1) and
subthalamic nucleus (STN). Panels show the relative change in spectral power with respect to
a pre-​movement baseline window. Participants performed a simple self-​paced button press
movement with three fingers simultaneously at time point 0. Beta power starts to decrease be-
fore movement onset (ERD) and shows a clear post-​movement rebound (ERS). Gamma power
increases around movement onset. In STN, another movement-​related increase with smaller
amplitude can be observed in the range for high-​frequency oscillations (HFOs). Note how time-​
frequency modulations look very similar for M1 and STN, suggesting generic principles of infor-
mation processing.
Spectra are based on MEG and DBS-​LFP recordings from
eleven Parkinson’s disease patients on dopaminergic medication taken from Litvak et al., 2012.
262    Bernadette C. M. van Wijk

12.2  A traditional view

on frequency bands

Ever since the first recordings, researchers have divided EEG/​MEG time series into fre-
quency bands that are presumed to have their own functional roles. This section focuses
on the properties of frequency bands that are thought to be central to sensorimotor
function.

12.2.1 The Difference Between Alpha, Mu, and Beta

The alpha rhythm was the first rhythm observed by Berger (1929). Soon after, it was
discovered that the alpha rhythm is suppressed when closing the eyes, has its origin
in the occipital lobes (Adrian & Matthews, 1934), and that another alpha rhythm can
be observed close to the central sulcus that, together with a beta rhythm, is suppressed
upon tactile stimulation (Jasper & Andrews, 1938). Later studies showed that the central
rhythms are also modulated by passive, voluntary, and imagined movements (Chatrian
et al., 1959; Gastaut, 1952; Jasper & Penfield, 1949). The alpha rhythm close to the cen-
tral sulcus (or “Rolandic fissure”) was named mu—​after the arch-​like shape of the oscil-
lation. However, in the current literature mu and alpha are used interchangeably. Mu/​
alpha oscillations are usually defined to have a peak frequency between 8–​13 Hz. Beta
oscillations are considered to occur within the approximate range of 13–​30 Hz. Both
alpha/​mu and beta oscillations show a distinctive decrease in amplitude prior to and
during movement execution (event-​related desynchronization, ERD), followed by a
rebound that exceeds baseline after the movement has been terminated (event-​related
synchronization, ERS) (Pfurtscheller & Lopes Da Silva, 1999). Still, dissimilarities in
time course, spatial origin, and coupling to other regions indicate that the two bands are
functionally distinct.
Beta ERD might start as early as 2 s before movement initiation and is often thought to
reflect a general state of motor preparation (Neuper & Pfurtscheller, 2001). It starts over
sensorimotor cortex contralateral to the moving hand and becomes bilateral during
movement. Alpha/​mu ERD starts a bit later in time and is spatially more diffuse and
somatotopically less specific (Crone et al., 1998b). Beta ERS is often more pronounced
and occurs at a shorter latency compared alpha ERS (Alegre et al., 2003; Erbil & Ungan,
2007; Pfurtscheller et al., 1996; Salmelin & Hari, 1994). The two rhythms are likely to
originate from distinct sources as different source localization methods ascribed beta
modulations to precentral (motor) cortex and mu/​alpha modulations to postcentral
(somatosensory) cortex (Cheyne et al., 2003; Ritter et al., 2009; Salmelin et al., 1995;
Salmelin & Hari, 1994). As explained in the subsequent sections, the beta band often
shows the most specific modulations with experimental conditions and pathology
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    263

and dominates the functional connectivity profile for sensorimotor cortex. For these
reasons, beta oscillations are considered most associated with motor control.

12.2.2 A Prominent Role for Beta Oscillations

The primary functional role of beta oscillations seems to be the facilitation and inhib-
ition of movements. Beta ERD already starts during the movement preparation phase
and appears stronger when the action that needs to be prepared is known in advance.
The ERD is lateralized with stronger suppression over contralateral M1 when the re-
sponse hand is known, also resulting in faster reaction times (Doyle et al., 2005b; van
Wijk et al., 2009). On the other hand, ERS only appears after the movement has been
terminated, and therefore has been proposed to reflect a period of inactivation to re-
cover from previous activation (Pfurtscheller et al., 1996), or processing of afferent som-
atosensory information (Cassim et al., 2001). Chen and colleagues (1998) tracked the
time course of corticospinal excitability around self-​paced and instructed movements
using transcranial magnetic stimulation. Pulses were delivered at different time points
around movement onset to see how the amplitude of motor evoked potentials varied
during the time windows of ERD and ERS. An increase in corticospinal excitability was
found in the final 100 ms of the pre-​movement preparation phase and around 100 ms
after movement onset, which are time periods during which ERD is often strongest. By
contrast, a decrease in corticospinal excitability was found between 500 and 1000 ms
after movement, which is around the time of ERS.
Beta oscillations are not simply an idling state, but also have a functional impact
on the initiation and stabilization of motor output. Movements are performed more
slowly when initiated during periods of high-​amplitude beta oscillations in the ongoing
EEG (Gilbertson et al., 2005). Entrainment of cortical beta oscillations by transcranial
alternating-​current stimulation at 20 Hz has a similar effect (Pogosyan et al., 2009).
Cortico-​spinal beta phase synchronization increases when the current motor output
needs to be maintained (van Wijk et al., 2009), for example, in anticipation of upcoming
perturbations to finger position (Androulidakis et al., 2007a). This implies that both a
down-​and up-​regulation of beta oscillations is employed by the nervous system to tune
motor output.
What happens at a neurobiological level that determines the amplitude of beta
oscillations? Motor cortical architecture consists of intricately and reciprocally
connected excitatory pyramidal cells and inhibitory interneurons within and across
layers (Keller, 1993). In order to determine the contribution of individual receptor types
to network activity they can be activated or blocked with pharmacological agents in in
vitro slice preparations of animal cortex. This revealed GABAA receptors to be critical
for the generation of beta oscillations together with an influence of gap junctions, but
not AMPA receptors (Yamawaki et al., 2008). There are strong indications that beta
oscillations originate in layer V while also clearly present in layer II. IPSPs on layer 5
pyramidal cells are phase locked with the LFP beta oscillation, as is the spiking of
264    Bernadette C. M. van Wijk

pyramidal cells but at much sparser rates (Lacey et al., 2014). The dependence of beta
oscillation amplitude on GABAA receptors has also been established through in vivo
pharmacological studies in humans. After administration of benzodiazepines, a class
of GABAergic drugs often prescribed as anticonvulsants, sedatives, or muscle relaxants,
spectral beta power in EEG/​MEG appears enhanced (Baker & Baker, 2003; Hall et al.,
2010; Jensen et al., 2005). Along these lines, computational modelling work suggests
that stronger synaptic inputs between pyramidal cells in different layers might underlie
the beta suppression that is observed during movement (Bhatt et al., 2016).
Despite the prominence of beta band oscillations in sensorimotor function,
movement-​related modulations only seem to encode general motor aspects. More
forceful movements induce stronger alpha/​mu and beta ERD (Mima et al., 1999; Stančák
et al., 1997; Stančák & Pfurtscheller, 1996) as do movements that are performed with a
higher frequency (Toma et al., 2002) or involving more complex sequences (Hummel
et al., 2003; Manganotti et al., 1998). Movements with more muscle mass involved do not
influence ERD but rather lead to stronger beta ERS (Pfurtscheller et al., 1998; Stančák
et al., 2000). Movement duration has little effect on either ERD or ERS (Cassim et al.,
2000; Stančák & Pfurtscheller, 1996). It is however difficult to pinpoint ERD and ERS
patterns to specific motor parameters.

12.2.3 Prokinetic Gamma
To find a mechanistic link between beta oscillations and the control of movement tra-
jectory and muscle force, it can be useful to consider the behavior of individual neurons.
Pyramidal tract neurons (PTNs) in infragranular layers project to motoneurons of in-
dividual muscles and groups of muscles in the spinal cord, and appear to be function-
ally organized in small clusters (Asanuma et al., 1979). They only form a minority of
cells in motor cortex and form intricate connections with other neurons within and
between cortical modules that together encode movement patterns (Keller, 1993).
Microelectrode recordings in sensorimotor cortices of the macaque monkey revealed
spikes of individual neurons to be phase-​locked to the LFP beta oscillation during time
periods when the oscillation is well pronounced (Baker et al., 1997; Denker et al., 2007;
Murthy & Fetz, 1996a). Although the phase locking of individual PTNs to the beta os-
cillation may only be weak, summation over a population of neurons can give a clearer
picture (Baker et al., 2003). We also know that the encoding of parameters such as hand
position, direction of motion, velocity, and force emerges from the joint firing rates of
a group of neurons that are individually tuned (Ashe & Georgopoulos, 1994; Fu et al.,
1995; Georgopoulos et al., 1986; Moran & Schwartz, 2017; Paninski et al., 2004). This is
termed population coding.
When movements are executed, phase locking of spikes with the beta oscillation
drops and spike rates strongly increase (Baker et al., 2001; Spinks et al., 2008). There
is a crude inverse correlation between spike rates and LFP beta power. Spike rates
reach frequencies above 30 Hz (Baker et al., 2001; Grammont and Riehle, 2003) and
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    265

may well correspond to the brief increases in gamma power (~30–​100 Hz) that can
be observed in EEG and MEG recordings in a time window around movement onset
(Cheyne et al., 2008; Muthukumaraswamy, 2010; Ohara et al., 2001; Pfurtscheller et al.,
1993; Pfurtscheller & Neuper, 1992). Unlike the alpha/​mu and beta ERD, the increase
in gamma only occurs in the hemisphere contralateral to the moving body part and
is somatotopically more focused (Crone et al., 1998a; Miller et al., 2007; Szurhaj et al.,
2005). Some studies report the gamma amplitude increase to vary with movement dir-
ection in invasive recordings (Leuthardt et al., 2004; Rickert et al., 2005). However, it
remains to be seen whether gamma power in EEG and MEG recordings has the same
specificity. Taken together, one may hypothesize that the beta oscillation inhibits, or
constrains, neuronal spiking. That is, a suppression of the beta rhythm can lead to an in-
crease in excitability of individual neurons that together encode movement parameters.

12.2.4 High-​Frequency Oscillations
The latest addition to the repertoire of movement-​related oscillations is a spectral
component with a clear peak in the 150–​400 Hz frequency range, aptly coined high-​
frequency oscillations (HFO). HFO have been observed in LFP recordings from DBS
electrodes in the STN and internal pallidum. They are of interest to sensorimotor
function as they show a characteristic increase in amplitude during movement (Foffani
et al., 2003; Litvak et al., 2012; López-​Azcárate et al., 2010; Tan et al., 2013; Tsiokos et al.,
2013), like the gamma band. Their peak frequency is modulated by dopaminergic medi-
cation (López-​Azcárate et al., 2010; Özkurt et al., 2011; van Wijk et al., 2016) and indica-
tive of tremor symptoms in patients with Parkinson’s disease (Hirschmann et al., 2016).
Yet, a similar movement-​related HFO component in the cortex has not been reported
although this may simply be due to the poor signal-​to-​noise ratio of commonly used
EEG/​MEG compared to more focal, invasive techniques.

12.3  Coherence as a measure of

functional connectivity within
the sensorimotor system

Any understanding of sensorimotor function will not be complete if the information ex-
change between regions that comprise the sensorimotor system is ignored. Rhythmic
synchronization in the form of oscillations has been recognized as a means by which
neural populations selectively gate their sensitivity to input from other populations (Fries,
2005). The degree of synchronization between neural populations can be estimated by
computing coherence between time series as a measure of functional connectivity. This
measure can be understood as spectral counterpart of conventional correlation.
266    Bernadette C. M. van Wijk

12.3.1 Cortico-​Spinal Coherence
Cortico​spinal coherence, also called cortico​muscular coherence, refers to the syn-
chronization between oscillations in cortex and motoneuron activity in the spinal cord.
Firing of motoneurons yields motor unit action potentials that induce contraction of
muscle fibers. Repetitive firing is necessary in order to build up force. The rate at which
this occurs ranges from 6 Hz in rest to 35 Hz during forceful isometric contractions
and bursts of 80–​120 Hz in case of rapid, ballistic movements (Freund, 1983). As such,
corticospinal coherence may reflect whether synchronized activity in cortex also
reaches the muscles.
Several studies report weak but significant beta-​band coherence between the EMG of
hand or foot muscles and EEG over contralateral sensorimotor regions during sustained
isometric muscle contractions (Conway et al., 1995; Gross et al., 2000; Halliday et al.,
1998; Salenius et al., 1997; van Wijk et al., 2012). Coherence levels increase for muscle
contractions with higher force levels (Chakarov et al., 2009; Witte et al., 2007) and peak
frequencies shift into the gamma range during maximal force production (Brown et al.,
1998; Mima et al., 1999). Task-​dependent coherence has also been found for the EEG
with different muscle groups, thereby forming functional synergies (Zandvoort et al.,
2019), or between EMG recordings of different muscles themselves (Boonstra et al.,
2016). While beta-​band corticospinal coherence diminishes during movement (Baker
et al., 1997; Kilner et al., 2000), alpha-​band coherence between active muscle groups
increases (Boonstra et al., 2009). Typically, no significant coherence can be observed in
rest unless a strong tremor is present (Hellwig et al., 2001).
Corticospinal beta coherence can be modulated by cognitive factors. The division of
attention during dual task performance decreases coherence levels (Johnson et al., 2011;
Kristeva-​Feige et al., 2002; Safri et al., 2007), whereas task instructions to maintain
force output at a target level with high precision lead to increased coherence (Kristeva
et al., 2007). Using a pre-​cued choice reaction time task, Van Wijk and colleagues
(2009) demonstrated that corticospinal coherence can be up-​regulated in anticipation
of an upcoming movement decision. Key to their experimental paradigm was the pre-​
activation of muscles in each trial via a precision grip before stimuli were displayed.
This led to a build-​up of corticospinal coherence that allows for modulations to be ob-
servable. After presentation of a warning cue of the likely upcoming response hand,
corticospinal synchronization increased for the non-​selected hand, while cortical beta
power decreased for the selected hand. These and other findings jointly suggest that
the role of beta oscillations to facilitate or inhibit movements extends to the level of the
spinal cord.
Does corticospinal coherence reflect mere entrainment of motoneurons by cortical
output? Feedback signals from muscle afferents ascend the spinal cord to somatosen-
sory cortex, which through strong connections with primary motor cortex, closes the
corticospinal loop. Riddle and Baker (2005) sought to tackle this question experimen-
tally by cooling subjects’ arms. Cooling caused an additional time delay (inferred from
phase-​frequency regression) that was about twice the conduction time in one direction.
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    267

The authors therefore concluded that both ascending and descending pathways con-
tribute to the occurrence of corticospinal coherence. One may determine the direction-
ality of coupling by using measures such as Granger causality. This similarly revealed
significant contributions of both ascending and descending pathways (Witham
et al., 2011). It is worth noting that corticospinal coherence does not strictly follow
modulations of cortical power. Baker and Baker (2003) demonstrated this by recording
subjects before and after intake of diazepam, a benzodiazepine that enhances inhibitory
post-​synaptic potentials via GABAA receptors. EEG beta power doubled in amplitude,
but corticospinal coherence was little altered. Interactions between cortex and spinal
cord might therefore be more complex than a simple one-​way drive.

12.3.2 Cortico-​Subcortical Coherence
With EEG and MEG being most sensitive to cortical sources, it is easy to forget the
contribution of more deeply located brain structures. Many of these are highly rele-
vant for sensorimotor and cognitive functions. DBS treatment allows for invasively
recording electrophysiological activity from subcortical structures in humans. The
subthalamic nucleus (STN) and internal pallidum (GPi) are primary targets for the
treatment of Parkinson’s disease and dystonia, the pedunculopontine nucleus (PPN)
for postural instability and gait freezing, and the ventrolateral thalamus (including
ventral intermediate nucleus) for tremor. It is possible, albeit challenging, to combine
LFP recordings from DBS electrodes with simultaneous EEG or MEG to study cortico-​
subcortical interactions.
Early simultaneous LFP-​MEG studies sought to map functional connectivity with
cortical regions across different frequency ranges during rest. Litvak and colleagues
(2011) and Hirschmann and colleagues (2011) showed converging evidence for the
presence of two spatially distinct and frequency-​specific networks for the STN and
ipsilateral cortical areas: alpha-​band coherence with temporoparietal cortex and
beta-​band coherence with pre-​motor cortex. Coherence values for these sources
were little altered with dopaminergic medication. Using directionality analysis, cor-
tical activity was found to drive STN activity for both frequency bands (Litvak et al.,
2011). Both research labs followed up on these studies by investigating movement-​
related coherence but found more conflicting results. Litvak and colleagues (2012)
reported an increase in gamma band coherence during movement execution that was
further increased by dopaminergic mediation. Beta coherence increased during the
post-​movement beta rebound period but was unaltered by medication. In a separate
study, they describe a reduction of alpha-​band coherence during movement that was
more pronounced with medication (Oswal et al., 2013). By contrast, Hirschmann
and colleagues (2013) found that medication reduced beta-​band coherence during
movement but not alpha.
Simultaneous LFP-​MEG recordings identified functional networks also for other
subcortical structures. Activity in PPN appeared coherent with that of the brainstem
268    Bernadette C. M. van Wijk

Beta coherence 0.03 Rest

Movement

Coherence
0.02

0.01

0
10 20 30 40 50
Right GPi
Frequency [Hz]

Figure 12.3  Beta band coherence between the right internal pallidum (GPi) and ipsilateral
sensorimotor cortex. Left: Topography with darker colors indicating stronger coherence values.
Right: Coherence is reduced during movement compared to rest.
Both panels are based on MEG and DBS-​LFP recordings from eight dystonia patients taken from Van Wijk et al., 2017.

and cingulate cortex in the alpha band, and with medial cortical motor areas in the
beta band (Jha et al., 2017). For GPi, coherence was found with temporal cortex in the
theta band, cerebellum in the alpha band, and sensorimotor cortex in the beta band
(Neumann et al., 2015). This study was conducted in dystonia patients, for whom dis-
ease severity significantly correlated only with theta band coherence. Beta-​band co-
herence was unrelated to symptoms but showed a movement-​related reduction (van
Wijk et al., 2017; see Figure 12.3). The lack of clear alterations of cortico-​subcortical co-
herence by medication or correlation with clinical symptoms suggests that this form of
functional coupling might be physiological rather than disease-​related. Experimental
paradigms with more refined task designs will be needed to unravel their func-
tional roles.

12.3.3 Cortico-​Cortical Coherence
Many motor tasks call upon the coordinated activation of multiple cortical regions.
Researchers have used coherence analysis with the aim to find traces of functional
coupling between EEG/​MEG time series recorded at different locations. Some of
these findings confirmed inter-​regional coupling patterns as one would expect from
postulated sensorimotor functions of individual brain regions. For example, the ob-
servation of higher coherence values between sensorimotor cortex and mesial pre-
motor areas for internally compared to externally paced movement is in line with the
presumed involvement of SMA in self-​initiated movements (Gerloff et al., 1998; Serrien,
2008). Other findings are arguably more open for interpretation, like the increased level
of interhemispheric coherence between sensorimotor regions during more complex
unimanual and bimanual tasks (Gerloff et al., 1998; Gross et al., 2005; Manganotti et al.,
1998; Mima et al., 2000), or the observed gamma band coherence between cerebellar
hemispheres during bimanual finger tapping (Pollok et al., 2007). Notably, cortico-​
cortical coherence can be used to reveal the integration of information from sensory
modalities during motor tasks. Classen and colleagues (1998) demonstrated that beta-​
band coherence between motor and visual cortex is higher when participants make
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    269

use of visual information to perform a visuomotor tracking task compared to when the
visual stimulus is a mere distractor. Similarly, significant alpha-​band coherence between
auditory cortices and the motor network can be found when finger tapping is paced by a
metronome (Pollok et al., 2005).
Coherence analysis between EEG/​MEG time series is easily prone to volume con-
duction: multiple electrodes or sensors pick up the same neural activity leading to
an overestimation of functional connectivity. This prompted the development of
alternative connectivity measures like the imaginary part of coherency (Nolte et al.,
2004), where the real part of the cross-​spectrum is ignored as it may contain volume
conduction artifacts. The authors applied this measure to EEG data of a unimanual
finger tapping task and demonstrated a weak but significant 20 Hz coupling from
contralateral to ipsilateral sensorimotor cortex in the time period before movement
onset and in the reverse direction after movement. Another measure is the phase
lag index (Stam et al., 2007), which eliminates instantaneous coupling by looking at
the asymmetry of the relative phase distribution. Hillebrand and colleagues (2012)
showed that this measure removes volume conduction effects that are still present
after projecting MEG data to source space and identified a strongly connected sen-
sorimotor network in the beta band. The disadvantage of these measures is that any
true coupling with zero time-​lag is also ignored, therefore their estimates are on the
conservative side.
Invasive recordings reduce the problem of volume conduction if electrodes can
be placed sufficiently far apart. Murthy and Fetz (1996b) studied the occurrence of
synchronized oscillations in LFP signals from bilateral sensorimotor areas in the ma-
caque monkey. Oscillations occurred spontaneously at rest but only infrequently. They
appeared more often during exploratory arm movements with fine use of the fingers,
during which they were frequently synchronized between M1 and S1, and between bi-
lateral M1s. Both occurred at near zero time-​lags. Oscillations, however, did not seem to
occur at consistent points in time related to the movements. Other studies did observe
a systematic increase in synchronous oscillations between M1, S1, and premotor areas
of the same hemisphere or between bilateral M1s around or before movement onset
in more standardized tasks (Cardoso de Oliveira et al., 2001; Ohara et al., 2001; Sanes
& Donoghue, 1993), therefore providing support for the involvement of oscillations in
functional coupling between cortical areas.

12.4  Long-​term changes

in oscillatory activity

Measures of sensorimotor beta oscillations appear to be highly consistent within

individuals across repeated recording sessions (Espenhahn et al., 2017). However, their
characteristics might change over time due to several factors.
270    Bernadette C. M. van Wijk

12.4.1 Altered Oscillations Due to Development

and Aging
Physiological changes occur throughout our body as we grow older. Alterations in grey
matter volume, myelination, structural connectivity, neurotransmitters, receptors,
and skull conductivity (when recording EEG) potentially affect amplitudes and peak
frequencies of neural oscillations. In a cross-​sectional study, Heinrichs-​Graham and
colleagues (2018) investigated the age-​dependency of movement-​related oscillations by
measuring MEG of 57 healthy participants between the ages of 9 and 75 years. Absolute
(baseline) beta power showed a quadratic relation with age, with smallest values for
young adults, somewhat larger values for children, and clearly largest values for older
adults. The magnitude of beta ERD linearly increased across all ages, whereas post-​
movement ERS was most pronounced for young adults. Similar patterns were found
by other studies (Gaetz et al., 2010; Schmiedt-​Fehr et al., 2016) that also reported a re-
duction of peak frequency for ERD (Rossiter et al., 2014) or ERS (Espenhahn et al.,
2019) in older adults. Gamma ERS around movement onset has been reported to de-
crease in amplitude from childhood to adolescence (Trevarrow et al., 2019). While
gamma ERS typically only occurs in contralateral sensorimotor cortex in adults, it may
also be observed over ipsilateral cortex in younger children. Huo and colleagues (2011)
reported ipsilateral gamma ERS for 12 out of 20 children in the 6–​9-​year-​old age group
and significantly fewer instances for older age groups. These findings are likely related to
maturation of the corpus collosum and development of transcallosal inhibition that still
continues at that age (Müller et al., 1997). Changes in oscillatory activity are hence evi-
dent throughout the lifespan; this should be considered when the experimental design
includes between-​group comparisons.

12.4.2 Altered Oscillations Due to Learning

On short time scales, oscillatory activity may depend on experience in the context of
sensorimotor learning. Synaptic plasticity can lead to a strengthening or weakening of
synaptic transmissions that may affect the amplitude of oscillations at a neural popu-
lation level. Such reorganization has been observed during the course of learning new
visuomotor tracking tasks or bimanual coordination patterns.
Tan and colleagues (2014) showed that the magnitude of post-​movement beta ERS
depends on kinematic error in a reaching task with rotational perturbations. In these
experiments, single-​trial beta ERS was negatively correlated with the angular discrep-
ancy between the target movement trajectory and the actual performed trajectory. This
effect was strongest when the perturbation angle was constant over trials compared to
random. Hence, post-​movement beta ERS does not merely reflect afferent feedback
of the performed movement; rather, it represents a combination of prediction error
and uncertainty of expected sensory consequences (Tan et al., 2016). Alayrangues and
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    271

colleagues (2019) suggested that reorganization of the internal representation itself is

not reflected by the post-​movement ERS but by lower beta amplitudes during the pre-
paratory period of movements in the next trial.
Motor skill learning is also associated with stronger beta ERD (Andres et al., 1999;
Boonstra et al., 2007) and ERS (Moisello et al., 2015) in sensorimotor cortex, and more
pronounced alpha band modulations in the cerebellum (Houweling et al., 2008) during
task performance. More widespread changes in spectral power may also occur in
these frequency bands that are stronger in young compared to older adults (Rueda-​
Delgado et al., 2019). Learning bimanual patterns impacts on functional connectivity
within the sensorimotor network. In a study by Andres et al. (1999), healthy adult
participants performed a 30-​minute training session during which they learned to fuse
two overlearned unimanual finger-​tapping sequences into a new bimanual sequence.
Interhemispheric coherence between sensorimotor regions in the alpha and beta band
was increased during early stages of the training phase and decreased again after the bi-
manual sequence was learned. Interhemispheric interactions might be initially recruited
to learn a new bimanual coordination pattern but are seemingly less needed after the
pattern has been acquired. By contrast, Houweling and colleagues (2010) showed that
the time course of bimanual learning is reflected in the build-​up of corticospinal phase
synchronization. There, it appears as if the synchronization is needed to perform the
task adequately.
Changes in oscillatory activity can also be observed directly after a training session in
the amplitude of ongoing beta oscillations. Espenhahn and colleagues (2019) recorded
EEG before and after a 30-​minute training session of a unimanual visuomotor tracking
task. Absolute beta power during rest was significantly higher after training and
returned to pre-​training levels the following day. A similar effect was found by Moisello
and colleagues (2015) and was suggested to reflect a reduction in cortical excitability
after extended use. It would be of interest to conduct more longitudinal studies to see
whether learning induces long-​lasting changes to oscillatory activity or whether the
system returns to baseline levels when the newly learned skills are fully consolidated.

12.4.3 Altered Oscillations in Movement Disorders

Given the contributions of beta oscillations in facilitating and inhibiting movements, it
comes as no surprise that this rhythm may deviate in patients with movement disorders.
This is most evident in Parkinson’s disease, a neurodegenerative disorder where a loss
of dopaminergic cells in substantia nigra may be accompanied by symptoms of ri-
gidity (muscle stiffness), bradykinesia (slowness of movement), tremor, posture and
balance problems, slurred speech, and several non-​motor symptoms. The disease is
initially treated with dopaminergic medication, but in a more advanced stage patients
might be referred to DBS. Electrodes with multiple contacts are typically implanted in
either STN or GPi in both left and right hemispheres. Both targets are known for the
effect of 130-​Hz stimulation on improvement of motor function (Deuschl et al., 2006;
272    Bernadette C. M. van Wijk

Weaver et al., 2009). Besides stimulation, the electrodes can be used to record LFPs,
though recordings are typically limited to a time window of about a week after elec-
trode implantation when wires are still externalized. Such recordings have revealed
elevated levels of beta oscillations in patients off medication during rest (Figure 12.4;
e.g., Brown et al., 2001; Levy et al., 2002; Priori et al., 2004), and some studies report less-​
pronounced beta ERD during self-​paced movement (Doyle et al., 2005a).
One of the challenges with invasive recordings in patients is to determine the degree
to which observed activities are physiological or disease-​related. Acquiring the same
recordings from healthy subjects for comparison is not an option as they would need to
undergo the same surgical procedures. Still there are strong reasons to believe that ex-
cessive beta oscillations in the STN are a marker of Parkinsonism:

1. The amplitude of beta oscillations correlates with severity of bradykinesia and ri-
gidity as measured with the Unified Parkinson’s Disease Rating Scale (Neumann
et al., 2016; van Wijk et al., 2016).
2. The amplitude of beta oscillations decreases after dopaminergic medication or
DBS in parallel with clinical improvement (Kühn et al., 2009, 2008, 2006b; Ray
et al., 2008).
3. The amplitude of beta oscillations in STN and GPi is higher in patients with
Parkinson’s disease than in patients with dystonia (Piña-​Fuentes et al., 2019).
4. Stimulation at 20 Hz instead of the clinically effective 130 Hz impedes motor per-
formance (Chen et al., 2007), therefore underscoring a causal role of excessive
beta oscillations in motor impairment.

While bradykinesia and rigidity are associated with beta oscillations, tremor typ-
ically manifests at frequencies below 12 Hz. Several forms of physiological and patho-
logical tremors with central or peripheral origins can be distinguished, all characterized
by involuntary rhythmic movements in one or more body parts (Deuschl et al., 2001;
McAuley & Marsden, 2000). Essential tremor is the most common movement disorder,

PAC Off Med PAC On Med

Amplitude Freq [Hz]

0.25 Off Med 400 400 PAC

Spectral Power

0.20 On Med 350 350 0.04

0.15 300 300 0.03

0.10 250 250 0.02

0.05 200 200 0.01

0 150 150 0
10 20 30 40 50 5 10 15 20 25 30 35 5 10 15 20 25 30 35
Frequency [Hz] Phase Freq [Hz] Phase Freq [Hz]
Figure 12.4 Abnormal subthalamic nucleus oscillatory activity in Parkinson’s disease.
Left: Spectral power in the beta frequency range is elevated when the patient is withdrawn from
dopaminergic medication. Right: Phase-​amplitude coupling (PAC) between beta and high-​
frequency oscillations is another marker of motor impairment.
Example of single subject DBS-​LFP recordings taken from Van Wijk et al., 2016.
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    273

an action tremor that occurs with voluntary muscle contraction. Neural entrainment
between inferior olive, cerebellum, thalamus, and motor cortex is believed to underlie
its emergence (Raethjen and Deuschl, 2012). Activity at the tremor frequency within
this network has been found to be coherent with EMG (Hellwig et al., 2001; Schnitzler
et al., 2009). By contrast, Parkinsonian tremor presents during rest and may have its
origin in the basal ganglia (Deuschl et al., 2001). Both Parkinsonian and essential
tremor can be suppressed by 130-​Hz DBS in the ventrolateral thalamus (Benabid et al.,
1996). Stimulation at the tremor frequency could either enhance or reduce tremor
amplitude, depending on the phase at which stimulation pulses are delivered (Cagnan
et al., 2013).
Dystonia is another hyperkinetic movement disorder that can be associated with
increased power for frequencies below the beta band in GPi (Chen et al., 2006; Liu et al.,
2008; Sharott et al., 2008; Silberstein et al., 2003). This arguably reflects diminished and
more irregular neuronal firing that is considered distinctive of the disorder (Hendrix
& Vitek, 2012). Clinical symptoms include twisting movements and abnormal posture
resulting from involuntary sustained and sometimes repetitive muscle contractions
(Fahn, 1988). Also in dystonia symptoms might be suppressed via DBS but improve-
ment may not become evident before several weeks or months of continuous stimula-
tion (Vidailhet et al., 2005). Barow et al. (2014) showed that 4–​12 Hz pallidal activity is
reduced upon DBS with more immediate effects for phasic compared to tonic dystonia
subtypes.
Elevated levels of oscillatory activity seem to be a common feature of a number of
movement disorders. Effective treatments are frequently associated with a reduction of
this activity although causal relations are often difficult to establish.

12.5  A dynamic view on frequency bands

Until now, averaging of spectral power within frequency bands or across long time
windows has been common practice in the field. Recently, dynamical properties of
oscillations have received more attention. For example, beta oscillations are not present
with constant amplitude but appear in short bursts of varying amplitude and duration
(Feingold et al., 2015; Murthy and Fetz, 1996b). In Parkinson’s disease, bursts with long
duration occur more frequently in the STN of patients with larger clinical impair-
ment and also have a higher amplitude than short bursts (Tinkhauser et al., 2017a).
Dopaminergic medication significantly reduces the number of long bursts (Tinkhauser
et al., 2017b). These new insights help to further constrain computational models, like
that proposed by Sherman and colleagues (2016) for S1, which explore the synaptic
mechanisms by which beta bursts emerge.
Another example is the notion that functions may arise from the interaction be-
tween frequency bands as opposed to individual frequency bands forming parallel
communication channels. Using recordings from rat motor cortex, Igarashi et al. (2013)
274    Bernadette C. M. van Wijk

demonstrated gamma oscillations comprised of a slow and fast component that were
both coupled with an ongoing theta rhythm. Slow gamma oscillations were pronounced
when rats were holding on to a lever and were phase-​locked to peaks of the theta oscilla-
tion, whereas fast gamma oscillations emerged around the time of pulling the lever and
were phase-​locked to a trough of the theta oscillation. These findings are reminiscent of
phase precession in hippocampal cortex where firing of place cells in the gamma range is
nested in the ongoing theta rhythm. With individual gamma cycles representing a par-
ticular location in space, these progressively shift forward to earlier phases of the theta
cycle as the rat navigates towards that location (O’Keefe & Recce, 1993). The nesting of
oscillations allows for the encoding of near and far locations, i.e. information that is not
contained in the individual frequencies. On the other hand, cross-​frequency coupling
might also arise due to pathology. We have found the strength of phase-​amplitude coup-
ling between beta and HFOs in the STN to correlate with the severity of bradykinesia
and rigidity symptoms in Parkinson’s disease (Figure 12.4; van Wijk et al., 2016).
Cross-​frequency coupling could also be indicative of non-​sinusoidal waveforms as
these would appear at higher frequencies in the spectrum (van Wijk, 2017). Cole et al.
(2017) demonstrated that the waveform shape of beta oscillations could indeed explain
beta-​gamma phase-​amplitude coupling patterns observed in M1 of Parkinson’s patients
(de Hemptinne et al., 2013). It is interesting that DBS reduces the asymmetry of the beta
oscillation waveform (de Hemptinne et al., 2015) as it hints at less-​synchronous synaptic
input from the basal ganglia. A focus on the detailed time dynamics, cross-​frequency
coupling, and waveform shape of oscillations holds great promise to further unravel
their role in sensorimotor function.

12.6  Cognitive aspects of

sensorimotor function

We move to interact with the external world in a meaningful way. Our actions depend
on goals and intentions, which in turn depend on the context we are in. Cognition and
motor control are highly intertwined. Several lines of research indeed suggest that sen-
sorimotor regions contribute beyond the classical view on motor control.
First of all, (pre-​)motor cortex is already activated during the process of action selec-
tion instead of merely being informed on the final outcome that needs to be executed
(Cisek and Kalaska, 2005). Donner and colleagues (2009) demonstrated that lateralized
beta suppression and gamma increase in motor cortex could predict on a single trial
level which left/​right choice participants were going to make during a perceptual de-
tection task. Instructions to emphasize decision speed versus accuracy decrease pre-​
stimulus M1 beta levels, which might explain the upsurge of errors under speed stress
(Pastötter et al., 2012; Steinemann et al., 2018). Pre-​decision activation of the motor
system is therefore likely to speed-​up or even influence behavioral performance.
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    275

The ability to inhibit actions is seen as an important marker of cognitive control.

Pro-​active inhibition and reactive stopping of actions are often studied with go/​no-​go
and stop-​signal paradigms, respectively. Both are thought to rely on the “stopping net-
work” of inferior frontal gyrus (IFG), pre-​SMA, and STN (Aron, 2011). In IFG, trials
with a stop signal induce an increase in beta power that is larger for successful vs. un-
successful stop trials (Swann et al., 2009). In STN, task-​related beta suppression is
weaker for successful compared to unsuccessful stops (Kühn et al., 2004; Wessel et al.,
2016). In turn, successful stops are also characterized by a weaker beta suppression in
M1 compared to unsuccessful stops (Swann et al., 2009). More generally, fronto-​basal
ganglia circuits are considered to act as a brake to stop actions, resolve conflict, or pro-
cess surprising events (Aron et al., 2016).
Execution of movements is not strictly necessary for the sensorimotor system
to become active. Beta ERD can be observed in contralateral M1 and the STN when
participants are merely imagining that they are making a movement albeit with lower
magnitude compared to real movements (Kühn et al., 2006a; Pfurtscheller and Neuper,
1997; Schnitzler et al., 1997). Researchers have gratefully taken advantage of this phe-
nomenon for the development of brain computer interfaces (Wolpaw et al., 2002). Even
patients in an advanced stage of ALS have been able to learn how to control vertical
cursor movement on a computer screen by up-​or down-​regulating the amplitude of
sensorimotor EEG rhythms via motor imagery (Kübler et al., 2005). With the use of
machine learning it is possible to reduce the training time needed to successfully op-
erate such a device to just 20 minutes in healthy individuals (Blankertz et al., 2007).
Controlling a robot arm or computer cursor by imagining movement of your own limb
is appealing as it relies to a large extent on how the brain controls real movements.
Observing movements performed by others can also induce alpha/​mu and beta
suppression in human sensorimotor cortex (Babiloni et al., 2002; Cochin et al., 1998;
Hari et al., 1998; Kilner et al., 2009). The suppression is slightly larger when the action
is target-​directed (Avanzini et al., 2012; Muthukumaraswamy et al., 2004) and when the
observer is more experienced with the action him/​herself (Cannon et al., 2014). A cred-
ible hypothesis for the activation of motor regions during perception is that the observed
action needs to be internally simulated in order to understand the other person’s actions
and intentions (Jeannerod, 2001). As such, the discovery of mirror neurons in (pre-​)
motor regions (Cattaneo & Rizzolatti, 2009) means that considerable ground is shared
with the field of social neuroscience.

12.7  Conclusions

Oscillations are omnipresent in the sensorimotor system and show distinct modulations
with experimental tasks and pathology. In particular beta oscillations seem to have a
prominent role by means of their association with movement facilitation and inhib-
ition. Movement-​related beta ERD and ERS are among the most robust time-​frequency
276    Bernadette C. M. van Wijk

patterns in EEG/​MEG studies. Intriguingly, the cortex is not alone in displaying these
characteristic modulations. Very similar movement-​related beta ERD/​ERS and gamma
ERS can be observed in LFP recordings from the STN (Alegre et al., 2005; Androulidakis
et al., 2007b; Cassidy et al., 2002; Kühn et al., 2004; Litvak et al., 2012), GPi (Brücke et al.,
2008; Talakoub et al., 2016; Tsang et al., 2012), and the ventral lateral thalamus (Brücke
et al., 2013; Klostermann et al., 2007; Paradiso et al., 2004). This implies that these
modulations are generic principles of information processing that might have different
functional meaning in different regions of the sensorimotor network.
Over the years, the main focus of the field at large has been on oscillations in contra-
lateral M1. While simple flexion/​extension movements of the fingers indeed seem to
be fairly restricted to activation in the primary sensorimotor cortices, more complex
rhythmic or bimanual movement patterns recruit additional regions like ipsilateral M1,
SMA, premotor cortex, cerebellum, and also primary and secondary sensory and asso-
ciation cortices if the task involves strong visual or auditory components (Heinrichs-​
Graham & Wilson, 2015; Houweling et al., 2008; Hummel et al., 2003; Pollok et al., 2005;
Rueda-​Delgado et al., 2014). The contribution of subcortical structures is more difficult
to study in humans but should not be overlooked. Intriguingly, lesions to motor cortex
do not affect execution of a task-​specific motor sequence in rats once the sequence
has been learned, suggesting reliance on subcortical controllers with projections to
the spinal cord (Kawai et al., 2015). Simultaneous MEG and DBS-​LFP recordings have
revealed a number of spatially and spectrally distinct cortico-​subcortical networks that
appear to be disease-​unrelated. The functional relevance of these networks deserves fur-
ther exploration in future studies.
Although we have learned a great deal about the neural control of movement by
studying oscillations, several aspects remain unexplained. Important questions that are
still open are mostly of mechanistic nature. For example, how does beta ERD lead to
muscle activations? What causes beta ERD to start and initiate movement in the first
place? Why is desynchronization so widespread even for simple finger movement?
Why are movement-​related modulations so similar across various parts of the motor
system? How are movement plans translated into motor commands? How are they
encoded? Oscillations reflect the summed activity of numerous neurons, from which
it might be difficult to infer details of individual muscle control especially with non-​
invasive techniques such as EEG and MEG. Instead, they are more likely to reflect gen-
eral states of activation or deactivation. I believe there is still much more to gain from
studying oscillations through the combination of recordings techniques, the use of
advanced signal processing algorithms and the development of computational models.
Fortunately, grasping a cup of coffee is much easier than understanding how we do it.

REFERENCES
Adrian, E. D. & Matthews, B. H. C. (1934). The Berger rhythm: Potential changes from the oc-
cipital lobes in man. Brain, 57, 355–​385. https://​doi.org/​10.1093/​brain/​57.4.355
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    277

Alayrangues, J., Torrecillos, F., Jahani, A., & Malfait, N. (2019). Error-​related modulations of
the sensorimotor post-​movement and foreperiod beta-​band activities arise from distinct
neural substrates and do not reflect efferent signal processing. NeuroImage 184, 10–​24.
https://​doi.org/​10.1016/​j.neu​roim​age.2018.09.013
Alegre, M., Alonso-​Frech, F., Rodríguez-​Oroz, M. C., Guridi, J., Zamarbide, I., Valencia,
M., . . . Artieda, J. (2005). Movement-​related changes in oscillatory activity in the human
subthalamic nucleus: Ipsilateral vs. contralateral movements. European Journal of
Neuroscience, 22, 2315–​2324. https://​doi.org/​10.1111/​j.1460-​9568.2005.04409.x
Alegre, M., Labarga, A., Gurtubay, I., Iriarte, J., Malanda, A., & Artieda, J. (2003). Movement-​
related changes in cortical oscillatory activity in ballistic, sustained and negative movements.
Experimental Brain Research, 148, 17–​25. https://​doi.org/​10.1007/​s00​221-​002-​1255-​x
Andres, F. G., Mima, T., Schulman, A. E., Dichgans, J., Hallett, M., & Gerloff, C. (1999).
Functional coupling of human cortical sensorimotor areas during bimanual skill acquisi-
tion. Brain, 122, 855–​870. https://​doi.org/​10.1093/​brain/​122.5.855
Androulidakis, A. G., Doyle, L. M. F., Yarrow, K., Litvak, V., Gilbertson, T. P., & Brown, P.
(2007a). Anticipatory changes in beta synchrony in the human corticospinal system and
associated improvements in task performance. European Journal of Neuroscience, 25, 3758–​
3765. https://​doi.org/​10.1111/​j.1460-​9568.2007.05620.x
Androulidakis, A. G., Kühn, A. A., Chen, C. C., Blomstedt, P., Kempf, F., Kupsch, A., . . . Brown,
P. (2007b). Dopaminergic therapy promotes lateralized motor activity in the subthalamic
area in Parkinson’s disease. Brain, 130, 457–​68. https://​doi.org/​10.1093/​brain/​awl​358
Aron, A. R. (2011). From reactive to proactive and selective control: Developing a richer model
for stopping inappropriate responses. Biological Psychiatry, 69, e55–​e68. https://​doi.org/​
10.1016/​j.biops​ych.2010.07.024
Aron, A. R., Herz, D. M., Brown, P., Forstmann, B. U., & Zaghloul, K. (2016). Frontosubthalamic
circuits for control of action and cognition. Journal of Neuroscience, 36, 11489–​11495. https://​
doi.org/​10.1523/​JNEURO​SCI.2348-​16.2016
Asanuma, H., Zarzecki, P., Jankowska, E., Hongo, T., & Marcus, S. (1979). Projection of indi-
vidual pyramidal tract neurons to lumbar motor nuclei of the monkey. Experimental Brain
Research, 34, 73–​89. https://​doi.org/​103​742
Ashe, J. & Georgopoulos, A. P. (1994). Movement parameters and neural activity in motor
cortex and area 5. Cerebral Cortex, 4, 590–​600. https://​doi.org/​10.1093/​cer​cor/​4.6.590
Avanzini, P., Fabbri-​Destro, M., Dalla Volta, R., Daprati, E., Rizzolatti, G., & Cantalupo,
G. (2012). The dynamics of sensorimotor cortical oscillations during the observation of
hand movements: An EEG study. PLoS One, 7, e37534. https://​doi.org/​10.1371/​jour​nal.
pone.0037​534
Babiloni, C., Babiloni, F., Carducci, F., Cincotti, F., Cocozza, G., Del Percio, C., Moretti, D. V.,
& Rossini, P. M. (2002). Human cortical electroencephalography (EEG) rhythms during the
observation of simple aimless movements: A high-​resolution EEG study. NeuroImage, 17,
559–​572. https://​doi.org/​10.1006/​nimg.2002.1192
Baker, M. R. & Baker, S. N. (2003). The effect of diazepam on motor cortical oscillations and
corticomuscular coherence studied in man. Journal of Physiology, 546, 931–​942. https://​doi.
org/​10.1113/​jphys​iol.2002.029​553
Baker, S. N., Olivier, E., & Lemon, R. N. (1997). Coherent oscillations in monkey motor cortex
and hand muscle EMG show task-​dependent modulation. Journal of Physiology, 501, 225–​
241. https://​doi.org/​10.1111/​j.1469-​7793.1997.225bo.x
278    Bernadette C. M. van Wijk

Baker, S. N., Pinches, E. M., & Lemon, R. N. (2003). Synchronization in monkey motor cortex
during a precision grip task. II. Effect of oscillatory activity on corticospinal output. Journal
of Neurophysiology, 89, 1941–​1953. https://​doi.org/​10.1152/​jn.00832.2002
Baker, S. N., Spinks, R., Jackson, A., & Lemon, R. N. (2001). Synchronization in monkey motor
cortex during a precision grip task. I. Task-​dependent modulation in single-​unit synchrony.
Journal of Neurophysiology, 85, 869–​885. https://​doi.org/​10.1152/​jn.00832.2002
Barow, E., Neumann, W. J., Brücke, C., Huebl, J., Horn, A., Brown, P., . . . Kühn, A.A., 2014.
Deep brain stimulation suppresses pallidal low frequency activity in patients with phasic
dystonic movements. Brain, 137, 3012–​3024. https://​doi.org/​10.1093/​brain/​awu​258
Benabid, A. L., Pollak, P., Gao, D., Hoffmann, D., Limousin, P., Gay, E., Payen, I., & Benazzouz,
A. (1996). Chronic electrical stimulation of the ventralis intermedius nucleus of the thal-
amus as a treatment of movement disorders. Journal of Neurosurgery, 84, 203–​214. https://​
doi.org/​10.3171/​jns.1996.84.2.0203
Berger, H. (1929). Über das Elektroenkephalogramm des Menschen. Archiv für Psychiatrie und
Nervenkrankheiten, 87, 527–​570.
Bhatt, M. B., Bowen, S., Rossiter, H. E., Dupont-​Hadwen, J., Moran, R.J., Friston, K.J., Ward,
N.S., 2016. Computational modelling of movement-​ related beta-​
oscillatory dynamics
in human motor cortex. Neuroimage 133, 224–​232. https://​doi.org/​10.1016/​j.neu​roim​
age.2016.02.078
Blankertz, B., Dornhege, G., Krauledat, M., Müller, K.-​R., & Curio, G. (2007). The non-​invasive
Berlin Brain–​Computer Interface: Fast acquisition of effective performance in untrained
subjects. NeuroImage, 37, 539–​550. https://​doi.org/​10.1016/​j.neu​roim​age.2007.01.051
Boonstra, T. W., Daffertshofer, A., Breakspear, M., & Beek, P. J. (2007). Multivariate time–​
frequency analysis of electromagnetic brain activity during bimanual motor learning.
NeuroImage, 36, 370–​377. https://​doi.org/​10.1016/​j.neu​roim​age.2007.03.012
Boonstra, T. W., Danna-​Dos-​Santos, A., Xie, H.-​B., Roerdink, M., Stins, J. F., & Breakspear,
M. (2016). Muscle networks: Connectivity analysis of EMG activity during postural control.
Scientific Reports, 5, 17830. https://​doi.org/​10.1038/​srep17​830
Boonstra, T. W., van Wijk, B. C. M., Praamstra, P., & Daffertshofer, A. (2009). Corticomuscular
and bilateral EMG coherence reflect distinct aspects of neural synchronization. Neuroscience
Letters, 463, 17–​21. https://​doi.org/​10.1016/​j.neu​let.2009.07.043
Brown, P., Oliviero, A., Mazzone, P., Insola, A., Tonali, P., & Di Lazzaro, V. (2001). Dopamine
dependency of oscillations between subthalamic nucleus and pallidum in Parkinson’s
disease. Journal of Neuroscience, 21, 1033–​1038. https://​doi.org/​10.1523/​JNEURO​
SCI.21-​03-​01033.2001
Brown, P., Salenius, S., Rothwell, J. C., & Hari, R. (1998). Cortical correlate of the Piper
rhythm in humans. Journal of Neurophysiology, 80, 2911–​2917. https://​doi.org/​10.1152/​
jn.1998.80.6.2911
Brücke, C., Bock, A., Huebl, J., Krauss, J. K., Schönecker, T., Schneider, G. H., Brown, P., &
Kühn, A. A. (2013). Thalamic gamma oscillations correlate with reaction time in a go/​no-​go
task in patients with essential tremor. NeuroImage, 75, 36–​45. https://​doi.org/​10.1016/​j.neu​
roim​age.2013.02.038
Brücke, C., Kempf, F., Kupsch, A., Schneider, G. H., Krauss, J.K., Aziz, T., . . . Kühn, A. A.
(2008). Movement-​related synchronization of gamma activity is lateralized in patients
with dystonia. European Journal of Neuroscience, 27, 2322–​2329. https://​doi.org/​10.1111/​
j.1460-​9568.2008.06203.x
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    279

Cagnan, H., Brittain, J.-​S., Little, S., Foltynie, T., Limousin, P., Zrinzo, L., . . . Brown, P. (2013).
Phase dependent modulation of tremor amplitude in essential tremor through thalamic
stimulation. Brain, 136, 3062–​3075. https://​doi.org/​10.1093/​brain/​awt​239
Cannon, E. N., Yoo, K. H., Vanderwert, R. E., Ferrari, P. F., Woodward, A.L., & Fox, N. A. (2014).
Action experience, more than observation, influences mu rhythm desynchronization. PLoS
One, 9, e92002. https://​doi.org/​10.1371/​jour​nal.pone.0092​002
Cardoso de Oliveira, S., Gribova, A., Donchin, O., Bergman, H., & Vaadia, E. (2001). Neural
interactions between motor cortical hemispheres during bimanual and unimanual arm
movements. European Journal of Neuroscience, 14, 1881–​1896. https://​doi.org/​10.1046/​
j.0953-​816X.2001.01801.x
Cassidy, M., Mazzone, P., Oliviero, A., Insola, A., Tonali, P., Di Lazzaro, V., & Brown, P. (2002).
Movement-​related changes in synchronization in the human basal ganglia. Brain, 125, 1235–​
1246. https://​doi.org/​10.1093/​brain/​awf​135
Cassim, F., Monaca, C., Szurhaj, W., Bourriez, J.-​L., Defebvre, L., Derambure, P., & Guieu,
J.-​D. (2001). Does post-​movement beta synchronization reflect an idling motor cortex?
Neuroreport, 12, 3859–​3863. https://​doi.org/​10.1097/​00001​756-​200112​040-​00051
Cassim, F., Szurhaj, W., Sediri, H., Devos, D., Bourriez, J.-​L., Poirot, I., . . . Guieu, J.-​D.
(2000). Brief and sustained movements: Differences in event-​related (de)synchronization
(ERD/​ERS) patterns. Clinical Neurophysiology, 111, 2032–​2039. https://​doi.org/​10.1016/​
S1388-​2457(0  0)00455-​7
Cattaneo, L. & Rizzolatti, G. (2009). The mirror neuron system. Archives of Neurology, 66, 557–​
560. https://​doi.org/​10.1001/​arc​hneu​rol.2009.41
Chakarov, V., Naranjo, J.R., Schulte-​Monting, J., Omlor, W., Huethe, F., & Kristeva, R. (2009).
Beta-​range EEG-​EMG coherence with isometric compensation for increasing modulated low-​
level forces. Journal of Neurophysiology, 102, 1115–​1120. https://​doi.org/​10.1152/​jn.91095.2008
Chatrian, G. E., Petersen, M. C., & Lazarte, J. A. (1959). The blocking of the Rolandic wicket
rhythm and some central changes related to movement. Electroencephalography and Clinical
Neurophysiology, 11, 497–​510. https://​doi.org/​10.1016/​0013-​4694(59)90048-​3
Chen, C.C., Kühn, A.A., Hoffmann, K.T., Kupsch, A., Schneider, G.H., Trottenberg,
T., . . . Brown, P. (2006). Oscillatory pallidal local field potential activity correlates with in-
voluntary EMG in dystonia. Neurology, 66, 418–​420. https://​doi.org/​10.1212/​01.wnl.000​0196​
470.00165.7d
Chen, C. C., Litvak, V., Gilbertson, T., Kühn, A., Lu, C., Lee, S., . . . Hariz, M. (2007). Excessive
synchronization of basal ganglia neurons at 20 Hz slows movement in Parkinson’s disease.
Experimental Neurology, 205, 214–​221. https://​doi.org/​10.1016/​j.expneu​rol.2007.01.027
Chen, R., Yaseen, Z., Cohen, L. G., & Hallett, M. (1998). Time course of corticospinal excit-
ability in reaction time and self-​paced movements. Annals of Neurology, 44, 317–​325. https://​
doi.org/​10.1002/​ana.410440​306
Cheyne, D., Bells, S., Ferrari, P., Gaetz, W., & Bostan, A. C. (2008). Self-​paced movements in-
duce high-​frequency gamma oscillations in primary motor cortex. NeuroImage, 42, 332–​342.
https://​doi.org/​10.1016/​j.neu​roim​age.2008.04.178
Cheyne, D., Gaetz, W., Garnero, L., Lachaux, J.-​P., Ducorps, A., Schwartz, D., & Varela, F. J.
(2003). Neuromagnetic imaging of cortical oscillations accompanying tactile stimulation.
Cognitive Brain Research, 17, 599–​611. https://​doi.org/​10.1016/​S0926-​6410(03)00173-​3
Cisek, P. & Kalaska, J. F. (2005). Neural correlates of reaching decisions in dorsal premotor
cortex: specification of multiple direction choices and final selection of action. Neuron, 45,
801–​814. https://​doi.org/​10.1016/​j.neu​ron.2005.01.027
280    Bernadette C. M. van Wijk

Classen, J., Gerloff, C., Honda, M., & Hallett, M. (1998) Integrative visuomotor behavior
is associated with interregionally coherent oscillations in the human brain. Journal of
Neurophysiology, 79, 1567–​1573. https://​doi.org/​10.1152/​jn.1998.79.3.1567
Cochin, S., Barthelemy, C., Lejeune, B., Roux, S., & Martineau, J. (1998). Perception of motion
and qEEG activity in human adults. Electroencephalography and Clinical Neurophysiology,
107, 287–​295. https://​doi.org/​10.1016/​S0013-​4694(98)00071-​6
Cole, S. R., van der Meij, R., Peterson, E. J., de Hemptinne, C., Starr, P. A., & Voytek, B. (2017).
Nonsinusoidal beta oscillations reflect cortical pathophysiology in Parkinson’s disease.
Journal of Neuroscience, 37, 2208–​2216. https://​doi.org/​10.1523/​JNEURO​SCI.2208-​16.2017
Conway, B. A., Halliday, D. M., Farmer, S. F., Shahani, U., Maas, P., Weir, A. I., & Rosenberg, J.
R. (1995). Synchronization between motor cortex and spinal motoneuronal pool during the
performance of a maintained motor task in man. Journal of Physiology, 489, 917–​924. https://​
doi.org/​10.1113/​jphys​iol.1995.sp021​104
Crone, N. E., Miglioretti, D. L., Gordon, B., & Lesser, R. P. (1998a). Functional mapping of
human sensorimotor cortex with electrocorticographic spectral analysis. II. Event-​related
synchronization in the gamma band. Brain, 121, 2301–​2315. https://​doi.org/​10.1093/​brain/​
121.12.2301
Crone, N. E., Miglioretti, D. L., Gordon, B., Sieracki, J. M., Wilson, M. T., Uematsu, S., & Lesser,
R. P. (1998b). Functional mapping of human sensorimotor cortex with electrocorticographic
spectral analysis. I. Alpha and beta event-​related desynchronization. Brain, 121, 2271–​2299.
https://​doi.org/​10.1093/​brain/​121.12.2271
de Hemptinne, C., Ryapolova-​Webb, E. S., Air, E. L., Garcia, P. A., Miller, K. J., Ojemann, J.
G.,. . . Starr, P. A. (2013). Exaggerated phase-​amplitude coupling in the primary motor cortex
in Parkinson disease. Proceedings of the National Academy of Sciences of the United States of
America, 110, 4780–​4785. https://​doi.org/​10.1073/​pnas.121​4546​110
de Hemptinne, C., Swann, N. C., Ostrem, J. L., Ryapolova-​Webb, E. S., San Luciano, M.,
Galifianakis, N. B., & Starr, P. A. (2015). Therapeutic deep brain stimulation reduces cortical
phase-​amplitude coupling in Parkinson’s disease. Nature Neuroscience, 18, 779–​786. https://​
doi.org/​10.1038/​nn.3997
Denker, M., Roux, S., Timme, M., Riehle, A., & Grün, S. (2007). Phase synchronization between
LFP and spiking activity in motor cortex during movement preparation. Neurocomputing,
70, 2096–​2101. https://​doi.org/​10.1016/​j.neu​com.2006.10.088
Deuschl, G., Raethjen, J., Lindemann, M., & Krack, P. (2001). The pathophysiology of tremor.
Muscle Nerve, 24, 716–​735. https://​doi.org/​10.1002/​mus.1063
Deuschl, G., Schade-​Brittinger, C., Krack, P., Volkmann, J., Schäfer, H., Bötzel, K., . . . Voges, J.
(2006). A randomized trial of deep-​brain stimulation for Parkinson’s disease. New England
Journal of Medicine, 355, 896–​908. https://​doi.org/​10.1056/​nejmo​a060​281
Donner, T. H., Siegel, M., Fries, P., & Engel, A. K. (2009). Buildup of choice-​predictive activity
in human motor cortex during perceptual decision making. Current Biology, 19, 1581–​1585.
https://​doi.org/​10.1016/​j.cub.2009.07.066
Doyle, L. M. F., Kühn, A. A., Hariz, M., Kupsch, A., Schneider, G. H., & Brown, P. (2005a).
Levodopa-​ induced modulation of subthalamic beta oscillations during self-​ paced
movements in patients with Parkinson’s disease. European Journal of Neuroscience,. 21, 1403–​
1412. https://​doi.org/​10.1111/​j.1460-​9568.2005.03969.x
Doyle, L. M. F., Yarrow, K., & Brown, P. (2005b). Lateralization of event-​related beta desyn-
chronization in the EEG during pre-​cued reaction time tasks. Clinical Neurophysiology, 116,
1879–​1888. https://​doi.org/​10.1016/​j.cli​nph.2005.03.017
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    281

Erbil, N. & Ungan, P. (2007). Changes in the alpha and beta amplitudes of the central EEG
during the onset, continuation, and offset of long-​duration repetitive hand movements.
Brain Research, 1169, 44–​56. https://​doi.org/​10.1016/​j.brain​res.2007.07.014
Espenhahn, S., de Berker, A. O., van Wijk, B. C. M., Rossiter, H. E., & Ward, N. S. (2017).
Movement-​related beta oscillations show high intra-​individual reliability. NeuroImage, 147,
175–​185. https://​doi.org/​10.1016/​j.neu​roim​age.2016.12.025
Espenhahn, S., van Wijk, B. C. M., Rossiter, H. E., de Berker, A. O., Redman, N. D., Rondina,
J., Diedrichsen, J., & Ward, N. S. (2019). Cortical beta oscillations are associated with motor
performance following visuomotor learning. NeuroImage, 195, 340–​353. https://​doi.org/​
10.1016/​j.neu​roim​age.2019.03.079
Fahn, S. (1988). Concept and classification of dystonia. Advances in Neurology, 50, 1–​8.
Feingold, J., Gibson, D. J., DePasquale, B., & Graybiel, A. M. (2015). Bursts of beta oscilla-
tion differentiate postperformance activity in the striatum and motor cortex of monkeys
performing movement tasks. Proceedings of the National Academy of Sciences of the United
States of America, 112, 13687–​92. https://​doi.org/​10.1073/​pnas.151​7629​112
Foffani, G., Priori, A., Egidi, M., Rampini, P., Tamma, F., Caputo, E., . . . Barbieri, S. (2003). 300-​
Hz subthalamic oscillations in Parkinson’s disease. Brain, 126, 2153–​2163. https://​doi.org/​
10.1093/​brain/​awg​229
Freund, H. J. (1983). Motor unit and muscle activity in voluntary motor control. Physiological
Reviews, 63, 387–​436. https://​doi.org/​10.1152/​phys​rev.1983.63.2.387
Fries, P. (2005). A mechanism for cognitive dynamics: Neuronal communication through
neuronal coherence. Trends in Cognitive Science, 9, 474–​480. https://​doi.org/​10.1016/​
j.tics.2005.08.011
Fu, Q. G., Flament, D., Coltz, J. D., & Ebner, T. J. (1995). Temporal encoding of movement
kinematics in the discharge of primate primary motor and premotor neurons. Journal of
Neurophysiology, 73, 836–​854. https://​doi.org/​10.1152/​jn.1995.73.2.836
Gaetz, W., MacDonald, M., Cheyne, D., & Snead, O. C. (2010). Neuromagnetic imaging of
movement-​related cortical oscillations in children and adults: Age predicts post-​movement
beta rebound. NeuroImage, 51, 792–​807. https://​doi.org/​10.1016/​j.neu​roim​age.2010.01.077
Gastaut, H. (1952). Etude électrocorticographique de la réactivité des rythmes rolandiques.
Revue neurologique, 87, 176–​82.
Georgopoulos, A., Schwartz, A., & Kettner, R. (1986). Neuronal population coding of
movement direction. Science, 233, 1416–​1419. https://​doi.org/​10.1126/​scie​nce.3749​885
Gerloff, C., Richard, J., Hadley, J., Schulman, A.E., Honda, M., Hallett, M., 1998. Functional
coupling and regional activation of human cortical motor areas during simple, internally
paced and externally paced finger movements. Brain 121, 1513–​1531. https://​doi.org/​10.1093/​
brain/​121.8.1513
Gilbertson, T., Lalo, E., Doyle, L., Lazzaro, V. Di, Cioni, B., & Brown, P. (2005). Existing motor
state is favored at the expense of new movement during 13–​35 Hz oscillatory synchrony in
the human corticospinal system. Journal of Neuroscience, 25, 7771–​7779. https://​doi.org/​
10.1523/​JNEURO​SCI.1762-​05.2005
Grammont, F. & Riehle, A. (2003). Spike synchronization and firing rate in a population of
motor cortical neurons in relation to movement direction and reaction time. Biological
Cybernetics, 88, 360–​373. https://​doi.org/​10.1007/​s00​422-​002-​0385-​3
Gross, J., Pollok, B., Dirks, M., Timmermann, L., Butz, M., & Schnitzler, A. (2005). Task-​
dependent oscillations during unimanual and bimanual movements in the human primary
282    Bernadette C. M. van Wijk

motor cortex and SMA studied with magnetoencephalography. NeuroImage, 26, 91–​98.
https://​doi.org/​10.1016/​j.neu​roim​age.2005.01.025
Gross, J., Tass, P. A., Salenius, S., Hari, R., Freund, H. J., & Schnitzler, A. (2000). Cortico-​
muscular synchronization during isometric muscle contraction in humans as revealed
by magnetoencephalography. Journal of Physiology, 527, 623–​631. https://​doi.org/​10.1111/​
j.1469-​7793.2000.00623.x
Hall, S. D., Barnes, G. R., Furlong, P. L., Seri, S., & Hillebrand, A. (2010). Neuronal network
pharmacodynamics of GABAergic modulation in the human cortex determined using
pharmaco-​magnetoencephalography. Human Brain Mapping, 31, 581–​594. https://​doi.org/​
10.1002/​hbm.20889
Halliday, D. M., Conway, B. A., Farmer, S. F., and Rosenberg, J. R. (1998). Using electroen-
cephalography to study functional coupling between cortical activity and electromyograms
during voluntary contractions in humans. Neuroscience Letters, 241, 5–​8. https://​doi.org/​
10.1016/​S0304-​3940(97)00964-​6
Hari, R., Forss, N., Avikainen, S., Kirveskari, E., Salenius, S., & Rizzolatti, G. (1998). Activation
of human primary motor cortex during action observation: A neuromagnetic study.
Proceedings of the National Academy of Sciences of the United States of America, 95, 15061–​
15065. https://​doi.org/​10.1073/​pnas.95.25.15061
Heinrichs-​Graham, E., McDermott, T. J., Mills, M. S., Wiesman, A. I., Wang, Y.-​P., Stephen, J.
M., Calhoun, V. D., & Wilson, T. W. (2018). The lifespan trajectory of neural oscillatory ac-
tivity in the motor system. Developmental Cognitive Neuroscience, 30, 159–​168. https://​doi.
org/​10.1016/​j.dcn.2018.02.013
Heinrichs-​Graham, E. & Wilson, T. W. (2015). Coding complexity in the human motor circuit.
Human Brain Mapping, 36, 5155–​5167. https://​doi.org/​10.1002/​hbm.23000
Hellwig, B., Häußler, S., Schelter, B., Lauk, M., Guschlbauer, B., Timmer, J., & Lücking, C. H.
(2001). Tremor-​correlated cortical activity in essential tremor. The Lancet, 357, 519–​523.
https://​doi.org/​10.1016/​S0140-​6736(0  0)04044-​7
Hendrix, C. M. & Vitek, J. L. (2012). Toward a network model of dystonia. Annals
of the New York Academy of Sciences, 1265, 46–​55. https://​doi.org/​10.1111/​
j.1749-​6632.2012.06692.x
Hillebrand, A., Barnes, G. R., Bosboom, J. L., Berendse, H. W., & Stam, C. J. (2012). Frequency-​
dependent functional connectivity within resting-​state networks: An atlas-​based MEG
beamformer solution. NeuroImage, 59, 3909–​3921. https://​doi.org/​10.1016/​j.neu​roim​
age.2011.11.005
Hirschmann, J., Butz, M., Hartmann, C. J., Hoogenboom, N., Özkurt, T. E., Vesper, J., Wojtecki,
L., & Schnitzler, A. (2016). Parkinsonian rest tremor is associated with modulations of
subthalamic high-​frequency oscillations. Movement Disorders, 31, 1551–​1559. https://​doi.org/​
10.1002/​mds.26663
Hirschmann, J., Özkurt, T. E., Butz, M., Homburger, M., Elben, S., Hartmann, C.
J., . . . Schnitzler, A. (2011). Distinct oscillatory STN-​cortical loops revealed by simultaneous
MEG and local field potential recordings in patients with Parkinson’s disease. NeuroImage,
55, 1159–​1168. https://​doi.org/​10.1016/​j.neu​roim​age.2010.11.063
Hirschmann, J., Özkurt, T.E., Butz, M., Homburger, M., Elben, S., Hartmann, C.J., . . . Schnitzler,
A. (2013). Differential modulation of STN-​cortical and cortico-​muscular coherence by
movement and levodopa in Parkinson’s disease. NeuroImage, 68, 203–​213. https://​doi.org/​
10.1016/​j.neu​roim​age.2012.11.036
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    283

Houweling, S., Daffertshofer, A., van Dijk, B. W., & Beek, P. J. (2008). Neural changes induced
by learning a challenging perceptual-​motor task. NeuroImage, 41, 1395–​1407. https://​doi.org/​
10.1016/​j.neu​roim​age.2008.03.023
Houweling, S., van Dijk, B. W., Beek, P. J., & Daffertshofer, A. (2010). Cortico-​spinal syn-
chronization reflects changes in performance when learning a complex bimanual task.
NeuroImage, 49, 3269–​3275. https://​doi.org/​10.1016/​j.neu​roim​age.2009.11.017
Hummel, F., Kirsammer, R., & Gerloff, C. (2003). Ipsilateral cortical activation during finger
sequences of increasing complexity: representation of movement difficulty or memory
load? Clinical Neurophysiology, 114, 605–​613. https://​doi.org/​10.1016/​S1388-​2457(02)00417-​0
Huo, X., Wang, Y., Kotecha, R., Kirtman, E.G., Fujiwara, H., Hemasilpin, N., . . . Xiang, J.
(2011). High gamma oscillations of sensorimotor cortex during unilateral movement in the
developing brain: A MEG study. Brain Topography, 23, 375–​384. https://​doi.org/​10.1007/​s10​
548-​010-​0151-​0
Igarashi, J., Isomura, Y., Arai, K., Harukuni, R., & Fukai, T. (2013). A θ-​γ oscillation code for
neuronal coordination during motor behavior. Journal of Neuroscience, 33, 18515–​18530.
https://​doi.org/​10.1523/​JNEURO​SCI.2126-​13.2013
Jasper, H. & Penfield, W. (1949). Electrocorticograms in man: Effect of voluntary
movement upon the electrical activity of the precentral gyrus. Archiv für Psychiatrie und
Nervenkrankheiten, 183, 163–​174. https://​doi.org/​10.1007/​BF0​1062​488
Jasper, H. H. & Andrews, H. L. (1938). Electro-​encephalography. III. Normal differentiation of
occipital and precentral regions in man. Archiv für Psychiatrie und Nervenkrankheiten, 39,
96–​115.
Jeannerod, M. (2001). Neural simulation of action: A unifying mechanism for motor cogni-
tion. NeuroImage, S103–​S109. https://​doi.org/​10.1006/​nimg.2001.0832
Jensen, O., Goel, P., Kopell, N., Pohja, M., Hari, R., & Ermentrout, B. (2005). On the human
sensorimotor-​cortex beta rhythm: Sources and modeling. NeuroImage, 26, 347–​355. https://​
doi.org/​10.1016/​j.neu​roim​age.2005.02.008
Jha, A., Litvak, V., Taulu, S., Thevathasan, W., Hyam, J.A., Foltynie, T., . . . Brown, P. (2017).
Functional connectivity of the pedunculopontine nucleus and surrounding region in
Parkinson’s disease. Cerebral Cortex, 27, 54–​67. https://​doi.org/​10.1093/​cer​cor/​bhw​340
Johnson, A. N., Wheaton, L. A., & Shinohara, M. (2011). Attenuation of corticomuscular co-
herence with additional motor or non-​motor task. Clinical Neurophysiology, 122, 356–​363.
https://​doi.org/​10.1016/​j.cli​nph.2010.06.021
Kawai, R., Markman, T., Poddar, R., Ko, R., Fantana, A. L., Dhawale, A. K., Kampff, A.R., &
Ölveczky, B. P. (2015). Motor cortex is required for learning but not for executing a motor
skill. Neuron, 86, 800–​812. https://​doi.org/​10.1016/​j.neu​ron.2015.03.024
Keller, A. (1993). Intrinsic synaptic organization of the motor cortex. Cerebral Cortex, 3, 430–​
441. https://​doi.org/​10.1093/​cer​cor/​3.5.430
Kilner, J. M., Baker, S. N., Salenius, S., Hari, R., & Lemon, R. N. (2000). Human cortical muscle
coherence is directly related to specific motor parameters. Journal of Neuroscience, 20, 8838–​
8845. https://​doi.org/​10.1523/​JNEURO​SCI.20-​23-​08838.2000
Kilner, J. M., Marchant, J. L., & Frith, C. D. (2009). Relationship between activity in human pri-
mary motor cortex during action observation and the mirror neuron system. PLoS One, 4,
e4925. https://​doi.org/​10.1371/​jour​nal.pone.0004​925
Klostermann, F., Nikulin, V. V., Kühn, A. A., Marzinzik, F., Wahl, M., Pogosyan, A., . . . Curio,
G. (2007). Task-​related differential dynamics of EEG alpha-​and beta-​band synchronization
284    Bernadette C. M. van Wijk

in cortico-​basal motor structures. European Journal of Neuroscience, 25, 1604–​1615. https://​

doi.org/​10.1111/​j.1460-​9568.2007.05417.x
Kristeva-​Feige, R., Fritsch, C., Timmer, J., & Lücking, C.-​H. (2002). Effects of attention and
precision of exerted force on beta range EEG-​EMG synchronization during a maintained
motor contraction task. Clinical Neurophysiology, 113, 124–​31. https://​doi.org/​10.1016/​
S1388-​2457(01)00722-​2
Kristeva, R., Patino, L., & Omlor, W. (2007). Beta-​range cortical motor spectral power and
corticomuscular coherence as a mechanism for effective corticospinal interaction during
steady-​ state motor output. NeuroImage, 36, 785–​792. https://​doi.org/​10.1016/​j.neu​roim​
age.2007.03.025
Kübler, A., Nijboer, F., Mellinger, J., Vaughan, T. M., Pawelzik, H., Schalk, G., . . . Wolpaw, J. R.
(2005). Patients with ALS can use sensorimotor rhythms to operate a brain-​computer inter-
face. Neurology, 64, 1775–​7. https://​doi.org/​10.1212/​01.WNL.000​0158​616.43002.6D
Kühn, A. A., Doyle, L., Pogosyan, A., Yarrow, K., Kupsch, A., Schneider, G.-​H. H., . . . Brown,
P. (2006a). Modulation of beta oscillations in the subthalamic area during motor imagery in
Parkinson’s disease. Brain, 129, 695–​706. https://​doi.org/​10.1093/​brain/​awh​7 15
Kühn, A. A., Kempf, F., Brucke, C., Gaynor Doyle, L., Martinez-​ Torres, I., Pogosyan,
A., . . . Brown, P. (2008). High-​frequency stimulation of the subthalamic nucleus suppresses
oscillatory activity in patients with Parkinson’s disease in parallel with improvement
in motor performance. Journal of Neuroscience, 28, 6165–​6173. https://​doi.org/​10.1523/​
JNEURO​SCI.0282-​08.2008
Kühn, A. A., Kupsch, A., Schneider, G.-​H., & Brown, P. (2006b). Reduction in subthalamic 8-​35
Hz oscillatory activity correlates with clinical improvement in Parkinson’s disease. European
Journal of Neuroscience, 23, 1956–​60. https://​doi.org/​10.1111/​j.1460-​9568.2006.04717.x
Kühn, A. A., Tsui, A., Aziz, T., Ray, N., Brücke, C., Kupsch, A., Schneider, G.-​H., & Brown, P.
(2009). Pathological synchronisation in the subthalamic nucleus of patients with Parkinson’s
disease relates to both bradykinesia and rigidity. Experimental Neurology, 215, 380–​7. https://​
doi.org/​10.1016/​j.expneu​rol.2008.11.008
Kühn, A. A., Williams, D., Kupsch, A., Limousin, P., Hariz, M., Schneider, G. H., Yarrow, K.,
& Brown, P. (2004). Event-​related beta desynchronization in human subthalamic nucleus
correlates with motor performance. Brain, 127, 735–​746. https://​doi.org/​10.1093/​brain/​
awh​106
Lacey, M. G., Gooding-​Williams, G., Prokic, E. J., Yamawaki, N., Hall, S. D., Stanford, I. M.,
& Woodhall, G. L. (2014). Spike firing and IPSPs in layer V pyramidal neurons during beta
oscillations in rat primary motor cortex (M1) in vitro. PLoS One, 9, e85109. https://​doi.org/​
10.1371/​jour​nal.pone.0085​109
Leuthardt, E. C., Schalk, G., Wolpaw, J. R., Ojemann, J. G., & Moran, D. W. (2004). A brain–​
computer interface using electrocorticographic signals in humans. Journal of Neural
Engineering, 1, 63–​7 1. https://​doi.org/​10.1088/​1741-​2560/​1/​2/​001
Levy, R., Ashby, P., Hutchison, W. D., Lang, A. E., Lozano, A. M., & Dostrovsky, J. O. (2002).
Dependence of subthalamic nucleus oscillations on movement and dopamine in Parkinson’s
disease. Brain, 125, 1196–​1209. https://​doi.org/​10.1093/​brain/​awf​128
Litvak, V., Eusebio, A., Jha, A., Oostenveld, R., Barnes, G., Foltynie, T., . . . Brown, P. (2012).
Movement-​related changes in local and long-​range synchronization in Parkinson’s disease
revealed by simultaneous magnetoencephalography and intracranial recordings. Journal of
Neuroscience, 32, 10541–​10553. https://​doi.org/​10.1523/​JNEURO​SCI.0767-​12.2012
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    285

Litvak, V., Jha, A., Eusebio, A., Oostenveld, R., Foltynie, T., Limousin, P., . . . Brown, P. (2011).
Resting oscillatory cortico-​subthalamic connectivity in patients with Parkinson’s disease.
Brain, 134, 359–​374. https://​doi.org/​10.1093/​brain/​awq​332
Liu, X., Wang, S., Yianni, J., Nandi, D., Bain, P. G., Gregory, R., Stein, J. F., & Aziz, T. Z. (2008).
The sensory and motor representation of synchronized oscillations in the globus pallidus in
patients with primary dystonia. Brain, 131, 1562–​1573. https://​doi.org/​10.1093/​brain/​awn​083
López-​Azcárate, J., Tainta, M., Rodríguez-​Oroz, M. C., Valencia, M., González, R., Guridi,
J., . . . Alegre, M. (2010). Coupling between beta and high-​frequency activity in the human
subthalamic nucleus may be a pathophysiological mechanism in Parkinson’s disease. Journal
of Neuroscience, 30, 6667–​6677. https://​doi.org/​10.1523/​JNEURO​SCI.5459-​09.2010
Manganotti, P., Gerloff, C., Toro, C., Katsuta, H., Sadato, N., Zhuang, P., Leocani, L., & Hallett,
M. (1998). Task-​related coherence and task-​related spectral power changes during sequen-
tial finger movements. Electroencephalography and Clinical Neurophysiology, 109, 50–​62.
https://​doi.org/​10.1016/​S0924-​980X(97)00074-​X
McAuley, J. H. & Marsden, C. D. (2000). Physiological and pathological tremors and rhythmic
central motor control. Brain, 123, 1545–​1567. https://​doi.org/​10.1093/​brain/​123.8.1545
Miller, K. J., Leuthardt, E. C., Schalk, G., Rao, R. P. N., Anderson, N. R., Moran, D. W., Miller,
J. W., & Ojemann, J. G. (2007). Spectral changes in cortical surface potentials during motor
movement. Journal of Neuroscience, 27, 2424–​2432. https://​doi.org/​10.1523/​JNEURO​
SCI.3886-​06.2007
Mima, T., Matsuoka, T., & Hallett, M. (2000). Functional coupling of human right and left cor-
tical motor areas demonstrated with partial coherence analysis. Neuroscience Letters, 287,
93–​96. https://​doi.org/​10.1016/​S0304-​3940(0  0)01165-​4
Mima, T., Simpkins, N., Oluwatimilehin, T., & Hallett, M. (1999). Force level modulates human
cortical oscillatory activities. Neuroscience Letters, 275, 77–​80. https://​doi.org/​10.1016/​
S0304-​3940(99)00734-​X
Moisello, C., Blanco, D., Lin, J., Panday, P., Kelly, S.P., Quartarone, A., . . . Ghilardi, M. F. (2015).
Practice changes beta power at rest and its modulation during movement in healthy subjects
but not in patients with Parkinson’s disease. Brain and Behavior, 5, e00374. https://​doi.org/​
10.1002/​brb3.374
Moran, D. W. & Schwartz, A. B. (2017). Motor cortical representation of speed and direc-
tion during reaching. Journal of Neurophysiology, 82, 2676–​2692. https://​doi.org/​10.1152/​
jn.1999.82.5.2676
Müller, K., Kass-​ Iliyya, F., & Reitz, M. (1997). Ontogeny of ipsilateral corticospinal
projections: A developmental study with transcranial magnetic stimulation. Annals of
Neurology, 42, 705–​7 11. https://​doi.org/​10.1002/​ana.410420​506
Murthy, V. N. & Fetz, E. E. (1996a). Synchronization of neurons during local field potential
oscillations in sensorimotor cortex of awake monkeys. Journal of Neurophysiology, 76, 3968–​
3982. https://​doi.org/​10.1152/​jn.1996.76.6.3968
Murthy, V. N. & Fetz, E. E. (1996b). Oscillatory activity in sensorimotor cortex of awake
monkeys: synchronization of local field potentials and relation to behavior. Journal of
Neurophysiology, 76, 3949–​3967. https://​doi.org/​10.1152/​jn.1996.76.6.3949
Muthukumaraswamy, S. D. (2010). Functional properties of human primary motor cortex gamma
oscillations. Journal of Neurophysiology, 104, 2873–​2885. https://​doi.org/​10.1152/​jn.00607.2010
Muthukumaraswamy, S. D., Johnson, B. W., & McNair, N. A. (2004). Mu rhythm modula-
tion during observation of an object-​directed grasp. Cognitive Brain Research, 19, 195–​201.
https://​doi.org/​10.1016/​j.cogb​rain​res.2003.12.001
286    Bernadette C. M. van Wijk

Neumann, W.-​J., Degen, K., Schneider, G.-​H., Brücke, C., Huebl, J., Brown, P., & Kühn, A. A. (2016).
Subthalamic synchronized oscillatory activity correlates with motor impairment in patients with
Parkinson’s disease. Movement Disorders, 31, 1748–​1751. https://​doi.org/​10.1002/​mds.26759
Neumann, W.-​J., Jha, A., Bock, A., Huebl, J., Horn, A., Schneider, G., . . . Kühn, A. A. (2015).
Cortico-​pallidal oscillatory connectivity in patients with dystonia. Brain, 138, 1894–​1906.
https://​doi.org/​10.1093/​brain/​awv​109
Neuper, C. & Pfurtscheller, G. (2001). Event-​related dynamics of cortical rhythms: Frequency-​
specific features and functional correlates. International Journal of Psychophysiology, 43, 41–​
58. https://​doi.org/​10.1016/​S0167-​8760(01)00178-​7
Nolte, G., Bai, O., Wheaton, L., Mari, Z., Vorbach, S., & Hallett, M. (2004). Identifying
true brain interaction from EEG data using the imaginary part of coherency. Clinical
Neurophysiology, 115, 2292–​307. https://​doi.org/​10.1016/​j.cli​nph.2004.04.029
O’Keefe, J. & Recce, M. L. (1993). Phase relationship between hippocampal place units and the
EEG theta rhythm. Hippocampus 3, 317–​330. https://​doi.org/​10.1002/​hipo.450030​307
Ohara, S., Mima, T., Baba, K., Ikeda, A., Kunieda, T., Matsumoto, R., . . . Shibasaki, H. (2001).
Increased synchronization of cortical oscillatory activities between human supplemen-
tary motor and primary sensorimotor areas during voluntary movements. Journal of
Neuroscience, 21, 9377–​9386. https://​doi.org/​10.1523/​JNEURO​SCI.21-​23-​09377.2001
Oswal, A., Brown, P., & Litvak, V. (2013). Movement related dynamics of subthalmo-​cortical
alpha connectivity in Parkinson’s disease. NeuroImage, 70, 132–​142. https://​doi.org/​10.1016/​
j.neu​roim​age.2012.12.041
Özkurt, T. E., Butz, M., Homburger, M., Elben, S., Vesper, J., Wojtecki, L., & Schnitzler, A.
(2011). High-​frequency oscillations in the subthalamic nucleus: A neurophysiological
marker of the motor state in Parkinson’s disease. Experimental Neurology, 229, 324–​31.
https://​doi.org/​10.1016/​j.expneu​rol.2011.02.015
Paninski, L., Fellows, M. R., Hatsopoulos, N. G., & Donoghue, J. P. (2004). Spatiotemporal
tuning of motor cortical neurons for hand position and velocity. Journal of Neurophysiology,
91, 515–​532. https://​doi.org/​10.1152/​jn.00587.2002
Paradiso, G., Cunic, D., Saint-​Cyr, J. A., Hoque, T., Lozano, A. M., Lang, A. E., & Chen, R.
(2004). Involvement of human thalamus in the preparation of self-​paced movement. Brain,
127, 2717–​2731. https://​doi.org/​10.1093/​brain/​awh​288
Pastötter, B., Berchtold, F., & Bäuml, K.-​H. T. (2012). Oscillatory correlates of controlled speed-​
accuracy tradeoff in a response-​conflict task. Human Brain Mapping, 33, 1834–​49. https://​
doi.org/​10.1002/​hbm.21322
Pfurtscheller, G. & Lopes Da Silva, F. H. (1999). Event-​related EEG/​MEG synchronization and
desynchronization: Basic principles. Clinical Neurophysiology, 110, 1842–​1857. https://​doi.
org/​10.1016/​S1388-​2457(99)00141-​8
Pfurtscheller, G. & Neuper, C. (1992). Simultaneous EEG 10 Hz desynchronization and 40 Hz
synchronization during finger movements. Neuroreport, 3(12), 1057–​1060. https://​doi.org/​
10.1097/​00001​756-​199212​000-​00006
Pfurtscheller, G. & Neuper, C. (1997). Motor imagery activates primary sensorimotor area in
humans. Neuroscience Letters, 239, 65–​8. https://​doi.org/​10.1016/​s0304-​3940(97)00889-​6
Pfurtscheller, G., Neuper, C., & Kalcher, J. (1993). 40-​Hz oscillations during motor behavior in
man. Neuroscience Letters, 164, 179–​182. https://​doi.org/​10.1016/​0304-​3940(93)90886-​P
Pfurtscheller, G., Stančák, A., & Neuper, C. (1996). Post-​movement beta synchronization.
A correlate of an idling motor area? Electroencephalography and Clinical Neurophysiology,
98, 281–​293. https://​doi.org/​10.1016/​0013-​4694(95)00258-​8
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    287

Pfurtscheller, G., Zalaudek, K., & Neuper, C. (1998). Event-​related beta synchronization after
wrist, finger and thumb movement. Electroencephalography and Clinical Neurophysiology,
109, 154–​160. https://​doi.org/​10.1016/​S0924-​980X(97)00070-​2
Piña-​Fuentes, D., van Dijk, J. M. C., Drost, G., van Zijl, J. C., van Laar, T., Tijssen, M.
A. J., & Beudel, M. (2019). Direct comparison of oscillatory activity in the motor system
of Parkinson’s disease and dystonia: A review of the literature and meta-​analysis. Clinical
Neurophysiology, 130, 917–​924. https://​doi.org/​10.1016/​j.cli​nph.2019.02.015
Pogosyan, A., Gaynor, L. D., Eusebio, A., & Brown, P. (2009). Boosting cortical activity at beta-​
band frequencies slows movement in humans. Current Biology, 19, 1637–​41. https://​doi.org/​
10.1016/​j.cub.2009.07.074
Pollok, B., Butz, M., Gross, J., & Schnitzler, A. (2007). Intercerebellar coupling contributes
to bimanual coordination. Journal of Cognitive Neuroscience, 19, 704–​7 19. https://​doi.org/​
10.1162/​jocn.2007.19.4.704
Pollok, B., Gross, J., Müller, K., Aschersleben, G., & Schnitzler, A. (2005). The cerebral oscilla-
tory network associated with auditorily paced finger movements. NeuroImage, 24, 646–​655.
https://​doi.org/​10.1016/​j.neu​roim​age.2004.10.009
Priori, A., Foffani, G., Pesenti, A., Tamma, F., Bianchi, A., Pellegrini, M., . . . Villani, R. (2004).
Rhythm-​specific pharmacological modulation of subthalamic activity in Parkinson’s dis-
ease. Experimental Neurology, 189, 369–​379. https://​doi.org/​10.1016/​j.expneu​rol.2004.06.001
Raethjen, J. & Deuschl, G. (2012). The oscillating central network of Essential tremor. Clinical
Neurophysiology, 123, 61–​64. https://​doi.org/​10.1016/​j.cli​nph.2011.09.024
Ray, N. J., Jenkinson, N., Wang, S., Holland, P., Brittain, J. S., Joint, C., Stein, J. F., & Aziz, T.
(2008). Local field potential beta activity in the subthalamic nucleus of patients with
Parkinson’s disease is associated with improvements in bradykinesia after dopamine and
deep brain stimulation. Experimental Neurology, 213, 108–​113. https://​doi.org/​10.1016/​
j.expneu​rol.2008.05.008
Rickert, J., de Oliveira, S. C., Vaadia, E., Aertsen, A., Rotter, S., & Mehring, C. (2005). Encoding
of movement direction in different frequency ranges of motor cortical local field potentials.
Journal of Neuroscience, 25, 8815–​24. https://​doi.org/​10.1523/​JNEURO​SCI.0816-​05.2005
Riddle, C. N. & Baker, S. N. (2005). Manipulation of peripheral neural feedback loops alters
human corticomuscular coherence. Journal of Physiology, 566, 625–​639. https://​doi.org/​
10.1113/​jphys​iol.2005.089​607
Ritter, P., Moosmann, M., & Villringer, A. (2009). Rolandic alpha and beta EEG rhythms’
strengths are inversely related to fMRI-​BOLD signal in primary somatosensory and motor
cortex. Human Brain Mapping, 30, 1168–​1187. https://​doi.org/​10.1002/​hbm.20585
Rossiter, H. E., Davis, E. M., Clark, E. V, Boudrias, M.-​H., & Ward, N. S. (2014). Beta oscillations
reflect changes in motor cortex inhibition in healthy ageing. NeuroImage, 91, 360–​5. https://​
doi.org/​10.1016/​j.neu​roim​age.2014.01.012
Rueda-​Delgado, L. M., Heise, K. F., Daffertshofer, A., Mantini, D., & Swinnen, S. P. (2019). Age-​
related differences in neural spectral power during motor learning. Neurobiology of Aging,
77, 44–​57. https://​doi.org/​10.1016/​j.neu​robi​olag​ing.2018.12.013
Rueda-​Delgado, L. M., Solesio-​Jofre, E., Serrien, D. J., Mantini, D., Daffertshofer, A., &
Swinnen, S. P. (2014). Understanding bimanual coordination across small time scales from
an electrophysiological perspective. Neuroscience & Biobehavioral Reviews, 47, 614–​635.
https://​doi.org/​10.1016/​j.neubio​rev.2014.10.003
288    Bernadette C. M. van Wijk

Safri, N. M., Murayama, N., Hayashida, Y., & Igasaki, T. (2007). Effects of concurrent visual
tasks on cortico-​muscular synchronization in humans. Brain Research, 1155, 81–​92. https://​
doi.org/​10.1016/​j.brain​res.2007.04.052
Salenius, S., Portin, K., Kajola, M., Salmelin, R., & Hari, R. (1997). Cortical control of human
motoneuron firing during isometric contraction. Journal of Neurophysiology, 77, 3401–​3405.
https://​doi.org/​10.1016/​j.conb.2003.10.008
Salmelin, R., Hämäläinen, M., Kajola, M., & Hari, R. (1995). Functional segregation of
movement-​related rhythmic activity in the human brain. NeuroImage, 2, 237–​243. https://​
doi.org/​10.1006/​nimg.1995.1031
Salmelin, R. & Hari, R. (1994). Spatiotemporal characteristics of sensorimotor neuromagnetic
rhythms related to thumb movement. Neuroscience, 60, 537–​550. https://​doi.org/​10.1016/​
0306-​4522(94)90263-​1
Sanes, J. N. & Donoghue, J. P. (1993). Oscillations in local field potentials of the primate motor
cortex during voluntary movement. Proceedings of the National Academy of Sciences of the
United States of America, 90, 4470–​4474. https://​doi.org/​10.1073/​pnas.90.10.4470
Schmiedt-​Fehr, C., Mathes, B., Kedilaya, S., Krauss, J., & Başar-​Eroğlu, C. (2016). Aging dif-
ferentially affects alpha and beta sensorimotor rhythms in a go/​ go task. Clinical
no-​
Neurophysiology, 127, 3234–​42. https://​doi.org/​10.1016/​j.cli​nph.2016.07.008
Schnitzler, A., Münks, C., Butz, M., Timmermann, L., & Gross, J. (2009). Synchronized
brain network associated with essential tremor as revealed by magnetoencephalography.
Movement Disorders, 24, 1629–​1635. https://​doi.org/​10.1002/​mds.22633
Schnitzler, A., Salenius, S., Salmelin, R., Jousmäki, V., & Hari, R. (1997). Involvement of pri-
mary motor cortex in motor imagery: A neuromagnetic study. NeuroImage, 6, 201–​8. https://​
doi.org/​10.1006/​nimg.1997.0286
Serrien, D. J. (2008). The neural dynamics of timed motor tasks: Evidence from a
synchronization–​continuation paradigm. European Journal of Neuroscience, 27, 1553–​1560.
https://​doi.org/​10.1111/​j.1460-​9568.2008.06110.x
Sharott, A., Grosse, P., Kühn, A.A., Salih, F., Engel, A.K., Kupsch, A., . . . Brown, P. (2008). Is the
synchronization between pallidal and muscle activity in primary dystonia due to peripheral
afferance or a motor drive? Brain, 131, 473–​484. https://​doi.org/​10.1093/​brain/​awm​324
Sherman, M. A., Lee, S., Law, R., Haegens, S., Thorn, C. A., Hämäläinen, M. S., Moore, C. I., &
Jones, S. R. (2016). Neural mechanisms of transient neocortical beta rhythms: Converging
evidence from humans, computational modeling, monkeys, and mice. Proceedings of the
National Academy of Sciences of the United States of America, 113, E4885–​E4894. https://​doi.
org/​10.1073/​pnas.160​4135​113
Silberstein, P., Kühn, A. A., Kupsch, A., Trottenberg, T., Krauss, J. K., Wöhrle, J.C., . . . Brown,
P. (2003). Patterning of globus pallidus local field potentials differs between Parkinson’s dis-
ease and dystonia. Brain, 126, 2597–​608. https://​doi.org/​10.1093/​brain/​awg​267
Spinks, R. L., Kraskov, A., Brochier, T., Umilta, M. A., & Lemon, R. N. (2008). Selectivity for
grasp in local field potential and single neuron activity recorded simultaneously from M1
and F5 in the awake macaque monkey. Journal of Neuroscience, 28, 10961–​7 1. https://​doi.org/​
10.1523/​JNEURO​SCI.1956-​08.2008
Stam, C. J., Nolte, G., & Daffertshofer, A. (2007). Phase lag index: Assessment of functional
connectivity from multi-​channel EEG and MEG with diminished bias from common
sources. Human Brain Mapping, 28, 1178–​1193. https://​doi.org/​10.1002/​hbm.20346
 OSCILLATORY ACTIVITY IN SENSORIMOTOR FUNCTION    289

Stančák, A., Feige, B., Lücking, C. H., & Kristeva-​Feige, R. (2000). Oscillatory cortical ac-
tivity and movement-​ related potentials in proximal and distal movements. Clinical
Neurophysiology, 111, 636–​650. https://​doi.org/​10.1016/​S1388-​2457(99)00310-​7
Stančák, A. & Pfurtscheller, G. (1996). Mu-​rhythm changes in brisk and slow self-​paced finger
movements. Neuroreport, 7, 1161–​1164. https://​doi.org/​10.1097/​00001​756-​199604​260-​00013
Stančák, A., Riml, A., & Pfurtscheller, G. (1997). The effects of external load on movement-​
related changes of the sensorimotor EEG rhythms. Electroencephalography and Clinical
Neurophysiology, 102, 495–​504. https://​doi.org/​10.1016/​S0013-​4694(96)96623-​0
Steinemann, N. A., O’Connell, R. G., & Kelly, S. P. (2018). Decisions are expedited through
multiple neural adjustments spanning the sensorimotor hierarchy. Nature Communications,
9, 3627. https://​doi.org/​10.1038/​s41​467-​018-​06117-​0
Swann, N., Tandon, N., Canolty, R., Ellmore, T. M., McEvoy, L. K., Dreyer, S., DiSano, M., &
Aron, A. R. (2009). Intracranial EEG reveals a time-​and frequency-​specific role for the right
inferior frontal gyrus and primary motor cortex in stopping initiated responses. Journal of
Neuroscience, 29, 12675–​12685. https://​doi.org/​10.1523/​JNEURO​SCI.3359-​09.2009
Szurhaj, W., Bourriez, J. L., Kahane, P., Chauvel, P., Mauguière, F., & Derambure, P. (2005).
Intracerebral study of gamma rhythm reactivity in the sensorimotor cortex. European
Journal of Neuroscience, 21, 1223–​1235. https://​doi.org/​10.1111/​j.1460-​9568.2005.03966.x
Talakoub, O., Neagu, B., Udupa, K., Tsang, E., Chen, R., Popovic, M. R., & Wong, W. (2016).
Time-​course of coherence in the human basal ganglia during voluntary movements.
Scientific Reports, 6, 34930. https://​doi.org/​10.1038/​srep34​930
Tan, H., Jenkinson, N., & Brown, P. (2014). Dynamic neural correlates of motor error
monitoring and adaptation during trial-​to-​trial learning. Journal of Neuroscience, 34, 5678–​
5688. https://​doi.org/​10.1523/​JNEURO​SCI.4739-​13.2014
Tan, H., Pogosyan, A., Anzak, A., Ashkan, K., Bogdanovic, M., Green, A.L., . . . Brown, P.
(2013). Complementary roles of different oscillatory activities in the subthalamic nucleus in
coding motor effort in Parkinsonism. Experimental Neurology, 248, 187–​195. https://​doi.org/​
10.1016/​j.expneu​rol.2013.06.010
Tan, H., Wade, C., & Brown, P. (2016). Post-​movement beta activity in sensorimotor cortex
indexes confidence in the estimations from internal models. Journal of Neuroscience, 36,
1516–​1528. https://​doi.org/​10.1523/​JNEURO​SCI.3204-​15.2016
Tinkhauser, G., Pogosyan, A., Little, S., Beudel, M., Herz, D. M., Tan, H., & Brown, P. (2017a).
The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson’s dis-
ease. Brain, 140, 1053–​1067. https://​doi.org/​10.1093/​brain/​awx​010
Tinkhauser, G., Pogosyan, A., Tan, H., Herz, D. M., Kühn, A. A., & Brown, P. (2017b). Beta
burst dynamics in Parkinson’s disease OFF and ON dopaminergic medication. Brain, 140,
2968–​2981. https://​doi.org/​10.1093/​brain/​awx​252
Toma, K., Mima, T., Matsuoka, T., Gerloff, C., Ohnishi, T., Koshy, B., Andres, F., & Hallett, M.
(2002). Movement rate effect on activation and functional coupling of motor cortical areas.
Journal of Neurophysiology, 88, 3377–​3385. https://​doi.org/​10.1152/​jn.00281.2002
Trevarrow, M. P., Kurz, M. J., McDermott, T. J., Wiesman, A. I., Mills, M. S., Wang, Y.-​
P., . . . Wilson, T. W. (2019). The developmental trajectory of sensorimotor cortical
oscillations. NeuroImage, 184, 455–​461. https://​doi.org/​10.1016/​j.neu​roim​age.2018.09.018
Tsang, E.W., Hamani, C., Moro, E., Mazzella, F., Lozano, A.M., Hodaie, M., Yeh, I.-​J., & Chen, R.
(2012). Movement related potentials and oscillatory activities in the human internal globus
pallidus during voluntary movements. Journal of Neurology, Neurosurgery, and Psychiatry,
83, 91–​7. https://​doi.org/​10.1136/​jnnp.2011.243​857
290    Bernadette C. M. van Wijk

Tsiokos, C., Hu, X., & Pouratian, N. (2013). 200–​300 Hz movement modulated oscillations in
the internal globus pallidus of patients with Parkinson’s Disease. Neurobiological Disorders,
54, 464–​474. https://​doi.org/​10.1016/​j.nbd.2013.01.020
van Wijk, B. C. M. (2017). Is broadband gamma activity pathologically synchronized to the
beta rhythm in Parkinson’s disease? Journal of Neuroscience, 37, 9347–​9349. https://​doi.org/​
10.1523/​JNEURO​SCI.2023-​17.2017
van Wijk, B. C. M., Beek, P. J., & Daffertshofer, A. (2012). Differential modulations of ipsilateral
and contralateral beta (de)synchronization during unimanual force production. European
Journal of Neuroscience, 36, 2088–​2097. https://​doi.org/​10.1111/​j.1460-​9568.2012.08122.x
van Wijk, B .C. M., Beudel, M., Jha, A., Oswal, A., Foltynie, T., Hariz, M. I., . . . Litvak, V. (2016).
Subthalamic nucleus phase-​amplitude coupling correlates with motor impairment in Parkinson’s
disease. Clinical Neurophysiology, 127, 2010–​2019. https://​doi.org/​10.1016/​j.cli​nph.2016.01.015
van Wijk, B. C. M., Daffertshofer, A., Roach, N., & Praamstra, P. (2009) A role of beta oscilla-
tory synchrony in biasing response competition? Cerebral Cortex, 19, 1294–​1302. https://​doi.
org/​10.1093/​cer​cor/​bhn​174
van Wijk, B. C. M., Neumann, W.-​J., Schneider, G.-​H., Sander, T. H., Litvak, V., & Kühn, A. A.
(2017). Low-​beta cortico-​pallidal coherence decreases during movement and correlates with
overall reaction time. NeuroImage, 159, 1–​8. https://​doi.org/​10.1016/​j.neu​roim​age.2017.07.024
Vidailhet, M., Vercueil, L., Houeto, J.-​L., Krystkowiak, P., Benabid, A.-​L., Cornu, P., . . . Pollak,
P. (2005). Bilateral deep-​brain stimulation of the globus pallidus in primary generalized dys-
tonia. New England Journal of Medicine, 352, 459–​467. https://​doi.org/​10.1056/​nejmo​a042​187
Weaver, F. M., Follett, K., Stern, M., Hur, K., Harris, C., Marks, . . . Huang, G.D.; CSP 468 Study
Group. (2009). Bilateral deep brain stimulation vs best medical therapy for patients with
advanced Parkinson disease: A randomized controlled trial. Journal of the American Medical
Association, 301, 63–​73. https://​doi.org/​10.1001/​jama.2008.929
Wessel, J. R., Ghahremani, A., Udupa, K., Saha, U., Kalia, S. K., Hodaie, M., . . . Chen, R. (2016).
Stop-​related subthalamic beta activity indexes global motor suppression in Parkinson’s dis-
ease. Movement Disorders, 12, 1846–​1853. https://​doi.org/​10.1002/​mds.26732
Witham, C. L., Riddle, C. N., Baker, M. R., & Baker, S. N. (2011). Contributions of descending
and ascending pathways to corticomuscular coherence in humans. Journal of Physiology,
589, 3789–​3800. https://​doi.org/​10.1113/​jphys​iol.2011.211​045
Witte, M., Patino, L., Andrykiewicz, A., Hepp-​Reymond, M.-​C., & Kristeva, R. (2007).
Modulation of human corticomuscular beta-​ range coherence with low-​ level static
forces. European Journal of Neuroscience, 26, 3564–​3570. https://​doi.org/​10.1111/​
j.1460-​9568.2007.05942.x
Wolpaw, J. R., Birbaumer, N., McFarland, D. J., Pfurtscheller, G., & Vaughan, T. M. (2002).
Brain–​computer interfaces for communication and control. Clinical Neurophysiology, 113,
767–​791. https://​doi.org/​10.1016/​S1388-​2457(02)00057-​3
Yamawaki, N., Stanford, I. M., Hall, S. D., & Woodhall, G. L. (2008). Pharmacologically induced
and stimulus evoked rhythmic neuronal oscillatory activity in the primary motor cortex in
vitro. Neuroscience, 151, 386–​395. https://​doi.org/​10.1016/​j.neuro​scie​nce.2007.10.021
Zandvoort, C. S., van Dieën, J. H., Dominici, N., & Daffertshofer, A. (2019). The human sen-
sorimotor cortex fosters muscle synergies through cortico-​synergy coherence. NeuroImage,
199, 30–​37. https://​doi.org/​10.1016/​j.neu​roim​age.2019.05.041
Pa rt I I I
 CHAPTER 13

EEG FREQU E NC Y
DEVEL OPM EN T AC RO S S
INFANCY AND C H I L DH O OD

KIMBERLY CUEVAS AND MARTHA ANN BELL

13.1  Introduction

Hans Berger (1929) published the first report of the electroencephalogram (EEG)
recorded on an adult scalp. After success with adult recordings, Berger began to record
electrical activity from the scalps of a wide age range of individuals and it was Berger’s
fifth report three years later (1932) that created the field of developmental neurophysi-
ology. Berger said in the earlier part of his fifth report that he had recorded EEG from
the scalps of a few children but had not yet recorded EEG from anyone under 5 years of
age. His rationale for avoiding younger children was that he was using needle electrodes
and did not want to use local anesthesia with such young individuals. Thus, for his initial
recordings with infants, Berger used silver foil electrodes on the forehead and occiput,
with each the size of the palm of his hand. On each section of silver foil was a piece of
flannel cloth soaked in saline. Another piece of silver foil was placed on top so that the
flannel would not dry out. He held this on the scalp with a rubber bandage (Berger, 1932).
Berger reported that he attempted to record EEG from six infants between 8 and
13 days old, but there were no characteristic alpha waves that he had come to expect
after doing so many adult and older child EEG recordings. He concluded that there was
no EEG in the first weeks after birth because the cerebral cortex had not yet assumed
its function. A 35-​day-​old infant (a “healthy and very strong boy”) was the youngest in
whom Berger could record EEG. The infant lay completely still and began to fall asleep
and there was some evidence of the posterior alpha activity that Berger had seen for the
past three years in older children and adults. Berger (1932) concluded in his fifth report
that one could see EEG in all healthy and strong children who are older than 2 months
294    KIMBERLY CUEVAS and MARTHA ANN BELL

of age and that by the age of 5 years, children show an EEG tracing comparable to that of
an adult.
The EEG recordings Berger accomplished from infants were highly intriguing. Infant
EEG had greater amplitude and cycled at a lower frequency than adult EEG. From
Berger’s time, researchers have assumed that EEG differences among infants, chil-
dren, and adults reflect differences in brain maturation. Longitudinal research studies,
including our own contributions (Bell & Fox, 1992; Cuevas & Bell, 2011), have verified
that position. Researchers continue to examine infant and young child EEG as a rela-
tively inexpensive, non-​invasive way to study brain development.
This chapter provides an overview of the ontogeny of EEG frequency bands during
infancy and early childhood. We include infant correlates of adult frequency bands
labeled as delta, theta, alpha family, beta, and gamma. We focus most intensely on
the 6–​9 Hz “infant alpha” frequency band, as it is the band that has received the most
attention in the developmental neurophysiology research literature and the frequency
band that we have examined so intensely in our own programs of research and our col-
laborative efforts. We organize the discussion of infant and child alpha around studies
focused on action-​perception processes, executive processes, and affective processes.
The chapter ends with a brief section on broader impacts of infant and child EEG and
future directions.

13.2  Ontogenesis of EEG Bands

This section focuses on the oscillatory rhythms that compose the waking EEG during
infancy and childhood. The primary frequency bands of normative EEG oscillatory ac-
tivity based on the adult literature are delta (1–​4 Hz), theta (4–​8 Hz), alpha (8–​13 Hz),
beta (13–​30 Hz), and gamma (36–​44 Hz). These oscillations often occur at slower rates
during early development. However, throughout ontogeny, EEG amplitude is typically
inversely related to frequency, with greater amplitude exhibited for slower oscillations.
The functional properties of oscillatory rhythms are defined here in terms of event-​
related changes in EEG power values (EEG reactivity) in response to external stimuli
and/​or psychological (e.g., cognitive, affective) processing. Specifically, the term syn-
chronization refers to an increase in EEG power values relative to resting baseline,
whereas desynchronization refers to a decrease in EEG power values.
We provide an overview of what is known about each of these EEG frequency bands
during early development, including functional properties as well as age-​ related
changes in frequency and amplitude. In general, there is a decrease in the amount of low
frequency activity (1–​5 Hz; i.e., delta, lower-​theta) and an increase in intermediate fre-
quency oscillations (6–​12 Hz; i.e., upper-​theta; alpha) from infancy through childhood
(Gibbs & Knott, 1949; Hagne, 1968; Marshall et al., 2002). As there is no standardization
of EEG rhythms in the developmental neurophysiology literature as found in adolescent
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    295

and adult EEG work, EEG researchers have used multiple techniques to determine ap-
propriate frequency band definitions for infants and young children.

13.2.1 Delta Band
Large, slow wave oscillations in the delta band are typically investigated in the con-
text of sleep. Although oscillatory activity within the delta frequency band is present
in the waking EEG during early development, descriptions of this band have primarily
focused on decreases in delta activity and corresponding increases in higher frequency
oscillations as a function of age (Hagne, 1968; Ogawa et al., 1984). Although Lindsley
(1938) recorded from only occipital sites, he noted the presence of “type V waves” in
subjects from 3 months of age through adulthood, with the average frequency increasing
gradually from 0.68 to 1.08 Hz over this developmental period. The delta rhythm was
unaffected by stimulation and reached the 1 Hz oscillation rate by 3 years of age.

13.2.2 Theta Band
Oscillatory activity within the theta range is faster than the adjacent delta band. Theta
rhythms are prominent in the waking EEG during early development, but the theta fre-
quency range is slightly lower than that of the adult 4–​8 Hz theta band. The adult litera-
ture has noted that emotional and cognitive processing is associated with increases in
theta power (e.g., Walter & Walter, 1949; see also Chapter 15). Theta oscillations have
been hypothesized to be linked to reward processing and active learning during early
development (Begus & Bonawitz, 2020). Visual perceptual-​stimulation techniques
have also been used to “entrain” (elicit) neural oscillatory activity at a particular fre-
quency, with specific focus on the functional properties of the theta rhythm (Köster
et al., 2019). To our knowledge, however, there have been no systematic examinations of
theta’s functional properties throughout development. Here, we highlight some of the
characteristics of theta reactivity during infancy and childhood.
In the context of examining 7-​to 12-​month-​olds’ alpha rhythms, Stroganova and
colleagues (Stroganova et al., 1999) identified 3.6–​6 Hz activity with unique functional
properties. This band exhibited increases in theta power during “internally controlled
(anticipatory) attention” as infants were engaged in a peek-​a-​boo game (Orekhova
et al., 1999; Stroganova et al., 1998). Recent analysis of 6-​to 12-​month-​olds’ sustained
attention, using heart-​rate-​defined phases of attention, has confirmed and extended
these findings. By 10–​12 months of age, sustained attention during a video clip was
associated with theta (2–​6 Hz) synchronization at multiple scalp sites, including frontal
pole, central, and parietal (Xie et al., 2018). Event-​related theta synchronization during
attentional processes may also be related to infants’ subsequent memory and cognitive
abilities. For instance, increases in 11-​month-​olds’ frontal theta (3–​5 Hz) power during
object exploration was associated with variability in infants’ future object recognition
296    KIMBERLY CUEVAS and MARTHA ANN BELL

(Begus et al., 2015). Likewise, measures of frontal theta (3–​6 Hz) enhancement during
a dynamic non-​social video at 6 months of age is associated with non-​verbal cognitive
abilities at 9 months (Braithwaite et al., 2020). Together, these findings indicate that
theta synchronization is intricately linked to aspects of infant attention and memory;
however, the precise developmental onset and trajectory of event-​related theta reactivity
are important open areas of inquiry.
Increases in theta power are also exhibited in response to positive and negative af-
fective processing during infancy (Futagi et al., 1998; Nikitina et al., 1985) as well as nu-
tritive sucking (Lehtonen et al., 2016; Paul et al., 1996). However, little is known about
age-​related changes in theta reactivity beyond infancy. To this end, Orekhova and
colleagues (Orekhova et al., 2006) directly compared infants’ and young children’s theta
reactivity to “theta-​provoking” stimuli—​toy exploration and attention to social stimula-
tion (i.e., adult speech). Theta scalp topography differed as a function of age and stimulus
type; though, both 8-​to 12-​month-​olds and 3-​to 6-​year-​olds exhibited increases in
theta (3.6–​5.6 Hz and 4–​8 Hz, respectively) power in response to these stimuli. Thus, in
some affective contexts, the adult theta range is developmentally appropriate by early
childhood. Recent evidence also indicates changes in the topography of infants’ theta
(3–​6 Hz) synchronization in response to social stimuli between 6 and 12 months of age
(Jones et al., 2015). In sum, theta synchronization is displayed in a variety of cognitive
and emotional settings early in development, but the precise nature of the scalp topog-
raphy of theta responsivity varies as a function of multiple factors, including age and
reactive context.

13.2.3 Alpha Band (“Alpha Family”)

The majority of developmental research on waking EEG has examined oscillatory ac-
tivity that falls within the alpha frequency range. The alpha band (or “alpha family”)
includes two rhythms that overlap in frequency, but differ in their functional properties,
scalp topographies, and developmental trajectories. Berger (1929) initially identified the
posterior alpha rhythm (or occipital alpha rhythm) in the adult waking EEG. This oscilla-
tory activity is prominent over posterior scalp locations (parietal, occipital) when there
is a homogenous visual field (e.g., dark room; eye closure) and it is suppressed by visual
stimulation (e.g., flashes of light; eye opening). The central alpha rhythm, also known
as the Rolandic mu rhythm or pre-​central alpha rhythm, is prominent over the sen-
sorimotor cortex during periods of stillness (i.e., no motor movement). Foundational
work with adults has revealed that mu oscillatory activity is suppressed in response to
motor movement (Gastaut et al., 1954) with more recent investigations extending these
findings to motor imagery and the perception of others’ actions (Muthukumaraswamy
& Johnson, 2004; Pfurtscheller et al., 2006). Thus, although the mu and posterior alpha
rhythms are both within the alpha frequency range, their unique topographic and func-
tional properties indicate that they are independent oscillations. The second half of this
chapter reviews developmental work focusing on frontal EEG activity within the alpha
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    297

band (6–​9 Hz) and its associations with affective and cognitive processes. Frontal alpha
activity is proposed to have unique neural generators by some, and to be associated with
central and/​or posterior alpha rhythms by others (see Stroganova & Orekhova, 2007 for
discussion).

13.2.3.1 Posterior Alpha
Early developmental EEG investigations using visual quantification noted posterior os-
cillatory activity that had similar rhythmic qualities to the adult posterior alpha rhythm,
though the rate of oscillation was slower. Around 3–​4 months of age, an occipital rhythm
with a frequency of 3–​5 Hz has been identified in the waking EEG (Lindsley, 1938,
1939; Smith, 1938, 1941). It increases in both amplitude and frequency during the first
postnatal year (6–​7 Hz), with the posterior alpha oscillation rate continuing to gradually
increase throughout childhood. The occipital alpha amplitude remains fairly stable until
3–​4 years when there is a sharp drop followed by a gradual decline to adult levels by
15–​16 years (Lindsley, 1939). The adult alpha frequency range is reached during middle
childhood, with mean occipital frequencies of 9 and 10 Hz at 8 and 11–​16 years, respect-
ively (Lindsley, 1938, 1939; Smith, 1938, 1941). Subsequent investigations using frequency
analyzers and spectral analysis have confirmed these early findings (Hagne, 1968; Hagne
et al., 1973; Miskovic et al., 2015).
The functional properties of the posterior alpha rhythm were first noted during
early development by Lindsley (1938). Visual stimuli (i.e., bright lights in a dark room)
blocked occipital oscillatory activity in young participants, including infants who were
a “few months” of age. However, scalp recordings were limited to occipital sites and
detailed developmental analyses were not reported. Using spectral analysis, Stroganova
and colleagues (1999) confirmed and extended these early findings by comparing 7-​to
12-​month-​olds’ posterior oscillatory activity during conditions of darkness (i.e., lights
off in the testing room) and quite visual attention (i.e., watching soap bubbles). These
conditions were designed to be developmentally appropriate analogues of the “eyes
closed versus eyes open” procedures used to identify posterior alpha reactivity with
older children and adults. Their work indicated that the 5.2–​9.6 Hz band exhibited
prominent posterior oscillatory activity in the response to the “lights off ” condition,
and this activity was attenuated during visual attention. Importantly, these properties
were not displayed at anterior/​central scalp locations, indicating similar functional
properties and scalp topography to the adult posterior alpha rhythm.

13.2.3.2 Central Alpha (Mu)

Initial visual examinations of EEG in the neonate indicated rhythmic activity at areas
over the sensorimotor cortex during sleep. However, this activity was not seen at oc-
cipital sites or when neonates were awake (Smith, 1941). By 3–​4 months, 7-​Hz rhythmic
activity has been found at central sites in awake infants (Smith, 1939, 1941). Using spec-
tral analysis, Hagne and colleagues (1973) noted the “hint of a frequency peak” at central
sites at 3 weeks of age around 4–​5 Hz, which reached 7–​8 Hz by 12 months. Similarly,
more recent longitudinal work extending from infancy through early childhood, has
298    KIMBERLY CUEVAS and MARTHA ANN BELL

indicated that the central peak frequency rises from 6–​7 Hz at 5 months to 9 Hz by
4 years of age (Marshall et al., 2002). These findings are consistent with Smith’s (1941)
original report of central alpha activity increasing to 8 Hz at 1.5 years, to 9 Hz at 3.5 years,
to 10 Hz at 10–​14 years. Prior to reaching adult frequency ranges, the oscillatory rate of
the mu rhythm is faster than the posterior alpha rhythm.
Although the mu rhythm is attenuated during various conditions related to action
perception and production, the functional properties of this rhythm are most robust
and reliably identified via conditions of discrete motor movement. Currently, the most
systematic developmental examination of the functional properties of the central alpha
rhythm comes from a cross-​sectional magnetoencephalography (MEG) study. Age-​
related changes in the peak frequency of mu rhythm attenuation during a discrete hand
movement (i.e., squeezing a pipette) were found from infancy through childhood.
There was a linear increase in peak mu frequency from 2.75 to 8.25 Hz between 11 and
47 weeks of age (Berchicci et al., 2011). This was followed by a more gradual increase
in peak mu frequency during early childhood (2–​5 years; average 8.5 Hz), which was
below the adult 10.2-​Hz peak. These findings have been confirmed and extended by a
recent cross-​sectional EEG study of mu rhythm attenuation during reaching-​grasping
actions. Mu peaks were found at 7.39, 8.81, and 10.51 Hz at 12 months, 4 years, and 18–​
21 years, respectively (Thorpe et al., 2016). A bourgeoning recent literature examining
the infant mu rhythm has found 6–​9 Hz attenuation during action perception and/​or
execution (Cuevas et al., 2014; Marshall & Meltzoff, 2011); a detailed description of the
EEG correlates of action-​perception processes is provided later in the chapter.

13.2.4 Beta Band
Berger (1929) identified beta waves in conjunction with alpha waves in the adult
waking EEG, but as higher frequency oscillations. Similar to the central alpha rhythm,
the “precentral” beta rhythm is associated with motor processes (Jasper & Andrews,
1938; Jasper & Penfield, 1949). The adult literature has revealed that the beta rhythm is
attenuated during action execution, motor planning, and action perception (Jarvelainen
et al., 2004; Pfurtscheller et al., 1997). The beta frequency is often a harmonic of the mu
rhythm frequency. Although these rhythms have overlapping functional properties,
there are a variety of unique characteristics of each band (see Crone et al., 1998; Hari &
Salmelin, 1997).
Initial description of developmental changes in beta rhythm comes from Lindsley
(1938), who identified “type IV waves” from the waking EEG activity at occipital sites
(the only recording sites); these waves had mean frequencies approximately double the
alpha wave frequency throughout development. This oscillatory activity exhibited sub-
stantial increases in frequency throughout infancy and childhood: 7 Hz at 3 months, 11.6
Hz at 12 months, and 16 Hz at 4 years. The adult 20-​Hz frequency was attained around 11–​
12 years. The literature is mixed, however, on whether there are age-​related increases or
decreases in beta band power (Gasser et al., 1988; Matsuura et al., 1985; Ogawa et al., 1984).
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    299

Contemporary developmental investigations of the beta rhythm have primarily

focused on its involvement in motor processes. Similar to the mu rhythm, discrete motor
movement has been used to characterize the beta rhythm’s functional properties. This
literature is rather limited in comparison to corresponding work on the central alpha
rhythm. Further, there is mixed evidence regarding beta rhythm attenuation during in-
fancy and early childhood. Meyer and colleagues (2016) identified age-​appropriate beta
rhythm frequencies for 8-​month-​olds (12–​15 Hz), 14-​month-​olds (14–​18 Hz), and adults
(16–​25 Hz) during reaching/​grasping movements. Attenuation of beta activity in re-
sponse to action production was evident only in 14-​month-​olds and adults, despite the
presence of mu rhythm attenuation in all age groups. Likewise, a recent cross-​sectional
analysis revealed that although 12-​month-​olds, 4-​year-​olds, and adults exhibited mu
rhythm attenuation during action execution, beta rhythm attenuation was present only
for adults (Thorpe et al., 2016).
Other MEG and EEG work with 3-​to 6-​year-​olds has found evidence of decreases
in beta oscillatory activity in response to discrete motor movements (EEG: Bryant &
Cuevas, 2019; Liao et al., 2015; MEG: Cheyne et al., 2014; Gaetz et al., 2010). However,
the magnitude of young children’s beta attenuation was smaller than beta changes
exhibited by older children (11–​13 years) and adults (Gaetz et al., 2010). Taken together,
these findings suggest that although there is evidence of beta oscillatory activity early
in ontogeny, its functional properties may not be as readily detected during early de-
velopment as compared to lower frequency oscillations, such as the mu rhythm. Given
their overlapping functional properties, concurrent developmental analysis of beta and
central alpha rhythms is essential to a more integrative understanding of the network
dynamics underlying motor and action-​perception processes (see also Section 13.3.1).

13.2.5 Gamma Band
Because of its low amplitude, high-​frequency oscillations, systematic analysis of gamma
band activity via visual examination was not feasible (Lindsley, 1938). A variety of
broadband and sub-​band definitions have been used to define the gamma oscillatory
activity, but the vast majority of the developmental and adult literature has focused on
oscillations near 40 Hz. Work with adults has revealed that increases in gamma band
power are associated with both motor and cognitive processes, including perceptual
binding and memory (see Başar, 2013, for review).
Early examination of the gamma (35–​45 Hz) band with a large sample of 3-​to 12-​
year-​olds (N =​707), noted increased power between 3 and 4 years at all recorded sites
(frontal, central, occipital) with a distinct peak at frontal sites between 4 and 5 years of
age (Takano & Ogawa, 1998). Although occipital gamma power was stable after 4 years
of age, there were some age-​related decreases in frontal and central gamma power be-
tween 4 and 11 years. A recent analysis of gamma (31–​50 Hz) oscillations with a compara-
tively smaller sample of 3-​to 38-​year-​olds (N =​156) also identified age-​related decreases
in resting gamma power; however, these changes were seen throughout the scalp
300    KIMBERLY CUEVAS and MARTHA ANN BELL

(Tierney et al., 2013). Tierney and colleagues proposed that decreases in gray matter—​
specifically, synaptic density via synaptic pruning (Whitford et al., 2007)—​may underlie
the widespread reductions in resting gamma power as a function of age. Additional
work is needed to characterize the development of gamma power during the first three
postnatal years. A recent large-​scale longitudinal investigation between 2 to 6 postnatal
months (N =​518) found gradual increases in gamma (30–​50 Hz) power across all scalp
sites (Pivik et al., 2019). Pivik and colleagues hypothesize that ontogenetic changes in
GABAergic (γ‑aminobutyric acid) interneurons contribute to emerging gamma activity
(Paredes et al., 2016; Xu et al., 2011).
During infancy, resting gamma power varies as a function of internal and ex-
ternal factors, such as socioeconomic status, sex, and diet (Pivik et al., 2019; Tomalski
et al., 2013, but see Brito et al., 2016). Further, higher levels of resting gamma oscilla-
tory activity are positively associated with both concurrent and future measures of
early cognitive development, including language, memory, and executive function
(Benasich et al., 2008; Brito et al., 2013; Tarullo et al., 2017). Developmental studies
have also revealed changes in gamma band activity associated with ongoing cognitive
processing. An initial investigation of gamma’s involvement in perceptual binding
revealed bursts of gamma oscillatory activity at frontal areas during the perception
of illusory objects in 8-​month-​olds, but not 6-​month-​olds (Csibra et al., 2000). These
findings confirmed behavioral evidence that younger infants were unsuccessful at
perceiving illusory objects (Ghim, 1990). Subsequent work also shows increases in
6-​month-​olds’ gamma oscillatory activity over temporal areas in the context of ob-
ject occlusion events; presumably contributing infants’ ability to maintain object
representations (Kaufman et al., 2003, 2006). Gamma oscillations are also associated
with aspects of language learning during infancy, including recognition of familiar
objects with verbal labels (Gliga et al., 2010) and phonemic perceptual narrowing
(Ortiz-​Mantilla et al., 2016).

13.3  6–​9 Hz Alpha Band:

Action-​P erception, Executive, and
Affective Processes

Our primary focus in this section is on the infant and child frontal alpha and central mu
rhythms, as the 6–​9 Hz alpha band has received the most attention in the developmental
literature. We noted at the beginning of this chapter that the developmental neurophysi-
ology literature has no standardization of EEG rhythms as found in adult EEG work. The
research we have reviewed thus far shows how individual research teams since Berger’s
time have worked toward defining specific frequency bands of interest, with clear indi-
cation that the traditional frequency band definitions used with adults (e.g., 8–​13 Hz for
alpha) do not apply to studies of infant and young child EEG.
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    301

After six decades of developmental EEG research, the Society for Psychophysiological
Research published a set of recommendations for recording and analyzing EEG in re-
search contexts (Pivik et al., 1993). Those guidelines included two suggestions for EEG
researchers who focus on infants and young children. The first was wide band analysis,
potentially including all frequencies with evidence of power after doing spectral plots.
Although some researchers working with infant samples have used this approach in
studies of infant emotion (e.g., 3–​13 Hz: Diego et al., 2006), the wide band approach was
never commonly adopted for use in infant and early childhood research. This may be
because of the assumption that there was the potential for the developmental EEG field
to eventually standardize frequency bands based on temporal, spatial, amplitude, and
functional characteristics much as the adult EEG field has done.
The second suggestion was that spectral plots be examined and frequency bands
determined that center around the peaks in the spectrum. This is the approach we used
with our first infant EEG data set (Bell & Fox, 1992). We recorded resting baseline EEG
from 13 infants from 7 to 12 months of age because we had hypotheses about relations
between the development of frontal EEG and performance on a classic infant task (i.e.,
Piaget’s A-​not-​B task). Spectral plots of the frontal EEG leads (F3, F4) were created for
each infant’s monthly EEG recording for a total of 91 frontal spectral plots. At each age
the plots revealed a dominant frequency around 6–​9 Hz. More importantly, the plots
revealed month-​to-​month changes in the peak frequency for some infants. The spectral
plots from one infant in our Bell and Fox (1992) data set are shown in Figure 13.1. The
four spectral plots represent this infant’s EEG data at F3 and F4 from 8 until 11 months of
age. One can observe a peak frequency at 7 Hz in the EEG recording made at 8 months
of age and the sharing of peak frequency between 7 and 8 Hz at 9 months of age. In
the 10-​month recording, peak frequency appears to be shifting toward 8 Hz, whereas at
11 months of age there is only one peak at 8 Hz. These spectral plots demonstrate a def-
inite shift in peak frequency on a month-​to-​month basis during infancy. They also show
a shift in this overall dominant frequency band from 5–​9 Hz at 8 months to 6–​10 Hz at
11 months for this one infant. After examining all 91 spectral plots, we determined that
6–​9 Hz frequency band captured the dominant frequency in this sample of infants.
Our selection of the 6–​9 Hz frequency band as dominant in our infant longitudinal
study was replicated and extended to early childhood by Marshall and colleagues (2002)
with a longitudinal data set that included recordings of baseline EEG from a group of
29 children at 5, 10, 14, 24, and 51 months of age. They reported a peak frequency in
the 6–​9 Hz band that emerged across multiple scalp locations. Although not evident
during the earliest recordings at 5 months of age, the 6–​9 Hz band was reliable across all
scalp locations by 10 months of age and continued to be the dominant frequency band
through the 51-​month EEG recordings. Thus, with each of these two small longitudinal
datasets, the 6–​9 Hz band contained infant and child peak frequency, much as adult
alpha band of 8–​13 Hz contains the typical mature peak frequency at 10 Hz, although
there are individual differences in specific peak during adulthood (Klimesch, 1999).
This section highlights our 6–​9 Hz alpha band research and selectively reviews other
work examining the alpha band’s relation to critical action-​perception, cognitive,
302    KIMBERLY CUEVAS and MARTHA ANN BELL

8 months 9 months

F3 F3
F4 F4

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
HERTZ HERTZ

10 months 11 months

F3 F3
F4 F4

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
HERTZ HERTZ

Figure 13.1  Month-​to-​month spectral plots from one infant. Note the change in peak fre-
quency from 8 to 11 months. The x-​axis is frequency in single hertz (Hz) bins and the y-​axis is
EEG power (mean square microvolts).
From the Bell & Fox, 1992 dataset.

and affective processes during early development. Although 6–​9 Hz oscillatory ac-
tivity has been linked to multiple aspects of early cognition, including future thinking
(Blankenship et al., 2018) and memory (Cuevas et al., 2012c), the most extensive area
of research has investigated emerging executive functions. Here, we provide a develop-
mental analysis of the characteristics and individual variations in alpha band activity in
association with action-​perception, executive, and affective processes.

13.3.1 Action-​Perception Processes
The functional properties of the mu and beta rhythms during motor movement were
established by early investigations with adults. A relatively recent area of inquiry in the
developmental literature has focused on these sensorimotor rhythms and their involve-
ment in action-​perception processes. Specifically, there is evidence that the mu and beta
rhythms exhibit “neural mirroring” properties: oscillatory activity is attenuated during
both action execution and observation (Lepage & Théoret, 2006; Liao et al., 2015).
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    303

Characterizing the conditions under which the sensorimotor mu and beta rhythms are
reactive has been an area of substantial interest for developmental research as neural
mirroring systems have been proposed to be involved in action understanding as well as
broader socio-​cognitive development (e.g., imitation; Marshall & Meltzoff, 2011).
Research with non-​ human primates has found evidence of neural mirroring
during the observation and execution of facial gestures in 1-​to 7-​day-​old rhesus ma-
caque monkeys (Ferrari et al., 2012). Subsequent work has revealed that early experi-
ence with the mother, as compared to nursery-​rearing, is associated with (1) greater mu
rhythm attenuation when observing facial gestures and (2) more frequent imitation of
these gestures (Vanderwert et al., 2015). These findings have been recently extended to
human infants, with 9-​month-​olds exhibiting attenuation of the mu rhythm during fa-
cial expression perception and production (Rayson et al., 2017). Further, variability in
9-​month mu rhythm reactivity was related to their mothers’ tendency to mirror their
facial gestures at 2 months of age, with more frequent maternal mirroring at 2 months
of age being associated with greater action perception mu attenuation at age 9 months.
Together, these findings highlight the biopsychosocial underpinnings of emerging
action-​perception processes.
Another line of research has examined the impact of children’s action experience on
the neural correlates of action perception. Recent evidence indicates that the effects of
early motor experience are evident shortly after birth. Newborn monkeys with more
frequent reaching attempts display greater beta rhythm reactivity when observing
goal-​directed reaching movements (Festante et al., 2018). Likewise, 9-​and 12-​month-​
old human infants with more advanced manual motor skills (e.g., reaching, grasping)
show enhanced mu rhythm attenuation during manual action perception (Cannon
et al., 2016; Upshaw et al., 2016; Yoo et al., 2016). Training paradigms have extended
these findings by controlling children’s short-​term motor or perceptual experience with
novel tools/​actions. In an action-​sound perception paradigm, 10-​month-​olds exhibited
greater mu rhythm attenuation when hearing sounds associated with actions that they
had received motor (active training), as compared to observational (passive training),
experience (Gerson et al., 2015). A recent extension of this work to 3-​to 6-​year-​olds has
revealed greater EEG indices of visual processing (occipital alpha attenuation) as chil-
dren observed tool-​use actions that they had received active training (Bryant & Cuevas,
2019). However, there were no experience-​related effects on sensorimotor rhythms,
indicating that their role in action understanding might vary depending on age and
context.
Other work has taken a broader perspective to consider whether individual
differences in motor system activation are related to aspects of socio-​cognitive de-
velopment. For instance, in the context of a goal-​directed reaching task, 7-​month-​
olds with greater mu rhythm attenuation were more likely to express the same goal
as an adult; thus, selecting the goal toy more often than the non-​goal toy (Filippi
et al., 2016). These early socially-​contingent behavioral and neural responses may
provide the foundation for more advanced socio-​cognitive skills that emerge during
early childhood. Recent evidence indicates that 3-​to 5-​year-​olds’ motor skills,
304    KIMBERLY CUEVAS and MARTHA ANN BELL

action-​representation abilities, and theory of mind (i.e., understanding others’ mental

states and their effects on behavior) are intricately linked for children with greater
mu rhythm reactivity when performing goal-​directed actions (Bowman et al., 2017).
Likewise, 4-​year-​olds with enhanced beta rhythm reactivity during action percep-
tion display more successful cooperation with peers (Endedijk et al., 2017). These
findings highlight the complexity of interrelations among action-​perception and
socio-​cognitive processes. Although sensorimotor rhythms were linked with socio-​
cognitive development, the precise nature of these associations (e.g., beta vs. mu
rhythm; action perception EEG vs. action execution EEG) varied. Additional work,
including systematic longitudinal and cross-​sectional investigations, are essential
next steps toward a comprehensive analysis of action-​perception processes and their
involvement in socio-​cognitive development.

13.3.2 Executive Processes
Executive function (EF) is an umbrella term that captures a wide array of higher-​order
cognitive processes—​working memory, inhibitory control, cognitive flexibility—​that
organize and coordinate behavior to support complex goal-​directed actions. This con-
struct has been a major focus of developmental research as proficiency in executive pro-
cessing is associated with optimal behavioral and academic outcomes (see Diamond,
2013 for review). EF emerges during the first postnatal year, with substantial advances
throughout childhood and beyond (see Bell & Cuevas, 2016; Cuevas et al., 2018, for
reviews). Individual differences in the developmental progression of EF are linked to
biopsychosocial factors, including frontal lobe development, temperament, and co-​
occurring socialization experiences. Here, we discuss our cross-​sectional and longitu-
dinal work examining associations between EF and both resting-​state and task-​related
EEG measures throughout early development.

13.3.2.1 EF and Resting-​State EEG

One approach to examining associations between EF and neural activity has been to
use measures of resting-​state (or baseline) EEG when participants are awake, calm, still,
and not engaged in cognitive tasks. Work with adults and older children accomplish
this by measuring EEG during conditions of eyes open and closed; developmentally ap-
propriate modifications to extend these procedures to infancy and early childhood typ-
ically include periods of “quiet visual attention” in which participants observe a visual
stimulus (e.g., bubbles or images on a screen; see Anderson & Perone, 2018 for review
and discussion). Resting-​stating measures are often associated with brain maturation
and provide information about neural oscillations when individuals are not involved in
active cognitive processing. Our EF work with infants and young children has focused
primarily on the 6–​9 Hz “alpha” band, unless otherwise stated (Table 13.1). Below, we re-
view findings using resting-​stating measures of EEG power (oscillatory amplitude) and
frontal intra-​hemisphere EEG coherence (functional connectivity between two cortical
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    305

Table 13.1 Overview of executive function and 6–​9 Hz EEG findings

EEG Power & Coherence Findings Infants Toddlers & Preschoolers

Resting-​state (baseline) EEG Bell & Fox, 1992, 1997; Perone et al. 2018;*
is associated with EF (task MacNeill et al. 2018 Wolfe & Bell, 2004
performance)
Changes in EEG during executive Bell, 2001, 2002; Bell & Wolfe, 2007;
processing (baseline-​to-​task Bell & Wolfe, 2007; Swingler et al., 2011
related changes) Cuevas & Bell, 2011;
Cuevas et al., 2012a, 2012d
Changes in EEG during increased Cuevas et al., 2012e Broomell & Bell, 2017;
inhibitory demands Cuevas et al., 2016
Executive processing-​related EEG Bell, 2001, 2002; 2012; Cuevas et al., 2016;
is associated with EF Cuevas et al., 2012a, 2012d Morasch & Bell, 2011;
Swingler et al., 2011;
Watson & Bell, 2013;
Wolfe & Bell, 2004, 2007a,
2007b
Resting-​state EEG is associated Broomell et al. 2019; Cuevas et al., 2012b
with future EF Kraybill & Bell, 2013

Note. * =​theta/​beta ratio.

regions; squared cross-​correlation of EEG power at two scalp electrodes; Thatcher

et al., 1986).
To examine executive processing during infancy, we have used the A-​not-​B task, a
variant of the delayed response task. Infants observe as a desirable object is hidden; their
gaze to the hiding location is broken during a brief delay interval; and then they search
for the toy (Bell & Adams, 1999; Cuevas & Bell, 2010). This task requires both working
memory (to maintain the item location in active memory) and inhibitory control (to
withhold responding to a previously rewarded location). Longitudinal and cross-​
sectional work has revealed that resting-​state frontal-​posterior power and coherence
are associated with infants’ task performance, including how long they can maintain
the object location in working memory (Bell & Fox, 1992, 1997; MacNeill et al., 2018).
Convergent evidence from diffusion tensor imaging (DTI) indicates that white matter
tract microstructure connecting frontal, parietal, and temporal regions is associated
with infants’ delayed response task performance (Short et al., 2013). Differences in
resting-​state oscillatory activity and neural networks that are evident during infancy
may have cascading effects on the developmental trajectory of EF. For instance, EEG
measures of infant resting-​state frontal power and frontal-​temporal coherence account
for variability in toddler and early childhood EF (Broomell et al., 2019; Kraybill &
Bell, 2013).
306    KIMBERLY CUEVAS and MARTHA ANN BELL

During early childhood, EF tasks require children to withhold prepotent responses

and/​or keep up with changing task rules (requiring cognitive flexibility and working
memory). In Stroop-​like tasks, children must do something that conflicts with their
natural tendencies, such as saying “day” when shown a picture of a moon (Day-​
Night task) or making a fist when shown a flat hand (Luria’s Hand game). In sorting
tasks (Dimensional Change Card Sort), children first place items in groups based on
one dimension (e.g., color), and then sort items based on another feature (e.g., shape).
Consistent with the infant findings, concurrent and predictive links between EF and
resting-​state frontal power are also evident during early childhood (Cuevas et al.,
2012b; Wolfe & Bell, 2004). A recent cross-​sectional investigation with 3-​to 9-​year-​olds
examined resting-​state oscillatory activity across multiple frequency bands, revealing
that variations in resting-​state frontal theta/​beta ratio are inversely related to EF per-
formance (Perone et al., 2018). Thus, in line with anticipated maturational changes in
“slow-​” versus “fast-​wave” rhythms (see Section 13.2), children with more beta oscilla-
tory resting-​state activity in comparison to theta activity, displayed enhanced execu-
tive processing. Taken together, these findings suggest that measures of resting-​state
activity and brain maturation in regions that support EF in older children and adults
(e.g., Klingberg, 2006) are associated with individual differences in infant and early
childhood EF.

13.3.2.2 Executive Processing-​Related EEG

Developmental investigations have also examined task-​ related changes in EEG
measures during executive processing in comparison to a baseline/​resting-​state, thus
providing information about changes in brain activation and organization as a function
of mental activity. Early childhood EF tasks are similar to the ones described earlier,
and looking versions of the infant A-​not-​B task are used to minimize motor artifacts (as
compared to reaching versions) (see Bell & Adams, 1999; Cuevas & Bell, 2010; Morasch
& Bell, 2011).
Longitudinal and cross-​sectional work indicates that infants and children exhibit
task-​related changes in EEG power and frontal intra-​hemisphere EEG coherence (e.g.,
Bell & Wolfe, 2007; Cuevas & Bell, 2011; Cuevas et al., 2012a). These findings have been
extended to characterize the impact of task difficulty on executive processing-​related
EEG. For example, 10-​month-​olds exhibit more frontal EEG coherence on reversal
trials of the A-​not-​B task that require both working memory and inhibitory control as
compared to nonreversal, working memory-​only trials (Cuevas et al., 2012e). Similarly,
4-​year-​olds display increases in frontal, temporal, and parietal EEG power in response to
added EF demands (i.e., Stroop vs. non-​Stroop Day-​Night task; Broomell & Bell, 2017);
although the scalp distribution of these changes was more widespread for boys than
girls despite equivalent task performance (Cuevas et al., 2016). These findings highlight
the importance of considering both neural and behavioral measures when examining a
particular construct, including the value of testing the role of potential moderators (e.g.,
sex, socio-​economic status, race/​ethnicity; see Gatzke-​Kopp, 2016 for discussion).
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    307

As with resting-​ state measures, executive processing-​ related EEG is associated

with variations in behavioral indicators of EF. Within-​subjects analyses have revealed
enhanced EEG power (6–​9 Hz) and frontal intra-​hemisphere EEG coherence (10–​13
Hz) during trials in which infants make correct, as opposed to incorrect, responses
(Bell, 2002; Cuevas et al., 2012d). Likewise, between-​ subjects comparisons indi-
cate: (a) different patterns of EEG power and coherence as a function of EF task per-
formance (Bell, 2001, 2012; Wolfe & Bell, 2004); and (b) that EEG power and coherence
measures are unique predictors of EF task performance (Bell, 2012; Cuevas et al., 2012a,
2016; Swingler et al., 2011; Watson & Bell, 2013). In sum, executive-​processing related
measures of EEG are informative of emerging executive processes, likely reflecting the
contributions from frontal-​parietal networks.

13.3.3 Affective Processes
Developmental evidence suggests that resting state 6-​9 Hz frontal EEG activation
patterns are associated with individual differences in general affective style from at least
4 or 5 months of age (e.g., Fox et al., 1992). Resting state frontal EEG patterns also dif-
ferentiate between infants born to women who experienced prenatal depression versus
nondepressed women as early one week after birth at the broader 3–​9 Hz band (e.g.,
Diego et al., 2010). These types of EEG findings are based on the measurement of frontal
alpha-​band EEG asymmetry, which highlights relative activation patterns between
homologous left and right frontal scalp electrodes. Specifically, right frontal asymmetry
reflects greater relative right frontal activation (i.e., lower EEG power values at right
hemisphere) and left frontal asymmetry reflects the opposite pattern.
Frontal EEG asymmetry is typically conceptualized as reflecting approach and
avoidance motivational tendencies across the lifespan (Coan & Allen, 2004; Harmon-​
Jones & Allen, 1998). During infancy and early childhood, frontal EEG asymmetry
is also associated with temperament-​ based differences in emotion reactivity and
emotion regulation (Fox, 1994). Thus, when examining resting state (or baseline) EEG,
left frontal asymmetry is linked to approach motivation, positive emotions (plus the
approach emotion of anger; Harmon-​Jones & Allen, 1998), and better emotion regula-
tion abilities. Right frontal asymmetry is associated with withdrawal motivation, nega-
tive emotions, and less skill at emotion regulation. Baseline frontal EEG asymmetry
patterns are conceptualized as trait or biomarker indicators of motivational and emotion
tendencies, whereas task-​related frontal EEG asymmetry patterns are considered to be
state indicators of reactivity and regulation (Allen & Reznik, 2015; Coan & Allen, 2004;
Diaz & Bell, 2012).
Developmental research has examined links between frontal alpha (6–​9 Hz) EEG
asymmetry and temperament, which is defined as biologically based individual
differences in emotion reactivity and emotion regulation (Rothbart & Bates, 2006).
Other work has used resting frontal EEG asymmetry in early development to pre-
dict later socioemotional outcomes. A third line of frontal EEG asymmetry research
308    KIMBERLY CUEVAS and MARTHA ANN BELL

includes parenting behaviors in examining both simple and complex links between
child trait asymmetry and later outcomes. We briefly discuss each of these three areas by
highlighting our research and selectively reviewing the work of others.

13.3.3.1 Temperament and Frontal EEG Asymmetry

Early research on frontal asymmetry and infant temperament focused on resting state
6-​9 Hz EEG recordings, with reports that 10-​month-​old infants with right frontal asym-
metry were more likely to later cry during maternal separation than infants with left
frontal asymmetry (Davidson & Fox, 1989). In a longitudinal study from 7 to 12 months
of age, infants with a longer latency to cry at maternal separation (i.e., did not cry until
25 seconds after mother left the room) had a pattern of left frontal asymmetry at each
age. In contrast, infants with a much shorter latency to cry from 7 to 12 months had a
pattern of symmetry or right frontal asymmetry across age (Fox et al, 1992).
State-​related frontal EEG asymmetry research captures frontal EEG asymmetry
during an emotion-​eliciting situation that captures infant emotion reactivity. These
studies report right frontal asymmetry during (a) the approach of a stranger at age
6 months (Buss et al., 2003), (b) presentation of scary masks at age 10 months (Diaz
& Bell, 2012), and (c) maternal restraint of infants’ arms at age 10 months (Gartstein
et al., 2014). Ten-​month-​old infants displaying felt smiles during the approach of their
mothers exhibited left frontal asymmetry; when those same infants displayed unfelt
smiles (i.e., smiles did not involve the action of orbicularis oculi) during the approach of
a stranger, they exhibited right frontal EEG asymmetry (Fox & Davidson, 1988).
As noted, resting frontal alpha EEG asymmetry is conceptualized as a trait—​a stable
marker of approach-​avoidance motivation. Stability can be seen across four measures
of frontal EEG asymmetry during a two-​year time period in a small group of first and
second graders (Poole et al., 2018). Work with a large community sample across a period
of four years, however, did not show a high level of stability for frontal asymmetry at
the group level, but did show a pattern of associations between frontal EEG asymmetry
and parent-​report of child temperament (Howarth et al., 2016). Specifically, in a sample
of children who came to the research lab at 10, 24, 36, and 48 months of age, parent re-
port of temperament-​based fear and activity level were highly correlated across infancy,
toddlerhood, and early childhood. Frontal EEG asymmetry scores were uncorrelated
across age; however, frontal EEG asymmetry at 10 months positively predicted child
activity level at age 24 months, suggesting a link between early left frontal asymmetry
and later approach temperament. Conversely, child fear at age 36 months negatively
predicted frontal EEG asymmetry at age 48 months, suggesting a link between early
avoidance temperament and later right frontal asymmetry. With this same sample and
considering developmental change at individual frontal EEG leads separately (i.e., not
asymmetry scores) from 5 to 72 months, different temperament-​frontal EEG patterns
emerged for girls and boys (Gartstein et al, 2019). Parent-​report of temperament re-
activity at 5 months of age and changes in frontal EEG power across age occurred in
later development for boys (after 24 months of age) and in earlier development for girls.
Furthermore, early left frontal EEG power at 6–​9 Hz predicted later change in right
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    309

hemisphere frontal EEG power for girls, whereas early right hemisphere EEG power
predicted subsequent later change in left hemisphere frontal EEG power for boys. These
findings might account for reports of sex differences in temperament and related be-
havior problems (e.g., Else-​Quest et al., 2006).

13.3.3.2 Frontal EEG Asymmetry and Socioemotional Outcomes

Although frontal EEG asymmetry might not be highly stable at the group level across
the early years, it is the case that some children do exhibit stable asymmetry patterns.
Infants with stable left or right frontal 6–​9 Hz EEG asymmetry at age 10 and 24 months
were high in parent-​rated externalizing or internalizing behaviors at age 30 months, re-
spectively (Smith & Bell 2010). Infants who changed from left to right, or vice versa, were
rated between the two stable groups on both internalizing and externalizing behaviors.
Likewise, work with older children, 6-​year-​olds who had four EEG recordings across
two years, identified stable left and stable right frontal alpha EEG asymmetry groups
(10–​13 Hz; Poole et al., 2018). Parent-​report, child-​report, and child self-​presentation
behaviors were assessed for approach-​avoidance tendencies. As predicted, the stable
left group had higher approach-​related behavioral tendencies, whereas the stable right
group had higher avoidance-​related tendencies. Both studies highlight that stability in
frontal EEG asymmetry may be implicated in later behavior problems.
Importantly, one-​time frontal EEG asymmetry measures are informative of future
outcomes. Temperamental negative affectivity during infancy is related to regulatory
problems during toddlerhood only for children with right frontal EEG asymmetry
during infancy (Smith et al., 2016). Infant negativity is not associated with later regu-
latory problems for children with left frontal asymmetry. A similar pattern is seen
with older children. Children with right frontal EEG asymmetry at 4 years of age show
greater physiological arousal during a self-​presentation task at 9 years of age and have
greater problems with emotion regulation according to parent report (Hannesdottir
et al., 2010). In sum, although not stable for all children, early frontal EEG asymmetry
can predict later child outcomes in the socio-​emotional domain.

13.3.3.3 Parenting and Child Frontal EEG Asymmetry

Previously we noted EEG research that examines frontal asymmetry in context. There is
no more important context than the parenting environment. Women with depression
exhibit right frontal alpha EEG asymmetry during baseline recordings (e.g., Henriques
& Davidson, 1990) and so do their infants (e.g., Dawson et al., 1997). If the women are
depressed while pregnant, then their infants exhibit right frontal asymmetry by 1 week
of age (Diego et al., 2010). For older infants, prenatal depression and infant frontal EEG
asymmetry are linked only for women with postpartum depression as well, with asym-
metry stable from 3 to 6 months of age (Lusby et al., 2014).
It is not only maternal depression that is correlated with child frontal EEG asymmetry
scores; it is also maternal behavior. We hyperscanned mothers and their 3-​year-​old chil-
dren while they played together with puzzles. Mothers who were high in behaviorally
coded negativity while playing with their children had children with right frontal asym-
metry after controlling for child’s own negativity. Conversely, children who exhibited
310    KIMBERLY CUEVAS and MARTHA ANN BELL

challenging and negative behaviors while playing with mothers had mothers with right
frontal EEG asymmetry after controlling for mother’s own negativity (Atzaba-​Poria
et al., 2017). Thus, mother and child frontal EEG asymmetry patterns during dyadic
recordings are influenced by partner’s level of negativity.
Although there exist associations between frontal 6-​9 Hz EEG asymmetry and some
aspect of emotion during infancy and early childhood (and beyond), the link between
frontal asymmetry and emotion is likely more than a simple association, as we have
described them here. It may be that frontal EEG asymmetry is either a mediator or a
moderator of emotion (Coan & Allen, 2004; Reznick & Allen, 2018). Two examples from
our own work highlight frontal asymmetry as a moderator. Resting frontal EEG asym-
metry was recorded in a large group of 5-​month-​old infants. Behavioral coding included
mothers’ responsive behaviors during free play with her infant, as well as infants’ regula-
tory behaviors and level of negativity during the arm restraint procedure where mother
faces her infant and prevents the infant from moving his/​her arms. Maternal responsive
behaviors during free play with infants prior to the arm restraint procedure predicted
infant regulatory behaviors for infants with left frontal asymmetry but predicted infant
negativity for infants with right frontal asymmetry (Swingler et al., 2014). Thus, the same
maternal behavior is associated with different infant regulatory behaviors depending on
infant frontal EEG asymmetry pattern, suggesting an advantage for infants with both
left frontal EEG asymmetry and an environment with responsive parenting.
In this same large group of infants, we examined age 5-​month frontal EEG asymmetry
as a moderator of the link between maternal behavior and child negative affect at age
24 months. Maternal sensitive and responsive behaviors at age 5 months were associated
with less toddler negative affect only for children who also had left frontal EEG asymmetry
at age 5 months. The same pattern held when examining maternal behaviors at 24 months
of age (Diaz et al., 2019). We interpreted this to mean that the level of toddler negative
affect is influenced by the child’s own neurophysiology as well as the parenting context.
In sum, frontal alpha EEG asymmetry, conceptualized as approach-​avoidance mo-
tivation, has been examined in studies of temperament, socio-​emotional outcomes, and
parenting. The underlying neurological basis for frontal EEG asymmetry is typically
focused on reciprocal metabolic connections between prefrontal cortex and the amyg-
dala. Activation of the right amygdala is associated with increased dispositional (i.e.,
temperament-​based) negative affect (Abercrombie et al., 1998); conversely, individuals
with greater left frontal metabolic rate exhibit decreased amygdala activation and thus
decreased negative affect (Davidson, 2001). Although frontal EEG asymmetry does not
measure amygdala activity, it may be measuring the frontal cortical activation linked
with amygdala connectivity.

13.3.4 Differential Functions of 6–​9 Hz Activity

during Cognitive and Affective Processing
There appear to be two patterns for 6–​9 Hz activity during infancy and early childhood.
In studies of affective processes, decreases in EEG power values in one hemisphere
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    311

relative to the other are associated with emotion reactivity or emotion regulation. In
studies of cognition, increases in EEG power values are associated with higher levels
of performance on cognitive tasks. In the adult EEG literature, researchers have long
focused on the 8–​13 Hz peak in the adult spectrum. It is commonly reported that alpha
activity (8–​13 Hz) exhibits desynchronization (decreased power values) during increased
cortical processing (cognitive, affective), although there are some reports of alpha syn-
chronization (increased power values) during long-​term memory tasks (Klimesch et al.,
1999). There are also suggestions that alpha power is related to an inhibitory filter that is
reflected in alpha synchronization (Klimesch, 2012).
Researchers have noted that adult theta activity (4–​7 Hz) exhibits synchronization
during memory and attention tasks (e.g., Burgess & Gruzelier, 2000; Klimesch, 1999).
Thus, for the mature EEG signal, unique patterns of fluctuations in power levels at the
defined frequency bands are associated with different types of cognitive processing
(Cavanaugh, 2019). This type of information is lacking with respect to the EEG signal
recorded from infants and young children. Currently, it appears that infant and child
6–​9 Hz alpha behaves like adult theta or adult alpha depending on the type of cogni-
tive processing, and definitely behaves like adult alpha during affective processing
(Anderson & Perone, 2018; Bell & Cuevas, 2012; Saby & Marshall, 2012). Systematic de-
velopmental research is needed to understand the neurophysiological and functional
significance of infant and child alpha at 6–​9 Hz.

13.4  Broader impact and

future directions

The brain’s electrical activity consists of multiple, co-​occurring oscillatory rhythms that
underlie neural computation, communication, and transmission of information be-
tween brain networks—​functions critical to simple and complex brain processes (Lopes
da Silva, 2013). Transient interactions among neural rhythms are critical for the coord-
ination of neural, cognitive, affective, and behavioral processes (Jensen & Colgin, 2007);
yet, holistic ontogenetic analysis is largely missing from the field. As shown throughout
this chapter, developmental analyses of EEG rhythms typically focus on a single oscil-
latory rhythm either cross-​sectionally or at a particular age. These approaches preclude
integrative analysis of co-​occurring oscillatory rhythms, including associated ontogen-
etic changes in neural activity.
The current review focused on individual frequency bands during early develop-
ment, with emphasis on the infant and child alpha 6–​9 Hz band. We were among the
first to emphasize this particular frequency band, based on spectral plots of our ini-
tial infant longitudinal study (Figure 13.1; Bell & Fox, 1992). Stroganova and colleagues
(1999) were among the first to label 6–​9 Hz as “alpha” based on their spectral plots of the
spatial and amplitude properties of this frequency band when infants were in a room
312    KIMBERLY CUEVAS and MARTHA ANN BELL

with lights turned off compared with quiet alert baseline. More recently, developmental
investigations of the central 6–​9 Hz band have identified functional properties of the
mu rhythm during action perception and execution (see Cuevas et al., 2014, for review).
Furthermore, resting-​state 6–​9 Hz alpha rhythm measures are associated with con-
current and future affective, cognitive, and motor processes during infancy and early
childhood (see Anderson & Perone, 2018, for review). Despite the potential functional
significance of alpha (and gamma) resting-​state activity, relatively little is known about
other co-​occurring resting-​state oscillatory rhythms, such as theta and beta frequency
bands. In sum, what is missing is systematic examination of the alpha family frequency
in conjunction with other co-​occurring oscillatory rhythms to aid our understanding of
their frequency signatures, spatial topography, and functional significance, all within a
developmental time course.
Klimesch (2012) proposed that the alpha rhythm plays a central role in inhibition
and timing of brain activity, and thus may be importantly involved in activity at other
frequency bands. Accordingly, he proposed that for adult EEG, other frequency bands
are best defined by a frequency architecture focused on the alpha band and its activity.
Because alpha is a central process in modulating resting state and task behaviors in the
awake brain, the best way to understand frequency bands is by examining bands that
have a harmonic mean with alpha. The neurophysiology literature is missing this type of
functional thinking about alpha from a developmental point of view.
At the same time, there is increasing interest in how multiple oscillatory rhythms
interact to produce complex brain functions. Cross-​frequency coupling and band
power ratios are example measures that permit more integrative analysis of resting-​state
EEG as well as during cognitive, perceptual, affective, and motor processes. Their ap-
plication in the developmental literature has been limited to date (e.g., Brooker et al.,
2016; Perone et al., 2018; Stamoulis et al., 2015), but they provide a promising avenue
for understanding ontogenetic changes in neural oscillations and corresponding brain-​
behavior associations (e.g., Brooker et al., 2021).
Finally, there have been recent initiatives aimed at enhancing the interpretability
and scientific rigor of pediatric EEG. One line of work has focused on factors related
to attrition and EEG data loss for developmental samples with recommendation for
the field (e.g., van der Velde & Junge, 2020). Concurrently, efforts to establish standard
automated, freely-​available, data preprocessing pipelines designed specifically for pedi-
atric EEG (e.g., MADE and HAPPE) are promising in terms of increasing the amount of
useable data as well as improving reliability and cross-​lab comparisons (Debnath et al.,
2020; Gabard-​Durnam et al., 2018). Furthermore, recent evidence suggests that analysis
of infant and child oscillatory rhythms will be enhanced via techniques that extract the
periodic and aperiodic (1/​f) components from the neural power spectra (Cellier et al.,
2021; Schaworonkow & Voytek, 2021). Even with the aforementioned strategies, analysis
of the psychometric properties of developmental EEG measures (e.g., longitudinal sta-
bility, reliability, validity) highlights important considerations for pediatric data (Anaya
et al., 2021; Vincent et al., 2021). At a time of pre-​registration and open-​access initiatives,
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    313

we are particularly excited about the widespread effects these methodological, theoret-
ical, and analytical approaches will have on the field.

Related Topics

Alpha Activity for Inhibiting Distractors to Facilitate Attention and Memory

Asymmetric Activation of the Frontal Cortices
Cross-​Frequency/​Phase-​Amplitude Coupling
Development Across Adolescence and early Adulthood
Frequency Activity over the Motor Cortex: Alpha, Beta, and Mu Suppression
Theta Activity in Working Memory and Performance Monitoring
Acknowledgements: Preparation of this manuscript was supported by Research
Excellence Program, University of Connecticut (Cuevas) and College of Science Faculty
Fellowship, Virginia Tech (Bell). Much of our research highlighted in this chapter
was supported by grants R01 HD049878 and R03 HD043057 (PI: M. A. Bell) from the
Eunice Kennedy Shriver National Institute of Child Health and Human Development
(NICHD). The content of this manuscript is solely the responsibility of the authors and
does not necessarily represent the official views of the NICHD or the National Institutes
of Health.

References
Abercrombie, H. C., Schaefer, S. M., Larson, K. L., Oakes, T. R., Lindgre, K. A., . . . Davidson, R.
J. (1998). Metabolic rate in the right amygdala predicts negative affect in depressed patients.
NeuroReport, 9, 3301–​3307.
Allen, J. J. B. & Reznik, S. J. (2015). Frontal EEG asymmetry as a promising marker of depression
vulnerability: Summary and methodological considerations. Current Opinion in Psychology,
4, 93–​97. https://​doi.org/​10.1016/​j.cop​syc.2014.12.017
Anaya, B., Ostlund, B., LoBue, V., Buss, K., & Pérez-​Edgar, K. (2021). Psychometric properties
of infant electroencephalography: Developmental stability, reliability, and construct val-
idity of frontal alpha asymmetry and delta-​beta coupling. Developmental Psychobiology, 63,
e22178. https://​doi.org/​10.1002/​dev.22178
Anderson, A. J. & Perone, S. (2018). Developmental change in the resting state electroenceph-
alogram: Insights into cognition and the brain. Brain and Cognition, 126, 40–​52. https://​doi.
org/​10.1016/​j.bandc.2018.08.001
Atzaba-​Poria, N., Deater-​Deckard, K., & Bell, M. A. (2017). Mother-​child interaction: Links
between mother and child frontal electroencephalograph asymmetry and negative be-
havior. Child Development, 88, 544–​554. doi:10.111/​cdev.12583
Başar, E. (2013). A review of gamma oscillations in healthy subjects and in cognitive impair-
ment. International Journal of Psychophysiology, 90, 99–​117. http://​dx.doi.org/​10.1016/​j.ijpsy​
cho.2013.07.005
314    KIMBERLY CUEVAS and MARTHA ANN BELL

Begus, K. & Bonawitz, E. (2020). The rhythm of learning: Theta oscillations as an index of
active learning in infancy. Developmental Cognitive Neuroscience, 45, 100810. https://​doi.
org/​10.1016/​j.dcn.2020.100​810
Begus, K., Southgate, V., & Gliga, T. (2015). Neural mechanisms of infant learning: differences
in frontal theta activity during object exploration modulate subsequent object recognition.
Biology Letters, 11, 20150041. http://​dx.doi.org/​10.1098/​rsbl.2015.0041
Bell, M. A. (2001). Brain electrical activity associated with cognitive processing during a
looking version of the A-​not-​B task. Infancy, 2, 311–​330.
Bell, M. A. (2002). Power changes in infant EEG frequency bands during a spatial working
memory task. Psychophysiology, 39, 450–​458.
Bell, M. A. (2012). A psychobiological perspective on working memory performance at 8 months
of age. Child Development, 83, 251–​265. http://​dx.doi.org/​10.1111/​j.1467-​8624.2011.01684.x
Bell, M. A. & Adams, S. E. (1999). Comparable performance on looking and reaching versions
of the A-​not-​B task at 8 months of age. Infant Behavior and Development, 22, 221–​235.
Bell, M. A. & Cuevas, K. (2012). The use of EEG to study cognitive development: Issues and
practices. Journal of Cognition and Development, 13, 281–​294. http://​dx.doi.org/​10.1080/​
15248​372.2012.691​143
Bell, M. A. & Cuevas, K. (2016). Psychobiology of executive function in early development.
In J. A. Griffin, P. McCardle, & L. S. Freund (Eds.), Executive function in preschool-​age chil-
dren: Integrating measurement, neurodevelopment, and translational research (pp. 157–​179).
APA Press. http://​dx.doi.org/​10.1037/​14797-​008
Bell, M. A. & Fox, N. A. (1992). The relations between frontal brain electrical activity and cog-
nitive development during infancy. Child Development, 63, 1142–​1163.
Bell, M. A. & Fox, N. A. (1997). Individual differences in object permanence performance at
8 months: Locomotor experience and brain electrical activity. Developmental Psychobiology,
31, 287–​297.
Bell, M. A. & Wolfe, C. D. (2007). Changes in brain functioning from infancy to early
childhood: Evidence from EEG power and coherence during working memory tasks.
Developmental Neuropsychology, 31, 21–​38.
Benasich, A. A., Gou, Z., Choudhury, N., & Harris, K. D. (2008). Early cognitive and language
skills are linked to resting frontal gamma power across the first 3 years. Behavioural Brain
Research, 195, 215–​222. doi:10.1016/​j.bbr.2008.08.049
Berchicci, M., Zhang, T., Romero, L., Peters, A., Annett, R., Teuscher, U., . . . Comani, S. (2011).
Development of mu rhythm in infants and preschool children. Developmental Neuroscience,
33, 130–​143. doi:10.1159/​000329095
Berger, H. (1929). Über das Elektrenkephalogramm des Menschen. Archiv für Psychiatrie und
Nervenkrankheiten, 87, 527–​570.
Berger, H. (1932). Über das Elektroenzephalogramm des Menschen. Fünfter Bericht. Archiv für
Psychiatrie und Nervenkrankheiten, 98, 231–​254.
Blankenship, T. L., Broomell, A. P. R., & Bell, M. A.(2018). Semantic future thinking and execu-
tive functions at age 4: The moderating role of frontal brain electrical activity. Developmental
Psychobiology, 60, 608–​614. https://​doi.org/​10.1002/​dev.21629
Bowman, L. C., Thorpe, S. G., Cannon, E. N., & Fox, N. A. (2017). Action mechanisms for social
cognition: Behavioral and neural correlates of developing Theory of Mind. Developmental
Science, 20, e12447. https://​doi.org/​10.1111/​desc.12447
Braithwaite, E. K., Jones, E. J. H., Johnson, M. H., & Holmboe, K. (2020). Dynamic modu-
lation of frontal theta power predicts cognitive ability in infancy. Developmental Cognitive
Neuroscience, 45, 100818. https://​doi.org/​10.1016/​j.dcn.2020.100​818
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    315

Brito, N. H., Fifer, W. P., Myers, M. M., Elliott, A. J., & Noble, K. G. (2016). Associations
among family socioeconomic status, EEG power at birth, and cognitive skills during in-
fancy. Developmental Cognitive Neuroscience, 19, 144–​151. http://​dx.doi.org/​10.1016/​
j.dcn.2016.03.004
Brooker, R. J., Mistry-​Patel, S., Kling, J. L., & Howe, H. A. (2021). Deriving within-​person
estimates of delta-​beta coupling: A novel measure for identifying individual differences in
emotion and neural function in childhood. Developmental Psychobiology, 63, e22172. https://​
doi.org/​10.1002/​dev.22172
Brooker, R. J., Phelps, R. A., Davidson, R. J., & Goldsmith, H. H. (2016). Contextual
differences in delta beta coupling are associated with neuroendocrine reactivity in infants.
Developmental Psychobiology, 58, 406–​418. doi:10.1002/​dev.21381
Broomell, A. P. R. & Bell, M. A. (2017). Inclusion of a mixed condition makes the day/​night
task more analogous to the adult Stroop. Developmental Neuropsychology, 42, 241–​252.
doi:10.1080/​87565641.2017.1309655
Broomell, A. P. R., Salva, J., & Bell, M. A. (2019). Infant electroencephalogram coherence and
toddler inhibition are associated with social responsiveness at age 4. Infancy, 24, 43–​56.
doi:10.1111/​infa.12273
Bryant, L. J. & Cuevas, K. (2019). Effects of active and observational experience on EEG activity
during early childhood. Psychophysiology, 56, e13360. https://​doi.org/​10.1111/​psyp.13360
Burgess, A. P. & Gruzelier, J. H. (2000). Short duration power changes in the EEG during
recognition memory for words and faces. Psychophysiology, 37, 596–​606. https://​doi.org/​
10.1111/​1469-​8986.3750​596
Buss, K. A., Schumacher, J. R. M., Dolski, I., Kalin, N. H., Goldsmith, H. H., & Davidson R.
J. (2003). Right frontal brain activity, cortisol, and withdrawal behavior in 6-​month-​old
infants. Behavioral Neuroscience, 117, 11–​20. doi:10.1037/​0735-​7044.117.1.11
Cannon, E. N., Simpson, E. A., Fox, N. A., Vanderwert, R. E., Woodward, A. L., & Ferrari, P. F.
(2016). Relations between infants’ emerging reach-​grasp competence and event-​related de-
synchronization in EEG. Developmental Science, 19, 50–​62. https://​doi.org/​10.1111/​desc.12295
Cavanaugh, J. F. (2019). Electrophysiology as a theoretical and methodological hub for the
neural sciences. Psychophysiology, 56, e13314. https://​doi.org/​10.1111/​psyp.13314
Cellier, D., Riddle, J., Petersen, I., & Hwang, K. (2021). The development of theta and alpha
neural oscillations from ages 3 to 34 years. Developmental Cognitive Neuroscience, 50,
100969. https://​doi.org/​10.1016/​j.dcn.2021.100​969
Cheyne, D., Jobst, C., Tesan, G., Crain, S., & Johnson, B. (2014). Movement-​ related
neuromagnetic fields in preschool age children. Human Brain Mapping, 35, 4858–​4875.
doi:10.1002/​hbm.22518
Coan, J. A. & Allen, J. J. B. (2004). Frontal EEG asymmetry as a moderator and mediator of
emotion. Biological Psychology, 67, 7–​50. https://​doi.org/​10.1016/​j.biopsy​cho.2004.03.002
Crone, N. E., Miglioretti, D. L., Gordon, B., Sieracki, J. M., Wilson, M. T., Uematsu,
S., & Lesser, R. P. (1998). Functional mapping of human sensorimotor cortex with
electrocorticographic spectral analysis. I. Alpha and beta event-​related desynchron-
ization. Brain, 121, 2271–​2299.
Csibra, G., Davis, G., Spratling, M. W., & Johnson, M. H. (2000). Gamma oscillations and ob-
ject processing in the infant brain. Science, 290, 1582–​1585. doi:10.1126/​science.290.5496.1582
Cuevas, K. & Bell, M. A. (2010). Developmental progression of looking and reaching perform-
ance of the A-​not-​B task. Developmental Psychology, 46, 1363–​1371. http://​dx.doi.org/​10.1037/​
a0020​185
316    KIMBERLY CUEVAS and MARTHA ANN BELL

Cuevas, K. & Bell, M. A. (2011). EEG and ECG from 5 to 10 months of age: Developmental
changes in baseline activation and cognitive processing during a working memory task.
International Journal of Psychophysiology, 80, 119–​128. http://​dx.doi.org/​10.1016/​j.ijpsy​
cho.2011.02.009
Cuevas, K., Bell, M. A., Marcovitch, S., & Calkins, S. D. (2012a). EEG and heart rate measures of
working memory at 5 and 10 months of age. Developmental Psychology, 48, 907–​917. http://​
dx.doi.org/​10.1037/​a0026​448
Cuevas, K., Calkins, S. D., & Bell, M. A. (2016). To Stroop or not to Stroop: Sex-​related
differences in brain-​behavior associations during early childhood. Psychophysiology, 53, 30–​
40. http://​dx.doi.org/​10.1111/​psyp.12464
Cuevas, K., Cannon, E. N., Yoo, K., & Fox, N. A. (2014). The infant EEG mu
rhythm: Methodological considerations and best practices. Developmental Review, 34, 26–​
43. http://​dx.doi.org/​10.1016/​j.dr.2013.12.001
Cuevas, K., Hubble, M., & Bell, M. A. (2012b). Early childhood predictors of post-​kindergarten
executive function: Behavior, parent-​report, and psychophysiology. Early Education and
Development, 23, 59–​73. http://​dx.doi.org/​10.1080/​10409​289.2011.611​441
Cuevas, K., Raj, V., & Bell, M. A. (2012c). A frequency band analysis of two-​year-​olds’ memory
processes. International Journal of Psychophysiology, 83, 315–​322. http://​dx.doi.org/​10.1016/​
j.ijpsy​cho.2011.11.009
Cuevas, K., Raj, V., & Bell, M. A. (2012d). Functional connectivity and infant spatial working
memory: A frequency band analysis. Psychophysiology, 49, 271–​280. http://​dx.doi.org/​
10.1111/​j.1469-​8986.2011.01304.x
Cuevas, K., Rajan, V., & Bryant, L. J. (2018). Emergence of executive function in infancy. In S. A.
Wiebe & J. Karbach (Eds.), Executive function: Development across the life span (pp. 11–​28).
Routledge.
Cuevas, K., Swingler, M. M., Bell, M. A., Marcovitch, S., & Calkins, S. D. (2012e). Measures
of frontal functioning and the emergence of inhibitory control processes at 10 months
of age. Developmental Cognitive Neuroscience, 2, 235–​243. http://​dx.doi.org/​10.1016/​
j.dcn.2012.01.002
Davidson, R. J. (2001). Toward a biology of personality and emotion. Annals of the New York
Academy of Sciences, 935, 191–​207.
Davidson, R. J. & Fox, N. A. (1989). Frontal brain asymmetry predicts infants’ response to
maternal separation. Journal of Abnormal Psychology, 98, 127–​131. https://​doi.org/​10.1037/​
0021-​843X.98.2.127
Dawson, G., Frey, K., Panagiotides, H., Osterling, J., & Hessl, D. (1997). Infants of depressed
mothers exhibit atypical frontal brain activity: A replication and extension of previous
findings. Journal of Child Psychology and Psychiatry, 38, 179–​186. https://​doi.org/​10.1111/​
j.1469-​7610.1997.tb01​852.x
Debnath R., Buzzell G. A., Morales S., Bowers M. E., Leach S. C., Fox N. A. (2020). The
Maryland analysis of developmental EEG (MADE) pipeline. Psychophysiology, 57, e13580.
https://​doi.org/​10.1111/​psyp.13580
Diamond, A. (2013). Executive functions. Annual Review of Psychology, 64, 135–​168. http://​
dx.doi.org/​10.1146/​annu​rev-​psych-​113​011-​143​750
Diaz, A. & Bell, M. A. (2012). Frontal EEG asymmetry and fear reactivity in different contexts
at 10 months. Developmental Psychobiology, 54, 536–​545. doi:10.1002/​dev.20612
Diaz, A., Swingler, M. M., Tan, L., Smith, C. L., Calkins, S. D., & Bell, M. A. (2019). Infant
frontal EEG asymmetry moderates the association between maternal behavior and toddler
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    317

negative affectivity. Infant Behavior and Development, 55, 88–​99. https://​doi.org/​10.1016/​j.inf​

beh.2019.03.002
Diego, M. A., Field, T., Jones, N. A., & Hernandez-​Reif, M. (2006). Withdrawn and intrusive
maternal interaction style and frontal EEG asymmetry shifts in infants of depressed and
non-​depressed mothers. Infant Behavior and Development, 29, 220–​229. https://​doi.org/​
10.1016/​j.inf​beh.2005.12.002
Diego, M. A., Jones, N. A., & Field, T. (2010). EEG in 1-​week, 1-​month, and 3-​month-​old infants
of depressed and non-​depressed mothers. Biological Psychology, 83, 7–​14. https://​doi.org/​
10.1016/​j.biopsy​cho.2009.09.007
Else-​Quest, N. M., Hude, J. S., Goldsmith, H. H., & Van Hulle, C. A. (2006). Gender differences
in temperament: A meta-​analysis. Psychological Bulletin, 132, 33–​72. https://​doi.org/​10.1037/​
0033-​2909.132.1.33
Endedijk, H. M., Meyer, M., Bekkering, H., Cillessen A. H. N., & Hunnius, S. (2017). Neural
mirroring and social interaction: Motor system involvement during action observation
relates to early peer cooperation. Developmental Cognitive Neuroscience, 24, 33–​41. https://​
doi.org/​10.1016/​j.dcn.2017.01.001
Ferrari, P. F., Vanderwert, R. E., Paukner, A., Bower, S., Suomi, S. J., & Fox, N. A. (2012). Distinct
EEG amplitude suppression to facial gestures as evidence for a mirror mechanism in new-
born monkeys. Journal of Cognitive Neuroscience, 24, 1165–​1172.
Festante, F., Vanderwert, R. E., Sclafani, V., Paukner, A., Simpson, E. A., Suomi, S. J., . . . Ferrari,
P. F. (2018). EEG beta desynchronization during hand goal-​directed action observation in
newborn monkeys and its relation to the emergence of hand motor skills. Developmental
Cognitive Neuroscience, 30, 142–​149. https://​doi.org/​10.1016/​j.dcn.2018.02.010
Filippi, C. A., Cannon, E. N., Fox, N. A., Thorpe, S. G., Ferrari, P. F., & Woodward, A. L. (2016).
Motor system activation predicts goal imitation in 7-​month-​old infants. Psychological
Science, 27, 675–​684. doi:10.1177/​0956797616632231
Fox, N. A. (1994). Dynamic cerebral processes underlying emotion regulation. Monographs of
the Society for Research in Child Development, 59(2–​3), 152–​166. https://​psyc​net.apa.org/​doi/​
10.2307/​1166​143
Fox, N. A., Bell, M. A., & Jones, N. A. (1992). Individual differences in response to stress and
cerebral asymmetry. Developmental Neuropsychology, 8, 161–​184. https://​doi.org/​10.1080/​
875656​4920​9540​523
Fox, N. A. & Davidson, R. J. (1988). Patterns of brain electrical activity during facial signs of
emotion in 10-​month-​old infants. Developmental Psychology, 24, 230–​236. https://​doi.org/​
10.1037/​0012–​1649.24.2.230
Futagi, Y., Ishihara, T., Tsuda, K., Suzuki, Y., & Goto, M. (1998). Theta rhythms associated
with sucking, crying, gazing and handling in infants. Electroencephalography and Clinical
Neurophysiology, 106, 392–​399.
Gabard-​Durnam, L. J., Mendez Leal, A. S., Wilkinson, C. L., & Levin, A. R. (2018). The Harvard
automated processing pipeline for electroencephalography (HAPPE): Standardized pro-
cessing software for developmental and high-​artifact data. Frontiers in Neuroscience, 12(97),
1–​24. https://​doi.org/​10.3389/​fnins.2018.00097
Gaetz, W., MacDonald, M., Cheyne, D., & Snead, O. C. (2010). Neuromagnetic imaging of
movement-​related cortical oscillations in children and adults: Age predicts post-​movement
beta rebound. NeuroImage, 51, 792–​807. doi:10.1016/​j.neuroimage.2010.01.077
Gartstein, M. A., Bell, M. A., & Calkins, S. D. (2014). EEG asymmetry at 10 months of age: Are
temperament trait predictors different for boys and girls? Developmental Psychobiology, 56,
1327–​1340. https://​doi.org/​10.1002/​dev.21212
318    KIMBERLY CUEVAS and MARTHA ANN BELL

Gartstein, M. A., Hancock, G. R., Potapova, N. V., Calkins, S. D., & Bell, M. A. (2019). Modeling
development of frontal electroencephalogram (EEG) asymmetry: Sex differences and links
with temperament. Developmental Science, 23, e12891. https://​doi.org/​10.1111/​desc.12891
Gasser, T., Verleger, R., Bacher, P., & Sroka, L. (1988). Development of the EEG of school-​age
children and adolescents. I. Analysis of band power. Electroencephalography and Clinical
Neurophysiology, 69, 91–​99.
Gastaut, H., Dongier, M., & Courtois, G. (1954). On the significance of “wicket rhythms”
(“rythmes en arceau”) in psychosomatic medicine. Electroencephalography and Clinical
Neurophysiology, 6, 687.
Gatzke-​Kopp, L. M. (2016). Diversity and representation: Key issues for psychophysiological
science. Psychophysiology, 53, 3–​13. https://​doi.org/​10.1111/​psyp.12566
Gerson, S. A., Bekkering, H., & Hunnius, S. (2015). Short-​term motor training, but not obser-
vational training, alters neurocognitive mechanisms of action processing in infancy. Journal
of Cognitive Neuroscience, 27, 1207–​1214. https://​doi.org/​10.1162/​jocn_​a_​00​774
Ghim, H.-​R. (1990). Evidence for perceptual organization in infants: Perception of subjective
contours by young infants. Infant Behavior and Development, 13, 221–​248. https://​doi.org/​
10.1016/​0163-​6383(90)90032-​4
Gibbs, F. A. & Knott, J. R. (1949). Growth of the electrical activity of the cortex.
Electroencephalography and Clinical Neurophysiology, 1, 223–​229.
Gliga, T., Volein, A., & Csibra, G. (2010). Verbal labels modulate perceptual object processing
in 1-​year-​old children. Journal of Cognitive Neuroscience, 22, 2781–​2789.
Hagne, I. (1968). Development of the waking EEG in normal infants during the first year of life.
A longitudinal study including automatic frequency analysis. In P. Kellaway and I. Petersen
(Eds.), Clinical electroencephalography of children (pp. 97–​118). Grune & Stratton.
Hagne, I., Persson, J., Magnusson, R., & Petersen, I. (1973). Spectral analysis via fast Fourier
transform of waking EEG in normal infants. In P. Kellaway and I. Petersen (Eds.),
Automation of clinical electroencephalography (pp. 103–​143). Raven Press.
Hannesdottir, D. K., Doxie, J., Bell, M. A., Ollendick, T. H., & Wolfe, C. D. (2010). A longi-
tudinal study of emotion regulation and anxiety in middle childhood: Associations with
frontal EEG asymmetry in early childhood. Developmental Psychobiology, 52, 197–​204.
doi:10.1002/​dev.20425
Hari, R., & Salmelin, R. (1997). Human cortical oscillations: a neuromagnetic view through the
skull. Trends in Neurosciences, 20, 44–​49.
Harmon-​Jones, E. & Allen, J. J. B. (1998). Anger and frontal brain activity: EEG asymmetry con-
sistent with approach motivation despite negative affective valence. Journal of Personality
and Social Psychology, 74, 1310–​1316. https://​doi.org/​10.1037/​0022-​3514.74.5.1310
Henriques, J. B. & Davidson, R. J. (1990). Regional brain electrical asymmetries discriminate
between previously depressed and healthy control subjects. Journal of Abnormal Psychology,
99, 22–​31. https://​doi.org/​10.1037/​0021-​843X.99.1.22
Howarth, G. Z., Fettig, N. B., Curby, T. W., & Bell, M. A. (2016). Frontal electroencephalogram
asymmetry and temperament across infancy and early childhood: An exploration of sta-
bility and bidirectional relations. Child Development, 87, 465–​476. doi:10.1111/​cdev.12466
Jarvelainen, J., Schurmann, M., & Hari, R. (2004). Activation of the human primary
motor cortex during observation of tool use. NeuroImage, 23, 187–​ 192. doi:10.1016/​
j.neuroimage.2004.06.010
Jasper, H. H. & Andrews, H. L. (1938). Electro-​encephalography. III. Normal differenti-
ation of occipital and precentral regions in man. Archives of Neurology and Psychiatry, 39,
96–​115.
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    319

Jasper, H. & Penfield, W. (1949). Electrocorticograms in man: Effect of voluntary movement

upon the electrical activity of the precentral gyrus. Archiv für Psychiatrie und Zeitschrift
Neurologie, 183, 163–​174.
Jensen, O. & Colgin, L. L. (2007). Cross-​frequency coupling between neuronal oscillations.
Trends in Cognitive Sciences, 11, 267–​269.
Jones, E. J. H., Venema, K., Lowy, R., Earl, R. K., & Webb, S. J. (2015). Developmental changes in
infant brain activity during naturalistic social experiences. Developmental Psychobiology, 57,
842–​853. doi:10.1002/​dev.21336
Kaufman, J., Csibra, G., & Johnson, M. H. (2003). Representing occluded objects in the human
infant brain. Proceedings of the Royal Society of London. Series B: Biological Sciences (Suppl.),
270, S140–​S143. doi:10.1098/​rsbl.2003.0067
Kaufman, J., Csibra, G., & Johnson, M. H. (2006). Oscillatory activity in the infant brain
reflects object maintenance. Proceedings of the National Academy of Sciences of the United
States of America, 102, 15271–​15274. https://​doi.org/​10.1073/​pnas.050​7626​102
Klimesch, W. (1999). EEG alpha and theta oscillations reflect cognitive and memory per-
formance: A review and analysis. Brain Research Reviews, 29, 169–​ 195. doi:10.1016/​
S0165-​0173(98)00056-​3
Klimesch, W. (2012). Alpha-​band oscillations, attention, and controlled access to store infor-
mation. Trends in Cognitive Sciences, 16, 606–​617. doi:10.1016/​j.tics.2012.10.007
Klimesch, W., Doppelmayr, M., Schwaiger, J., Auinger, P., & Winkler, T. (1999).“Paradoxical”
alpha synchronization in a memory task. Cognitive Brain Research, 7, 493–​501. https://​doi.
org/​10.1016/​S0926-​6410(98)00056-​1
Klingberg, T. (2006). Development of a superior frontal-​intraparietal network for visuo-​spatial
working memory. Neuropsychologia, 44, 2171–​2177.
Köster, M., Langeloh, M., & Hoehl, S. (2019). Visually entrained theta oscillations increase for
unexpected events in the infant brain. Psychological Science, 30, 1656–​1663. https://​doi.org/​
10.1177/​09567​9761​9876​260
Kraybill, J. H. & Bell, M. A. (2013). Infancy predictors of preschool and post-​kindergarten
executive function. Developmental Psychobiology, 55, 530–​538. http://​dx.doi.org/​10.1002/​
dev.21057
Lehtonen, J., Valkonen-​Korhonen, M., Georgiadis, S., Tarvainen, M. P., Lappi, H., Niskanen, J.-​
P., . . . Karhalainen, P. A. (2016). Nutritive sucking induces age-​specific EEG-​changes in 0–​24
week-​old infants. Infant Behavior and Development, 45, 98–​108. http://​dx.doi.org/​10.1016/​
j.inf​beh.2016.10.005
Lepage, J. & Théoret, H. (2006). EEG evidence for the presence of an action observation-​
execution matching system in children. European Journal of Neuroscience, 23, 2505–​2510.
https://​doi.org/​10.1111/​j.1460-​9568.2006.04769.x
Liao, Y., Acar, Z. A., Makeig, S., & Deak, G. (2015). EEG imaging of toddlers during dyadic turn-​
taking: Mu-​rhythm modulation while producing or observing social actions. NeuroImage,
112, 52–​60. http://​dx.doi.org/​10.1016/​j.neu​roim​age.2015.02.055
Lindsley, D. B. (1938). Electrical potentials of the brain in children and adults. The Journal of
General Psychology, 19, 285–​306.
Lindsley, D. B. (1939). A longitudinal study of the occipital alpha rhythm in normal chil-
dren: Frequency and amplitude standards. The Journal of Genetic Psychology, 55,
197–​213.
Lopes da Silva, F. (2013). EEG and MEG: Relevance to neuroscience. Neuron, 80, 1112–​1128.
doi:10.1016/​j.neuron.2013.10.017
320    KIMBERLY CUEVAS and MARTHA ANN BELL

Lusby, C. M., Goodman, S. H., Bell, M. A., & Newport, D. J. (2014). Electroencephalogram
patterns in infants of depressed mothers. Developmental Psychobiology, 56, 459–​473.
doi:10.1002/​dev.21112
MacNeill, L. A., Ram, N., Bell, M. A., Fox, N. A., & Perez-​Edgar, K. (2018). Trajectories of
infants’ biobehavioral development: Timing and rate of A-​not-​B performance gains and
EEG maturation. Child Development, 89, 711–​724. doi:10.1111/​cdev.13022
Marshall, P. J., Bar-​Haim, Y., & Fox, N. A. (2002). Development of the EEG from 5 months to
4 years of age. Clinical Neurophysiology, 113, 1199–​1208.
Marshall, P. J. & Meltzoff, A. N. (2011). Neural mirroring systems: Exploring the EEG mu
rhythm in human infancy. Developmental Cognitive Neuroscience, 1, 110–​123. https://​doi.org/​
10.1016/​j.dcn.2010.09.001
Matsuura, M., Yamamoto, K., Fukuzawa, H., Okubo, Y., Uesugi, H., Moriiwa, M., . . . Shimazono,
Y. (1985). Age development and sex differences of various EEG elements in healthy chil-
dren and adults—​ Quantification by a computerized wave form recognition method.
Electroencephalography and Clinical Neurophysiology, 60, 394–​406.
Meyer, M., Braukmann, R., Stapel, J. C., Bekkering, H., & Hunnius, S. (2016). Monitoring
others’ errors: The role of the motor system in early childhood and adulthood. British
Journal of Developmental Psychology, 34, 66–​85. doi:10.1111/​bjdp.12101
Miskovic, V., Ma, X., Chou, C.-​A., Fan, M., Owens, M., Sayama, H., & Gibb, B. E. (2015).
Developmental changes in spontaneous electrocortical activity and network organization
from early to late childhood. NeuroImage, 118, 237–​247. http://​dx.doi.org/​10.1016/​j.neu​roim​
age.2015.06.013
Morasch, K. C. & Bell, M. A. (2011). The role of inhibitory control in behavioral and physio-
logical expressions of toddler executive function. Journal of Experimental Child Psychology,
108, 593–​606. https://​doi.org/​10.1016/​j.jecp.2010.07.003
Muthukumaraswamy, S. D. & Johnson, B. W. (2004). Changes in Rolandic mu rhythm
during observation of a precision grip. Psychophysiology, 41, 152–​ 156. doi:10.1046/​
j.1469-​8986.2003.00129.x
Nikitina, G. M., Posikera, I. N., & Stroganova, T. A. (1985). Central organization of emotional
reaction of infants during first year of life. Ontogenesis of the Brain, 4, 223–​227.
Ogawa, T., Sugiyama, A., Ishiwa, S., Suzuki, M., Ishihara, T., & Sato, K. (1984). Ontogenic devel-
opment of autoregressive component waves of waking EEG in normal infants and children.
Brain & Development, 6, 289–​303.
Orekhova, E. V., Stroganova, T. A., & Posikera, I. N. (1999). Theta synchronization during
sustained anticipatory attention in infants over the second half of the first year of life.
International Journal of Psychophysiology, 32, 151–​172.
Orekhova, E. V., Stroganova, T. A., Posikera, I. N., & Elam, M. (2006). EEG theta rhythm in
infants and preschool children. Clinical Neurophysiology, 117, 1047–​ 1062. doi:10.1016/​
j.clinph.2005.12.027
Ortiz-​Mantilla, S., Hamalainen, J. A., Realpe-​Bonilla, T., & Benasich, A. A. (2016). Oscillatory
dynamics underlying perceptual narrowing of native phoneme mapping from 6 to 12 months
of age. The Journal of Neuroscience, 36, 12095–​12105. doi:10.1523/​JNEUROSCI.1162-​16.2016
Paredes, M. F., James, D., Gil-​Perotin, S., Kim, H., Cotter, J. A., Ng, C., . . . Alvarez-​Buylla, A.
(2016). Extensive migration of young neurons into the infant human frontal lobe. Science,
354, aaf7073. doi:10.1126/​science.aaf7073
Paul, K., Dittrichova, J., & Papousek, H. (1996). Infant feeding behavior: Development in
patterns and motivation. Developmental Psychobiology, 29, 563–​576.
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    321

Perone, S., Palanisamy, J., & Carlson, S. M. (2018). Age-​related change in brain rhythms from
early to middle childhood: Links to executive function. Developmental Science, 21, e12691.
https://​doi.org/​10.1111/​desc.12691
Pfurtscheller, G., Brunner, C., Schlogel, A., & Lopes da Silva, F. H. (2006). Mu rhythm (de)
synchronization and EEG single-​ trial classification of different motor imagery tasks.
NeuroImage, 31, 153–​159. doi:10.1016/​j.neuroimage.2005.12.003
Pfurtscheller, G., Stančák, A., & Edlinger, G. (1997). On the existence of different types of cen-
tral beta rhythms below 30 Hz. Electroencephalography and Clinical Neurophysiology, 102,
316–​325.
Pivik R. T., Andres, A., Tennal, K. B., Gu, Y., Downs, H., Bellando, B. J. . . . Badger, T. M. (2019).
Resting gamma power during the postnatal critical period for GABAergic system develop-
ment is modulated by infant diet and sex. International Journal of Psychophysiology, 135, 73–​
94. https://​doi.org/​10.1016/​j.ijpsy​cho.2018.11.004
Pivik, R. T., Broughton, R. J., Coppola, R., Davidson, R. J., Fox, N. A., & Nuwer, M. R. (1993).
Guidelines for the recording and quantitative analysis of electroencephalographic activity
in research contexts. Psychophysiology, 30, 547–​558. https://​doi.org/​10.1111/​j.1469-​8986.1993.
tb02​081.x
Poole, K. L., Santesso, D. L., Van Lieshout, R. J., & Schmidt, L. A. (2018). Trajectories of frontal
brain activity and socio-​emotional development in children. Developmental Psychobiology,
60, 353–​363. doi:10.1002/​dev.21620
Rayson, H., Bonaiuto, J. J., Ferrari, P. F., & Murray, L. (2017). Early maternal mirroring predicts
infant motor system activation during facial expression observation. Scientific Reports, 7,
11738. doi:10.1038/​s41598-​017-​12097-​w
Reznik, S. J. & Allen, J. J. B. (2018). Frontal asymmetry as a mediator and moderator of
emotion: An updated review. Psychophysiology, 55, e12965. https://​doi.org/​10.1111/​psyp.12965
Rothbart, M. K., & Bates, J. E. (2006). Temperament. In W. Damon & R.M. Lerner (Series Eds.)
& N. Eisenberg (Vol. Ed.), Handbook of child psychology: Vol. 3. Social, emotional, and per-
sonality development, 6th ed. (pp. 99–​166). Wiley.
Saby, J. N. & Marshall, P. J. (2012). The utility of EEG band power analysis in the study of in-
fancy and early childhood. Developmental Neuropsychology, 37, 253–​273. https://​doi.org/​
10.1080/​87565​641.2011.614​663
Schaworonkow, N. & Voytek, B. (2021). Longitudinal changes in aperiodic and periodic ac-
tivity in electrophysiological recordings in the first seven months of life. Developmental
Cognitive Neuroscience, 47, 100895. https://​doi.org/​10.1016/​j.dcn.2020.100​895
Short, S. J., Elison, J. T., Goldman, B. D., Styner, M., Gu, H., Connelly, M., ... Gilmore, J. H.
(2013). Associations between white matter microstructure and infants’ working memory.
NeuroImage, 64, 156–​166. https://​doi.org/​10.1016/​j.neu​roim​age.2012.09.021
Smith, C. L. & Bell, M. A. (2010). Stability in infant frontal asymmetry as a predictor of toddler-
hood internalizing and externalizing behaviors. Developmental Psychobiology, 52, 158–​167.
doi:10.1002/​dev.20427
Smith, C. L., Diaz, A., Day, K. L., & Bell, M. A. (2016). Infant frontal electroencephalogram
asymmetry and negative emotional reactivity as predictors of toddlerhood effortful control.
Journal of Experimental Child Psychology, 142, 262–​273. doi:10.1016/​j.jecp.2015.09.031
Smith, J. R. (1938). The electroencephalogram during normal infancy and childhood: II. The
nature of the growth of the alpha waves. The Journal of Genetic Psychology, 53, 455–​469.
Smith, J. R. (1939). The “occipital” and “pre-​central” alpha rhythms during the first two years.
The Journal of Psychology, 7, 223–​226.
322    KIMBERLY CUEVAS and MARTHA ANN BELL

Smith, J. R. (1941). The frequency growth of the human alpha rhythms during normal infancy
and childhood. The Journal of Psychology, 11, 177–​198.
Stamoulis, C., Vanderwert, R. E., Zeanah, C. H., Fox, N. A., & Nelson, C. A. (2015). Early psy-
chosocial neglect adversely impacts developmental trajectories of brain oscillations and their
interactions. Journal of Cognitive Neuroscience, 27, 2512–​2528. doi:10.1162/​jocn_​a_​00877
Stroganova, T. A. & Orekhova, E. V. (2007). EEG and infant states. In M. de Haan (Ed.), Infant
EEG and event-​related potentials (pp. 251–​287). Psychology Press.
Stroganova, T. A., Orekhova, E. V., & Posikera, I. N. (1998). Externally and internally controlled
attention in infants: An EEG study. International Journal of Psychophysiology, 30, 339–​351.
Stroganova, T. A., Orekhova, E. V., & Posikera, I. N. (1999). EEG alpha rhythm in infants.
Clinical Neurophysiology, 110, 997–​1012.
Swingler, M. M., Perry, N. B., Calkins, S. D., & Bell, M. A. (2014). Maternal sensitivity and in-
fant response to frustration: The moderating role of EEG asymmetry. Infant Behavior &
Development, 37, 523–​535. doi:10.1016.j.infbeh.2014.06.010
Swingler, M. M., Willoughby, M. T., & Calkins, S. D. (2011). EEG power and coherence during
preschoolers’ performance of an executive function battery. Developmental Psychobiology,
53, 771–​784. doi:10.1002/​dev.20588
Takano, T. & Ogawa, T. (1998). Characterization of developmental changes in EEG-​gamma
band activity during childhood using the autoregressive model. Acta Paediatrica Japonica,
40, 446–​452.
Tarullo, A. R., Obradovic, J., Keehn, B., Rasheed, M. A., Siyal, S., Nelson, C. A., & Yousafzai,
A. K. (2017). Gamma power in rural Pakistani children: Links to executive function and
verbal ability. Developmental Cognitive Neuroscience, 26, 1–​8. http://​dx.doi.org/​10.1016/​
j.dcn.2017.03.007
Thatcher, R. W., Krause, P. J., & Hrybyk, M. (1986). Cortico-​ cortical associations and
EEG coherence: A two-​ compartmental model. Electroencephalography and Clinical
Neurophysiology, 64, 123–​143. https://​doi.org/​10.1016/​0013-​4694(86)90107-​0
Thorpe, S. G., Cannon, E. N., & Fox, N. A. (2016). Spectral and source structural development
of mu and alpha rhythms from infancy through adulthood. Clinical Neurophysiology, 127,
254–​269. http://​dx.doi.org/​10.1016/​j.cli​nph.2015.03.004
Tierney, A., Strait, D. L., O’Connell, S., & Kraus, N. (2013). Developmental changes in resting
gamma power from age three to adulthood. Clinical Neurophysiology, 124, 1040–​1042. http://​
dx.doi.org/​10.1016/​j.cli​nph.2012.09.023
Tomalski, P., Moore, D. G., Ribeiro, H., Axelsson, E. L., Murphy, E., Karmiloff-​Smith,
A., . . . Kushnerenko, E. (2013). Socioeconomic status and functional brain development –​
associations in early infancy. Developmental Science, 16, 676–​687. doi:10.1111/​desc.12079
Upshaw, M. B., Bernier, R. A., & Sommerville, J. A. (2016). Infants’ grip strength predicts
mu rhythm attenuation during observation of lifting actions with weighted blocks.
Developmental Science, 19, 195–​207. doi:10.1111/​desc.12308
van der Velde, B., & Junge, C. (2020). Limiting data loss in infant EEG: putting hunches to
the test. Developmental Cognitive Neuroscience, 45, 100809. https://​doi.org/​10.1016/​
j.dcn.2020.100​809
Vanderwert, R. E., Simpson, E. A., Paukner, A., Suomi, S. J., Fox, N. A., & Ferrari, P. F. (2015).
Early social experience affects neural activity to affiliative facial gestures in newborn
nonhuman primates. Developmental Neuroscience, 37, 243–​252. doi:10.1159/​000381538
Vincent, K. M., Xie, W., & Nelson, C. A. (2021). Using different methods for calculating
frontal alpha asymmetry to study its development from infancy to 3 years of age in a large
 EEG FREQUENCY DEVELOPMENT ACROSS INFANCY AND CHILDHOOD    323

longitudinal sample. Developmental Psychobiology, 63, e22163. https://​doi.org/​10.1002/​

dev.22163
Walter, V. J. & Walter, W. G. (1949). The central effects of rhythmic sensory stimulation.
Electroencephalography and Clinical Neurophysiology, 1, 57–​86.
Watson, A. J. & Bell, M. A. (2013). Individual differences in inhibitory control skills at three
years of age. Developmental Neuropsychology, 38, 1–​21. https://​doi.org/​10.1080/​87565​
641.2012.718​818
Whitford, T., Rennie, C. J., Grieve, S. M., Clark, C. R., Gordon, E., & Williams, L. M. (2007).
Brain maturation in adolescence: Concurrent changes in neuroanatomy and neurophysi-
ology. Human Brain Mapping, 28, 228–​237. doi:10.1002/​hbm.20273
Wolfe, C. D. & Bell, M. A. (2004). Working memory and inhibitory control in early
childhood: Contributions from physiology, temperament, and language. Developmental
Psychobiology, 44, 68–​83. doi:10.1002/​dev.10152
Wolfe, C.D., & Bell, M.A. (2007a). Sources of variability in working memory in early
childhood: A consideration of age, temperament, language, and brain electrical activity.
Cognitive Development, 22, 431–455.
Wolfe, C.D., & Bell, M.A. (2007b). The integration of cognition and emotion during infancy
and early childhood: Regulatory processes associated with the development of working
memory. Brain and Cognition, 65, 3–13.
Xie, W., Mallin, B. M., & Richards, J. E. (2018). Development of infant sustained attention and
its relation to EEG oscillations: an EEG and cortical source analysis study. Developmental
Science, 21, e12562. https://​doi.org/​10.1111/​desc.12562
Xu, G., Broadbelt, K. G., Haynes, R. L., Folkerth, R. D., Borenstein, N. S., Belliveau, R.
A. . . . Kinney, H. C. (2011). Late development of the GABAergic system in the human cere-
bral cortex and white matter. Journal of Neuropathology & Experimental Neurology, 70, 841–​
858. https://​doi.org/​10.1097/​NEN.0b013​e318​22f4​7 1c
Yoo, K. H., Cannon, E. N., Thorpe, S. G., & Fox, N. A. (2016). Desynchronization in EEG during
perception of means-​end actions and relations with infants’ grasping skill. British Journal of
Developmental Psychology, 34, 24–​37. https://​doi.org/​10.1111/​bjdp.12115
 CHAPTER 14

DEVEL OPMENTA L RE SE A RC H
ON TIME-​F RE QU E NC Y
ACTIVIT Y IN A D OL E S C E NC E
AND EARLY ADU LT H O OD

STEPHEN M. MALONE, JEREMY HARPER, AND

WILLIAM G. IACONO

The notion that any complex system depends critically on its history (D’Souza &
Karmiloff-​Smith, 2016) is central to a developmental perspective, which holds that the
state of an organism at any moment in its lifetime reflects its history, or trajectory in
developmental time. A full understanding of a human characteristic is only possible
through a systematic examination of how it came to be. The time-​frequency features
of an adult study participant’s response to target stimuli in a visual oddball task, for
instance, also reflect the current state of the dynamic interplay among genetic, bio-
logical, psychological, and external forces over time that have given rise to the psy-
chological and neural processes, motivational state, and personality characteristics
influencing activity recorded in the laboratory. Understanding the nature of this
interplay is critical to understanding the response, whether frontal theta or parietal
delta activity.
An approach informed by this type of perspective examines phenotypic variation
over time to ask questions about mechanisms underlying a psychological, behavioral,
or psychopathological process (Rutter, 1988). A developmental perspective on cogni-
tive control, for example, can help elucidate the mechanisms underlying it by examining
how time-​frequency features related to cognitive control develop over the course of the
lifespan. Discontinuities or inflection points in this process might reflect important
transitions, which can be exploited to test hypotheses about causal mechanisms. A de-
velopmental approach thus has the potential to inform us about how time-​frequency
features come about, as well as what those features are.
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     325

14.1  Advantages inherent in the

developmental study of
time-​frequency activity

A developmental approach confers several advantages.

14.1.1 Fine-​Grained Analysis
Although a developmental perspective offers a unique view of time-​frequency features,
developmental research on time-​frequency features can also offer purely pragmatic
advantages. Time-​ frequency decompositions of electroencephalographic (EEG)
signals into moment-​by-​moment activity at different frequencies lend themselves to a
fine-​grained analysis of brain activity, with accumbent advantages for developmental
research.

14.1.2 Tracking Developmental Change

Time-​frequency components correlate more strongly with age than time-​domain
components (Bowers et al., 2018). At the same time, change in time-​frequency
features correlates more strongly with change in time-​ domain characteristics
than participants’ chronological age (Yordanova & Kolev, 1996). In both instances,
then, time-​frequency activity appears to represent something particularly salient
developmentally.

14.1.3 Stability of Time-​Frequency Measures

Time-​frequency features may be more stable over time than ERP amplitudes (DuPuis
et al., 2015), which makes them particularly attractive for detecting change in an out-
come between two time points. This follows from the fact that statistical power in a
paired t-​test is a function in part of the standard error of the difference in means, which
is in turn a function of the correlation between measurements of the variable at the two
time points, σY 1−Y 2 = (σY 12 + σY 22 − 2ρ122 )1/2 , where σY 1−Y 2 is the standard error of the
difference in means, σY 12 is the variance at Time 1, σY12 is the variance at Time 2, and
ρ12 is the Time 1–​Time 2 correlation. Hence, holding sample and effect sizes constant,
the greater the Time 1–​Time 2 correlation (stability), the greater the power to detect
change.
326    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

35
40
Age 11 Age 11
30
Age 14 20
25
Age 17 0 Age 24
20
V)

0 500 1000 1500

Amplitude (

15
Age 20

10
Age 24
5

-5
-200 0 200 400 600 800 1000 1200 1400
Latency (ms)
Figure 14.1 Grand mean ERP waveforms across five assessment waves spanning
preadolescence to early adulthood. ERPs represent the average response to target stimuli at Pz
among subjects assessed longitudinally at target ages of 11, 14, 17, 20, and 24. ERPs for successive
assessment waves are progressively smaller in amplitude, with the ERP at age 11 being the largest
and the ERP at age 24 the smallest. The inset depicts the same ERPs for the age-​11 and age-​24
assessments only.

14.1.4 Insight into ERP Dynamics

Characterizing stability and change in time-​frequency features can help us to under-
stand the developmental course of event-​related potential (ERP) responses to experi-
mental events (Malone et al., 2021; Mathes et al., 2016; Yordanova & Kolev, 2008). In
Malone and colleagues (2021) we reported results of a longitudinal investigation into
time-​frequency activity in participants first assessed at the age of 11, with follow-​up
assessments at 3-​to 4-​year-​intervals to a target age of 24. Participants were administered
the oddball task at each assessment wave. Figure 14.1 depicts the grand-​average ERP
at Pz, the midline parietal electrode location, for the different assessment waves.
Amplitude of the ERP decreases monotonically across waves. The morphology of the
grand mean ERPs is broadly similar across waves, with an immediately recognizable
P3 component. Nevertheless, subtle change in ERP morphology across the different
assessments is evident as well. We examined the time-​frequency representation of trial-​
level EEG activity at each assessment wave, described in greater detail later. Figure 14.2
consists of false color maps (heatmaps) of the magnitude of time-​frequency activity at
each discrete time-​frequency bin for the features that best accounted for the EEG data at
each wave. The overall similarity in components is striking. Yet differences in structure
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     327

Age 11 Age 14 Age 17 Age 20 Age 24

6 6 6 6 6
4 4 4 4 4
2 2 2 2 2

0 500 1000 0 500 1000 0 500 1000 0 500 1000 0 500 1000

6 6 6 6 6
4 4 4 4 4
2 2 2 2 2

0 500 1000 0 500 1000 0 500 1000 0 500 1000 0 500 1000
Frequency (Hz)

6 6 6 6 6
4 4 4 4 4
2 2 2 2 2

0 500 1000 0 500 1000 0 500 1000 0 500 1000 0 500 1000

6 6 6 6 6
4 4 4 4 4
2 2 2 2 2

0 500 1000 0 500 1000 0 500 1000 0 500 1000 0 500 1000

6 6 6 6 6
4 4 4 4 4
2 2 2 2 2

0 500 1000 0 500 1000 0 500 1000 0 500 1000 0 500 1000

Time (ms)

Figure 14.2 Component weights (loadings) across assessment waves. The figure consists
of false color maps (heatmaps) of weights at each time-​frequency bin from PCA of time-​
frequency energy for all target trials. PCA was conducted separately for each assessment wave.
Components were matched by congruence coefficients computed between loadings at successive
assessment waves.

across assessments are evident as well, including shifts in the latency of the maximum
amount of energy in Component 5 and a trend toward increasing compactness in time-​
frequency space of Component 1.
Thus, a common set of time-​frequency features characterizes the EEG data across de-
velopment from early adolescence to early adulthood. Yet at the same time the subtle
developmental change in ERP morphology across waves evident in Figure 14.1 occurred
through small changes in this common set of features. Investigating differences between
those components that shifted in time and/​or frequency with development and those
that did not will contribute to a full understanding of the decision-​making processes
elicited by a visual oddball task.

14.2  Overview of the Chapter

In the remainder of this chapter we summarize the main findings of research on devel-
opmental aspects of time-​frequency activity, which highlights the importance of meth-
odological choices for interpreting developmental trends. We then discuss advantages
328    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

and disadvantages of cross-​sectional and longitudinal designs, with a treatment of

missing data and planned missingness. We briefly summarize statistical approaches
to characterizing developmental time-​ frequency activity and how the different
approaches implicitly or explicitly treat (developmental) time. We discuss methodo-
logical issues related to developmental time-​frequency research, namely, age differences
in task difficulty or degree of contamination by artifacts and variation in pubertal status
among study participants. We then present empirical findings from two longitudinal
investigations to illustrate what can be gleaned from a longitudinal design. Finally, we
conclude with thoughts about how a developmental perspective might profitably influ-
ence future work.

14.3  Time-​frequency activity

and development

This section reviews findings from selected studies that highlight the range of develop-
mental insights contributed by time-​frequency research.

14.3.1 Time-​Frequency Activity in the Auditory

Oddball Paradigm
The vast majority of the early work on age differences and developmental trends in time-​
and frequency-​specific activity consisted of the pioneering work of Yordanova, Kolev,
and colleagues (much of which is summarized in Yordanova & Kolev, 2008). Using an
auditory oddball paradigm, Yordanova and Kolev conducted a number of studies of
age-​related change in key time-​frequency features: power, or magnitude, modulation
of power by stimulus onset, and phase-​locking of the EEG response over trials. Several
key broad findings emerged from this work. Amplitude in different frequency bands was
commonly observed to decrease across age groups of increasing age. This was true of pre-​
stimulus as well as post-​stimulus amplitude. The latency of the maximal theta response
also decreased across groups of increasing age. In contrast, the single-​sweep wave index
(SSWI), a measure of the consistency of responses across trials (Kolev & Yordanova, 1997;
Yordanova & Kolev, 1998), increased with age (except in the gamma band). In a finding
that anticipates our subsequent treatment of the topic, Yordanova and Kolev found that
the enhancement factor (Basar, 1980) of event-​related oscillatory activity, which reflects
change in the amplitude of the signal following stimulus onset relative to pre-​stimulus
amplitude, increased with age as well. Thus, there was substantial developmental change
in time-​frequency features, which varied somewhat by frequency band and the particular
measure examined. The authors conclude that developmental changes in theta activity in
particular may be related to cognitive development.
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     329

14.3.2 Time-​Frequency Activity Related to Specific

Psychological and Cognitive Processes
Building on this earlier work, several recent studies have examined time-​frequency
activity in a visual oddball task or variant thereof (Chorlian et al., 2015; Chorlian
et al., 2017; Malone et al., 2021; Mathes et al., 2016; Wienke et al., 2018). Other work has
examined age differences in focused on time-​frequency activity related to the develop-
ment of error or feedback processing (Bowers et al., 2018; Crowley et al., 2014; DuPuis
et al., 2015), response preparation (Bender et al., 2005) and inhibition (Hwang et al.,
2016; Liu et al., 2014; Papenberg et al., 2013), perception (Ehlers et al., 2016; Uhlhaas
et al., 2009), and working memory (Sander et al., 2012). Although several studies have
examined synchrony in activity recorded at different pairs of electrodes or between
different frequency bands, the measures of interest in this research are largely the same
as in the work of Yordanova and Kolev: the magnitude of time-​frequency power and
intertrial phase consistency (ITPC) (Tallon-​Baudry et al., 1996),1 a measure of the de-
gree to which the timing of time-​frequency activity is consistent across trials which is
similar to the SSWI.

14.3.3 General Developmental Trends

A review of this work reveals consistent trends. ITPC is positively associated with age or
age groups of increasing age. Time-​frequency power is also associated with age in a con-
sistent direction, where the direction of association depends on the nature of baseline
correction. Studies using raw baseline correction, most often consisting of subtracting
the mean level of power in a pre-​stimulus period from all post-​stimulus power values,
typically report a negative association between total power and age. By contrast, studies
using baseline normalization, such as a dB transformation of post-​stimulus power rela-
tive to pre-​stimulus power, defined as 10log 10 Aposttf / A pref , where Aposttf is power at a
particular time-​frequency bin in the post-​stimulus period and A pref is the mean pre-​
stimulus power at the same frequency, typically report a positive association between
age and time-​frequency power. Simple baseline subtraction is comparable to removing
a DC offset in the time series recorded from a single electrode and thus simply centers
power values at all frequencies around the same baseline level, whereas baseline normal-
ization expresses post-​stimulus activity in terms of proportional change from baseline.
If y represents post-​stimulus activity and x , mean pre-​stimulus activity, then it is clear

1  ITPC is also known as intertrial phase coherence or clustering and phase-​locking factor. Because

time-​frequency activity is often expressed as a complex number, it has both magnitude and phase. ITPC
is a measure of the degree to which the phase of the complex-​valued signal at a given time-​frequency bin
is consistent across trials.
330    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

 y
why this would be true because log ( y ) − log ( x ) = log   . (See ­chapter 18 in Cohen,
 x
2014, for a treatment of the issue of baseline correction in time-​frequency analysis).
Several of the studies using baseline normalization also examined time-​frequency
power in the pre-​stimulus period (without baseline correction), which serves to help
reconcile the divergent findings. All report an inverse association between partici-
pant age and raw theta and delta power, which contrasts with the positive association
with post-​stimulus power modulation but mirrors the inverse association between age
and power commonly reported in studies using raw baseline correction (e.g., Mathes
et al., 2016).
In summary, the phasic brain response to an experimental event (stimulus onset or
incorrect or inappropriate response) becomes increasingly aligned temporally with the
event, which is reflected in the positive association between age and ITPC commonly
observed. Although there are exceptions (Bowers et al., 2018; Crowley et al., 2014),
baseline subtraction most often results in finding overall reductions in power with age,
which is sometimes interpreted to reflect increased processing efficiency. However,
baseline normalization most often results in overall increases with age, which is not as
easily explained in terms of efficiency. In addition, time-​frequency power in the pre-​
stimulus baseline period also decreases. This suggests that pre-​and post-​stimulus power
both decrease with development, but at different rates. It may be that with development,
fewer neurons are recruited in response to an experimental event, leading to reduced
power overall, but children and adolescents become better able to maintain an appro-
priate task set, resulting in greater phase consistency in the EEG response and increased
post-​stimulus power. Both interpretations are speculative but point to the fact that the
different methods of accounting for baseline activity can be complementary.

14.3.4 Specific Age-​Related Associations

Age differences in specific aspects of time-​frequency activity have been reported in sev-
eral studies, in addition to the general overall developmental trend. Investigators using a
gambling task with participants ranging in age from 8 to 17 found a negative association
between theta power and age only on trials in which participants won points, not when
they lost them (Bowers et al., 2018). Studies of cognitive control report age differences
in specific time-​frequency features. Papenberg and colleagues (2013) found that theta
ITPC was relatively equal among four age groups (children, adolescents, young adults,
and older adults) during the go condition of a go/​no-​go task, whereas it varied signifi-
cantly by groups during the no-​go condition. Thus, the degree to which ITPC was differ-
entially related to cognitive control and the behavioral demands of making a response
versus withholding one depended on age. Liu and colleagues, also using a go/​no-​go
task with children and adolescents, found that ITPC was greatest on go and no-​go trials
requiring extra effort to withhold a response in order to regain points previously lost
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     331

only among the oldest adolescents. In a study using MEG (magnetoencephalography),

Hwang and colleagues (2016) observed differences between adolescents and young
adults in the magnitude of preparatory activity in the frontal eye fields (FEF) bilaterally
before antisaccades versus prosaccades. Power between 10 and 18 Hz was lesser in mag-
nitude throughout the preparatory period among adolescents. Preparatory activity in
the ventrolateral and dorsolateral prefrontal cortex of the right hemisphere (VLPFC and
DLPFC) did not differ between groups, suggesting equivalent levels of motor inhibition
and task-​rule representations, but coupling between beta activity in DLPFC and alpha
activity in the frontal eye fields did. Thus, these three studies taken together indicate that
time-​frequency activity implicated in different aspects of cognitive control differs across
developmental stages.
Finally, researchers have looked for age differences in the scalp distribution of
frequency-​specific responses, rather than the magnitude of responses. Children show
more broadly distributed theta-​band activity and smaller magnitude beta-​and theta-​
frequency responses to grammatical errors than adults (Schneider et al., 2018; Schneider
et al., 2016), which the authors interpret to indicate that children use semantic information
to process grammatical errors, whereas adults use syntactic information. Age differences
in the topography or frequency-​specific pattern of responses to Mooney faces have been
reported as well, taken to reflect a reorganization of the brain response and increasing spe-
cialization for face processing with development (Mišić et al., 2014; Uhlhaas et al., 2009).
Thus, there is evidence for both general and specific age-​related differences. From
a developmental perspective, observing age differences is only the first step along the
way to understanding a phenomenon (Rutter, 1988). Age differences in time-​frequency
features might reflect hormonal differences, differences in cognitive development, or
differences in the salience of a monetary reward or other task demands, not simply
differences in chronological age. Unpacking findings of mean differences between age
groups is likely to be informative about the mechanisms underlying them, which in turn
may have implications for better understanding normative cognitive development as
well as psychopathological processes.

14.4  Research Design Issues

Several considerations emerge from reviewing the literature on age-​related differences

in time-​frequency features. The first involves use of a cross-​sectional or longitudinal de-
sign, although these clearly can complement one another. The vast majority of studies
we reviewed used a cross-​sectional design, which obviously requires less time to con-
duct than longitudinal studies, a significant practical advantage. However, they can
present interpretive difficulties. The primary threat to validity derives from the possi-
bility of cohort or group differences in characteristics that might affect time-​frequency
responses. Cohort differences are more likely to be problematic in studies of aging than
in studies of participants spanning a narrow range of ages. However, cross-​sectional
designs can nevertheless be susceptible to age-​group or age-​related differences due
332    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

to sampling variation, especially if sample sizes are small. As a result, cross-​sectional

studies can lead researchers to under-​or overestimate the true magnitude of change,
and we cannot know to what extent, if any, this is true.
Longitudinal designs are clearly superior for studying change rather than age-​
related differences in mean levels, permitting a characterization of normative develop-
mental trajectories and individual differences therein. Change can be characterized by
a small number of parameters that represent the nature of developmental trajectories
in a meaningful way. There are many possible parametric models that might be ap-
propriate for the phenomenon under study. Furthermore, longitudinal designs allow
the researcher to determine whether developmental trajectories are modulated by
characteristics of the individual, such as sex, genotype, or risk status for psychopath-
ology (e.g., Carlson & Iacono, 2008; Chorlian et al., 2015; Chorlian et al., 2017; Hill &
Shen, 2002). Developmental trajectories may also constitute useful endophenotypes
(Iacono & Malone, 2011; Iacono et al., 2017). An important paper by Curran and Bauer
(2011) advocates disaggregating between-​and within-​individual change in longitudinal
models when assessing correlates of change.
Yet longitudinal designs suffer from challenges of their own. The most obvious is prac-
tical: longitudinal studies take longer to conduct than cross-​sectional ones. We return to
this issue later. Longitudinal designs are also vulnerable to participant attrition and missed
assessments. However, recent developments in statistical methods allow researchers to use
all available data, rather than having to resort to crude methods, such as listwise deletion
of cases missing any data. Provided the mechanism that generates missing data is such that
there is not a relationship between the likelihood of a value being missing and the value it-
self, missingness can be considered “ignorable” (Little & Rubin, 2002).
Longitudinal studies are vulnerable to possible changes in the orientation or
motivation of participants to engage fully as well as the possibility of familiarity
or exposure effects. Although perhaps more obvious in regard to neuropsycho-
logical tasks than the tasks used to elicit and study time-​frequency features, we
must not overlook the possibility of familiarity effects in regard to a gambling or
go/​no-​go task. In fact, we have observed likely familiarity effects in an oddball task
despite time intervals between assessments of three to four years (Malone et al.,
2021). Fortunately, when more than two measurements are available per participant,
separating practice or familiarity effects from true developmental change becomes
possible (Ferrer et al., 2004). Comparing results from a longitudinal design with
those from a cross-​sectional study of participants spanning the same age range also
permits assessing the degree to which familiarity effects may have influenced the
longitudinal results.

14.4.1 Missingness by Design and Cohort-​Sequential Designs

One way to increase the efficiency of longitudinal designs that may not be widely
recognized is through incorporating planned missingness in the study design. In such
designs, each individual participant is observed at a subset of the possible time points or
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     333

(a) T1 T2 T3 T4 T5 T6 T7 T8 T9

(b) T1 T2 T3 T4 T5 T6 T7 T8 T9

Figure 14.3 Schematic of two variants of planned missingness designs. The hypothetical

sample in this scenario consists of three age groups of adolescents assessed three times over a
two-​year period. Panel A depicts a cohort-​sequential design, in which each age group shares
an assessment age with at least one other, which allows an assessment of cohort differences in a
dependent measure. In panel B, the age range spanned by the sample is maximized at the expense
of the ability to assess cohort differences. Both are examples of missingness by design.

ages rather than at all of them. This design is illustrated in Figure 14.3, which depicts two
possible data collection plans for a hypothetical study of adolescents between the ages of
14 and 20 or older. (What we present here is purely hypothetical; see Brandmaier et al.,
2020 for guidelines for planned missingness in latent growth curve designs.) There are
three age cohorts in this example, with all participants assessed annually for a period
of two years. Subjects in the three respective cohorts were 14, 16, or 18 years old at the
initial assessment for the first design plan (Plan A) and 14, 17, and 20 years old at the
initial assessment for the second design plan. Plan A depicts a cohort-​sequential de-
sign, in which participants’ mean age at the last assessment for each of the two youngest
age groups is the same as the mean age of participants in the next older age group at
their initial visit. Overlap in ages allows the researcher to compare cohorts. In Plan B,
participants in the three age cohorts are assessed at nonoverlapping ages, effectively
increasing the age range spanned by the sample. In both cases, the missing data are
missing by virtue of the experimental design, which makes missingness ignorable and
yields unbiased parameter estimation. Thus, they allow the researcher to characterize
developmental change across the entire age range of the sample despite the fact that each
subject is only observed three times.

14.5  Methodological issues

14.5.1 Task Difficulty Versus Task Demands

An experimental task may be more difficult for younger participants than older ones,
confounding task demands with task difficulty and necessitating modifications to the
334    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

experimental procedure to equate task difficulty across participants of different ages.

Several of the studies we reviewed adjusted stimulus delivery or response windows
to accomplish this. Two used tasks requiring cognitive control, which develops grad-
ually throughout adolescence (Casey et al., 2008; Luciana & Collins, 2012; Somerville
& Casey, 2010). One was a “simple” oddball task (Wienke et al., 2018). In all three, some
of the participants were as young as eight or nine years old. An additional consideration
is the need to equate the number of trials that go into estimating power or ITPC, which
affects the reliability of the estimate, if there is age-​related variation in the number of
trials lost due to artifacts.

14.5.2 Pubertal Stage
The ages of participants spanned middle childhood to late adolescence or
adulthood in several studies, which creates a potential confound between age and
pubertal status, and thus neuroendocrinological development. A chronological age
of 13, say, may not be equivalent for boys and girls with respect to the phenomenon
under study. Sample sizes may not be large enough for a careful analysis of effects
of puberty, but it should not be overlooked. Indeed, we found that incorporating
a measure of pubertal status in growth curve models eliminated apparent sex
differences in rates of change in time-​frequency power in adolescence. In addition,
accounting for individual differences in pubertal status in this manner resulted
in superior correspondence between the observed data and predicted trajectories
of change in the amplitude of one particular time-​frequency component (Malone
et al., 2021).

14.6  Statistical analysis

14.6.1  Age as discrete or continuous

Cross-​sectional studies with groups of participants at distinctly different ages typic-
ally make use of t-​tests or analysis of variance (ANOVA) for the purpose of statis-
tical analysis. The focus of analysis is necessarily on differences in mean levels among
groups. Repeated measures ANOVAs with longitudinal data in distinct age groups
also model mean levels within and between subjects. By contrast, the explicit goal of
regression models is to describe the form of change, such as whether it is linear with
age (such that change is additive) or nonlinear, as well as the rate of change. Modern
linear mixed effects (LME) regression models allow for participants to be measured at
different ages or times or even to have been assessed a different number of times, and
LMEs also allow a great deal of flexibility with respect to characterizing the covariance
structure of repeated measures (within subjects) in addition to characterizing trends
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     335

in mean levels of the outcome measure. Thus, these models are well suited for lon-
gitudinal analysis.2 An additional advantage of an LME framework over traditional
ANOVA models is that it uses all available data as long as missingness is ignorable.
Of course, one is not limited to linear models: a nonlinear or nonparametric model
may be appropriate for capturing growth that follows a well-​specified form, such as ex-
ponential and logistic growth models. Models with a latent age or time basis can be an
attractive way to model nonlinearity in mean levels of an outcome; we illustrate the use
of such a model in the next section. Kernel regression is a form of locally weighted re-
gression that has been used to model change in time-​frequency features (Chorlian et al.,
2015). Nonparametric regression can be useful when a simple parametric model is not ap-
propriate or as a preliminary step in choosing an appropriate model (Helwig, 2019). Thus,
a wide variety of models are available in regression analysis, whether the data are from a
longitudinal design or a cross-​sectional one, which should prompt the researcher to think
about the most appropriate model of change for the data at hand and the question asked.

14.6.2 The Form of Developmental Change in

Time-​Frequency Characteristics
Although the form of developmental change is rarely explicitly addressed, there is
agreement among the studies examining it that the association between age and time-​
frequency features in an oddball task is non-​additive (nonlinear) in adolescence and
early adulthood. Wienke and colleagues (2018) found that a quadratic polynomial
function of age best explained the association between age and theta power amplitude
modulation and ITPC. Chorlian and colleagues (2015), in a longitudinal study of 2,170
subjects assessed every two years and spanning the ages of 12 to 25, observed striking
sex differences in the pattern of change in theta power elicited by a novelty oddball task.
A steeper decline in power was observed among males than females, with a subsequent
leveling off between approximately 21 and 25. Power declined more gradually among
females but continued to do so even when power had leveled off among males. We also
observed nonlinear change in a large sample studied longitudinally and spanning essen-
tially the same age rage, described in the next section (Malone et al., 2021).

14.7  An Empirical Exploration

The preceding sections discussed several issues involved in developmental research

of time-​frequency activity: the utility of longitudinal designs; planned and accidental

2 
ANOVA models can now incorporate a variety of residual covariance structures, which overcomes
some of their limitations (Liu et al., 2012).
336    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

missingness; influences of puberty; and the appeal of regression approaches. This

section illustrates the relevance of these issues to time-​frequency research. Our pres-
entation is largely descriptive and intended to be illustrative, with a focus on longitu-
dinal methods, to serve as something of a counterpoint to the existing literature, which
is predominantly cross-​sectional. First, we briefly summarize results of our recent
paper (Malone et al., 2021), some of which we discussed earlier. We then present pre-
liminary results of an investigation extending these results in a second independent
sample with high-​density EEG recordings. Each is based on a population-​based co-
hort from the Minnesota Center for Twin and Family Research (MCTFR) (Wilson
et al., 2019) consisting of twin pairs (and their parents). Approximately 60% are mono-
zygotic, or identical, twins. Twins are same-​sex pairs who were raised together who
have been followed since a target age of 11 at approximately three-​to five-​year intervals.
Participants in both cohorts were administered the same task—​Begleiter’s rotated heads
oddball task (Begleiter, Porjesz, Bihari, & Kissin, 1984).
In Malone and colleagues (2021) we report findings from a longitudinal investigation
into time-​frequency activity in 1,692 twin subjects (917 of them female). The majority
(N =​1,512; 760 females) comprised the younger cohort of the MCTFR (Iacono et al.,
1999). Subjects were first assessed at the age of 11, with four follow-​up assessments at
three-​to four-​year-​intervals to a target age of 24. An additional 205 participants (172
females) from the separate ES cohort (Keyes et al., 2009) who completed an iden-
tical intake assessment were included. EEG activity was collected by means of a Grass
Neurodata 12 system at three or four scalp electrodes, with linked ears serving as refer-
ence. A pair of electrodes arranged in a transverse montage above and to the side of one
eye allowed for identification of eye blinks and other EOG activity.
Time-​frequency energy was derived from individual EEG signals by means of
the reduced interference distribution (RID; Williams, 2001; Chapter 4.) Meaningful
features in time-​frequency energy on target trials were identified by means of principal
component analysis (PCA) (Bernat et al., 2007; Bernat et al., 2005) via singular value
decomposition on centered columns of the “matricized” or unfolded matrix of baseline-​
corrected time-​frequency energy values (see Figure 14.2). PCA accounted well for the
data and yielded components that were highly similar from one time point to the next.
That is, after ordering components based on their timing, we computed Tucker congru-
ence coefficients (Tucker, 1951) between all pairs of components for a given assessment
and the successive assessment. These were uniformly large and approached 1 for
matched pairs of components, indicating nearly perfect congruence, whereas the off-​
diagonal elements in each matrix of congruence coefficients were small and approached
0, indicating lack of congruence between the unmatched pairs.
This degree of component congruence allowed the use of scores on matched
components to characterize longitudinal change. Examining plots of mean scores across
waves as well as individual trajectories of randomly selected individuals suggested
that piecewise linear regression models might be appropriate. LME models, treating
assessment wave as nested within individuals who were in turn nested within twin
pair, with component scores as the dependent measure accounted well for the observed
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     337

trends in the data. The change point, or knot, in each regression was identified empir-
ically and ranged from 16 to 19.5. Developmental trajectories in time-​frequency power
were characterized by an initial decrease in (baseline-​corrected) raw power, followed by
a flatter trajectory in later adolescence and early adulthood. Although the rate of change
was smaller in magnitude for the second phase of these models, it was still significant
(and negative). Data for one representative component are plotted in Figure 14.4. Panel
(a) depicts the component structure across waves. This recapitulates the first row of
Figure 14.2 and indicates that the component structure became less dispersed in time-​
frequency space with development. Panel (b) consists of violin plots representing the
distribution of scores across waves, separately for male and female participants. This
illustrates the overall trend for this component, its similarity for participants of both

Age 11
(a) (b)
6
6
4

Males
4
2
Component Score

0 200 400 600 800 1000 2

Age 14 0
6
7.5
4

Females
2 5.0

0 200 400 600 800 1000 2.5

Age 17
0.0
Frequency (Hz)

6 11 14 17 20 24
4 Assessment Age

2
SEX Male Female
0 200 400 600 800 1000
Age 20
(c)
6 3

4
Component Score

2
2
0 200 400 600 800 1000
Age 24
6
1
4
2

0 200 400 600 800 1000 11 14 17 20 23 26

Time (ms) Participant Age

Figure 14.4  Component scores from a PCA analysis of time-​frequency energy plotted against
assessment age. Subjects are the same as in Figure 14.1. Data are for Component 1 in Figure 14.2,
chosen to illustrate key results. Panel A depicts the component weights. This is identical to the first
row of time-​frequency weights in Figure 14.2. Panel B consists of violin plots of the distribution
of Component 1 scores across assessment waves, separately for the two sexes. A nonparametric
smoother (loess) represents the average developmental trend. Panel C depicts trajectories
implied by a piecewise linear model fit to these scores together with the observed mean scores at
each wave and 95% confidence intervals around them.
338    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

sexes and a striking decrease in variance with development. Finally, Panel (c) depicts the
mean trajectory implied by our piecewise linear regression model along with observed
means and confidence intervals. The (nonlinear) model-​implied trajectory accounts for
the observed data well.
That the magnitude of time-​frequency activity could be modeled by piecewise linear
trajectories suggests that there were distinct developmental phases in this sample with
respect to the brain response to target stimuli in the oddball paradigm used. These
results also illustrate one of the advantages of LME models: only 485 participants had
data from all five assessments, yet all data were used in fitting models, including age-​11
data from the approximately 200 ES twins, who were assessed at subsequent visits using
a different EEG recording system (described next) and as a result contributed only a
single observation in this investigation.

14.7.1 Extending These Findings

We extended these findings using high-​density EEG data from the ES cohort of the
MCTFR (Keyes et al., 2009), which comprises 998 twins, first assessed at the target age
of 11 and subsequently followed up at target ages of 14 and 17. Participants completed the
same rotated heads task as participants in the MTFS (programmed in E-​Prime software)
and EEG were recorded from 61 scalp electrodes using a Biosemi ActiveTwo system. An
additional four electrodes were placed just above and beside each eye for the purpose
of identifying vertical and horizontal EOG activity. Data were screened for eye blinks,
horizontal eye movement and other artifacts using an in-​house pipeline (see Burwell
et al., 2014; Harper et al., 2019).3 A total of 942 subjects had usable data: 601 at age 11 (270
females; ages 10.9 to 12.9, with a mean of 11.8); 717 at the first follow-​up (347 females;
ages 13.6 to 16.7, with a mean of 14.9); 763 at the second follow-​up (375 females; ages
16.8 to 19.2, with a mean of 17.8). As described above, the initial assessment of 204 twins
followed the MTFS protocol, whereas they completed this version of the task at the two
follow-​ups. Approximately 80% had data from at least two of the three assessments.
A time-​frequency representation of EEG responses to target stimuli was obtained by
means of a complex Morlet wavelet convolution. Frequencies ranged from 1 to 40 Hz,
with the number of cycles ranging from 3 to 8 (with 25 logarithmic steps for both). The
resulting signal was downsampled in time to 64 Hz and an estimate of power at each
time point obtained as the modulus of the complex signal at that time point. Total power
was averaged over 25 subsets of trials sampled randomly without replacement from each
experimental condition (target or nontarget) so as to equate the number of trials across
conditions. Power for each discrete frequency bin was represented by means of a dB
transformation relative to the average activity in that frequency between 450 and 250
ms prior to stimulus onset, which complements the approach in Malone and colleagues
(2021). In addition, we computed ITPC, as in Tallon-​Baudry and colleagues (1996).

3 
https://​www.git​hub.com/​sjburw​ell/​eeg_​co​mman​der
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     339

We again identified meaningful time-​frequency feature by means of PCA on centered

columns of the matrix of time-​frequency power values for all subject-​electrodes. Scree
plots suggested that eight components were appropriate for characterizing the data at
each assessment wave, which accounted for 75–​80% of the total variance at each wave. As
in Malone and colleagues (2021), components were varimax-​rotated in order to obtain a
more meaningful solution, and we computed Tucker’s congruence coefficient for pairs of
components that were visually matched between successive assessment waves. Coefficients
were uniformly large in magnitude, ranging from 0.96 to 0.99 for all pairs of matched
components, whether for age-​11 and age-​14 solutions or age-​14 and age-​17 solutions.
Components were highly similar across assessment waves, as in our previous investigation.

14.7.2 Characterizing the Results

We selected delta and theta components for presentation. False color maps of the
components are plotted in the left-​hand column of Figure 14.5, which illustrate how
similar the components are across assessment waves. Nevertheless, the delta compo-
nent shifts in time, appearing earlier in the response window at the later follow-​up
assessments, while both components become more compact in time. Both trends echo
findings from the previous investigation. The topographic distribution of theta power
(see the head plots inset in each heatmap) is also more diffuse at age 11.
Figure 14.5 also presents mean levels of component scores at the different assessment
waves, averaged over electrodes. ITPC scores were obtained by multiplying ITPC values
for each subject-​electrode by the weights (loadings) for delta and theta components,
respectively, and summing weighted values. Trajectories are plotted in the right-​hand
portion of panel (a) and (b) in Figure 14.5. These are somewhat nonlinear, distinctly so
in the case of theta ITPC. To keep the numbers of parameters to a minimum, we used a
latent age basis model. This is a form of structural equation model (SEM) similar to la-
tent growth curve (LGC) models (themselves similar to regression-​based approaches).
In both, change in a dependent measure is modeled in terms of a latent intercept and
slope (or slopes, if a higher-​order polynomial is used to model time). Time (or age)
enters the model via the slope loadings, rather than being an observed variable as in
regression models. However, whereas in the LGC model the slope parameters are fixed,
in the latent basis model one or more are freely estimated, which allows one to capture
nonlinearity in developmental trajectory.4 Rate of change is proportional over time, as
determined by the age basis coefficients (Grimm et al., 2011).
Models were estimated using Mplus version 7.2 (Muthén & Muthén, 1998–​2012)
via MplusAutomation (Hallquist & Wiley, 2018), an R package that serves as a flex-
ible wrapper to Mplus. Mplus permits using a subject’s actual age at each assessment

4  If there are T time points, T –​2 parameters can be estimated; two parameters must be fixed to

identify these models. With only three time points, there is a single free parameter, but the number of
parameters estimated can increase substantially with more time points.
340    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

Figure 14.5 Developmental course and topographic distribution of time-​ frequency

components. Loadings of two components from a PCA of dB-​transformed time-​frequency
power at each of three assessment waves in a large sample of adolescents in a longitudinal investi-
gation. Component loadings at each wave are depicted in the form of a heat map representing the
magnitude (and sign) of the component weights on each time-​frequency bin. Insets in the upper
right-​hand corner of each heat map depict the mean score on the two components respectively at
each electrode on a schematic representation of a head. The color map indicates the magnitude of
mean score. Red indicates the largest mean values, whereas blue indicates the smallest. The right-​
hand plot in each panel depicts the mean component score, averaged over all electrodes, at each
assessment wave, separately for males and females.
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     341

wave, rather than assuming they are exactly the same, as SEM software often requires.
Because our interest is in individual trajectories we used a cluster-​robust sandwich es-
timator via the COMPLEX samples option to derive appropriate standard errors given
that this sample comprises twins. In light of evidence of sex differences in level or shape
of trajectories of time-​frequency activity (Chorlian et al., 2015; Malone et al., 2021), we
allowed for (estimated) sex differences in intercept and slope. Only the sex effect on the
intercept of theta ITPC was significant, p =​.005, which is evident in the difference in
overall level between males and females in panel (b) of Figure 14.5. The rate of change
in all four measures could be considered roughly equivalent for males and females (p-​
values ≥ .110). Loadings for the age-​11 and age-​17 data on the slope latent variable were
fixed to the average age at the age-​11 and age-​17 assessments, respectively, in order to
identify the model, whereas the slope loading on age-​14 scores (or, strictly speaking,
the offset in years from the average age at this assessment) was estimated from the data.
This coefficient was positive for all four time-​frequency measures, indicating greater
change by the age-​14 assessment than assumed by a strictly linear age basis. Wald z
tests of the slope coefficient were significant, with the exception of theta total power,
indicating a meaningful departure from linearity. Intercept and slope were significantly
inversely correlated for both ITPC measures, indicating that those with higher levels
of ITPC at age 11 tended to show a slower rate of change with development. (See Table
14.1 for a close approximation to these correlations from the bivariate models examined

Table 14.1 Cross-​process correlations from bivariate parallel process models.

Delta Theta Theta-​Delta Theta-​Delta ITPC
ITPC-​Power ITPC-​Power Power
r p-​value r p-​value r p-​value r p-​value

Intercept1-​Slope1 -​.614 .001 -​0.902 <.001 -​0.173 .649 -​0.932 <.001

Intercept2-​Slope2 -​.319 .422 -​0.087 .846 -​0.433 .355 -​0.840 <.001

Intercept1-​ .551 <.001 0.240 .094 0.308 .145 -​0.035 .736

Intercept2
Slope1-​Slope2 .557 .016 0.118 .214 -​0.148 .679 0.000 .957

Age-​11 Residuals NA NA NA NA 0.201 .220 NA NA

Age-​14 Residuals .438 <.001 0.246 <.001 0.274 .001 0.092 .067
Age-​17 Residuals -​.193 .018 -​0.034 .589 0.338 .009 0.166 .003

Tabled values are correlations between pairs of latent variables and their associated p-​values for each
model: ITPC and power for delta and theta, respectively, and theta and delta power or ITPC, respectively.
Intercept1 and Slope1 refer to the first measure in each heading, whereas Intercept2 and Slope2 refer to the
second. For instance, in the Delta ITPC-​Power model, Intercept1 is the delta ITPC intercept and Intercept2 is
for delta power. Age-​specific residuals are the correlations between residual variance in the two measures,
independent of growth trajectories. Age-​11 residuals for three of the four measures were constrained to 0 to
avoid negative estimates. Correlations involving these measures were therefore indeterminate.
342    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

next.) These analyses thus indicate similarities and differences in trajectories of delta
and theta power and ITPC, as well as illustrate the potential of a latent time basis model
in representing a nonlinear trend, which in the present situation captured nonlinear
change in a particularly parsimonious model.

14.7.3 Covariation in Patterns of Change

In addition to analyses of univariate trajectories, longitudinal designs also permit one to
assess how different trajectories of change are related to one another. As an illustration,
we extend the univariate analyses described to the bivariate case, fitting the model to
all four pairs of measures. We first examined Pearson correlation coefficients between
all pairs of measures using the heatmap function in the R computing environment (R
Development Team, 2019) (Figure 14.6), combined with dendrograms displaying the

Figure 14.6 Matrix of correlations among time-​ frequency measures. The matrix of

correlations among all pairs of delta and theta power and ITPC at the three waves of assessment is
displayed graphically in false color (heatmap). Correlations are grouped on the basis of the results
of a hierarchical clustering algorithm. Dendrograms of the clustering results are displayed on the
margins. Theta and delta are indicated by their respective Greek letters and power is abbreviated
as “powr.” The number suffix indicates the assessment wave by its target age.
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     343

results of hierarchical clustering of the correlations. Correlations among theta and delta
measures segregated into separate respective clusters, with the former in the upper
right-​hand corner of the correlation matrix and the latter in the lower left.5 Within the
theta cluster, measures of total power were particularly closely related, with correlations
ranging from .47 to .58, whereas ITPC at 11 and 14 formed a subcluster. By contrast,
delta total power and ITPC at 14 and total power at 17 tended to cluster together, and the
measures that formed a subcluster were the two age-​11 measures. The largest correlation
coefficient was .58, between age-​14 and age-​17 theta power (between waves) as well as
between age-​14 delta power and ITPC (within a wave). Age-​17 ITPC for both theta and
delta were relatively independent of the other measures, with a median correlation of
.06 and .10, respectively. This pattern suggests a greater degree of shared variance among
delta power and ITPC than among theta power and ITPC, and relative independence
of ITPC measures at age 17. In addition, a shift in the pattern of associations around the
age-​14 assessment is suggested.
To determine the degree to which change in one measure was associated with change
in another, we fit a bivariate parallel process model. The parallel process model allows
for the latent influences on each measure to be related to the latent influences on the
other measure. Specifically, the model includes correlations (covariances) between the
two intercepts and the two slopes as well as a regression of the slope of change in one
measure on the intercept of the other measure. The latter permits an assessment of the
degree to which the level of time-​frequency ITPC, say, affects the rate of change in time-​
frequency power. This model is illustrated in Figure 14.7.
We fit four such models, one for each pairing of measures. Modeling the trajectory
in each measure recapitulates the univariate analyses just described. This is evident in
Table 14.1, which presents the most relevant parameter estimates from these models,
in that the first two rows present correlations between the latent intercept and slope
characterizing growth in a given measure. These were significant only for delta and theta
ITPC. The parameters of greatest interest here are those that characterize relationships
between the two measures: the correlations between latent intercepts (ρITPIITPC in
Figure 14.7) and slopes (ρSTPSITPC) and the effect of one latent intercept on slope of the
other measure (γITPSITPC and γIITPCSTP). The former, cross-​domain correlations appear
in the shaded rows in Table 14.1. Only the correlations between intercepts and slopes
for delta were significant, with results indicating that the greater the initial level of
delta ITPC power, the greater the initial level of delta ITPC and the greater the rate of
change in ITPC, the greater the rate of change in power. In addition, mean initial level
in delta power was inversely associated with the rate of change in ITPC (p =​.008). This
would lead delta power and ITPC become somewhat more distinct with development,
consistent with the pattern of correlations in Figure 14.6. It is also consistent with the

5 Although PCA yields orthogonal components and varimax is an orthogonal rotation method,

any type of rotation of the PCA solution results in lack of orthogonality of scores, loadings or both,
depending on the form of normalization used (Jolliffe, 2002). Normalizing eigenvectors to unit length,
as we did, sacrifices independence of component scores while maintaining orthogonality of the loadings.
344    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

Figure 14.7  Partial path diagram for a parallel process bivariate growth model. Latent variables
are represented by circles, whereas manifest variables are represented by squares. TP is time-​
frequency total power, ITPC is intertrial phase coherence. Each is measured at three different
assessment waves in a longitudinal design. The left-​hand panel focuses on the growth model for
total power (top) and ITPC (bottom). The mean level of each is modeled as a linear function of
a latent intercept (ITP and IITPC) and latent slope (STP and SITPC). The loadings of each observed
variable on its latent intercept are fixed at 1. The Greek letter a is used to represent the loadings on
the latent slope. In the latent age basis model used in the example described in the text, a0 is fixed
at 0 and a2 at 1, but a1 is estimated from the data. The coefficient corresponding to a1 thus gives the
proportion of total growth between 11 and 17 observed at age 14. At each assessment wave, the two
regression residuals covary (are correlated), which allows for age-​specific influences common
to power and ITPC. These are drawn for ages 11 and 17 but not for age 14 so as to avoid an un-
necessarily crowded diagram. The right-​hand panel “explodes” the center of the left-​hand figure
to emphasize the relationships between the two latent growth processes. These consist of two
correlations, between the two latent intercepts and the two latent slopes, and two regression paths
predicting mean change in TP from initial level of ITPC and vice versa. The triangle containing
the number 1 is used to represent the mean level of intercept and slope for TP and ITPC, respect-
ively. In reality, these are intercepts, rather than means, because the model includes regressions of
the latent variables on sex (not shown). In both panels, unlabeled circular double-​headed arrows
indicate residual variances.

principle of development toward progressive commitment and differentiation (Stiles

& Jernigan, 2010), which implies that power and ITPC become increasingly function-
ally specialized. The effect was small, however; expressing the regression coefficient as
a proportion of the residual variance in ITPC slope, this effect accounted for 1.6% of
the variance. For the other three models—​theta ITPC-​power, theta-​delta ITPC, and
theta-​delta power—​neither regression of slope in one on intercept of the other nor the
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     345

correlations between the two intercepts or the two slopes were significant. All p-​values
were greater than .360, although the ersatz effect size for the regression of delta ITPC on
rate of change in theta ITPC was somewhat larger than that of the significant effect in
the delta model. In addition, the correlations between paired intercepts and slopes were
not significant. Thus, the two processes in each model developed independently.
In broad terms, aspects of these results were anticipated by the pattern of correlations
in Figure 14.6 in that correlations between theta and delta measures were relatively
small in magnitude and total power and ITPC correlations tended to segregate for theta
compared to delta. However, most of the covariances between wave-​specific residuals
were significant and positive for both the age-​14 and age-​17 assessment waves. That is,
in the absence of significant cross-​measure regression effects for the most part, most of
the covariance between measures was due to age-​specific influences. This was especially
true of the age-​14 wave (and to a lesser extent the age-​17 wave). Individual differences
in pubertal status may induce correlations between time-​frequency measures that are
independent of developmental trajectories in these measures through hormonal effects
on brain organization, an inference not readily gleaned from the correlation matrix.

14.7.4  Conclusion
We do not by any means consider these results definitive. For one thing, the parallel pro-
cess model is only one possible approach, and it does not provide a direct assessment of
influences of one measure on change in the other. This requires a more complex model
with more time points (McArdle, 2009). Our results here are intended solely to illus-
trate some of the types of insights that longitudinal-​developmental designs provide.
In both investigations, we found that a common set of dimensions of time-​frequency
power, whether raw or dB-​transformed, accounted well for time-​frequency activity in
adolescence and, in the first investigation, into early adulthood. The consistency of these
dimensions across age in both instances was striking. Nevertheless, the particular con-
figuration of these dimensions shifted in subtle ways with age. For instance, congruence
coefficients between successive assessment waves for the component depicted in Figure
14.4 were all 0.95 or greater, indicating very close congruence between one wave and the
next. Nevertheless, the coefficient for the same component between age-​11 and age-​24
waves was 0.77, indicating much less congruence over the course of adolescence. Thus,
developmental change occurred through a gradual shift in time-​frequency space of the
locus of activity.
In our original investigation, we found that piecewise linear regression models
accounted well for mean levels of the data, which suggests distinct phases charac-
terize the development of time-​frequency activity in the rotated heads oddball task.
The timing of the transition between phases varied among components, which helps
to illuminate age-​related differences in the nature of the brain response. In our second,
more preliminary investigation, our ability to replicate this finding was hamstrung by
the fact that only three data points were available. Nevertheless, we found evidence of
346    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

nonlinearity with development. For the purposes of this investigation, we averaged

component scores over electrodes, but future work can benefit from the availability of
a denser electrode array to further illuminate developmental aspects of time-​frequency
activity.

14.8  Final Thoughts

Research conducted to date has yielded several consistent general findings. The ma-
jority of studies have reported consistent associations between age and time-​frequency
power and phase-​locking (ITPC). The association with ITPC is positive, such that
phase-​locking increases with age. As discussed, the nature of the association with power
tends to be negative in studies using raw power or baseline subtraction but positive
in studies examining modulation of power, such as by means of a dB transform, what
Makeig and colleagues have called event-​related spectral perturbations (ERSP; Makeig,
1993). These general trends are interpreted to mean that time-​frequency responses
to stimuli and events in an experimental setting become more mature in some sense.
However, the consistency of these trends across paradigms presents something of an
interpretive challenge for researchers. If more “efficient” responses are observed in a go/​
no-​go task among older participants, does this reflect a change in the processes involved
in withholding a response specifically or a developmental change in information pro-
cessing more generally? Comparing age-​related trends across a variety of tasks differing
in processing and response demands will be necessary to begin answering this question.
A developmental perspective prompts a shift in the types of questions one asks. For
instance, finding age-​related differences in mean levels of a time-​frequency phenom-
enon is really the first step of inquiry into the phenomenon (Rutter, 1988). This is in
part because age differences involve other differences among individuals as well that are
correlated with age. Observing age differences also suggests lines of follow-​up research.
If younger adolescents differ from older ones on a measure such as time-​frequency
power, how is this related to other time-​frequency or performance measures (e.g., Liu
et al., 2014; Papenberg et al., 2013)? At what point in development do these differences
disappear? Do age-​related differences in time-​frequency features related to cognitive
control in one task, such as increased theta power, predict similar age-​related differences
in those same features in another task? Failure to find such differences might call into
question whether these features truly reflect cognitive-​control processes. It might also
indicate that the developmental course of these time-​frequency features varies because
of differences in the cognitive control processes required by tasks that appear similar
on the surface. Control of interference in the attentional field by flanking stimuli in an
Eriksen flanker tasks is likely somewhat different from control of response selection
or inhibition in a go/​no-​go task. Yet at the same time, the similarities between these
two forms of control suggest that the time-​frequency activity elicited by each should be
related and the relationship between them can be traced longitudinally within subjects.
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     347

Comprehensive examination of developmental aspects of time-​frequency features

thought to reflect specific psychological or neural processes can also shed light on those
processes. For example, developmental neuroscience models differ somewhat with re-
spect to how sensitivity to reward develops during adolescence. Some propose a rapid
increase early in adolescence followed by a plateau (e.g., Casey et al., 2008; Somerville
& Casey, 2010) whereas others propose that the early increase is followed by a subse-
quent decrease (Luciana & Collins, 2012). Time-​frequency features associated with the
reward positivity, for example, are thought to reflect activity of the ventral striatum and
areas involved in reward processing (Bowers et al., 2018). These models make different
predictions about the developmental course of reward-​related time-​frequency features.
If, the developmental course of time-​frequency features thought to reflect reward pro-
cessing differs from that predicted by neuroscience models, it might suggest the models
are wrong. But it might also suggest that our interpretation of the meaning of those
time-​frequency features is wrong.
Finally, in addition to characterizing age-​related trends in a given time-​frequency
feature, a developmental perspective is concerned with understanding how aspects
that develop early might affect those that develop later. For instance, a developmental
approach to time-​frequency connectivity analysis might ask how network patterns
characteristic of children constrain the subsequent development of these patterns in
adolescence? Are any such constraints more or less continuous with development or
are they characterized by significant discontinuities? Answering questions such as
these will require a longitudinal approach, perhaps in combination with cross-​sectional
studies. The number of studies addressing age-​related differences in time-​frequency ac-
tivity has increased in recent years, an encouraging development that is expanding our
knowledge in important ways. We suggest that expanding the types of questions being
asked is likely to be fruitful as well if we are to move from description to explanation.

REFERENCES
Basar, E. (1980). EEG-​brain dynamics: Relation between EEG and brain evoked potentials.
Amsterdam.
Begleiter, H., Porjesz, B., Bihari, B., & Kissin, B. (1984). Event-​related brain potentials in boys at
risk for alcoholism. Science, 225, 1493–​1496.
Bender, S., Weisbrod, M., Bornfleth, H., Resch, F., & Oelkers-​Ax, R. (2005). How do children
prepare to react? Imaging maturation of motor preparation and stimulus anticipation by late
contingent negative variation. NeuroImage, 27, 737–​752.
Bernat, E. M., Malone, S. M., Williams, W. J., Patrick, C. J., & Iacono, W. G. (2007).
Decomposing delta, theta, and alpha time–​frequency ERP activity from a visual oddball
task using PCA. International Journal of Psychophysiology, 64, 62–​74.
Bernat, E. M., Williams, W. J., & Gehring, W. J. (2005). Decomposing ERP time-​frequency en-
ergy using PCA. Clinical Neurophysiology, 116, 1314–​1334.
348    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

Bowers, M. E., Buzzell, G. A., Bernat, E. M., Fox, N. A., & Barker, T. V. (2018). Time-​frequency
approaches to investigating changes in feedback processing during childhood and adoles-
cence. Psychophysiology, 55, e13208.
Brandmaier, A. M., Ghisletta, P., & Oertzen, T. V. (2020). Optimal planned missing data de-
sign for linear latent growth curve models. Behavioral Research Methods, 52, 1445–​1458.
doi:10.3758/​s13428-​019-​01325-​y
Burwell, S. J., Malone, S. M., Bernat, E. M., & Iacono, W. G. (2014). Does electroencephalogram
phase variability account for reduced P3 brain potential in externalizing disorders? Clinical
Neurophysiology, 125, 2007–​2015.
Carlson, S. R. & Iacono, W. G. (2008). Deviant P300 amplitude development in males is
associated with paternal externalizing psychopathology. Journal of Abnormal Psychology,
117, 910–​923. https://​doi.org/​10.1037/​a0013​443
Casey, B. J., Jones, R. M., & Hare, T. A. (2008). The adolescent brain. Annals of the New York
Academy of Sciences, 1124, 111–​126. https://​doi.org/​10.1196/​ann​als.1440.010
Chorlian, D. B., Rangaswamy, M., Manz, N., Kamarajan, C., Pandey, A. K., Edenberg,
H., . . . Porjesz, B. (2015). Gender modulates the development of theta event related
oscillations in adolescents and young adults. Behavioral Brain Research, 292, 342–​352.
doi:10.1016/​j.bbr.2015.06.020
Chorlian, D. B., Rangaswamy, M., Manz, N., Meyers, J. L., Kang, S. J., Kamarajan, C., . . . Porjesz,
B. (2017). Genetic correlates of the development of theta event related oscillations in
adolescents and young adults. International Journal of Psychophysiology, 115, 24–​39.
doi:10.1016/​j.ijpsycho.2016.11.007
Cohen, M. X. (2014). Analyzing neural time series data: theory and practice: MIT press.
Crowley, M. J., van Noordt, S. J. R., Wu, J., Hommer, R. E., South, M., Fearon, R. M. P., & Mayes,
L. C. (2014). Reward feedback processing in children and adolescents: medial frontal theta
oscillations. Brain and Cognition, 89, 79–​89.
Curran, P. J., & Bauer, D. J. (2011). The disaggregation of within-​person and between-​person
effects in longitudinal models of change. Annual Review of Psychology, 62, 583–​619.
doi:10.1146/​annurev.psych.093008.100356
D’Souza, D. & Karmiloff-​Smith, A. (2016). Why a developmental perspective is critical for
understanding human cognition. Behavioral and Brain Sciences, 39, e122. doi:10.1017/​
S0140525X15001569
DuPuis, D., Ram, N., Willner, C. J., Karalunas, S., Segalowitz, S. J., & Gatzke-​Kopp, L. M. (2015).
Implications of ongoing neural development for the measurement of the error-​related nega-
tivity in childhood. Developmental Science, 18, 452–​468.
Ehlers, J., Struber, D., & Başar-​Eroğlu, C. (2016). Multistable perception in children: Prefrontal
delta oscillations in the developing brain. International Journal of Psychophysiology, 103, 129–​
134. doi:10.1016/​j.ijpsycho.2015.02.013
Ferrer, E., Salthouse, T. A., Stewart, W. F., & Schwartz, B. S. (2004). Modeling age and retest
processes in longitudinal studies of cognitive abilities. Psychology and Aging, 19, 243–​259.
Grimm, K. J., Ram, N., & Hamagami, F. (2011). Nonlinear growth curves in developmental re-
search. Child Development, 82, 1357–​1371. doi:10.1111/​j.1467-​8624.2011.01630.x
Hallquist, M. N. & Wiley, J. F. (2018). Mplus Automation: An R package for facilitating
large-​scale latent variable analyses in Mplus. Structural Equation Modeling, 48(2), 1–​18.
doi:10.1080/​10705511.2017.1402334
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     349

Harper, J., Malone, S. M., & Iacono, W. G. (2019). Target-​related parietal P3 and medial frontal
theta index the genetic risk for problematic substance use. Psychophysiology, 56(8), e13383.
doi:10.1111/​psyp.13383
Helwig, N. E. (2019). Robust nonparametric tests of general linear model coefficients: A com-
parison of permutation methods and test statistics. NeuroImage, 201, 116030. doi:10.1016/​
j.neuroimage.2019.116030
Hill, S. Y. & Shen, S. (2002). Neurodevelopmental patterns of visual P3b in association with
familial risk for alcohol dependence and childhood diagnosis. Biological Psychiatry, 51,
621–​631.
Hwang, K., Ghuman, A. S., Manoach, D. S., Jones, S. R., & Luna, B. (2016). Frontal pre-
paratory neural oscillations associated with cognitive control: A developmental study
comparing young adults and adolescents. NeuroImage, 136, 139–​ 148. doi:10.1016/​
j.neuroimage.2016.05.017
Iacono, W. G., Carlson, S. R., Taylor, J., Elkins, I. J., & McGue, M. (1999). Behavioral disinhib-
ition and the development of substance use disorders: Findings from the Minnesota Twin
Family Study. Development and Psychopathology, 11, 869–​900.
Iacono, W. G. & Malone, S. M. (2011). Developmental endophenotypes: Indexing genetic
risk for substance abuse with the P300 brain event‐related potential. Child Development
Perspectives, 5, 239–​247.
Iacono, W. G., Malone, S. M., & Vrieze, S. I. (2017). Endophenotype best practices. International
Journal of Psychophysiology, 111, 115–​144. doi:10.1016/​j.ijpsycho.2016.07.516
Jolliffe, I. T. (2002). Principal component analysis. Springer.
Keyes, M. A., Malone, S. M., Elkins, I. J., Legrand, L. N., McGue, M., & Iacono, W. G. (2009).
The enrichment study of the Minnesota twin family study: Increasing the yield of twin
families at high risk for externalizing psychopathology. Twin Research and Human Genetics,
12, 489.
Kolev, V. & Yordanova, J. (1997). Analysis of phase-​locking is informative for studying event-​
related EEG activity. Biological Cybernetics, 76, 229–​235. doi:10.1007/​s004220050335
Little, R. J. & Rubin, D. B. (2002). Statistical analysis with missing data (2nd ed.). Wiley.
Liu, S., Rovine, M. J., & Molenaar, P. (2012). Selecting a linear mixed model for longitudinal
data: Repeated measures analysis of variance, covariance pattern model, and growth curve
approaches. Psychological Methods, 17, 15.
Liu, Z.-​X., Woltering, S., & Lewis, M. D. (2014). Developmental change in EEG theta activity in
the medial prefrontal cortex during response control. NeuroImage, 85, 873–​887.
Luciana, M., & Collins, P. F. (2012). Incentive motivation, cognitive control, and the adolescent
brain: Is it time for a paradigm shift? Child Development Perspectives, 6, 392–​399. doi:10.1111/​
j.1750-​8606.2012.00252.x
Makeig, S. (1993). Auditory event-​related dynamics of the EEG spectrum and effects of ex-
posure to tones. Electroencephalography and Clinical Neurophysiology, 86, 283–​293.
doi:10.1016/​0013-​4694(93)90110-​h
Malone, S. M., Harper, J., Bernat, E. M., & Iacono, W. G. (2021). Stability and change in the de-
velopment of time-​frequency activity in adolescence and early adulthood. Preprint [online]
https://​doi.org/​10.31219/​osf.io/​8kdh
Mathes, B., Khalaidovski, K., Wienke, A. S., Schmiedt-​Fehr, C., & Basar-​Eroglu, C. (2016).
Maturation of the P3 and concurrent oscillatory processes during adolescence. Clinical
Neurophysiology, 127, 2599–​2609.
350    STEPHEN M. MALONE, JEREMY HARPER, and WILLIAM G. IACONO

McArdle, J. J. (2009). Latent variable modeling of differences and changes with longitudinal
data. Annual Review of Psychology, 60, 577–​605.
Mišić, B., Mills, T., Vakorin, V. A., Taylor, M. J., & McIntosh, A. R. (2014). Developmental trajec-
tory of face processing revealed by integrative dynamics. Journal of Cognitive Neuroscience,
26, 2416–​2430.
Muthén, L. K., & Muthén, B. O. (1998-​2012). Mplus User’s Guide (7th ed.). Muthén & Muthén.
Papenberg, G., Hämmerer, D., Müller, V., Lindenberger, U., & Li, S.-​C. (2013). Lower theta
inter-​trial phase coherence during performance monitoring is related to higher reaction
time variability: a lifespan study. NeuroImage, 83, 912–​920.
R Development Team. (2019). R: A Language and Environment for Statistical Computing. R
Foundation for Statistical Computing. Retrieved from https://​www.R-​proj​ect.org/​
Rutter, M. (1988). Epidemiological approaches to developmental psychopathology. Archives of
General Psychiatry, 45, 486–​495. doi:10.1001/​archpsyc.1988.01800290106013
Sander, M. C., Werkle-​Bergner, M., & Lindenberger, U. (2012). Amplitude modulations
and inter-​ trial phase stability of alpha-​ oscillations differentially reflect working
memory constraints across the lifespan. NeuroImage, 59, 646–​ 654. doi:10.1016/​
j.neuroimage.2011.06.092
Schneider, J. M., Abel, A. D., Ogiela, D. A., McCord, C., & Maguire, M. J. (2018). Developmental
differences in the neural oscillations underlying auditory sentence processing in children
and adults. Brain and Language, 186, 17-​25.
Schneider, J. M., Abel, A. D., Ogiela, D. A., Middleton, A. E., & Maguire, M. J. (2016).
Developmental differences in beta and theta power during sentence processing.
Developmental Cognitive Neuroscience, 19, 19–​-​30.
Somerville, L. H. & Casey, B. J. (2010). Developmental neurobiology of cognitive control
and motivational systems. Current Opinion in Neurobiology, 20, 236–​241. doi:10.1016/​
j.conb.2010.01.006
Stiles, J. & Jernigan, T. L. (2010). The basics of brain development. Neuropsychology Review, 20,
327–​348. doi:10.1007/​s11065-​010-​9148-​4
Tallon-​Baudry, C., Bertrand, O., Delpuech, C., & Pernier, J. (1996). Stimulus specificity
of phase-​locked and non-​phase-​locked 40 Hz visual responses in human. Journal of
Neuroscience, 16, 4240–​4249.
Tucker, L. R. (1951). A method for synthesis of factor analysis studies (Vol. No. PRS-​984).
Educational Testing Service.
Uhlhaas, P. J., Roux, F., Singer, W., Haenschel, C., Sireteanu, R., & Rodriguez, E. (2009). The
development of neural synchrony reflects late maturation and restructuring of functional
networks in humans. Proceedings of the National Academy of Sciences of the United States of
America, 106, 9866–​9871.
Wienke, A. S., Basar-​Eroglu, C., Schmiedt-​Fehr, C., & Mathes, B. (2018). Novelty N2-​P3a
complex and theta oscillations reflect improving neural coordination within frontal brain
networks during adolescence. Frontiers in Behavioral Neuroscience, 12, 218.
Williams, W. J. (2001). Reduced interference time-​ frequency distributions: Scaled
decompositions and interpretations. In L. Debnath (Ed.), Wavelet transforms and time-​
frequency signal analysis (pp. 381–​417). Birkhauser.
Wilson, S., Haroian, K., Iacono, W. G., Krueger, R. F., Lee, J. J., Luciana, M., . . . Vrieze, S. (2019).
Minnesota Center for Twin and Family Research. Twin Research and Human Genetics, 22(6),
746–​752. doi:10.1017/​thg.2019.107
 DEVELOPMENTAL RESEARCH ON TIME-FREQUENCY     351

Yordanova, J., & Kolev, V. (1996). Brain theta response predicts P300 latency in children.
Neuroreport, 8, 277–​280. doi:10.1097/​00001756-​199612200-​00055
Yordanova, J. & Kolev, V. (1998). Developmental changes in the theta response system: a single-​
sweep analysis. Journal of Psychophysiology, 12, 113–​126.
Yordanova, J., & Kolev, V. (2008). Event-​related brain oscillations in normal development. In L.
A. Schmidt & S. J. Segalowitz (Eds.), Developmental psychophysiology: Theory, systems, and
methods (pp. 15–​68). Cambridge University Press.
 CHAPTER 15

THETA-​B ETA P OW E R RAT I O

An Electrophysiological Signature of Motivation,
Attention and Cognitive Control

DENNIS J. L. G. SCHUTTER AND

J. LEON KENEMANS

15.1  Introduction

The preservation of frequencies across mammalian species is testament to the import-

ance of rhythmic neural activity. Indeed, oscillatory activity at its multiple temporal
scales is proposed to have guided the large volumetric expansion of the mammalian
brain and its functions throughout the course of evolution (Buzsaki & Watson, 2012).
The unique amplitude and frequency modulatory properties of electric signals suggest
a neural syntax by which the brain can function on the different functional neuro-​
anatomical levels (Buzsaki & Watson, 2012). Even though the localization of EEG ac-
tivity in the brain is challenging, the different frequencies that make up the human EEG
signal, which typically range between 1 to 50 Hz, correspond to more or less identifiable
structures in the brain.
In agreement with this view, electric stimulation of the ascending reticular activating
system in the brain-​stem elicits 1–​4 Hz (delta) cortical responses (Guyton, 1976). Delta
activity is also a dominant rhythm during deep sleep and unconscious states and reflects
large deactivation of the cerebral cortex and dominant activity associated with activity
in the brain stem. Electric stimulation of limbic areas, on the other hand, can elicit 7-​
Hz (theta) activity in mammals (Gray, 1982). Activity in the theta frequency range (4–​
7Hz) has been observed in limbic areas, including the septo-​hippocampal complex,
amygdala, and anterior cingulate cortex (ACC) (Asada et al., 1999: Gray, 1982: Rahman
et al., 2018).
EEG activity between 8 and 12 Hz (alpha) is the strongest frequency band produced
in adult humans, and results in a wide area of cortical structures under the influence
of functional decoupling with the thalamus. For example, alpha waves are generated
 THETA-BETA POWER RATIO    353

when the visual cortex is deprived of sensory input (i.e., eyes closed), yet instantly dis-
appear when the thalamocortical coupling is restored and the thalamus starts to transfer
signals from our eyes to the visual cortex again (i.e., eyes open). This observation had
led researchers to propose that alpha waves represent a so-​called cortical idling rhythm
that is inversely related to processing activity (Adrian & Matthews, 1934). In addition to
the posterior areas, activity in the alpha band is also present in the more anterior regions
and involved in motor, cognitive, and emotion-​related functions (e.g., Hoptman &
Davidson, 1998: Harmon-​Jones & Gable, 2018).
Furthermore, EEG frequencies of 13 Hz and higher (beta) have been proposed to re-
flect synchronized field potentials in more local cortico-​cortical circuits (Lubar, 1997).
Beta activity can be registered across the cerebral cortex including the more anterior
regions of the cerebral cortex (Engel & Fries, 2010). The association between beta ac-
tivity and an anterior distribution concurs with the proposed posterior-​anterior gra-
dient model in which the natural peak EEG frequency increases from the posterior
perceptual to the anterior action dedicated areas of the cerebral cortex (Rosanova et al.,
2009). In sum, neural rhythms are preserved across the mammalian species, and they
provide a signature of functionally dedicated brain regions and circuits.
The ratio of frequency bands is the relative contribution of neural rhythms to charac-
terize the interdependency between these neural signals that can be recorded from the
scalp. For example, scalp-​recorded resting state frontocentral theta activity can at least
in part be explained by input from signals coming from the subcortical system, whereas
beta activity represents endogenous inhibitory activity that is more cortical of origin
(Schutter & van Honk, 2005). Hence, the ratio between theta and beta power arguably
reflects the balance between bottom-​up excitatory subcortical signals and the cortical
signals associated with top-​down regulation and attentional control (Schutte et al.,
2017). In this conceptual framework, a high theta-​beta power ratio indicates a dominant
bottom-​up subcortical input over top-​down cortical regulation, whereas a low theta-​
beta power ratio implies a dominant top-​down cortical regulation over the bottom-​up
subcortical system. The general idea behind the theta-​beta power ratio is that the ratio
captures the interaction of more motivation-​driven processes (theta) on the one hand,
and attention-​and cognitive-​related processes (beta) on the other.

15.2  Theta-​beta power ratio

in attention deficit/​hyperactivity
disorder (ADHD): A meta-​
analytic perspective

Given the importance of rhythms as an organizing principle underlying brain function,

EEG activity is increasingly being examined in studies on the biological underpinnings
of normal and abnormal human behavior.
354    DENNIS J. L. G. SCHUTTER and J. LEON KENEMANS

In the 1970s clinical-​oriented scientists started to investigate possible associations be-

tween EEG rhythms and psychological functioning.
Among the first ideas that came under scientific investigation was the hypothesis
that inattention and hyperactivity seen in children with ADHD result from a chron-
ically under-​aroused central nervous system (CNS) causing higher-​than-​normal
resting state theta activity (Satterfield & Cantwell, 1974). The so-​called hypo-​arousal
model of ADHD was postulated after observations of children with ADHD showing
lower-​than-​normal electrodermal activity (Satterfield & Dawson, 1971). Paralleled by
observations of dominant theta (4–​7 Hz) and alpha activity (8–​12 Hz) during rest
and increased activity in the beta band (>13 Hz) during mental activity in healthy
individuals (Jasper et al., 1938), Joel Lubar proposed that ADHD children may par-
ticularly have an underactive cortical system as indicated by the increased theta and
reduced beta wave activity (Lubar, 1991). Further support for the EEG hypothesis was
provided by a study that deployed a quantitative analysis of EEG in boys with ADHD
(Mann et al., 1992). Results led to the idea that an elevated resting state theta-​beta
power ratio may in fact be an electrophysiological EEG marker of ADHD (Karakas &
Barry, 2017). While the link between theta-​beta power ratio and ADHD has proven
reliable, the original idea of linking higher ratios with low CNS activity as indexed by
electrodermal activity has not received much additional support ever since (Barry
et al., 2004).
ADHD is a disorder marked by an ongoing pattern of inattention and/​ or
hyperactivity-​impulsivity that interferes with daily-​life functioning and normal
development. (https://​www.nimh.nih.gov/​hea​lth/​top​ics/​attent​ion-​defi​cit-​hypera​
ctiv​ity-​disor​der-​adhd/​index.shtml). Features of inattention are lack of persist-
ence, difficulties in sustaining focus, and disorganized thoughts. Importantly,
these problems are not related to intelligence. Hyperactivity is the constant moving
about both in appropriate and inappropriate situations. Furthermore, hyperactivity
is associated with extreme restlessness and behaviors such as excessive fiddling,
tapping, and talking. Persons with ADHD tend to be impulsive and engage in hasty
actions without considering the possible negative consequences of their actions. As
a result, they prefer immediate rewards and show an inability to delay gratification.
Impulsive individuals can be socially demanding and may appear indifferent to the
needs of others.
Research over the last 40 years has identified a number of EEG patterns associated
with ADHD. In addition to elevated theta activity over the anterior scalp regions, lower
alpha and beta activity over the posterior scalp regions have been reported. In addition,
higher than normal posterior delta activity, as well as increases in the theta-​alpha and
theta-​beta power ratio have been found in children with ADHD (Clarke et al., 2001a).
As previously mentioned, increased slow wave activity (<8 Hz) and decreased fast wave
activity (>10 Hz), elevations of theta activity and theta-​beta power ratio are among the
most consistent findings (Saad et al., 2018). Figure 15.1 shows an example of resting
state theta and beta oscillations obtained with a non-​invasive EEG scalp recording in a
healthy young adult.
 THETA-BETA POWER RATIO    355

theta: 4–7 Hz μV2

10.0
μV
–40.0
–20.0

20.0
40.0
0
1 sec 0 10 20 30 40 50 Hz
beta: 13–30 Hz μV2
μV 1.2
–40.0
–20.0

20.0
40.0
0
1 sec 0 10 20 30 40 50 Hz

Figure 15.1  Example of band-​pass filtered scalp recorded theta and beta oscillations and spec-
tral power distributions.

15.3  Theta-​beta power ratio

in ADHD diagnostics

The replicability of these findings together with results showing that the pharma-
cological agent methylphenidate (Ritalin) improves ADHD symptoms paralleled
by a lowering of theta activity and decrease in the theta-​beta power ratio (Arns et al.,
2018) has led to the suggestion that the resting state theta-​beta power ratio may be a
biomarker for ADHD and can be used in diagnostics. In one of the first studies, three
experiments were reported that aimed to replicate previous findings, examine criterion-​
related validity of EEG on inattention, and determine test-​retest reliability of the EEG
(Monastra et al., 2001).
In the first experiment, earlier findings of significantly higher theta-​beta power
ratios in patients aged between 6–​20 years with inattentive and hyperactive-​combined
ADHD as compared to controls, were replicated. The second experiment showed that
the theta-​beta power ratio derived attentional index could reliably differentiate between
ADHD and non-​ADHD participants (sensitivity: 90%, specificity: 94%). In the third
experiment a high test-​retest correlation coefficient (0.96) of the theta-​beta power ratio
was found in a sample of fifty-​five volunteers that underwent an EEG session on two
occasions thirty days apart. Comparable sensitivity (87%) and specificity (94%) scores
356    DENNIS J. L. G. SCHUTTER and J. LEON KENEMANS

in identifying ADHD within a clinical sample (n =​159) were reported by another multi-​
center validation study (Snyder et al., 2008). However, the theta-​beta power ratio could
not reliably differentiate between ADHD and comorbidities or alternative diagnoses.
Based on these findings the authors advised the use of EEG as a complementary measure
in the clinical evaluation of ADHD (Snyder et al., 2008).
This conclusion follows up results from the first meta-​analysis by Snyder & Hall
(2006), who investigated the presence of specific EEG traits in ADHD and evaluated
nine high quality studies (n =​1498) in which the primary analysis of interest concerned
a group comparison between ADHD patient’s diagnosis according to the criteria
of the Diagnostic and Statistical Manual of Mental Disorders and controls on resting
state theta and beta activity. Standardized mean effect size (Glass’ delta) and 95% confi-
dence intervals (CI) were calculated. Results showed significantly higher theta (pooled
effect size: 1.31; 95% CI: 1.14–1.48) and lower beta activity (pooled effect size: −0.51; 95%
CI: −0.65 to −0.35) in patients compared to controls.
Consistent with these observations a strong significant effect was observed for an
increase of theta-​beta power ratio in ADHD patients versus controls (pooled effect
size: 3.08; 95% CI: 2.90 ̶ 3.26). A second fixed effects model meta-​analysis published
in 2013 reported a notably lower overall effect size, Hedges’ d: 0.75; 95% CI: 0.57 ̶ 0.93,
favoring increased theta-​beta power ratio in children and adolescents with ADHD as
compared to controls (Arns et al., 2013).1 Furthermore, considerable heterogeneity in
effect sizes across studies was observed, indicating that the variance of the effect size
across the included studies was greater than to be expected from sampling error. Even
though the effect size was still large, subsequent analyses showed no strong support for
the applicability of the theta-​beta power ratio in diagnostics (Arns et al., 2013).
Despite the inconclusive scientific evidence, in July 2013, the U.S. Food and
Drug Administration (FDA) approved the use of the Neuropsychiatric EEG-​Based
Assessment Aid Health for the assessment of ADHD based on the theta-​beta power
ratio (FDA, 2013). To further examine this, we updated the meta-​analysis by Arns
et al. (2013) and included additional studies that reported group differences between
theta-​beta power ratios of children and adolescent with and without an ADHD diag-
nosis. In total, eighteen studies that were published in peer-​reviewed English scientific
journals including 2425 participants (1600 patients and 825 controls) were analysed.
The standardized effect size (Hedges’ delta) and variance were calculated for each study
(Hedges & Olkin, 1985).
Based on the assumption that, in addition to sampling error, effect sizes contain a
true random component, a random effects model was performed. Results showed an
estimated mean effect size of 0.92 (95% CI: 0.40–1.44) (Figure 15.2).

1 
This meta-​analysis included nine studies and used different selection criteria compared to the earlier
meta-​analysis. As a result, only two of the nine studies used in the original meta-​analysis by Snyder and
colleagues (2008) were considered eligible. In addition, this study-​based effect size calculation used the
pooled standard deviation of the ADHD and control groups instead of exclusively using the SD of the
control group in computing the Glass’ delta.
 THETA-BETA POWER RATIO    357

Clarke et al. (2002a)

Sohn et al. (2010)
Nazari et al. (2011)
Buyck & Wiersema (2015)
Barry et al. (2009)
Monastra et al. (2001)
Markovska-Simoska et al. (2017)
Halawa et al. (2017)
Shi et al. (2012)
Zhang et al. (2019)
Lansbergen et al. (2011)
Ogrim et al. (2012)
González Castro et al. (2010)
Snyder et al. (2008)
Jarrett et al. (2017)
Monastra et al. (1999)
Loo et al. (2012)
Williams et al. (2010)
mean

-1.00 0 0.25 1.50 2.75 4.00

Effect size (95%CI)

Figure 15.2  Forest plot of the mean effect size and 95% CI intervals of the included studies.

The test for study heterogeneity was not significant, Qtotal =​12.95, p =​0.74. Rosenberg’s
fail-​safe number analysis indicates that 2415 studies with null findings (p< 0.05) are
required to change the significant meta-​analytic result into a non-​significant finding.
In addition, Orwin’s method shows that 68 studies are needed to reduce the mean effect
size of 0.92 to a small effect size of 0.2. As neither method accounts for sample size or
variance of the studies, these fail-​safe number results should be interpreted with caution.
While the mean effect size observed in the current meta-​analysis is larger than the effect
size reported in 2013, the overlapping 95% CIs show that the difference between the
effect sizes is not statistically significant at the p=​0.05 level. The wide 95% CI interval
indicates considerable uncertainty in terms of the true value of the effect size and the use
of the theta-​beta power ratio for diagnosing ADHD in children and adolescents remains
unclear (Arns et al., 2013). Several authors have proposed that adding cognitive, emotive
and genetic information to the theta-​beta power ratio may have substantial diagnostic
as well as prognostic value (Williams et al., 2010).
It is suggested that determining theta activity relative to the individual alpha peak-​
frequency may contribute to the diagnostic value of the resting state theta-​beta power
ratio (Saad et al., 2018). This suggestion adds to the idea of multiple theta rhythms and
that the dependency on conventional fixed frequency bands may be problematic in the
classification of ADHD as well as for gaining a deeper understanding on the relation be-
tween EEG ratios and their functional meaning.
Determining the so-​ called transition-​ frequency reflects the true physiological
boundary between theta and alpha activity, and may present a physiological plausible
358    DENNIS J. L. G. SCHUTTER and J. LEON KENEMANS

alternative as this frequency marks the intersection of resting state with active EEG
(Saad et al., 2018: Klimesch, 1999). Perhaps the individualized peak alpha frequency may
also be useful to indicate the transition from alpha to beta.
Personalized approaches like these may be able to control for individual differences in
EEG make-​up unrelated to ADHD symptoms and improve the specificity (true negative
rate) and sensitivity (true positive rate) of the theta-​beta power ratio in diagnostics.
Even although the concept of resting state theta-​beta power ratio as a biomarker for
diagnostic purposes is promising, further research is needed to further develop this
concept. In addition, higher resting state theta-​beta power ratio in ADHD children has
been suggested to be indicative for treatment outcome (Loo et al., 1999: Clarke et al.,
2002b). Support for this idea comes from results showing that good as compared to poor
responders to methylphenidate have higher resting state theta-​beta power ratio prior to
treatment (Clarke et al., 2002a). This fits the observation that stimulant medication can
increase beta activity in children with ADHD, particularly in frontal cortical regions, in
addition to improving symptoms related to attentional focus and response inhibition
(Loo et al., 2004).
Together, the normalization of dopaminergic activity in the subcortical circuits as
indicated by a reduction in theta activity, and the increase in beta activity, may explain
the lowering of the power ratio in response to methylphenidate. Indeed, oscillatory beta
activity is in turn linked to dopamine levels at sites of cortical input to subcortical areas
including the basal ganglia (Jenkinson & Brown, 2011). While the resting state theta-​
beta power ratio may be a positive response predictor, a multi-​center, prospective open-​
label trial found that lower frontal alpha (9 Hz) peak frequency, but not the resting state
theta-​beta ratio in male adolescent ADHD patients, is a predictor for non-​response to
methylphenidate (Arns et al., 2018). This negative predictor response was found to be
independent from age, medication dosage, and baseline symptom severity. The lower
individual anterior alpha peak is suggestive of a maturational lag in the structural de-
velopment of the frontal cortex (Whitford et al., 2007). Together these findings stress
the importance of considering both functional (e.g., theta-​beta power ratio) and struc-
tural aspects (e.g., alpha peak) of brain organization for understanding the efficacy of
treatments. More recent work points towards the direction that EEG measures may be
more useful biomarkers of ADHD outcome or treatment response rather than diagnosis
(Sari Gokten et al., 2019: Loo et al., 2018). Finally, the different findings leave open the
possibility that ADHD symptoms can have several neuro-​etiological origins and should
be evaluated within an environmental context.

15.4  Functional correlates of the

theta-​beta power ratio

In addition to research on the clinical features and applicability of the theta-​beta power ratio
in ADHD, basic neuroscientific research has also made considerable progress in identifying
 THETA-BETA POWER RATIO    359

cognitive and affective processes associated with the theta-​beta power ratio. This line of re-
search provides insights not only into the specific symptomatology of ADHD, but also in
understanding the neurocognitive processes within the general population.
Experimental human brain research has shown that the prefrontal cortex (PFC) plays
a prominent role in the regulation of attention and motivational tendencies, and other
executive control functions (Corbetta et al., 2008).
On the other hand, for theta specifically, based on combined fMRI and
electrocorticography, significant associations have been reported between theta power
and BOLD activity in “intrinsic” resting-​state networks, including the default-​mode
network (DMN, the “idling network”) and a network involved in episodic and working
memory (Hacker et al., 2017). Furthermore, the CNS stimulant nicotine reduces both
theta power (Knott et al., 2007), as well DMN activity (Hahn et al., 2007). Nicotine-​
induced reduction in DMN activity correlates positively with nicotine-​ induced
improvements in task performance (Hahn et al., 2007). These data support an interpret-
ation that theta power indexes idling and/​or hypo-​arousal.
In addition, patients responding to the CNS stimulant methylphenidate dem-
onstrate reductions in the theta-​beta power ratio (Isiten et al., 2017). Notably, the
methylphenidate-​related change was driven by an increase in beta, rather than a reduc-
tion in theta, power. If indeed beta power is more closely related to cerebral cortical
activity, then the reductions in ADHD symptoms may be due to improved executive
control functions. Raclopride positron emission tomography (PET) showed that me-
thylphenidate (dose: 0.8 ± 0.11 mg/​kg) potentiates dopaminergic activity by blocking
dopamine transporters causing an increase of synaptically available DA in the human
brain (especially the striatum, Volkow et al., 2001). The findings were replicated at lower
dosages which are more commonly prescribed in daily practice (Gottlieb, 2001).
As methylphenidate also increases noradrenergic activity (Kuczenski & Segal,
2001), catecholaminergic dysfunctions is argued to contribute to elevated theta-​beta
power ratios in individuals with ADHD who respond to methylphenidate (Isiten
et al., 2017).
Based on the proposed neural generators of theta and beta oscillations, in conjunc-
tion with the dopaminergic dysfunctions described earlier, a neuroanatomical model
has been developed to explain the motivational, cognitive, and motoric symptoms
of ADHD. The model is a midbrain ventral tegmental area (VTA)-​centered frame-
work that includes both the mesolimbic and mesocortical dopaminergic pathway. The
mesolimbic pathway refers to the connection between the VTA and nucleus accumbens
(ventral striatum), implicated in reward motivation and subcortical motor planning
routines. In addition, the VTA extensively projects to the septo-​hippocampal complex
and amygdala indicative of a complex subcortical circuit dedicated to instrumental
learning and memory processes (Hefco et al., 2003).
The connection between the VTA and PFC constitutes the backbone of the
mesocortical pathway. In particular, the VTA projections to the medial frontal cortex
and ACC provide a neural basis for monitoring and top-​down regulatory functions (Di
Michele et al., 2005).
360    DENNIS J. L. G. SCHUTTER and J. LEON KENEMANS

Next to the septo-​hippocampal complex, the ACC is another brain area that operates
in the theta f​requency range (Asada et al., 1999). It is suggested that together these
regions make up a circuit dedicated to monitoring and goal-​directed motor planning,
whereas the ventral and dorsolateral parts of the FC take part in executive functions
including working memory, attentional control, and top-​down regulation.
The functionality of the latter anterior cortical regions is suggested to involve beta
activity. From this viewpoint, the theta-​beta power ratio may provide a global index
for cortico-​subcortical interactions wherein slow wave (theta) activity represents the
subcortical bottom up and fast wave (beta) activity in cortical top-​down processes
(Schutter et al., 2006). In particular, the low tonic dopaminergic activity in the cortico-​
subcortical circuits and subsequently elevated theta-​beta power ratio could perhaps
provide a neural marker for attention, impulsivity, reward sensitivity and motor activity
in individuals with and without ADHD (Heilman et al., 1991: Robbins, 2000). A more
specific formulation of this idea holds that a reduction in dopamine level is associated
with disinhibition of the ACC causing an increase in spontaneous theta oscillations
and higher responsivity (e.g., the frontal-​related negativity (FRN)) to external feedback
(Holroyd & Coles, 2002).
Thus, high theta relative to low beta activity may reflect a state of heightened subcor-
tical drive in conjunction with cortical hypoarousal. Furthermore, the ACC is among
the prime neural generators of theta oscillations and may a take central position between
the subcortical and prefrontal brain areas. This idea is further supported by research
showing that the ACC and the anterior portions of the medial PFC can exert direct
top-​down control over the VTA via monosynaptic excitatory projections (Holroyd and
Yeung, 2012: Elston et al., 2019). Increased 4 Hz (theta) oscillatory signaling between the
ACC and VTA has been demonstrated during anticipatory decision making, feedback
processing, and behavioral flexibility (Elston et al., 2019).
Studies on the spectral density of local field potentials in the ACC and VTA show that
while the ACC shows peaks between 3–​5 Hz, the VTA emits signals between 3–​5 Hz and
7–​9 Hz (Elston et al., 2019). The frequency specificity of theta activity across regions
suggests the earlier proposed existence of multiple theta rhythms that each have a dis-
tinct functional role in behavior. Rhythmic excitability allows for temporal windows of
coordinated spike timing to exchange signals between distal regions (Buzsáki & Watson,
2012: Cavanagh et al., 2012). Further evidence for frequency specificity was provided by
a study showing that administering exogenous oscillatory field potentials at 4 Hz (low
theta) increases working memory capacity, while at 7 Hz (high theta) working memory
performance deteriorates (Wolinski et al., 2008). The latter idea also fits the proposed
role of theta activity carrying information encoded in gamma oscillations (>30 Hz) from
the hippocampus to the cerebral cortex in memory formation (Jensen and Lisman, 1996).
Taken together the studies imply the existence of multiple functionally inde-
pendent theta activity related to (1) arousal, (2) motivation, (3) cognitive flexibility, and
(4) memory-​related processes.
 THETA-BETA POWER RATIO    361

Studying the frequency specific of theta and beta may therefore be particularly inform-
ative about whether a higher theta-​beta power ratio, for example, reflects drowsiness as
indicated by a broad increase in the theta EEG spectrum or heightened motivation as
reflected by increased information transfer between the ACC and VTA as reflected by
4 Hz oscillations. As the conventional calculations of theta-​beta power ratio are based
on the averaging of power values in the 4–​7 Hz (theta) and 13–​30 Hz (beta) frequency
range, the study of specific theta, as well as beta oscillatory, components may be relevant
for understanding the meaning of the power ratio within a given neural and behavioral
context.

15.5  Reward and punishment sensitivity

Several psychological studies have examined the proposed interrelations between theta-​
beta power ratio and cognitive-​affective processes in healthy volunteers.
On the basis of the proposed relation between the theta-​beta power ratio and im-
pulsivity in ADHD, the predictive value of resting state theta-​beta power ratio on
risky decision making was investigated in a sample of healthy volunteers (Schutter
& van Honk, 2005). Risky decision making was measured with the Iowa gambling
task. In the Iowa gambling task, players are instructed to try to gain as much money
as possible by drawing selections from a choice of four decks. Two of the decks are
disadvantageous, producing immediate large rewards, but on the long term cause
an overall loss due to even higher punishments. The other two decks are advan-
tageous in the sense that immediate rewards are modest but more consistent and
punishment rate is low. Decisions to choose from the decks become motivated by
the reward and punishment schedules associated with the advantageous and disad-
vantageous decks.
Results showed that higher resting state theta-​beta power ratio was associated
with more risky decisions. These findings can be understood in terms of increased
reward sensitivity and/​or lower punishment sensitivity. Importantly, participants
did show a cumulative increase in advantageous decision making during the
course of the task. Even though volunteers acquired knowledge about the reward-​
punishment contingency, subjects with high theta-​beta power ratio were none-
theless more inclined to take risky decisions as compared to subjects with a lower
theta-​beta power ratio.
The association between theta-​beta power ratio and disadvantageous decision
making was replicated in a follow-​up experiment (Massar et al., 2014) which also
explored the specific contributions of reward and punishment sensitivity to the
theta-​beta power ratio by testing how well subjects were able to learn associations be-
tween symbols that signal a high probability of winning money and low probability
362    DENNIS J. L. G. SCHUTTER and J. LEON KENEMANS

of winning nothing (reward learning), and symbols that signal a high probability of
losing money and low probability of losing nothing (punishment learning). Results
showed that the association between theta-​beta power ratio and associative learning
was driven by the positive correlation between theta oscillations and reward learning.
This finding fits with the proposed role of theta oscillations in the dopaminergic
mesolimbic pathway.
Results of an earlier study demonstrated that the nature of the relation between
theta-​beta power ratio and risk-​taking involved feedback-​related processing in the
ACC (Massar et al., 2012). More specifically, a higher theta-​beta power ratio was found
to correlate with reduced feedback processing as reflected in lower FRN amplitudes.
Additionally, this association varied as a function of punishment sensitivity as evaluated
by the behavioral inhibition system questionnaire. The data suggest a bias toward mo-
tivationally driven behavior as a result of suboptimal action monitoring, leading to
top-​down executive control being subsequently less involved due to reduced ACC
signaling. This effect becomes more prominent when subjects score higher on punish-
ment sensitivity and arguably already experience higher default levels of uncertainty.
In accordance, a meta-​analysis has shown that midfrontal theta activity is linked to
ACC activity during action-​outcome uncertainty and cognitive control (Cavanagh &
Shackman, 2015).
Notably, much like children with an anxiety disorder, children with ADHD display
an intolerance of uncertainty (Gramszlo et al., 2018). Indeed, if the ACC is central to
the integration of bottom-​up feedback signals originating from midbrain structures
and top-​down executive functioning and control, disturbances in the ACC may sub-
serve the lack of coordinated and goal-​directed behaviors in ADHD. Furthermore,
increased theta-​beta power ratios may signify compromised ACC-​related feed-
back processes that contribute to subjective states of uncertainty. Uncertainty is
experienced when there is a lack of subjectively perceived contingency between action
and outcome.
Thorndike’s law of effect dictates that reward and punishment-​related feedback
signals are responsible for shaping situation appropriate action-​outcome contingencies.
In other words, the structural occurrence of rewards and punishment following a
specific action leads to the formation of stronger action-​outcome links (Seth, 2013).
Experimentally, uncertainty can be manipulated by introducing unpredictable changes
in reward-​punishment contingencies. Earlier findings indicate that particularly in un-
predictable environments, a situation-​dependent balance between the exploitation
of acquired knowledge and exploration of new options is the best behavioral strategy
to maximize profit (Daw et al., 2006). In the event of a change in reward-​punishment
schemes, individuals have to relearn the contingencies to adjust decision making ac-
cordingly (Clark et al., 2004: Bechara et al., 1997). The presence of theta activity is
associated with the experience of conflict and reward sensitivity, so it is reasonable to
assume that high theta-​beta power ratio is associated with suboptimal reversal learning
 THETA-BETA POWER RATIO    363

when reward-​associated responses suddenly are punished, and punishment-​related

responses become rewarded.
To test this hypothesis, healthy volunteers performed a reversal learning gambling
task (Schutte et al., 2017). Unknown to the participant, the task consisted of different
reward-​punishment (R​P) schedules for high-​risk decision making. During phase 1
(trials 1–​40) high-​risk choices were rewarded in 80% of the trials, while in phase 2
(trials 41–​80) the RP schedule was reversed, and high-​risk choices were now punished
in 80% of the trials. In phase 3 (trials 81–​120), the RP schedule used in phase 1 (i.e.,
80% reward for high risks) was reintroduced. The spontaneous resting state theta-​
beta power ratio recorded prior to the task was found to be inversely related to re-
versal learning, indicative of lower cognitive flexibility during unexpected changes
when theta-​beta power ratio is high. The results can be interpreted along the lines of
lowered cortical cognitive involvement in the processing of subcortical reward and
punishment signals.
In an additional study, transcranial alternating current stimulation (tACS) was
applied to evaluate the effects of applying 5-​Hz (theta) oscillatory electric fields to
left and right frontal cortex on reversal learning in healthy volunteers (Wischnewski
et al., 2016). Active, as compared to sham theta tACS, resulted in faster learning of
newly introduced reward-​and punishment contingencies during the task, but sur-
prisingly subjects also became more hesitant to apply the learned contingencies to
optimize decision making. Furthermore, a significant decrease of the left frontal
resting state theta-​beta power ratio was observed after tACS. While the lowering
of the power ratio concurs with increased apprehension, left-​sided lowering was
accompanied by less-​optimal decision making. This paradoxical finding can be
explained by the anterior cortical asymmetry model of motivational direction. More
specifically, lower left-​sided power ratio may reflect reductions in approach-​related
motivation and increased behavioral inhibition (Schutter et al., 2008). In a follow up
double-​blind randomized cross-​over study, 20 Hz (beta) tACS applied to the frontal
cortex of healthy volunteers improved rule implementation during reversal learning
(Wischnewski et al., 2020). Additionally, a global frontal reduction of the theta-​beta
EEG power ratio was observed (Wischnewski et al., 2020). The latter results fit the
cognitive flexibility interpretation, whereas the reduction observed after theta tACS
can be better explained as a change in motivation.
In another study by Lansbergen and colleagues (2007), a stop-​signal task was
administered that involved two types of trials: go-​trials (i.e., square wave gratings
presented on a computer screen) and stop-​trials (i.e., 1000 Hz auditory tone).
Whereas go-​trials only contained go-​signals, stop-​trials contained both the go-​
and stop-​signal. In contrast to expectations, results showed that participants with
high resting state theta-​beta power ratio demonstrated shorter stop-​signal reac-
tion times and fewer failures to respond to the go-​stimulus on time. Perhaps, the
opposite results indicate a curvilinear relationship between the theta-​beta power
364    DENNIS J. L. G. SCHUTTER and J. LEON KENEMANS

ratio and executive control in which under certain (less complex?) circumstances
higher ratios can have a positive effect on performance. This implies that during
high cognitive load and motivational value the positive relations turn into negative
correlations. These seemingly paradoxical results highlight the possibility that, de-
pending on the operational and conceptual perspective adopted by researchers and
theorists, high theta activity, and therefore a high theta-​beta power ratio, can reflect
cortical hypo-​arousal and increased cortical drive, as well as enhanced working-​
memory function and cognitive control. This line of argumentation concurs with
the proposed existence of different functions of theta waves. Finally, a recent study
highlighted prestimulus high theta during the task as an indicator of drowsiness,
but also stimulus-​elicited theta specifically in high-​conflict conditions, supposedly
reflecting enhanced demands for cognitive control (Canales-​Johnson et al., 2020; see
also Cooper et al., 2019).

15.6  Central executive and

attentional control function

The theta-​beta power ratio is proposed to index a cortico-​subcortical balance and

reflects interactions between the brain’s cognitive and motivational systems. In add-
ition to the involvement of the motivational systems as outlined in the previous
section, central-​executive control functions have been associated with the theta-​beta
power ratio. The central executive serves three major control functions (Miyake et al.,
2000). The first function (inhibition) is the ability to inhibit automatic or prepotent
responses and requires attentional control to actively withstand intrusions from
task-​irrelevant stimuli or motivational tendencies. The second function (shifting)
involves adaptive changes in attentional control based on a change in environmental
demands and is the capacity to switch between mental sets and operations. The
third function (updating) involves the monitoring and renewal of working memory
representations. Attentional control processes play a key role in the different central
executive functions as they involve the conscious regulation of bottom-​up, stimulus-​
driven information processing streams. Within this dual-​process system concept, the
top-​down strategic network resides in the anterior frontal cortical areas, whereas the
stimulus-​driven systems are localized in the more posterior (sensory) cortical and
subcortical (motivation) regions.
Researchers have proposed that a high theta-​beta power ratio reflects a matur-
ational lag of frontal cortical development that can explain the suboptimal attentional
control of posterior cortical and subcortical signals in children with ADHD (Clarke
et al., 2001b). The discovery that the theta-​beta power ratio is inversely correlated to
 THETA-BETA POWER RATIO    365

self-​reported attentional control in healthy young adults (Putman et al., 2010) has
prompted a series of scientific studies that further investigated the latter association
in the context of stress and anxiety (Putman et al., 2014). High levels of stress and
anxiety have a negative impact on central executive functioning and performance.
For example, cognitive performance anxiety (CPA) is the phenomenon in which anx-
iety/​uncertainty about one’s cognitive competence causes lower and even impaired
performance.
The interaction between the theta-​beta power ratio and CPA-​related stress on per-
formance was examined in healthy participants who performed a stress induction
or control task. In addition to replicating the earlier inverse association between
the theta-​beta power ratio and self-​reported attentional control, lower levels of the
ratio were found to be protective for the negative effects of CPA. These finding can be
explained by the inverse relation between theta-​beta power ratio and attentional con-
trol (Putman et al., 2010).
In a subsequent study, a pictorial dot-​probe paradigm was deployed to further
investigate a role for the theta-​beta power ratio in attention resource allocation to
emotionally arousing stimuli. Healthy volunteers were instructed to fixate on the
center of a screen and to locate a black dot that appeared either on the left or right
side immediately following the simultaneous presentation of two stimuli in the left
and right periphery of the visual field. Statistical analyses revealed that subjects with
a relatively high theta-​beta power ratio directed attention towards mildly arousing
and avoided highly arousing negative pictures. Consequently, subjects with low
theta-​beta power ratios displayed more attention towards high arousing negative
material. Even though correlational findings do not allow inferences on the direc-
tionality of statistical associations, the authors interpret these findings as further
support for the idea that an increased theta-​beta power ratio reflects an enhanced
ability to regulate the impact of negative emotional information (Angelidis
et al., 2018).
An independent follow-​ up experiment replicated this finding and also found
that lower self-​reported trait attentional control predicted more attention to mild as
compared to high arousing negative stimuli (Van Son et al., 2018). These findings concur
with earlier research that administered a go/​no-​go task in healthy volunteers. In this
particular study subjects were instructed to respond (go) or inhibit responses (no-​go)
to fearful and happy facial expressions (Putman et al., 2010). In line with the ADHD
literature (Metin et al., 2012), a significant correlation was found between response in-
hibition and the theta-​beta power ratio (Putman et al., 2010). More specifically, stronger
response inhibition to the fearful relative to the happy facial expressions was predicted
by lower theta-​beta power ratios (Putman et al., 2010).
Furthermore, evidence was found for a positive relation between the theta-​beta
power ratio and the drive scale of the behavioral activation system (Gray, 1985).
The drive scale is related to the brain’s seeking system, which promotes energized
366    DENNIS J. L. G. SCHUTTER and J. LEON KENEMANS

appetitive and approach-​related behaviors that include exploration, foraging and fu-
ture anticipation of rewards (Panksepp, 1998, 2012). Neuroanatomically, the seeking
system corresponds to the mesolimbic dopaminergic pathway and provides input
to the higher cortical areas and promotes reward-​driven actions. Within this frame-
work, theta activity may be a correlate of the seeking system that feeds information
into the PFC. This information is then used in attentional control and regulatory
processes, arguably reflected by the beta activity component of the ratio, to shape
context-​appropriate behaviors. More recently, temperamental shyness was found to
correlate with higher levels of social anxiety in children with large baseline-​to-​task
decreases in frontal theta-​beta power ratio in the anticipation of having to give a
speech (Poole et al., 2021). These findings were interpreted as increased attentional
control and emotion regulation during the experience of stress in shy children (Poole
et al., 2021). Observations that resting state the theta-​beta power ratio is positively
associated with distraction tendency and not re-​appraisal strategies (Kobayashi et al.,
2020) concur with the proposed link between theta-​beta power ratio and attentional
control (Putman et al., 2014).
Due to the low spatial resolution of scalp-​recorded electric field potentials, localizing
their neural generators is challenging. However, interleaving resting state func-
tional magnetic resonance imaging with resting state EEG recording provides a way
to examine the relations between different cortical and subcortical brain regions and
the theta-​beta power ratio. Recently, associations between the theta-​beta power ratio
and the brain’s executive control network (ECN) were explored in a sample of healthy
volunteers (Van Son et al., 2019b). The ECN consists of the dorsolateral PFC, ACC and
parietal cortex, and governs top-​down regulation and attentional control processes
(Corbetta et al., 2008).
Reductions in attentional control and brain activity were investigated during mind
wandering. Mind wandering refers to transient changes of attentional focus from a task
to non-​task related mental states and is accompanied by an increase in the theta-​beta
power ratio (Braboszcz & Delorme, 2011: Van Son et al., 2019a). As compared to an at-
tentional focus condition, the reduction in ECN functional connectivity was correlated
to an increase in theta-​beta power ratio during mind wandering. Even though this
finding does not imply that the ECN is the generator of theta activity, the result-concurs
with the positive relation between mind wandering and ADHD symptomatology
(Seli et al., 2015) as well as with aberrant functional connectivity of the executive con-
trol network in ADHD subjects (McCarthy et al., 2013). The results not only provide
a functional neuro-​anatomical substrate for the theta-​beta power ratio, but also fur-
ther strengthens construct validity of the ratio as a functional signature of the balance
between bottom-​up motivational and top-​down cognitive aspects of normal and ab-
normal human behavior. Figure 15.3 depicts a functional neuro-​anatomic framework
of the theta-​beta power ratio which represents a synthesis of the concepts and empir-
ical work reviewed in this chapter.
 THETA-BETA POWER RATIO    367

DLPFC
beta

MPFC

ACC

VTA

theta

SH NA

Figure 15.3  A functional neuro-​anatomic framework of the theta-​beta power ratio.

Abbreviations: ACC, Anterior cingulate cortex; DLPFC, Dorsolateral prefrontal cortex; MPFC, Medial prefrontal cortex;
NA, Nucleus accumbens; SH, Septohippocampal complex; VTA, Ventral tegmental area.

15.7  Some methodological issues

While resting state EEG is robust and has a high test-​retest reliability within a time
frame of one week (Angelidis et al., 2018), longer inter-​assessment intervals and meth-
odological factors can nonetheless provide a source of error variance which can nega-
tively affect the reliability of the theta-​beta power ratio. Results can among other factors
be influenced by wrong electrode placement, artifact contamination, drowsiness,
changes in medication use, and comparison with suboptimal control groups. The lack of
a standardized EEG protocol could make comparisons between studies and groups less
reliable. So, in addition to differences already mentioned, differences in, for example,
applied reference method and varying epoch and Fast Fourier Transform window
lengths can yield heterogenous results. Also, age has been found to influence the relation
368    DENNIS J. L. G. SCHUTTER and J. LEON KENEMANS

between the theta-​beta power ratio and ADHD (Clarke et al., 2001a). One line of evi-
dence comes from work showing that the ratio is able to differentiate between ADHD in
children, but not in adults (Markovska-​Simoska & Jordanova, 2017).
It should furthermore be noted that whereas scientific studies are well suited to pre-
dict and demonstrate effects on the group level, specifying these effects to the individual
level is more problematic. Finally, there is a difference between statistical significance
and clinical relevance, as in that a reliable systematic finding is too small to have a mean-
ingful contribution to the diagnosis, prognosis and/​or treatment of a disorder. In sum,
the relation between available scientific evidence and clinical usefulness of EEG in
ADHD and other conditions remains a topic of research.

15.8  Beyond the theta-​beta

power ratio

In addition to the theta-​beta power ratio, only a limited number of studies have looked
at the functional relevance of other ratios. For example, an increase in parietal delta-​
beta power ratio has been positively associated with spontaneous emotion regulation
as shown by lower ratings of discomfort after the offset of negative pictures (Tortella-​
Feliu et al., 2014). These results suggest that the posterior delta-​beta power ratio reflects
an electrophysiological dispositional feature for faster automatic recovery of unpleasant
emotional responses (Tortella-​Feliu et al., 2014). These findings are in agreement
with a study that found a positive associations between parietal delta-beta waves and
self-​reported attentional control in a group of healthy volunteers (Morillas-​Romero
et al., 2015). In another study both the parietal delta-​beta and frontal theta-​beta power
ratio were correlated to risky decision making (Schutter & van Honk, 2005). A study
investigating ADHD subtypes in children by analyzing their EEG found that inatten-
tive type of ADHD was associated with increased delta-​beta power ratios as compared
to matched controls (Aldemir et al., 2018). Although the underlying mechanism
remains unclear, cognitive impairments in neurological populations go accompanied
by increases in slow wave oscillations, including delta waves, in conjunction with a de-
crease in alpha and beta wave activity (Klass & Brenner, 1995). Perhaps, relative higher
delta power as a result of lower alpha activity is linked to reduced perceptual sensitivity
to external stimuli that results in less attentional resource allocation and in-​depth pro-
cessing. Additionally, higher delta relative to alpha oscillations has been shown to suc-
cessfully discriminate between patients with acute ischemic stroke and healthy controls
(Finnigan et al., 2016). Moreover, in a group of twenty patients with ischemic stroke, a
significant inverse association was found between the delta-​alpha EEG ratio assessed at
approximately 72 hours poststroke onset and cognitive performance after 3.5 months
(Schleiger et al., 2014). Similar to what was mentioned earlier, the ratio between slow
delta and alpha (and beta) oscillations may be a sign of cortical (dys)function and/​
 THETA-BETA POWER RATIO    369

or a possible attenuation of functional cortico-​subcortical interactions (Schutter &

Knyazev, 2012).
Future studies will continue to broaden our understanding of the structural and func-
tional nature underlying slow-​fast wave EEG ratios and will further shape the use of
EEG ratios in research and the clinic. Additional questions that may be worth of in-
vestigation are the role of delta-​theta and alpha-​beta power ratios, and the effects of
abandoning the conventional bandwidths and focus on frequency-​specific oscillations.2

15.9  Summary and conclusion

Following the first observation of elevated theta-​beta power ratios in children with
ADHD, many studies have replicated this finding. In 2013 the FDA formally approved
the use of the theta-​beta power ratio as a criterion for the diagnosis of ADHD. However,
recent meta-​analyses suggest that the theta-​beta power ratio does not reliably differen-
tiate between individuals with and without ADHD. Recently, psychological research in
healthy volunteers has established reliable associations between the theta-​beta power
ratio and indices of motivation and executive functioning. Consistent with observations
in individuals with ADHD, higher theta-​beta power ratios are associated with reduced
top-​down attentional control paralleled by approach-​related motivation and seeking
behavior. These associations are conceptualized as a cortico-​limbic balance wherein
beta activity stands for cortical top-​down executive control and theta activity represents
the bottom up limbic motivational incentives. Together with the high test-​retest reli-
ability coefficients (Angelidis et al., 2016), the theta-​beta power ratio can be considered
a trait marker for capturing the reciprocal relationship between cognitive control and
motivational tendencies, and may have complementary value in diagnosis and treating
ADHD and/​or related disorders.

REFERENCES
Adrian, E. D. & Matthews, B. H. (1934). The Berger rhythm: Potential changes from the oc-
cipital lobes in man. Brain, 57, 355–​385.
Aldemir, R., Demirci, E., Per, H., Canpolat, M., Özmen, S., & Tokmakçi, M. (2018).
Investigation of attention deficit hyperactivity disorder (ADHD) sub-​types in children via
EEG frequency domain analysis. International Journal of Neuroscience, 128, 349–​336.
Angelidis, A., van der Does, W., Schakel, L., & Putman, P. (2016). Frontal EEG theta/​beta
ratio as an electrophysiological marker for attentional control and its test-​retest reliability.
Biological Psychology, 121, 49–​52

2 
Strictly speaking, an oscillation refers to rhythmic electrical activity in one specific frequency (e.g., 5
Hz) and not to a range of frequencies (e.g., theta: 4–​7 Hz)
370    DENNIS J. L. G. SCHUTTER and J. LEON KENEMANS

Angelidis, A., Hagenaars, M., van Son, D., van der Does, W., & Putman, P. (2018). Do not look
away! Spontaneous frontal EEG theta/​beta ratio as a marker for cognitive control over
attention to mild and high threat. Biological Psychology, 135, 8–​17.
Arns, M., Conners, C. K., & Kraemer, H. C. (2013). A decade of EEG theta/​beta ratio research
in ADHD: A meta-​analysis. Journal of Attention Disorders, 17, 374–​383.
Arns, M., Vollebregt, M. A., Palmer, D., Spooner, C., Gordon, E., Cohn, M., . . . Buitelaar, J. K.
(2018). Electroencephalographic biomarkers as predictors of methylphenidate response in
attention-​deficit/​hyperactivity disorder. European Neuropsychopharmacology, 28, 881–​891.
Asada, H., Fukuda, Y., Tsunoda, S., Yamaguchi, M., & Tonoike, M. (1999). Frontal midline
theta rhythms reflect alternative activation of prefrontal cortex and anterior cingulate cortex
in humans. Neuroscience Letters, 274, 29–​32.
Barry, R. J., Clarke, A. R., McCarthy, R., Selikowitz, M., Rushby, J. A., & Ploskova, E.
(2004). EEG differences in children as a function of resting-​state arousal level. Clinical
Neurophysiology, 115, 402–​408.
Bechara, A., Damasio, H., Tranel, D., & Damasio, A. R. (1997). Deciding advantageously before
knowing the advantageous strategy. Science, 275, 1293–​1295.
Braboszcz, C. & Delorme, A. (2011). Lost in thoughts: Neural markers of low alertness during
mind wandering. Neuroimage, 54, 3040–​3047.
Buyck, I. & Wiersema, J. R. (2015). Electroencephalographic activity before and after cog-
nitive effort in children with attention deficit/​hyperactivity disorder. Clinical EEG and
Neuroscience, 46, 88–​93.
Buzsaki, G. & Watson, B. O. (2012). Brain rhythms and neural syntax: Implications for effi-
cient coding of cognitive content and neuropsychiatric disease. Dialogues in Clinical
Neuroscience, 14, 345–​367.
Canales-​Johnson, A., Beerendonk, L., Blain, S., Kitaoka, S., Ezquerro-​Nassar, A., Nuiten,
S., . . . Bekinschtein, T. A. (2020). Decreased alertness reconfigures cognitive control
networks. Journal of Neuroscience, 40, 7142–​7 154.
Cavanagh, J. F., Zambrano-​Vazquez, L., & Allen, J. J. (2012). Theta lingua franca: A common
mid-​frontal substrate for action monitoring processes. Psychophysiology, 49, 220–​238.
Cavanagh, J. F. & Shackman, A. J. (2015). Frontal midline theta reflects anxiety and cognitive
control: Meta-​analytic evidence. Journal of Physiology, 109, 3–​15.
Clarke, A. R., Barry, R. J., McCarthy, R., & Selikowitz, M. (2001a). EEG-​defined subtypes
of children with attention-​deficit/​hyperactivity disorder. Clinical Neurophysiology, 112,
2098–​2105.
Clarke, A. R., Barry, R. J., McCarthy, R., & Selikowitz, M. (2001b). Age and sex effects in the
EEG: Development of the normal child. Clinical Neurophysiology, 112, 806–​814.
Clarke, A. R., Barry, R. J., McCarthy, R., Selikowitz, M., & Croft, R. J. (2002a). EEG differences
between good and poor responders to methylphenidate in boys with the inattentive type of
attention-​deficit/​hyperactivity disorder. Clinical Neurophysiology, 113, 1191–​1198.
Clarke, A. R., Barry, R. J., Bond, D., McCarthy, R., & Selikowitz, M. (2002b). Effects of stimu-
lant medications on the EEG of children with attention-​deficit/​hyperactivity disorder.
Psychopharmacology, 164, 277–​284.
Clark, L., Cools, R., & Robbins, T. W. (2004). The neuropsychology of ventral prefrontal
cortex: Decision-​making and reversal learning. Brain and Cognition, 55, 41–​53.
Cooper, P.S., Karayanidis, F., McKewen, M., McLellan-​Hall, S., Wong, A.S., Skippen, P., &
Cavanagh, J. F. (2019). Frontal theta predicts specific cognitive control-​induced behavioural
changes beyond general reaction time slowing. NeuroImage, 189, 130–​140.
 THETA-BETA POWER RATIO    371

Corbetta, M., Patel, G., & Shulman, G. L. (2008). The reorienting system of the human
brain: from environment to theory of mind. Neuron, 58, 306–​324.
Daw, N. D., O’Doherty, D. P., Seymour, B., & Dolan R. J. (2006). Cortical substrates for explora-
tory decision making. Nature, 441, 876–​879.
Di Michele, F., Prichep, L., John, E. R., & Chabot, R. J. (2005). The neurophysiology of attention-​
deficit/​hyperactivity disorder. International Journal of Psychophysiology, 58, 81–​93.
Elston, T. W., Croy, E., & Bilkey, D. K. (2019). Communication between the anterior cingu-
late cortex and ventral tegmental area during a cost-​benefit reversal task. Cell Reports, 26,
2353–​2361.
Engel, A. K. & Fries, P. (2010). Beta-​band oscillations: Signalling the status quo? Current
Opinion in Neurobiology, 20, 156–​165.
Finnigan, S., Wong, A., & Read, S. (2016). Defining abnormal slow EEG activity in acute is-
chaemic stroke: Delta/​alpha ratio as an optimal QEEG index. Clinical Neurophysiology, 127,
1452–​1459.
Food and Drug Administration (2013). De novo classification request for Neuropsychiatric
EEG-​Based Assessment Aid for ADHD (NEBA) System. Retrieved from http://​www.acc​
essd​ata.fda.gov/​cdrh_​d​ocs/​revi​ews/​K112​7 11.pdf
Gottlieb, S. (2001). Methylphenidate works by increasing dopamine levels. British Medical
Journal, 322, 259.
González Castro, P., Alvarez Pérez, L., Núñez Pérez, J. C., González-​Pienda García, J. A.,
Alvarez García, D., & Muñiz Fernández, J. (2010). Cortical activation and attentional control
in ADAH subtypes. International Journal of Clinical and Health Psychology, 10, 23–​39.
Gramszlo, C., Fogleman, N. D., Rosen, P. J., & Woodruff-​Borden, J. (2018). Intolerance of
uncertainty in children with attention-​ hyperactivity disorder. Attention Deficit
deficit/​
Hyperactivity Disorders, 10, 189–​197.
Gray, J. A. (1982). The neuropsychology of anxiety: An enquiry into the septo-​hippocampal system.
Oxford University Press.
Gray, J. A. (1985). Emotional behaviour and the limbic system. Advances in Psychosomatic
Medicine, 13, 1–​25.
Guyton, A. C. (1976). Organ physiology: Structure and function of the nervous system. W.B. Saunders.
Hacker, C. D., Snyder, A. Z., Pahwa, M., Corbetta, M., & Leuthardt, E. C. (2017). Frequency-​specific
electrophysiologic correlates of resting state fMRI networks. NeuroImage, 149, 446–​457.
Hahn, B., Ross, T. J., Yang, Y., Kim, I., Huestis, M. A., & Stein, E. A. (2007). Nicotine enhances
visuospatial attention by deactivating areas of the resting brain default network. Journal of
Neuroscience, 27, 3477–​3489.
Halawa, I. F., El Sayed, B. B., Amin, O. R., Meguid, N. A., & Abdel Kader, A. A. (2017). Frontal
theta/​beta ratio changes during TOVA in Egyptian ADHD children. Neurosciences (Riyadh),
22, 287–​291.
Harmon-​Jones, E. & Gable P. A. (2018). On the role of asymmetric frontal cortical activity in
approach and withdrawal motivation: An updated review of the evidence. Psychophysiology
[Epub], 55. doi:10.1111/​psyp.12879.
Hedges, L. V. & Olkin, I. (1985). Statistical methods for meta-​analysis. Academic Press.
Hoptman, M. J. & Davidson, R. J. (1998). Baseline EEG asymmetries and performance on
neuropsychological tasks. Neuropsychologia, 36, 1343–​1353.
Hefco, V., Yamada, K., Hefco, A., Hritcu, L., Tiron, A., & Nabeshima, T. (2003). Role of the
mesotelencephalic dopamine system in learning and memory processes in the rat. European
Journal of Pharmacology, 475, 55–​60.
372    DENNIS J. L. G. SCHUTTER and J. LEON KENEMANS

Heilman, K. M., Voeller, K. K., & Nadeau, S. E. (1991). A possible pathophysiologic substrate of
attention deficit hyperactivity disorder. Journal of Child Neurology, 6, S76–​81.
Holroyd, C. B. & Coles, M. G. H. (2002). The neural basis of human error processing: re-
inforcement learning, dopamine, and the error-​related negativity. Psychological Review, 109,
679–​709.
Holroyd, C. B. & Yeung, N. (2012). Motivation of extended behaviors by anterior cingulate
cortex. Trends in Cognitive Sciences, 16, 122–​128.
Isiten, H. N., Cebi, M., Sutcubasi Kaya, B., Metin, B., & Tarhan, N. (2017). Medication effects on
EEG biomarkers in attention-​deficit/​hyperactivity disorder. Clinical EEG and Neuroscience,
48, 246–​250.
Jarrett, M. A., Gable, P. A., Rondon, A. T., Neal, L. B., Price, H. F., & Hilton, D. C. (2017). An
EEG study of children with and without ADHD symptoms: Between-​group differences
and associations with sluggish cognitive tempo symptoms. Journal of Attention Disorders, 1,
1087054717723986.
Jasper, H., Solomon, P., & Bradley, C. (1938) Electroencephalographic analyses of behaviour
problem children. American Journal of Psychiatry, 95, 641–​658.
Jenkinson, N. & Brown, P. (2011). New insights into the relationship between dopamine, beta
oscillations and motor function. Trends in Neurosciences, 34, 611–​618.
Jensen, O. & Lisman, J.E. (1996). Novel lists of 72 known items can be reliably stored in an
oscillatory short-​term memory network: Interaction with long-​term memory. Learning &
Memory, 3, 257–​263.
Karakaş, S. & Barry, R. J. (2017). A brief historical perspective on the advent of brain oscillations
in the biological and psychological disciplines. Neuroscience and Biobehavioral Reviews, 75,
335–​347
Klass, D. W. & Brenner, R. P. (1995). Electroencephalography of the elderly. Journal of Clinical
Neurophysiology, 12, 116–​131.
Klimesch, W. (1999). EEG alpha and thetaoscillations reflect cognitive and memory perform-
ance: A review and analysis. Brain Research Reviews, 29, 169–​195.
Knott, V. J. & Fisher, D. J. (2007). Naltrexone alteration of the nicotine-​induced EEG and
mood activation response in tobacco-​deprived cigarette smokers. Experimental and Clinical
Psychopharmacology, 15, 368–​381.
Kobayashi, R., Honda, T., Hashimoto, J., Kashihara, S., Iwasa, Y., Yamamoto, K., . . . Nakao, T.
(2020). Resting-​state theta/​beta ratio is associated with distraction but not with reappraisal.
Biological Psychology, 155, 107942.
Kuczenski, R. & Segal, D.S. (2001). Locomotor effects of acute and repeated threshold doses of
amphetamine and methylphenidate: relative roles of dopamine and norepinephrine. Journal
of Pharmacology and Experimental Therapeutics, 296, 876–​83.
Lansbergen, M. M., Schutter, D. J., & Kenemans, J. L. (2007). Subjective impulsivity and base-
line EEG in relation to stopping performance. Brain Research, 1148, 161–​169.
Lansbergen, M. M., Arns, M., van Dongen-​Boomsma, M., Spronk, D., & Buitelaar, J. K.
(2011). The increase in theta/​beta ratio on resting-​state EEG in boys with attention-​
hyperactivity disorder is mediated by slow alpha peak frequency. Progress in
deficit/​
Neuropsychopharmacology & Biological Psychiatry, 35, 47–​52.
Loo, S. K., Teale, P. D., & Reite, M. L. (1999). EEG correlates of methylphenidate response
among children with ADHD: A preliminary report. Biological Psychiatry, 45, 1657–​1660.
 THETA-BETA POWER RATIO    373

Loo, S. K., Hopfer, C., Teale, P. D., & Reite, M. L. (2004). EEG correlates of methylphenidate
response in ADHD: Association with cognitive and behavioral measures. Journal of Clinical
Neurophysiology, 21, 457–​464.
Loo, S. K. & Makeig, S. (2012). Clinical utility of EEG in attention-​deficit/​hyperactivity dis-
order: a research update. Neurotherapeutics, 9, 569–​587.
Loo, S. K., McGough, J. J., McCracken, J. T., & Smalley, S. L. (2018). Parsing heterogeneity in
attention-​ deficit hyperactivity disorder using EEG-​ based subgroups. Journal of Child
Psychology and Psychiatry, 59, 223–​231.
Lubar, J. F. (1991). Discourse on the development of EEG diagnostics and biofeedback for
attention-​deficit/​hyperactivity disorders. Biofeedback and Self-​Regulation, 16, 201–​225.
Lubar, J. F. (1997). Neocortical dynamics: Implications for understanding the role of
neurofeedback and related techniques for the enhancement of attention. Applied
Psychophysiology and Biofeedback, 22, 111–​126.
Mann C., Lubar, J., Zimmerman, A., Miller, C., & Muenchen, R. (1992). Quantitative analysis
of EEG in boys with attention deficit hyperactivity disorder: Controlled study with clinical
implications. Pediatric Neurology, 8, 30–​36.
Markovska-​Simoska, S. & Pop-​Jordanova, N. (2017). Quantitative EEG in children and adults
with attention deficit hyperactivity disorder: Comparison of absolute and relative power
spectra and theta/​beta ratio. Clinical EEG and Neuroscience, 48, 20–​32.
Massar, S. A., Rossi, V., Schutter, D. J., Kenemans, J. L. (2012). Baseline EEG theta/​beta ratio
and punishment sensitivity as biomarkers for feedback-​related negativity (FRN) and risk-​
taking. Clinical Neurophysiology, 123, 1958–​1965.
Massar, S. A., Kenemans, J. L., & Schutter, D. J. (2014). Resting-​state EEG theta activity and risk
learning: sensitivity to reward or punishment? International Journal of Psychophysiology, 91,
172–​177.
McCarthy, H., Skokauskas, N., Mulligan, A., Donohoe, G., Mullins, D., Kelly,
J., . . . Frold, T. (2013). Attention network hypoconnectivity with default and affective net-
work hyperconnectivity in adults diagnosed with attention-​deficit/​hyperactivity disorder in
childhood. JAMA Psychiatry, 70, 1329–​1337.
Metin, B., Roeyers, H., Wiersema, J.R., van der Meere, J., & Sonuga-​Barke, E. (2012). A meta-​
analytic study of event rate effects on go/​no-​go performance in attention-​deficit/​hyper-
activity disorder. Biological Psychiatry, 72, 990–​996.
Miyake, A., Friedman, N. P., Emerson, M. J., Witzki, A. H., Howerter, A., & Wager, T. D. (2000).
The unity and diversity of executive functions and their contributions to complex “frontal
lobe” tasks: A latent variable analysis. Cognitive Psychology, 41, 49–​100.
Monastra, V. J., Lubar, J. F., Linden, M., van Deusen, P., Green, G., Wing, W., et al. (1999).
Assessing attention deficit hyperactivity disorder via quantitative electroencephalog-
raphy: An initial validation study. Neuropsychology, 13, 424–​433.
Monastra, V. J., Lubar, J. F., & Linden, M. (2001). The development of a quantitative
electroencephalographic scanning process for attention deficit-​ hyperactivity dis-
order: Reliability and validity studies. Neuropsychology, 15, 136–​144.
Morillas-​Romero, A., Tortella-​Feliu, M., Bornas, X., & Putman, P. (2015). Spontaneous EEG
theta/​beta ratio and delta-​beta coupling in relation to attentional network functioning
and self-​reported attentional control. Cognitive Affective and Behavioral Neuroscience, 15,
598–​560.
374    DENNIS J. L. G. SCHUTTER and J. LEON KENEMANS

Nazari, M. A., Wallois, F., Aarabi, A., & Berquin, P. (2011). Dynamic changes in quantitative
electroencephalogram during continuous performance test in children with attention-​
deficit/​hyperactivity disorder. International Journal of Psychophysiology, 81, 230–​236.
Ogrim, G., Kropotov, J., & Hestad, K. (2012). The quantitative EEG theta/​beta ratio in attention
deficit/​hyperactivity disorder and normal controls: Sensitivity, specificity, and behavioral
correlates. Psychiatry Research, 198, 482–​488.
Panksepp, J. (1998). Affective neuroscience: The foundations of human and animal emotions.
Oxford University Press.
Panksepp J. & Biven, L. (2012). The archeology of mind: Neuroevolutionary origins of human
emotions. W.W. Norton & Company.
Poole, K. L., Hassan, R., & Schmidt, L. A. (2021). Temperamental shyness, frontal EEG theta/​
beta ratio, and social anxiety in children. Child Development, 92, 2006–​2019.
Putman, P., van Peer, J., Maimari, I., & van der Werff, S. (2010). EEG theta/​beta ratio in relation
to fear-​modulated response-​inhibition, attentional control, and affective traits. Biological
Psychology, 83, 73–​78.
Putman, P., Verkuil, B., Arias-​Garcia, E., Pantazi, I., & van Schie, C. (2014). EEG theta/​beta
ratio as a potential biomarker for attentional control and resilience against deleterious
effects of stress on attention. Cognitive Affective and Behavioral Neuroscience, 14, 782–​791.
Rahman, M. M., Shukla, A., & Chattarji, S. (2018). Extinction recall of fear memories formed
before stress is not affected despite higher theta activity in the amygdala. Elife, 7, e35450.
Robbins, T. W. (2000). Chemical neuromodulation of frontal-​executive functions in humans
and other animals. Experimental Brain Research, 133, 130–​138.
Rosanova, M., Casali, A., Bellina, V., Resta, F., Mariotti, M., & Massimini, M. (2009). Natural
frequencies of human corticothalamic circuits. Journal of Neuroscience, 29, 7679–​7685.
Saad, J. F., Kohn, M. R., Clarke, S., Lagopoulos, J., & Hermens, D. F. (2018). Is the theta/​beta
EEG marker for ADHD inherently flawed? Journal of Attention Disorders, 22, 815–​826.
Satterfield, J. H. & Cantwell, D. P. (1974). Proceedings: CNS function and response to methyl-
phenidate in hyperactive children. Psychopharmacology Bulletin, 10, 36–​38.
Satterfield, J. H. & Dawson, M. E. (1971). Electrodermal correlates of hyperactivity in children.
Psychophysiology, 8, 191-​197.
Schleiger, E., Sheikh, N., Rowland, T., Wong, A., Read, S., & Finnigan, S. (2014). Frontal
EEG delta/​alpha ratio and screening for post-​stroke cognitive deficits: the power of four
electrodes. International Journal of Psychophysiology, 94, 19–​24.
Schutte, I., Kenemans, J. L., & Schutter, D. J. (2017). Resting-​state theta/​beta EEG ratio is
associated with reward-​and punishment-​related reversal learning. Cognitive Affective and
Behavioral Neuroscience, 17, 754–​763.
Schutter, D. J. & Knyazev, G. G. (2012). Cross-​frequency coupling of brain oscillations in
studying motivation and emotion. Motivation and Emotion, 36, 46–​54.
Schutter, D. J. & van Honk, J. (2005). Electrophysiological ratio markers for the balance be-
tween reward and punishment. Cognitive Brain Research, 24, 685–​690.
Schutter, D. J., Leitner, C., Kenemans, J. L., & van Honk, J. (2006). Electrophysiological
correlates of cortico-​subcortical interaction: A cross-​frequency spectral EEG analysis.
Clinical Neurophysiology, 117, 381–​387.
Schutter, D. J., de Weijer, A. D., Meuwese, J. D., Morgan, B., & van Honk, J. (2008). Interrelations
between motivational stance, cortical excitability, and the frontal electroencephalogram
asymmetry of emotion: A transcranial magnetic stimulation study. Human Brain Mapping,
29, 574–​80.
 THETA-BETA POWER RATIO    375

Sari Gokten, E., Tulay, E.E., Beser, B., Elagoz Yukse, M., Arikan, K., Tarhan, N., & Metin, B .
(2019). Predictive value of slow and fast EEG oscillations for methylphenidate response in
ADHD. Clinical EEG and Neuroscience, 50, 332–​338.
Seli, P., Smallwood, J., Cheyne, J. A., & Smilek, D. (2015). On the relation of mind wandering
and ADHD symptomatology. Psychonomic Bulletin & Review, 22, 629–​636.
Seth, A. K. (2013). Interoceptive inference, emotion, and the embodied self. Trends in Cognitive
Sciences, 17, 565–​573.
Shi, T., Li, X., Song, J., Zhao, N., Sun, C., et al. (2012). EEG characteristics and visual cogni-
tive function of children with attention deficit hyperactivity disorder (ADHD). Brain &
Development, 34, 806–​811.
Snyder, S. M. & Hall, J. R. (2006). A meta-​analysis of quantitative EEG power associated with
attention-​deficit hyperactivity disorder. Journal of Clinical Neurophysiology, 23, 440–​455.
Snyder, S. M., Quintana, H., Sexson, S. B., Knott, P., Haque, A. F. M., & Reynolds, D. A. (2008).
Blinded, multi-​center validation of EEG and rating scales in identifying ADHD within a
clinical sample. Psychiatry Research, 159, 346–​358.
Sohn, H., Kim, I., Lee, W., Peterson, B.S., Hong, H., et al. (2010). Linear and non-​linear EEG
analysis of adolescents with attention-​deficit/​hyperactivity disorder during a cognitive task.
Clinical Neurophysiology, 121, 1863–​1870.
Tortella-​Feliu, M., Morillas-​Romero, A., Balle, M., Llabrés, J., Bornas, X., & Putman, P. (2014).
Spontaneous EEG activity and spontaneous emotion regulation. International Journal of
Psychophysiology, 94, 365–​372.
Van Dongen-​Boomsma, M., Lansbergen, M. M., Bekker, E. M., Sandra Kooij, J. J., van der
Molen, M., Kenemans, J. L., & Buitelaar, J. K. (2010). Relation between res-​ting EEG to cog-
nitive performance and clinical symptoms in adults with attention-​deficit/​hyperactivity dis-
order. Neuroscience Letters, 469, 102–​106.
Van Son, D., Angelidis, A., Hagenaars, M. A., van der Does, W., & Putman, P. (2018). Early and
late dot-​probe attentional bias to mild and high threat pictures: Relations with EEG theta/​
beta ratio, self-​reported trait attentional control, and trait anxiety. Psychophysiology, 55,
e13274.
Van Son, D., de Blasio, F. M., Fogarty, J. S., Angelidis, A., Barry, R. J., & Putman, P. (2019a).
Frontal EEG theta/​beta ratio during mind wandering episodes. Biological Psychology,
140, 19–​27.
Van Son, D., de Rover, M., De Blasio, F. M, van der Does, W., Barry, R. J., & Putman, P. (2019b).
Electroencephalography theta/​beta ratio covaries with mind wandering and functional connect-
ivity in the executive control network. Annals of the New York Academy of Sciences, 1452, 52–​64.
Volkow, N. D., Wang, G., Fowler, J. S., Logan, J., Gerasimov, M., Maynard, L., . . . Franceschi, D.
(2001). Therapeutic doses of oral methylphenidate significantly increase extracellular dopa-
mine in the human brain. Journal of Neuroscience, 21, RC121.
Whitford, T. J., Rennie, C. J., Grieve, S. M., Clark, C. R., Gordon, E., & Williams, L. M. (2007).
Brain maturation in adolescence: concurrent changes in neuroanatomy and neurophysi-
ology. Human Brain Mapping, 28, 228–​237.
Williams, L. M., Hermens, D. F., Thein, T., Clark, C. R., Cooper, N. J., Clarke, S. D., . . . Kohn,
M. R. (2010). Using brain based cognitive measures to support clinical decisions in ADHD.
Pediatric Neurology, 42, 118–​126.
Williams, L. M., Tsang, T. W., Clarke, S., & Kohn, M. (2010). An ‘integrative neuroscience’
perspective on ADHD: linking cognition, emotion, brain and genetic measures with
implications for clinical support. Expert Review of Neurotherapeutics, 10, 1607–​1621.
376    DENNIS J. L. G. SCHUTTER and J. LEON KENEMANS

Wischnewski, M., Zerr, P., & Schutter, D. J. (2016). Effects of theta transcranial alternating
current stimulation over the frontal cortex on reversal learning. Brain Stimulation, 9,
705–​7 11.
Wischnewski, M., Joergensen M. L., Compen, B., & Schutter, D. J. (2020). Frontal beta
transcranial alternating current stimulation improves reversal learning. Cerebral Cortex,
30(, 3286–​3295.
Wolinski, N., Cooper, N., Sauseng, P., & Romei, V. (2018). The speed of parietal theta frequency
drives visuospatial working memory capacity. PLoS Biology, 16, e2005348.
Zhang. D. W., Li, H., Wu, Z., Zhao, Q., Song, Y., Liu, L., . . . Sun, L. (2019). Electroencephalogram
Theta/​Beta Ratio and Spectral Power Correlates of Executive Functions in Children and
Adolescents With AD/​HD. Journal of Attention Disorders, 23, 721–​732.
 CHAPTER 16

C ORTICAL S OU RC E
L O CALIZ ATION I N E E G
F REQU ENCY A NA LYSI S

WANZE XIE AND JOHN E. RICHARDS

16.1 Introduction
to Source Localization

EEG signals recorded via electrodes placed on the scalp represent the postsynaptic
potentials generated by mass synchronized pyramidal neurons perpendicular to the
cortical surface. Source localization or source analysis is the activity that aims to iden-
tify the underlying cortical generators or sources of the EEG potentials measured on the
scalp. The sources of the EEG signals may be modeled as electrical dipoles with both dir-
ectionality and amplitude. The identification of the location of dipoles is often obscured
because the current generated by these sources spreads in all directions in the brain and
is smeared by the skull. However, recent advances made in improving the techniques
for source localization have substantially increased the spatial resolution of this method
and led to the tendency towards using it as a brain imaging tool (Michel & Murray, 2012).
Source localization consists of procedures creating a forward (Hallez et al., 2007) and
an inverse (Grech et al., 2008) model. The forward model is created with a head model
and electrodes and describes the effect of an electrical source inside the head on the
EEG. The inverse model is the “inverse” of the forward model and is used with the EEG
recording to compute the location and amplitude of the sources that generated the given
EEG. The present chapter provides an overview of some widely adopted source ana-
lysis techniques and their applications to EEG frequency analysis. The importance of
using realistic head models for source analysis is also discussed. In the last section of the
chapter, we present examples for using source analysis as a neuroimaging tool in EEG
frequency analysis.
378    WANZE XIE and JOHN E. RICHARDS

16.2  Source Localization Techniques

and Solutions to the Inverse Problem

There are two major approaches to source localization. Equivalent current dipole (ECD)
models use a limited number of electrical dipoles that are computed with the forward
model to explain the distribution of the EEG on the scalp. Distributed source models use
a large set of dipole locations distributed across the brain and are calculated using the in-
verse model and the observed EEG to generate the amplitude of the current density (He
et al., 2018; Michel et al., 2004). This section presents both models and describes how
these models are used for source analysis.

16.2.1  Equivalent Current Dipole Source Localization

ECD modeling assumes that the electrical potential over the entire scalp can be
explained by a small set of source dipoles (He et al., 1987). These hypothetical dipoles
can vary in position, magnitude, and orientation in a 3D space. We can estimate the
dipole parameters by repeated optimization of the parameters of the model so that
the dipoles multiplied by the forward model fit the scalp distribution. Alternatively,
a set of a priori fixed locations can be set based on theoretical specifications of
the known effects, and thus only the parameters of orientation and magnitude
are estimated. The ECD models are overdetermined because the number of di-
pole parameters is significantly less than the number of surface sensors (i.e., EEG
electrodes), as the number of the estimated dipole parameters needs to be smaller
than the number of electrodes on the scalp to guarantee a unique (overdetermined)
solution (Michel et al., 2004).
A forward model needs to be constructed to estimate the electrical activity over the
scalp in ECD modeling, as well as distributed source modeling. The forward model
represents the head geometry and tissue conductivity and delineates how the activation
generated by the dipoles propagates to the scalp; the so called “lead-​field” matrix. The
estimated electrical activity over the scalp is calculated by applying the forward model
to the current dipoles with certain orientations and magnitudes (i.e., the forward solu-
tion). For ECD modeling, the output of this so-​called forward solution can be compared
to the actual electrical activity on the scalp, and thus the amount of variance explained
by the selected current dipoles can be calculated (Richards, 2003; Scherg, 1992). The
optimal solution is gained through the iteration of the forward solution with different
parameters (location, orientation, and magnitude) of the dipoles until the minimal re-
sidual variance is obtained (Scherg et al., 1999).
A practical concern associated with equivalent current dipole modeling is the un-
certainty about the number of dipoles and their locations that should be tested by the
forward solution. One solution to this concern is to make a priori assumptions of the
 CORTICAL SOURCE LOCALIZATION IN EEG FREQUENCY ANALYSIS    379

number and location of dipoles based on other neuroimaging data, such as functional
magnetic resonance imaging (fMRI) and positron emission tomography (PET) (Agam
et al., 2011; Foxe et al., 2003). For example, a meta-​analysis of previous fMRI reports was
conducted by Foxe and colleagues (2003) to find out the brain regions that were consist-
ently activated in the attention task used by the authors. The location of these regions
was used as a guide in their source analysis, such that the MRI coordinates of these
areas were used as the seeds for the dipoles in the forward solution, with the assumption
that the task-​related EEG activity was generated in these areas. A priori assumptions
can also be made based on theoretical rationale and findigns from previous research,
such as using the fusiform and occipital face area (FFA; OFA) as the potential sources
for the N170 component (Gao et al., 2019), the occipital and parietal regions for alpha
oscillations (Xie et al., 2017), and the pre-​central cortex for the mu rhythm (Thorpe
et al., 2016). Gao and colleagues (2019) conducted a thorough literature review of the
cortical source locations of the N170 ERP component found by previous EEG studies
and the 3D coordinates of the FFA identified by previous fMRI research, and then used
these locations as a priori defined regions of interest (ROIs) in their cortical source lo-
calization. Section 2.3 provides further information about how to define a priori ROIs
for source localization.

16.2.2  Distributed Source Modeling

In distributed source models, cortical dipoles are distributed over the entire source
space, and each dipole has a fixed location. The locations of the dipoles are called the
“source space”. The source space can be GM voxels derived from a structural MRI, the
surface of the brain or “inner compartment” in boundary element methods, or the en-
tire brain volume. A forward model is also needed for distributed source modeling. For
distributed source modeling, the forward model is combined with the source space
to estimate an inverse spatial filter (Grech et al., 2008). The inverse spatial filter, when
multiplied by the observed scalp electrical current distribution, reconstructs the current
density across the entire set of potential source locations (e.g., the current-​density re-
construction [CDR] method).
The computation of the inverse spatial filter is problematic because the inverse of the
lead-​field matrix is “underdetermined”. The relation between the scalp EEG potentials
and the source activation can be simplified and illustrated by the following equation with
the assumption that this relation is linear: Y (scalp potential) =​K∙X (source moments) +​
E (noise). In this equation, K stands for the transfer matrix from brain sources (the elec-
trical “field”) to the scalp potentials (the sensor “leads”) and is referred to as the lead-​
field matrix. Mathematically, the source moments can be calculated by a transform of
the previous equation: X =​K-​1 ∙ Y. Here, K-​1 is the inverse of the lead-​field matrix and
referred to as the inverse spatial filter, which can be used to project the measured data on
the scalp to the source space. The matrix inversion of K is “underdetermined” because
the number of sources is substantially larger than the number of surface electrodes.
380    WANZE XIE and JOHN E. RICHARDS

Thus, additional constraints must be imposed to obtain unique and well-​posed linear
inverse solutions (Grech et al., 2008; He et al., 2018).
The solution to the underdetermined construction of the inverse spatial filter is to
constrain the solution by mathematical or quantitative procedures (Grech et al., 2008;
Michel & He, 2012). The following paragraphs introduce a couple of widely adopted
solutions in distributed source modeling: minimum norm estimation (MNE), low-​
resolution electromagnetic tomography (LORETA), standardized low-​ resolution
electromagnetic tomography (sLORETA), and exact low-​resolution electromagnetic
tomography (eLORETA). Pascual-​Marqui and colleagues have made great contribution
to the development of the “LORETA family” in the past two decades (Sherlin, 2009).
A number of additional solutions have been developed and utilized by the EEG re-
search community, such as weighted MNE, shrinking LORETA FOCUSS (SLF), local
autoregressive average, and beamforming techniques. Detailed description of these
methods can be found elsewhere (Grech et al., 2008; Green & McDonald, 2009; Hallez
et al., 2007; He et al., 2018).
The first introduced algorithm or constraint to the inverse solution in distributed
source modeling was the minimum norm least-​ squares inverse (Hämäläinen &
Ilmoniemi, 1994), often called the MNE. This algorithm minimizes the least-​square
error of the estimated inverse solution X in the equation described earlier, which means
it results in an inverse solution with the lowest overall intensity (Hauk, 2004). The in-
verse solution obtained from MNE tends to be biased towards weak and superficial
sources (Michel et al., 2004). To overcome the problem of this surface-​restricted MNE
algorithm, several methods have been developed that keep the basic mathematical
relations of the MNE but alter its characteristics to resolve its weaknesses. For example,
an early modification was to use a depth-​weighting matrix in the formula to account for
the MNE’s bias toward superficial surfaces.
The LORETA algorithm was devised to add to the MNE by the additional constraint
to smooth the sources with a Laplacian filter (Pascual-​Marqui et al., 1994). The LORETA
method was also designed to solve the “surface source” issue of MNE, such that it favors
solutions with strong activation of a large number of sources and punishes solutions
with small number of surface sources. The Laplacian of the sources is a measure of spa-
tial roughness. Minimizing the Laplacian of sources leads to lower resolution in the
source space, and thus the solution of LORETA algorithm is smoother than MNE and
weighted MNE algorithms.
Pascual-​Marqui (2002) developed the more widely used inverse algorithm sLORETA,
which uses the current density estimate given by the MNE solution and weights the so-
lution by the standardized values of the current density estimate. This partially alleviates
the emphasis on superficial sources found in the MNE by enhancing the smaller deeper
sources with their lower standard deviation. It was found that sLORETA results in fewer
errors in reconstructed sources than MNE (Pascual-​Marqui, 2002). The source local-
ization accuracy has been compared using weighted MNE, LORETA, and sLORETA
by Monte-​Carlo analysis of data with different noise levels and sources with different
depth in the brain (Grech et al., 2008). Grech and colleagues found that the sLORETA
 CORTICAL SOURCE LOCALIZATION IN EEG FREQUENCY ANALYSIS    381

algorithm had the lowest level of localization error and fewest ghost sources, which are
sources estimated from the inverse solution but not actually present in the simulated
data. Therefore, sLORETA outperforms the other methods regarding the accuracy of
source localization using simulated data with different levels of artifacts.
The eLORETA algorithm is another member of the “MNE family” that is also built
upon the linear weighted MNE inverse solution and has been regarded as improvement
over the previously developed LORETA and sLORETA algorithms (Pascual-​Marqui,
2007). The eLORETA algorithm provides exact localization with zero error (i.e., no
localization bias) to the inverse solution even in the presence of measurement and
structured noise in the data. Assuming there is an activated dipole in the brain with an
arbitrary orientation and known magnitude, the scalp EEG potentials generated by this
dipole can be simulated. Applying the eLORETA algorithm as the inverse solution to
the scalp measurement would give reconstructed current density fields. The “zero error
localization” property of eLORETA means that there is zero distance between the actual
point-​test source and the reconstructed source with the absolute maximum amplitude.
It should be noted this property has not been achieved by previously published discrete
linear distributed source modeling algorithms (Pascual-​Marqui, 2007).
Jatoi and colleagues (2014) compared the source localization accuracy between
sLORETA and eLORETA for EEG data collected in an experiment with visual stimuli.
The eLORETA algorithm was found to have enhanced ability to suppress less-​significant
sources in the brain compared to sLORETA. Jatoi and colleagues also found that
eLORETA gave less localization error and clearer (less blurry) images as compared to
sLORETA. As a member of the LORETA family, the moments in neighboring neuronal
sources are also highly correlated for eLORETA.

16.2.3  The “Inverse Problem” with EEG Source Analysis

A common criticism of EEG source analysis is the “inverse problem”. The complaint is
that a unique solution to the underlying dipole sources is not possible, which occurs be-
cause an infinite number of dipole distributions can be constructed, combined with the
forward model, and produce the same distribution of EEG potentials on the scalp.
The extent to which the inverse problem affects source analysis depends on a number
of factors. The ECD modeling is the most problematic type of inverse modeling, as the
resulting model can always be improved by adding one more parameter (e.g., another
dipole), or a completely different set of dipole parameters (Hallez et al., 2007). There
is no perfect solution to the number of dipoles necessary to find a solution with ECD
modeling. Some programs using blind optimization techniques result in solutions that
are physiologically unsound.
Distributed source modeling partially alleviates the major concerns with the inverse
program. Distributed source models require no a priori assumption (nonparametric) of
the number of dipoles (sources) in the model. This minimizes the error in source local-
ization due to misspecification of the number and location of the dipoles (Grech et al.,
382    WANZE XIE and JOHN E. RICHARDS

2008; Michel et al., 2004). For example, using the CDR approach, all potential source
locations (e.g., brain volumes) are simultaneously estimated and the relative magni-
tude of the reconstructed source activity, also called the current source density (CSD),
provides the putative locations of the sources. The source space of the distributed source
models may be used to constrain the solution to physiologically reasonable positions.
For example, since the generation of the EEG occurs in the postsynaptic potentials of
the columnar pyramidal cells, the dipoles may be limited to gray matter (GM) and the
dipole directions fixed as perpendicular to the cortical surface. These characteristics
have led to a growing tendency in the past two decades to replace ECD optimization
methods with distributed source modeling.

16.2.4  Applying a priori Information as Constraints to the

EEG Inverse Solution
The linear distributed approaches devised to solve the inverse problem estimate all
possible source locations simultaneously. However, there are still an infinite number
of configurations of source activation that could generate the EEG scalp potentials,
unless a specific set of locations are selected in advance. Anatomical and physio-
logical information derived from other imaging modalities like fMRI, PET, and
magnetoencephalography (MEG) have been be applied as constraints to the EEG in-
verse solution (Michel & He, 2012). In these studies, a priori anatomical and psycho-
physiological information is used as constraints on the inverse modeling in order to
obtain a unique solution or reduce the number of potential solutions. The following two
paragraphs introduce a few examples.
These external constraints can be imposed on the construction of the forward and in-
verse models to reduce the inverse solution space a priori (Lei et al., 2011; Phillips et al.,
2002a; Phillips et al., 2002b; Yang et al., 2010) or used as a priori defined ROIs in statis-
tical analyses to reduce the family-​wise error rate (Gao et al., 2019; Xie et al., 2017). For
example, Lei and colleagues (2011) used temporally coherent brain networks derived
from fMRI data as the covariance priors of the EEG source reconstruction. This fMRI
networks-​based source imaging approach outperformed the traditional distributed
source localization methods without fMRI priors and efficiently integrated the
astonishing temporal resolution of EEG with the high spatial resolution of fMRI. In an-
other study, an fMRI activation map was used as a spatial constraint to the MNE inverse
solution, i.e., a fMRI-​weighted MNE (Yang et al., 2010). The authors first conducted in-
dependent component analysis (ICA) of the EEG time-​series. The ICs are then used to
construct a regressor to fit in the fMRI signals. The output fMRI activation map was
used as a spatial constraint to the estimation of the source distribution underlying its
corresponding IC. Reliable source reconstructed time-​frequency configuration and
functional connectivity maps were obtained by using this method for both simulated
and experimental data (Yang et al., 2010).
 CORTICAL SOURCE LOCALIZATION IN EEG FREQUENCY ANALYSIS    383

A recent study by Gao and colleagues (2019) investigated the cortical sources of the
N170 face-​sensitive ERP component. Individual structural MRI, fMRI, and EEG data
were collected. The anatomical information of the head and brain was used to create
individual realistic head models for source localization. The face-​sensitive regions
identified during the fMRI scan were used as the a priori defined ROIs in the analyses
of the reconstructed source activity of the N170 component. This procedure reduces
the family-​wise error rate that would otherwise be caused by multiple comparisons or
analyses across all source volumes in the brain.

16.3  Using Realistic Models

and Structural MRI
for Source Localization

The forward model that is used in both equivalent current dipole models and
distributed source models and is created with a head model. The head model in
EEG source localization describes media inside the head with their relative elec-
trical conductivity. The head model is the link between the source volumes and
the electrical potentials on the scalp in source analysis. The head models for
EEG source localization have progressed from spherical models with only two or
three compartments to realistic models with all different tissues of the head being
segmented and assigned for their own conductivity values. This section introduces
the importance of using realistic head models in EEG source analysis and its usage
in empirical research. Since this chapter mostly focuses on realistic head models, an
overview of other types of head models can be found elsewhere (Grech et al., 2008;
Hallez et al., 2007).

16.3.1 The Effect of Distinction between Head Tissues

in the Realistic Models for Source Analysis
An accurate head model that describes the materials inside the head and their relative
conductivity is beneficial for source analysis (Reynolds & Richards, 2009; Vorwerk
et al., 2014). The two most commonly used methods to create a realistic volume conduc-
tion head model are the boundary element method (BEM) and finite element method
(FEM). The BEM model segments the head into hierarchical compartments with homo-
geneous conductivity profiles within a compartment. The FEM model defines the con-
ductivity of individual voxels inside the head based on its material. For example, GM,
white matter (WM), and cerebrospinal fluid (CSF) would each have its own conduct-
ivity value in a FEM model.
384    WANZE XIE and JOHN E. RICHARDS

The creation of the FEM model used to be much more computational demanding
than the BEM model (Michel et al., 2004), but the computational efficiency of computers
has now been substantially improved, which makes the FEM model more applic-
able in source analysis. In a recent paper, Vorwerk and colleagues (2018) introduced
a MATLAB-​based pipeline, the “Fieldtrip-​SimBio” pipeline, that aims to reduce the
workload for the generation of multicompartment FEM models. This pipeline has been
added to the existing package of functions to create FEM models in the Fieldtrip toolbox
(Oostenveld et al., 2011), which allows for an easy construction and application of a FEM
model for source analysis (Vorwerk et al., 2018).
Many studies have found that it is important to model the inhomogeneous distri-
bution of brain and head tissues (Cho et al., 2015; Vorwerk et al., 2014). Vorwerk and
colleagues (2014) comprehensively investigated the influence of modeling versus not
modeling certain conductive tissues of the head on the EEG and MEG forward so-
lution. They tested the effect of hierarchically adding new materials to a basic three-​
compartment head model (brain, skull, scalp) on the accuracy of source localization.
Specifically, they tested the effect of the addition of realistic distribution of CSF, GM,
and WM, differentiation of the skull spongiosa and compacta, and anisotropic WM
conductivities on source localization. The largest increase in the accuracy of signal
topography and amplitude from model to model came with the addition of CSF to the
three-​compartment model, followed by lesser (but still appreciable) increases when
adding GM and WM and the anisotropic WM conductivities into the head models. The
lack of the GM/​WM distinction, or CSF, in the BEM compartment models, would re-
sult in considerable errors in the reconstructed source activities, which concurs with
Cho and colleagues’ (2015) study, which showed that the distinction between these brain
tissues in source localization is important for analyzing EEG and MEG functional con-
nectivity between cortical regions. Taken together, these findings highlight the import-
ance of modeling the head conductive compartments as realistically as possible in order
to increase the accuracy of source localization.
By contrast, a few other studies have compared the difference between using BEM
and FEM models for source localization but found no substantial difference in the
reconstructed source activation (Michel & He, 2012). For example, Birot and colleagues
(2014) compared the source localization accuracy with LORETA using BEM and FEM
models with 38 epileptic patients. These patients underwent scalp EEG and intracranial
EEG recordings and subsequent resection surgery. The results of this study implicated
that using the BEM and FEM models did not cause a significant difference in the ac-
curacy of source localization (Birot et al., 2014). This finding suggests that the choice of a
head model may not be a crucial factor for source localization using distributed localiza-
tion algorithm for some applications.

16.3.2  The Uncertainty of the Skull-​to-​Brain Conductivity

Ratio in Realistic Head Models
Another important consideration determining the accuracy of the forward and in-
verse solutions is to correctly model the conductivity of different tissues, especially the
 CORTICAL SOURCE LOCALIZATION IN EEG FREQUENCY ANALYSIS    385

brain-​to-​skull conductivity ratio (Acar & Makeig, 2013). There is a consensus that the
human skull has a much lower conductivity value than the other tissues inside the head.
However, there is dispute about the correct skull conductivity value or the skull-​to-​brain
conductivity ratio to use for creating head models (Michel & He, 2012). The ratio of 1/​
80 is commonly specified as the skull-​to-​brain conductivity ratio in head models (ei-
ther spherical or realistic), with their conductivity values being 0.0042 and 0.33 S/​m
(Siemens per meter, reciprocal of ohm Ω), respectively. The skull-​to-​brain conductivity
ratio of 1/​80 originated from studies that measured the electrical properties of brain and
head tissues (Gabriel et al., 1996; Rush & Driscoll, 1969). This ratio has been set up as
the default in several source localization toolboxes, such as brain electrical source ana-
lysis (BESA; Megis Software GmbH, Gräfelfing, Germany) and Fieldtrip (Oostenveld
et al., 2011), and widely used in empirical research and simulated studies (Ryynanen
et al., 2006).
More recent studies have suggested that the traditional skull to brain conductivity
ratio of 1/​80 might be misestimated. A few studies have been conducted to estimate
or measure the conductivity of human skull, and findings have shown that the correct
skull-​to-​brain conductivity ratio may be between 1/​15 to 1/​30, which is much higher than
the traditional ratio, and using a lower skull-​to-​brain conductivity ratio (e.g., 1/​80) may
result in shallower source locations (Acar et al., 2016; Acar & Makeig, 2013; Dannhauer
et al., 2011; Lai et al., 2005; Oostendorp et al., 2000). Therefore, the traditional ratio of
skull-​to-​brain conductivity may need to be adjusted when creating head models for cor-
tical source localization.
Bone conductivities are age dependent, with infants and children having much
higher skull conductivity values compared to adults (Odabaee et al., 2014). This
means that using the adult skull conductivity values to create head models for infant
and child participants could lead to inaccurate source localization results (Reynolds
& Richards, 2009). To this end, some source localization software, for example,
BESA, provides references for the skull-​to-​brain conductivity ratio for children and
adolescents at different ages. Recent studies have also started to adopt age-​appropriate
skull conductivity values for source localization on infant EEG data (Xie, Jensen,
et al., 2019).

16.3.3  The Importance of Realistic Head Models

for Source Localization in Pediatric Populations
Using age-​specific realistic head models for source analysis may be especially important
for pediatric populations. This is because there are substantial neuroanatomical changes
of the tissues inside the head over childhood, and the structure of a child brain differs
greatly from an adult brain (Phan et al., 2018; Reynolds & Richards, 2009; Richards, W.,
2015). For example, skull conductivity value and thickness are age dependent (Wendel,
Vaisanen, Seemann, Hyttinen, & Malmivuo, 2010), such that the skull conductivity
value is much higher for infants than adults (Odabaee et al., 2014). Using the adult skull
conductivity values for infant EEG data may have the effect of inferring the source of the
current as being shallower in the cortex than where it actually occurs.
386    WANZE XIE and JOHN E. RICHARDS

A significant advance in cortical source analysis with pediatric participants is to use

realistic head models created with individual MRIs or an age-​appropriate MRI template
(Guy et al., 2016; Hämäläinen et al., 2011; Ortiz-​Mantilla et al., 2012; Xie et al., 2017).
Although systematic estimation of skull conductivity for infants and children at different
ages has not been conducted, studies have tried to use higher skull conductivity values
for source localization for infants and young children data (Hämäläinen et al., 2011;
Ortiz-​Mantilla et al., 2012; Xie et al., 2018). There are now age-​specific MRI templates
available to the public for research purposes, which can be used to create realistic head
models for children (e.g., the Neurodevelopment MRI Database) (Richards et al., 2016).
Since the fontanels and unmended skull sutures of an infant head could allow current
flow to the scalp unimpeded by the skull, a future direction is to take the fontanels and
skull sutures and the conductivity and topographical differences between infants’ and
adults’ heads into account when creating the realistic head models for infants.

16.4  Application of Source

Localization in EEG
Frequency Analysis

Human brain oscillatory activity is generated by neural tissue in the central nervous
system spontaneously or in response to stimuli in the environment. The significance
of these oscillatory signals in sensory-​cognitive processes has become increasingly
evident. Using source localization in EEG (time) frequency analysis has made great
contributions to our understanding of the cortical mechanisms of cognitive processes
associated with oscillatory activities in various frequency bands. Using source localiza-
tion of EEG signals to obtain reconstructed cortical activities also allows us to investi-
gate functional connectivity withing and between brain networks during cognitive tasks
and resting-​state. The current section reviews the application of source localization
techniques in EEG frequency analysis and how this method has provided insights into
brain functions and network organizations.

16.4.1  EEG Source Localization in Frequency Analysis

for Cognitive Functions
The neural generators of brain oscillatory activity in different frequency bands during
cognitive tasks are of great interests to the EEG community. The functional signifi-
cance of cortical oscillations in low and high frequency bands has been specified using
source localization techniques for various cognitive processes, such as spatial attention
orienting and attentional control (Doesburg et al., 2009; Jones et al., 2010; Sauseng
 CORTICAL SOURCE LOCALIZATION IN EEG FREQUENCY ANALYSIS    387

et al., 2007), sustained attention and vigilance (Kim et al., 2017), error monitoring and
conflict processing (Cohen, 2011; Cohen & Ridderinkhof, 2013; Yeung et al., 2007),
working memory (Maurer et al., 2015; Michels et al., 2010; Michels et al., 2008; Onton
et al., 2005), motion observation and execution (Nystrom et al., 2011; Ritter et al., 2009;
Thorpe et al., 2016). There is a large body of literature on the developmental origin of
the relation between these cognitive processes and corresponding EEG oscillations (Bell
& Cuevas, 2012). EEG source localization has also made it possible to investigate the
cortical sources of EEG oscillatory activities associated with cognitive performance in
infants and children (see Section 16.4.4).
The source localization techniques discussed in the previous sections open the av-
enue to unravel the crucial role of EEG oscillatory activity in human brain functions.
For instance, Sauseng and colleagues (2007) investigated the function of the theta-​
band oscillations in sustained attention and executive control. They examined how
EEG theta-​band activity changed as a function of task difficulty and memory load. The
participants were required to execute complex sequential finger movements requiring
different levels of memory load, such as execution of a previously trained simple se-
quence, an overlearned complex sequence, or a novel complex sequence. Local frontal-​
midline theta activity on the scalp was found to be associated with the general level of
cognitive demand, with the highest power found for the most demanding condition.
This theta activity was reconstructed to the source space using the LORETA method.
Specifically, the CSD was reconstructed for more than 2000 cortical voxels across the
brain using distributed source modeling, separately for different cognitive conditions.
The source activity was then compared voxel by voxel between the conditions, and mul-
tiple comparisons were statistically controlled. The authors found that the CSD in the
anterior cingulate gyrus was significantly different between the conditions, suggesting
that theta-​band oscillations generated by this region may reflect the activation of an at-
tentional system responsible for allocating cognitive resources (Sauseng et al., 2007).
Theta-​band activity generated by the frontal cortex also plays an important role
in error monitoring (Cohen, 2011). Cohen found that EEG theta-​band activity in the
frontal electrodes was associated with error-​monitoring behaviors in adults. The author
subsequently conducted source localization of the theta-​band activity using equiva-
lent current dipole modeling with subject-​specific BEM models created with individual
MRIs. One dipole that explained the most amount of variance of the scalp potentials was
estimated per subject. The author found that the dipoles in the medial prefrontal and
anterior cingulate cortexes best explained the variance in the frontal theta activity across
subjects, suggesting that these areas are the potential sources of the distribution of the
theta activity on the scalp.
EEG oscillations generated by the frontal area has been found to play an important
role in maintaining vigilance (sustained attention) during cognitive tasks. Kim and
colleagues (2017) investigated which brain areas are engaged in controlling the mainten-
ance of vigilance using source analysis of EEG signals. Distributed source modeling with
the sLORETA algorithm was conducted to obtain smooth source activation in different
frequency bands across the entire cortex. The authors found that the activity in the left
388    WANZE XIE and JOHN E. RICHARDS

prefrontal cortex was significantly correlated with vigilance variation in the delta, beta,
and gamma bands, which suggests the involvement of this brain region in maintaining
vigilance. To sum up, these empirical studies demonstrated how using EEG source ana-
lysis in frequency analysis could advance our understanding of the neural mechanisms
underlying different cognitive processes.

16.4.2  EEG Source Localization for Clinical Applications

Imaging the neuronal activity that generates the scalp EEG oscillations is also desir-
able for clinical purposes. EEG source imaging offers a useful tool to help presurgical
evaluation of patients with epilepsy in a noninvasive way, as identifying the cortical epi-
leptic zone for ictal oscillations is crucial for surgical resection. The decent accuracy
(~80%) of using EEG source localization in determining the subsequently resected zone
has been consistently achieved across studies on pediatric (Lu et al., 2012) and adult
patients (Brodbeck et al., 2011; Yang et al., 2011). For example, Brodbeck and colleagues
investigated the sensitivity and specificity of using EEG source imaging to detect the
epileptic zone for over 150 patients who underwent surgery later. The authors found
that using EEG source imaging resulted in high sensitivity (84%) and specificity (88%)
in detecting the seizure zone. The obtained sensitivity and specificity values were even
higher than some conventional neuroimaging tools (e.g., fMRI and PET). It should be
noted that acceptable localization results were only obtained when a large number of
electrodes (>128 channels) were used for data collection (Brodbeck et al., 2011), which
suggests the importance of using sufficient electrodes to obtain a better resolution of the
topographic features, that is, to avoid distortions of the distribution of scalp potentials
due to large distances between electrodes (see Michel et al., 2004 for a thorough review
of the effect of the number of electrodes). Spectral analysis of EEG with source localiza-
tion techniques has also been applied to characterize difficulties in brain functioning
for other clinical populations, such as children with ADHD (Liotti et al., 2005), people
with tonic pain (Canuet et al., 2012), and Parkinsonian patients (Moazami-​Goudarzi
et al., 2008).

16.4.3  Applying EEG Source Analysis to Studying

Functional Brain Connectivity in the Frequency Domain
One critical question in the field of cognitive neuroscience is how brain regions in
large-​scale networks communicate and cooperate with each other during tasks and
resting-​state. The application of neuroimaging tools makes it possible for researchers
to investigate the dynamic interregional communications inside the brain and their de-
velopment throughout the lifespan. Using fMRI allows people to obtain images of the
blood-​oxygen-​level dependent (BOLD) signals in brain voxels. However, the temporal
resolution of the BOLD response in fMRI depends on blood flow occurring several
 CORTICAL SOURCE LOCALIZATION IN EEG FREQUENCY ANALYSIS    389

seconds following the demand for glucose via oxygenated hemoglobin. This restricts
fMRI connectivity analyses to “seconds” resolution and prohibits this technique from
studying dynamic changes in neural oscillations in sub-​second frequency ranges. By
contrast, EEG and MEG directly measure synchronized neuronal activity with msec
time resolution and thus can measure dynamic changes in neural oscillations at the
resolution of the neural system (e.g., sub-​seconds resolution).
The examination of EEG functional connectivity between electrodes on the scalp
has been used to study synchronized fluctuations in various rhythms that may reflect
the dynamic coordination and network structure inside the brain (Bastos & Schoffelen,
2016; Stam, 2005). A variety of methods have been developed to evaluate the “correl-
ation or synchronization” between the signals from two electrodes, such as the correl-
ation between power envelope (Hipp et al., 2012), coherence analysis (Bowyer, 2016),
and phase synchronization (Stam et al., 2007). In addition, previous work studying EEG
functional connectivity on the scalp level with infants and children provides insights
into the developmental origin of integrated brain networks (see Chu-​Shore et al., 2011
for a review). For example, Cuevas and colleagues (2012) investigated the association be-
tween infants’ working memory and inhibitory control performance in cognitive tasks
and the coherence between frontal electrodes in the alpha band. The authors found that
frontal alpha coherence was associated with inhibitory control processes in 10-​month-​
old infants, which suggests that the cooperation between brain regions already plays an
important role in cognitive performance in infancy (Cuevas et al., 2012).
The volume conduction/​field spread issue of surface EEG and the effect of the ref-
erence electrode on phase synchronization and correlation values impede our under-
standing of the underlying neural mechanisms from the EEG functional connectivity
results on the scalp (Bastos & Schoffelen, 2016; Guevara et al., 2005; Schiff, 2005).
Specifically, this problem means that the activity of a cortical source can be “visible” at
multiple electrodes due to the field smearing on the scalp. This will cause spurious cor-
relation or synchronization values between electrodes. Consequently, the interpretation
of the scalp-​level connectivity requires considerable caution because two “connected
or synchronized” electrodes may not reflect the brain regions that are functionally
connected.
Applying cortical source reconstruction methods to EEG data could substantially
mitigate the consequence of volume conduction. Brain functional connectivity using
EEG could be done by first estimating the sources of the surface signals, deriving time-​
domain activity of the cortical sources via the time-​domain activity of the surface ac-
tivity, and then doing functional connectivity in the source-​space by calculating the
correlation between amplitudes (or power envelope) of times-​series in cortical sources
or phase synchronization in different frequency bands after Fourier transformation of
the time-​series in cortical sources into the frequency domain. For example, Xie and
colleagues (2018) developed a pipeline to estimate functional connectivity in the cor-
tical source space to investigate the function of different brain networks of awake infants
(Figure 16.1). This pipeline includes cortical source reconstruction of EEG recordings
with age-​ appropriate MRIs, parcellation of the source activity into brain ROIs,
390    WANZE XIE and JOHN E. RICHARDS

estimating brain functional connectivity between ROIs by calculating the weighted

phase-​lag index (wPLI) (Vinck et al., 2011), and applying graph theory measures to
examine the overall architecture of brain networks (Figure 16.1). Using this pipeline, the
authors studied how functional connectivity in infant brain networks, such as the dorsal
and ventral attention, default mode, and somatosensory networks, changes across
different attentional states. For instance, they showed that infant sustained attention is

EGI electrodes on Source model

infant MRI template
Preprocessed EEG data
in electrodes

Infant FEM
model

Source Reconstruction

Reconstructed EEG data LPBA40 Atlas

in source voxels

20 seed-based ROIs

Parcellation of the data into ROIs

Connectivity between
LPBA40 ROIs
Parcellated EEG data
inbrain ROIs

Connectivity
analysis
wPLI

Connectivity between
the 20 seed-based ROIs

Figure 16.1  The pipeline for EEG functional connectivity analysis in the source space used by
Xie et al. (2018).
 CORTICAL SOURCE LOCALIZATION IN EEG FREQUENCY ANALYSIS    391

associated with attenuated connectivity in the alpha band within the dorsal attention
network and the DMN, as well as distinct network organization and efficiency indicated
by graph theory measures (Xie et al., 2018). This work highlights the possibility of
using source-​space functional connectivity analysis to study the development of brain
networks in early childhood. The following paragraphs introduce more recent advances
that have been made in combining EEG source localization and functional brain con-
nectivity analysis in the frequency domain.
EEG source localization can be used to detect brain functional connectivity during
tasks. The functional connectivity between frontal and parietal cortices plays an
important role in executive control. Sauseng and colleagues (2007) found a more
distributed pattern of functional connectivity in the theta band between frontal
and parietal regions when participants executed novel compared to memorized
figure movement sequences. In a more recent study, Cohen and Ridderinkhof (2013)
investigated the functional coupling between EEG signals in different frequency bands
during spatial conflict processing. Inter-​regional connectivity in the source space
was found to differ between the congruent and incongruent conditions in a Simon
task. Congruent trials induced stronger coupling between frontal theta and par-
ietal alpha and gamma power, while incongruent trials induced stronger coupling of
the theta power between the medial and lateral frontal regions. Studies also show that
the inter-​regional phase synchrony in low-​and high-​frequency bands is associated
with top-​down control of visual and auditory spatial attention (Doesburg et al., 2009;
Doesburg et al., 2012). For example, Doesburg and colleagues (2009) found increased
phase synchronization in the alpha band between the visual cortex and parietal regions
contralateral to the attended visual hemifield and decreased phase synchronization be-
tween those brain regions ipsilateral to the attended visual hemifield. The Cohen and
Doesburg studies used the beamforming technique for cortical source reconstruction.
The beamforming techniques are not covered here and have been reviewed elsewhere
(Green & McDonald, 2009).
The functional connectivity analysis in the source space of spontaneous EEG during
resting-​state has provided insights into the structure and functioning of brain networks,
as well as the development of brain networks over childhood. Liu and colleagues (2017)
detected large-​scale brain networks in human adults using high-​density EEG recordings
along with the eLORETA technique and realistic head models for source analysis. ICA
analysis of source reconstructed power envelops was conducted to extract functionally
connected brain regions (networks) in different frequency bands. Their results showed
that the brain networks identified with resting-​state EEG data (e.g., the DMN, attention
and language networks) were comparable to the brain networks obtained from prior
resting-​state fMRI research (Liu et al., 2017). Mantini and colleagues’ (2007) simultan-
eous EEG-​fMRI data were collected during resting-​state to unravel the direct relation-
ship between functional connectivity measured by the two metrics. Six major brain
networks (e.g., the DMN, auditory, visual, and attention networks) were identified from
the BOLD signals using ICA. The fluctuations in each of these fMRI-​defined resting-​
state networks were found to be correlated with EEG power in different frequency bands
392    WANZE XIE and JOHN E. RICHARDS

(e.g., delta, theta, alpha, beta, and gamma). This study was one of the first attempts to ex-
plore the link between EEG brain rhythms and low-​frequency coherent fluctuations of
the BOLD signal during resting-​state.

16.4.4  EEG Source Localization in Frequency Analysis

for Pediatric Populations
High-​density EEG offers an easy-​to-​use tool to measure brain functions for pediatric
populations. It is often the method of choice when measuring brain activity in awake
infants and older children due to its superb temporal resolution, easy application, low-​
cost of recordings and relatively higher tolerance to children’s movements compared to
other neuroimaging tools. Using EEG also makes it possible to monitor infant brain ac-
tivity corresponding to infant behaviors during cognitive tasks, for example, attention
(Xie et al., 2017), emotion processing (Xie et al., 2018) and recognition memory
(Reynolds & Richards, 2005) tasks, which could not be done with fMRI. In addition,
recent advances made in EEG source localization techniques, as reviewed earlier in the
chapter, have made EEG a comprehensive and powerful brain imaging tool with rea-
sonable spatial and superior temporal resolution (Michel & Murray, 2012). Therefore,
there is growing interest in using source analysis techniques with high-​density EEG
recordings to examine the development of the cortical sources of neural oscillations
in different frequency bands during childhood. This section gives an overview of re-
cent progress made in using EEG source localization along with frequency analysis as a
neuroimaging tool to study brain and cognitive development.
The mu rhythm (“central alpha”) has been proposed to be associated with a puta-
tive human mirror neuron system (Marshall & Meltzoff, 2011). EEG source localiza-
tion has been utilized to study the neurodevelopmental origin of the mirror neuron
system and the functional significance of the mu rhythm during early childhood.
Thorpe and colleagues (2016) investigated the structural development of the mu rhythm
during motor execution. The source analysis of the mu rhythm was conducted using
the sLORETA algorithm with age-​appropriate head models. The results of this study
showed distributed frontoparietal patterns of cortical activation in the mu rhythm.
Specifically, the source locations of the mu rhythm were concentrated in the pre-​and
post-​central gyri and the precuneus and inferior parietal regions. The source locations
of the mu rhythm were found to be consistent across three age groups—​the 1-​and 4-​
year-​olds and the adults. The finding of the posterior regions as part of the sources
generating the mu rhythm is reminiscent of two previous studies exploring the cortical
generators of the infant mu rhythm using ECD models (Nystrom, 2008; Nystrom et al.,
2011). The findings of these studies shed light on the neural generators of the mu rhythm
in children and its association with motion observation and execution.
Prior studies have suggested that brain rhythms can be manipulated by infant visual
sustained attention. However, the cortical generators of attention associated brain
rhythmic activity remained unclear. To fill this knowledge gap, a study by Xie and
colleagues (2017) explored the complex patterns of EEG oscillations and their cortical
 CORTICAL SOURCE LOCALIZATION IN EEG FREQUENCY ANALYSIS    393

sources observed during infant sustained attention. Specifically, the authors examined
whether infant sustained attention, defined with the infant heart-​rate attention model
(Richards, 2003), was accompanied by distinct EEG rhythmic activities in the theta,
alpha and beta bands in attention-​related cortical areas. Cortical source reconstruc-
tion of EEG power in different frequency bands was conducted using the eLORETA
method. Realistic head models were created for each participant using individual MRIs.
Infant sustained attention was found to be accompanied by increased theta power in the
orbitofrontal and ventral temporal areas and decreased alpha power in brain regions
within the default mode network (DMN). The relation between infant sustained
attention and EEG power was not found among infants aged 6 and 8 months, but the re-
lation emerged at age 10 months and became well established by age 12 months (Figure
16.2). This study established the a connection between infant sustained attention and
cortical oscillatory activity in the theta and alpha bands.

(a) Theta Synchronization

Sustained Attention Minus Attention Termination

6 Mos 8 Mos 10 Mos 12 Mos

12

(b) Temporal Pole Orbital Frontal Lobe Ventral Temporal Area

60 50 60
CDR amplitude [μA/mm1]

CDR amplitude [μA/mm1]

CDR amplitude [μA/mm1]

50 50
40
40 40
30
30 30
20
20 20
SO

SO

SO

SA
SA

SA

AT
AT

AT

10 10
10
0 0 0
10 Mos 12 Mos 10 Mos 12 Mos 10 Mos 12 Mos

Figure 16.2  Development of the effect of sustained attention on infant theta source activation.
(A) 3D displays for the difference in CDR amplitude between sustained attention and attention
termination separately for the four ages. Age-​appropriate average MRI templates were used for
the display for each age. Sustained attention effect was primarily shown in the temporal pole,
orbital frontal, and ventral temporal regions, especially for 10 and 12 months. (B) Bar graphs
for the average CDR amplitudes in these brain networks for 10 and 12 months. Error bars repre-
sent SEMs.
Adapted from Xie et al., 2017.
394    WANZE XIE and JOHN E. RICHARDS

Functional connectivity analysis of source reconstructed resting-​state EEG signals

has recently been adopted to study the development of brain networks with children.
Bathelt and colleagues (2013) examined the development of brain network communities
using EEG data collected when children between 2 and 6 years of age were in “resting-​
state” (watching a video clip of calming scenes). Cortical source reconstruction was
conducted with age-​ appropriate head models. Graph theory measures were also
employed to assess the organization and efficiency of brain networks. The authors
found functional modules that resembled hub networks described for fMRI and de-
velopmental changes in graph theory measures (e.g., path length) with age (Bathelt
et al., 2013). Similar methods have been used to study how deviations in early experi-
ence, such as poverty and growth faltering, shape brain networks in children living in
low-​income countries (Xie et al., 2019). In a recent study Xie and colleagues explored
brain functional connectivity as a mediator of the relation between growth faltering and
future cognitive outcomes in a longitudinal sample of impoverished Bangladeshi chil-
dren. Their results revealed that whole-​brain functional connectivity predicted future
cognitive function and, perhaps more importantly, that brain functional connectivity
at age 36 months mediated the effect of growth faltering on children’s IQ assessed one
year later.

16.5  Conclusion

This chapter introduces EEG source localization and its usage in (time) frequency
analysis. EEG source localization offers superb temporal resolution and increasingly
improved spatial resolution. Methodological progress helped to improve the accuracy
of source localization, for example, techniques developed to constrain the inverse
solutions in distributed source reconstruction. The importance of using realistic head
models and age-​appropriate conductivity values for source localization is also increas-
ingly recognized by the field, especially for research with pediatric populations. These
advances extended the application of source localization in clinical diagnosis and sci-
entific research. Studies using EEG source localization and frequency analysis provide
importance insights into the functional significance of oscillatory activities in different
frequency rhythms in cognitive processes, as well as the maturation of functional brain
networks over development.

REFERENCES
Acar, A. Z., Acar, C. E., & Makeig, S. (2016). Simultaneous head tissue conductivity
and EEG source location estimation. Neuroimage, 124(Pt A), 168–​ 180. doi:10.1016/​
j.neuroimage.2015.08.032
 CORTICAL SOURCE LOCALIZATION IN EEG FREQUENCY ANALYSIS    395

Acar, A. Z., & Makeig, S. (2013). Effects of forward model errors on EEG source localization.
Brain Topography, 26(3), 378–​396. doi:10.1007/​s10548-​012-​0274-​6
Agam, Y., Hamalainen, M. S., Lee, A. K., Dyckman, K. A., Friedman, J. S., Isom, M., . . . Manoach,
D. S. (2011). Multimodal neuroimaging dissociates hemodynamic and electrophysiological
correlates of error processing. Proceedings of the National Academy of Sciences of the United
States of America, 108(42), 17556–​17561. doi:10.1073/​pnas.1103475108
Bastos, A. M. & Schoffelen, J. M. (2016). A tutorial review of functional connectivity ana-
lysis methods and their interpretational pitfalls. Frontiers in Systems Neuroscience, 9, 175.
doi:10.3389/​fnsys.2015.00175
Bathelt, J., O’Reilly, H., Clayden, J. D., Cross, J. H., & de Haan, M. (2013). Functional brain net-
work organisation of children between 2 and 5 years derived from reconstructed activity
of cortical sources of high-​density EEG recordings. Neuroimage, 82, 595-​604. doi:10.1016/​
j.neuroimage.2013.06.003
Bell, M. A., & Cuevas, K. (2012). Using EEG to study cognitive development: issues and practices.
Journal of Cognition and Development, 13(3), 281–​294. doi:10.1080/​15248372.2012.691143
Birot, G., Spinelli, L., Vulliemoz, S., Megevand, P., Brunet, D., Seeck, M., & Michel, C.
M. (2014). Head model and electrical source imaging: a study of 38 epileptic patients.
Neuroimage: Clinical, 5, 77–​83. doi:10.1016/​j.nicl.2014.06.005
Bowyer, S. M. (2016). Coherence a measure of the brain networks: past and present.
Neuropsychiatric Electrophysiology, 2(1), 1. doi:10.1186/​s40810-​015-​0015-​7
Brodbeck, V., Spinelli, L., Lascano, A. M., Wissmeier, M., Vargas, M. I., Vulliemoz, S., . . . Seeck,
M. (2011). Electroencephalographic source imaging: a prospective study of 152 operated epi-
leptic patients. Brain, 134(Pt 10), 2887–​2897. doi:10.1093/​brain/​awr243
Cho, J. H., Vorwerk, J., Wolters, C. H., & Knosche, T. R. (2015). Influence of the head model
on EEG and MEG source connectivity analyses. Neuroimage, 110, 60–​77. doi:10.1016/​
j.neuroimage.2015.01.043
Chu-​Shore, C. J., Kramer, M. A., Bianchi, M. T., Caviness, V. S., & Cash, S. S. (2011). Network
analysis: Applications for the developing brain. Journal of Child Neurology, 26(4), 488–​500.
doi:10.1177/​0883073810385345
Cohen, M. X. (2011). Error-​related medial frontal theta activity predicts cingulate-​related
structural connectivity. Neuroimage, 55(3), 1373–​1383. doi:10.1016/​j.neuroimage.2010.12.072
Cohen, M. X. & Ridderinkhof, K. R. (2013). EEG source reconstruction reveals frontal-​
parietal dynamics of spatial conflict processing. PLoS One, 8(2), e57293. doi:10.1371/​journal.
pone.0057293
Cuevas, K., Swingler, M. M., Bell, M. A., Marcovitch, S., & Calkins, S. D. (2012). Measures of
frontal functioning and the emergence of inhibitory control processes at 10 months of age.
Developmental and Cognitive Neuroscience, 2(2), 235–​243. doi:10.1016/​j.dcn.2012.01.002
Dannhauer, M., Lanfer, B., Wolters, C. H., & Knosche, T. R. (2011). Modeling of the human skull
in EEG source analysis. Human Brain Mapping, 32(9), 1383–​1399. doi:10.1002/​hbm.21114
Doesburg, S. M., Green, J. J., McDonald, J. J., & Ward, L. M. (2009). From local inhibition
to long-​ range integration: A functional dissociation of alpha-​ band synchronization
across cortical scales in visuospatial attention. Brain Research, 1303, 97–​110. doi:10.1016/​
j.brainres.2009.09.069
Doesburg, S. M., Green, J. J., McDonald, J. J., & Ward, L. M. (2012). Theta modulation of inter-​
regional gamma synchronization during auditory attention control. Brain Research, 1431,
77–​85. doi:10.1016/​j.brainres.2011.11.005
396    WANZE XIE and JOHN E. RICHARDS

Foxe, J. J., McCourt, M. E., & Javitt, D. C. (2003). Right hemisphere control of visuospatial
attention: Line-​bisection judgments evaluated with high-​density electrical mapping and
source analysis. Neuroimage, 19(3), 710–​726.
Gabriel, C., Gabriel, S., & Corthout, E. (1996). The dielectric properties of biological tissues.
1. Literature survey. Physics in Medicine and Biology, 41(11), 2231–​2249. doi:10.1088/​0031-​
9155/​41/​11/​001
Gao, C., Conte, S., Richards, J. E., Xie, W., & Hanayik, T. (2019). The neural sources of
N170: Understanding timing of activation in face-​selective areas. Psychophysiology, 56(6),
e13336. doi:10.1111/​psyp.13336
Grech, R., Cassar, T., Muscat, J., Camilleri, K. P., Fabri, S. G., Zervakis, M., . . . Vanrumste,
B. (2008). Review on solving the inverse problem in EEG source analysis. Journal of
Neuroengineering and Rehabilitation, 5, 25. doi:10.1186/​1743-​0003-​5-​25
Green, J. J. & McDonald, J. J. (2009). A practical guide to beamformer source reconstruc-
tion for EEG. In T. C. Handy (Ed.), Brain signal analysis: Advances in neuroelectric and
neuromagnetic methods (pp. 76–​98). MIT Press
Guevara, R., Velazquez, J. L., Nenadovic, V., Wennberg, R., Senjanovic, G., & Dominguez,
L. G. (2005). Phase synchronization measurements using electroencephalographic
recordings: what can we really say about neuronal synchrony? Neuroinformatics, 3(4), 301–​
314. doi:10.1385/​NI:3:4:301
Guy, M. W., Zieber, N., & Richards, J. E. (2016). The cortical development of specialized face
processing in infancy. Child Development, 87(5), 1581–​1600. doi:10.1111/​cdev.12543
Hallez, H., Vanrumste, B., Grech, R., Muscat, J., De Clercq, W., Vergult, A., . . . Lemahieu,
I. (2007). Review on solving the forward problem in EEG source analysis. Journal of
Neuroengineering and Rehabilitation, 4, 46. doi:10.1186/​1743-​0003-​4-​46
Hämäläinen, J. A., Ortiz-​Mantilla, S., & Benasich, A. A. (2011). Source localization of event-​
related potentials to pitch change mapped onto age-​appropriate MRIs at 6 months of age.
Neuroimage, 54(3), 1910–​1918. doi:10.1016/​j.neuroimage.2010.10.016
Hämäläinen, M. S. & Ilmoniemi, R. J. (1994). Interpreting magnetic fields of the brain: Minimum
norm estimates. Medical & Biological Engineering & Computing, 32(1), 35–​42.
Hauk, O. (2004). Keep it simple: a case for using classical minimum norm estima-
tion in the analysis of EEG and MEG data. Neuroimage, 21(4), 1612–​1621. doi:10.1016/​
j.neuroimage.2003.12.018
He, B., Musha, T., Okamoto, Y., Homma, S., Nakajima, Y., & Sato, T. (1987). Electric dipole
tracing in the brain by means of the boundary element method and its accuracy. IEEE
Transactions on Biomedical Engineering, 34(6), 406–​414.
He, B., Sohrabpour, A., Brown, E., & Liu, Z. (2018). Electrophysiological source imaging: A
noninvasive window to brain dynamics. Annual Review of Biomedical Engineering, 20, 171–​
196. doi:10.1146/​annurev-​bioeng-​062117-​120853
Hipp, J. F., Hawellek, D. J., Corbetta, M., Siegel, M., & Engel, A. K. (2012). Large-​scale cortical
correlation structure of spontaneous oscillatory activity. Nature Neuroscience, 15(6), 884–​
890. doi:10.1038/​nn.3101
Jatoi, M. A., Kamel, N., Malik, A. S., & Faye, I. (2014). EEG-​based brain source localization
comparison of sLORETA and eLORETA. Australasian Physical & Engineering Sciences in
Medicine, 37(4), 713–​721. doi:10.1007/​s13246-​014-​0308-​3
Jones, S. R., Kerr, C. E., Wan, Q., Pritchett, D. L., Hamalainen, M., & Moore, C. I. (2010).
Cued spatial attention drives functionally relevant modulation of the mu rhythm in
 CORTICAL SOURCE LOCALIZATION IN EEG FREQUENCY ANALYSIS    397

primary somatosensory cortex. Journal of Neuroscience, 30(41), 13760–​13765. doi:10.1523/​

JNEUROSCI.2969-​10.2010
Kim, J.-​H., Kim, D.-​W., & Im, C.-​H. (2017). Brain areas responsible for vigilance: An EEG
source imaging study. Brain Topography, 30(3), 343–​351. doi:10.1007/​s10548-​016-​0540-​0
Lai, Y., van Drongelen, W., Ding, L., Hecox, K. E., Towle, V. L., Frim, D. M., & He, B. (2005).
Estimation of in vivo human brain-​to-​skull conductivity ratio from simultaneous extra-​
and intra-​cranial electrical potential recordings. Clinical Neurophysiology, 116(2), 456–​465.
doi:10.1016/​j.clinph.2004.08.017
Lei, X., Xu, P., Luo, C., Zhao, J., Zhou, D., & Yao, D. (2011). fMRI functional networks for EEG
source imaging. Human Brain Mapping, 32(7), 1141–​1160. doi:10.1002/​hbm.21098
Liotti, M., Pliszka, S. R., Perez, R., Kothmann, D., & Woldorff, M. G. (2005). Abnormal brain
activity related to performance monitoring and error detection in children with ADHD.
Cortex, 41(3), 377–​388.
Liu, Q., Farahibozorg, S., Porcaro, C., Wenderoth, N., & Mantini, D. (2017). Detecting large-​
scale networks in the human brain using high-​density electroencephalography. Human
Brain Mapping, 38(9), 4631–​4643. doi:10.1002/​hbm.23688
Lu, Y., Yang, L., Worrell, G. A., Brinkmann, B., Nelson, C., & He, B. (2012). Dynamic imaging
of seizure activity in pediatric epilepsy patients. Clinical Neurophysiology, 123(11), 2122–​2129.
doi:10.1016/​j.clinph.2012.04.021
Mantini, D., Perrucci, M. G., Del Gratta, C., Romani, G. L., & Corbetta, M. (2007).
Electrophysiological signatures of resting state networks in the human brain. Proceedings
of the National Academy of Sciences of the United States of America, 104(32), 13170–​13175.
doi:10.1073/​pnas.0700668104
Marshall, P. J., & Meltzoff, A. N. (2011). Neural mirroring systems: exploring the EEG mu
rhythm in human infancy. Dev Cogn Neurosci, 1(2), 110–​123. https://​doi.org/​10.1016/​
j.dcn.2010.09.001
Maurer, U., Brem, S., Liechti, M., Maurizio, S., Michels, L., & Brandeis, D. (2015). Frontal mid-
line theta reflects individual task performance in a working memory task. Brain Topography,
28(1), 127–​134. doi:10.1007/​s10548-​014-​0361-​y
Michel, C. & He, B. (2012). EEG mapping and source imaging. In D. Schomer & F. H. Lopes da
Silva (Eds.), Niedermeyer’s electroencephalography (pp. 1179–​1202). Lippincott Williams &
Wilkins.
Michel, C. M., & Murray, M. M. (2012). Towards the utilization of EEG as a brain imaging tool.
Neuroimage, 61(2), 371–​385. doi:10.1016/​j.neuroimage.2011.12.039
Michel, C. M., Murray, M. M., Lantz, G., Gonzalez, S., Spinelli, L., & Grave de Peralta, R.
(2004). EEG source imaging. Clinical Neurophysiology, 115(10), 2195–​2222. doi:10.1016/​
j.clinph.2004.06.001
Michels, L., Bucher, K., Luchinger, R., Klaver, P., Martin, E., Jeanmonod, D., & Brandeis, D.
(2010). Simultaneous EEG-​fMRI during a working memory task: Modulations in low-​and
high-​frequency bands. PLoS One, 5(4), e10298. doi:10.1371/​journal.pone.0010298
Michels, L., Moazami-​Goudarzi, M., Jeanmonod, D., & Sarnthein, J. (2008). EEG alpha
distinguishes between cuneal and precuneal activation in working memory. Neuroimage,
40(3), 1296–​1310. doi:10.1016/​j.neuroimage.2007.12.048
Moazami-​Goudarzi, M., Sarnthein, J., Michels, L., Moukhtieva, R., & Jeanmonod, D. (2008).
Enhanced frontal low and high frequency power and synchronization in the resting EEG
of parkinsonian patients. Neuroimage, 41(3), 985–​997. doi:10.1016/​j.neuroimage.2008.03.032
398    WANZE XIE and JOHN E. RICHARDS

Nystrom, P. (2008). The infant mirror neuron system studied with high density EEG. Social
Neuroscience, 3(3-​4), 334–​347. doi:10.1080/​17470910701563665
Nystrom, P., Ljunghammar, T., Rosander, K., & von Hofsten, C. (2011). Using mu rhythm de-
synchronization to measure mirror neuron activity in infants. Developmental Science, 14(2),
327–​335.
Odabaee, M., Tokariev, A., Layeghy, S., Mesbah, M., Colditz, P. B., Ramon, C., & Vanhatalo, S.
(2014). Neonatal EEG at scalp is focal and implies high skull conductivity in realistic neo-
natal head models. Neuroimage, 96, 73–​80. doi:10.1016/​j.neuroimage.2014.04.007
Onton, J., Delorme, A., & Makeig, S. (2005). Frontal midline EEG dynamics during working
memory. Neuroimage, 27(2), 341–​356. doi:10.1016/​j.neuroimage.2005.04.014
Oostendorp, T. F., Delbeke, J., & Stegeman, D. F. (2000). The conductivity of the human
skull: Results of in vivo and in vitro measurements. IEEE Transactions on Biomedical
Engineering, 47(11), 1487–​1492. doi:10.1109/​Tbme.2000.880100
Oostenveld, R., Fries, P., Maris, E., & Schoffelen, J. M. (2011). FieldTrip: Open source software
for advanced analysis of MEG, EEG, and invasive electrophysiological data. Computational
Intelligence and Neuroscience, 2011, 156869. doi:10.1155/​2011/​156869
Ortiz-​Mantilla, S., Hamalainen, J. A., & Benasich, A. A. (2012). Time course of ERP generators
to syllables in infants: A source localization study using age-​appropriate brain templates.
Neuroimage, 59(4), 3275–​3287. doi:10.1016/​j.neuroimage.2011.11.048
Pascual-​Marqui, R. D. (2002). Standardized low-​resolution brain electromagnetic tomog-
raphy (sLORETA): technical details. Methods and Findings in Experimental and Clinical
Pharmacology, 24, 5–​12.
Pascual-​Marqui, R. D. (2007). Discrete, 3D distributed, linear imaging methods of electric
neuronal activity. Part 1: Exact, zero error localization. https://​arxiv.org/​abs/​0710.3341.
Pascual-​Marqui, R. D., Michel, C. M., & Lehmann, D. (1994). Low-​resolution electromagnetic
tomography -​A new method for localizing electrical activity in the brain. International
Journal of Psychophysiology, 18, 49–​65.
Phan, T. V., Smeets, D., Talcott, J. B., & Vandermosten, M. (2018). Processing of structural
neuroimaging data in young children: Bridging the gap between current practice and
state-​of-​the-​art methods. Developmental Cognitive Neuroscience, 33, 206–​223. doi:10.1016/​
j.dcn.2017.08.009
Phillips, C., Rugg, M. D., & Friston, K. J. (2002a). Anatomically informed basis functions for
EEG source localization: Combining functional and anatomical constraints. Neuroimage,
16(3 Pt 1), 678–​695.
Phillips, C., Rugg, M. D., & Fristont, K. J. (2002b). Systematic regularization of linear inverse
solutions of the EEG source localization problem. Neuroimage, 17(1), 287–​301.
Reynolds, G. D. & Richards, J. E. (2005). Familiarization, attention, and recognition memory
in infancy: An event-​related potential and cortical source localization study. Developmental
Psychology, 41(4), 598–​615. doi:10.1037/​0012-​1649.41.4.598
Reynolds, G. D. & Richards, J. E. (2009). Cortical source localization of infant cognition.
Developmental Neuropsychology, 34(3), 312–​329. doi:10.1080/​87565640902801890
Richards, J. E. (2003). Cortical sources of event-​related potentials in the prosaccade and
antisaccade task. Psychophysiology, 40(6), 878–​894.
Richards, J. E., Sanchez, C., Phillips-​Meek, M., & Xie, W. (2016). A database of age-​appropriate
average MRI templates. Neuroimage, 124, 1254–​1259. doi:10.1016/​j.neuroimage.2015.04.055
 CORTICAL SOURCE LOCALIZATION IN EEG FREQUENCY ANALYSIS    399

Richards, J. E. X. & Xie, W. (2015). Brains for all the ages: Structural neurodevelopment in
infants and children from a life-​span perspective. In J. Benson (Ed.), Advances in child devel-
opment and behavior (Vol. 48, pp. 1–​52). Elsevier.
Ritter, P., Moosmann, M., & Villringer, A. (2009). Rolandic alpha and beta EEG rhythms’
strengths are inversely related to fMRI-​BOLD signal in primary somatosensory and motor
cortex. Human Brain Mapping, 30(4), 1168–​1187. doi:10.1002/​hbm.20585
Rush, S. & Driscoll, D. A. (1969). EEG electrode sensitivity -​an application of reciprocity. IEEE
Transactions on Biomedical Engineering, 16(1), 15-​&. doi:10.1109/​Tbme.1969.4502598
Ryynanen, O. R., Hyttinen, J. A., & Malmivuo, J. A. (2006). Effect of measurement noise and
electrode density on the spatial resolution of cortical potential distribution with different re-
sistivity values for the skull. IEEE Transactions on Biomedical Engineering, 53(9), 1851–​1858.
doi:10.1109/​TBME.2006.873744
Sauseng, P., Hoppe, J., Klimesch, W., Gerloff, C., & Hummel, F. C. (2007). Dissociation of
sustained attention from central executive functions: local activity and interregional con-
nectivity in the theta range. European Journal of Neuroscience, 25(2), 587–​593. doi:10.1111/​
j.1460-​9568.2006.05286.x
Scherg, M. (1992). Functional imaging and localization of electromagnetic brain activity. Brain
Topography, 5(2), 103–​111.
Scherg, M., Bast, T., & Berg, P. (1999). Multiple source analysis of interictal spikes: goals,
requirements, and clinical value. Journal of Clinical Neurophysiology, 16(3), 214–​224.
Schiff, S. J. (2005). Dangerous phase. Neuroinformatics, 3(4), 315–​318. doi:10.1385/​NI:3:4:315
Sherlin, L. (2009). Diagnosing and treating brain function through the use of low resolution
electromagnetic tomography (LORETA). In T. Budzynski, H. K. Budzynski, J. Evans, & A.
Abarbanel (Eds.), Introduction to quantitative EEG and neurofeedback: Advanced theory and
applications (2nd ed.), (pp. 83–​102). Academic Press.
Stam, C. J. (2005). Nonlinear dynamical analysis of EEG and MEG: Review of an emerging
field. Clinical Neurophysiology, 116(10), 2266–​2301. doi:10.1016/​j.clinph.2005.06.011
Stam, C. J., Nolte, G., & Daffertshofer, A. (2007). Phase lag index: Assessment of functional
connectivity from multi channel EEG and MEG with diminished bias from common
sources. Human Brain Mapping, 28(11), 1178–​1193. doi:10.1002/​hbm.20346
Thorpe, S. G., Cannon, E. N., & Fox, N. A. (2016). Spectral and source structural development
of mu and alpha rhythms from infancy through adulthood. Clinical Neurophysiology, 127(1),
254–​269. doi:10.1016/​j.clinph.2015.03.004
Vinck, M., Oostenveld, R., van Wingerden, M., Battaglia, F., & Pennartz, C. M. (2011). An
improved index of phase-​synchronization for electrophysiological data in the presence of
volume-​conduction, noise and sample-​size bias. Neuroimage, 55(4), 1548–​1565. doi:10.1016/​
j.neuroimage.2011.01.055
Vorwerk, J., Cho, J. H., Rampp, S., Hamer, H., Knosche, T. R., & Wolters, C. H. (2014). A guide-
line for head volume conductor modeling in EEG and MEG. Neuroimage, 100, 590–​607.
doi:10.1016/​j.neuroimage.2014.06.040
Vorwerk, J., Oostenveld, R., Piastra, M. C., Magyari, L., & Wolters, C. H. (2018). The FieldTrip-​
SimBio pipeline for EEG forward solutions. Biomedical Engineering Online, 17, 37.
doi:10.1186/​s12938-​018-​0463-​y
Wendel, K., Vaisanen, J., Seemann, G., Hyttinen, J., & Malmivuo, J. (2010). The influence of
age and skull conductivity on surface and subdermal bipolar EEG leads. Computational
Intelligence and Neuroscience, 2010, 397272. doi:10.1155/​2010/​397272
400    WANZE XIE and JOHN E. RICHARDS

Xie, W., Jensen, K. G., Wade, M., Kumar, S., Westerlund, A., Kakon, S. H., ... Nelson, C. A.
(2019). Child growth predicts brain functional connectivity and future cognitive outcomes
in urban Bangladeshi children exposed to early adversities. BMC Medicine, 17, art. no. 199.
https://​doi.org/​10.1186/​s12​916-​019-​1431-​5
Xie, W., Mallin, B. M., & Richards, J. E. (2017). Development of infant sustained attention and
its relation to EEG oscillations: An EEG and cortical source analysis study. Developmental
Science, 21, e12562. doi:10.1111/​desc.12562
Xie, W., Mallin, B. M., & Richards, J. E. (2018). Development of brain functional connectivity
and its relation to infant sustained attention in the first year of life. Developmental Science,
22, e12703. doi:10.1111/​desc.12703
Xie, W., McCormick, S. A., Westerlund, A., Bowman, L. C., & Nelson, C. A. (2018). Neural
correlates of facial emotion processing in infancy. Developmental Science, 22, e12758.
doi:10.1111/​desc.12758
Xie, W., Jensen, S. K. G., Wade, M., Kumar, S., Westerlund, A., Kakon, S. H., Haque, R., Petri, W.
A., & Nelson, C. A. (2019). Growth faltering is associated with altered brain functional con-
nectivity and cognitive outcomes in urban Bangladeshi children exposed to early adversity.
BMC Med, 17(1), 199. https://​doi.org/​10.1186/​s12​916-​019-​1431-​5
Yang, L., Liu, Z., & He, B. (2010). EEG-​fMRI reciprocal functional neuroimaging. Clinical
Neurophysiology, 121(8), 1240–​1250. doi:10.1016/​j.clinph.2010.02.153
Yang, L., Wilke, C., Brinkmann, B., Worrell, G. A., & He, B. (2011). Dynamic imaging of
ictal oscillations using non-​invasive high-​resolution EEG. Neuroimage, 56(4), 1908–​1917.
doi:10.1016/​j.neuroimage.2011.03.043
Yeung, N., Bogacz, R., Holroyd, C. B., Nieuwenhuis, S., & Cohen, J. D. (2007). Theta phase
resetting and the error-​ related negativity. Psychophysiology, 44(1), 39–​ 49. doi:10.1111/​
j.1469-​8986.2006.00482.x
 CHAPTER 17

FREQU E NC Y
CHARACTERISTI C S OF SL E E P

ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND

RÓBERT BÓDIZS

17.1  Introduction

Our life unfolds around the 24-​hour clock, structured by the periodically alternating
episodes of sleep and wakefulness. This alternation is paralleled by a series of changes
in the pattern of EEG frequencies and the level of consciousness. Sleep is often regarded
as a state of inactivity and complete relaxation, securing a general brain recovery from
prior wakefulness. Nonetheless, the magnitude of variation in the pattern of EEG
frequencies in sleep are net higher compared to wakefulness, suggesting that sleep is not
a homogeneous physiological state. Indeed, sleep involves multiple transiently recurrent
stages characterized by specific oscillatory phenomena, often utterly absent from the
waking EEG (e.g. sleep spindles, slow oscillations). The rich diversity of neural rhythms
associated with total or partial lack of consciousness in non-​rapid (NREM) or rapid eye
movement sleep (REM), respectively, conceives sleep as a unique time window allowing
for a deep insight into the functional neuro-​architecture of the brain. As a result of the
remarkable advances in the acquisition and quantitative analysis techniques of EEG
data experienced in the last decades, as well as the continuously growing interest in sleep
research across the globe, our understanding of the nature and functional significance
of sleep dependent brain oscillatory phenomena has considerably evolved. There is a
wealth of evidence supporting a tight link between features of sleep-​dependent EEG ac-
tivity and waking experience and cognitive performance. What is more, sleep EEG is
a promising source of reliable biomarkers of the disease process in neurodegenerative
disorders affecting the brain. Indeed, while sleep EEG is highly sensitive to extrinsic
factors (e.g., pharmacological agents, physical and electric stimulation), it is remarkably
modulated by intrinsic factors as well (e.g., age, sex, genetic polymorphisms, mental
health, neurological disorders). Prominent sleep dependent brain oscillations—​sleep
402    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

slow waves and sleep spindles—​are central to the cognitive and physiological function
of sleep and therefore have become the target of intervention studies aimed at boosting
sleep quality and cognitive performance by those sleep oscillations. This holds the
promise of a new line of future treatments aiming to slow down cognitive decline
associated with aging or various neurological conditions, as well as to help the rehabili-
tation process in acquired brain injury. The current chapter attempts to provide an over-
view of the most characteristic EEG rhythms and their complex coalescence/​interaction
in making up human sleep. The chapter aims at summarizing the state of the art without
being oblivious of the historical groundwork.

17.2  Human sleep and its EEG

features: The multiplicity of rhythms

The cyclic alternation of sleep and wakefulness follows a regular pattern governed by
several biological timekeeping systems that modulate a series of physiological processes,
including brain activity and sleep propensity, and thus govern the timing, duration, and
quality of sleep.

17.2.1 Circadian Rhythms
Circadian rhythms allow organisms to adapt more effectively to environmental changes
associated with the rotation of the earth (e.g., light, temperature, food availability, pre-
dation risk) and are generated by a molecular clockwork present across most cells of the
body. These individual clocks are synchronized by the master circadian clock located in
the suprachiasmatic nucleus (SCN) of the hypothalamus, which is entrained to the 24-​h
light period through the retinohypothalamic tract (Mohawk et al., 2012). The circadian
clock has a substantial impact on the organism. Its effects range from the modulation
of gene expressions and protein synthesis (Mohawk et al., 2012) through a variety of
physiological processes, including hormonal changes, immune functions (Kizaki et al.,
2015), brain arousal and neural rhythms (Cajochen et al., 2013; Dijk & Czeisler, 1995;
Lazar et al., 2015), to direct effects on cognitive performance, including learning and
memory (Santhi et al., 2016; Schmidt et al., 2007; Smarr et al., 2014; Wright et al., 2012).
Given the diurnal nature of wake-​sleep periodicity, it is not surprising that circadian
rhythms are at the heart of sleep regulation.

17.2.2 Sleep Homeostasis
The other major biological time-​related system involved in sleep regulation is the so-​
called sleep homeostasis or process H (originally called process S), which governs
 FREQUENCY CHARACTERISTICS OF SLEEP    403

Figure 17.1  Sleep-​wake cycles generated by the two-​process model (Borbely, 1982).
Thick line represents homeostatic pressure, pressure building up during wake and decaying in sleep following an
exponential dynamic; thin lines represent the circadian, C(t), modulated thresholds. White areas mark wake episodes,
shaded areas mark sleep periods. Switches between wakefulness and sleep occur at intersection points between the
homeostatic pressure and the circadian, C(t), modulated thresholds (thin lines).
Used parameters: T =​24 hours, α=​-​0.45, μ =​1, a =​0.1, χw =​18.2 hours, χs =​4.2 hours, H0–​=​0.17, H+0 ​=​0.6.

the balance between the duration and intensity of wakefulness and sleep. The longer
one stays awake and the more stimulation the brain is exposed to, the greater sleep
pressure is being accumulated, as reflected by increased slow oscillatory activity in the
following sleep episode. Process H, however, does not track time awake or asleep in a
linear manner, but builds up along an asymptotic function (see the thick lines within
non-​shaded regions in Figure 17.1), and following sleep onset it decreases exponen-
tially (see the thick lines within shaded regions in Figure 17.1). Sleep homeostasis is
closely linked to cellular metabolic-​energetic processes as well as synaptic plasticity,
and the most commonly used EEG marker for sleep homeostasis is delta or slow wave
activity (SWA) ranging between 0.5 and 4 Hz in sleep (discussed more later). Sleep
homeostasis is also under a strong age-​dependent regulation, presenting a mono-
tonically decreasing upper asymptote with aging, and is altered in depression and
neurodegenerative disorders.

17.2.3 The Two-​Process Model of Sleep Regulation

The effects of the two processes are synthesized in the so-​called two-​process model of
sleep regulation (Borbely, 1982; Daan et al., 1984). The model postulates that the timing,
duration, and the quality of sleep is defined by the interaction of the circadian and the
homeostatic processes. That is, the switch from wake to sleep happens when the homeo-
static pressure, building up exponentially towards an asymptotic value, reaches an
upper threshold that consists of a mean value (defined by age for example), modulated
by a circadian process (see the upper thin line in Figure 17.1.) (Borbely & Achermann,
1999; Skeldon et al., 2014). The switch from sleep to wake happens when homeostatic
pressure decaying exponentially reaches a lower threshold (see the lower thin line in
Figure 17.1.). Sleep duration and quality as well as numerous oscillations during sleep
show both a homeostatic and a circadian modulation (Dijk & Czeisler, 1995; Lazar
et al., 2015).
404    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

17.2.4 Ultradian Cycles
Besides circadian and homeostatic regulation, sleep is cyclical in itself—​periods of
NREM sleep alternate with REM along an ultradian rhythm in all mammals and pre-
sumably birds as well. In contrast with the largely universal period of the circadian
rhythm, which is clearly determined by alternating light-​dark cycles on Earth, the ul-
tradian sleep cycles seem to be allometrically (i.e., in a body size-​dependent manner)
regulated and are mainly a function of the metabolism ratio of the species. The average
(modal) duration of a complete NREM-​REM cycle is around 90 minutes in adult
human subjects repeating four to six times over a typical full night sleep, but the dur-
ation of a complete cycle in laboratory rats is around 11 minutes (Kaiser, 2013; Stupfel &
Pavely, 1990; Savage & West, 2007). The time structure of the consecutive sleep cycles
is complex and non-​random. Cyclic variations of various forms of sleep EEG micro-
structural phenomena, usually associated with autonomic activations, emerge with
infraslow periodicities (Halász & Bódizs, 2013). At a finer time scale, there are several
EEG frequencies that are more-​or-​less specific for either the NREM or the REM phase of
sleep. According to American Academy of Sleep Medicine (AASM) we can distinguish
non-​rapid eye movement sleep (N or NREM) that consists of three stages: N1 (NREM
1 or NREM stage 1), N2 (NREM 2 or NREM stage 2), and N3 (slow wave sleep, SWS), as
well as rapid eye movement sleep (REM). As soon as we initiate sleep, the EEG, elec-
tromyographic (EMG), and electro-​oculographic (EOG) activity goes through marked
changes compared to wakefulness (see Table 17.1). The transition from lighter (N1 or
NREM 1) to slow wave sleep (SWS) is associated with gradually decreasing muscle ac-
tivity, heart and breathing rate, and body temperature. Moreover, EEG becomes grad-
ually dominated by slower and slower frequency oscillations (in NREM 1 by theta, in
NREM 2 by mixed frequencies including K-​complexes and sleep spindles) until the en-
tire brain will present continuous slow oscillations and delta activity (slow wave activity,
SWA) in SWS. However, during REM, also called paradoxical sleep, the brain’s electric
and metabolic activity presents a significant increase as reflected in higher frequency,
low amplitude mixed EEG frequencies resembling waking brain activity. REM is also
accompanied by bursts of rapid eye movements, increased heart and breathing rates
paralleled by muscle atonia. This is the stage of sleep when most dreams are reported.
The scoring of sleep stages is based on conventions and, beyond characteristic EEG
features, it requires other polygraphic readouts such as electrooculography (EOG) and
electromyography (EMG) (Table 17.1 and Figure 17.2).

17.2.5 Infradian Rhythms
The circadian rhythm is far from being the slowest envelope of sleep rhythmicity. There
are rhythms with periods significantly longer than 24 hours (infradian). Several studies
suggest that circatrigintan (~30 days) periodicity in coherence with menstrual cycles
 FREQUENCY CHARACTERISTICS OF SLEEP    405

Table 17.1 EEG and polygraphic features of sleep stages according to the

American Academy of Sleep Medicine (Berry et al., 2017; Iber &
American Academy of Sleep, 2007).
EMG EOG
EEG (electroencephalography) (electromyography) (electrooculography)
Sleep stage features features features

N1 (NREM 1) Low-​amplitude, mixed frequency The chin EMG amplitude Slow-​rolling eye
activity in the range 4–​7 Hz is variable, often lower movements (conjugate,
and attenuated alpha activity than during wake. reasonably regular,
(<50% of the scoring epoch). sinusoidal eye
Vertex sharp waves. movements with an
initial deflection that
usually lasts >500 ms).
N2 (NREM 2) The presence of one or more K-​ The chin EMG is of Usually, eye movement
complexes unassociated with variable amplitude, but is not noticed during
arousal. usually lower than in N2.
One or more sleep spindles. wake.
N3 (SWS) SWS =​slow wave sleep. The chin EMG is of Usually, eye movements
Dominant slow wave activity: EEG variable amplitude, are not noticed during
waves of 0.5–​2 Hz and >75 often lower than in N3.
μV peak-​to-​peak amplitude, stage N2, sometimes as
measured over the frontal low as in REM sleep.
regions, referenced to the
contralateral ear or mastoid
(F4–​M1, F3–​M2).
≥20% of a staging epoch consists
of slow wave activity.
REM Low-​amplitude, mixed-​frequency Low-​amplitude chin Conjugated,
EEG activity without K-​ EMG—​baseline EMG episodic, sharply
complexes or sleep spindles. activity, usually is at peaked, irregular eye
Sawtooth waves may be present the lowest level of all movements.
as well. recording.

A staging epoch is either 20 or 30 seconds long.

of females is prevalent and well measurable in human sleep EEG (Baker & Lee, 2018).
Interestingly, a circatrigintan (circalunar) periodicity (~29.5 days) of sleep-​dependent
EEG activity has also been reported (Cajochen et al., 2013). According to this study, the
lunar cycle had a significant impact on the frequencies between 0.5 and 16 Hz. More
specifically, around the full moon, delta activity during NREM sleep decreased by 30%,
while spindles also exhibited a marked reduction compared to the days around the new
moon. This is intriguing given the role of delta waves and sleep spindles in the cognitive
and physiological function of sleep (discussed later). Although there are other studies
confirming an effect of lunar cycle on sleep duration and quality (Roosli et al., 2006;
406    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

Figure 17.2 Polysomnographic signal characteristics of sleep stages. Characteristic

electroencephalographic (EEG) and polygraphic samples (left panel) and corresponding power
spectra (right panel) measured over the left frontal (F3), central (C3), parietal (P3), and occipital
(O1) brain regions. EEG channels are referenced to the contralateral (A2 or M2) mastoid der-
ivation. Artifact free segments were concatenated into a single time series. The power spectral
density was calculated by employing Welch’s periodogram method. (Average of the squared ab-
solute value of the fast Fourier transform of four seconds long detrended and Hanning tapered
windows with 50% overlap.) Subsequently a Gaussian smoothing was applied.
 FREQUENCY CHARACTERISTICS OF SLEEP    407

Turanyi et al., 2014), these findings are still controversial due to multiple subsequent
studies failing to reproduce similar results (Cordi et al., 2014).
Details on these periodicities, rhythms, and regulatory mechanisms are discussed
across the rest of the chapter. Table 17.2 provides an overview of the relevant frequencies.

Table 17.2 An overview of the frequency characteristics of human sleep

Dominant
Frequency period/​
domain frequency Principal EEG signature Dominant method

Infradian 29.5 days Sleep architecture, Repeated sleep EEG

(circatrigintan/​ 0.392 µHz oscillatory peak frequency of recordings analyzed by FFT/​
circalunar)* sleep spindles. spindle detection.
Circadian ~24 hours Various: sleep architecture, Forced desynchrony
11.5 µHz modulation of slow wave protocol/​free running
and sleep spindle features. rhythms with continuous/​
repeated sleep EEG and FFT.
Ultradian—​sleep 90 (80–​120) min Characteristic sequence of FFT/​wavelet/​second order
cycle dynamics* 185 µHz NREM and REM sleep EEG spectra/​ modeling.
features.
Infraslow/​CAP 20–​40 s DC-​EEG recorded Full-​band EEG/​visual or
33 mHz fluctuations/​cyclic automatic detection/​
simultaneous variation of second order spectra.
sleep EEG patterns.
Slow 1–​10 s Surface-​negative large slow FFT/​slope and peak
1 Hz waves, cross-​frequency analysis.
coupling with higher
frequency oscillations
(NREM sleep).
Delta 0.25–​1 s Medium-​sized, background FFT/​autoregressive
2 Hz slow waves during NREM spectrum/​PAA
sleep.
Hippocampal RSA* 0.33–​0.66 s Rhythmic slow activity FFT/​PAA
2.25 Hz in the hippocampus/​
parahippocampal gyrus
during REM sleep.
Alpha 83.3–​125 ms (Quasi-​)sinusoidal waves FFT/​wavelet/​PAA
10 Hz with fluctuating amplitude
and posterior dominance
during eyes closed rest,
microarousals during sleep
and to some extent during
tonic REM sleep.
Sleep spindles/​ 62.5–​90.9 ms Waxing and waning FFT/​wavelet/​PAA/​ various
sigma 13 Hz oscillatory episodes in NREM detection methods.
sleep.

(continued)
408    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

Table 17.2  Continued

Dominant
Frequency period/​
domain frequency Principal EEG signature Dominant method
Beta 62.5–​33.3 ms Transient bouts of FFT/​wavelet/​PAA
22 Hz oscillations in REM sleep EEG
(“REM beta tufts”).
Gamma Locally synchronized, low FFT/​wavelet
12.5–​33.3 ms amplitude fast activity
40 Hz during SO up states and
phasic REM.
Ripples/​HFO* Short (70 ms) group Wavelet/​visual and
4–​12.5 ms of waxing and waning automatic detection.
100 Hz oscillations (0.95 µV)
primarily in NREM sleep.

FFT, Fast Fourier Transformation; PPA, Period Amplitude Analysis; *Evident allometry, human data
provided

17.3  An overall picture of sleep EEG

Before providing a detailed analysis of specific sleep EEG oscillations, we present some
core, defining features of the global picture of sleep EEG, like overall EEG amplitude,
the amplitude vs. frequency relationship, power law scaling behavior of EEG spectra,
H-​exponent, and fractality.
EEG amplitude reaches its maxima during SWS (N3 or NREM stages 3&4 according
to the Rechtschaffen and Kales criteria) in physiological circumstances (Agnew et al.,
1967). Sleep EEG total power values and/​or amplitudes are characterized by age-​related
decreases from childhood through the older ages (Astrom & Trojaborg, 1992). Moreover,
women are characterized by higher overall sleep EEG power values as compared to
men (Carrier et al., 2001; Bódizs et al., 2021). The age-​related decrease in EEG ampli-
tude power in children/​adolescents may reflect a combination of non-​neuronal factors,
like the increase in skull thickness, and neural maturation (decrease in overall synaptic
density). Women vs. men differences in overall sleep EEG amplitude are thought to
mainly reflect differences in skull thickness (Dijk et al., 1989).
EEG rhythms with lower frequency predominate in NREM sleep Stage 2 and SWS as
compared to REM sleep and wakefulness. The logarithm of sleep EEG amplitude has
been shown to be a linear function (negative correlate) of the logarithm of frequency in
NREM sleep of human volunteers (Feinberg et al., 1984). The steepness of the negative
relationship between log amplitude and log frequency is higher in young as compared to
elder subjects. The power law scaling behavior of the sleep EEG spectra is an expression
 FREQUENCY CHARACTERISTICS OF SLEEP    409

of the same phenomenon. EEG spectra can in fact be well approximated by a power law
decay function:

Pf = C × f α

where Pf denotes power at frequency f , C is a constant expressing the overall amplitude

of the EEG, and α is an exponent between −3 and −1 (Pereda et al., 1998). The power
law character is demonstrated by the linear profile of the log-​log representations of the
spectrum in Figure 17.2. A lower absolute value of the exponent α is characteristic for
wakefulness, REM sleep, and NREM Stage 2 sleep. Higher absolute α , that is, steeper
spectral slope, is seen in deeper sleep (e.g., first sleep cycle, SWS, younger subjects)
and more anterior recording sites. Figure 17.2 shows examples for steeper spectral
slopes in deeper sleep and more anterior recording sites (characterized by locally more
intense sleep). In the time domain, higher absolute α indicates a higher contribution
of low-​frequency components as compared to the high frequency ones. It is worth
noting that the α value depends on the derivation scheme and the type of recording
(surface scalp vs. electrocorticography) used for the electrophysiological recordings
during sleep. Bipolar intracranial records are characterized by higher absolute values
of α exponents (up to four during sleep) (Freeman & Zhai, 2009) as compared to sur-
face scalp referential derivations (Pereda et al., 1998; Bódizs et al., 2021). Although the
overall frequency composition of human sleep EEG can be approximated by power
law functions through fitting a straight line to the log-​log spectra and calculating
its parameters, there are characteristic upward deviations from this generally
descending trend, due to specific oscillatory events forming spectral peaks with spe-
cific frequencies (Bódizs et al., 2021; Chapter 23). In order to deliberately describe the
power spectrum by taking into account its prominent peaks, we suggest the inclusion
of a peak power function in the formula as follows (Bódizs et al., 2021):

P(f) =​C × fα × PPeak(f)

Peak power (PPeak) at frequency f equals 1 if there is no peak and is larger than 1 if there
is a spectral peak at that frequency. It has to be noted, that PPeak(f) is a whitened power
measure, because it is characterized by roughly equal power along the frequency axis and
is thus statistically independent from the spectral slope (α), which constitutes the colored
noise part of the spectrum, characterized by a power-​law type decrease along the fre-
quency scale. PPeak(f) is also normalized in terms of amplitude differences as the term C
is also partialed out from this function. By using these approaches, 191 spectral measures
were effectively reduced to 4, which were efficient in characterizing known age-​effects, sex-​
differences, and cognitive correlates of NREM sleep EEG (Figure 17.3; Bódizs et al., 2021).
Power law dependence is the hallmark of scale-​free phenomena, such as fractals.
Global sleep EEG features can be characterized by concepts related to self-​similarity
and quantified by a number of closely related measures (Ma et al., 2018; Stam, 2005).
These include the correlation dimension (Grassberger & Procaccia, 1983), the scaling
410    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

WAKE
REM
NREM1
NREM2
SWS
25 F3
Frequency (Hz) Frequency (Hz)

20
15
10
5
0
25 P3
20
15
10
5
0
0 1 2 3 4 5 6 7
Sleep time (hours)

Figure 17.3  Evolution of EEG power spectral density during one night’s sleep of a young adult
measured over the left frontal (F3) and parietal (P3) brain regions. Warmer colors represent
higher power (logarithmic scale). Temporal resolution is 10 seconds/​pixel, each representing
the average of the short-​time Fourier transforms of four segments of 4-​s long, Hanning tapered
windows with 50% overlap.

exponent emerging from detrended fluctuation analysis (Gu & Zhou, 2006), and the
Hurst exponent, H, which quantifies the smoothness of the signal (Hurst et al., 1965).
That is, a higher H, 0.5 < H < 1, indicates that the changes in the EEG voltage tend to
“go in the same direction”, or maintain the direction of the deflection for longer periods
(the signal is relatively smooth). In this case, there are positive correlations between the
successive increments in voltage. If 0 < H <0.5, the overall correlation between successive
increments is negative. The H-​exponent is closely related to the exponent, α, of the
power spectra as follows: α = 2H + 1. Moreover, the H-​exponent correlates with band-​
limited relative spectral power in a sleep stage-​and EEG derivation-​specific manner.
The H-​exponent of human sleep EEG is regularly larger than 0.5, which means that the
sleep EEG (both NREM and REM) is characterized by long-​term positive autocorrel-
ation. As expected, the H values have been reported higher during the deepest parts of
SWS compared to NREM2 and REM across all EEG derivations (Weiss et al., 2009).
In summary, sleep EEG spectra follows a power law function that is the state-​specific
features are best described by multiple frequency bands and their ratio, rather than
single band measures. In addition, the sleep EEG has fractal structure which should be
considered when characterizing different sleep-​waking states in terms of EEG criteria.

17.4  Infraslow oscillations

in sleep (ISO)

Infraslow oscillations in sleep (ISO) were originally defined as 0.01–​0.1 Hz rhythmic

or quasiperiodic changes in DC-​EEG (also known as full-​band EEG) recorded voltage.
They can be regarded as extremely low-​frequency Fourier components contributing
additively to the signal. Short-​ circuiting of skin potentials by applying Ag/​ AgCl
 FREQUENCY CHARACTERISTICS OF SLEEP    411

electrodes without Au coating and specific EEG gels are required in order to appropri-
ately detect these oscillations (Vanhatalo et al., 2005). Another class of periodic phe-
nomena in the ISO frequency range contribute multiplicatively to the signal, manifesting
as modulations of the higher frequency components (Parrino et al., 2014, Lecci et al.,
2017, Lazar et al.,2019). Evidence suggests that ISO modulates >0.5 Hz EEG activity, as
well as interictal epileptic activity during sleep (Vanhatalo et al., 2004). Long lasting (1–​5
s) occipital negative transients of 200–​700 µV are seen in the DC-​EEG records of pre-
term infants, which is probably an early form of ISO during sleep. Delta bursts have
been seen to be embedded in these transients (Vanhatalo et al., 2002). The power of ISO
correlates positively with the fMRI BOLD signal intensity of several subcortical regions,
including the cerebellum, thalamus, and the basal ganglia. In contrast, paramedian
heteromodal cortical BOLD signal intensities correlate negatively with ISO during sleep
(Picchioni et al., 2011). The ISO is a global modulation of neural excitability. The gener-
ation of ISO is hypothesized to reflect the long lasting hyperpolarizations of thalamo-
cortical cells, which might be due to the opening of some type of inwardly rectifying K
+​ channels. The latter are hypothesized to be opened by the activation of adenosine A1

receptors, while the endogenous ligand, adenosine, results from the degradation of ad-
enosine triphosphate (ATP) after its release from glial cells (Hughes et al., 2011).

17.4.1 The Cyclic Alternating Pattern (CAP)

According to Parrino, Grassi, and Milioli (2014), “Arousals during sleep would be better
conceived not as a single event but rather as part of the dynamic process, in which activating
phenomena of different intensity and morphology are organized in CAP sequences”. As the
inter-​arousal distance in CAP scoring is defined as 2–​60 s, CAP can be considered roughly an
EEG oscillation in the ISO frequency range, consisting in the alternation of two phases: the
A phase and the B phase. The A phase is thought to be the reactive part characterized by the
activation of several EEG, and in some cases autonomic, phenomena, whereas the B phase
is a background activity characteristic of the actual stage of NREM sleep. CAP A phase has
three subtypes. Increasing activation is a characteristic feature of these subtypes as follows: A1
contains only slow EEG components (SO), A2 is a mixture of slow and fast (alpha, beta) EEG
features, while A3 is characterized by purely fast EEG components (Parrino et al., 2014). It is
worth noting that A1 was recently considered a sleep defense mechanism, a so-​called delta
injection providing an instant sleep homeostasis in coherence with the actual sleep need and
the sleeper’s inner and outer environment (Halász & Bódizs, 2013). The relative time spent in
CAP as compared to non-​CAP sleep indicates the level of microstructural instability of sleep,
with more time spent in CAP indicating more instability.

17.4.2 Infraslow Oscillations (ISO) in Slow Wave Activity

and Sleep Spindles
Indirect measures (e.g. spectrum of spectra) of both ISO and CAP are reported in several
studies focusing on the periodicity of sleep EEG phenomena in humans. For example,
412    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

sleep EEG slow wave activity (0.5–​4.5 Hz) was shown to be characterized by a 20–​30 s
periodicity in human volunteers (Achermann & Borbely, 1997), which might indicate
a CAP-​like fluctuation of slow wave amplitude (involving A1 and/​or A2 phases). Sleep
spindle activity (see below) was shown to be organized in rhythmic wave sequences
according to multiple frequencies. One of these frequencies falls in the ISO range
and implies a sleep spindle periodicity of 50–​100 s (0.01–​0.02 Hz) in both mice and
humans (Lazar et al., 2019; Lecci et al., 2017). Using the spectrum of spectra approach
(calculating the power of the multivariate time series obtained from the short-​time
Fourier transform for the signal), it was shown that the ISO (0.01–​0.02 Hz) of the sigma
(10–​15 Hz) power (frequency range corresponding to sleep spindles) is coordinated
with cardiac oscillations and composed of two phases: one with enhanced and one with
decreased environmental alertness (Lecci et al., 2017). Moreover, the intensity of ISO
in the sigma power predominate in NREM 2 and over the posterior regions in humans,
and is positively associated with declarative memory recall performance following sleep
(Lecci et al., 2017). Recently, ISO in sleep spindle activity were also quantified. The novel
method computes the infrapower of an on/​off binary square signal corresponding with
individually detected sleep spindles. This infrapower is contrasted with that from a com-
putation where the same sleep spindles and inter-​spindle lapses are randomly reshuffled
so that large-​scale temporal structures are suppressed. The method validated using
surrogate data strictly addresses the large-​scale temporal structures in the sequence of
spindle events, does not manifest any obvious biases and is extensible to other phasic
phenomena such as slow waves. The study showed that ISO were strongest in the fast
sigma band (13–​15 Hz). Further, a robust infra peak of individually detected fast sleep
spindles was identified. This intensity and frequency of this peak were modulated by
topography, sleep stage, and sleep history. The power of ISO in fast sleep spindles is most
prominent in the centro-​parieto-​occipital brain regions, left hemisphere, and second
half of the night, independent of the number of sleep spindles. The frequency of ISO
is higher over the frontal and temporal brain regions and in the first half of the night
(Lazar et al., 2019).

17.5  The sleep slow oscillation (SO)

Slow EEG waves are among the most well established neurophysiological features
of sleep (Figure 17.2). Their presence was apparent in the very first all-​night sleep
EEG records (Loomis et al., 1937). The most prominent type of slow wave activity in
the sleep EEG is the slow oscillation (SO; 0.1–​1 Hz). The first comprehensive descrip-
tion and experimental analysis of the sleep SO was given by Mircea Steriade and his
colleagues (Steriade, Contreras et al., 1993; Steriade et al., 1993a, 1993b). Cycles of the SO
are characterized by a more-​or-​less regular sequence of neuronal silence/​disfacilitation,
characterized by a surface negative deflection (down state) and a burst-​like neuronal
firing, taking the form of a surface positive component (up state). Down states are
 FREQUENCY CHARACTERISTICS OF SLEEP    413

characterized by a non-​selectively reduced neural oscillations, while the up states are

accompanied by higher frequency rhythms (delta waves, spindles, gamma oscillations,
ripples). It is worth noting that down states are more synchronized over the cortex than
the up states. The preferential time for the emergence of SO events is slow wave sleep
(SWS) or Stage N3, although they are present in NREM Stage 2 sleep as well (to a lower
extent). Sleep SO is a travelling wave. That is, the majority of the events are generated
over the prefrontal cortex. The antero-​posterior direction is the most common, but not
exclusive, route of travelling, with a speed of 1.2–​7 m/​s (Massimini et al., 2004).
SO emergence is non-​monotonic during the deepening of sleep. Spontaneous or re-
active (stimulation-​triggered) SO down states emerge in any part of NREM sleep, except
Stage 1. Some of these events are known as K-​complexes, composed predominantly by
a singular down state (Cash et al., 2009). K-​complexes can be elicited by any kind of
stimulation. Spontaneous events are thought to emerge at an average frequency of 1–​1.7
events per minute. The highest K-​complex emergence is seen in the ascending Stage 2
sleep periods of NREM phases (Halasz, 2005; Halász & Bódizs, 2013).
In addition to the K-​complexes, NREM Stage 2 sleep is rich in SO cycles. These cycles
are frequently grouped in the A phases of the CAP, which means that the gradual in-
crease of SO during the descending slope (deepening part) of sleep cycles is periodic
and burst-​like (Ujma et al., 2018).
The characteristic features of the SO depend on several factors, but most of these
factors (e.g., age, sleep cycles, sleep deprivation) converge as sleep pressure. High sleep
pressure (early sleep, prepubertal age, rebound sleep) is characterized by higher amp-
litude, higher frequency (up to 1 Hz and perhaps sometimes even slightly above), and
steeper SO events, which are less-​frequently interrupted by secondary peaks. Aging is
characterized by decreased sleep pressure, and thus decreased amplitude, frequency,
and steepness of SO events. The age-​related decrease in SO/​delta power is attenuated in
subjects with high intelligence as compared to subjects with average intelligence (Potari
et al., 2017).
Sleep SO are generated in the cortex (Steriade & Amzica, 1998). Likewise, cortico-​
cortical connections are needed to synchronize sleep SO over cortex. However, SO
spread over and are expressed in several subcortical and non-​(neo)cortical structures,
including the thalamus, the basal forebrain, and the hippocampus. Powerful inward
transmembrane currents, mainly localized to the supragranular layers, characterize SO
up states in humans. Although neuronal firing is present, it is sparse, and significantly
lower, when compared to animal studies (Csercsa et al., 2010). Suppressed cell firing and
hyperpolarizing currents are found in the SO down state (Csercsa et al., 2010).

17.6  Delta waves

Delta waves (activity) are medium-​sized EEG waves of 1–​4 Hz, prevailing in the NREM
phase of sleep (maximal delta is present in SWS). The term delta activity (the spectral
414    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

component corresponding to the frequency range of delta waves) is interchangeably

used with slow wave activity (SWA), which normally refers to a slightly broader fre-
quency range (0.5–​4.5 Hz). Thus, delta frequency is higher than SO frequency, whereas
its amplitude is lower than SO amplitude. In addition, SWA usually refers to a composite
spectral measure of SO and delta activity.
Delta activity and SWA peak in the middle of consecutive sleep cycles and present
a strong homeostatic regulation: their amplitude (power) declines across successive
sleep cycles and increases linearly as a function of the amount of pre-​sleep wake-
fulness (Campbell et al., 2006). Delta waves also present a strong fronto-​posterior
gradient with higher values over the frontal region and are associated with local
sleep regulation. Those brain regions present higher homeostatic sleep pressure as
reflected by higher sleep dependent delta activity, which undergoes more intense
stimulation/​plastic changes during the wake period prior to sleep onset (Huber et al.,
2007; Huber et al., 2006; Huber et al., 2004; Kattler et al., 1994). Neural synchroniza-
tion, as mediated by synaptic strength that increases with presleep stimulation and
decreases with slow wave sleep, is thought to be one of the mechanisms underpin-
ning local sleep and the homeostatic sleep drive. This theory has received significant
experimental support, framing the synaptic homeostasis theory of sleep (Tononi &
Cirelli, 2014).
Slow waves in sleep within the broader delta wave frequency range (0.5–​4 Hz)
show marked circadian regulation in a topographical manner, albeit under signifi-
cant homeostatic regulation. The slope of delta waves that had been considered a sur-
rogate marker of sleep homeostasis and shown to reflect synaptic strength (steeper
slope =​higher synaptic strength and higher sleep pressure) (Vyazovskiy et al.,
2009) presents greater circadian than homeostatic modulation over the central brain
regions (Lazar, et al., 2015). This suggests that synaptic strength and plasticity are both
under a homeostatic use dependent modulation, as well as a direct circadian modula-
tion (Frank & Cantera, 2014).
There is ongoing debate whether sleep EEG delta waves should be considered sep-
arate entities and not only reflections of the relatively sharper surface negative waves
of the SO, or reflections of the faster up-​down alternation caused by increased sleep
pressure. Historically, delta waves have been considered separate entities (Steriade,
Contreras, et al., 1993; Steriade et al., 1993a, 1993b). Two separate origins of delta ac-
tivity were hypothesized: clock-​like thalamocortical delta oscillations and cortical delta
oscillations (Amzica & Steriade, 1998). The view of a distinct SO and delta frequency
range is supported by the clear differences in delta vs. SO generation mechanisms. In
contrast to SO, delta waves are generated in the thalamocortical system with the in-
volvement of T-​type Ca2 +​ channels (Crunelli et al., 2018; Lee et al., 2004). This mech-
anism is similar to the sleep spindle rhythmogenesis and is hypothesized to differ in
the overall level of hyperpolarization of thalamocortical neurons. In the case of delta
generation, the hyperpolarization of the wave is higher than in the case of sleep spindle
generation.
 FREQUENCY CHARACTERISTICS OF SLEEP    415

17.7  Theta waves and rhythmic

hippocampal slow activity

Perhaps one of the most persistent focuses of electrophysiological research is the phe-
nomenon of hippocampal rhythmic slow activity (RSA), or the so-​called hippocampal
theta rhythms during exploratory behavior and REM sleep of different mammalian
species. However, the term theta is confusing as there is evidence for clear allometry
in the frequency of hippocampal RSA. Animals with larger brains are characterized
by lower frequency hippocampal RSA (Blumberg, 1989), which means that human
hippocampal RSA measured in REM sleep falls in the delta (1.5–​3 Hz), but not in the
theta, frequency range (Bodizs et al., 2001). The confusion in the literature is further
increased by the fact that there are indeed clear theta frequency oscillations during
the REM phases of sleep in humans, but these oscillations are of frontomedial/​an-
terior cingular origin (frontal midline theta), and not hippocampal, as it was implicitly
assumed.

17.7.1 REM Sleep Hippocampal RSA

Given the peculiarities of human neuroanatomy, direct (para)hippocampal records can
only be done in clinical situations, primarily during (semi-​) invasive presurgical evalu-
ation procedures of patients suffering from pharmaco-​resistant epilepsy. Such records
clearly indicate that human hippocampal RSA emerges during REM sleep and its
modal frequency is roughly 2 Hz (Bodizs et al., 2001) or 3 Hz (Moroni et al., 2012). These
findings confirm the theory of the allometric nature of hippocampal RSA (Blumberg,
1989). There is no evidence for a phasic vs. tonic difference in REM sleep hippocampal
RSA. In addition, interhemispheric coherence of REM sleep human hippocampal RSA
is low (Bodizs et al., 2001; Moroni et al., 2012). Indeed, REM sleep hippocampal RSA is
phase coupled with high frequency (20–​240 Hz) oscillations, as has been reported in
several rodent studies (Clemens et al., 2009).

17.7.2 Frontal Midline Theta Activity during NREM Stage

1 and REM Sleep
Theta rhythms of frontal origin are evidently present in the period of sleep initi-
ation (NREM Stage 1), as well as during the REM phase of sleep. Based on the dom-
inant topography of this activity, some authors call it frontal midline theta activity.
The term refers to a train of rhythmic waves around the frequency of 6 Hz. There is
evidence for the relationship between frontal midline theta and dreaming (Inanaga,
416    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

1998). There is preliminary evidence for the anterior cingulate origin of the frontally
recorded theta rhythm in REM sleep (Nishida et al., 2004; Uchida et al., 2003). It has
been shown that REM sleep EEG frontal theta activity is involved in emotional memory
consolidation (Goldstein & Walker, 2014) and the incorporation of recent waking-​life
experiences in dreams (Eichenlaub et al., 2018). In addition, resilience against PTSD is
indexed by higher REM sleep EEG theta activity (Cowdin et al., 2014). More recently a
decrease in REM-​dependent theta activity has been identified as a marker of looming
neurodegeneration in pre-​manifest and manifest patients carrying the mutant gene for
Huntington’s disease (Lazar, Panin, et al., 2015; Piano et al., 2017).

17.8  Sawtooth waves during REM sleep

Sawtooth waves are 1.5–​5 Hz (mean frequency: 2.5 Hz) notched triangular waves that
occur in bursts with a mean duration of 7 s (range 2–​26 s) in the frontocentral region
of REM sleep EEG records (Figure 17.4). The bursts have the appearance of teeth on
a saw (Pearl et al., 2002). Evidence suggests the lower level of sawtooth wave activity
characterizes the first REM sleep episode (Pearl et al., 2002), as well as the early emer-
gence of sawtooth waves during the NREM-​REM transition (Sato et al., 1997).

17.9  Alpha waves during sleep

When compared to presleep quiet wakefulness, the level of EEG alpha activity is
attenuated during sleep. Various frequency limits for defining sleep EEG alpha ac-
tivity are seen in the literature. The major issue is the differentiation of alpha from
sleep spindles (Section 17.11). Realistic frequency boundaries in healthy adults are 7–​10,
7–​11, or 8–​11 Hz. However, sleep spindles (as well as waking alpha) are slower in pre-
pubertal children, thus the above criteria cannot be automatically transferred to all ages.
Individual alpha peak frequency in the presleep period is lower than the spindle peak
frequencies; thus presleep alpha peaks should be used as individual anchors for a delib-
erate and individualized frequency determination.
Continuous or intermittent alpha waves are most frequently considered as signs of
(micro)arousals. Transient increases in alpha power are parts of the A2 and A3 types
of microarousals embedded in CAP sequences, which are characterized by mixed low
and high frequency and exclusively high frequency EEG components, respectively,
indicating neural activation (Parrino et al., 2014). Moreover, ongoing posterior alpha ac-
tivity can be considered an index of covert waking brain activity during sleep, indicating
shallower/​more perturbated sleep and higher reactivity to external stimuli (McKinney
et al., 2011). A peculiar mix of alpha activity with sleep EEG delta waves is termed alpha-​
delta sleep. Alpha-​delta sleep consists of epochs made up by delta wave-​dominated
 FREQUENCY CHARACTERISTICS OF SLEEP    417

Vertex sharp transients

F3
NREM 1
C3

P3

O1

Positive occipital sharp transients (POST)

F3

C3
NREM 2

P3

O1

Sawtooth waves

F3

C3
REM

P3
20 μV

O1
1 sec

Figure 17.4 EEG samples with characteristic EEG oscillations including Vertex sharp
transients in NREM 1, positive occipital sharp transients (POST) in NREM 2 and Sawtooth waves
in REM sleep.

segments (5–​20%) mixed and filled up with large amplitude alpha waves (Hauri &
Hawkins, 1973). Fibromyalgia syndrome (Branco et al., 1994), major depressive disorder
(Jaimchariyatam et al., 2011) and psychological features, like insecure attachment (Sloan
et al., 2007), are associated with more alpha-​delta waves during sleep.
418    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

The issue of alpha activity in REM sleep is somewhat more complex, however.
Although, posterior alpha is a reliable measure of instantaneous sleep depth and re-
sponsiveness in REM sleep (McKinney et al., 2011), alpha activity is higher and more
synchronized in tonic (no actual rapid eye movements), as compared to phasic (actual
bursts of rapid eye movements) REM episodes (Simor et al., 2018; Simor et al., 2016). In
addition, there is evidence of increased high alpha frequencies (10–​14 Hz, which are not
sleep spindles) in the REM sleep records of subjects with frequent nightmares (Simor
et al., 2013).

17.10  Vertex sharp transients

and positive occipital sharp
transients (POSTs)

Sharp negative waves with a maximum at the vertex are frequently seen during the ini-
tiation of sleep, most frequently in NREM Stage 1 sleep (Figure 17.4). Although these
transients, called vertex sharp waves, resemble some interictal epileptic discharges,
these sharp waves are physiological and do not indicate the presence of any epileptic
processes, even if a complete lateralization of the phenomenon is seen (Brenton &
Mytinger, 2015). Vertex sharp waves and N300 components of averaged EEG responses
to stimuli with different modalities have been shown to have common sources (Colrain
et al., 2000).
Positive occipital sharp transients of sleep are also parts of the EEG picture of
shallower phases of sleep, however, unlike vertex sharp waves, they are often seen in
NREM Stage 2 sleep as well (Figure 17.4). The first thirty minutes of NREM sleep is the
period of preferred emergence of positive occipital sharp transients (Egawa et al., 1983).
The occipital maximum is hypothesized to be related to some activations in the visual
areas of the brain.

17.11  Sleep spindles

Putative sleep spindle-​like waveforms were first described by Hans Berger, the founder
of human EEG, as oscillatory episodes with a 72-​ms wavelength (equaling 13.89 Hz)
in a female schizophrenic patient in (rectally induced) tribromoethanol narcosis
(Berger, 1933). Soon thereafter, Alfred Lee Loomis described and named the sleep
spindles as being very regular 14-​Hz bursts, lasting 1–​1.5 seconds, adding that the amp-
litude increases and decreases steadily before and after reaching its maximum, respect-
ively (Loomis et al., 1935) (Figure 17.2). In the next decades, sleep spindles were mainly
considered as hallmarks of Stage 2 sleep, but experimental studies clearly indicated
 FREQUENCY CHARACTERISTICS OF SLEEP    419

their role in sleep protection or thalamic gating, also known as shock-​absorbing

function.

17.11.1 Frequency of Sleep Spindles

The frequency of sleep spindles (sigma rhythm) has been established as 14 Hz (Loomis
et al., 1935; Brazier, 1961), 12–​14 Hz (Rechtschaffen & Kales, 1968), 11–​15 Hz (A glossary of
terms most commonly used by clinical electroencephalographers, 1974; Noachtar et al.,
1999), 12–​16 Hz (Hori et al., 2001), and 11–​16 Hz (Berry et al., 2017; Iber & American
Academy of Sleep, 2007; Kane et al., 2017; Silber et al., 2007). Based on their frequency
and dominant topography, sleep spindles were categorized as frontal slow (12 Hz) and
centro-​parietal fast (14 Hz), as well as 10 Hz global spindles (Gibbs & Gibbs, 1958).
However, the 10-​Hz global sleep spindles were later considered as alpha waves during
sleep; thus, the existence of this type of spindle wave remained controversial (Jankel &
Niedermeyer, 1985). Other studies have provided evidence that the slow spindle fre-
quency decelerates as sleep deepens (Andrillon et al., 2011); thus, the 10-​Hz spindle
type of Gibbs and Gibbs (1958) might constitute a decelerated slow spindle during the
deepening stages of sleep. Among the factors determining/​modulating sleep spindle
frequencies, genetics, age, sex, circadian phase/​time of day, core body temperature,
menstrual cycle phase, and sleep depth are well known (Andrillon et al., 2011; De
Gennaro et al., 2008; de Zambotti et al., 2015; Dijk, 1999; Ujma et al., 2014). A common
feature of sleep spindles is a slowing down of spindle frequency in successive oscillatory
cycles, resulting in a frequency difference of 0.1–​0.4 Hz, between the first and the last os-
cillatory cycle (Schonwald et al., 2011).

17.11.2 Morphology of Sleep Spindles

Besides frequency, sleep spindles are characterized by wave morphology and/​or enve-
lope. The term spindle was used in order to characterize the shape of the envelope of
this wave group, characterized by an initial crescendo followed by decrescendo in amp-
litude reflecting the engagement of an increasing number of neurons into the rhythmic
spindle frequency activity pattern followed by a gradual decrease. There is little research
focusing on this aspect of sleep spindles. Some observations indicate that this spindle
morphology is more an exception than the rule (Jankel & Niedermeyer, 1985). The band-​
pass filtered signals, as well as the so-​called grouping of sleep spindles by the slow (<1
Hz) oscillation (Molle et al., 2002; Steriade & Amzica, 1998), clearly support that sleep
spindle frequencies are characterized by progressively increasing amplitude followed
by a gradual decrease. Regarding the polarity, sleep spindle-​like waveforms induced by
rhythmic thalamic stimulation in the midline areas have been shown to be surface nega-
tive (Dempsey & Morison, 1941). In the case of scalp EEG recordings, there is much
controversy regarding the reference montage. The morphology of the single wave
420    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

constituents of sleep spindles (single cycles) is most often tacitly considered as quasi-​
sinusoidal. However, there are important specifications in this regard: sleep spindles
have been shown to reflect both subthreshold depolarizations of apical dendrites
(smooth surface negative waves) and apical dendritic depolarization (sharp negative-​
positive waves) (Urakami et al., 2012). Sleep spindles with unipolar sharp peaks have
been registered near the parahippocampal region in epilepsy patients undergoing
presurgical examination with foramen ovale electrodes. Sharp peaks have been
associated with nested (phase-​coupled) 80–​140 Hz ripples in these patients (Clemens
et al., 2011). Sleep spindles with unusual sharp negative peaks have also been observed in
infancy, up to 2 years of age (Fois, 1961). However, there is no direct evidence indicating
that the above findings reflect enhanced neuronal firing during parahippocampal and
cortical sleep spindles in epilepsy patients and infants, respectively.

17.11.3 Duration of Sleep Spindles

Since the publication of the scoring rules for sleep by Rechtschaffen and Kales (1968),
the shortest duration of individual sleep spindles is usually defined at half-​seconds.
However, this is just a consensual value. In their original work describing and
characterizing sleep spindles, Loomis and colleagues (1935) mention sleep spindles as
short as third-​or even quarter-​seconds. There is no theoretical work indicating that a
half-​second length is a critical minimum value for a sleep spindle per se. Different ex-
perimental settings and subjects are characterized by different sleep spindle durations.
The most important factor determining sleep spindle duration is age: unusually long (up
to 10 seconds) sleep spindles are seen in infants, while a significant shortening progres-
sively emerges during maturation and development, until typical 1–​2-​s-​long spindles
emerge (Spinosa & Garzon, 2007). Initial thalamic inhibition (Bartho et al., 2014) and
corticothalamic feedback (Bonjean et al., 2011) are hypothesized to play a crucial role in
the precise regulation of sleep spindle duration.

17.11.4 Amplitude of Sleep Spindles

The amplitude of sleep spindles depends on several specific and non-​specific factors.
Some trivial non-​specific factors include electrode impedance, derivation (reference),
and skull thickness. Specific factors include age, sleep cycle effects, sleep homeo-
stasis, and circadian phase. In addition, several sleep spindle measures, among which
amplitude is perhaps the most pertinent, depend on the method used for and criteria
of defining sleep spindles. Sleep spindle amplitude is shown to be the direct function
of thalamocortical entrainment of neurons to spindle frequency. There is evidence
supporting the view that the more widespread a spindle is, the higher its amplitude
(Andrillon et al., 2011; Dempsey & Morison, 1941).
 FREQUENCY CHARACTERISTICS OF SLEEP    421

17.11.5 Topography of Sleep Spindles

The characteristic topography of sleep spindles is twofold. The prefrontal cortices are the
sites of origin of slow (~12 Hz) sleep spindles, whereas parietal cortex is characterized by
the fast type (~14 Hz) sleep spindles. The central region expresses a roughly equivalent
amount of slow and fast sleep spindle power.

17.11.6 The Density and Periodicity of Sleep Spindles

The ability to elicit local sleep spindles is enhanced by increasing local neural plasticity,
namely, the induction of long-​term potentiation (Werk et al., 2005). There are two major
hypotheses on the specific mechanism of sleep spindle initiation in the thalamocor-
tical network. The classical hypothesis was put forward by (Destexhe et al., 1998). In this
view, SO up states impinge a high level of excitation in the thalamic reticular neurons
by thalamoreticular (descending, thalamofugal) connections. Consequently, thalamic
reticular neurons induce a high level of hyperpolarization in thalamocortical neurons,
which in turn begin to fire in rebound depolarization sequences. Ascending thalamo-
cortical pathways transfer the effects of rebound depolarizations to the cortex.
Another hypothesis implies the leading role of SO down states in the induction of
a sufficient thalamic hyperpolarization by descending thalamofugal tracts. Thus, thal-
amic down states lag cortical ones. Thalamic sleep spindles initiate at the times of thal-
amic down states; they are then transferred to the cortex with a lag, which results in
the coincidence of cortical sleep spindles with the forthcoming up state of the ongoing
SO (Mak-​McCully et al., 2017). Evidence suggests that Stage 2 sleep spindles emerge
with a modal frequency of 0.25 Hz, that is the modal inter-​spindle interval is 4 s (3–​5
s) long (Achermann & Borbely, 1997; Evans & Richardson, 1995; Kubicki et al., 1986).
According to some reports, the 4-​s periodicity of sleep spindles is a characteristic fea-
ture of fast, but not of slow, sleep spindles (Spieweg et al., 1992). With the deepening of
sleep, spindles become less dense, but persist during the whole NREM period. SO Up
states are the preferred periods of emergence of sleep spindles in Stage 3 sleep (Fell et al.,
2002; Molle et al., 2002; Staresina et al., 2015). Given the fact that the 0.5 s minimum dur-
ation criteria for sleep spindles is still in use, the spindle-​like waveforms that are nested
in the depolarized phases of the SO are often not considered as sleep spindles per se,
but rather sleep spindle-​like or spindle frequency activity. Thus, sleep spindles and/​or
sleep spindle-​like oscillations are phase coupled with the SO; however, the frontal slow
types and the parietal fast type of sleep spindles are characterized by distinct coales-
cence patterns. Fast sleep spindles are shown to prefer the peaks of the SO up states,
whereas slow sleep spindles most frequently emerge during the transitional phase of the
up and the down states of the SO (Molle et al., 2011). This is in coherence with the finding
that in case of the co-​occurrence of the two types of sleep spindles, the fast type precedes
the slow one by several milliseconds (Zygierewicz et al., 1999).
422    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

17.11.7 Sleep Spindle Rhythmogenesis

Sleep spindles are shown to reflect the recurrent hyperpolarization rebound sequences
of thalamocortical cells, the inhibition of which is caused by the NREM-​dependent
activation of GABAergic neurons in the reticular thalamic nucleus (Huguenard &
McCormick, 2007; Steriade, 2000). The synchronization of individual thalamo-​cortico-​
reticular loops is thought to be performed by descending inputs of the concerted up and
down states of the cortical SO.

17.11.8 Sleep Spindles and Cognition

Similar to sleep slow waves, there is a wealth of evidence supporting the association be-
tween sleep spindles and cognition. On the one hand, sleep spindles have been identified
as highly sensitive to individual differences often related to general and specific learning
abilities. Thus, sleep spindles have been repeatedly (Ujma et al., 2018), albeit not un-
equivocally (Pesonen et al., 2019), shown to correlate with measures of general intelli-
gence and memory performance (Bodizs et al., 2014; Bodizs et al., 2005; Chatburn et al.,
2013; Clemens et al., 2005, 2006; Geiger et al., 2011; Hoedlmoser et al., 2014; Lustenberger
et al., 2012; Schabus et al., 2006; Tessier et al., 2015; Ujma et al., 2016). On the other hand,
the targeted modulation of sleep spindle activity using Transcranial Alternating Current
Stimulation (tACS) and closed loop auditory stimulation has resulted in significant
sleep dependent enhancement of motor learning (Lustenberger et al., 2016) and spatial
navigation performance (Shimizu et al., 2018), respectively. Changes in sleep spindles
(e.g. reduction in the amplitude and/​or incidence of sleep spindles) have been shown
to predict the development of dementia in Parkinson’s disease (Latreille et al., 2015) and
are associated with various neurodevelopmental disorders, such as autism spectrum
disorders (Godbout et al., 2000; Limoges et al., 2005) and Williams syndrome (Bodizs
et al., 2012), as well as with various mental health disorders including schizophrenia
(Schilling et al., 2017), bipolar disorder (Ritter et al., 2018), and major depression (Plante
et al., 2013).
Overall, there is convincing evidence that sleep spindles are generated in the thal-
amus, grouped by cortical slow oscillations (Steriade & Amzica, 1998). Spindles
are modulated by infraslow oscillations (Lazar et al., 2019; Lecci et al., 2017) and bio-
logical timekeepers (Cajochen et al., 2013; Dijk & Czeisler, 1995; Knoblauch, Martens,
Wirz-​Justice, Krauchi, & Cajochen et al., 2003; Knoblauch, Martens, Wirz-​Justice, &
Cajochen, 2003; Knoblauch et al., 2005). They are dependent on the intrinsic features
of the functional neuro-​architecture of an individual’s brain, and, as such, are inher-
ently linked to cognition and mental health. However, in spite of multiple competing
theories, the neural underpinnings of the associations of sleep spindles with cognition
are not clear. One theory suggests memories are reinstated by spindle events and further
reprocessed during subsequent spindle refractory periods (Antony et al., 2018). Another
 FREQUENCY CHARACTERISTICS OF SLEEP    423

theory posits that sleep slow oscillations preferentially consolidate the stronger memory
traces, which also leads to the extinction of weak memories. Sleep spindles are thought
to contribute to a slow but reliable consolidation of the multiple competing memories
(Wei et al., 2018).

17.12  Beta and gamma activity

during sleep

Historically, beta waves have been defined as EEG frequencies above 13 Hz (Kozelka &
Pedley, 1990). However, it is now clear that sleep spindles constitute a specific phenom-
enon, thus spindles and beta oscillations have to be defined separately in spite of the
clear overlap in the frequency of these phenomena. Consequently, frequencies higher
than sleep spindles, but lower than gamma (16–​30 Hz), can be considered as beta ac-
tivity in NREM sleep, whereas a somewhat broader frequency is acceptable in states
without sleep spindling, like REM sleep and wakefulness (13–​30 Hz). NREM sleep beta
EEG activity with frontocentral maxima is an integral part of sleep initiation, especially
in children (Kellaway & Fox, 1952). Moreover, the up states of the SO are associated with
an increase in beta/​gamma activity (up to 80 Hz), indicating the entrainment of higher
frequency oscillations by SO commonly referred to as grouping effect (Neske, 2016). SO/​
delta and beta activity fluctuate reciprocally across NREM and REM sleep indicating
that an inverse relationship between the two activities (Uchida et al., 1992). Beta activity
is evidently higher in REM as compared to NREM sleep. The anterior cingulate and the
dorsolateral prefrontal cortices are characterized by prominent and coherent beta ac-
tivity during REM sleep in humans (Vijayan et al., 2017).
Several reports suggest that enhanced beta/​gamma EEG power (activity) is an index
of cortical arousal, or disturbed sleep. Most of the reports indicate that sleep EEG (both
NREM and REM) records of insomnia patients are characterized by heightened beta/​
gamma power as compared to records of subjects who sleep well (Perlis, Merica et al.,
2001; Perlis, Smith et al., 2001).
Gamma oscillations are usually defined as 30–​80 Hz waves indicating arousal and
(local) activation of the cortex. If gamma oscillations are coherent, they are related to
perceptual binding. As mentioned previously, there are several reports indicating
similar behavior of beta and gamma oscillations during sleep (see also those indicating
enhanced gamma in patients suffering from primary and secondary insomnia: Perlis,
Merica, et al., 2001; Perlis, Smith, et al., 2001). The specificity of gamma waves is seen
in cases in which consciousness is part of the story. Thus, frontal gamma EEG power
and coherence is increased in periods of lucid dreaming, as compared to non-​lucid
dreaming (dream lucidity indicates the state in which the dreamer is aware of the
dream-​like nature of the ongoing mental activity; see Voss et al., 2009). In addition, beta
and gamma activity are differentially expressed in tonic and phasic REM sleep: tonic
424    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

REM is characterized by increased beta, whereas phasic REM by increased gamma ac-
tivity (Simor et al., 2016).

17.13  Ripples/​HFO oscillations

Ripples are usually recorded in the invasive epilepsy monitoring setting. Slow (80–​140
Hz) and fast (250–​500 Hz) ripples are considered physiological and pathological (epi-
leptic enhancement) signals, respectively. The hippocampal formation and the medial
temporal lobe is the most frequent, but not exclusive origin of ripple oscillations in
all wake-​sleep states. It has been shown that hippocampal ripples are nested in spe-
cific phases of sleep spindle oscillations, resulting in a fine-​tuned coupling of the two
oscillations in human subjects (Clemens et al., 2011; Staresina et al., 2015). This hierarch-
ical nesting (SO-​sleep spindle-​ripple) is thought to play a crucial role in off-​line memory
consolidation processes involving the reactivation of transient memory traces during
sleep. Recent investigations indicate that ripples can be recorded in the scalp EEG of
children as well. Mean frequency has been reported to be 102 Hz, mean duration 70
ms, and mean root mean square amplitude 0.95 µV (Mooij et al., 2017). Scalp-​recorded
ripples have been associated with several sleep EEG transients (Mooij et al., 2018).

17.14  Conclusion

Sleep EEG is characterized by a multitude of salient oscillatory and phasic phe-

nomena that reflect the functional neuroarchitecture of the brain and are tightly linked
with neural plasticity associated to learning and memory. The network of biological
mechanisms driving sleep and interacting with sleep dependent brain oscillations
are intricate, ranging from molecular mechanisms to complex behavioral and cog-
nitive patterns. Given the small number of measurable behaviors occurring during
sleep, studying the sleeping brain via EEG frequencies is a critical measure to see into
the sleeping brain. Like opening a window to see and learn about the constellations in
the night sky, EEG frequencies allow us to open a window to see and learn about the
working brain during sleep.

REFERENCES
Achermann, P. & Borbely, A. A. (1997). Low-​frequency (< 1 Hz) oscillations in the human sleep
electroencephalogram. Neuroscience, 81(1), 213–​222.
Agnew, H. W., Jr., Parker, J. C., Webb, W. B., & Williams, R. L. (1967). Amplitude measurement
of the sleep electroencephalogram. Electroencephalography and Clinical Neurophysiology,
22(1), 84–​86.
 FREQUENCY CHARACTERISTICS OF SLEEP    425

Amzica, F. & Steriade, M. (1998). Electrophysiological correlates of sleep delta waves.

Electroencephalography and Clinical Neurophysiology, 107(2), 69–​83.
Andrillon, T., Nir, Y., Staba, R. J., Ferrarelli, F., Cirelli, C., Tononi, G., & Fried, I. (2011).
Sleep spindles in humans: insights from intracranial EEG and unit recordings. Journal of
Neuroscience, 31(49), 17821–​17834. doi:10.1523/​jneurosci.2604–​11.2011
Antony, J. W., Piloto, L., Wang, M., Pacheco, P., Norman, K. A., & Paller, K. A. (2018). Sleep
Spindle Refractoriness Segregates Periods of Memory Reactivation. Current Biology, 28(11),
1736–​1743.
Astrom, C. & Trojaborg, W. (1992). Relationship of age to power spectrum analysis of EEG
during sleep. Journal of Clinical Neurophysiology, 9(3), 424–​430.
Baker, F. C. & Lee, K. A. (2018). Menstrual cycle effects on sleep. Sleep Medicine Clinics, 13(3),
283–​294.
Bartho, P., Slezia, A., Matyas, F., Faradzs-​Zade, L., Ulbert, I., Harris, K. D., & Acsady, L. (2014).
Ongoing network state controls the length of sleep spindles via inhibitory activity. Neuron,
82(6), 1367–​1379.
Berger, H. (1933). Über das Elektrenkephalogramm des Menschen. Siebente Mitteilung. Archiv
für Psychiatrie und Nervenkrankheiten, 100, 317–​319.
Berry, R. B., Brooks, R., Gamaldo, C., Harding, S. M., Lloyd, R. M., Quan, S. F., . . . Vaughn, B.
V. (2017). AASM Scoring Manual Updates for 2017 (Version 2.4). Journal of Clinical Sleep
Medicine, 13(5), 665.
Blumberg, M. S. (1989). An allometric analysis of the frequency of hippocampal theta: the sig-
nificance of brain metabolic rate. Brain Behaviour and Evolution, 34(6), 351–​356.
Bodizs, R., Gombos, F., & Kovacs, I. (2012). Sleep EEG fingerprints reveal accelerated thalamo-
cortical oscillatory dynamics in Williams syndrome. Research in Developmental Disabilities,
33(1), 153–​164.
Bodizs, R., Gombos, F., Ujma, P. P., & Kovacs, I. (2014). Sleep spindling and fluid intelligence
across adolescent development: sex matters. Frontiers in Human Neuroscience, 8, 952.
Bodizs, R., Kantor, S., Szabo, G., Szucs, A., Eross, L., & Halasz, P. (2001). Rhythmic hippocampal
slow oscillation characterizes REM sleep in humans. Hippocampus, 11(6), 747–​753.
Bodizs, R., Kis, T., Lazar, A. S., Havran, L., Rigo, P., Clemens, Z., & Halasz, P. (2005). Prediction
of general mental ability based on neural oscillation measures of sleep. Journal of Sleep
Research, 14(3), 285–​292.
Bodizs, R., Szalárdy, O., Horváth, C., Ujma, P. P., Gombos, F., Simor, P., . . . Dresler, M. (2021).
A set of composite, non-​redundant EEG measures of NREM sleep based on the power law
scaling of the Fourier spectrum. Scientific Reports, 11, 2041.
Bonjean, M., Baker, T., Lemieux, M., Timofeev, I., Sejnowski, T., & Bazhenov, M. (2011).
Corticothalamic feedback controls sleep spindle duration in vivo. Journal of Neuroscience,
31(25), 9124–​9134.
Borbely, A. A. (1982). A two process model of sleep regulation. Human Neurobiology, 1(3),
195–​204.
Borbely, A. A. & Achermann, P. (1999). Sleep homeostasis and models of sleep regulation.
Journal of Biological Rhythms, 14(6), 557–​568.
Branco, J., Atalaia, A., & Paiva, T. (1994). Sleep cycles and alpha-​delta sleep in fibromyalgia syn-
drome. Journal of Rheumatology, 21(6), 1113–​1117.
Brazier, M. A. (1961). Preliminary proposal for an EEG terminology by the Terminology
Committee of the International Federation for Electroencephalography and Clinical
Neurophysiology. Electroencephalography and Clinical Neurophysiology, 13, 646–​650.
426    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

Brenton, J. N. & Mytinger, J. R. (2015). Sporadic occurrence of completely lateralized vertex

sharp transients of sleep is a normal phenomenon: a retrospective, blinded, case-​control
study. Journal of Clinical Neurophysiology, 32(2), 171–​174.
Cajochen, C., Altanay-​Ekici, S., Munch, M., Frey, S., Knoblauch, V., & Wirz-​Justice, A. (2013).
Evidence that the lunar cycle influences human sleep. Current Biology, 23(15), 1485–​1488.
Campbell, I. G., Higgins, L. M., Darchia, N., & Feinberg, I. (2006). Homeostatic behavior of
fast Fourier transform power in very low frequency non-​rapid eye movement human elec-
troencephalogram. Neuroscience, 140(4), 1395–​1399.
Carrier, J., Land, S., Buysse, D. J., Kupfer, D. J., & Monk, T. H. (2001). The effects of age and
gender on sleep EEG power spectral density in the middle years of life (ages 20–​60 years
old). Psychophysiology, 38(2), 232–​242.
Cash, S. S., Halgren, E., Dehghani, N., Rossetti, A. O., Thesen, T., Wang, C., . . . Ulbert, I. (2009).
The human K-​complex represents an isolated cortical down-​state. Science, 324(5930),
1084–​1087.
Chatburn, A., Coussens, S., Lushington, K., Kennedy, D., Baumert, M., & Kohler, M. (2013).
Sleep spindle activity and cognitive performance in healthy children. Sleep, 36(2), 237–​243.
doi:10.5665/​sleep.2380
Clemens, Z., Fabo, D., & Halasz, P. (2005). Overnight verbal memory retention correlates with
the number of sleep spindles. Neuroscience, 132(2), 529–​535.
Clemens, Z., Fabo, D., & Halasz, P. (2006). Twenty-​four hours retention of visuospatial
memory correlates with the number of parietal sleep spindles. Neuroscience Letters, 403(1–​
2), 52–​56.
Clemens, Z., Molle, M., Eross, L., Jakus, R., Rasonyi, G., Halasz, P., & Born, J. (2011). Fine-​tuned
coupling between human parahippocampal ripples and sleep spindles. European Journal of
Neuroscience, 33(3), 511–​520.
Clemens, Z., Weiss, B., Szucs, A., Eross, L., Rasonyi, G., & Halasz, P. (2009). Phase coup-
ling between rhythmic slow activity and gamma characterizes mesiotemporal rapid-​eye-​
movement sleep in humans. Neuroscience, 163(1), 388–​396.
Colrain, I. M., Webster, K. E., Hirst, G., & Campbell, K. B. (2000). The roles of vertex sharp
waves and K-​complexes in the generation of N300 in auditory and respiratory-​related
evoked potentials during early stage 2 NREM sleep. Sleep, 23(1), 97–​106.
Cordi, M., Ackermann, S., Bes, F. W., Hartmann, F., Konrad, B. N., Genzel, L., . . . Dresler, M.
(2014). Lunar cycle effects on sleep and the file drawer problem. Current Biology, 24(12),
R549–​R550.
Cowdin, N., Kobayashi, I., & Mellman, T. A. (2014). Theta frequency activity during rapid eye
movement (REM) sleep is greater in people with resilience versus PTSD. Experimental Brain
Research, 232(5), 1479–​1485.
Crunelli, V., Lorincz, M. L., Connelly, W. M., David, F., Hughes, S. W., Lambert,
R. C., . . . Errington, A. C. (2018). Dual function of thalamic low-​ vigilance state
oscillations: Rhythm-​regulation and plasticity. Nature Reviews Neuroscience, 19(2), 107–​118.
Csercsa, R., Dombovari, B., Fabo, D., Wittner, L., Eross, L., Entz, L., . . . Ulbert, I. (2010). Laminar
analysis of slow wave activity in humans. Brain, 133(9), 2814–​2829. doi:10.1093/​brain/​awq169
Daan, S., Beersma, D. G., & Borbely, A. A. (1984). Timing of human sleep: Recovery process
gated by a circadian pacemaker. American Journal of Physiology, 246(2 Pt 2), R161–​183.
Dempsey, E. W. & Morison, R. S. (1941). The production of rhythmically recurrent cortical
potentials after localized thalamic stimulation. American Journal of Physiology (Legacy
Content),135(2), 293–​300.
 FREQUENCY CHARACTERISTICS OF SLEEP    427

Destexhe, A., Contreras, D., & Steriade, M. (1998). Mechanisms underlying the synchronizing
action of corticothalamic feedback through inhibition of thalamic relay cells. Journal of
Neurophysiology, 79(2), 999–​1016.
De Gennaro, L., Marzano, C., Fratello, F., Moroni, F., Pellicciari, M. C., Ferlazzo, F., . . . Rossini,
P. M. (2008). The electroencephalographic fingerprint of sleep is genetically determined: A
twin study. Annals of Neurology, 64(4), 455–​460.
de Zambotti, M., Willoughby, A. R., Sassoon, S. A., Colrain, I. M., & Baker, F. C. (2015).
Menstrual cycle-​related variation in physiological sleep in women in the early menopausal
transition. The Journal of Clinical Endocrinology and Metabolism, 100(8), 2918–​2926.
Dijk, D. J., Beersma, D. G., & Bloem, G. M. (1989). Sex differences in the sleep EEG of young
adults: Visual scoring and spectral analysis. Sleep, 12(6), 500–​507.
Dijk, D. J. & Czeisler, C. A. (1995). Contribution of the circadian pacemaker and the sleep
homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and
sleep spindle activity in humans. Journal of Neuroscience, 15(5 Pt 1), 3526–​3538.
Dijk, D. J. (1999). Circadian variation of EEG power spectra in NREM and REM sleep in
humans: dissociation from body temperature. Journal of Sleep Research, 8(3), 189–​195
Egawa, I., Yoshino, K., & Hishikawa, Y. (1983). Positive occipital sharp transients in the human
sleep EEG. Psychiatry and Clinical Neuroscience, 37(1), 57–​65.
Eichenlaub, J. B., van Rijn, E., Gaskell, M. G., Lewis, P. A., Maby, E., Malinowski, J. E., . . . Blagrove,
M. (2018). Incorporation of recent waking-​life experiences in dreams correlates with frontal
theta activity in REM sleep. Social Cognitive and Affective Neuroscience, 13(6), 637–​647.
Evans, B. M. & Richardson, N. E. (1995). Demonstration pf a 3–​5-​s periodicity between the
spindle bursts in NREM sleep in man. Journal of Sleep Research, 4(3), 196–​197.
Feinberg, I., March, J. D., Fein, G., & Aminoff, M. J. (1984). Log amplitude is a linear
function of log frequency in NREM sleep EEG of young and elderly normal subjects.
Electroencephalography and Clinical Neurophysiology, 58(2), 158–​160.
Fell, J., Elfadil, H., Roschke, J., Burr, W., Klaver, P., Elger, C. E., & Fernandez, G. (2002). Human
scalp recorded sigma activity is modulated by slow EEG oscillations during deep sleep.
International Journal of Neuroscience, 112(7), 893–​900.
Fois, A. (1961). The electroencephalogram of the normal child. Charles C Thomas.
Frank, M. G. & Cantera, R. (2014). Sleep, clocks, and synaptic plasticity. Trends in Neuroscience,
37(9), 491–​501.
Freeman, W. J. & Zhai, J. (2009). Simulated power spectral density (PSD) of background elec-
trocorticogram (ECoG). Cognitive Neurodynamics, 3(1), 97–​103.
Geiger, A., Huber, R., Kurth, S., Ringli, M., Jenni, O. G., & Achermann, P. (2011). The sleep EEG
as a marker of intellectual ability in school age children. Sleep, 34(2), 181–​189.
Gibbs, E. A. & Gibbs, E. L. (1958). Atlas of electroencephalography (2nd ed.). Addison Wesley.
A glossary of terms most commonly used by clinical electroencephalographers. (1974).
Electroencephalography and Clinical Neurophysiology, 37(5), 538–​548.
Godbout, R., Bergeron, C., Limoges, E., Stip, E., & Mottron, L. (2000). A laboratory study of
sleep in Asperger’s syndrome. Neuroreport, 11(1), 127–​130.
Goldstein, A. N. & Walker, M. P. (2014). The role of sleep in emotional brain function. Annual
Review of Clinical Psychology, 10, 679–​708.
Grassberger, P. & Procaccia, I. (1983). Characterization of strange attractors. Physical Review
Letters, 50(5), 346–​349.
Gu, G.-​F., & Zhou, W.-​X. (2006). Detrended fluctuation analysis for fractals and multifractals
in higher dimensions. Physical Review E, 74(6), 061104.
428    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

Halasz, P. (2005). K-​complex, a reactive EEG graphoelement of NREM sleep: An old chap in a
new garment. Sleep Med Rev, 9(5), 391–​412.
Halász, P. & Bódizs, R. (2013). Dynamic structure of NREM sleep. Springer.
Hauri, P. & Hawkins, D. R. (1973). Alpha-​delta sleep. Electroencephalography and Clinical
Neurophysiology, 34(3), 233–​237.
Hoedlmoser, K., Heib, D. P., Roell, J., Peigneux, P., Sadeh, A., Gruber, G., & Schabus, M. (2014).
Slow sleep spindle activity, declarative memory, and general cognitive abilities in children.
Sleep, 37(9), 1501–​1512.
Hori, T., Sugita, Y., Koga, E., Shirakawa, S., Inoue, K., Uchida, S., . . . Fukuda, N. (2001).
Proposed supplements and amendments to ‘A manual of standardized terminology,
techniques and scoring system for sleep stages of human subjects’, the Rechtschaffen & Kales
(1968) standard. Psychiatry and Clinical Neuroscience, 55(3), 305–​310.
Huber, R., Esser, S. K., Ferrarelli, F., Massimini, M., Peterson, M. J., & Tononi, G. (2007). TMS-​
induced cortical potentiation during wakefulness locally increases slow wave activity during
sleep. PLoS One, 2(3), e276.
Huber, R., Ghilardi, M. F., Massimini, M., Ferrarelli, F., Riedner, B. A., Peterson, M. J., &
Tononi, G. (2006). Arm immobilization causes cortical plastic changes and locally decreases
sleep slow wave activity. Nature Neuroscience, 9(9), 1169–​1176.
Huber, R., Ghilardi, M. F., Massimini, M., & Tononi, G. (2004). Local sleep and learning.
Nature, 430(6995), 78–​81.
Hughes, S. W., Lorincz, M. L., Parri, H. R., & Crunelli, V. (2011). Infraslow (<0.1 Hz) oscillations
in thalamic relay nuclei basic mechanisms and significance to health and disease states.
Progress in Brain Research, 193, 145–​162.
Huguenard, J. R. & McCormick, D. A. (2007). Thalamic synchrony and dynamic regulation of
global forebrain oscillations. Trends in Neuroscience, 30(7), 350–​356.
Hurst, H. E., Black, R. P., & Simaika, Y. M. (1965). Long-​term storage, an experimental study.
Constable.
Iber, C. & American Academy of Sleep Medicine. (2007). The AASM manual for the scoring
of sleep and associated events: Rules, terminology and technical specifications. American
Academy of Sleep Medicine.
Inanaga, K. (1998). Frontal midline theta rhythm and mental activity. Psychiatry and Clinical
Neuroscience, 52(6), 555–​566.
Jaimchariyatam, N., Rodriguez, C. L., & Budur, K. (2011). Prevalence and correlates of alpha-​
delta sleep in major depressive disorders. Innovations in Clinical Neuroscience, 8(7), 35–​49.
Jankel, W. R. & Niedermeyer, E. (1985). Sleep spindles. Journal of Clinical Neurophysiology,
2(1), 1–​35.
Kaiser, D. (2013). Infralow frequencies and ultradian rhythms. Seminars in Pediatric Neurology,
20(4), 242–​245.
Kane, N., Acharya, J., Benickzy, S., Caboclo, L., Finnigan, S., Kaplan, P. W., . . . van Putten,
M. J. A. M. (2017). A revised glossary of terms most commonly used by clinical
electroencephalographers and updated proposal for the report format of the EEG findings.
Revision 2017. Clinical Neurophysiology Practice, 2, 170–​185.
Kattler, H., Dijk, D. J., & Borbely, A. A. (1994). Effect of unilateral somatosensory stimulation
prior to sleep on the sleep EEG in humans. Journal of Sleep Research, 3(3), 159–​164.
Kellaway, P. & Fox, B. J. (1952). Electroencephalographic diagnosis of cerebral pathology
in infants during sleep: I. Rationale, technique, and the characteristics of normal sleep in
infants. The Journal of Pediatrics, 41(3), 262–​287.
 FREQUENCY CHARACTERISTICS OF SLEEP    429

Kizaki, T., Sato, S., Shirato, K., Sakurai, T., Ogasawara, J., Izawa, T., . . . Ohno, H. (2015). Effect of
circadian rhythm on clinical and pathophysiological conditions and inflammation. Critical
Reviews in Immunology, 35(4), 261–​275.
Knoblauch, V., Martens, W., Wirz-​Justice, A., Krauchi, K., & Cajochen, C. (2003). Regional
differences in the circadian modulation of human sleep spindle characteristics. European
Journal of Neuroscience, 18(1), 155–​163.
Knoblauch, V., Martens, W. L., Wirz-​Justice, A., & Cajochen, C. (2003). Human sleep spindle
characteristics after sleep deprivation. Clinical Neurophysiology, 114(12), 2258–​2267.
Knoblauch, V., Munch, M., Blatter, K., Martens, W. L., Schroder, C., Schnitzler, C., . . . Cajochen,
C. (2005). Age-​related changes in the circadian modulation of sleep-​spindle frequency
during nap sleep. Sleep, 28(9), 1093–​1101.
Kozelka, J. W. & Pedley, T. A. (1990). Beta and mu rhythms. Journal of Clinical Neurophysiology,
7(2), 191–​207.
Kubicki, S., Meyer, C., & Rohmel, J. (1986). [The 4 second sleep spindle periodicity]. EEG-​
EMG Zeitschrift fur Elektroenzephalogrphie, Elektromyographie und Verwandte Gebiete,
17(2), 55–​61.
Latreille, V., Carrier, J., Lafortune, M., Postuma, R. B., Bertrand, J. A., Panisset, M., . . . Gagnon,
J. F. (2015). Sleep spindles in Parkinson’s disease may predict the development of dementia.
Neurobiology of Aging, 36(2), 1083–​1090.
Lazar, A. S., Lazar, Z. I., & Dijk, D. J. (2015). Circadian regulation of slow waves in human
sleep: Topographical aspects. Neuroimage, 116, 123–​134.
Lazar, A. S., Panin, F., Goodman, A. O., Lazic, S. E., Lazar, Z. I., Mason, S. L., . . . Barker, R. A.
(2015). Sleep deficits but no metabolic deficits in premanifest Huntington’s disease. Annals of
Neurology, 78(4), 630–​648.
Lázár, Z. I., Dijk, D. J., & Lázár, A. S. (2019). Infraslow oscillations in human sleep spindle ac-
tivity. Journal of Neuroscience Methods, 316, 22–​34. .
Lecci, S., Fernandez, L. M., Weber, F. D., Cardis, R., Chatton, J. Y., Born, J., & Luthi, A. (2017).
Coordinated infraslow neural and cardiac oscillations mark fragility and offline periods in
mammalian sleep. Science Advances, 3(2), e1602026.
Lee, J., Kim, D., & Shin, H.-​S. (2004). Lack of delta waves and sleep disturbances during non-​
rapid eye movement sleep in mice lacking alpha1G-​subunit of T-​type calcium channels.
Proceedings of the National Academy of Sciences of the United States of America, 101(52),
18195–​18199.
Limoges, E., Mottron, L., Bolduc, C., Berthiaume, C., & Godbout, R. (2005). Atypical sleep
architecture and the autism phenotype. Brain, 128(Pt 5), 1049–​1061.
Loomis, A. L., Harvey, E. N., & Hobart, G. (1935). Potential rhythms of the cerebral cortex
during sleep. Science, 81(2111), 597–​598.
Loomis, A. L., Harvey, E. N., & Hobart, G. A. (1937). Cerebral states during sleep, as studied by
human brain potentials. Journal of Experimental Psychology, 21(2), 127–​144.
Lustenberger, C., Boyle, M. R., Alagapan, S., Mellin, J. M., Vaughn, B. V., & Frohlich, F. (2016).
Feedback-​controlled transcranial alternating current stimulation reveals a functional role of
sleep spindles in motor memory consolidation. Current Biology, 26(16), 2127–​2136.
Lustenberger, C., Maric, A., Durr, R., Achermann, P., & Huber, R. (2012). Triangular relation-
ship between sleep spindle activity, general cognitive ability and the efficiency of declarative
learning. PLoS One, 7(11), e49561.
Ma, Y., Shi, W., Peng, C. K., & Yang, A. C. (2018). Nonlinear dynamical analysis of sleep elec-
troencephalography using fractal and entropy approaches. Sleep Medicine Review, 37, 85–​93.
430    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

Mak-​ McCully, R. A., Rolland, M., Sargsyan, A., Gonzalez, C., Magnin, M., Chauvel,
P., . . . Halgren, E. (2017). Coordination of cortical and thalamic activity during non-​REM
sleep in humans. Nature Communications, 8, 15499.
Massimini, M., Huber, R., Ferrarelli, F., Hill, S., & Tononi, G. (2004). The sleep slow oscillation
as a traveling wave. Journal of Neuroscience, 24(31), 6862–​6870.
McKinney, S. M., Dang-​Vu, T. T., Buxton, O. M., Solet, J. M., & Ellenbogen, J. M. (2011). Covert
waking brain activity reveals instantaneous sleep depth. PLoS One, 6(3), e17351.
Mohawk, J. A., Green, C. B., & Takahashi, J. S. (2012). Central and peripheral circadian clocks
in mammals. Annual Review of Neuroscience, 35, 445–​462.
Molle, M., Bergmann, T. O., Marshall, L., & Born, J. (2011). Fast and slow spindles during the
sleep slow oscillation: Disparate coalescence and engagement in memory processing. Sleep,
34(10), 1411–​1421.
Molle, M., Marshall, L., Gais, S., & Born, J. (2002). Grouping of spindle activity during slow
oscillations in human non-​rapid eye movement sleep. Journal of Neuroscience, 22(24),
10941–​10947.
Mooij, A. H., Frauscher, B., Goemans, S. A. M., Huiskamp, G. J. M., Braun, K. P. J., & Zijlmans,
M. (2018). Ripples in scalp EEGs of children: Co-​occurrence with sleep-​specific transients
and occurrence across sleep stages. Sleep, 41(11), zsy169-​zsy169.
Mooij, A. H., Raijmann, R. C. M. A., Jansen, F. E., Braun, K. P. J., & Zijlmans, M. (2017).
Physiological ripples (± 100 Hz) in spike-​free scalp EEGs of children with and without epi-
lepsy. Brain Topography, 30(6), 739–​746.
Moroni, F., Nobili, L., De Carli, F., Massimini, M., Francione, S., Marzano, C., . . . Ferrara, M.
(2012). Slow EEG rhythms and inter-​hemispheric synchronization across sleep and wakeful-
ness in the human hippocampus. Neuroimage, 60(1), 497–​504.
Neske, G. T. (2016). The slow oscillation in cortical and thalamic networks: Mechanisms and
functions. Frontiers in Neural Circuits, 9, 88).
Nishida, M., Hirai, N., Miwakeichi, F., Maehara, T., Kawai, K., Shimizu, H., & Uchida, S.
(2004). Theta oscillation in the human anterior cingulate cortex during all-​night sleep: An
electrocorticographic study. Neuroscience Research, 50(3), 331–​341.
Noachtar, S., Binnie, C., Ebersole, J., Mauguiere, F., Sakamoto, A., & Westmoreland, B. (1999).
A glossary of terms most commonly used by clinical electroencephalographers and pro-
posal for the report form for the EEG findings. The International Federation of Clinical
Neurophysiology. Electroencephalography and Clinical Neurophysiology Supplement,
52, 21–​41.
Parrino, L., Grassi, A., & Milioli, G. (2014). Cyclic alternating pattern in polysomnography: What
is it and what does it mean? Current Opinion in Pulmonary Medicine, 20(6), 533–​541.
Pearl, P. L., LaFleur, B. J., Reigle, S. C., Rich, A. S., Freeman, A. A., McCutchen, C., & Sato,
S. (2002). Sawtooth wave density analysis during REM sleep in normal volunteers. Sleep
Medicine, 3(3), 255–​258.
Pereda, E., Gamundi, A., Rial, R., & Gonzalez, J. (1998). Non-​linear behaviour of human
EEG: Fractal exponent versus correlation dimension in awake and sleep stages. Neuroscience
Letters, 250(2), 91–​94.
Perlis, M. L., Merica, H., Smith, M. T., & Giles, D. E. (2001). Beta EEG activity and insomnia.
Sleep Medicine Review, 5(5), 363–​374.
Perlis, M. L., Smith, M. T., Andrews, P. J., Orff, H., & Giles, D. E. (2001). Beta/​gamma EEG ac-
tivity in patients with primary and secondary insomnia and good sleeper controls. Sleep,
24(1), 110–​117.
 FREQUENCY CHARACTERISTICS OF SLEEP    431

Pesonen, A.-​K., Ujma, P., Halonen, R., Räikkönen, K., & Kuula, L. (2019). The associations
between spindle characteristics and cognitive ability in a large adolescent birth cohort.
Intelligence, 72, 13–​19.
Piano, C., Mazzucchi, E., Bentivoglio, A. R., Losurdo, A., Calandra Buonaura, G., Imperatori,
C., . . . Della Marca, G. (2017). Wake and sleep EEG in patients with Huntington disease: An
eLORETA study and review of the literature. Clinical EEG and Neuroscience, 48(1), 60–​7 1.
Picchioni, D., Horovitz, S. G., Fukunaga, M., Carr, W. S., Meltzer, J. A., Balkin, T. J., . . . Braun, A.
R. (2011). Infraslow EEG oscillations organize large-​scale cortical-​subcortical interactions
during sleep: a combined EEG/​fMRI study. Brain Research, 1374, 63–​72.
Plante, D. T., Goldstein, M. R., Landsness, E. C., Peterson, M. J., Riedner, B. A., Ferrarelli,
F., . . . Benca, R. M. (2013). Topographic and sex-​related differences in sleep spindles in major
depressive disorder: A high-​density EEG investigation. Journal of Affective Disorders, 146(1),
120–​125.
Potari, A., Ujma, P. P., Konrad, B. N., Genzel, L., Simor, P., Kormendi, J., . . . Bodizs, R.
(2017). Age-​related changes in sleep EEG are attenuated in highly intelligent individuals.
Neuroimage, 146, 554–​560.
Rechtschaffen, A. & Kales, A. (1968). A manual of standardized terminology, techniques and
scoring system for sleep stages of human subjects. University of California Los Angeles Brain
Information Service.
NINDB Neurological Information Network (US), Bethesda, Md., U. S. National Institute of
Neurological Diseases and Blindness, Neurological Information Network.
Ritter, P. S., Schwabedal, J., Brandt, M., Schrempf, W., Brezan, F., Krupka, A., . . . Nikitin, E.
(2018). Sleep spindles in bipolar disorder -​a comparison to healthy control subjects. Acta
Psychiatrica Scandinavica, 138(2), 163–​172.
Roosli, M., Juni, P., Braun-​Fahrlander, C., Brinkhof, M. W., Low, N., & Egger, M. (2006).
Sleepless night, the moon is bright: Longitudinal study of lunar phase and sleep. Journal of
Sleep Research, 15(2), 149–​153.
Santhi, N., Lazar, A. S., McCabe, P. J., Lo, J. C., Groeger, J. A., & Dijk, D. J. (2016). Sex differences
in the circadian regulation of sleep and waking cognition in humans. Proceedings of the
National Academy of Sciences of the United States of America, 113(19), E2730–​2739.
Sato, S., McCutchen, C., Graham, B., Freeman, A., von Albertini-​Carletti, I., & Alling, D.
W. (1997). Relationship between muscle tone changes, sawtooth waves and rapid eye
movements during sleep. Electroencephalography and Clinical Neurophysiology, 103(6),
627–​632.
Savage, V. M. & West, G. B. (2007). A quantitative, theoretical framework for understanding
mammalian sleep. Proceedings of the National Academy of Sciences of the United States of
America, 104(3), 1051.
Schabus, M., Hodlmoser, K., Gruber, G., Sauter, C., Anderer, P., Klosch, G., . . . Zeitlhofer, J.
(2006). Sleep spindle-​related activity in the human EEG and its relation to general cognitive
and learning abilities. European Journal of Neuroscience, 23(7), 1738–​1746.
Schilling, C., Schlipf, M., Spietzack, S., Rausch, F., Eisenacher, S., Englisch,
S., . . . Schredl, M. (2017). Fast sleep spindle reduction in schizophrenia and healthy first-​
degree relatives: Association with impaired cognitive function and potential intermediate
phenotype. European Archives of Psychiatry and Clinical Neuroscience, 267(3), 213–​224.
Schmidt, C., Collette, F., Cajochen, C., & Peigneux, P. (2007). A time to think: Circadian
rhythms in human cognition. Cognitive Neuropsychology, 24(7), 755–​789. doi:10.1080/​
02643290701754158
432    ALPÁR S. LÁZÁR, ZSOLT I. LÁZÁR, AND RÓBERT BÓDIZS

Schonwald, S. V., Carvalho, D. Z., Dellagustin, G., de Santa-​Helena, E. L., & Gerhardt, G. J.
(2011). Quantifying chirp in sleep spindles. Journal of Neuroscience Methods, 197(1), 158–​164.
Shimizu, R. E., Connolly, P. M., Cellini, N., Armstrong, D. M., Hernandez, L. T., Estrada,
R., . . . Simons, S. B. (2018). Closed-​loop targeted memory reactivation during sleep improves
spatial navigation. Frontiers in Human Neuroscience, 12, 28.
Silber, M. H., Ancoli-​Israel, S., Bonnet, M. H., Chokroverty, S., Grigg-​Damberger, M. M.,
Hirshkowitz, M., . . . Iber, C. (2007). The visual scoring of sleep in adults. Journal of Clinical
Sleep Medicine, 3(2), 121–​131.
Simor, P., Gombos, F., Blaskovich, B., & Bodizs, R. (2018). Long-​range alpha and beta and
short-​range gamma EEG synchronization distinguishes phasic and tonic REM periods.
Sleep, 41(3), zsx210. https://​doi.org/​10.1093/​sleep/​zsx​210
Simor, P., Gombos, F., Szakadat, S., Sandor, P., & Bodizs, R. (2016). EEG spectral power in
phasic and tonic REM sleep: different patterns in young adults and children. Journal of Sleep
Research, 25(3), 269–​277.
Simor, P., Horváth, K., Ujma, P. P., Gombos, F., & Bódizs, R. (2013). Fluctuations between
sleep and wakefulness: Wake-​like features indicated by increased EEG alpha power during
different sleep stages in nightmare disorder. Biological Psychology, 94(3), 592–​600.
Skeldon, A. C., Dijk, D. J., & Derks, G. (2014). Mathematical models for sleep-​wake dy-
namics: Comparison of the two-​process model and a mutual inhibition neuronal model.
PLoS One, 9(8), e103877.
Sloan, E. P., Maunder, R. G., Hunter, J. J., & Moldofsky, H. (2007). Insecure attachment is
associated with the alpha-​EEG anomaly during sleep. Biopsychosocial Medicine, 1, 20.
Smarr, B. L., Jennings, K. J., Driscoll, J. R., & Kriegsfeld, L. J. (2014). A time to remember: The
role of circadian clocks in learning and memory. Behavioral Neuroscience, 128(3), 283–​303.
Spieweg, I., Sanders, S., & Kubicki, S. (1992). Periodische Entladungen von Schlafspindeln
unter Plazebo und Zopiclone. [Periodical discharges of sleep spindles under placebo and
Zopiclone]. Klinische Neurophysiologie, 23(04), 215–​220.
Spinosa, M. J. & Garzon, E. (2007). Sleep spindles: Validated concepts and breakthroughs.
Journal of Epilepsy and Clinical Neurophysiology, 13, 179–​182.
Stam, C. J. (2005). Nonlinear dynamical analysis of EEG and MEG: Review of an emerging
field. Clinical Neurophysiology, 116(10), 2266–​2301.
Staresina, B. P., Bergmann, T. O., Bonnefond, M., van der Meij, R., Jensen, O., Deuker, L., . . . Fell,
J. (2015). Hierarchical nesting of slow oscillations, spindles and ripples in the human hippo-
campus during sleep. Nature Neuroscience, 18(11), 1679–​1686.
Steriade, M. (2000). Corticothalamic resonance, states of vigilance and mentation.
Neuroscience, 101(2), 243–​276.
Steriade, M., & Amzica, F. (1998). Coalescence of sleep rhythms and their chronology in
corticothalamic networks. Sleep Research Online, 1(1), 1–​10.
Steriade, M., Contreras, D., Curro Dossi, R., & Nunez, A. (1993). The slow (< 1 Hz) oscillation
in reticular thalamic and thalamocortical neurons: Scenario of sleep rhythm generation in
interacting thalamic and neocortical networks. Journal of Neuroscience, 13(8), 3284–​3299.
Steriade, M., Nunez, A., & Amzica, F. (1993a). Intracellular analysis of relations between the
slow (< 1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram.
Journal of Neuroscience, 13(8), 3266–​3283.
Steriade, M., Nunez, A., & Amzica, F. (1993b). A novel slow (< 1 Hz) oscillation of neocortical
neurons in vivo: Depolarizing and hyperpolarizing components. Journal of Neuroscience,
13(8), 3252–​3265.
Stupfel, M., & Pavely, A. (1990). Ultradian, circahoral and circadian structures in endothermic
vertebrates and humans. Comparative Biochemistry & Physiology A: Physiology, 96(1), 1–​11.
 FREQUENCY CHARACTERISTICS OF SLEEP    433

Tessier, S., Lambert, A., Chicoine, M., Scherzer, P., Soulieres, I., & Godbout, R. (2015).
Intelligence measures and stage 2 sleep in typically-​developing and autistic children.
International Journal of Psychophysiology, 97(1), 58–​65.
Tononi, G., & Cirelli, C. (2014). Sleep and the price of plasticity: From synaptic and cellular
homeostasis to memory consolidation and integration. Neuron, 81(1), 12–​34.
Turanyi, C. Z., Ronai, K. Z., Zoller, R., Veber, O., Czira, M. E., Ujszaszi, A., . . . Novak, M. (2014).
Association between lunar phase and sleep characteristics. Sleep Medicine, 15(11), 1411–​1416.
Uchida, S., Maehara, T., Hirai, N., Kawai, K., & Shimizu, H. (2003). Theta oscillation in the an-
terior cingulate and beta-​1 oscillation in the medial temporal cortices: A human case report.
Journal of Clinical Neuroscience, 10(3), 371–​374.
Uchida, S., Maloney, T., & Feinberg, I. (1992). Beta (20–​28 Hz) and delta (0.3–​3 Hz) EEGs oscil-
late reciprocally across NREM and REM sleep. Sleep, 15(4), 352–​358.
Ujma, P. P., Halasz, P., Simor, P., Fabo, D., & Ferri, R. (2018). Increased cortical involvement and
synchronization during CAP A1 slow waves. Brain Structure & Function, 223(8), 3531–​3542.
Ujma, P. P., Sandor, P., Szakadat, S., Gombos, F., & Bodizs, R. (2016). Sleep spindles and in-
telligence in early childhood-​developmental and trait-​dependent aspects. Developmental
Psychology, 52(12), 2118–​2129.
Urakami, Y., Ioannides, A. A., & Kostopoulos, G. K. (2012). Sleep spindles –​as a Biomarker of
brain function and plasticity. In I. Ajeena (Ed.), Advances in clinical neurophysiology (pp.
73–​108). IntechOpen.
Vanhatalo, S., Palva, J. M., Holmes, M. D., Miller, J. W., Voipio, J., & Kaila, K. (2004). Infraslow
oscillations modulate excitability and interictal epileptic activity in the human cortex during
sleep. Proceedings of the National Academy of Sciences of the United States of America, 101(14),
5053–​5057.
Vanhatalo, S., Tallgren, P., Andersson, S., Sainio, K., Voipio, J., & Kaila, K. (2002). DC-​EEG
discloses prominent, very slow activity patterns during sleep in preterm infants. Clinical
Neurophysiology, 113(11), 1822–​1825.
Vanhatalo, S., Voipio, J., & Kaila, K. (2005). Full-​band EEG (FbEEG): An emerging standard in
electroencephalography. Clinical Neurophysiology, 116(1), 1–​8.
Vijayan, S., Lepage, K. Q., Kopell, N. J., & Cash, S. S. (2017). Frontal beta-​theta network during
REM sleep. eLife, 6, e18894.
Voss, U., Holzmann, R., Tuin, I., & Hobson, J. A. (2009). Lucid dreaming: a state of conscious-
ness with features of both waking and non-​lucid dreaming. Sleep, 32(9), 1191–​1200.
Vyazovskiy, V. V., Olcese, U., Lazimy, Y. M., Faraguna, U., Esser, S. K., Williams, J. C., . . . Tononi,
G. (2009). Cortical firing and sleep homeostasis. Neuron, 63(6), 865–​878.
Wei, Y., Krishnan, G. P., Komarov, M., & Bazhenov, M. (2018). Differential roles of sleep
spindles and sleep slow oscillations in memory consolidation. PLoS Computational Biology,
14(7), e1006322
Weiss, B., Clemens, Z., Bodizs, R., Vago, Z., & Halasz, P. (2009). Spatio-​temporal analysis of
monofractal and multifractal properties of the human sleep EEG. Journal of Neuroscience
Methods, 185(1), 116–​124.
Werk, C. M., Harbour, V. L., & Chapman, C. A. (2005). Induction of long-​term potentiation leads
to increased reliability of evoked neocortical spindles in vivo. Neuroscience, 131(4), 793–​800.
Wright, K. P., Lowry, C. A., & Lebourgeois, M. K. (2012). Circadian and wakefulness-​sleep
modulation of cognition in humans. Frontiers in Molecular Neuroscience, 5, 50.
Zygierewicz, J., Blinowska, K. J., Durka, P. J., Szelenberger, W., Niemcewicz, S., & Androsiuk, W.
(1999). High resolution study of sleep spindles. Clinical Neurophysiology, 110(12), 2136–​2147.
 CHAPTER 18

A REVIEW OF OS C I L L ATORY
BRAIN DY NA MI C S I N
SCHIZOPH RE NIA

KEVIN M. SPENCER

18.1  Introduction

Schizophrenia is a serious neuropsychiatric disorder that affects about one percent

of the world’s population (Perälä et al., 2007), and imposes high social and economic
costs due to its severity (Davidson et al., 2016). Schizophrenia is characterized primarily
by psychotic symptoms such as auditory hallucinations and delusions, which are com-
monly accompanied by negative symptoms such as social withdrawal and reduced
motivation, and cognitive deficits in domains such as working memory and sustained
attention. This disorder has a complex etiology comprised of a number of genetic and
environmental factors, and its pathophysiology includes abnormalities at the neuronal,
local circuit, region-​wide, and whole-​brain levels (Owen et al., 2016). Schizophrenia is
considered to be a neurodevelopmental disorder (Murray & Lewis, 1987; Weinberger,
1987), with a typical progression beginning with a prodromal phase in the teenage
years in which subclinical symptoms become apparent, to the first psychotic episode
that leads to hospitalization and diagnosis, to the chronic phase that lasts the rest of the
individual’s life, which may be characterized by periods of psychosis and possibly remit-
tance (Rapoport et al., 2012). Schizophrenia is also conceptualized as part of a spectrum
(Siever & Davis, 2004) that includes disorders which feature subclinical manifestations
of symptoms in individuals with schizotypal personality disorder, individuals in the pro-
drome or at high risk for developing schizophrenia, and first-​degree relatives of persons
with schizophrenia. In addition, schizophrenia may occur atypically early in develop-
ment, in what is termed early-​onset schizophrenia, and may be mixed with symptoms of
affective disorder, in schizoaffective disorder. Bipolar I disorder shares similarities with
schizophrenia, including psychosis, and may be a related disorder.
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    435

Electroencephalography (EEG) has been applied to the study of schizophrenia for

over 80 years (Lemere, 1936). With the advent of digital computerized spectral ana-
lysis in the 1960s, “quantitative” EEG analysis came to supplant the traditional analyt-
ical approaches based on visual inspection and analog methods (reviewed in Itil, 1977).
The modern era of research into neural oscillations in schizophrenia dates from the
seminal studies of the Singer and Eckhorn labs (e.g., Eckhorn et al., 1988; Gray et al.,
1989), which impacted neuroscience in the 1990s. The results of these studies suggested
that highly precise synchronization of the spike trains of neurons in visual cortex might
serve as a mechanism whereby individual stimulus features could be bound together
into coherent representations of complex objects (Singer & Gray, 1995). This neuronal
synchronization was mediated by oscillations in the gamma band (30–​100 Hz) of the
EEG, which were generated in the local neuronal population (Gray & Singer, 1989).
More generally, information might be represented throughout the brain not just by
the firing rates of neurons, but by precise correlations in the timing of their firing that
were organized by oscillations (Singer, 1999), defining cell assemblies as predicted by
Hebb (1949). Subsequent research has led to a new view of brain function in which
oscillations across the frequency spectrum mediate perceptual, cognitive, motor, and
emotional functions through neuronal synchronization across a multitude of hier-
archically organized time scales (Buzsáki, 2006). This view of brain function based on
oscillatory brain dynamics has had a large impact on the study of the neural bases of
schizophrenia.
This chapter aims to summarize the major findings to date of studies of neural
oscillations in schizophrenia within the context of the development of the field of os-
cillatory brain dynamics in general and in schizophrenia research more particularly. It
begins with research into sensory gamma oscillations, which have been the main focus
of research. This is followed by research into oscillations involved in working memory
processes, TMS-​evoked oscillations, and spontaneous oscillatory activity. It concludes
with a discussion of emerging future directions in the field.

18.2  Sensory and Perceptual

Gamma Oscillations

The idea that synchronous neural activity in the gamma band mediated information pro-
cessing in the brain arrived at a time in which schizophrenia was being conceptualized
as a disorder not just of malfunctioning of particular brain regions, but of connectivity
in both local microcircuits (McGlashan & Hoffman, 2000), and large-​scale, distributed
networks (e.g., Friston & Frith, 1995). Gamma oscillations had been proposed to be
the primary means by which brain networks were functionally connected (e.g., Singer,
1999). When taken together with the idea that schizophrenia was a “splitting of the
mind”, characterized by a “disintegration of thought and personality” (Bleuler, 1911/​
436   KEVIN M. SPENCER

1950), it followed that schizophrenia might be closely associated with dysfunctional

gamma oscillations.
Clementz and colleagues (1997) conducted the earliest study examining gamma ac-
tivity in schizophrenia in the modern era of oscillation research, and suggested that
the P50 event-​related potential (ERP) sensory gating abnormality might be due to an
underlying sensory gating abnormality in the early auditory-​evoked gamma band re-
sponse (EAGBR), one of the first gamma responses identified in humans (Pantev
et al., 1991). Kwon and colleagues (1999) were the first to hypothesize that schizophrenia
might be associated with a specific deficit in the generation of oscillations in the gamma
band, and used the auditory steady-​state response (ASSR) to examine the ability of the
auditory system to be driven at frequencies in the beta (13–​30 Hz) and gamma ranges.
Kwon and colleagues (1999) presented click trains at frequencies of 20, 30, and 40 Hz to
chronic schizophrenia patients and healthy controls. The principal finding of the study
was the patients had reduced ASSR power to 40 Hz stimulation, but not to stimulation
at 20 or 30 Hz, suggesting that schizophrenia was associated with a specific deficit in
gamma-​frequency synchronization. This finding spurred the development of a new
area of research in the neuroscience of schizophrenia, the study of oscillatory brain dy-
namics in schizophrenia.

18.2.1 Auditory Gamma Oscillations

Two types of auditory oscillations have been studied in schizophrenia: the ASSR
(Galambos et al., 1981; Picton et al., 2003), and the EAGBR (Pantev et al., 1991). ASSRs
are evoked by trains of simple stimuli such as clicks presented at a constant rate, or by
amplitude-​modulated tones, and the scalp-​recorded potentials/​magnetic fields are pri-
marily generated in the primary auditory cortex (e.g., Draganova et al., 2008; Herdman
et al., 2003), with subcortical sources also being detectable (e.g., Herdman et al., 2002;
Farahani et al., 2017). In humans, ASSRs show maximum amplitude/​power for stimu-
lation in the gamma band at ~40 Hz, which likely reflects the resonant frequency of
its generating circuits in the auditory system (e.g., Pastor et al., 2002). The EAGBR is
evoked by sounds in general. It has a peak latency of ~50 ms, coincident with the P50
ERP component, and a peak frequency of ~40 Hz. The EAGBR and ASSR frequencies
have been shown to be correlated across individuals, suggesting that they share a
common neural generator (Zaehle et al., 2010).

18.2.1.1 ASSR Studies
The ASSR is the most commonly studied gamma oscillation in schizophrenia,
and deficits in the power and/​or phase locking factor (PLF; Tallon-​Baudry et al.,
1996) aspects of this oscillation in individuals with schizophrenia have been consistently
replicated (reviewed in O’Donnell et al., 2013; for meta-​analysis see Thuné et al., 2016).
Following Kwon and colleagues’ (1999) seminal report, others have reported gamma
(40 Hz, sometimes also 30 Hz) ASSR power and/​or PLF deficits in chronic patients
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    437

(Brenner et al., 2003; Hong et al., 2004; Light et al., 2006; Teale et al., 2008; Krishnan
et al., 2009: Spencer et al., 2009; Hamm et al., 2011; Tsuchimoto et al., 2011: Edgar et al.,
2014; Hirano et al., 2015; Zhou et al., 2018).
However, an important factor to consider in schizophrenia research is that the
results of studies conducted with chronic patients, that is, patients who have had
schizophrenia for some time, could be confounded to some degree by the duration
of the patients’ illness and their exposure to medications, especially antipsychotic
drugs (e.g., Leung et al., 2011). Therefore, it is important to test whether patients who
have never been medicated, first-​episode patients (who were recently diagnosed with
schizophrenia), and unmedicated individuals within the schizophrenia spectrum
show the same abnormalities as chronic patients. In general, these studies have found
the same pattern of gamma-​frequency ASSR deficits as in chronic schizophrenia. The
gamma ASSR deficit has been reported in ultra-​high-​risk individuals (Tada et al.,
2016), first-​degree relatives (Hong et al., 2004; Puvvada et al., 2018; Rass et al., 2012),
schizotypal personality disorder (Brenner et al., 2003; but not observed in Rass et al.,
2012), first-​episode schizophrenia (Spencer et al., 2008a; Tada et al., 2016), early-​onset
psychosis (Wilson et al., 2008), schizoaffective disorder (Zhou et al., 2018), and bipolar
I disorder (Isomura et al., 2016; Spencer et al., 2008a; Zhou et al., 2018). One study
also found the gamma ASSR deficit in bipolar I disorder without psychosis (Parker
et al., 2019), which raises the question of whether this deficit is particular to psychosis.
Additional studies of the ASSR in non-​psychotic bipolar disorder need to be done to
confirm this result.
Thus, the deficit in gamma ASSR generation appears to affect individuals with psych-
osis in general, soon after the first episode of psychosis. The gamma ASSR deficit is even
present in first degree relatives of individuals with schizophrenia, who share genetic (and
possibly environmental) risk factors with persons with schizophrenia, even though they
are not psychotic and have not received antipsychotic medication. A limited amount of
evidence suggests that the gamma ASSR deficit is also present in individuals at high risk
of developing schizophrenia. As more studies take place with this population, it is im-
portant to ask whether the degree of the gamma ASSR deficit is predictive of the prob-
ability of their conversion to psychosis.
While the gamma ASSR is clearly sensitive to neural circuit abnormalities in psych-
osis, it is not so clearly associated with particular psychotic symptoms. Given the na-
ture of the ASSR as an auditory sensory response, and the hypothesized relationships
between gamma oscillations and perception, hallucination symptoms may be expected
to be correlated with gamma ASSR measures. Indeed, some studies have found
correlations between gamma ASSR measures and hallucination symptoms (Mulert
et al., 2011; Spencer et al., 2008a,2009; Zhou et al., 2018), although the direction of these
correlations is not consistent across studies.
The ASSR has become the most widely-​studied gamma oscillation in schizophrenia
research because of several factors:

1. It has a relatively high signal-​to-​noise ratio and is readily obtained.

438   KEVIN M. SPENCER

2. It is easy to analyze, as the frequency is known a priori and the power of the ASSR
can be measured with basic spectral analysis methods that are commonly found in
EEG analysis software.
3. The gamma ASSR deficit in schizophrenia appears to be independent of whether
or not the stimuli are attended (e.g., Hamm et al., 2015).
4. The basic set of neural generators of the ASSR are known (e.g., Herdman et al.,
2002, 2003).
5. The ASSR exhibits good test-​retest reliability (Legget et al., 2017; McFadden et al.,
2014; Tan et al., 2015).

For these reasons, the ASSR is being extensively used in translational neuroscience
studies of animal models relevant to schizophrenia. While rodents do not appear to
have a clearly defined resonance frequency as humans, they do exhibit gamma ASSR
deficits when administered drugs that are commonly used to model aspects of psych-
osis, such as N-​methyl-​D-​aspartate receptor (NMDAR) antagonists (e.g., Leishman
et al., 2015; Sivarao et al., 2016; Sullivan et al., 2015). Therefore, the ASSR is a promising
tool for translational neuroscience research.

18.2.1.2 EAGBR Studies
The next most-​studied gamma oscillation in schizophrenia is the EAGBR, owing
to the extensive use of the auditory oddball and sensory gating paradigms in schizo-
phrenia ERP research, from which the EAGBR can be readily measured (typically in
the responses to the standard stimuli). In general, the evoked power and PLF aspects of
the EAGBR are decreased in the schizophrenia spectrum. EAGBR deficits in chronic
schizophrenia patients have been reported in auditory oddball (e.g., Hall et al., 2011a;
Lenz et al., 2011; Oribe et al., 2019; Roach & Mathalon, 2008), sensory gating (e.g., Hall
et al., 2011b; Popov et al., 2011), and tone discrimination (e.g., Leicht et al., 2010) tasks,
although some studies have failed to find deficits (Brenner et al., 2009; Spencer et al.,
2008b). In first-​episode schizophrenia patients, various studies all reported reduced
evoked power and PLF (Leicht et al., 2015; Oribe et al., 2019; Taylor et al., 2013), although
Gallinat and colleagues (2004) did not find EAGBR deficits in a sample of unmedicated
patients. Studies of clinical high-​risk individuals are mixed: Perez and colleagues (2013)
found that EAGBR evoked power was reduced but PLF did not differ compared with
healthy individuals, while Oribe and colleagues (2019) did not find any reductions in
clinical high-​risk individuals.
Three studies of the EAGBR have provided some insight into the genetic basis of audi-
tory gamma oscillation deficits in schizophrenia. Leicht and colleagues (2011) found
EAGBR power and PLF deficits in both schizophrenia patients and their first-​degree
relatives in a tone discrimination task, pointing to the EAGBR deficit being an inher-
itable trait. Hall and colleagues (2011a) examined the EAGBR from an oddball task in
a sample of schizophrenia patients and their monozygotic twins who were concordant
or discordant for schizophrenia, and compared them to a sample of healthy twin pairs.
Hall and colleagues (2011a) found EAGBR power and PLF deficits in the patients, with
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    439

deficits to lesser degrees in the well co-​twins of discordant pairs. These results were
clearly indicative of a strong genetic factor in the EAGBR deficits. But in contrast to
those studies, Hall and colleagues (2011b) did not find an EAGBR power deficit in the
unaffected first-​degree relatives of schizophrenia patients in data from a sensory gating
task, which suggests that there is no heritable component of the EAGBR deficit in
schizophrenia. One possible explanation for these discrepant findings is that attention
plays a role in producing the EAGBR deficit, as the standard sensory gating task used by
Hall and colleagues (2011b) was passive (unlike the active tasks in Hall et al., 2011a and
Leicht et al., 2011, which found deficits). Thus, the EAGBR deficit in the schizophrenia
spectrum and its genetic basis could involve a major contribution from reduced top-​
down attentional modulation of the EAGBR, rather than a dysfunctional EAGBR per se.
Further work is needed to test this hypothesis.

18.2.1.3 Summary
The ASSR and EAGBR studies provide strong evidence for impaired generation of
stimulus-​evoked gamma oscillations in the auditory cortex in schizophrenia, although
the ASSR results as a whole are stronger than the EAGBR findings. A natural question
to ask is whether the gamma ASSR and EAGBR deficits are correlated. Roach and
colleagues (2013) found that 40-​Hz ASSR PLF and EAGBR PLF were indeed correlated
within both patient and controls groups. Thus, auditory-​evoked gamma oscillations
may provide biomarkers of cortical circuit abnormalities that are heritable and present
across the schizophrenia spectrum.

18.2.2 Visual Gamma Oscillations

18.2.2.1 Gestalt Perception
The first studies that investigated the role of gamma synchronization in perception had
found evidence that gamma oscillations mediated the “binding” of visual features into
coherent objects (Singer & Gray, 1995). Therefore, if schizophrenia was the result of dys-
functional binding of information in the brain via gamma oscillations, it made sense
to study visual feature binding in schizophrenia. Psychophysical studies had reported
abnormalities in visual perception in schizophrenia that were consistent with dys-
functional Gestalt formation (reviewed in Phillips & Silverstein, 2003). Inspired by
Rodriguez and colleagues (1999), who demonstrated local and distributed gamma os-
cillatory activity supporting Gestalt perception (Mooney faces; Mooney & Ferguson,
1951), Spencer and colleagues (2003) had participants with schizophrenia and healthy
controls perform an illusory contour detection task. In the controls, the illusory con-
tour pattern (a Kanisza square) evoked an early visual gamma oscillation, but the non-​
contour pattern did not evoke this oscillation. In the schizophrenia patients, neither
pattern evoked the visual gamma oscillation. Furthermore, the patients showed an
abnormal pattern of inter-​electrode phase synchrony (cf. Lachaux et al., 1999) in the
gamma band.
440   KEVIN M. SPENCER

In a follow-​up study (Spencer et al., 2004), the oscillations phase-​locked to the

manual response in the same task were investigated, as these oscillations were
hypothesized to be more closely related to the perception of the Gestalt than stimulus-​
evoked oscillations. Spencer and colleagues (2004) found that a response-​locked os-
cillation in the gamma band occurred in controls for the illusory contour but not the
non-​contour pattern. In the schizophrenia patients, there was a similar response-​locked
oscillation, but it occurred in the beta band (13–​30 Hz). The PLF aspect of this beta os-
cillation was correlated with some of the patients’ psychotic symptom ratings, including
visual hallucinations and disorganization. In a replication study with briefly presented
stimuli, Spencer and Ghorashi (2014) used a dense electrode array with statistical non-​
parametric mapping. The illusory contour effect on the early visual evoked gamma os-
cillation was not found, although an enhancement of PLF for the illusory contour was
found for a later evoked oscillation in controls that appeared to be an offset response.
In the response-​locked oscillations there was a high gamma (74–​99 Hz) oscillation at
fronto-​central electrodes just prior to the button press that showed greater PLF for the
illusory contour than the non-​contour pattern in controls, and the opposite pattern in
patients. The illusory contour effect on this oscillation in patients was correlated with
their formal thought disorder symptoms. Further, in a study using Kanisza squares as
well as diamonds, Wynn and colleagues (2015) found that in controls the early visual-​
evoked gamma oscillation showed enhanced PLF for illusory contours compared to
the non-​contour pattern, but this effect was absent in the patients. The illusory contour
effect in patients was negatively correlated with their psychotic symptoms.
In another series of studies, Uhlhaas and colleagues (2006a) provided further im-
portant evidence for links between abnormal oscillatory synchronization in Gestalt per-
ception and schizophrenia using a task in which schizophrenia patients were impaired
in the perception of a Gestalt, the discrimination of upright from inverted Mooney
faces (as in Rodriguez et al., 1999). Uhlhaas and colleagues (2006a) found that inter-​
electrode phase synchrony in the beta band elicited by upright face stimuli was delayed
and reduced in schizophrenia patients compared to controls. Furthermore, this beta
phase synchrony effect was correlated with the patients’ psychotic symptom scores,
particularly delusions and hallucinations. Thus, Uhlhaas and colleagues’ (2006a) main
findings were broadly consistent with those of Spencer and colleagues (2004). However,
no differences were found between controls and patients in induced gamma oscillation
power or gamma phase synchrony.
Magnetoencephalography (MEG) has been shown to be more sensitive than
EEG to oscillations in the “high gamma” band (approximately 60–​ 100 Hz)
(Muthukumaraswamy & Singh, 2013), likely owing to its relative insensitivity to scalp
muscle activity (e.g., Pope et al., 2009). Induced gamma oscillations elicited by visual
stimuli that are found in local field potential recordings in animals are also readily de-
tectable with MEG (Hall et al., 2005; Hoogenboom et al., 2006). In a follow-​up study
to Uhlhaas and colleagues (2006a) using MEG, Grützner and colleagues (2013) found
that induced high gamma responses to upright Mooney faces were reduced in schizo-
phrenia patients compared to controls. This deficit was inversely correlated with the
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    441

patients’ disorganization symptoms, consistent with psychophysical studies showing

associations between disorganization and impaired Gestalt perception (e.g., Uhlhaas
et al., 2006b). And in a study examining first-​episode schizophrenia patients who had
never been treated with antipsychotic medication, Sun and colleagues (2013) replicated
this high gamma finding, which was localized to ventral visual areas, and also found that
that low gamma oscillations (30–​60 Hz) were intact while beta power was increased in
the patients.
In the years after the publication of studies by Spencer and colleagues (2003) and
Uhlhaas and colleagues (2006a), it became apparent that the calculation of EEG inter-​
electrode phase synchrony to measure oscillatory synchronization between brain
regions was confounded by several factors, such as common reference and source
mixing (e.g., Guevara et al., 2005; Palva & Palva, 2012). Revisiting the issue of long-​
distance synchronization between brain regions, Hirvonen and colleagues (2017)
analyzed the MEG data of Grützner and colleagues (2013) using a source-​based phase
synchronization method that avoided the common reference problem and minimized
the contribution of source mixing, and found reduced gamma phase synchronization
between visual and prefrontal cortical areas in individuals with schizophrenia compared
to healthy controls, and the reduction in inter-​areal synchronization was correlated with
the patients’ total clinical symptoms.
These studies investigating Gestalt perception in schizophrenia generally found
associations between oscillation abnormalities and psychotic symptoms, particularly
disorganization, and are in line with the results of psychophysical studies of Gestalt per-
ception in schizophrenia. Taken together, the results of these studies are consistent with
the proposed role of gamma synchronization in visual feature binding, and support the
hypothesis that schizophrenia is associated with abnormal oscillatory synchronization
that is functionally related to impaired information processing and clinically relevant
symptoms.

18.2.2.2 Visual Evoked and Induced Gamma

Taking a step back from the domain of Gestalt perception, it can be asked whether visual
gamma activity in general is abnormal in schizophrenia. Visual stimulation elicits two
kinds of high-​frequency oscillatory activity in visual cortex (e.g., Muthukumaraswamy
et al., 2010):

1. an early (~100 ms) evoked, transient oscillation that is phase-​locked to stimulus

onset, with a frequency that varies across the upper beta and gamma bands; and
2. an induced oscillation in the high gamma band with a later onset, that lasts for the
duration of stimulation.

However, for long-​duration stimuli, a transient evoked offset oscillation is also found
with similar characteristics as the early evoked oscillation.
These three visual oscillations have been investigated in schizophrenia. Spencer and
colleagues (2003, 2004, 2008b) found reduced PLF of the early visual evoked gamma
442   KEVIN M. SPENCER

oscillation in chronic schizophrenia patients, but in other studies this oscillation did
not differ from healthy controls (Ghorashi & Spencer, 2015; Spencer & Ghorashi,
2014). Grent-​‘t-​Jong and colleagues (2020) reported reduced PLF of the early evoked
gamma oscillation in first-​episode patients and clinical high-​risk individuals. Grent-​
‘t-​Jong and colleagues (2016, 2020) showed that the power of the visual induced oscil-
lation was reduced in schizophrenia patients during visual stimulation with a moving
grating stimulus, and during stimulation with upright and inverted Mooney face
stimuli (Grützner et al., 2013; Sun et al., 2013). And, the power of the offset response was
also reduced overall in schizophrenia patients compared to controls in Grützner and
colleagues (2013) and Sun and colleagues (2013). Thus, several studies have found some
impairments in gamma oscillations elicited by visual stimuli in schizophrenia, but the
causes for the discrepancies among studies are not clear.
As in the auditory system, steady-​state stimulation has been used in the visual system
to probe the integrity of its circuitry in schizophrenia, although with little consistency
in the stimulation frequencies tested among studies. Using 1-​Hz stimulation, Jin and
colleagues (2000) found that schizophrenia patients had reduced visual steady-​state re-
sponse (VSSR) power at harmonics in the alpha band (10–​12 Hz) compared to healthy
controls. Clementz and colleagues (2004) found that the temporal dynamics of the VSSR
to stimulation at 6.4 Hz were abnormal in schizophrenia, showing a delayed buildup and
a longer decay time. Similarly, using 12.5-​Hz stimulation, Ethridge and colleagues (2011)
found a decline in VSSR power during the stimulation period in persons with schizo-
phrenia compared to controls. Krishnan and colleagues (2005) investigated VSSRs
at stimulation frequencies from 4–​40 Hz and found reduced VSSR power in patients
for beta and gamma frequency stimulation. But in contrast, Riečanský and colleagues
(2010) found increased PLF of the initial transient phase of the VSSR for 40 Hz stimula-
tion in patients.
In sum, there is evidence for deficits in visual gamma generation in schizophrenia,
although these deficits may not be as general as with auditory gamma oscillations. There
is a substantial degree of inconsistency in the early visual-​evoked oscillation and gamma
VSSR findings, while visual induced gamma power seems to be consistently decreased in
schizophrenia (although relatively few studies have investigated this oscillation). More
experiments assessing different types of stimuli, tasks, and multiple VSSR stimulation
frequencies are needed to better understand visual gamma generation in schizophrenia.

18.3  Oscillations Related to Working

Memory Processes

Schizophrenia is characterized by impairments in prefrontal cortex (PFC) function

(e.g., Minzenberg et al., 2009), microcircuitry (e.g., Hoftman et al., 2018), and cognitive
domains associated with PFC circuits: working memory and executive control (Barch,
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    443

2005). Since most of the evidence for neural circuit abnormalities in schizophrenia
comes from studies of PFC microcircuitry, deficits should be found gamma oscillations
elicited in tasks that engage PFC circuits. Several studies have indeed reported gamma
oscillations deficits in working memory and executive control tasks in schizophrenia.
One notable series of studies employed the “preparing to overcome prepotency”
(POP) task, in which a rule governing the spatial correspondence between a response
cue and the manual response is maintained in working memory. On low cognitive
control trials, the response cue matches the response hand, while on high cognitive
control trials, the response cue signals the opposite response hand. In the first study
reporting strong evidence for PFC gamma deficits in working memory in schizo-
phrenia, Cho and colleagues (2006) examined gamma power in chronic schizophrenia
patients and controls performing the POP task, finding that increased cognitive control
requirements elicited higher PFC gamma power during the delay period at electrodes
over the PFC in controls but not in patients, who made more errors in the high con-
trol condition. Gamma power during the late part of the delay was correlated with ac-
curacy in the controls, and negatively correlated with disorganization symptoms in the
patients. In a study comparing medicated and unmedicated first-​episode patients with
controls in the POP task, Minzenberg and colleagues (2010) found a similar pattern
of cognitive control-​related gamma deficits at frontal electrodes in both groups of
patients, indicating that the gamma deficit was not related to antipsychotic medication,
and was present early in the course of the disorder. In healthy individuals, cognitive-​
control-​related gamma in the POP task was correlated with gamma-​amino-​butyric acid
(GABA) neurotransmission, but not in schizophrenia patients (Frankle et al., 2015).
And Minzenberg and colleagues (2015) showed that the administration of modafinil, a
drug that improves cognition through its actions on the dopamine and norepinephrine
systems, enhanced performance on the POP task and the associated cognitive control-​
related gamma power in schizophrenia patients.
Using a version of the Sternberg paradigm, Haenschel and colleagues (2009) provided
further support for the findings of impaired gamma oscillations associated with working
memory maintenance in schizophrenia. Participants had to encode from one to three
objects in working memory and then maintain them for 12 seconds, until a probe
item was presented. Hence, this task enabled the dissociation of processes involved in
working memory encoding, rehearsal, and retrieval. The study found that their early-​
onset schizophrenia patients had worse performance than controls as memory load
(number of objects) increased and showed deficits in stimulus-​evoked oscillations in
several bands in the encoding phase. In the late delay period, induced gamma power at
frontal sites in the controls peaked in the three-​item load condition, whereas induced
gamma power peaked for the patients in the two-​item condition. This kind of abnormal
memory load/​response function has been observed in functional neuroimaging studies
(e.g., Jansma et al., 2004). The patients also had reduced induced theta and gamma
power during the retrieval phase compared to controls.
These studies demonstrate that gamma activity likely originating in the PFC involved
in working memory and executive control processes is impaired in schizophrenia, and
444   KEVIN M. SPENCER

point to avenues for restoring cognitive function to normal levels. This area of research
makes the best link between studies of neural microcircuits and oscillatory activity
related to particular cognitive functions in schizophrenia.

18.4  Transcranial Magnetic

Stimulation (TMS)-​Evoked
Oscillations

Single TMS pulses evoke EEG oscillations in the cortex underneath the stimulated
scalp site. Evidence suggests that the frequency of these TMS-​evoked EEG oscillations
varies for different cortical areas (Ferrarelli et al., 2012; Rosanova et al., 2009): ~10 Hz
for visual cortex, ~20 Hz for parietal cortex, and ~30 Hz for prefrontal cortex. It has
been proposed that the frequency of these oscillations reflects the resonant frequency
of the stimulated cortical area (Rosanova et al., 2009), which is likely to be determined
by specific characteristics of the circuitry in that area. Therefore, TMS-​evoked EEG
oscillations could be used to directly probe the integrity of cortical circuits in neuro-
psychiatric disorders.
To date, only a handful of studies have been conducted in this area. Ferrarelli and
colleagues (2008) examined the oscillations evoked by TMS to the frontal cortex in
healthy persons and schizophrenia patients and found that the oscillations were reduced
in total power and PLF in the patients. In a follow-​up study, Ferrarelli and colleagues
(2012) obtained TMS-​evoked oscillations to stimulation over prefrontal, premotor,
motor, and parietal cortex. They found that the frequency, total power, and PLF of the
TMS-​evoked oscillation were lower in patients than controls for stimulation at the pre-
frontal and premotor sites. Canali and colleagues (2015) stimulated over premotor cortex
in patients with schizophrenia, bipolar disorder, and depression, and found a reduction
in the TMS-​evoked oscillation frequency in all the patient groups compared to controls.
And in a study of first-​episode psychosis patients, Ferrarelli and colleagues (2019) found
reduced beta/​low gamma oscillations evoked by TMS of the motor cortex. The results of
these studies are consistent with the hypothesized gamma oscillation deficits in frontal
cortical areas in schizophrenia (see Section 18.3). TMS-​evoked oscillations could thus
provide a powerful approach to investigate cortical circuits directly without needing to
use particular sensory stimuli or tasks to engage the brain region of interest.

18.5  Spontaneous Oscillations

In modern neuroscience, brain activity is measured with methods at different spa-

tial and temporal scales: single-​unit spiking, local field potentials, intracranial and
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    445

scalp EEG, and functional neuroimaging, among others. The patterns of activity
observed with all of these methods can be classified into two categories: evoked
activity, which results directly from sensory or other stimulation; and intrinsic or
spontaneous activity, which is the ongoing activity does not directly result from
stimulation. Due to the highly recurrent architecture of connections in the brain,
spontaneous activity makes up most of neural activity, while evoked activity makes
up only a small portion (Raichle, 2010). Classical views of brain function have
considered spontaneous activity to be simply “noise”, with evoked activity simply
being added to the random ongoing activity. However, more recent evidence has
demonstrated that spontaneous activity is structured in space and time (Tsodyks
et al., 1999), and much of the variance in evoked responses can be accounted for
by spontaneous activity (Arieli et al., 1996). Spontaneous activity appears to reflect
the spatial and temporal connectivity patterns in local and large-​scale networks,
and in part represents “predictions” of expected sensory input based on past ex-
perience, which interact with and modulate incoming stimulus evoked responses
(Ringach, 2009).
EEG is a powerful method with which to study spontaneous and evoked activity
in the brain as it is sensitive to neural activity across most of the neural frequency
spectrum. However, the neural generators and functional significance of many types
of spontaneous activity in the EEG are largely unknown. Infraslow (0.01–​0.1 Hz) and
slow (0.1–​1 Hz) oscillations in the EEG may correspond to fluctuations in the blood
oxygenation level dependent signal measured with functional magnetic resonance im-
aging, as these kinds of activity occur in the same frequency bands and may share the
same neural generators in large-​scale networks of brain regions (Hiltunen et al., 2014).
At the opposite ends of the frequency and spatial spectra, broadband (as opposed
to narrowband) gamma activity (30–​100 Hz) in the EEG may reflect asynchronous
neuronal spiking in local circuits (e.g., Burke et al., 2015; Yizhar et al., 2011). Recent
studies suggest that oscillatory activity across the frequency spectrum is hierarchically
organized (Buzsáki & Draguhn, 2004), with the phase of low-​frequency oscillations
modulating the power of higher-​ frequency oscillations (reviewed in Canolty &
Knight, 2010).
EEG studies have repeatedly demonstrated that various types of sensory-​and task-​
evoked responses tend to be decreased in individuals with schizophrenia compared
to healthy control subjects. ERPs ranging from early sensory evoked components like
the P50, to purely cognitive components like the P300, generally show decreased, ra-
ther than increased amplitudes in schizophrenia (Javitt et al., 2008). And as reviewed
earlier, event-​related oscillations typically show decreased evoked power and/​or phase
locking. But while schizophrenia is generally associated with decreases in evoked
brain activity, spontaneous oscillatory activity during waking appears to be generally
increased in particular frequency bands. (In fact, findings of increased spontaneous
oscillation power in schizophrenia go back several decades; see Itil, 1977.) One major
question is whether evoked activity deficits are caused to some degree by increased
spontaneous activity.
446   KEVIN M. SPENCER

18.5.1 Resting State Oscillations

There have been many reports of increased low-​frequency power in the resting state
EEG of individuals with schizophrenia, typically in the delta (1–​4 Hz) and/​or theta (4–​8
Hz) bands, although alpha (8–​13 Hz) power does not seem to show a consistent pattern
in the literature (e.g., Boutros et al., 2008; Clementz et al., 1994; Narayanan et al., 2014;
Schulman et al., 2011; Sponheim et al., 2000). Increased delta/​theta power in individuals
with psychotic bipolar disorder has been reported as well (e.g., Clementz et al., 1994;
Narayanan et al., 2014; Sponheim et al., 2000). Increased delta/​theta power has been
found in first-​episode psychosis patients (Clementz et al., 1994; Sponheim et al., 2000),
although Ranlund and colleagues (2014) found increased delta/​theta power in chronic
but not first-​episode psychosis patients. Increased delta/​theta power has not gener-
ally been found in relatives of psychosis patients (e.g., Clementz et al., 1994; Ranlund
et al., 2014), although Narayanan and colleagues (2014) reported an increase in delta
power in SZ relatives. Finally, van Tricht and colleagues (2014) observed increased delta
and theta power in individuals at clinical high risk for psychosis who later transitioned
to psychosis, in comparison to controls and to clinical high-​risk individuals who did
not transition to psychosis. Thus, the sum of the evidence suggests that increased delta
and/​or theta power is associated with psychosis and may even occur before the onset of
psychosis in at-​risk individuals. Furthermore, increased delta/​theta power is found in
unmedicated schizophrenia patients (Boutros et al., 2008), so it does not appear to be an
effect of antipsychotic treatment.
Reports of increased spontaneous high frequency (beta [13–​30 Hz] and gamma
bands) power during the resting state also go back decades (Itil, 1977), but the con-
tribution of artifacts to those reports has been debated, as scalp muscle (e.g., Pope
et al., 2009) and saccadic spike potential (e.g., Keren et al., 2010) artifacts can confound
measurements of high frequency power. Recent studies have used independent compo-
nent analysis (Jung et al., 2000) to remove such artifacts. For example, Narayanan and
colleagues (2014) analyzed the resting EEG in a large sample of individuals with schizo-
phrenia and psychotic bipolar disorder and their relatives. They found increased resting
power in participants with schizophrenia and psychotic bipolar disorder in the low beta
range (13–​20 Hz), but not in the upper beta and gamma bands. Using MEG (which is
less sensitive to scalp muscular artifacts than EEG) in conjunction with ICA artifact
correction, Grent-​‘t-​Jong and colleagues (2018) found widespread reductions of resting
gamma power in chronic schizophrenia patients. However, different gamma patterns
were observed in other illness stages: first-​episode patients showed increased gamma
in visual areas with gamma decreases elsewhere, and clinical high-​risk individuals
demonstrated widespread increases in high gamma power. Consistent with the latter
finding, Ramyead and colleagues (2015) also found increased resting gamma power in
at-​risk individuals who subsequently converted to psychosis. Thus, the evidence so far
suggests that different stages of schizophrenia may be associated with different patterns
of spontaneous gamma activity in the resting state. Further studies of clinical high-​risk
and first-​episode patients are necessary to confirm this hypothesis, particularly longitu-
dinal studies.
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    447

18.5.2 Spontaneous Oscillations During Tasks

If schizophrenia is associated with increased EEG power in particular frequency bands
during the resting state, what about during sensory stimulation or task performance?
Winterer and colleagues (2000, 2004, 2006) found increased induced or “noise” power
with decreased “signal” (ERP) amplitude in schizophrenia patients in the delta/​theta range
at frontal electrodes during auditory oddball tasks. This pattern was also found in un-
affected siblings (Winterer et al., 2004, 2006), and was associated with the COMT genotype,
which affects dopamine signaling in the cortex (Winterer et al., 2006). Dopamine has been
hypothesized to affect the signal-​to-​noise ratio of cortical responses (e.g., Rolls et al., 2008).
In ASSR tasks, Spencer (2012) and Hirano and colleagues (2015) examined induced
gamma power during the baseline and stimulus periods, using dipole source localization
to construct a spatial filter to focus on auditory cortex activity. They found that broadband
induced gamma power was increased in the auditory cortex of individuals with schizo-
phrenia compared to healthy individuals during both the baseline and stimulus periods.
Induced gamma power was inversely correlated with ASSR PLF for 40-​Hz stimulation,
demonstrating an interaction between evoked and spontaneous EEG activity. In addition,
auditory hallucination symptoms in the patients were correlated with broadband gamma
power in the left auditory cortex only during 40-​Hz stimulation (Hirano et al., 2015).
These studies suggest that spontaneous EEG activity is increased in schizophrenia
during sensory stimulation and task performance, although the affected frequency bands
may depend on stimulus and task factors. An important question is whether increased
spontaneous activity in the baseline period of a task is responsible for the apparent deficit
in subsequent evoked activity in individuals with schizophrenia. An increase in baseline
power in schizophrenia patients could cause the power of an evoked response, typic-
ally measured against the baseline, to appear to be reduced in comparison to healthy
individuals, even if the true magnitude of the evoked response was unaffected. Winterer
and colleagues (2000) proposed such an effect of decreased signal-​to-​noise ratio and
evidence of this effect appears in a schizophrenia-​related animal model (Lazarewicz
et al., 2010) and in a VSSR task (Ethridge et al., 2011). The negative correlation between
40-​Hz ASSR PLF and spontaneous gamma power in Hirano and colleagues (2015) may
reflect a different effect: the interference of noise on the PLF measure, as PLF is reduced
as overlapping noise increases (e.g., Ding & Simon, 2013; Muthukumaraswamy & Singh,
2011). These signal-​to-​noise ratio effects could be considered artifactual, in that they pro-
duce apparent effects due to the imperfect nature of the measures. Another possibility is
that increased noise in a neural circuit actually disrupts oscillatory synchronization in
that circuit. Distinguishing that phenomenon from artifactual effects may require meas-
urement of the affected oscillation at the local circuit level.

18.5.3 Sleep Oscillations
Investigations of spontaneous oscillatory activity during sleep in schizophrenia have
focused on two oscillations: slow (delta) waves and sleep spindles (7–​15 Hz). Slow waves
448   KEVIN M. SPENCER

are generated in the cortex, whereas spindles originate in the thalamic reticular nu-
cleus (TRN) and are transmitted to the cortex (Steriade, 2006). Spindle generation in
the thalamus involves interactions among inhibitory interneurons and excitatory thal-
amocortical projection neurons in the TRN (e.g., Jacobsen et al., 2001). Corticothalamic
projections initiate spindles through glutamatergic inputs to TRN cells at NMDARs.
The oscillations tend to be linked through phase-​amplitude coupling, such that sleep
spindles are more likely to occur during the up-​state phase of the slow wave (e.g.,
Staresina et al., 2015). Both oscillations are hypothesized to support the consolidation of
long-​term memories during sleep (Diekelmann & Born, 2010).
Compared to gamma oscillations, there have been relatively few studies of sleep
oscillations in schizophrenia, despite the detailed knowledge of the circuitry that
generates these oscillations. While spontaneous EEG activity during the resting state
or task performance tends to be increased in schizophrenia, spontaneous oscilla-
tory patterns during sleep tend to be reduced. The findings on slow waves are mixed,
with some reports of deficits (e.g., D’Agostino et al., 2018; Sarkar et al., 2010; Sekimoto
et al., 2011) but other studies not finding slow wave abnormalities (e.g., Ferrarelli et al.,
2007, 2010). In contrast, there is strong evidence that spindle generation is impaired in
schizophrenia (e.g., Ferrarelli et al., 2007, 2010; Manoach et al., 2014; Wamsley et al.,
2012). Spindle deficits have been reported in medication-​naïve first-​episode patients
(Manoach et al., 2014) and unaffected first-​degree relatives of schizophrenia patients
(D’Agostino et al., 2018; Manoach et al., 2014), indicating that spindle impairment is a
trait marker of schizophrenia and is not due to antipsychotic medication. While spindle
impairment is associated with reduced thalamic volume (Buchmann et al., 2014), it has
also been correlated with abnormally increased thalamocortical functional connect-
ivity (Baran et al., 2019). With regards to symptomatology, spindle deficits have been
associated with psychotic symptom ratings (Ferrarelli et al., 2010; Wamsley et al., 2012).
Notably, there is substantial evidence that sleep spindle deficits are associated with
impairments in memory consolidation in schizophrenia (reviewed in Manoach et al.,
2016), pointing to spindle-​generating circuitry as a potential target for treatment of both
psychotic symptoms and impaired cognition in schizophrenia.

18.6  Circuit Mechanisms Underlying

Oscillation Abnormalities
in Schizophrenia

Neural oscillation research has made an important impact on our understanding of

schizophrenia due to the cross-​fertilization of this field with basic research into os-
cillation mechanisms and neuropathological studies of neural circuit abnormalities
in schizophrenia. Unlike ERPs, for which the generating mechanisms are unknown,
the basic mechanisms underlying some oscillations are known to a fair degree. For
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    449

example, cortical gamma oscillations are generated by recurrent interactions between

excitatory pyramidal cells and fast-​spiking, parvalbumin-​expressing (PV+​) inhibi-
tory interneurons (Buzsáki & Wang, 2012). Neuropathological research has identified
deficits in pyramidal cells and PV+​interneurons (e.g., Lewis et al., 2012) that can be
used to inform models of gamma generation, enabling researchers to test hypotheses
about gamma abnormalities in schizophrenia with methods such as neuropharma-
cology (e.g., Sivarao et al., 2016), optogenetics (e.g., Carlén et al., 2012; Yizhar et al.,
2011), and computational modeling (e.g., Jadi et al., 2016; Kömek et al., 2012; Spencer,
2009). This section reviews some of the integrative research into the neural circuit
mechanisms of oscillation abnormalities in schizophrenia and focuses on the areas of
NMDAR hypofunction and reduced synaptic connectivity in which a major proportion
of research has been done.

18.6.1 NMDAR Hypofunction
The glutamate hypothesis of schizophrenia (Moghaddam & Javitt, 2012) offers clues to
the neural circuit abnormalities that may be responsible for both evoked gamma oscil-
lation deficits and increased spontaneous gamma activity in this disorder. In healthy
people, acute administration of NMDAR antagonists produces a constellation of posi-
tive and negative symptoms, cognitive deficits, and neurophysiological abnormalities
that resemble those found in schizophrenia (Krystal et al., 2003). In animals, the be-
havioral and neurophysiological abnormalities resulting from acute administra-
tion of NMDAR antagonists (reviewed in Amann et al., 2010) and genetic knockouts
of NMDARs (e.g., Belforte et al., 2010; Korotkova et al., 2010) resemble those found
in schizophrenia. In particular, acute NMDAR antagonism reduces the amplitude of
some ERPs (Amann et al., 2010) and gamma oscillations (e.g., Lazarewicz et al., 2010;
Leishman et al., 2015; Sivarao et al., 2016; Sullivan et al., 2015), in addition to increasing
broadband spontaneous gamma power (reviewed in Hunt & Kasicki, 2013). Genetic
ablation of NMDARs also increases spontaneous gamma power in adult animals (e.g.,
Carlén et al., 2012; Korotkova et al., 2010; Tatard-​Leitman et al., 2015). Increased spon-
taneous gamma as a result of NMDAR hypofunction results from increased excitability
of pyramidal cells, either through disinhibition from reduced excitatory drive to fast-​
spiking interneurons (Carlén et al., 2012; Homayoun & Moghaddam, 2007), and/​or
by alterations in cell membrane properties of the pyramidal cells themselves (Tatard-​
Leitman et al., 2015). With regard to increased spontaneous delta/​theta power, in the
thalamus, NMDAR antagonism increases delta band activity, which is transmitted to
the hippocampus (Zhang et al., 2012) and the cortex (Hunt & Kasicki, 2013).
In healthy humans, besides the behavioral effects that resemble psychotic symptoms,
NMDAR antagonism via acute ketamine administration decreases the amplitude of
some ERPs (e.g., Gunduz-​Bruce et al., 2012) and increases broadband gamma power
during rest (Muthukumaraswamy et al., 2015; Rivolta et al., 2015). This increase in spon-
taneous gamma power is consistent with increased cortical excitability, which has
450   KEVIN M. SPENCER

been shown with TMS to result from NMDAR antagonist administration (Di Lazzaro
et al., 2003). But in contrast to the animal model studies, ketamine in humans decreases
resting state cortical delta activity (Muthukumaraswamy et al., 2015).

18.6.2 Reduced Synaptic Connectivity

The scalp-​recorded EEG and MEG mainly reflect the spatially and temporally
summated post-​synaptic potentials in the dendritic trees of cortical pyramidal cells
(Nunez, 1981). Dendritic spines are the main sources of excitatory input to pyram-
idal cells, and reductions in dendritic spine density have been consistently reported
in the prefrontal cortex in schizophrenia (e.g., Glantz & Lewis, 2000; Sweet et al.,
2009). Decreased dendritic spine density is thought to reflect a general reduction
in synaptic connectivity (both excitatory and inhibitory) in local cortical circuits,
and is manifested as reduced cortical volume and thickness at the macroscopic
level of structural magnetic resonance imaging studies of schizophrenia (Selemon
& Goldman-​R akic, 1999). Thus, deficits of oscillation power in schizophrenia could
be caused by reduced synaptic connectivity in the generating cortex. In support
of this hypothesis, a few studies have found correlations between the structure of
the superior temporal gyrus (STG) (which contains auditory sensory and associ-
ation cortex) and ASSR measures. Edgar and colleagues (2014) found a correlation
between left STG cortical thickness and 40-​Hz ASSR total power in the left hemi-
sphere, although in controls and not schizophrenia patients. Similarly, Kim and
colleagues (2019) reported a correlation between right STG gray volume and 40-​Hz
ASSR evoked power in controls but not patients. Hirano and colleagues (2020) found
that the gray matter volume of left Heschl’s gyrus (located in the anterior portion
of the STG and containing primary auditory cortex, the main ASSR generator) was
correlated with 40-​Hz ASSR PLF and inversely correlated with spontaneous gamma
power in patients. While these three sets of findings involve different oscillation
measures and diagnostic groups, they do provide support for the idea that cortical
structure can influence gamma oscillations.
Using a computational model, we simulated the reduction of excitatory and inhibi-
tory connections in a cortical region and found that pyramidal cell excitability increased
as excitatory and inhibitory connections were eliminated (Spencer, 2009). A recent ex-
perimental study showed that reduced density of dendritic spines was associated with
increased pyramidal cell excitability and schizophrenia-​like behaviors in rodents, which
could be reversed with antipsychotic medication (Kim et al., 2015). Thus, increased
spontaneous gamma power in schizophrenia might also be associated with decreased
dendritic spine density and cortical volume/​thickness deficits (Hirano et al., 2020).
As subchronic administration of phencyclidine, an NMDAR antagonist, can result in
decreased dendritic spine density (Hajszan et al., 2006), NMDAR hypofunction could
be involved in synaptic connectivity reductions in schizophrenia as well.
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    451

18.7  Conclusions and

Future Directions

Within the last two decades, research into neural oscillations has generated a body of
findings that has made a substantial impact on our conceptualization of schizophrenia,
understanding of its pathophysiology, and methods of testing new treatments. The
study of gamma oscillations has had the most success, due to the cross-​fertilization of
clinical studies with neuropathological, basic, and computational research. As details
of the specific cellular elements that are disturbed in schizophrenia are revealed, it is
possible to construct hypotheses about the consequences of these circuit abnormalities
in animal and computational models and try to relate them to the human clinical data.
The field has matured in step with the broader field of oscillatory brain dynamics. In
most studies the potential sources of EEG artifacts are now understood and corrected
for, and the importance of having adequate numbers of epochs is appreciated. Studies
have better statistical power, and mass univariate statistics are being used with the ap-
propriate corrections for multiple tests. The influence of confounds like common refer-
ence and volume conduction is more widely appreciated for connectivity studies. Thus,
the potential for false positive findings seems to be less than before.
And yet, to this researcher, the promise of oscillation research for ultimately helping
develop new treatments for schizophrenia (and other neuropsychiatric disorders)
seems far from being fulfilled. The most complete body of research has been on the
gamma ASSR, which is being used as a biomarker in translational research, yet this
oscillation has limited relevance for cognition or symptoms in schizophrenia (except
possibly for auditory hallucinations). The areas of research into perceptual organ-
ization and working memory, while being the best motivated by psychological and
mechanistic theories, have not yet yielded reliable measures that can be used in transla-
tional research. So, much more work remains to be done. I still believe that as research
progresses into the neural mechanisms underlying different oscillations, and the nature
of neural circuit abnormalities in schizophrenia is understood in greater detail, it will
become possible to construct and test mechanistic hypotheses with greater precision,
both in vivo and in silico. Ultimately this research effort may come full circle, leading to
the use of neurostimulation methods to modulate and “correct” aberrant oscillations in
individuals with schizophrenia, and in this way, re-​integrate the broken mind.

ACKNOWLEDGMENTS

This work was supported by grants I01 CX001443 from the US Department of Veterans
Affairs, R01 MH093450 from the National Institutes of Health, and an Independent
452   KEVIN M. SPENCER

Investigator Award from the Brain and Behavior Research Foundation. The author
reports no conflicts of interest.

REFERENCES
Amann, L. C., Gandal, M. J., Halene, T. B., Ehrlichman, R. S., White, S. L., McCarren, H. S.,
& Siegel, S. J. (2010). Mouse behavioral endophenotypes for schizophrenia. Brain Research
Bulletin, 83(3–​4), 147–​161.
Arieli, A., Sterkin, A., Grinvald, A., & Aertsen, A. (1996). Dynamics of ongoing ac-
tivity: Explanation of the large variability in evoked cortical responses. Science, 273,
1868–​1871.
Baran, B., Karahanoğlu, F. I., Mylonas, D., Demanuele, C., Vangel, M., Stickgold, R., Anticevic,
A., & Manoach, D. S. (2019). Increased thalamocortical connectivity in schizophrenia
correlates with sleep spindle deficits: evidence for a common pathophysiology. Biological
Psychiatry: Cognitive Neuroscience and Neuroimaging, 4, 706–​7 14.
Barch, D. M. (2005). The cognitive neuroscience of schizophrenia. Annual Review of Clinical
Psychology, 1, 321–​353.
Belforte, J. E., Zsiros, V., Sklar, E. R., Jiang, Z., Yu, G., Li, Y., . . . Nakazawa, K. (2010). Postnatal
NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-​ like
phenotypes. Nature Neuroscience, 13(1), 76–​83.
Bleuler, E. (1911/​ 1950). Dementia Praecox or the Group of Schizophrenias. International
Universities Press.
Boutros, N. N., Arfken, C., Galderisi, S., Warrick, J., Pratt, G., & Iacono, W. (2008). The status
of spectral EEG abnormality as a diagnostic test for schizophrenia. Schizophrenia Research,
99(1–​3), 225–​237.
Brenner, C. A., Kieffaber, P. D., Clementz, B. A., Johannesen, J. K., Shekhar, A., O’Donnell, B. F.,
& Hetrick, W. P. (2009). Event-​related potential abnormalities in schizophrenia: A failure to
“gate in” salient information? Schizophrenia Research, 113(2–​3), 332–​338.
Brenner, C., Sporns, O., Lysaker, P. H., & O’Donnell, B. F. (2003). EEG synchronization to
modulated auditory tones in schizophrenia, schizoaffective disorder, and schizotypal per-
sonality disorder. American Journal of Psychiatry, 160(December), 2238–​2240.
Buchmann, A., Dentico, D., Peterson, M. J., Riedner, B. A., Sarasso, S., Massimini, M., Tononi,
G., & Ferrarelli, F. (2014). Reduced mediodorsal thalamic volume and prefrontal cortical
spindle activity in schizophrenia. NeuroImage, 102, 540–​547.
Burke, J. F., Ramayya, A. G., & Kahana, M. J. (2015). Human intracranial high-​frequency ac-
tivity during memory processing: neural oscillations or stochastic volatility? Current
Opinion in Neurobiology, 31, 104–​110.
Buzsáki, G. (2006). Rhythms of the brain. Oxford University Press.
Buzsáki, G. & Draguhn, A. (2004). Neuronal oscillations in cortical networks. Science, 304,
1926–​1929.
Buzsáki, G. & Wang, X.-​J. (2012). Mechanisms of gamma oscillations. Annual Review of
Neuroscience, 35, 203–​225.
Canali, P., Sarasso, S., Rosanova, M., Casarotto, S., Sferrazza-​ Papa, G., Gosseries,
O., . . . Benedetti, F. (2015). Shared reduction of oscillatory natural frequencies in bipolar
disorder, major depressive disorder and schizophrenia. Journal of Affective Disorders, 184,
111–​115.
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    453

Canolty, R. T. & Knight, R. T. (2010). The functional role of cross-​frequency coupling. Trends in
Cognitive Sciences, 14, 506–​515.
Carlén, M., Meletis, K., Siegle, J. H., Cardin, J. A, Futai, K., Vierling-​Claassen, D., . . . Tsai, L.-​H.
(2012). A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm
induction and behavior. Molecular Psychiatry, 17(5), 537–​548.
Cho, R. Y., Konecky, R. O., & Carter, C. S. (2006). Impairments in frontal cortical gamma
synchrony and cognitive control in schizophrenia. Proceedings of the National Academy of
Sciences of the United States of America, 103(52), 19878–​19883.
Clementz, B. A., Blumenfeld, L. D., & Cobb, S. (1997). The gamma band response may account
for poor P50 suppression in schizophrenia. Neuroreport, 8(18), 3889–​3893.
Clementz, B. A., Keil, A., & Kissler, J. (2004). Aberrant brain dynamics in schizo-
phrenia: Delayed buildup and prolonged decay of the visual steady-​state response. Cognitive
Brain Research, 18(2), 121–​129. doi:10.1016/​j.cogbrainres.2003.09.007
Clementz, B., Sponheim, S., Iacono, W. G., & Beiser, M. (1994). Resting EEG in first-​episode
schizophrenia patients, bipolar psychosis patients, and their first-​ degree relatives.
Psychophysiology, 31, 486–​494.
D’Agostino, A., Castelnovo, A., Cavallotti, S., Casetta, C., Marcatili, M., Gambini, O., Canevini,
M., Tononi, G., Riedner, B., Ferrarelli, F., & Sarasso, S. (2018). Sleep endophenotypes of
schizophrenia: slow waves and sleep spindles in unaffected first-​degree relatives. NPJ
Schizophrenia, 4(1), 2.
Davidson, M., Kapara, O., Goldberg, S., Yoffe, R., Noy, S., & Weiser, M. (2016). A nation-​wide
study on the percentage of schizophrenia and bipolar disorder patients who earn minimum
wage or above. Schizophrenia Bulletin, 42(2), 443–​447.
Diekelmann, S. & Born, J. (2010). The memory function of sleep. Nature Reviews Neuroscience,
11, 114–​126.
Di Lazzaro, V., Oliviero, A., Profice, P., Pennisi, M. A., Pilato, F., Zito, G., . . . Tonali, P. A. (2003).
Ketamine increases human motor cortex excitability to transcranial magnetic stimulation.
The Journal of Physiology, 547(Pt 2), 485–​496.
Ding, N. & Simon, J. Z. (2013). Power and phase properties of oscillatory neural responses in
the presence of background activity. Journal of Computational Neuroscience, 34(2), 337–​343.
Draganova, R., Ross, B., Wollbrink, A., & Pantev, C. (2008). Cortical steady-​state responses to
central and peripheral auditory beats. Cerebral Cortex, 18(5), 1193–​1200.
Eckhorn, R., Bauer, R., Jordan, W., Brosch, M., Kruse, W., Munk, M., & Reitboeck, H. (1988).
Coherent oscillations: a mechanism of feature linking in the visual cortex? Multiple elec-
trode and correlation analyses in the cat. Biological Cybernetics, 60, 121–​130.
Edgar, J. C., Chen, Y.-​H., Lanza, M., Howell, B., Chow, V. Y., Heiken, K., . . . Cañive, J. M.
(2014). Cortical thickness as a contributor to abnormal oscillations in schizophrenia?
NeuroImage: Clinical, 4, 122–​129.
Ethridge, L., Moratti, S., Gao, Y., Keil, A., & Clementz, B. A. (2011). Sustained versus tran-
sient brain responses in schizophrenia: The role of intrinsic neural activity. Schizophrenia
Research, 133(1–​3), 106–​111.
Farahani, E. D., Goossens, T., Wouters, J., & van Wieringen, A. (2017). Spatiotemporal recon-
struction of auditory steady-​state responses to acoustic amplitude modulations: Potential
sources beyond the auditory pathway. NeuroImage, 148, 240–​253.
Ferrarelli, F., Huber, R., Peterson, M. J., Massimini, M., Murphy, M., Riedner, B. A., . . . Tononi,
G. (2007). Reduced sleep spindle activity in schizophrenia patients. American Journal of
Psychiatry, 164(3), 483–​492.
454   KEVIN M. SPENCER

Ferrarelli, F., Kaskie, R. E., Graziano, B., Reis, C. C., & Casali, A. G. (2019). Abnormalities
in the evoked frontal oscillatory activity of first-​episode psychosis: A TMS/​EEG study.
Schizophrenia Research, 206, 436–​439.
Ferrarelli, F., Massimini, M., Peterson, M. J., Riedner, B. A., Lazar, M., Murphy, M. J., . . . Tononi,
G. (2008). Reduced evoked gamma oscillations in the frontal cortex in schizophrenia
patients: A TMS/​EEG study. American Journal of Psychiatry, 165(8), 996–​1005.
Ferrarelli, F., Peterson, M., Sarasso, S., Riedner, B. A., Murphy, M. J., Benca, R. M., . . . Tononi,
G. (2010). Thalamic dysfunction in schizophrenia suggested by whole-​night deficits in slow
and fast spindles. American Journal of Psychiatry, 167(November), 1339–​1348.
Ferrarelli, F., Sarasso, S., Guller, Y., Riedner, B. A, Peterson, M. J., Bellesi, M., ... Tononi, G.
(2012). Reduced natural oscillatory frequency of frontal thalamocortical circuits in schizo-
phrenia. Archives of General Psychiatry, 69, 766–​774.
Frankle, W. G., Cho, R. Y., Prasad, K. M., Mason, N. S., Paris, J., Himes, M. L., . . . Narendran, R.
(2015). In vivo measurement of GABA transmission in healthy subjects and schizophrenia
patients. American Journal of Psychiatry, 172, 1148–​1159.
Friston, K. J. & Frith, C. D. (1995). Schizophrenia: A disconnection syndrome? Clinical
Neuroscience, 3, 89–​97.
Galambos, R., Makei, S., & Talmachoff, P. J. (1981). A 40-​Hz auditory potential recorded from
the human scalp. Proceedings of the National Academy of Sciences of the United States of
America, 78(4), 2643–​2647.
Gallinat, J., Winterer, G., Herrmann, C. S., & Senkowski, D. (2004). Reduced oscillatory
gamma-​band responses in unmedicated schizophrenic patients indicate impaired frontal
network processing. Clinical Neurophysiology, 115(8), 1863–​1874.
Ghorashi, S. & Spencer, K. M. (2015). Attentional load effects on beta oscillations in healthy and
schizophrenic individuals. Frontiers in Psychiatry, 6(October), 149.
Glantz, L. A. & Lewis, D. A. (2000). Decreased dendritic spine density on prefrontal cortical
pyramidal neurons in schizophrenia. Archives of General Psychiatry, 57(1), 65–​73.
Gray, C. M., Konig, P., Engel, A. K., & Singer, W. (1989). Oscillatory responses in cat visual
cortex exhibit inter-​columnar synchronization which reflects global stimulus properties.
Nature, 338, 334–​337.
Gray, C. M. & Singer, W. (1989). Stimulus-​specific neuronal oscillations in orientation columns
of cat visual cortex. Proceedings of the National Academy of Sciences of the United States of
America, 86, 1698–​1702.
Grent-​‘t-​Jong, T., Gajwani, R., Gross, J., Gumley, A. I., Krishnadas, R., Lawrie, S. M., . . . Uhlhaas,
P. J. (2020). Association of magnetoencephalographically measured high-​ frequency
oscillations in visual cortex with circuit dysfunctions in local and large-​scale networks
during emerging psychosis. JAMA Psychiatry, 77(8), 852–​862.
Grent-​’t-​Jong, T., Gross, J., Goense, J., Wibral, M., Gajwani, R., Gumley, A. I., ... Uhlhaas, P.
J. (2018). Resting-​state gamma-​band power alterations in schizophrenia reveal E/​I-​balance
abnormalities across illness-​stages. eLife, 7, e37799.
Grent-​‘t-​Jong, T., Rivolta, D., Sauer, A., Grube, M., Singer, W., Wibral, M., & Uhlhaas, P. J.
(2016). MEG-​measured visually induced gamma-​band oscillations in chronic schizo-
phrenia: Evidence for impaired generation of rhythmic activity in ventral stream regions.
Schizophrenia Research, 176(2–​3), 177–​185.
Grützner, C., Wibral, M., Sun, L., Rivolta, D., Singer, W., Maurer, K., & Uhlhaas, P. J. (2013).
Deficits in high-​(>60 Hz) gamma-​band oscillations during visual processing in schizo-
phrenia. Frontiers in Human Neuroscience, 7(March), 88.
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    455

Guevara, R., Luis Pérez Velazquez, J., Nenadovic, V., Wennberg, R., Senjanovic, G., & Garcia
Dominguez, L. (2005). Phase synchronization measurements using electroencephalographic
recordings: What can we really say about neuronal synchrony? Neuroinformatics, 3, 301–​313.
Gunduz-​Bruce, H., Reinhart, R. M. G., Roach, B. J., Gueorguieva, R., Oliver, S., D’Souza, D.
C., . . . Mathalon, D. H. (2012). Glutamatergic modulation of auditory information pro-
cessing in the human brain. Biological Psychiatry, 71(11), 969–​977.
Haenschel, C., Bittner, R. a, Waltz, J., Haertling, F., Wibral, M., Singer, W., . . . Rodriguez, E.
(2009). Cortical oscillatory activity is critical for working memory as revealed by deficits in
early-​onset schizophrenia. Journal of Neuroscience, 29(30), 9481–​9489.
Hajszan, T., Leranth, C., & Roth, R. H. (2006). Subchronic phencyclidine treatment decreases
the number of dendritic spine synapses in the rat prefrontal cortex. Biological Psychiatry,
60(6), 639–​644.
Hall, M., Taylor, G., Salisbury, D. F., & Levy, D. L. (2011a). Sensory gating event-​related
potentials and oscillations in schizophrenia patients and their unaffected relatives.
Schizophrenia Bulletin, 37(6), 1187–​1199.
Hall, M., Taylor, G., Sham, P., Schulze, K., Rijsdijk, F., Picchioni, M., . . . Salisbury, D. F. (2011).
The early auditory gamma-​band response is heritable and a putative endophenotype of
schizophrenia. Schizophrenia Bulletin, 37(4), 778–​787.
Hall, S. D., Holliday, I. E., Hillebrand, A., Singh, K. D., Furlong, P. L., Hadjipapas, A., & Barnes,
G. R. (2005). The missing link: Analogous human and primate cortical gamma oscillations.
NeuroImage, 26, 13–​17.
Hamm, J. P., Bobilev, A. M., Hayrynen, L. K., Hudgens-​Haney, M. E., Oliver, W. T., Parker, D.
A., . . . Clementz, B. A. (2015). Stimulus train duration but not attention moderates γ-​band
entrainment abnormalities in schizophrenia. Schizophrenia Research, 165(1), 97–​102.
Hamm, J. P., Gilmore, C. S., Picchetti, N. A. M., Sponheim, S. R., & Clementz, B. A. (2011).
Abnormalities of neuronal oscillations and temporal integration to low-​and high-​frequency
auditory stimulation in schizophrenia. Biological Psychiatry, 69(10), 989–​996.
Hebb, D. O. (1949). The organization of behavior. Wiley.
Herdman, A. T., Lins, O., Roon, P. Van, Stapells, D. R., Scherg, M., & Picton, T. W. (2002).
Intracerebral sources of human auditory steady-​state responses. Brain Topography, 15, 69–​86.
Herdman, A. T., Wollbrink, A., Chau, W., Ishii, R., Ross, B., & Pantev, C. (2003). Determination
of activation areas in the human auditory cortex by means of synthetic aperture magnetom-
etry. NeuroImage, 20(2), 995–​1005.
Hiltunen, T., Kantola, J., Abou Elseoud, A., Lepola, P., Suominen, K., Starck, T., . . . Palva JM
(2014). Infra-​slow EEG fluctuations are correlated with resting-​state network dynamics in
fMRI. Journal of Neuroscience, 34, 356–​362.
Hirano, Y., Oribe, N., Kanba, S., Onitsuka, T., Nestor, P. G., & Spencer, K. M. (2015).
Spontaneous gamma activity in schizophrenia. JAMA Psychiatry, 72(8), 813–​821.
Hirano, Y., Oribe, N., Onitsuka, T., Kanba, S., Nestor, P. G., Hosokawa, T., ... Spencer, K. M.
(2020). Auditory cortex volume and gamma oscillation abnormalities in schizophrenia.
Clinical EEG and Neuroscience, 51, 244–​251.
Hirvonen, J., Wibral, M., Palva, J. M., Singer, W., Uhlhaas, P., & Palva, S. (2017). Whole-​brain
source-​reconstructed MEG-​data reveal reduced long-​range synchronization in chronic
schizophrenia. eNeuro, 4(5), e0338–​17.2017.
Hoftman, G. D., Dienel, S. J., Bazmi, H. H., Zhang, Y., Chen, K., & Lewis, D. A. (2018). Altered
gradients of glutamate and gamma-​aminobutyric acid transcripts in the cortical visuo-
spatial working memory network in schizophrenia. Biological Psychiatry, 83(8), 670–​679.
456   KEVIN M. SPENCER

Homayoun, H. & Moghaddam, B. (2007). NMDA receptor hypofunction produces opposite

effects on prefrontal cortex interneurons and pyramidal neurons. Journal of Neuroscience,
27(43), 11496–​11500.
Hong, L. E., Summerfelt, A., McMahon, R., Adami, H., Francis, G., Elliott, A., . . . Thaker,
G. K. (2004). Evoked gamma band synchronization and the liability for schizophrenia.
Schizophrenia Research, 70(2–​3), 293–​302.
Hoogenboom, N., Schoffelen, J., Oostenveld, R., Parkes, L. M., & Fries, P. (2006). Localizing
human visual gamma-​band activity in frequency, time and space. NeuroImage, 29(3),
764–​773.
Hunt, M. J. & Kasicki, S. (2013). A systematic review of the effects of NMDA receptor
antagonists on oscillatory activity recorded in vivo. Journal of Psychopharmacology, 27(11),
972–​986.
Isomura, S., Onitsuka, T., Tsuchimoto, R., Nakamura, I., Hirano, S., Oda, Y., . . . Kanba, S.
(2016). Differentiation between major depressive disorder and bipolar disorder by auditory
steady-​state responses. Journal of Affective Disorders, 190, 800–​806.
Itil, T. M. (1977). Qualitative and quantitative EEG findings in schizophrenia. Schizophrenia
Bulletin, 3(1), 61–​79.
Jacobsen, R. B., Ulrich, D., & Huguenard, J. R. (2001). GABA(B) and NMDA receptors con-
tribute to spindle-​like oscillations in rat thalamus in vitro. Journal of Neurophysiology, 86,
1365–​1375.
Jadi, M. P., Behrens, M. M., & Sejnowski, T. J. (2016). Abnormal gamma oscillations in N-​
methyl-​D-​aspartate receptor hypofunction models of schizophrenia. Biological Psychiatry,
79(9), 716–​726.
Jansma, J. M., Ramsey, N. F., van der Wee, N. J. A., & Kahn, R. S. (2004). Working memory cap-
acity in schizophrenia: A parametric fMRI study. Schizophrenia Research, 68(2–​3), 159–​171.
Javitt, D. C., Spencer, K. M., Thaker, G. K., Winterer, G., & Hajós, M. (2008). Neurophysiological
biomarkers for drug development in schizophrenia. Nature Reviews Drug Discovery,
7(1), 68–​83.
Jin, Y., Castellanos Jr, A., Solis Jr, E. R., & Potkin, S. G. (2000). EEG resonant responses in
schizophrenia: A photic driving study with improved harmonic resolution. Schizophrenia
Research, 44, 213–​220.
Jung, T. P., Makeig, S., Humphries, C., Lee, T. W., McKeown, M. J., Iragui, V., & Sejnowski,
T. J. (2000). Removing electroencephalographic artifacts by blind source separation.
Psychophysiology, 37, 163–​178.
Keren, A. S., Yuval-​Greenberg, S., & Deouell, L. Y. (2010). Saccadic spike potentials in gamma-​
band EEG: characterization, detection and suppression. NeuroImage, 49(3), 2248–​2263.
Kim, S., Jang, S.-​K., Kim, D.-​W., Shim, M., Kim, Y.-​W., Im, C.-​H., & Lee, S.-​H. (2019). Cortical
volume and 40-​Hz auditory-​steady-​state responses in patients with schizophrenia and
healthy controls. NeuroImage: Clinical, 22, 101732.
Kim, I. H., Rossi, M. A., Aryal, D. K., Racz, B., Kim, N., Uezu, A., . . . Soderling, S. H. (2015).
Spine pruning drives antipsychotic-​sensitive locomotion via circuit control of striatal dopa-
mine. Nature Neuroscience, 18(6), 883–​891.
Kömek, K., Bard Ermentrout, G., Walker, C. P., & Cho, R. Y. (2012). Dopamine and gamma
band synchrony in schizophrenia—​insights from computational and empirical studies.
European Journal of Neuroscience, 36(2), 2146–​2155.
Korotkova, T., Fuchs, E. C., Ponomarenko, A., von Engelhardt, J., & Monyer, H. (2010). NMDA
receptor ablation on parvalbumin-​positive interneurons impairs hippocampal synchrony,
spatial representations, and working memory. Neuron, 68(3), 557–​569.
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    457

Krishnan, G. P., Hetrick, W. P., Brenner, C. A., Shekhar, A., Steffen, A. N., & O’Donnell, B. F.
(2009). Steady state and induced auditory gamma deficits in schizophrenia. NeuroImage,
47(4), 1711–​1719.
Krishnan, G. P., Vohs, J. L., Hetrick, W. P., Carroll, C. A., Shekhar, A., Bockbrader, M. A., &
O’Donnell, B. F. (2005). Steady state visual evoked potential abnormalities in schizophrenia.
Clinical Neurophysiology, 116(3), 614–​624.
Krystal, J. H., D’Souza, D. C., Mathalon, D., Perry, E., Belger, A., & Hoffman, R. (2003). NMDA
receptor antagonist effects, cortical glutamatergic function, and schizophrenia: Toward a
paradigm shift in medication development. Psychopharmacology, 169(3–​4), 215–​233.
Kwon, J. S., O’Donnell, B. F., Wallenstein, G. V, Greene, R. W., Hirayasu, Y., Nestor, P.
G., . . . McCarley, R. W. (1999). Gamma frequency-​range abnormalities to auditory stimula-
tion in schizophrenia. Archives of General Psychiatry, 56(11), 1001–​1005.
Lachaux, J. P., Rodriguez, E., Martinerie, J., & Varela, F. J. (1999). Measuring phase synchrony in
brain signals. Human Brain Mapping, 8(4), 194–​208.
Lazarewicz, M. T., Ehrlichman, R. S., Maxwell, C. R., Gandal, M. J., Finkel, L. H., & Siegel,
S. J. (2010). Ketamine modulates theta and gamma oscillations. Journal of Cognitive
Neuroscience, 22(7), 1452–​1464.
Legget, K. T., Hild, A. K., Steinmetz, S. E., Simon, S. T., & Rojas, D. C. (2017). MEG and EEG
demonstrate similar test-​retest reliability of the 40 Hz auditory steady-​state response.
International Journal of Psychophysiology, 114, 16–​23.
Leicht, G., Andreou, C., Polomac, N., Lanig, C., Schöttle, D., Lambert, M., & Mulert, C. (2015).
Reduced auditory evoked gamma band response and cognitive processing deficits in first
episode schizophrenia. The World Journal of Biological Psychiatry, 16(6), 387–​397.
Leicht, G., Karch, S., Karamatskos, E., Giegling, I., Möller, H.-​J., Hegerl, U., . . . Mulert, C. (2011).
Alterations of the early auditory evoked gamma-​band response in first-​degree relatives of
patients with schizophrenia: Hints to a new intermediate phenotype. Journal of Psychiatric
Research, 45(5), 699–​705.
Leicht, G., Kirsch, V., Giegling, I., Karch, S., Hantschk, I., Möller, H.-​J., . . . Mulert, C. (2010).
Reduced early auditory evoked gamma-​band response in patients with schizophrenia.
Biological Psychiatry, 67(3), 224–​231.
Leishman, E., O’Donnell, B. F., Millward, J. B., Vohs, J. L., Rass, O., Krishnan, G. P., . . . Morzorati,
S. L. (2015). Phencyclidine disrupts the auditory steady state response in rats. PLoS One,
10(8), e0134979.
Lemere, F. (1936). The significance of individual differences in the Berger rhythm. Brain, 59,
366–​375.
Lenz, D., Fischer, S., Schadow, J., Bogerts, B., & Herrmann, C. S. (2011). Altered evoked γ-​
band responses as a neurophysiological marker of schizophrenia? International Journal of
Psychophysiology, 79(1), 25–​31.
Leung, M., Cheung, C., Yu, K., Yip, B., Sham, P., Li, Q., . . . McAlonan, G. (2011). Gray matter in
first-​episode schizophrenia before and after antipsychotic drug treatment. Anatomical like-
lihood estimation meta-​analyses with sample size weighting. Schizophrenia Bulletin, 37(1),
199–​211.
Lewis, D. A., Curley, A. A., Glausier, J. R., & Volk, D. W. (2012). Cortical parvalbumin
interneurons and cognitive dysfunction in schizophrenia. Trends in Neurosciences,
35(1), 57–​67.
Light, G. A., Hsu, J. L., Hsieh, M. H., Meyer-​Gomes, K., Sprock, J., Swerdlow, N. R., & Braff, D.
L. (2006). Gamma band oscillations reveal neural network cortical coherence dysfunction
in schizophrenia patients. Biological Psychiatry, 60(11), 1231–​1240.
458   KEVIN M. SPENCER

Manoach, D. S., Demanuele, C., Wamsley, E. J., Vangel, M., Montrose, D. M., Miewald,
J., . . . Keshavan, M. S. (2014). Sleep spindle deficits in antipsychotic-​naive early course
schizophrenia and in non-​psychotic first-​degree relatives. Frontiers in Human Neuroscience,
8(October), 762.
Manoach, D. S., Pan, J. Q., Purcell, S. M., & Stickgold, R. (2016). Reduced sleep spindles in
schizophrenia: A treatable endophenotype that links risk genes to impaired cognition?
Biological Psychiatry, 80(8), 599–​608.
McFadden, K. L., Steinmetz, S. E., Carroll, A. M., Simon, S. T., Wallace, A., & Rojas, D. C.
(2014). Test-​retest reliability of the 40 Hz EEG auditory steady-​state response. PLoS One,
9(1), e85748.
McGlashan, T. H. & Hoffman, R. E. (2000). Schizophrenia as a disorder of developmentally
reduced synaptic connectivity. Archives of General Psychiatry, 57(7), 637–​648.
Minzenberg, M. J., Firl, A. J., Yoon, J. H., Gomes, G. C., Reinking, C., & Carter, C. S. (2010).
Gamma oscillatory power is impaired during cognitive control independent of medication
status in first-​episode schizophrenia. Neuropsychopharmacology, 35(13), 2590–​2599.
Minzenberg, M. J., Laird, A. R., Thelen, S., Carter, C. S., & Glahn, D. C. (2009). Meta-​analysis
of 41 functional neuroimaging studies of executive function in schizophrenia. Archives of
General Psychiatry, 66(8), 811–​822.
Minzenberg, M. J., Yoon, J. H., Cheng, Y., & Carter, C. S. (2015). Sustained modafinil
treatment effects on control-​ related gamma oscillatory power in schizophrenia.
Neuropsychopharmacology, 41(5), 1231–​1240.
Moghaddam, B. & Javitt, D. (2012). From revolution to evolution: the glutamate hypothesis of
schizophrenia and its implication for treatment. Neuropsychopharmacology, 37(1), 4–​15.
Mooney, C. M. & Ferguson, G. A. (1951). A new closure test. Canadian Journal of Psychology, 5,
129–​133.
Mulert, C., Kirsch, V., Pascual-​Marqui, R., McCarley, R. W., & Spencer, K. M. (2011). Long-​
range synchrony of γ oscillations and auditory hallucination symptoms in schizophrenia.
International Journal of Psychophysiology, 79(1), 55–​63.
Murray, R. M. & Lewis, S. W. (1987). Is schizophrenia a neurodevelopmental disorder? British
Medical Journal, 295(6600), 681–​682.
Muthukumaraswamy, S. D., Shaw, A. D., Jackson, L. E., Hall, J., Moran, R., & Saxena, N. (2015).
Evidence that subanesthetic doses of ketamine cause sustained disruptions of NMDA and
AMPA-​mediated frontoparietal connectivity in humans. Journal of Neuroscience, 35(33),
11694–​11706.
Muthukumaraswamy, S. D. & Singh, K. D. (2011). A cautionary note on the interpretation
of phase-​locking estimates with concurrent changes in power. Clinical Neurophysiology,
122(11), 2324–​2325.
Muthukumaraswamy, S. D. & Singh, K. D. (2013). Visual gamma oscillations: The effects of
stimulus type, visual field coverage and stimulus motion on MEG and EEG recordings.
NeuroImage, 69, 223–​230.
Muthukumaraswamy, S. D., Singh, K. D., Swettenham, J. B., & Jones, D. K. (2010). Visual
gamma oscillations and evoked responses: variability, repeatability and structural MRI
correlates. NeuroImage, 49(4), 3349–​3357.
Narayanan, B., O’Neil, K., Berwise, C., Stevens, M. C., Calhoun, V. D., Clementz, B.
A., . . . Pearlson, G. D. (2014). Resting state electroencephalogram oscillatory abnormalities
in schizophrenia and psychotic bipolar patients and their relatives from the bipolar and
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    459

schizophrenia network on intermediate phenotypes study. Biological Psychiatry, 76(6),

456–​465.
Nunez, P. L. (1981). Electric Fields of the Brain. Oxford University Press.
O’Donnell, B. F., Vohs, J. L., Krishnan, G. P., Rass, O., Hetrick, W. P., & Morzorati, S. L. (2013).
The auditory steady-​state response (ASSR): A translational biomarker for schizophrenia.
Supplements to Clinical Neurophysiology, 62, 101–​112.
Oribe, N., Hirano, Y., del Re, E., Seidman, L. J., Mesholam-​Gately, R. I., Woodberry, K.
A., . . . Spencer, K. M. (2019). Progressive reduction of auditory evoked gamma in first epi-
sode schizophrenia but not clinical high risk individuals. Schizophrenia Research, 208,
145–​152.
Owen, M. J., Sawa, A., & Mortensen, P. B. (2016). Schizophrenia. The Lancet, 388(10039), 86–​97.
Parker, D. A., Hamm, J. P., McDowell, J. E., Keedy, S. K., Gershon, E. S., Ivleva, E. I., . . . Clementz,
B. A. (2019). Auditory steady-​state EEG response across the schizo-​bipolar spectrum.
Schizophrenia Research, 209, 218–​226.
Palva, S. & Palva, J. M. (2012). Discovering oscillatory interaction networks with M/​
EEG: challenges and breakthroughs. Trends in Cognitive Sciences, 16(4), 219–​230.
Pantev, C., Makeig, S., Hoke, M., Galambos, R., Hampson, S., & Gallen, C. (1991). Human audi-
tory evoked gamma-​band magnetic fields. Proceedings of the National Academy of Sciences of
the United States of America, 88, 8996–​9000.
Perälä, J., Suvisaari, J., Saarni, S. I., Kuoppasalmi, K., Isometsä, E., Pirkola, S., . . . Lönnqvist,
J. (2007). Lifetime prevalence of psychotic and bipolar I disorders in a general population.
Archives of General Psychiatry, 64(1), 19–​28.
Perez, V. B., Roach, B. J., Woods, S. W., Srihari, V. H., McGlashan, T. H., Ford, J. M., & Mathalon,
D. H. (2013). Early auditory gamma-​band responses in patients at clinical high risk for
schizophrenia. Supplements to Clinical Neurophysiology, 62(415), 147–​162.
Pastor, M. A., Artieda, J., Arbizu, J., Marti-​climent, J. M., Pen, I., & Masdeu, J. C. (2002).
Activation of Human Cerebral and Cerebellar Cortex by Auditory Stimulation at 40 Hz.
Journal of Neuroscience, 22(23), 10501–​10506.
Phillips, W. A. & Silverstein, S. M. (2003). Convergence of biological and psychological
perspectives on cognitive coordination in schizophrenia. Behavioral and Brain Sciences,
26, 65–​82.
Picton, T. W., John, M. S., Dimitrijevic, A., & Purcell, D. (2003). Human auditory steady-​state
responses. International Journal of Audiology, 42, 177–​219.
Pope, K. J., Fitzgibbon, S. P., Lewis, T. W., Whitham, E. M., & Willoughby, J. O. (2009). Relation
of gamma oscillations in scalp recordings to muscular activity. Brain Topography, 22(1), 13–​17.
Popov, T., Jordanov, T., Weisz, N., Elbert, T., Rockstroh, B., & Miller, G. A. (2011). Evoked and
induced oscillatory activity contributes to abnormal auditory sensory gating in schizo-
phrenia. NeuroImage, 56(1), 307–​314.
Puvvada, K. C., Summerfelt, A., Du, X., Krishna, N., Kochunov, P., Rowland, L. M., . . . & Hong,
L. E. (2018). Delta vs gamma auditory steady state synchrony in schizophrenia. Schizophrenia
Bulletin, 44(2), 378–​387.
Raichle, M. E. (2010). Two views of brain function. Trends in Cognitive Sciences, 14, 180–​190.
Ramyead, A., Kometer, M., Studerus, E., Koranyi, S., Ittig, S., Gschwandtner, U., . . . Riecher-​
Rossler, A. (2015). Aberrant current source-​density and lagged phase synchronization
of neural oscillations as markers for emerging psychosis. Schizophrenia Bulletin, 41(4),
919–​929.
460   KEVIN M. SPENCER

Ranlund, S., Nottage, J., Shaikh, M., Dutt, A., Constante, M., Walshe, M., . . . Bramon, E.
(2014). Resting EEG in psychosis and at-​risk populations -​A possible endophenotype?
Schizophrenia Research, 153(1–​3), 96–​102.
Rapoport, J. L., Giedd, J. N., & Gogtay, N. (2012). Neurodevelopmental model of schizo-
phrenia: Update 2012. Molecular Psychiatry, 17(12), 1228–​1238.
Rass, O., Forsyth, J. K., Krishnan, G. P., Hetrick, W. P., Klaunig, M. J., Breier, A., . . . Brenner,
C. A. (2012). Auditory steady state response in the schizophrenia, first-​degree relatives, and
schizotypal personality disorder. Schizophrenia Research, 136(1–​3), 143–​149.
Riečanský, I., Kašpárek, T., Rehulová, J., Katina, S., & Přikryl, R. (2010). Aberrant EEG
responses to gamma-​frequency visual stimulation in schizophrenia. Schizophrenia Research,
124(1–​3), 101–​109.
Ringach, D. L. (2009). Spontaneous and driven cortical activity: Implications for computation.
Current Opinion in Neurobiology, 19, 439–​444.
Rivolta, D., Heidegger, T., Scheller, B., Sauer, A., Schaum, M., Birkner, K., . . . Uhlhaas,
P. J. (2015). Ketamine dysregulates the amplitude and connectivity of high-​frequency
oscillations in cortical-​ subcortical networks in humans: evidence from resting-​ state
magnetoencephalography-​recordings. Schizophrenia Bulletin, 41(5), 1105–​1114.
Roach, B. J., Ford, J. M., Hoffman, R. E., & Mathalon, D. H. (2013). Converging evidence for
gamma synchrony deficits in schizophrenia. Supplements to Clinical Neurophysiology, 62,
163–​180.
Roach, B. J. & Mathalon, D. H. (2008). Event-​related EEG time-​frequency analysis: An over-
view of measures and an analysis of early gamma band phase locking in schizophrenia.
Schizophrenia Bulletin, 34(5), 907–​926.
Rodriguez, E., George, N., Lachaux, J.-​P., Martinerie, J., Renault, B., & Varela, F. J. (1999).
Perception’s shadow: Long-​distance synchronization of human brain activity. Nature, 397,
430–​433.
Rolls, E. T., Loh, M., Deco, G., & Winterer, G. (2008). Computational models of schizophrenia
and dopamine modulation in the prefrontal cortex. Nature Reviews Neuroscience, 9(9),
696–​709.
Rosanova, M., Casali, A., Bellina, V., Resta, F., Mariotti, M., & Massimini, M. (2009). Natural
frequencies of human corticothalamic circuits. Journal of Neuroscience, 29(24), 7679–​7685.
Sarkar, S., Katshu, M. Z. U. H., Nizamie, S. H., & Praharaj, S. K. (2010). Slow wave sleep deficits
as a trait marker in patients with schizophrenia. Schizophrenia Research, 124(1–​3), 127–​133.
https://​doi.org/​10.1016/​j.sch​res.2010.08.013
Schulman, J. J., Cancro, R., Lowe, S., Lu, F., Walton, K. D., & Llinás, R. R. (2011). Imaging of thal-
amocortical dysrhythmia in neuropsychiatry. Frontiers in Human Neuroscience, 5(July), 69.
Selemon, L. D., & Goldman-​Rakic, P. S. (1999). The reduced neuropil hypothesis: a circuit
based model of schizophrenia. Biological Psychiatry, 45, 17–​25.
Sekimoto, M., Kato, M., Watanabe, T., Kajimura, N., & Takahashi, K. (2011). Cortical regional
differences of delta waves during all-​night sleep in schizophrenia. Schizophrenia Research,
126(1–​3), 284–​290.
Siever, L. J. & Davis, K. L. (2004). The pathophysiology of schizophrenia disorders: perspectives
from the spectrum. American Journal of Psychiatry, 161(March), 398–​413.
Singer, W. (1999). Neuronal synchrony: A versatile code for the definition of relations? Neuron,
24, 49–​65.
Singer, W. & Gray, C. M. (1995). Visual feature integration and the temporal correlation hy-
pothesis. Annual Review of Neuroscience, 18, 555–​586.
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    461

Sivarao, D. V, Chen, P., Senapati, A., Yang, Y., Fernandes, A., Benitex, Y., . . . Ahlijanian, M. K.
(2016). 40 Hz auditory steady-​state response is a pharmacodynamic biomarker for cortical
NMDA receptors. Neuropsychopharmacology, 41(9), 2232–​2240.
Spencer, K. M. (2009). The functional consequences of cortical circuit abnormalities on
gamma oscillations in schizophrenia: insights from computational modeling. Frontiers in
Human Neuroscience, 3, 33.
Spencer, K. M. (2012). Baseline gamma power during auditory steady-​state stimulation in
schizophrenia. Frontiers in Human Neuroscience, 5(January), 190.
Spencer, K. M., & Ghorashi, S. (2014). Oscillatory dynamics of Gestalt perception in schizo-
phrenia revisited. Frontiers in Psychology, 5(February), 68.
Spencer, K., Nestor, P., Niznikiewicz, M. A., Salisbury, D. F., Shenton, M. E., & McCarley, R.
W. (2003). Abnormal neural synchrony in schizophrenia. Journal of Neuroscience, 23(19),
7407–​7411.
Spencer, K. M., Nestor, P. G., Perlmutter, R., Niznikiewicz, M. A, Klump, M. C., Frumin,
M., . . . McCarley, R. W. (2004). Neural synchrony indexes disordered perception and cogni-
tion in schizophrenia. Proceedings of the National Academy of Sciences of the United States of
America, 101(49), 17288–​17293.
Spencer, K. M., Niznikiewicz, M. A, Nestor, P. G., Shenton, M. E., & McCarley, R. W. (2009).
Left auditory cortex gamma synchronization and auditory hallucination symptoms in
schizophrenia. BMC Neuroscience, 10, 85.
Spencer, K. M., Niznikiewicz, M. A., Shenton, M. E., & McCarley, R. W. (2008b). Sensory-​
evoked gamma oscillations in chronic schizophrenia. Biological Psychiatry, 63(8),
744–​747.
Spencer, K. M., Salisbury, D. F., Shenton, M. E., & McCarley, R. W. (2008a). Gamma-​band
auditory steady-​state responses are impaired in first episode psychosis. Biological Psychiatry,
64(5), 369–​375.
Sponheim, S. R., Clementz, B. a, Iacono, W. G., & Beiser, M. (2000). Clinical and biological
concomitants of resting state EEG power abnormalities in schizophrenia. Biological
Psychiatry, 48(11), 1088–​1097.
Staresina, B. P., Bergmann, T. O., Bonnefond, M., van der Meij, R., Jensen, O., Deuker, L., . . . Fell,
J. (2015). Hierarchical nesting of slow oscillations, spindles and ripples in the human hippo-
campus during sleep. Nature Neuroscience, 18(11), 1679–​1686.
Steriade, M. (2006). Grouping of brain rhythms in corticothalamic systems. Neuroscience,
137(4), 1087–​1106.
Sullivan, E. M., Timi, P., Hong, L. E., & O’Donnell, P. (2015). Effects of NMDA and GABA-​
A receptor antagonism on auditory steady-​state synchronization in awake behaving rats.
International Journal of Neuropsychopharmacology, 18(7), pyu118.
Sun, L., Castellanos, N., Grützner, C., Koethe, D., Rivolta, D., Wibral, M., . . . Uhlhaas, P. J.
(2013). Evidence for dysregulated high-​frequency oscillations during sensory processing
in medication-​ naïve, first episode schizophrenia. Schizophrenia Research, 150(2–​3),
519–​525.
Sweet, R. A., Henteleff, R. A., Zhang, W., Sampson, A. R., & Lewis, D. A. (2009).
Reduced dendritic spine density in auditory cortex of subjects with schizophrenia.
Neuropsychopharmacology, 34(2), 374–​389.
Tada, M., Nagai, T., Kirihara, K., Koike, S., Suga, M., Araki, T., . . . Kasai, K. (2016). Differential
alterations of auditory gamma oscillatory responses between pre-​onset high-​risk individuals
and first-​episode schizophrenia. Cerebral Cortex, 26(3), 1027–​1035.
462   KEVIN M. SPENCER

Tallon-​Baudry, C., Bertrand, O., Delpuech, C., & Pernier, J. (1996). Stimulus specificity
of phase-​locked and non-​phase-​locked 40 Hz visual responses in human. Journal of
Neuroscience, 16(13), 4240–​4249.
Tan, H.-​R. M., Gross, J., & Uhlhaas, P. J. (2015). MEG—​measured auditory steady-​state
oscillations show high test–​ retest reliability: A sensor and source-​ space analysis.
NeuroImage, 122, 417–​426.
Tatard-​Leitman, V. M., Jutzeler, C. R., Suh, J., Saunders, J. A., Billingslea, E. N., Morita,
S., . . . Siegel, S. J. (2015). Pyramidal cell selective ablation of N-​methyl-​D-​aspartate receptor
1 causes increase in cellular and network excitability. Biological Psychiatry, 77(6), 556–​568.
Taylor, G. W., McCarley, R. W., & Salisbury, D. F. (2013). Early auditory gamma band response
abnormalities in first hospitalized schizophrenia. Supplements to Clinical Neurophysiology,
62, 131–​145.
Teale, P., Collins, D., Maharajh, K., Rojas, D. C., Kronberg, E., & Reite, M. (2008). Cortical
source estimates of gamma band amplitude and phase are different in schizophrenia.
NeuroImage, 42(4), 1481–​1489.
Thuné, H., Recasens, M., & Uhlhaas, P. J. (2016). The 40-​Hz auditory steady-​state response in
patients with schizophrenia. JAMA Psychiatry, 73(11), 1145–​1153.
Tsodyks, M., Kenet, T., Grinvald, A., & Arieli, A. (1999). Linking spontaneous activity of single
cortical neurons and the underlying functional architecture. Science, 286, 1943–​1946.
Tsuchimoto, R., Kanba, S., Hirano, S., Oribe, N., Ueno, T., Hirano, Y., . . . Onitsuka, T. (2011).
Reduced high and low frequency gamma synchronization in patients with chronic schizo-
phrenia. Schizophrenia Research, 133(1–​3), 99–​105.
Uhlhaas, P. J., Linden, D. E. J., Singer, W., Haenschel, C., Lindner, M., Maurer, K., & Rodriguez,
E. (2006a). Dysfunctional long-​range coordination of neural activity during Gestalt percep-
tion in schizophrenia. Journal of Neuroscience, 26(31), 8168–​8175.
Uhlhaas, P. J., Phillips, W. a, Mitchell, G., & Silverstein, S. M. (2006b). Perceptual grouping in
disorganized schizophrenia. Psychiatry Research, 145(2–​3), 105–​117.
van Tricht, M. J., Ruhrmann, S., Arns, M., Müller, R., Bodatsch, M., Velthorst, E., . . . Nieman,
D. H. (2014). Can quantitative EEG measures predict clinical outcome in subjects at clin-
ical high risk for psychosis? A prospective multicenter study. Schizophrenia Research, 153(1–​
3), 42–​47.
Wamsley, E. J., Tucker, M. A., Shinn, A. K., Ono, K. E., McKinley, S. K., Ely, A. V, . . . Manoach,
D. S. (2012). Reduced sleep spindles and spindle coherence in schizophrenia: Mechanisms of
impaired memory consolidation? Biological Psychiatry, 71(2), 154–​161.
Weinberger, D. R. (1987). Implications of normal brain development for the pathogenesis of
schizophrenia. Archives of General Psychiatry, 44(7), 660–​669.
Wilson, T. W., Hernandez, O. O., Asherin, R. M., Teale, P. D., Reite, M. L., & Rojas, D. C. (2008).
Cortical gamma generators suggest abnormal auditory circuitry in early-​onset psychosis.
Cerebral Cortex, 18(2), 371–​378.
Winterer, G., Coppola, R., Goldberg, T. E., Egan, M. F., Jones, D. W., Sanchez, C. E., &
Weinberger, D. R. (2004). Prefrontal broadband noise, working memory, and genetic risk
for schizophrenia. American Journal of Psychiatry, 161(March), 490–​500.
Winterer, G., Egan, M. F., Kolachana, B. S., Goldberg, T. E., Coppola, R., & Weinberger, D. R.
(2006). Prefrontal electrophysiologic “noise” and catechol-​O-​methyltransferase genotype
in schizophrenia. Biological Psychiatry, 60(6), 578–​584.
 A REVIEW OF OSCILLATORY BRAIN DYNAMICS IN SCHIZOPHRENIA    463

Winterer, G., Ziller, M., Dorn, H., Frick, K., Mulert, C., Wuebben, Y., . . . Coppola, R. (2000).
Schizophrenia: Reduced signal-​to-​noise ratio and impaired phase-​locking during informa-
tion processing. Clinical Neurophysiology, 111(5), 837–​849.
Wynn, J. K., Roach, B. J., Lee, J., Horan, W. P., Ford, J. M., Jimenez, A. M., & Green, M. F. (2015).
EEG findings of reduced neural synchronization during visual integration in schizophrenia.
PLoS One, 10(3), e0119849.
Yizhar, O., Fenno, L. E., Prigge, M., Schneider, F., Davidson, T. J., O’Shea, D. J., . . . Deisseroth, K.
(2011). Neocortical excitation/​inhibition balance in information processing and social dys-
function. Nature, 477(7363), 171–​178.
Zaehle, T., Lenz, D., Ohl, F. W., & Herrmann, C. S. (2010). Resonance phenomena in the human
auditory cortex: Individual resonance frequencies of the cerebral cortex determine electro-
physiological responses. Experimental Brain Research, 203(3), 629–​635.
Zhang, Y., Yoshida, T., Katz, D. B., & Lisman, J. E. (2012). NMDAR antagonist action in thal-
amus imposes δ oscillations on the hippocampus. Journal of Neurophysiology, 107(11),
3181–​3189.
Zhou, T.-​H., Mueller, N. E., Spencer, K. M., Mallya, S. G., Lewandowski, K. E., Norris, L.
A., . . . Hall, M.-​H. (2018). Auditory steady state response deficits are associated with
symptom severity and poor functioning in patients with psychotic disorder. Schizophrenia
Research, 201, 278–​286.
 CHAPTER 19

EEG FREQU E NC Y
T ECHNIQU ES FOR I MAG I NG
C ONTROL FU NC T I ONS I N
ANXIET Y

JASON S. MOSER, COURTNEY LOUIS, LILIANNE

GLOE, STEFANIE RUSSMAN BLOCK, AND
SPENCER FIX

19.1  Overview and Introduction

This chapter reviews and discusses the application of EEG frequency techniques to
imaging and understanding motivational/​emotional and cognitive control functions
in anxiety. The first three sections present a historical account of how EEG frequency
techniques have been used to understand emotional, motivational, and cognitive
components of anxiety. The final section considers these different EEG frequency
metrics vis-​à-​vis theoretical models of anxiety and how they are being, or could be, used
to advance both science and treatment. Particularly, this chapter focuses on how anxiety
relates to motivational/​emotional and cognitive control dynamics involved in balancing
bottom-​up and top-​down influences on behavior. As previous chapters in this volume
primarily review the measurement and nature of EEG frequency signals, here we in-
stead focus on the applications of these methods to the study of anxiety.
Anxiety is a common human experience that often involves a mix of cognitive,
physiological, and behavioral manifestations (Barlow, 2002). It lies on a continuum from
mild levels that can motivate individuals to increase vigilance and respond adaptively to
threat or challenge (Barlow, 2002), but at excessive levels represents the most common
mental health problem worldwide (U.S. Burden of Disease Collaborators, 2018). It is a
multi-​dimensional construct that many have separated into anxious apprehension and
 EEG FREQUENCY TECHNIQUES In Anxiety    465

anxious arousal subtypes, with the former dominated by verbal worries and ruminations
focused on future ambiguous threat and the latter by somatic tension and physiological
hyperactivity centered on clear immediate threats (Heller et al., 1997, Heller & Nitschke,
1998). Given its multifaceted nature, anxiety and its associated impairments have been
tackled from motivational/​emotional, cognitive and neuropsychological perspectives
(Eysenck et al., 2007; Gray & McNaughton, 2000; Heller et al., 1997, Heller & Nitschke,
1998). In the review that follows, we examine anxiety across the spectrum of severity
and, thus, how EEG frequency metrics reflect the dynamic interplay of motivation,
emotion, and cognition in adaptive and maladaptive forms of anxiety.

19.2  The First Wave: Alpha and Anxiety

19.2.1 Early Foundations and the Right-​Sided Bias

Historically, the largest body of research examining anxiety and EEG frequency band
activity focused on alpha frontal asymmetry, or the difference in alpha power at lat-
eral frontal electrode sites between the right and left hemispheres. This is examined by
subtracting the natural log of alpha power in the left hemisphere from that of the right
hemisphere (i.e., F4−F3, F6−F5, and F8−F7), resulting in an asymmetry score (Reznik &
Allen, 2018). Because alpha power is thought to reflect reduced cortical activity, greater
relative right alpha asymmetry is interpreted as decreased cortical activity in the right
hemisphere (Allen et al., 2004).
Such research grew out of an emerging interest in understanding emotion in the
1970s (e.g., Ekman & Friesen, 1971; Ledoux, 1978) and simultaneous observations of the
hemispheric specialization of emotions in patients with brain lesions (Gainotti, 1972;
Sackeim et al., 1982; Silberman & Weingartner, 1986) as well as patients undergoing
neurological procedures (see Davidson & Fox, 1982). Specifically, it was proposed that
the left hemisphere is involved the generation of positive affect, whereas the right hemi-
sphere is involved in the generation of negative affect, including anxiety.
Davidson and colleagues (Davidson, 1979, 1984, 1988; Davidson & Fox, 1982) were
the first to apply EEG methodology to this framework. In a series of novel papers, they
introduced an approach-​withdrawal model of behavior to explain frontal laterality and
the neural basis of emotion. According to this model, greater relative left-​frontal activity
(i.e., reduced alpha power in the left hemisphere) is related to approach behaviors and
positive affect, whereas greater relative right-​frontal activity is related to withdrawal
behavior and negative affect. Here, anxiety is positioned as a manifestation of negative
affect and withdrawal (Fox, 1991).
In support of this model, several studies across a variety of populations—​infants, chil-
dren, non-​human primates, and adults—​have implicated right alpha frontal asymmetry
in anxiety. In several papers, Davidson and Fox (Davidson & Fox, 1989; Fox et al., 1992;
466    JASON S. MOSER et al.

Fox & Davidson, 1987) reported that in 10-​month-​old infants, distress, gaze aversion,
and crying in response to maternal separation was associated with greater relative right-​
frontal brain activity. This was found to be both a trait and state marker of behavior,
as resting-​state asymmetry was predictive of later anxious behaviors during the separ-
ation (Davidson & Fox, 1989; Fox et al., 1992), and asymmetry scores increased during
the separation (Fox & Davidson, 1987). Anxious behaviors, internalizing problems, and
diagnoses of anxiety disorders (based on direct observation and parent report) in pre-
school (Fox et al., 1995; Fox et al., 1996) and school-​age children (Baving et al., 2002;
Schmidt et al., 1999) also demonstrated a relationship to relative right-​frontal activa-
tion both at rest and during a stress induction. Similarly, child anxious temperament
(e.g., high reactivity and behavioral inhibition), which is predictive of the development
of clinically significant social anxiety (Hirshfeld-​Becker et al., 2007), has been reported
to be associated with right anterior activity (McManis et al., 2002). The same patterns of
alpha frontal asymmetry can be observed in non-​human primates (Kalin et al., 1998),
and can be decreased with the administration of anxiolytic benzodiazepines (Davidson
et al., 1992). In adults, self-​reported trait-​anxiety on the State-​Trait-​Anxiety Inventory
(STAI) (Spielberger, 1983) has been reported to correlate with relative right-​frontal
asymmetry in healthy young adults (Adolph & Margraf, 2017; Blackhart et al., 2006).
In clinical populations, those with obsessive compulsive disorder (OCD) were found to
have greater relative right-​frontal asymmetry (Ischebeck et al., 2014; Kuskowski et al.,
1993) and cognitive behavioral therapy has been found to shift asymmetry from relative
right to left activity in patients with social anxiety disorder (Moscovitch et al., 2011). In
summary, relative right-​frontal alpha asymmetry seems to reflect tendencies to with-
draw from stress or novelty and a propensity towards anxious temperament.

19.2.2 Conflicting Findings and Anxiety Subtypes

An equally large body of work, however, has not supported the hypothesis that anx-
iety relates to greater right compared to left-​frontal activation. Indeed, several studies
have reported no frontal asymmetry differences in anxious populations (Kemp et al.,
2010; Metzger et al., 2004; Nitschke et al., 1999; Shankman et al., 2008; Smith et al.,
2018), whereas others have reported greater relative left-​frontal activation in anxiety
(Heller et al., 1997). These mixed findings could be due to the fact that anxiety is not
a unitary construct and led to the proposal that anxiety subtypes may show different
patterns of alpha asymmetry (Heller et al., 1997). Anxious apprehension, characterized
by worry and rumination typically observed in generalized anxiety disorder (GAD)
(Barlow, 1991), has been posited to be associated with greater left-​frontal activity due
to the lateralization of language to the left hemisphere (Heller et al., 1997). On the other
hand, anxious arousal, characterized by somatic symptoms of anxiety that are typically
observed in panic disorder and post-​traumatic stress disorder (PTSD), has been posited
to be associated with greater relative right-​frontal activation (Heller et al., 1997).
 EEG FREQUENCY TECHNIQUES In Anxiety    467

The few EEG studies of alpha frontal asymmetry in patient populations (Buchsbaum
et al., 1985; Smith et al., 2016) have supported the hypothesis that anxious apprehen-
sion is predominately related to greater left-​hemisphere activity, though findings in
non-​patient populations have been mixed, possibly due to methodological differences.
For example, Heller and colleagues (1997) found that anxious apprehension, defined
as scores above the 90th percentile on the STAI, was associated with left-​frontal asym-
metry, though as noted earlier, other studies have reported the opposite findings using
this measure (Adolph & Margraf, 2017; Blackhart et al., 2006) and one study found
no asymmetry differences (Smith et al., 2018). Studies that have used the Penn State
Worry Questionnaire (Meyer et al., 1990) as a measure of anxious apprehension have
also been mixed, with one study reporting greater left-​frontal asymmetry (Smith et al.,
2016), and two reporting no asymmetry differences (Nitschke et al., 1999; Smith et al.,
2018). Hofmann et al. (2005) reported that a worry induction in healthy college students
resulted in increased left-​frontal alpha asymmetry, whereas, Carter, Johnson, and
Borkovec (1986) reported no association between a worry induction and alpha asym-
metry, though greater left asymmetry was reported in the beta band. Recently, Nusslock
and colleagues (2018) reported that the typical pattern of relative right-​frontal activity in
patients with depression was no longer present when considering those with comorbid
anxiety disorders (e.g., separation, GAD, and OCD). Together, these findings highlight
the importance of considering anxiety measurement and population in the interpret-
ation of alpha asymmetry findings.
With regards to anxious arousal and relative right-​ frontal asymmetry, all
investigations, with the exception of those in PTSD, have supported the hypothesis that
anxious arousal can be distinguished from anxious apprehension by relative right-​frontal
activation. Self-​reported anxious arousal (Mathersul et al., 2008; Nitschke et al., 1999;
Smith et al., 2016), anxiety inductions (Avram et al., 2010; Davidson et al., 2000; Isotani
et al., 2001) and clinical levels of anxious arousal (e.g., panic disorder) (Wiedemann
et al., 1999) have all been shown to correlate with relative right-​frontal activation.
Reports in participants with PTSD have failed to find frontal asymmetry differences
in either direction (Kemp et al., 2010; Metzger et al., 2004; Rabe et al., 2006; Shankman
et al., 2008), though Rabe and colleagues (2006) did find right-​frontal activity to be
associated with greater symptom severity when participants viewed trauma-​related
pictures. Kemp and colleagues (2010) did not find differences between healthy controls
and participants with PTSD; however, they did find an association between PTSD se-
verity and right-​frontal asymmetry within the PTSD group. These mixed findings in
PTSD could be due to the heterogeneous presentation of the disorder, age differences
in the populations studied, and the possibility that PTSD may be neurobiologically dis-
tinct from other anxiety disorders (Lobo et al., 2015; Shankman et al., 2008).
In addition to being associated with frontal alpha asymmetry, arousal has also been
related to alpha power in posterior regions (i.e., parietal and temporal) (Heller, 1993).
Indeed, PTSD patients demonstrate greater relative right-​parietal activity (Kemp et al.,
2010; Metzger et al., 2004; Rabe, Beauducel, et al., 2006). Although some have reported
468    JASON S. MOSER et al.

similar findings in other anxious populations (Bruder et al., 1997; Heller et al., 1997;
Mathersul et al., 2008; Smith et al., 2016), there have been insufficient studies focusing
on posterior alpha activity to draw definitive conclusions.

19.2.3 The Devil is in the Details: Methodological

Heterogeneity and Ambiguity in Neural Sources
Several other methodological issues may limit the interpretation of alpha asymmetry
findings. First, there are inconsistencies regarding electrode site selection, with some
studies examining only lateral frontal sites and others examining only midfrontal
sites—​although there is no current theory that predicts why alpha at these sites would be
different (Reznik & Allen, 2018). Second, past studies have differed in EEG processing
and referencing procedures. For instance, referencing procedures have included the
use of an average scalp reference, the vertex (i.e., CZ), the linked mastoids, or current-​
source-​density (CSD) transform. The majority of alpha activity in the brain is found over
the parietal and occipital cortices (Smith et al., 2018), and referencing procedures that do
not use CSD are susceptible to contaminating activity from more central and posterior
sites (Reznik & Allen, 2018). Third, frontal alpha asymmetry is not specific to anxiety.
It has also been linked to other types of psychopathology including major depressive
disorder (Allen & Reznik, 2015), attention deficit hyperactivity disorder (Keune et al.,
2011), and bipolar disorder (Nusslock et al., 2015). Thus, reported differences in anxiety
and asymmetry could (a) either be due to comorbidities if these are not accounted for
and/​or (b) reflect cognitive, behavioral, or emotional processes affected across multiple
disorders in a dimensional manner. Beyond psychopathology, alpha frontal asymmetry
has been linked with a multitude of constructs such as guilt (Amodio et al., 2007), anger
(Harmon-​Jones, 2007), racial bias (Amodio, 2010), day and time of year (Peterson &
Harmon-​Jones, 2009; Velo et al., 2012), liking of dessert (Gable & Harmon-​Jones, 2008),
homesickness in college freshman (Steiner & Coan, 2011), feelings towards exercise
(Hall et al., 2010), listening to rock music (Field et al., 1998), handedness (Brookshire
& Casasanto, 2012), and attractiveness of the experimenter (Wacker et al., 2013). These
findings suggest that there could be unaccounted moderators in previous studies on
anxiety, thus making it difficult to determine the functional significance of frontal
asymmetry.
Finally, a significant question remaining in EEG frontal asymmetry research is the
underlying biological mechanism producing hemispheric differences. Occipital and
thalamic brain regions have been described as alpha generators (Smith et al., 2018),
and combined EEG-​functional magnetic resonance imaging (fMRI) research has
demonstrated that alpha power correlates positively with functional connectivity be-
tween occipital and thalamic areas (Scheeringa et al., 2012). Additionally, alpha power is
positively correlated with resting-​state functional connectivity of the default-​mode net-
work, but negatively correlated with functional connectivity and activity of the dorsal
 EEG FREQUENCY TECHNIQUES In Anxiety    469

attention network (Laufs et al., 2003; Mantini et al., 2007). Studies that have directly
examined correlates of alpha asymmetry have implicated the anterior cingulate cortex
(ACC; Gorka et al., 2015; Nash et al., 2012; Smith et al., 2018), the dorsal lateral prefrontal
cortex (Smith et al., 2018), the pre and postcentral gyri (Lubar et al., 2003) and the amyg-
dala (Zotev et al., 2016). Collectively, this suggests that alpha asymmetry could reflect
attention to motivationally relevant information and the execution of intended actions.
In sum, there has been great interest over the past 50 years in understanding how
alpha asymmetry relates to anxiety. Models of emotional valence, motivation, physio-
logical arousal, and verbal processing have been proposed to explain the reported
findings. However, because anxiety is a heterogeneous construct that may involve and/​
or interact in complex ways with cognitive processes such as attention and motivation,
further research is needed to fully understand the functional significance of alpha asym-
metry in anxiety.

19.3  The Second Wave: Frontal Midline

Theta and Anxiety

A more detailed treatment of frontal-​midline theta (FMT), itself, is provided in

Chapter 9; therefore, the focus of our review centers on how FMT has been used to
understand cognitive and related processes in anxiety. As such, research on FMT and
anxiety is relatively new.

19.3.1 Early Days and a Primer on FMT as an Index of

Medial Frontal Cortex Function
Prior to landmark observations by Cavanaugh & Schackman (2015), research on
FMT and anxiety was scarce and methodologically limited. An early series of studies
conducted by Mizuki and colleagues examined how anxiolytics, state and trait anxiety
assessed using the STAI and Generalized Anxiety Disorder were related to FMT during
a continuous addition task (Mizuki et al., 1983; Mizuki et al., 1989; Mizuki et al., 1992;
Suetsugi et al., 2000). Findings showed that lower levels of trait anxiety were related
to greater theta activity during the arithmetic test; however, they also revealed that
reductions in state anxiety in those with high trait anxiety were related to decreases in
theta activity (Mizuki et al., 1992). However, these results are difficult to interpret in
light of a number of limitations. First, all but one study utilized only male participants.
Second, all of the studies were significantly hampered by small samples. Finally, these
studies involved tasks that are quite different from the typical two-​choice reaction
time tasks commonly used today. Thus, it is difficult to conclude much from these
470    JASON S. MOSER et al.

early attempts to understand relations between anxiety and FMT. Nonetheless, they
demonstrated that FMT was modulated in the context of anxiety.
A large number of studies has examined the role of medial frontal cortical activity
in cognitive control efforts, particularly when these efforts are aimed at reducing anx-
iety or the circumstances which contribute to anxiety. The cingulate, especially the an-
terior and midcingulate cortices (ACC and MCC, respectively), is a cortical area which
is highly interconnected with other brain systems, including emotional centers in the
limbic system, cognitive association areas in the prefrontal cortex, sensory and motor
processing areas in the parietal and occipital lobes, and deeper structures within the
brain (Van Den Heuvel et al., 2009). As such, the cingulate is well positioned to inte-
grate information from a variety of inputs and coordinate action-​oriented outputs to
maximize behavioral adaptability (Laurienti et al., 2003). Furthermore, the MCC’s in-
volvement is critical whenever new or conflicting information must be evaluated for its
relevance to the current behavioral set (Botvinick et al., 2004). Indeed, researchers have
suggested the MCC has domain-​general functionality that is engaged whenever there
is uncertainty about behavior and its outcomes (Cavanagh et al., 2012). Because uncer-
tainty is a central aspect to feelings of anxiety and to anxiety disorders, the MCC has
been a target for research efforts aimed at understanding the underpinnings of anxiety-​
related brain dynamics (Cavanagh & Shackman, 2015; Shackman et al., 2011).
A growing body of work suggests a primary function of the MCC is to integrate cog-
nitive, affective, and sensory information to enable behavioral adaptation (Shackman
et al., 2011). MCC activity has been implicated when incoming information is novel,
conflicting, punishing, or difficult to assimilate into the current action plan. In par-
ticular, FMT oscillations in the MCC have been observed across a variety of tasks when-
ever cognitive control is needed to alter behavior (Cavanagh & Frank, 2014). Because of
its ability to facilitate long-​range communication between disparate brain regions, theta
oscillations are a candidate mechanism for how the MCC helps organize and coordinate
neural processes related to action monitoring and response selection. Indeed, FMT has
been posited to represent an alarm signal that is integral for the recruitment of areas in
the prefrontal cortex that mediate cognitive control (Cavanagh & Frank, 2014). A wide
range of studies demonstrate that individuals high in anxiety generate larger FMT power
during cognitive tasks, suggesting anxiety and FMT hyperactivity are intimately related.
Moreover, larger FMT control signals are associated with more cautious or inhibited
responding, providing strong evidence that FMT is a biomarker that can be used to
study the intersection of anxiety and cognitive control (Cavanagh & Shackman, 2015).

19.3.2 Relationships Between Anxiety and FMT-​Related

ERP Components
Among individuals high in anxiety, heightened FMT responses to novel, conflicting,
or punishing stimuli have been observed indirectly for several decades within typical
 EEG FREQUENCY TECHNIQUES In Anxiety    471

event-​related potential (ERP) paradigms. The wide array of tasks that elicit FMT is evi-
dence of the domain-​general role that FMT plays in dealing with uncertainty through
the recruitment of cognitive control resources. Time-​domain ERP components that
have been consistently related to FMT include the error-​related negativity (ERN; Luu
et al., 2004; Trujillo & Allen, 2007), feedback negativity (FN; Foti et al., 2014; Watts
et al., 2018), and the N2 (Harper et al., 2014), all of which tend to be increased in anxious
individuals.
The ERN is a response-​locked ERP component that is thought to reflect action-​
monitoring that is involved in the recruitment of cognitive control during post-​error
behavioral adjustment (Gehring et al., 2018). Studies investigating the time-​frequency
dynamics have demonstrated that the ERN primarily reflects theta-​band activity that
is generated in the MCC (Luu et al., 2004; Trujillo & Allen, 2007). ERN amplitude has
been positively associated with anxiety, worry, and behavioral inhibition in flanker
(Moser et al., 2012; Riesel et al., 2017), go/​no-​go (Moadab et al., 2010), and trial and
error learning (Judah et al., 2016) tasks (for reviews see (Cavanagh & Shackman, 2015;
Moser et al., 2013). The functional significance of the larger ERN in anxiety is hotly
debated, with some suggesting it reflects the degree to which errors are seen as aver-
sive (Weinberg et al., 2016), whereas others suggest it reflects compensatory deployment
of cognitive control to counteract the distracting effects of worry (Moser et al., 2013;
Schroder et al., 2017).
Another FMT-​related ERP component thought to be generated by the MCC and
associated with anxiety is the feedback-​locked FN (Foti et al., 2014; Watts et al., 2018).
Like other FMT-​related ERP components, the FN can be understood as a signal from
the salience network indicating new information (e.g., feedback) is highly relevant for
adapting to changing circumstances. As such, the future-​oriented emotional state of
anxiety can prime the salience network to be hypersensitive to performance-​related
feedback, making individuals high in trait anxiety more likely to consistently produce
an elevated FN (Grupe & Nitschke, 2013). Congruent with this framework, FN ampli-
tude has shown positive associations with negative affect during a monetary incentive
delay task (Santesso et al., 2011) and behavioral inhibition in go/​no-​go (De Pascalis et al.,
2010) and spatial matching (Balconi & Crivelli, 2010) tasks.
Parallel to the ERN and FN, the N2 ERP component has been shown to be highly
related to FMT (Harper et al., 2014; Van Noordt et al., 2016) and is also sensitive to trait
and state anxiety differences. Although there is some debate as to which process(es) the
N2 most likely reflects, it is associated with performance monitoring, conflict resolution,
and response inhibition. Individuals high in anxiety have been shown to produce larger
N2s in a variety of contexts, including during go/​no-​go (Righi et al., 2009; Sehlmeyer
et al., 2010) and flanker (Schmid et al., 2015) tasks. Larger N2 amplitude to conflict trials
in anxious individuals might reflect the recruitment of compensatory effort to over-
come distraction by anxious thoughts or a regulation strategy aimed at reducing current
and future negative affect (Dreisbach & Fischer, 2012; Kool et al., 2010; Lindström et al.,
2013; Schouppe et al., 2012).
472    JASON S. MOSER et al.

19.3.3 Anxiety and Time-​Frequency Representations of

MCC Activity
Recent work has utilized time-​frequency analyses to directly examine the relationship
between FMT and anxiety during a variety of tasks. Congruent with studies using time-​
domain metrics, time-​frequency representations of MCC activity consistently show a
positive association between anxiety and FMT (Cavanagh & Shackman, 2015).
A growing body of work demonstrates that time-​frequency representations of the
ERN show a similar relationship to state and trait anxiety as time-​domain measures.
During a flanker task, individuals diagnosed with GAD were found to produce larger
ERN, error-​related FMT, and correlations between single-​trial FMT and reaction time
during a flanker task than did control participants (Cavanagh et al., 2017). Furthermore,
each of these three variables uniquely predicted group membership, suggesting FMT
may not exclusively be an evoked signal (Cohen & Donner, 2013). In another study,

Frontal Midline Theta & Interchannel Phase synchrony

Theta: 4–8 Hz

F8

Cz

Theta: 4–8 Hz

Time

Cross Frequency Coupling (intra-channel)

Delta: 0.5–4 Hz

Cz Beta: >13 Hz

Figure 19.1 Simplistic graphic illustrating frontal midline theta and interchannel phase
synchrony cross frequency coupling, described in the text. Frontal midline theta metrics are
calculated at midline sites as theta power and phase synchrony between sites. Cross frequency
coupling metrics include correlations between amplitudes of slower (i.e., delta) and faster (i.e.,
beta) frequencies as well as correlations between phase and amplitude of these frequencies or
ratios of frequency power (i.e., slow wave/​fast wave).
 EEG FREQUENCY TECHNIQUES In Anxiety    473

adolescent participants engaged in a flanker task while in a social anxiety-​producing

situation and displayed greater error-​related FMT and medial-​to-​lateral inter-​channel
phase synchrony (ICPS; Buzzell et al., 2018; see Figure 19.1). This finding provides some
evidence that state anxiety can also lead to greater performance monitoring and cogni-
tive control. There are mixed findings, however, concerning the relationship between
chronic anxiety—​in this case chronic worry—​and medial-​to-​lateral ICPS, with one
study showing reduced ICPS (Moran et al., 2015) and another reporting the opposite
(Cavanagh et al., 2017).
Studies utilizing time-​frequency analyses have also revealed associations between
anxiety and feedback-​related FMT. One study found that FMT was positively correlated
with general worry during a gambling task for both gains and losses in a community
sample with clinically elevated levels of anxiety (Ellis et al., 2018). Moreover, FMT
displayed a stronger relationship to loss feedback in this study further supporting the
hypothesis that individuals high in anxiety over-​utilize cognitive control to regulate be-
havior in the face of aversive outcomes (Cavanagh & Shackman, 2015). Cavanagh and
colleagues (2019) found a similar positive relationship between FMT and loss feedback
among individuals high in anxiety, suggesting heightened FMT may be used to boost
avoidance and cautious behavior. Another study using path analyses revealed pre-​
decision FMT fully mediated the relationship between trait anxiety and risk behavior
during a decision-​making task, with individuals high in anxiety making less risky
decisions, as a function of pre-​decision FMT, than those with low trait anxiety (Schmidt
et al., 2018). Similarly, increased FMT has been found to predict less risky gambling
decisions in the Balloon Analogue Risk Task (Zhang & Gu, 2018). Although bidirec-
tional theta information flow was detected between medial and lateral frontal areas
during decision making, trait anxiety was only correlated with theta power generated
in the lateral PFC. This provides further evidence that anxiety’s effect on theta dynamics
may not be limited to FMT power and likely includes lateral PFC power and connect-
ivity between MCC and lateral PFC.
More socially-​oriented studies have found relationships between anxiety and FMT
that run parallel to those found with more traditional cognitive tasks. For example, one
study found that FMT responses during International Affective Picture System image
viewing depended on an individual’s level of anxiety (Aftanas et al., 2003). Individuals
high in trait anxiety produced the largest FMT increase after threatening images, while
those low in trait anxiety displayed greater FMT increases to pleasant images. This inter-
action is congruent with the gambling literature described earlier, which supports an
association between high anxiety and punishment-​sensitive enhanced FMT. Greater
FMT has also been found to associate with unexpected social rejection feedback among
participants with social anxiety disorder (Harrewijn et al., 2018a).
In sum, there is ample evidence indicating that anxiety is associated with a range of
FMT metrics. Anxiety appears to be associated with larger FMT signals, which may re-
flect a greater need for cognitive control of behavior in chronically anxious individuals
or consequential anxious states. There is some inconsistency regarding the direction
474    JASON S. MOSER et al.

of the association between anxiety and network-​related FMT metrics (i.e., ICPS) that
will require further investigation to disentangle potentially confounding or moderating
effects.

19.4  The Third Wave: Cross Frequency

Coupling and Anxiety

19.4.1 A Primer on Cross Frequency Coupling

Cross frequency coupling (CFC) metrics are also emerging as tools for understanding
cognition and emotion in anxiety. CFC is often computed between slow waves (SW),
such as delta (1–​3 Hz) or theta (4–​7 Hz), and fast waves (FW), such as alpha (8–​12),
beta (13–​30 Hz), or gamma (>30 Hz; see Figure 19.1 for an illustration). Work in this
area has generally considered delta and theta to reflect reward seeking and emotional
arousal, respectively, generated by subcortical brain regions (Knayzev, 2003). Alpha,
beta, and gamma are considered to reflect heightened attentional vigilance (Knayazev,
2003), inhibitory control (Engel & Fried, 2010; Jenkinson & Brown, 2011), and sustained
attention/​working memory (Jenson et al., 2007), respectively, in the neocortex. As such,
SW-​FW coupling is thought to index increased communication between subcortical
and cortical regions of the brain.
CFC metrics in the anxiety literature mostly include amplitude-​amplitude coup-
ling during resting or anticipatory states, although some have also investigated phase-​
amplitude coupling (i.e., the power of a higher frequency along specific phases of
a lower frequency; Poppelaars et al., 2018). On the other hand, SW/​FW ratios of fre-
quency power are computed to examine the relative strength of frequencies, with
higher ratios indicating a predominance of slow waves (i.e., less control over emotional
processes). Therefore, coupling provides an index of the associated strength of SW and
FW power or phase, whereas ratios provide information on the relative strength of SW
to FW power.
An early study by Knyazev and Slobodskaya (2003) investigated the relationship be-
tween the behavioral inhibition system (BIS), a motivational system highly implicated
in anxiety-​related symptoms and behaviors (Gray & McNaughton, 2000), and CFC
anticorrelations (i.e., negative relationships between frequencies). BIS, as conceived
by Gray and McNaughton, is similar in many ways to behaviorally inhibited tempera-
ment in toddlers and young children described earlier yet developed separately in
parallel as a way to understand motivational processes involved in personality and psy-
chopathology. They found that BIS was related to a higher alpha-​delta anticorrelation,
concluding that behaviorally inhibited adults experience heightened activation in cor-
tical regions combined with less activation in limbic regions of the brain. Although the
interpretation of alpha-​delta anticorrelations remains obscure, it provided a framework
 EEG FREQUENCY TECHNIQUES In Anxiety    475

to investigate SW-​FW relations as cortical “cross-​talk”, which has gone on to focus on

delta or theta and beta.

19.4.2 Delta-​Beta Coupling and Anxiety

Two early studies of particular relevance to the topic of this chapter demonstrated an as-
sociation between higher delta-​beta coupling and anxiety-​related individual differences.
Specifically, Schutter and Van Honk (2005) found increased delta-​beta coupling in
individuals with high baseline cortisol levels, relative to those with low cortisol levels.
Van Peer and colleagues (2008) subsequently reported that males characterized by
high BIS evinced high delta-​beta coupling in frontal sites that was further increased by
the administration of cortisol (vs. placebo). These findings led to further inquiry as to
whether delta-​beta coupling is related to trait individual differences in anxiety-​related
constructs, anxious states, or both.
Adopting Gray and McNaughton’s (2000) theory of anxiety, Knyazev, Savostyanov,
and Levin (2005) posited that apprehensive states are distinct from dispositional anx-
iety (i.e., BIS), because they involve coactivation of both BIS and the behavioral activa-
tion system (BAS). Theoretically, this occurs in uncertain contexts when the probability
of winning and losing are equal. As such, these contexts lead to the activation of both
BIS (i.e., cortical activation) and BAS (i.e., subcortical activation) with no particular
predominance of one over the other. In a series of studies with predominantly female
samples, high-​and low-​stress groups were given negative feedback on a behavioral task
and were told that this could potentially cause them to lose money. Results revealed that
those in the high-​stress groups showed greater delta-​beta and delta-​gamma1 coupling
than those in the control group (Knyazev et al., 2005; 2006, 2011). Notably, increases in
delta-​beta coupling were comparable for both high and low trait anxious individuals,
although high trait anxious individuals showed an even greater increase in coupling.
Thus, anxious states and traits may be additive with respect to increases in delta-​beta
coupling. Source analysis studies further suggest that increases in delta-​beta coupling
as a function of apprehensive states involves activity in ACC and orbitofrontal cortex
(OFC; Knyazev et al., 2011). How exactly delta-​beta coupling relates to ACC and OFC
activity remains unknown; however, delta may be the primary driver of this coupling
and coordination of brain regions involved in preparing an adaptive behavioral re-
sponse (Knyazev et al., 2011).
CFC studies of clinical anxiety have primarily focused on social anxiety. Miskovic and
colleagues (2010), for instance, observed increases in delta-​beta coupling during speech
anticipation (vs. resting) in socially anxious individuals. Research from the same group
also found that 12 weeks of cognitive behavioral therapy served to decrease delta-​beta

1  Only one study has examined delta-​gamma coupling (Knyazev et al., 2005), and the interpretation of

this result is consistent with general SW-​FW coupling interpretations.

476    JASON S. MOSER et al.

correlations over treatment during speech anticipation periods (Miskovic et al., 2011),
and that children of socially anxious parents showed increased delta-​beta coupling
(Miskovic et al., 2011). However, negative associations between delta and beta have
also been reported in social anxiety (Harrewijn et al., 2016). Moreover, Harrewjin and
colleagues (2018b) recently found that this negative association between delta and beta
is heritable and speculated that the differences in the direction of coupling could be due
to different stress manipulations utilized by research groups (anticipatory stress vs. task-​
induced stressor), or different ways of computing frequency power densities (i.e., abso-
lute vs. relative power). If the delta-​beta correlation, however, is generally understood
as reflecting increased neural communication, then the mere presence of a relationship
between their frequencies could still indicate important cross-​talk (regardless of direc-
tion), although the exact nature of this cross-​talk remains vague. Further complicating
the relationship between anxiety and delta-​beta coupling, one study showed that OCD
is characterized by delta-​beta decoupling (Velikova et al., 2010). Clearly more research
will be needed to clarify how clinical levels of anxiety-​related problems associate with
delta-​beta coupling.

19.4.3 Frontal Theta/​Beta Ratio and Anxiety

Beyond delta-​beta coupling, anxiety has also been examined in relation to frontal theta/​
beta ratio insomuch as frontal theta/​beta ratio is an index of attentional control (AC), a
core component of executive function involved in balancing bottom-​up selection and
top-​down control influences on behavior. As previously mentioned, the examination
of ratios provides a measure of relative dominance of SW over FW or vice versa. For
instance, Putman and colleagues (2010) found that higher self-​reported trait anxiety
and attentional control were related to lower theta/​beta ratio (i.e., more control) in an
all-​female sample. Subsequent studies replicated these associations (Angelidis et al.,
2018; Putman et al., 2014). Putman and colleagues (2014) further demonstrated that
individuals with a lower theta/​beta ratio showed lesser effects of a stress manipulation
on change in self-​reported AC. Theta/​beta ratio is also lower during on-​task periods
relative to mind wandering episodes (Van Son et al., 2019). Together, these findings have
been interpreted as indicating that theta/​beta ratio reflects the degree of top-​down con-
trol over bottom-​up processes, with higher theta/​beta ratio indicting less control and
lower theta/​beta ratio indicating greater control (Putman et al., 2014). It is interesting,
then, that trait anxiety shows a negative association with theta/​beta ratio rather than
a positive one, as anxiety has been related to poorer attentional control (Eysenck et al.,
2007; Shi et al., 2019). We return to this seeming contradiction in the next section.
In all, SW-​FW coupling and ratios appear to reflect a number of anxiety-​related
processes, including AC. Specifically, BIS, apprehensive states and clinical levels of
anxiety appear to relate to greater SW-​FW coupling, although there are quite mixed
findings regarding clinical anxiety. Higher trait anxiety and self-​reported AC associate
with lower SW/​FW ratios. Both CFC metrics appear to reflect interactions between
 EEG FREQUENCY TECHNIQUES In Anxiety    477

cognition and emotion—​that is, top-​down versus bottom-​up control of processing

resources—​that may serve compensatory or coping functions in anxious contexts and
for anxious individuals.

19.5  The New Wave: Theoretical

Considerations, Future Directions
and Conclusions

The previous section review indicates the exciting promise of EEG frequency techniques
to illuminate anxiety-​related processes, including motivation and cognitive control.
In this final section, we first consider relevant cognitive, motivational, and emotional
theories that might help synthesize the reviewed literature. We then turn to potential
avenues for future work and finish with some brief concluding remarks.

19.5.1 Theoretical Considerations
Throughout this review, much of the literature seems to point to the presence of a dy-
namic interplay between cognition, motivation, and emotion in the links between EEG
frequency metrics and anxious states and traits. In particular, the interplay between
emotional processes involved in the generation and detection of internal or external
threats, motivational processes dedicated to approaching and/​or avoiding these threats,
and cognitive processes involved in the monitoring and control of these forces seems to
be positioned front and center in anxiety-​related situations and symptoms. Figure 19.2
shows a hypothetical model of the interplay between motivational conflicts and cog-
nitive control in anxiety, which is seen as intimately related to the dynamic process of
co-​activation of approach and avoidance motivational systems that produce conflicts

Motivational Inhibition/Control Selected

Conflicts (BIS) Behavior
Alpha Asymmetry FMT
Delta-Beta Coupling Theta/Beta

Anxeity
Apprehension/
Arousal
Resolution/
Non-Resolution

Figure 19.2  A hypothetical model of the interplay between motivational conflicts and cogni-
tive control in anxiety.
478    JASON S. MOSER et al.

detected and weighed by the BIS during which ongoing behavior is inhibited and
controlled until there is a resolution of the conflict and a behavior is selected. Anxiety
is generally related to enhanced conflicts between motivational systems, inhibition, and
control. Alpha asymmetry and metrics and theta/​beta ratio may index BIS-​related in-
hibitory and related control functions. Apprehension and arousal subcomponents of
anxiety are proposed to have different relations to these dynamics. The model more
likely captures the role of apprehension whereas arousal is proposed to have more direct
links to fear and avoidance motivational systems that may be less related to control
systems.
There is much overlap between the concepts of emotion, motivation, and cogni-
tion, and, thus, we do not intend to communicate that they are completely separable
constructs (cf. Miller, 1996, 2010). Rather, we assert that consideration of these processes
is critical to better understanding what EEG frequency metrics might reflect with re-
spect to anxiety, as well as to evaluate the utility of EEG frequency metrics in detecting
risk, maintenance factors, and treatment targets for anxiety-​related interference and
disorders. In the next section, we consider merging the theoretical contributions of Gray
and McNaughton (2000), Eysenck and colleagues (2007), and Heller and colleagues
(Heller et al., 1997, Heller & Nitschke, 1998) with findings from the cognitive neurosci-
ence of inhibitory control (over emotion) as offering a unique window into advancing
our knowledge of how EEG frequency metrics might reflect the dynamic interplay of
emotion, motivation, and cognition in anxiety.
Gray and McNaughton’s (2000) neuropsychological model of anxiety draws on
earlier work by Gray (1975, 1982) regarding motivation and personality (see also Corr
et al., 2013 for a more recent review). This work largely delineated the BAS and BIS as
two motivational systems relevant to personality and anxiety. The updated version of
this model, the Reinforcement Sensitivity Theory (RST), further decomposed the BIS
into the BIS and the fight-​flight-​freeze system (FFFS), which is involved in fear-​related
behaviors aimed at defending an organism from active threat. The BIS, on the other
hand, is posited to be involved in the detection and resolution of approach-​avoidance
conflicts—​that is, conflicts driven by coactivation of the BAS and FFFS. The BIS there-
fore inhibits ongoing behavior to allow for risk assessment and scanning so as to resolve
the approach-​avoid conflict by enacting the appropriate behavior in context.
The attentional control theory (ACT) of anxiety (Eysenck et al., 2007) more specif-
ically aims to describe the nature of the relationship between anxiety and cognition.
Eysenck and colleagues conclude that anxiety disrupts the balance of the bottom-​up
salience system and the top-​down control system such that the bottom-​up system is
generally more active than the top-​down control system. To resolve this imbalance in
the presence of task-​related goals, anxious individuals are hypothesized to deploy com-
pensatory top-​down control to meet the demands of the task at hand. We suggest that
the interplay of the bottom-​up and top-​down control systems in anxiety proposed by
Eysenck and colleagues bears striking resemblance to the approach-​avoid conflicts
detected and resolved by the BIS in Gray’s RST. That is, anxiety often involves conflicts
between threat-​driven, avoidance, or distraction processes and goal-​driven, approach
 EEG FREQUENCY TECHNIQUES In Anxiety    479

processes involved in producing appropriate behaviors to meet the demands of the

current context.
To further add nuance to this interplay, however, consider the seminal work
by Heller and colleagues (Heller et al., 1997; Heller & Nitschke, 1998; Sharp et al.,
2015) disentangling different dimensions of anxiety and depression. This work makes
important distinctions between anxious apprehension (worry), anxious arousal (fear
and panic), and anhedonic depression across psychometric and neural measures.
Neurally, anxious apprehension has been associated with left-​frontal activity and anx-
ious arousal with right-​parietal activity (reviewed by Sharp et al., 2015). The associ-
ation between anxious apprehension and left-​frontal activity has been interpreted as
reflecting the involvement of language production and verbal working memory centers
in worry whereas anxious arousal may not only involve right-​parietal activity but ra-
ther several parietal and frontal regions involved in threat detection and environmental
scanning (Sharp et al., 2015). Nonetheless, findings have generally distinguished be-
tween anxious apprehension and anxious arousal, pointing to heterogeneity in the anx-
iety construct that must be considered when attempting to understand the involvement
of neural measures like EEG frequency metrics.
Together, we suggest that when interpreting the function of the various EEG fre-
quency metrics reviewed above, one must consider the important interplay of
emotion, motivation, and cognition as well as unique differences between dimensions
of anxiety—​e.g., anxious apprehension and arousal. Moreover, considering the context
in which associations between EEG frequency metrics and anxiety emerge is critical—​
i.e., at rest, in the presence of threat, and/​or during completion of an affective neu-
tral task.
One common theme that seems to arise from the review is the link between anxiety
and metrics of control. We see this most strikingly in the frontal midline theta (FMT)
and cross-​frequency coupling (CFC) literatures. We suggest that this link might reflect
the important role of the BIS in anxiety. That is, FMT and CFC metrics might reflect
the dynamic detection and attempted resolution of conflicts between approach and
avoidance motivations that arise when anxious individuals or individuals subjected
to anxious states attempt to complete a task at hand on which they have been given
instructions to perform well. Studies linking FMT and other CFC metrics to activity
of medial prefrontal cortices (most importantly, the ACC or MCC) seem to further
support this interpretation given the wealth of data indicating the ACC/​MCC’s role in
inhibition, conflict processing, and integration of negative affect and cognitive control
(Bartholomew et al., 2019; Popov et al., 2018; Shackman et al., 2011; Spielberg et al., 2015).
A seeming “hub” for emotion-​cognition interactions, the ACC/​MCC might be critically
involved in the BIS via FMT oscillations and their associations with other frequencies
(e.g., beta; see also Popov et al., 2018). As such, ACC/​MCC-​mediated processes may
reflect this “dance” between approach and avoidance motivations in contexts in which
fear-​related avoidance and goal-​directed behaviors stand in conflict with one another.
This process, as Gray and McNaughton (2000) propose, captures the very nature of the
BIS and associated anxiety symptoms. EEG frequency approaches may offer the ideal
480    JASON S. MOSER et al.

metrics to index these important dynamics given their millisecond precision and in-
herent ability to reflect activity of systems/​networks.

19.5.2 Future Directions
There is a strong foundation of knowledge produced by the extant studies on
associations between anxiety and EEG frequency metrics, although a number of areas
are ripe for further investigation and theory development. One particularly curious
contradiction is the functional significance of theta activity. In the literature on FMT,
theta is hypothesized to signal the need for control whereby a larger theta signal leads
to greater control and adaptive behavioral adjustments. On the other hand, in the CFC
literature, theta—​i.e., a slow wave—​is hypothesized to reflect emotional arousal and
related subcortical processes such that its preponderance or dominance over faster wave
activity indicates lesser control. It will be important to reconcile these two literatures, as
currently they appear to be evolving in parallel. This reconciliation may be challenging
at present given the differences in paradigms and calculations of theta used in these two
literatures. Both the FMT and CFC literatures focus on frontal theta, and, therefore, it
follows that there should be some relation between these different metrics.
It also seems important to gain new insights into the exact relationship between anx-
iety constructs and alpha asymmetry. Indeed, it represents the historically largest litera-
ture on the association between anxiety and EEG frequency metrics, yet much is still
left unknown. The various competing models of alpha asymmetry likely occlude clarity
with respect to its association with anxiety, however, perhaps Gray and McNaughton’s
(2000) model of motivation and personality could shed some light. For example, given
the important role of the BIS in anxiety and other related EEG frequency metrics, it
could be difficult to isolate associations between alpha asymmetry and anxiety be-
cause of the likely co-​activation of approach (left-​sided activity) and avoidance (right-​
sided activity) motivational systems. The work of Heller and colleagues (Sharp et al.,
2015) further demonstrates the importance of considering the heterogeneity of anxiety
constructs when examining associations between anxiety and alpha asymmetry, among
other neural measures of motivation and cognition. Thus, future work will need to be
more precise with setting up paradigms that test clearer predictions involving specific
motivational contexts and anxiety constructs.
In general, the literature on associations between anxiety and EEG frequency metrics
will have to grapple with different motivational contexts and anxiety constructs.
Enhanced precision in theory will drive more sophisticated methods for testing related
predictions concerning approach-​avoidance conflicts and separable dimensions of anx-
iety. For example, whereas some have shown associations between “lumped” anxiety
constructs and FMT (Cavanagh & Schackman, 2015), others have shown that “splitting”
anxiety constructs reveals important distinctions (e.g., Moser et al., 2013).
Beyond the EEG frequency metrics and anxiety constructs themselves, this litera-
ture must also incorporate the roles of development and gender, both of which show
 EEG FREQUENCY TECHNIQUES In Anxiety    481

important influences on anxiety and its associations with neural measures of mo-
tivation/​emotion and cognitive control. For instance, there is growing evidence
demonstrating important changes in the association between anxiety and the ERN—​a
theta-​based ERP—​across development (Moser et al., 2017). Gender also moderates this
association, such that females show a larger association (Moser et al., 2016) and a greater
change in association across development (Ip et al., 2019). Furthermore, racial, ethnic,
and cultural differences will have to be considered to fully understand the generaliz-
ability of these findings. For example, related research shows higher heart rate variability
(HRV) in Black individuals, which may reflect compensatory control mechanisms
deployed to manage the sustained and cumulative adverse effects of discrimination
(Kemp et al., 2016). Such a compensatory control response may also be reflected in the
EEG frequency metrics reviewed herein.
Additional methodological innovations will also further advance this area of clinical
neuroscience. For instance, the application of graph theoretic (Bolanos et al., 2013) and
directed network (Liu et al., 2014; Popov et al., 2018) methods to such EEG frequency
techniques is just beginning and will likely provide unique insights into associations
between anxiety and motivational and cognitive control systems. This work will also
further benefit from integrating data across the lab and the “real-​world” through
combining EEG imaging techniques with experience-​sampling methods and deploying
wearable technology (cf. Hur et al., 2019).
Finally, we would be remiss if we did not acknowledge the importance of considering
the psychological and philosophical machinations involved in attempting to make
meaning of associations between various psychological and biological measures. It is
important for future work in this area to avoid terminology such as “underlying” in
describing the involvement of neural oscillations in self-​reported experiences of anx-
iety as they incorrectly insinuate a causal mechanism and further the fallacy that more
micro-​level data (e.g., neural activity) are superior to more macro-​level data (e.g., self-​
report of anxiety; Sharp & Miller, 2019). Rather, such neural markers are likely involved
in the instantiation of experiences and resolution of motivational conflicts and anxiety
symptoms. The ways in which these neural, self-​report, and behavioral measures are
combined and weighed should involve careful consideration of the goals to be achieved
(e.g., intervention development; See Taschereau-​Dumouchel, Michel, Lau, Hofmann &
LeDoux, 2022 for a recent review of this approach).

19.5.3  Conclusions
The literature considering associations between anxiety and EEG frequency measures
has a long history and generally follows the historical trends present in other areas of
psychological science. More recently, early motivational and emotional models have
been overtaken by or integrated into cognitive models of anxiety and related constructs.
A long-​view perspective on the literature suggests strong associations between anxiety-​
related constructs and EEG frequency markers of motivational and cognitive control
482    JASON S. MOSER et al.

processes. A central theme in this literature is the involvement of the BIS that can be
seen reflected in a variety of EEG frequency metrics and generally reveals the dynamic
interplay between the co-​activation of approach and avoidance motivations in anxious
individuals and states as the execution of adaptive behavioral responses is attempted.
This area of clinical neuroscience is ripe for future work and should involve advances in
theory, generalizability, and methodology.

REFERENCES
Adolph, D. & Margraf, J. (2017). The differential relationship between trait anxiety, depression,
and resting frontal α-​asymmetry. Journal of Neural Transmission, 124(3), 379–​386. https://​
doi.org/​10.1007/​s00​702-​016-​1664-​9
Aftanas, L. I., Pavlov, S. V., Reva, N. V., & Varlamov, A. A. (2003). Trait anxiety impact on the
EEG theta band power changes during appraisal of threatening and pleasant visual stimuli.
International Journal of Psychophysiology, 50(3), 205–​212.
Allen, J. J. B., Coan, J. A., & Nazarian, M. (2004). Issues and assumptions on the road from raw
signals to metrics of frontal EEG asymmetry in emotion. Biological Psychology, 67(1–​2), 183–​
218. https://​doi.org/​10.1016/​j.biopsy​cho.2004.03.007
Allen, J. J. B. & Reznik, S. J. (2015). Frontal EEG asymmetry as a promising marker of depression
vulnerability: Summary and methodological considerations. Current Opinion in Psychology,
4, 93–​97.https://​doi.org/​10.1016/​j.cop​syc.2014.12.017
Amodio, D. M. (2010). Coordinated roles of motivation and perception in the regulation of
intergroup responses: Frontal cortical asymmetry effects on the P2 event-​related potential
and behavior. Journal of Cognitive Neuroscience, 22(11), 2609–​2617. https://​doi.org/​10.1162/​
jocn.2009.21395
Amodio, D. M., Devine, P. G., & Harmon-​ Jones, E. (2007). A dynamic model of
guilt: Implications for motivation and self-​regulation in the context of prejudice: Research
article. Psychological Science, 8(6), 524–​530. https://​doi.org/​10.1111/​j.1467-​9280.2007.01933.x
Angelidis, A., Hagenaars, M., van Son, D., van der Does, W., & Putman, P. (2018). Do not look
away! Spontaneous frontal EEG theta/​beta ratio as a marker for cognitive control over
attention to mild and high threat. Biological Psychology, 135, 8–​17.
Avram, J., Balteş, F. R., Miclea, M., & Miu, A. C. (2010). Frontal EEG activation asymmetry
reflects cognitive biases in anxiety: Evidence from an emotional face Stroop task. Applied
Psychophysiology Biofeedback, 35, 285–​292. https://​doi.org/​10.1007/​s10​484-​010-​9138-​6
Balconi, M. & Crivelli, D. (2010). FRN and P300 ERP effect modulation in response to feed-
back sensitivity: The contribution of punishment-​reward system (BIS/​BAS) and behaviour
identification of action. Neuroscience Research, 66(2), 162–​172.
Barlow, D. H. (1991). Disorders of emotion. Psychological Inquiry, 2(1), 58–​7 1. https://​doi.org/​
10.1207/​s153​2796​5pli​0201​_​15
Barlow, D. H. (2002). Anxiety and its disorders (2nd ed.). Guilford Press.
Bartholomew, M. E., Yee, C. M., Heller, W., Miller, G. A., & Spielberg, J. M. (2019).
Reconfiguration of brain networks supporting inhibition of emotional challenge.
NeuroImage, 186, 350–​357.
Baving, L., Laucht, M., & Schmidt, M. H. (2002). Frontal brain activation in anxious school
children. Journal of Child Psychology and Psychiatry and Allied Disciplines, 43(2), 265–​274.
https://​doi.org/​10.1111/​1469-​7610.00019
 EEG FREQUENCY TECHNIQUES In Anxiety    483

Blackhart, G. C., Minnix, J. A., & Kline, J. P. (2006). Can EEG asymmetry patterns predict fu-
ture development of anxiety and depression? A preliminary study. Biological Psychology,
72(1), 46–​50. https://​doi.org/​10.1016/​j.biopsy​cho.2005.06.010
Bolanos, M., Bernat, E.M., He, B., & Aviyente, S. (2013). A weighted small world network
measure for assessing functional con-​nectivity. Journal of Neuroscience Methods, 212, 133–​42.
Botvinick, M. M., Cohen, J. D., & Carter, C. S. (2004). Conflict monitoring and anterior cingu-
late cortex: an update. Trends in Cognitive Sciences, 8(12), 539–​546.
Brookshire, G., & Casasanto, D. (2012). Motivation and motor control: Hemispheric special-
ization for approach motivation reverses with handedness. PLoS One, 7(4), e36036. https://​
doi.org/​10.1371/​jour​nal.pone.0036​036
Bruder, G. E., Fong, R., Tenke, C. E., Leite, P., Towey, J. P., Stewart, J. E., . . . Quitkin, F. M. (1997).
Regional brain asymmetries in major depression with or without an anxiety disorder: A
quantitative electroencephalographic study. Biological Psychiatry, 41, 939–​948. https://​doi.
org/​10.1016/​S0006-​3223(96)00260-​0
Buchsbaum, M. S., Hazlett, E., Sicotte, N., Stein, M., Wu, J., & Zetin, M. (1985). Topographic
EEG changes with benzodiazepine administration in generalized anxiety disorder. Biological
Psychiatry, 20(8), P837–​842. https://​doi.org/​10.1016/​0006-​3223(85)90208-​2
Buzzell, G. A., Barker, T. V., Troller-​Renfree, S. V., Bernat, E. M., Bowers, M. E., Morales,
S., . . . Fox, N. A. (2018). Adolescent cognitive control, theta oscillations, and social motiv-
ation. bioRxiv [online], 366831.
Cavanagh, J. F., Bismark, A. W., Frank, M. J., & Allen, J. J. (2019). Multiple dissociations be-
tween comorbid depression and anxiety on reward and punishment processing: Evidence
from computationally informed EEG. Computational Psychiatry, 3, 1–​17.
Cavanagh, J. F. & Frank, M. J. (2014). Frontal theta as a mechanism for cognitive control. Trends
in Cognitive Sciences, 18(8), 414–​421.
Cavanagh, J. F., Meyer, A., & Hajcak, G. (2017). Error-​specific cognitive control alterations
in generalized anxiety disorder. Biological Psychiatry: Cognitive Neuroscience and
Neuroimaging, 2(5), 413–​420.
Cavanagh, J. F. & Shackman, A. J. (2015). Frontal midline theta reflects anxiety and cognitive
control: Meta-​analytic evidence. Journal of Physiology-​Paris, 109(1-​3), 3–​15.
Cavanagh, J. F., Zambrano‐Vazquez, L., & Allen, J. J. (2012). Theta lingua franca: A common
mid‐frontal substrate for action monitoring processes. Psychophysiology, 49(2), 220–​238.
Carter, W. R., Johnson, M. C., & Borkovec, T. D. (1986). Worry: An electrocortical analysis.
Advances in Behaviour Research and Therapy, 8(4), 193–​204. https://​doi.org/​10.1016/​
0146-​6402(86)90004-​4
Cohen, M. X. & Donner, T. H. (2013). Midfrontal conflict-​related theta-​band power reflects
neural oscillations that predict behavior. Journal of Neurophysiology, 110(12), 2752–​2763.
Corr, P. J., DeYoung, C. G., & McNaughton, N. (2013). Motivation and personality: A neuro-
psychological perspective. Social and Personality Psychology Compass, 7(3), 158–​175.
Davidson, R. J. (1979). Frontal versus perietal EEG asymmetry during positive and negative
affect. Psychophysiology, 16(2), 202–​203.
Davidson, R. J. (1984). Affect, Cognition, and Hemispheric Specialization. In C. E. Izard, J.
Kagan, & R. B. Zajonc (Eds.), Emotions, cognition, and behavior (pp. 320–​365). Cambridge
University Press.
Davidson, R. J. (1988). EEG measures of cerebral asymmetry: Conceptual and methodo-
logical issues. International Journal of Neuroscience, 39(1–​2), 71–​89. https://​doi.org/​10.3109/​
002074​5880​8985​694
484    JASON S. MOSER et al.

Davidson, R. J. & Fox, N. A. (1982). Asymmetrical brain activity discriminates between positive
and negative affective stimuli in human infants. Science, 218(4578), 1235–​1237. https://​doi.
org/​10.1126/​scie​nce.7146​906
Davidson, R. J. & Fox, N. A. (1989). Frontal brain asymmetry predicts infants’ response to ma-
ternal separation. Journal of Abnormal Psychology, 98(2), 127–​131. https://​doi.org/​10.1037/​
0021-​843X.98.2.127
Davidson, R. J., Kalin, N. H., & Shelton, S. E. (1992). Lateralized effects of diazepam on frontal
brain electrical asymmetries in rhesus monkeys. Biological Psychiatry, 32(5), 438–​451.
https://​doi.org/​10.1016/​0006-​3223(92)90131-​I
Davidson, R. J., Marshall, J. R., Tomarken, A. J., & Henriques, J. B. (2000). While a phobic
waits: Regional brain electrical and autonomic activity in social phobics during antici-
pation of public speaking. Biological Psychiatry, 47(2), 85–​95. https://​doi.org/​10.1016/​
S0006-​3223(99)00222-​X
De Pascalis, V., Varriale, V., & D’Antuono, L. (2010). Event-​related components of the punish-
ment and reward sensitivity. Clinical Neurophysiology, 121(1), 60–​76.
Dreisbach, G. & Fischer, R. (2012). Conflicts as aversive signals. Brain and Cognition,
78(2), 94–​98.
Ekman, P. & Friesen, W. V. (1971). Constants across cultures in the face and emotion. Journal of
Personality and Social Psychology, 17(2), 124–​129. https://​doi.org/​10.1037/​h0030​377
Ellis, J. S., Watts, A. T., Schmidt, N., & Bernat, E. M. (2018). Anxiety and feedback processing
in a gambling task: Contributions of time-​frequency theta and delta. Biological Psychology,
136, 1–​12.
Engel, A. K. & Fries, P. (2010). Beta-​band oscillations—​signaling the status quo? Current
Opinion in Neurobiology, 20(2), 156–​165.
Eysenck, M. W., Derakshan, N., Santos, R., & Calvo, M. G. (2007). Anxiety and cognitive per-
formance: Attentional control theory. Emotion, 7(2), 336.
Field, T., Martinez, A., Nawrocki, T., Pickens, J., Fox, N. A., & Schanberg, S. (1998). Music shifts
frontal EEG in depressed adolescents. Adolescence, 33(129), 109–​116.
Foti, D., Weinberg, A., Bernat, E. M., & Proudfit, G. H. (2014). Anterior cingulate activity to
monetary loss and basal ganglia activity to monetary gain uniquely contribute to the feed-
back negativity. Clinical Neurophysiology, 126(7), 1338–​1347.
Fox, N. A. (1991). If it’s not left, it’s right. American Psychologist, 46(8), 863–​872. https://​doi.org/​
10.1037/​0003-​066X.46.8.863
Fox, N. A., Bell, M. A., & Jones, N. A. (1992). Individual differences in response to stress and
cerebral asymmetry. Developmental Neuropsychology, 8(2–​3), 161–​184. https://​doi.org/​
10.1080/​875656​4920​9540​523
Fox, N. A., & Davidson, R. J. (1987). Electroencephalogram asymmetry in response to the
approach of a stranger and maternal separation in 10-​month-​old infants. Developmental
Psychology, 23(2), 233–​240. https://​doi.org/​10.1037/​0012-​1649.23.2.233
Fox, N. A., Rubin, K. H., Calkins, S. D., Marshall, T. R., Coplan, R. J., Porges, S. W., . . . Stewart,
S. (1995). Frontal activation asymmetry and social competence at four years of age. Child
Development, 66(6), 1770-​1784. https://​doi.org/​10.1111/​j.1467-​8624.1995.tb00​964.x
Fox, N. A., Schmidt, L. A., Calkins, S. D., Rubin, K. H., & Coplan, R. J. (1996). The role of frontal
activation in the regulation and dysregulation of social behavior during the preschool
years. Development and Psychopathology, 8(1), 89–​102. https://​doi.org/​10.1017/​S09545​7940​
0006​982
 EEG FREQUENCY TECHNIQUES In Anxiety    485

Gable, P., & Harmon-​ Jones, E. (2008). Relative left frontal activation to appetitive
stimuli: Considering the role of individual differences. Psychophysiology, 45(2), 275–​278.
https://​doi.org/​10.1111/​j.1469-​8986.2007.00627.x
Gainotti, G. (1972). Emotional Behavior and Hemispheric Side of the Lesion. Cortex, 8(1), 41–​
55. https://​doi.org/​10.1016/​S0010-​9452(72)80026-​1
Gehring, W. J., Goss, B., Coles, M. G. H., Meyer, D. E., & Donchin, E. (2018). The error-​related
negativity. Perspectives in Psychological Science, 13(2), 200–​204. doi:10.1177/​1745691617715310
Gorka, S. M., Phan, K. L., & Shankman, S. A. (2015). Convergence of EEG and fMRI measures
of reward anticipation. Biological Psychology, 112, 12–​19. https://​doi.org/​10.1016/​j.biopsy​
cho.2015.09.007
Gray, J. A. (1975). Elements of a two-​process theory of learning. Academic Press.
Gray, J. A. (1982). The neuropsychology of anxiety: An enquiry into the functions of the septo-​
hippocampal system. Oxford University Press.
Gray, J. A. & McNaughton, N. (2000). The neuropsychology of anxiety: An enquiry into the
functions of the septo-​hippocampal system (2nd ed.). Oxford University Press.
Grupe, D. W. & Nitschke, J. B. (2013). Uncertainty and anticipation in anxiety: an integrated
neurobiological and psychological perspective. Nature reviews Neuroscience, 14(7), 488.
Hall, E. E., Ekkekakis, P., & Petruzzello, S. J. (2010). Predicting affective responses to exercise
using resting EEG frontal asymmetry: Does intensity matter? Biological Psychology, 83(3),
201–​206. https://​doi.org/​10.1016/​j.biopsy​cho.2010.01.001
Harmon-​Jones, E. (2007). Trait anger predicts relative left frontal cortical activation to anger-​
inducing stimuli. International Journal of Psychophysiology, 66(2), 154–​160. https://​doi.org/​
10.1016/​j.ijpsy​cho.2007.03.020
Harper, J., Malone, S. M., & Bernat, E. M. (2014). Theta and delta band activity explain N2 and
P3 ERP component activity in a go/​no-​go task. Clinical Neurophysiology, 125(1), 124–​132.
Harrewijn, A., Van der Molen, M. J. W., & Westenberg, P. M. (2016). Putative EEG measures of
social anxiety: Comparing frontal alpha asymmetry and delta–​beta cross-​frequency correl-
ation. Cognitive, Affective, & Behavioral Neuroscience, 16(6), 1086–​1098.
Harrewijn, A., van der Molen, M. J., van Vliet, I. M., Houwing-​Duistermaat, J. J., & Westenberg,
P. M. (2018a). Delta-​beta correlation as a candidate endophenotype of social anxiety: A two-​
generation family study. Journal of Affective Disorders, 227, 398–​405.
Harrewijn, A., van der Molen, M. J., van Vliet, I. M., Tissier, R. L., & Westenberg, P. M. (2018b).
Behavioral and EEG responses to social evaluation: A two-​generation family study on social
anxiety. NeuroImage: Clinical, 17, 549–​562.
Heller, W. (1993). Neuropsychological mechanisms of individual differences in emotion,
personality, and arousal. Neuropsychology, 7(4), 476–​489. https://​doi.org/​10.1037/​
0894-​4105.7.4.476
Heller, W. & Nitschke, J. B. (1998). The puzzle of regional brain activity in and anxiety: The im-
portance of subtypes and comorbidity. Cognition & Emotion, 12(3), 421–​447.
Heller, W., Nitschke, J. B., Etienne, M. A., & Miller, G. A. (1997). Patterns of regional brain ac-
tivity differentiate types of anxiety. Journal of Abnormal Psychology, 106(3), 376–​385. https://​
doi.org/​10.1037/​0021-​843X.106.3.376
Hirshfeld-​Becker, D. R., Biederman, J., Henin, A., Faraone, S. V., Davis, S., Harrington, K., &
Rosenbaum, J. F. (2007). Behavioral inhibition in preschool children at risk is a specific pre-
dictor of middle childhood social anxiety: A five-​year follow-​up. Journal of Developmental and
Behavioral Pediatrics, 28(3), 225–​233. https://​doi.org/​10.1097/​01.DBP.000​0268​559.34463.d0
486    JASON S. MOSER et al.

Hofmann, S. G., Moscovitch, D. A., Litz, B. T., Kim, H. J., Davis, L. L., & Pizzagalli, D. A. (2005).
The worried mind: Autonomic and prefrontal activation during worrying. Emotion, 5(4),
464–​475. https://​doi.org/​10.1037/​1528-​3542.5.4.464
Hur, J., Stockbridge, M. D., Fox, A. S. & Shackman, A. J. (2019). Dispositional negativity, cogni-
tion, and anxiety disorders: An integrative translational neuroscience framework. Progress
in Brain Research, 247, 375–​436.
Ip, K. I., Liu, Y., Moser, J., Mannella, K., Hruschak, J., Bilek, E., . . . Fitzgerald, K. (2019).
Moderation of the relationship between the error-​related negativity and anxiety by age
and gender in young children: A preliminary investigation. Developmental Cognitive
Neuroscience, 39, 100702.
Ischebeck, M., Endrass, T., Simon, D., & Kathmann, N. (2014). Altered frontal EEG asymmetry
in obsessive-​compulsive disorder. Psychophysiology, 51(7), 596–​601. https://​doi.org/​10.1111/​
psyp.12214
Isotani, T., Tanaka, H., Lehmann, D., Pascual-​Marqui, R. D., Kochi, K., Saito, N., . . . Sasada,
K. (2001). Source localization of EEG activity during hypnotically induced anxiety and re-
laxation. International Journal of Psychophysiology, 41(2), 143–​153. https://​doi.org/​10.1016/​
S0167-​8760(0  0)00197-​5
Jenkinson, N. & Brown, P. (2011). New insights into the relationship between dopamine, beta
oscillations and motor function. Trends in Neurosciences, 34(12), 611–​618.
Jensen, O., Kaiser, J., & Lachaux, J. P. (2007). Human gamma-​frequency oscillations associated
with attention and memory. Trends in Neurosciences, 30(7), 317–​324.
Judah, M. R., Grant, D. M., Frosio, K. E., White, E. J., Taylor, D. L., & Mills, A. C. (2016).
Electrocortical evidence of enhanced performance monitoring in social anxiety. Behavior
Therapy, 47(2), 274–​285.
Kalin, N. H., Larson, C., Shelton, S. E., & Davidson, R. J. (1998). Asymmetric frontal brain
activity, cortisol, and behavior associated with fearful temperament in rhesus monkeys.
Behavioral Neuroscience, 112(2), 286–​292. https://​doi.org/​10.1037/​0735-​7044.112.2.286
Kemp, A. H., Griffiths, K., Felmingham, K. L., Shankman, S. A., Drinkenburg, W., Arns,
M., . . . Bryant, R. A. (2010). Disorder specificity despite comorbidity: Resting EEG alpha
asymmetry in major depressive disorder and post-​traumatic stress disorder. Biological
Psychology, 85(2), 350–​354. https://​doi.org/​10.1016/​j.biopsy​cho.2010.08.001
Kemp, A. H., Koenig, J., Thayer, J. F., Bittencourt, M. S., Pereira, A. C., Santos, I. S., ... &
Benseñor, I. M. (2016). Race and resting-​state heart rate variability in Brazilian civil servants
and the mediating effects of discrimination: An ELSA-​Brasil cohort study. Psychosomatic
Medicine, 78(8), 950–​958.
Keune, P. M., Schönenberg, M., Wyckoff, S., Mayer, K., Riemann, S., Hautzinger, M., & Strehl,
U. (2011). Frontal alpha-​asymmetry in adults with attention deficit hyperactivity dis-
order: Replication and specification. Biological Psychology, 87(2), 306–​310. https://​doi.org/​
10.1016/​j.biopsy​cho.2011.02.023
Knyazev, G. G., Savostyanov, A. N., & Levin, E. A. (2005). Uncertainty, anxiety and brain
oscillations. Neuroscience Letters, 387, 121–​125.
Knyazev, G. G. & Slobodskaya, H. R. (2003). Personality trait of behavioral inhibition is
associated with oscillatory systems reciprocal relationships. International Journal of
Psychophysiology, 48(3), 247–​261.
Knyazev, G. G., Schutter, D. J., & van Honk, J. (2006). Anxious apprehension increases coup-
ling of delta and beta oscillations. International Journal of Psychophysiology, 61(2), 283–​287
 EEG FREQUENCY TECHNIQUES In Anxiety    487

Knyazev, G. G. (2007). Motivation, emotion, and their inhibitory control mirrored in brain
oscillations. Neuroscience & Biobehavioral Reviews, 31(3), 377–​395.
Knyazev, G. G. (2011). Cross-​frequency coupling of brain oscillations: an impact of state anx-
iety. International Journal of Psychophysiology, 80(3), 236–​245.
Kool, W., McGuire, J. T., Rosen, Z. B., & Botvinick, M. M. (2010). Decision making and the
avoidance of cognitive demand. Journal of Experimental Psychology, 139(4), 665.
Kuskowski, M. A., Malone, S. M., Kim, S. W., Dysken, M. W., Okaya, A. J., & Christensen, K. J.
(1993). Quantitative EEG in obsessive-​compulsive disorder. Biological Psychiatry, 33(6), 423–​
430. https://​doi.org/​10.1016/​0006-​3223(93)90170-​I
Laufs, H., Kleinschmidt, A., Beyerle, A., Eger, E., Salek-​Haddadi, A., Preibisch, C., & Krakow,
K. (2003). EEG-​correlated fMRI of human alpha activity. NeuroImage, 19(4), 1463-​1476.
https://​doi.org/​10.1016/​S1053-​8119(03)00286-​6
Laurienti, P. J., Wallace, M. T., Maldjian, J. A., Susi, C. M., Stein, B. E., & Burdette, J. H. (2003).
Cross‐modal sensory processing in the anterior cingulate and medial prefrontal cortices.
Human Brain Mapping, 19(4), 213–​223.
Ledoux, J. (1978). The neurology of emotion. Casa Editrice.
Liu, Y., Moser, J. S., Aviyente, S. (2014). Network community structure detection for directional
neural networks inferred from multichannel multisubject EEG data. IEEE Transactions on
Biomedical Engineering, 61, 1919–​1930.
Lindström, B. R., Mattsson-​Mårn, I. B., Golkar, A., & Olsson, A. (2013). In your face: Risk
of punishment enhances cognitive control and error-​related activity in the corrugator
supercilii muscle. PloS One, 8(6), e65692.
Lobo, I., Portugal, L. C., Figueira, I., Volchan, E., David, I., Garcia Pereira, M., & De Oliveira, L.
(2015). EEG correlates of the severity of posttraumatic stress symptoms: A systematic review
of the dimensional PTSD literature. Journal of Affective Disorders, 183, 210–​220. https://​doi.
org/​10.1016/​j.jad.2015.05.015
LoBue, V., Coan, J. A., Thrasher, C., & DeLoache, J. S. (2011). Prefrontal asymmetry and Parent-​Rated
temperament in infants. PLoS One, 6(7): e22694. https://​doi.org/​10.1371/​jour​nal.pone.0022​694
Lubar, J. F., Congedo, M., & Askew, J. H. (2003). Low-​resolution electromagnetic tomog-
raphy (LORETA) of cerebral activity in chronic depressive disorder. International Journal of
Psychophysiology, 49(3), 175–​185. https://​doi.org/​10.1016/​S0167-​8760(03)00115-​6
Luu, P., Tucker, D. M., & Makeig, S. (2004). Frontal midline theta and the error-​related nega-
tivity: neurophysiological mechanisms of action regulation. Clinical Neurophysiology, 115(8),
1821–​1835.
Mantini, D., Perrucci, M. G., Del Gratta, C., Romani, G. L., & Corbetta, M. (2007).
Electrophysiological signatures of resting state networks in the human brain. Proceedings
of the National Academy of Sciences of the United States of America, 104(32), 13170–​13175.
doi:10.1073/​pnas.0700668104
Mathersul, D., Williams, L. M., Hopkinson, P. J., & Kemp, A. H. (2008). Investigating models of
affect: Relationships among EEG alpha asymmetry, depression, and anxiety. Emotion, 8(4),
560–​572. https://​doi.org/​10.1037/​a0012​811
McManis, M. H., Kagan, J., Snidman, N. C., & Woodward, S. A. (2002). EEG asymmetry,
power, and temperament in children. Developmental Psychobiology, 41(2), 169–​177. https://​
doi.org/​10.1002/​dev.10053
Metzger, L. J., Carson, M. A., Paulus, L. A., Paige, S. R., Lasko, N. B., Pitman, R. K., & Orr,
S. P. (2004). PTSD arousal and depression symptoms associated with increased right-​sided
488    JASON S. MOSER et al.

parietal EEG asymmetry. Journal of Abnormal Psychology, 113(2), 324–​329. https://​doi.org/​

10.1037/​0021-​843X.113.2.324
Meyer, T. J., Miller, M. L., Metzger, R. L., & Borkovec, T. D. (1990). Development and validation
of the Penn State Worry Questionnaire. Behaviour Research and Therapy, 28(6), 487–​495.
https://​doi.org/​10.1016/​0005-​7967(90)90135-​6
Miller, G. A. (1996). How we think about cognition, emotion, and biology in psychopathology.
Psychophysiology, 33, 615–​628.
Miller, G. A. (2010). Mistreating psychology in the decades of the brain. Perspectives on
Psychological Science, 5,716–​743.
Miskovic, V., Ashbaugh, A. R., Santesso, D. L., McCabe, R. E., Antony, M. M., & Schmidt, L.
A. (2010). Frontal brain oscillations and social anxiety: A cross-​frequency spectral analysis
during baseline and speech anticipation. Biological Psychology, 83(2), 125–​132.
Miskovic, V., Campbell, M. J., Santesso, D. L., Van Ameringen, M., Mancini, C. L., & Schmidt,
L. A. (2011). Frontal brain oscillatory coupling in children of parents with social phobia: A
pilot study. The Journal of Neuropsychiatry and Clinical Neurosciences, 23(1), 111–​114.
Miskovic, V., Moscovitch, D. A., Santesso, D. L., McCabe, R. E., Antony, M. M., & Schmidt, L.
A. (2011). Changes in EEG cross-​frequency coupling during cognitive behavioral therapy for
social anxiety disorder. Psychological Science, 22(4), 507–​516.
Mizuki, Y., Hashimoto, M., Tanaka, T., Inanaga, K., & Tanaka, M. (1983). A new physio-
logical tool for assessing anxiolytic effects in humans: frontal midline theta activity.
Psychopharmacology, 80(4), 311–​314.
Mizuki, Y., Suetsugi, M., Imai, T., Kai, S., Kajimura, N., & Yamada, M. (1989). A physiological
marker for assessing anxiety level in humans: frontal midline theta activity. Psychiatry and
Clinical Neurosciences, 43(4), 619–​626.
Mizuki, Y., Kajimura, N., Kai, S., Suetsugi, M., Ushijima, I., & Yamada, M. (1992). Differential
responses to mental stress in high and low anxious normal humans assessed by frontal mid-
line theta activity. International Journal of Psychophysiology, 12(2), 169–​178.
Moadab, I., Gilbert, T., Dishion, T. J., & Tucker, D. M. (2010). Frontolimbic activity in a
frustrating task: Covariation between patterns of coping and individual differences in
externalizing and internalizing symptoms. Development and Psychopathology, 22(2),
391–​404.
Moran, T. P., Bernat, E. M., Aviyente, S., Schroder, H. S., & Moser, J. S. (2015). Sending
mixed signals: Worry is associated with enhanced initial error processing but reduced
call for subsequent cognitive control. Social Cognitive and Affective Neuroscience, 10(11),
1548–​1556.
Morillas-​Romero, A., Tortella-​Feliu, M., Bornas, X., & Putman, P. (2015). Spontaneous EEG
theta/​beta ratio and delta–​beta coupling in relation to attentional network functioning
and self-​reported attentional control. Cognitive, Affective, & Behavioral Neuroscience, 15(3),
598–​606.
Moscovitch, D. A., Santesso, D. L., Miskovic, V., McCabe, R. E., Antony, M. M., & Schmidt, L.
A. (2011). Frontal EEG asymmetry and symptom response to cognitive behavioral therapy in
patients with social anxiety disorder. Biological Psychology. https://​doi.org/​10.1016/​j.biopsy​
cho.2011.04.009
Moser, J. S., Moran, T. P., & Jendrusina, A. A. (2012). Parsing relationships between
dimensions of anxiety and action monitoring brain potentials in female undergraduates.
Psychophysiology, 49(1), 3–​10.
 EEG FREQUENCY TECHNIQUES In Anxiety    489

Moser, J. S., Moran, T. P., Schroder, H. S., Donnellan, M. B., & Yeung, N. (2013). On the relation-
ship between anxiety and error monitoring: A meta-​analysis and conceptual framework.
Frontiers in Human Neuroscience, 7, 466. doi:10.3389/​fnhum.2013.00466
Moser, J. S., Moran, T. P., Kneip, C., Schroder, H. S., & Larson, M. J. (2016). Sex moderates the
association between symptoms of anxiety, but not obsessive compulsive disorder, and error-​
monitoring brain activity: A meta-​analytic review. Psychophysiology, 53, 21–​29.
Moser, J.S. (2017). The nature of the relationship between anxiety and the error-​related nega-
tivity across development. Current Behavior Neuroscience Reports, 4(4), 309–​321.
Nash, K., Inzlicht, M., & McGregor, I. (2012). Approach-​related left prefrontal EEG asymmetry
predicts muted error-​related negativity. Biological Psychology, 91(1), 96–​102. https://​doi.org/​
10.1016/​j.biopsy​cho.2012.05.005
Nitschke, J. B., Heller, W., Palmieri, P. A., & Miller, G. A. (1999). Contrasting patterns of brain
activity in anxious apprehension and anxious arousal. Psychophysiology, 36(5), 628–​637.
https://​doi.org/​10.1017/​S00485​7729​9972​013
Nusslock, R., Shackman, A. J., McMenamin, B. W., Greischar, L. L., Davidson, R. J., & Kovacs,
M. (2018). Comorbid anxiety moderates the relationship between depression history
and prefrontal EEG asymmetry. Psychophysiology, 55(1), e12953. https://​doi.org/​10.1111/​
psyp.12953
Nusslock, R., Walden, K., & Harmon-​Jones, E. (2015). Asymmetrical frontal cortical activity
associated with differential risk for mood and anxiety disorder symptoms: An RDoC per-
spective. International Journal of Psychophysiology, 98(2, Pt.2), 249–​261. https://​doi.org/​
10.1016/​j.ijpsy​cho.2015.06.004
Peterson, C. K. & Harmon-​Jones, E. (2009). Circadian and seasonal variability of resting
frontal EEG asymmetry. Biological Psychology, 80(3), 315–​320. https://​doi.org/​10.1016/​
j.biopsy​cho.2008.11.002
Poppelaars, E. S., Harrewijn, A., Westenberg, P. M., & van der Molen, M. J. W. (2018). Frontal
delta-​beta cross-​frequency coupling in high and low social anxiety: An index of stress regu-
lation? Cognitive, Affective & Behavioral Neuroscience, 18(4), 764–​777.
Popov, T., Westner, B. U., Silton, R. L., Sass, S. M., Spielberg, J. M., Rockstroh, B., Heller, W., &
Miller, G. A. (2018). Time course of brain network reconfiguration supporting inhibitory
control. Journal of Neuroscience, 38, 4348–​4356.
Putman, P., Verkuil, B., Arias-​Garcia, E., Pantazi, I., & van Schie, C. (2014). EEG theta/​beta
ratio as a potential biomarker for attentional control and resilience against deleterious
effects of stress on attention. Cognitive, Affective, & Behavioral Neuroscience, 14(2), 782–​791.
Putman, P., Arias-​Garcia, E., Pantazi, I., & van Schie, C. (2012). Emotional Stroop interference
for threatening words is related to reduced EEG delta–​beta coupling and low attentional
control. International Journal of Psychophysiology, 84, 194–​200.
Putman, P., van Peer, J., Maimari, I., & van der Werff, S. (2010). EEG theta/​beta ratio in relation
to fear-​modulated response-​inhibition, attentional control, and affective traits. Biological
Psychology, 83(2), 73–​78.
Rabe, S., Beauducel, A., Zöllner, T., Maercker, A., & Karl, A. (2006). Regional brain electrical
activity in posttraumatic stress disorder after motor vehicle accident. Journal of Abnormal
Psychology, 115(4), 687–​698. https://​doi.org/​10.1037/​0021-​843X.115.4.687
Rabe, S., Zöllner, T., Maercker, A., & Karl, A. (2006). Neural correlates of posttraumatic growth
after severe motor vehicle accidents. Journal of Consulting and Clinical Psychology, 74(5),
880–​886. https://​doi.org/​10.1037/​0022-​006X.74.5.880
490    JASON S. MOSER et al.

Reznik, S. J., & Allen, J. J. B. (2018). Frontal asymmetry as a mediator and moderator of
emotion: An updated review. Psychophysiology, 55(1), e12965. https://​doi.org/​10.1111/​
psyp.12965
Riesel, A., Goldhahn, S., & Kathmann, N. (2017). Hyperactive performance monitoring as a
transdiagnostic marker: Results from health anxiety in comparison to obsessive–​compulsive
disorder. Neuropsychologia, 96, 1–​8.
Righi, S., Mecacci, L., & Viggiano, M. P. (2009). Anxiety, cognitive self-​evaluation and per-
formance: ERP correlates. Journal of Anxiety Disorders, 23(8), 1132–​1138.
Sackeim, H. A., Greenberg, M. S., Weiman, A. L., Gur, R. C., Hungerbuhler, J. P., & Geschwind,
N. (1982). Hemispheric asymmetry in the expression of positive and negative emotions.
Neurologic evidence. Archives of Neurology, 39(4), 210–​218.
Santesso, D. L., Bogdan, R., Birk, J. L., Goetz, E. L., Holmes, A. J., & Pizzagalli, D. A. (2011).
Neural responses to negative feedback are related to negative emotionality in healthy adults.
Social Cognitive and Affective Neuroscience, 7(7), 794–​803.
Scheeringa, R., Petersson, K. M., Kleinschmidt, A., Jensen, O., & Bastiaansen, M. C. M. (2012).
EEG alpha power modulation of fMRI resting-​state connectivity. Brain Connectivity, 2(5),
254–​264. https://​doi.org/​10.1089/​brain.2012.0088
Schmid, P. C., Kleiman, T., & Amodio, D. M. (2015). Neural mechanisms of proactive and re-
active cognitive control in social anxiety. Cortex, 70, 137–​145.
Schmidt, L. A., Fox, N. A., Schulkin, J., & Gold, P. W. (1999). Behavioral and psycho-
physiological correlates of self-​ presentation in temperamentally shy children.
Developmental Psychobiology, 35(2), 119–​135. https://​doi.org/​10.1002/​(SICI)1098-​2302(199​
909)35:2<119::AID-​DEV5>3.0.CO;2-​G
Schmidt, B., Kanis, H., Holroyd, C. B., Miltner, W. H., & Hewig, J. (2018). Anxious
gambling: Anxiety is associated with higher frontal midline theta predicting less risky
decisions. Psychophysiology, 55(10), e13210.
Schouppe, N., De Houwer, J., Richard Ridderinkhof, K., & Notebaert, W. (2012).
Conflict: Run! Reduced Stroop interference with avoidance responses. The Quarterly
Journal of Experimental Psychology, 65(6), 1052–​1058.
Schroder, H. S., Glazer, J. E., Bennett, K. P., Moran, T. P., & Moser, J. S. (2017). Suppression of
error-​preceding brain activity explains exaggerated error monitoring in females with worry.
Biological Psychology, 122, 33–​41. doi:10.1016/​j.biopsycho.2016.03.013
Schutter, D. J. & Honk, J. V. (2004). Decoupling of midfrontal delta–​beta oscillations after tes-
tosterone administration. International Journal of Psychophysiology, 53, 71–​73.
Schutter, D. J. & Van Honk, E. J. (2005). Salivary cortisol levels and the coupling of midfrontal
delta-​beta oscillations. International Journal of Psychophysiology, 55, 127–​129.
Sehlmeyer, C., Konrad, C., Zwitserlood, P., Arolt, V., Falkenstein, M., & Beste, C. (2010).
ERP indices for response inhibition are related to anxiety-​ related personality traits.
Neuropsychologia, 48(9), 2488–​2495.
Shackman, A. J., Salomons, T. V., Slagter, H. A., Fox, A. S., Winter, J. J., & Davidson, R. J. (2011).
The integration of negative affect, pain and cognitive control in the cingulate cortex. Nature
Reviews Neuroscience, 12(3), 154–​167. doi:10.1038/​nrn2994
Shankman, S. A., Silverstein, S. M., Williams, L. M., Hopkinson, P. J., Kemp, A. H.,
Felmingham, K. L., . . . Clark, C. R. (2008). Resting electroencephalogram asymmetry and
posttraumatic stress disorder. Journal of Traumatic Stress, 21(2), 190–​198. https://​doi.org/​
10.1002/​jts.20319
 EEG FREQUENCY TECHNIQUES In Anxiety    491

Sharp, P. B., Miller, G. A., & Heller, W. (2015). Transdiagnostic dimensions of anx-
iety: neural mechanisms, executive functions, and new directions. International Journal of
Psychophysiology, 98(2), 365–​377.
Sharp, P. B. & Miller, G. A. (2019). Reduction and autonomy in psychology and neuroscience: A
call for pragmatism. Journal of Theoretical and Philosophical Psychology, 39(1), 18.
Shi, R., Sharpe, L., & Abbott, M. (2019). A meta-​analysis of the relationship between anxiety
and attentional control. Clinical Psychology Review, 72, 101754.
Silberman, E. K. & Weingartner, H. (1986). Hemispheric lateralization of functions related to
emotion. Brain and Cognition, 5(3), 322–​353. https://​doi.org/​10.1016/​0278-​2626(86)90035-​7
Smith, E. E., Cavanagh, J. F., & Allen, J. J. B. (2018). Intracranial source activity (eLORETA)
related to scalp-​level asymmetry scores and depression status. Psychophysiology, 55(1),
e13019. https://​doi.org/​10.1111/​psyp.13019
Smith, E. E., Zambrano-​Vazquez, L., & Allen, J. J. B. (2016). Patterns of alpha asymmetry in
those with elevated worry, trait anxiety, and obsessive-​compulsive symptoms: A test of the
worry and avoidance models of alpha asymmetry. Neuropsychologia, 85, 118–​126. https://​doi.
org/​10.1016/​j.neuro​psyc​holo​gia.2016.03.010
Spielberg, J. M., Miller, G. A., Heller, W., & Banich, M. T. (2015). Flexible brain network recon-
figuration supporting inhibitory control. Proceedings of the National Academy of Sciences of
the United States of America, 112(32), 10020–​10025.
Spielberger, C. D. (1983). State-​Trait Anxiety Inventory (STAI). Mind Garden, 94061(650), 261–​
3500. https://​doi.org/​10.1002/​978047​0479​216.cor​psy0​943
Steiner, A. R. W., & Coan, J. A. (2011). Prefrontal asymmetry predicts affect, but not beliefs
about affect. Biological Psychology, 88, 65–​7 1. https://​doi.org/​10.1016/​j.biopsy​cho.2011.06.010
Suetsugi, M., Mizuki, Y., Ushijima, I., Kobayashi, T., Tsuchiya, K., Aoki, T., & Watanabe, Y.
(2000). Appearance of frontal midline theta activity in patients with generalized anxiety dis-
order. Neuropsychobiology, 41(2), 108–​112.
Taschereau-​Dumouchel, V., Michel, M., Lau, H., Hofmann, S. G., & LeDoux, J. E. (2022).
Putting the “mental” back in “mental disorders”: a perspective from research on fear and
anxiety. Molecular Psychiatry. https://​doi.org/​10.1038/​s41​380-​021-​01395-​5
Trujillo, L. T. & Allen, J. J. (2007). Theta EEG dynamics of the error-​related negativity. Clinical
Neurophysiology, 118(3), 645–​668.
U.S. Burden of Disease Collaborators. (2018). The state of US health, 1990-​2016. Burden
of diseases, injuries, and risk factors among US states. Journal of the American Medical
Association, 319, 1444–​1472.
Van Den Heuvel, M. P., Mandl, R. C., Kahn, R. S., & Hulshoff Pol, H. E. (2009). Functionally
linked resting‐state networks reflect the underlying structural connectivity architecture of
the human brain. Human Brain Mapping, 30(10), 3127–​3141.
van der Molen, M. J., Harrewijn, A., & Westenberg, P. M. (2018). Will they like me? Neural and
behavioral responses to social-​evaluative peer feedback in socially and non-​socially anxious
females. Biological Psychology, 135, 18–​28.
Van Noordt, S. J., Campopiano, A., & Segalowitz, S. J. (2016). A functional classifica-
tion of medial frontal negativity ERPs: Theta oscillations and single subject effects.
Psychophysiology, 53(9), 1317–​1334.
Van Peer, J. M., Roelofs, K., & Spinhoven, P. (2008). Cortisol administration enhances the
coupling of midfrontal delta and beta oscillations. International Journal of Psychophysiology,
67, 144–​150.
492    JASON S. MOSER et al.

van Son, D., De Blasio, F. M., Fogarty, J. S., Angelidis, A., Barry, R. J., & Putman, P. (2019).
Frontal EEG theta/​beta ratio during mind wandering episodes. Biological Psychology,
140, 19–​27.
Velikova, S., Locatelli, M., Insacco, C., Smeraldi, E., Comi, G., & Leocani, L. (2010).
Dysfunctional brain circuitry in obsessive–​compulsive disorder: source and coherence ana-
lysis of EEG rhythms. NeuroImage, 49(1), 977–​983.
Velo, J. R., Stewart, J. L., Hasler, B. P., Towers, D. N., & Allen, J. J. B. (2012). Should it matter
when we record? Time of year and time of day as factors influencing frontal EEG asym-
metry. Biological Psychology, 91(2), 283–​291. https://​doi.org/​10.1016/​j.biopsy​cho.2012.06.010
Wacker, J., Mueller, E. M., Pizzagalli, D. A., Hennig, J., & Stemmler, G. (2013). Dopamine-​D2-​
receptor blockade reverses the association between trait approach motivation and frontal
asymmetry in an approach-​motivation context. Psychological Science, 24(4), 489–​497.
https://​doi.org/​10.1177/​09567​9761​2458​935
Watts, A. T., Tootell, A. V., Fix, S. T., Aviyente, S., & Bernat, E. M. (2018). Utilizing time-​
frequency amplitude and phase synchrony measure to assess feedback processing in a
gambling task. International Journal of Psychophysiology, 132, 203–​212.
Weinberg, A., Meyer, A., Hale-​Rude, E., Perlman, G., Kotov, R., Klein, D. N., & Hajcak, G.
(2016). Error-​related negativity (ERN) and sustained threat: Conceptual framework and
empirical evaluation in an adolescent sample. Psychophysiology, 53(3), 372–​385. doi:10.1111/​
psyp.12538
Wiedemann, G., Pauli, P., Dengler, W., Lutzenberger, W., Birbaumer, N., & Buchkremer, G.
(1999). Frontal brain asymmetry as a biological substrate of emotions in patients with
panic disorders. Archives of General Psychiatry, 56(1), 78–​84. https://​doi.org/​10.1001/​archp​
syc.56.1.78
Zhang, D. & Gu, R. (2018). Behavioral preference in sequential decision‐making and its associ-
ation with anxiety. Human Brain Mapping, 39(6), 2482–​2499.
Zotev, V., Yuan, H., Misaki, M., Phillips, R., Young, K. D., Feldner, M. T., & Bodurka, J. (2016).
Correlation between amygdala BOLD activity and frontal EEG asymmetry during real-​time
fMRI neurofeedback training in patients with depression. NeuroImage: Clinical, 11, 224–​238.
https://​doi.org/​10.1016/​j.nicl.2016.02.003
Pa rt I V
 CHAPTER 20

B IVARIATE FUNC T I ONA L

C ONNECTIVIT Y ME ASU RE S
F OR WITHIN-​ A ND C RO S S -​
F RE QUENCY C OU PL I NG OF
NEURONAL OSCI L L AT I ONS

J. MATIAS PALVA AND SATU PALVA

20.1  Introduction

Oscillations are ubiquitous in electrophysiological recordings of spontaneous brain

activity at all measurable scales, from single neurons and micro-​electrode recordings
to large neuronal masses observable with EEG and MEG from scalp. Numerous syn-
aptic mechanisms and neuronal microcircuit patterns serve the production of oscil-
latory behavior in neuronal populations ranging in size from some tens of neurons
to millions of neurons in macroscopic cortical areas. Functional correlations among
neuronal populations arise primarily through direct structural connections. However,
in neuronal systems operating near a critical phase transition, these correlations may
exceed the spatial and temporal range of the actual underlying structural interactions.
Several lines of evidence indicate that human brain activity exhibits such critical-​like
dynamics, which implies that correlations of neuronal activities are likely to exceed the
connections defined by direct axonal, or “structural”, connections and temporally the
time scales of the associated synaptic time constants.
In studies of brain dynamics, correlations between the activity time series of neurons
or populations of neurons are termed “functional” connectivity (FC). In this chapter, we
outline the key methods for measuring bivariate (pairwise) FC among electrophysio-
logical time series. As a preface, we provide an overview of the essential features of the
underlying (univariate) signals and the corresponding analysis methods. We aim to
496    J. MATIAS PALVA and SATU PALVA

dissect these methods both by the information they yield about the underlying physio-
logical interactions as well as by limitations posed by the typical confounders in MEG
and EEG data.

20.2  Dissecting broadband, quasi-​

periodic, and periodic signals
for functional connectivity analysis

Before decisions about time-​series analysis methods are made, it is important to

understand the to-​be-​studied system and grasp whether the system operates with
broadband or narrowband processes. This is because the analyses of broad-​and nar-
rowband signals involve distinct concepts and implications. In the context of brain
data and EEG in particular, a distinction has been drawn between supposedly aperi-
odic forms of activity, such as the “1/​f-​component” of the EEG power spectrum,
and activities that are clearly periodic, such as the alpha oscillations that exhibit a
power spectral peak (Cole & Voytek, 2017). However, in between genuine aperiodic
and periodic signals, that is, between genuine noise and oscillations, there is likely
to be a wide range of electrophysiological phenomena that are “quasi-​periodic”
(Palva & Palva, 2012; Palva & Palva 2018). Quasi-​periodic neuronal oscillations are
genuine oscillations that arise via oscillatory mechanisms and embody the func-
tional implications and consequences of oscillations, but that are short-​lived and have
such variance in frequency that they do not show up as a clear peak in power-​spectral
analyses (Palva & Palva, 2012; Palva & Palva, 2018). For example, infra-​slow (0.01–​0.1
Hz) and slow (0.1–​1 Hz) fluctuations, despite their 1/​f-​like power spectrum, have been
suggested to be quasi-​periodic oscillations in both EEG (Monto et al., 2008; Palva &
Palva, 2012; Palva & Palva, 2018) and fMRI (Abbas et al., 2019; Belloy et al., 2019; Zhang
et al., 2020) data.
Functional connectivity in genuine broadband activity can be meaningfully analyzed
only with methods such as the classical time-​ domain cross correlation measures
(Pearson and Spearman correlation coefficients, canonical correlation, and many
others) or information theoretical measures such as mutual information and its many
derivatives. These time-​domain measures can be applied also to quasi-​periodic or peri-
odic signals such as neuronal oscillations, but they are suboptimal because they ignore
the frequency-​limited nature of the periodicity and include “noise” and signals in other
frequency bands. Moreover, broadband coupling measures, by definition, ignore the
most important parameter of neuronal oscillations—​their phase. As this chapter focuses
on neuronal oscillations, we will not delve deeper into the analysis of aperiodic signals.
Measures intended for analyses of oscillations (discussed later) can also be applied to
broadband signals and will converge to the correct result. However, they are suboptimal
 BIVARIATE FUNCTIONAL CONNECTIVITY MEASURES    497

by involving narrow-​band filtering as well as phase-​estimation that is irrelevant in

broadband signals because in true aperiodic correlations, only time rather than phase
lags may exist. These measures also exploit only limited frequency ranges for correl-
ation estimation, which distributes the statistical power in the signal to multiple tests
(Figure 20.1).
The vast majority of brain signals are (i) quasi-​periodic or periodic, (ii) arise via
frequency-​limited, time-​scale specific neuronal mechanisms, (iii) are phenomeno-
logically confined to a limited frequency band, and finally, (iv) involve the notion of
phase as the central mechanistic concept that spans from neuronal firing to behavioral
correlations. Thus, initiation of any analysis with an analysis approach intended for
frequency-​resolved narrow-​band oscillations is justifiable and gives an appropriate rep-
resentation of the signal features.

20.3  Phase and amplitude correlations

of neuronal oscillations

Phase and amplitude time series of neuronal activity in electrophysiological signals can
be extracted by filtering. When estimated for two or more such time series, bivariate
correlation metrics for pairs of such phase and amplitude estimates can be applied to
uncover the patterns of correlations in these data, that is, to quantify the phase and amp-
litude FC.
Phase is a quantitative description of the state of a given process/​component and its
temporal evolution within a period (or a cycle) of the oscillation. From micro-​electrode
recordings to macroscopic EEG signals, observations of genuine phase correlations
imply correlations of neuronal excitability fluctuations at the cellular level and the po-
tential for consistent spike-​timing relationships.
The physiological and mechanistic implications of amplitude, on the other hand, are
always dependent on the experimental setting because the amplitude measurement is
dependent on biological and physical signal generation and conduction mechanisms.
The population-​level summation of electric fields leading to the measured signal amp-
litude is largely dependent on the coherence of the underlying synaptic inputs. This is
because cancellation of electric currents effectively suppresses signals from incoherent
sources. Thus, the amplitude of oscillations is primarily an approximate index of local
synchronization and only secondarily dependent on the net magnitude of source
currents.
Phase and amplitude of neuronal oscillations thus reflect partially distinct physio-
logical phenomena and, correspondingly, inter-​areal phase and amplitude correlations
tap into physiologically and functionally distinct forms of large-​scale coordination of
neuronal activities.
 (a)

(b)
Single trails Averaged data

Power
Arrhythmic signals/
‘1/f noise’

Frequency Frequency

(c)

(d)
Power

Quasiperiodic
oscillations
Power

(Periodic) oscillations

Frequency Frequency
(e)
Hit
Miss 100
μV
50 s

0.01 0.1 1 10 50
Frequency (Hz)

Figure 20.1  Conceptual illustration of aperiodic, quasiperiodic, and periodic signals. (A) The
time series of 1/​f noise yield both (B) in a single realization (left) and in averaged data (right)
1/​f power spectra. (C) Signals composed of mixtures of transient periodicities from multiple
sources or quasiperiodic oscillators with a large variability in oscillation frequencies give rise
to power spectra (D) that may exhibit peaks at the corresponding frequencies (green and blue
bars) in single trials and yet the averaged spectra may not exhibit peaks. Only oscillations with
a stable period retain peaks in averaged power spectra. (E) Human behavioral performance is
characterized by power-​law scale-​free dynamics where the detected (Hits) and undetected
(Misses) stimuli in a threshold-​stimulus detection task are clustered with power-​law and long-​
range temporal correlations. Adapted from Palva and Palva 2018.
 BIVARIATE FUNCTIONAL CONNECTIVITY MEASURES    499

20.4  Phase-​and amplitude-​time series

estimation for periodic and
quasi-​periodic signals

This chapter discusses the principal approaches for measuring phase and amplitude
correlations from neuronal data. Further, it aims to illustrate the adaptation of phase-​
locking methods to the assessment of frequency-​resolved amplitude correlations, as
well as to quantification of cross-​frequency correlations, such as phase-​amplitude and
cross-​frequency phase correlations, among signals in different frequency bands.
All these interaction metrics are based on estimates of phase and amplitude. To ex-
plicitly represent frequency-​band-​limited phase and amplitude dynamics, most real-​
valued continuous signals can be transformed by filtering to a complex form. A popular
choice is to convolve the signal with a complex wavelet, such as the Gabor or Morlet
wavelet (Sinkkonen et al., 1995; Tallon-​Baudry et al., 1996). Such Gaussian wavelet
filtering yields optimal time-​frequency-​resolution compromise and is superior to other
filtering approaches in most cases (Sinkkonen et al., 1995). The Morlet wavelet w is
defined by:

( )
W (t , f 0 ) = A exp −t 2 / 2σt2 exp (2iπ f 0t ) (1)

where t denotes time, i the imaginary unit, f0 the center frequency of the wavelet, and σt
the standard deviation of the wavelet’s Gaussian envelope in time domain. A is a scaling
parameter and for conventional filtering that aims to yield a filtered signal with the same
amplitude as the original signal, A should be set to A =​2/​∑ (w ) where∑ (w ) denotes
the integral of wavelet’s amplitude envelope (simply the sum of wavelet values for a dis-
crete realization). Notably, this yields a wavelet spectrum that is flat for 1/​f noise. The
wavelet family should be designed with a constant ratio m

m = f 0 / σ f (2)

where σf the standard deviation of the wavelet’s gaussian envelope in frequency do-
main and given by σf =​ 1/​2 πσt . This ratio, or “the m parameter” thus defines the time-​
frequency compromise so that small values (such as m =​5) favors time resolution
whereas larger values (such as m =​7.5) yields improved frequency resolution at the ex-
pense of time resolution.
In applications where other forms of filtering are used, and the filter yields real valued
output, the complex form can be obtained by finding the imaginary part with the Hilbert
transform. As an important non-​linear filtering approach, empirical mode decompos-
ition (Huang & Wu, 2008) is an adaptive and data-​driven method that identifies major
500    J. MATIAS PALVA and SATU PALVA

signal components iteratively from the fastest to slowest frequencies and yields time
series that may follow frequency fluctuations better than conventional fixed-​frequency
filtering.
For segments of stationary signals, the phase estimation can be achieved with spec-
tral measures as well, such as with the Fourier transform. These three approaches are
formally equivalent (Bruns, 2004). However, spectral methods yield constant-​sized
frequency bins while wavelets can and should be scaled with frequency so that they
have constant time-​frequency resolution. This is often overlooked but is as a funda-
mental disadvantage for the spectral methods. For any given fixed time-​window size,
different frequencies will have different amounts of cycles in the window where they
are presumed stationary. Because neuronal oscillations are “stationary” for just a few
cycles, spectral measures will be optimal for a very limited frequency range, and for
most other frequencies will include too few or too many cycles of the oscillations in the
time window.
In the filtering approach, let us denote the filtering operation with a center frequency
f generically with the operator Tf so that the filtered signal x(t,f) is obtained from the ori-
ginal signal xo(t) by

x(t , f ) = Tf,complex [x 0 (t)] = a x (t , f ) exp[iθ x (t,f)] (2)

where i is the imaginary unit, ax(t,f) denotes the amplitude and θ x (t , f ) the phase of
x(t,f), and Tf,complex a complex filter such as the Morlet wavelet transform. If the filtering
is performed with a real-​valued filter, Tf,real, the imaginary signal is obtained by the
Hilbert transform, so that

{ }
x(t , f ) = Tf,real [x 0 (t)] + i H Tf,real [x 0 (t)] (3)

where H denotes the Hilbert transform.

From either approach, let us denote an array of such time series by
X(t,f) =​[xj(t,f)] =​ Ax(t,f) exp[iΘ x(t,f)], where j =​1 . . . ns and ns is the number of sensors
or sources. Comparable phase time series can also be produced from point process time
series (Rosenblum et al., 2004).

20.5  Definition of phase difference

as the basis for a range of
interaction metrics

The time series of phase and amplitude enable the estimation of bivariate phase
and amplitude correlations between any pair of signals. In addition to phase
 BIVARIATE FUNCTIONAL CONNECTIVITY MEASURES    501

synchronization per se, a range of phase and amplitude interactions can be quantified
with the phase-​ locking estimation formalism and will be described here first.
Phase locking is statistically indicated by a non-​random phase or phase-​difference
distribution.
The generic n:m-​phase difference ωnm of signals x and y (Tass et al., 1998) is given by

ωn:m = nθ x − mθ y (4)

where the small integers n and m determine the frequency ratio nfx =​ mfy of the center
frequencies of filters Tfx and Tfy. For assessing the classical within-​frequency phase syn-
chrony, n =​ m =​1. This phase difference is conveniently obtained in complex form from
the filtered x and y simply by

exp[iωn:m ] = ( x / x ) (y/ y )*m (5)

n

where the asterisk* denotes the complex conjugate. Hence, for frequencies fx and fy, the
ns × ns-​sized pair-​wise complex phase difference matrix Φ n:m of a single sample with
each signal against each other signal is given by the complex outer product, ⊗, so that

Φn:m (t , f x f y ) = (X / X )n ⊗ (Y / Y )*m (6)

This expression thus provides the phase difference with which one may quantify
classical within-​frequency phase synchronization but also cross-​frequency phase syn-
chronization (CFS). CFS is a cross-​frequency coupling (CFC) mechanism that indicates
a non-​random phase difference between different low-​(LF) and high-​frequency (HF)
frequency pairs at small-​integer ratios n:m (LF:HF). CFS enables temporally precise co-
ordination of neuronal processing by establishing the possibility for systematic spike-​
timing relationships among oscillatory assemblies at different frequencies and can thus
serve functional integration and coordination across within-​frequency synchronized
large-​scale networks (Fell & Axmacher, 2011; Palva et al., 2005; Palva & Palva, 2017;
Siebenhühner et al., 2016; Siebenhühner et al., 2020).
The phase-​difference approach can also be used to represent more complex bivariate
relationships such as phase-​amplitude coupling (PAC), or “nested oscillations”, that are
characterized by the phase-​locking of the amplitude envelope of a faster oscillation with
the phase of a slower oscillation. PAC has been suggested to reflect the regulation of sen-
sory information processing in faster frequencies by excitability fluctuations imposed
by slower oscillations (Canolty & Knight, 2010; Fell & Axmacher, 2011; Jensen & Colgin,
2007; Jensen & Lisman, 2013, Schroeder & Lakatos, 2009). The complex phase difference
matrix, Φ PAC, is given by filtering the amplitude envelopes Ax of the faster oscillation at
fx with the filter Tfy that was used to obtain the slower oscillation at fy < fx (Vanhatalo
et al., 2004):
502    J. MATIAS PALVA and SATU PALVA

Φ PAC =  Tfy ( Ax )/Tfy ( Ax )| ⊗ (Y / Y )* (7)

It is important to note that this quantification of the non-​uniformity of Φ PAC with a

phase-​locking value (Section 20.6) assumes a unimodal distribution of the fast oscilla-
tion amplitudes along the slow oscillation’s phase. An interaction in which the ampli-
tude of the fast oscillation peaks twice, or more formally m times during the slow cycle,
can be explicitly assessed as a 1:m-​amplitude-​phase interaction. Here the amplitude
envelopes Ax are filtered with a filter Tmfy at frequency mfy and then the corresponding
metric, Φ PACm, is given simply by

ΦPACm =  T2fy ( Ax )/ | T2fy ( Ax ) | ⊗ (Y / Y )*m (8)

Φ PACm is quantifiable with the phase-​locking value. Alternatively, 1:m-​amplitude-​

phase coupling can be implicitly assessed with ΦPAC and a histogram-​based statistic
(Section 20.7).
Characterization of amplitude dynamics with phase differences and circular statistics
can be further extended to amplitude-​amplitude interactions by filtering the amplitude
envelopes Ax and Ay to a slower frequency band fz < fx, fy with Tfz. Now the complex
phase difference matrix, ΦAA, is

*
ΦAA =  Tfz ( Ax )/ | Tfz ( Ax ) | ⊗  Tfz ( Ay )/ | Tfz ( Ay ) | (9)

The advantage of characterizing amplitude interactions (Figure 20.2) with phase

estimators is that they yield frequency-​resolved estimates of amplitude correlations and
that phase dynamics of amplitude fluctuations are independent of variability in the ab-
solute amplitudes and hence large amplitude events do not exert a strong bias like they
do in cross-​correlation analyses for example. For broadband amplitude correlations,
however, conventional correlation-​coefficient based analysis, that is, simply obtaining
the correlation coefficient between two amplitude time series, is likely to be more
efficient.

20.6  Quantification of phase

locking: the phase-​l ocking value and
alternative measures

With the phase or phase difference data, the presence of statistically significant phase
locking can be assessed with a number of circular statistics. The most common of them
is the phase locking value/​factor (PLV, PLF) that is given by an average of complex
phases (Sinkkonen et al., 1995). Let us first define the complex PLV (cPLV) as simply the
average across the complex phase differences
 BIVARIATE FUNCTIONAL CONNECTIVITY MEASURES    503

(a) 1:1 phase synchrony

Real part Phase

Re(xf1)
Re(yf1)

arg(xf1)
arg(yf1)
(b) n:m phase synchrony

Re(xf1)

Re(yf 2)

arg(xf1)
(f2/f1)arg (xf1)
arg(yf 2)
(c) Phase-amplitude coupling

Amplitude
Re(xf1)
|yf 2|
Re(yf 2)
arg(xf1)
arg(Ff 1(|yf 2|))

Figure 20.2  Schematic illustration of within-​frequency and cross-​frequency phase and amp-
litude interactions. (A) Within-​frequency synchronization is a case of generic n:m-​phase syn-
chrony with n =​ m =​1. Re(.) denotes the real part of a complex filtered signal and arg(.) its phase.
(B) A simulated example of 1:4 phase synchronization. (C) An example of phase-​amplitude coup-
ling where the phase of the slow and the amplitude of the fast oscillations are correlated.
Adapted from Palva & Palva, 2012.

cPLV = nt−1 ∑ Φ (10)

where nt is the number of complex phase difference Φ samples pooled across trials and/​
or time. PLV is the absolute value of cPLV (PLV =​|cPLV|) and is 1 for perfect coup-
ling (delta-​function phase distribution) and approaches 0 for a uniform phase distribu-
tion when nt → ∞. If the phase-​difference samples Φ are independent and the marginal
phase distributions are uniform, the no-​interaction null hypothesis is characterized by
uniformly distributed Φ and can be tested with the Rayleigh test.
When Φ are pooled across time, that is, when the independence condition is not
met because of redundancy, and/​or when the underlying process is not sinusoidal (see
Nikulin et al., 2007), surrogate data are needed for statistical testing. For spontaneous
data, the surrogates may be constructed by random rotation of the time series before
estimation of the phase differences in order to preserve endogenous and filter-​induced
autocorrelations and avoid the underestimation of surrogate distribution (Palva
et al, 2005; Siebenhühner et al., 2020). For event-​related data, the surrogates may be
constructed by trial shuffling. If the interaction estimates involve components that are
time-​locked to the events, such as evoked responses, the artificial interactions that they
cause must be accounted for with forward-​and-​inversed-​modeled surrogate data in trial
shuffling (Hirvonen et al., 2018).
504    J. MATIAS PALVA and SATU PALVA

20.7  Considerations for using PLV

for measuring phase synchrony
and CFC

While PLV is a conceptually straightforward and computationally extremely efficient

“first choice” for interaction estimation in many applications, several characteristics of
PLV warrant attention. First, PLV is biased, that is, positively dependent on the number
of samples (Vinck et al., 2010; Aydore et al., 2013). Hence, if two conditions are to be
compared, the number of samples must be equalized. Alternatively, a similar but un-
biased metric, pairwise-​phase consistency (PPC, Vinck et al., 2010) that is equiva-
lent to squared PLV (Aydore et al., 2013) can be used but its computational cost scales
with ns2nt2 whereas the cost of PLV is proportional only to ns2nt. PPC yields sensitivity
similar to PLV. Second, PLV is appropriate only for unimodal phase distributions. The
non-​uniformity of arbitrary distributions can be estimated with Shannon-​entropy and
conditional-​probability based indices for phase (difference) histograms (Tass et al.,
1998). Third, PLV is a measure of correlation and does not disclose causal relationships
or the lack thereof between the signals. Directional phase-​specific interactions can be
estimated with histogram-​based phase transfer entropy without sample-​size or linear
mixing bias (Lobier et al., 2014). Directional interactions can be estimated with mixed
phase and amplitude information with a range of metrics such as Granger causality, par-
tial directed coherence, transfer entropy, and many others. Fourth, PLV among all other
interaction metrics is crucially dependent on the signal-​to-​noise ratio of the phase es-
timate. Only at signal-​to-​noise ratios greater than 2–​3, the phase estimates reach rela-
tive independence from amplitude. Hence, albeit phase is mathematically independent
of amplitude, the accuracy of phase estimates in noisy signals with variable amplitudes
will be dynamically dependent on the amplitude. When making inferences about
differences in phase locking, one needs to consider the putative contribution of concur-
rent differences in signal-​to-​noise ratio (Palva et al., 2010).

20.8  Linear mixing inflates PLV and

other correlation metrics and causes
artificial false positives

One-​to-​one-​phase and amplitude correlations, but not CFS or PAC, estimated with PLV
are directly influenced by linear mixing such as volume conduction in electrophysio-
logical recordings, which leads to inflated PLV values and false positive phase correl-
ation observations in the presence of no true correlations. For amplitude correlations,
 BIVARIATE FUNCTIONAL CONNECTIVITY MEASURES    505

the same applies also to correlation coefficients. This problem is pervasive across all
forms of electrophysiological recordings: from micro-​electrodes to intra-​cranial stereo-​
EEG and electrocorticography, and to scalp EEG, volume conduction causes linear
mixing of electric potentials. While volume conduction does little to influence MEG,
signal mixing between cortical sources and scalp sensors leads to comparable linear
mixing (Figure 20.3). Finally, demixing the sensor signals by source modeling leaves re-
sidual linear mixing, known as source leakage (Palva et al., 2018).
This problem can be partially solved by noting that linear mixing always has a zero-​
time and zero-​phase lag influence, which is fully captured by the real part of PLV or that
of coherence. On the other hand, as true neuronal interactions supposedly often involve
conduction-​delay-​related phase lags, excluding the zero-​lag contribution becomes an

(a) (b)
1 1

0.8 0.8
m=0
0.6 m = 0.1 0.6
m = 0.2
iPLV
PLV

m = 0.3
0.4 m = 0.4 0.4
m = 0.6
0.2 0.2

0 0
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1
(c) co (d) co
1 1

0.8 0.8

0.6 0.6
iPLV
PLV

0.4 0.4

0.2 0.2

0 0
–1 –0.75 –0.5 –0.25 0 0.25 0.5 0.75 1 –1 –0.75 –0.5 –0.25 0 0.25 0.5 0.75 1

Figure 20.3.  Phase coupling measures PLV and iPLV are influenced not only by the phase
coupling strength cΘ, but also by the phase difference nϕxy and linear mixing m between the
studied signals. Here, phase coupling and linear signal mixing (m =​0 (blue), 0.1 (green), 0.2 (red),
0.3 (violet), 0.4 (cyan), and 0.6 (orange)) were simulated between two signals for a range of coup-
ling and phase lag values. (A) PLV between the signals as a function of cΘ and m for nϕxy =​−0.3.
Open circles at cΘ =​0.4 indicate the coupling strength used in C and D. (B) iPLV between the
signals as a function of cΘ and m. (C) PLV as a function of nϕxy, when cΘ was set to 0.4. Notably,
PLV is greatly influenced by the phase difference when signal mixing is strong even though
without mixing, the magnitude of PLV is independent of the phase lag. Open circles at nϕxy =​−0.3
indicate the nϕxy used in A and B. (D) The strength of iPLV depends on the phase difference and is
biased towards large phase difference so that iPLV is abolished when nϕxy =​0 or nϕxy =​±π.
Adapted from Palva et al., 2018.
506    J. MATIAS PALVA and SATU PALVA

approach for obtaining a measure that focuses on neuronal phase coupling and is in-
sensitive to linear mixing. Measures such as imaginary coherence (iCoh, Nolte et al.,
2004), the imaginary part of PLV (iPLV) (Palva & Palva, 2012), and weighted phase-​lag
index (wPLI, Vinck et al., 2011) ignore the real part of the complex phase differences.
These measures are hence insensitive to linear mixing while revealing the true phase-​
lagged interactions. Of these, wPLI is superior to iPLV and iCoh in not being influenced
by the magnitude of linear mixing. The obvious shortcoming of each these approaches
is, nonetheless, their insensitivity to true near-​zero-​phase lag interactions and the
dependence of the correlation value on the phase difference per se in addition to the
strength of the interaction.
The equivalent for iPLV and wPLI for amplitude correlations is orthogonalized cross
correlation (oCC) where the two signals are orthogonalized prior to the estimation of
the correlation coefficient (Brookes et al., 2012, Hipp et al., 2012). It is important to note
that the orthogonalized amplitude correlation coefficients are not independent of con-
current phase coupling. In fact, they are non-​trivially affected by the presence of true
phase coupling and linear mixing in a phase-​difference dependent manner and may
yield both false positive and negative findings (Palva et al., 2018b).

20.9  Ghost interactions constitute

false positives in all bivariate
interaction estimates

The exclusion of artificial interactions with coupling measures that are not inflated by
linear mixing, such as iPLV, wPLI, and oCC, has been often claimed to categorically
“account” for the problem of linear mixing causing false positive detections. Although
these measures are de facto immune to artificial false positives and can be overly conser-
vative by missing true near-​zero-​phase interactions, they still yield abundant “spurious”
or “ghost” false positive interactions due to signal spread. This is because field spread
in the vicinity of a true nonzero phase interaction mirrors the true interactions into
spurious ghost interactions, that appear as false positives with any bivariate interaction
measure in a manner that can never be accounted for in bivariate fashion (Figure 20.4).
There are two principal approaches to addressing the problem of spurious “ghost”
interactions. One is to perform symmetric multivariate orthogonalization where the
cortical-​parcel-​source signals are orthogonalized in a multivariate fashion (rather than
bivariate as for oCC) (Colclough et al., 2015). Symmetric orthogonalization overcomes
the problem of spurious ghost interactions by simultaneously removing zero phase-​lag
components from all source time series using Löwdin orthogonalization for gradient
descent. All-​to-​all amplitude correlations are estimated with partial correlation of amp-
litude envelopes to keep direct and remove indirect interactions. Because the partial
correlation matrix is expected to be sparse, a graphical lasso regularization of the inverse
 BIVARIATE FUNCTIONAL CONNECTIVITY MEASURES    507

(a)
PLV (b)
iPLV
0.14 min
0.32

PLV
0.51
0.69 max
c=0

Artificial

(c) PLV (d) iPLV

0.08 min 0.07 min

iPLV
0.28 0.12
PLV

0.49 0.17
0.69 max 0.21 max

True
True
c = 0.4

Artificial
Spurious
Spurious

Figure 20.4 (A) Linear mixing leads to observations of false positive artificial PLV
interactions, within the mixing region even in the absence of true correlations. Activity of 169
uncoupled (c =​0) sources (black dots) in a 13 × 13 grid was simulated and the 20 strongest PLV
edges of the two sources-​of-​interest (centers of the cyan and red regions) are visualized. The cyan
and red color gradients indicate the Gaussian mixing strength. (B) iPLV analysis of the same
data as in A shows that iPLV does not lead to observations of artificial interactions in the ab-
sence of true interactions. (C) True phase correlations are mirrored into false positive spurious
correlations, between the two mixing regions in the condition where there is a true interaction
(c =​0.9) between two sources-​of-​interest (here the centers of the mixing regions). (D) Even
though iPLV does not yield artificial false positives, it detects the spurious “ghost” interactions
similarly to PLV. Spurious correlations arise because any two sources in separate mixing regions
partially retain the nonzero phase difference of their center sources.

covariance matrix is applied to penalize near-​zero elements, which reduces noise in the
partial correlation graph. This leads symmetric orthogonalization to attenuate both
signal-​leakage caused and true indirect couplings. The main limitations of this method
are that it is principally applicable only to the estimation of amplitude correlations and
508    J. MATIAS PALVA and SATU PALVA

that it is limited by the rank of the data due to its dependence on singular value decom-
position. For MEG/​EEG data that are preprocessed with signal space separation (SSS)
and temporal SSS methods, the rank of the data (~degrees of freedom) is often limited
to 60–​70 (Haumann et al., 2016). Thus, symmetric orthogonalization is applicable only
to cortical networks with less than ~60 parcels in total, such as the 19 regions per hemi-
sphere used in Colclough et al. (2015).
Another approach to controlling spurious connections is “hyperedge bundling”,
which uses any bivariate connectivity mapping as the basis and bundles observed
connections on the basis of their proximity in source geometry. Hyperedge bundling
reduces the false positive rate by a factor of 10-​100 with moderate to little decrease on
the true positive rate. The main advantages of this approach are that it does not involve
complex mathematical transformations prior to interaction estimation and may be used
with any bivariate metric in a manner that retains the metric’s sensitivity. Moreover,
hyperedge bundling enables high-​resolution analyses with hundreds of cortical parcels,
that is, redundant oversampling of the source space, which safeguards the analysis out-
come from the possibility that the actual neuronal source constellations or degrees of
freedom in the data are different from those of the used parcellation scheme. In the
worst-​case scenario, coarse parcellations can misrepresent or miss source areas that fall
in between the parcels or are much smaller than the parcels.
Finally, the overall effects of signal mixing on estimates of inter-​areal phase-​and
amplitude coupling can be mitigated by optimizing the MEG/​EEG inverse modelling
procedure. The inverse transformed source dipole time series can be collapsed into
parcel time series in a manner that maximizes the source reconstruction accuracy and
minimizes the effects of source leakage (Korhonen et al., 2014). The fidelity-​weighted
inverse modeling has higher reconstruction accuracy than a regular inverse operator for
the given parcellation, because it gives greater weight to sources with better reconstruc-
tion accuracy for the signals from the parcels they belong into.

20.10  Data-​driven approach

for mapping oscillatory connectomes

Initial MEG and EEG source connectivity studies used region-​ of-​
interest-​
based
approaches for phase and amplitude correlation analyses but this approach has been all
but replaced by data-​driven all-​to-​all connectivity mapping, or “connectomics”, studies.
Data-​driven analyses approaches reveal the most robust effects in data regardless of the
original hypothesis and as such provide more rigorous hypothesis testing compared to
hypothesis-​driven analyses that may be confounded by several forms of biases and ex-
plicit errors such as circularity in analysis targeting (Kriegeskorte, 2009). Data-​driven
analysis of both local and especially large-​scale oscillatory interactions provide a com-
prehensive view on brain dynamics that is not biased by selection criteria. In addition,
 BIVARIATE FUNCTIONAL CONNECTIVITY MEASURES    509

several approaches for network analysis as described below can be applied to compen-
sate for the presence of artefactual and spurious connections.
Graph theory and complex network theory enable the analysis and prediction of the
behaviors of a wide variety of complex systems. In human brain networks, these have
included graph theoretical network analysis (Bullmore & Sporns, 2009; Rubinov &
Sporns, 2010) that can also be used to characterize the properties of oscillatory networks
or connectomes that have been obtained with data-​driven analysis approaches (Palva
et al., 2010a; Palva et al., 2010b; Siebenhühner et al., 2016; Siebenhühner et al., 2020).
This approach describes oscillatory networks at three levels: at the entire graph level
(i.e., the connectome), level of edges (i.e., connections), and vertices (i.e., brain regions
or parcels). Vertex centrality estimates can be used to identify those vertices (brain
regions) that are hubs in networks of interareal oscillatory interactions and likely to
play an important role in neuronal communication. Several metrics can, in addition, be
used to characterize specific topological attributes such as clustering, path lengths, and
modularity of oscillatory networks (Palva et al., 2010b; Zhigalov et al., 2017).

20.11  Confounders in local and

inter-​areal CFC

In addition to source mixing described, estimates of CFC may be inflated by false posi-
tive couplings arising from non-​sinusoidal and nonzero mean signals. False positives
are caused by the artificial higher-​ frequency components produced when non-​
sinusoidal signals are filtered into narrow bands and by artificial lower-​frequency
components arising from filtering of nonzero-​mean waveforms. Because these are
ubiquitous in electrophysiological signals, their filter artefacts constitute a signifi-
cant confounder to CFS and PAC estimation. Approaches based on waveform analysis
(Kramer et al., 2008; Aru et al., 2015, Van Driel et al., 2015) have been proposed to reduce
the artefactual connections arising from non-​sinusoidal signals. Nevertheless, filter-​
artefact-​caused spurious CFC, in particular CFS, is difficult to dissociate from genuine
CFC by inspection of the waveform shape of any single signal in isolation. Local CFC
estimates are thus prone to ambiguous results. CFC is necessarily genuine when there
is evidence for two distinct coupled processes while spurious CFC arises from a single
process with signal components distributed to distinct frequency bands because of filter
artefacts (Figure 20.5). These two distinct processes can be identified by connection-​by-​
connection testing of whether CFC can unambiguously be attributed to two separable
processes using graph-​theoretical approaches (Figure 20.5, Siebenhühner et al., 2020).
If CFC is spurious between areas A and B, these regions are necessarily also connected
by 1:1 phase synchrony and local CFC that together may lead to a spurious observation
of inter-​areal CFC. The absence of either PS or local CFC, in contrast, indicates that the
observed inter-​areal CFC cannot be attributable to a single source and is thus genuine.
510    J. MATIAS PALVA and SATU PALVA

(a) measured signal Truth Observation

sor
sen =

Frequency
two sinusoidal processes high

+ low

OR:

Frequency Frequency
one non-sinusoidal process high

low
(b) two separable processes

B high

A low
A B A B
Area Area
1:1 coupled slow osciallations
B

Frequency
B high

A low
A
A B A B
Area Area
1:1 coupled fast oscillations
B B Frequency high

A low
A A B A B
Area Area
(c)
Genuine inter-areal CFC, unambiguous Genuine inter-areal CFC, ambiguous
high high
Frequency

low low
high high
low low
A B A B A B A B A B A B

Spurious inter-areal CFC Genuine Spurious

high observed observed
interaction interaction
low PS (LF)
high PS (HF)
CFC (local)
low CFC (inter-areal)
A B A B A B A B

Figure 20.5  Schemata for dissociating the genuine from putatively spurious CFC. (A) Spurious
observations of local are seen when a non-​sinusoidal signal is filtered. (B) Inter-​areal CFC can be
proven to be genuine if it unambiguously originates from separable neuronal signals. Spurious
inter-​areal CFC is always accompanied by spurious local CFC at one or both locations that are
also inter-​areally coupled via 1:1 phase synchrony either at low frequency or high frequency
so that a “triangle motif ” with the observed (spurious) inter-​areal CFC is formed. (C) Graph-​
theory based approach can identify all triangle motifs that might contain spurious inter-​areal
CFC. This approach only identifies those inter-​areal CFC observations as genuine, which are not
part of a full triangle motif, whereas all others are discarded. Since this may include also genuine
connections, this approach provides a lower bound for the number of genuine connections.
Modified from Siebenhühner et al., 2020.
 BIVARIATE FUNCTIONAL CONNECTIVITY MEASURES    511

REFERENCES
Abbas, A., Belloy, M., Kashyap, A., Billings, J., Nezafati, M., Schumacher, E., & Keilholz,
S. (2019). Quasi-​periodic patterns contribute to functional connectivity in the brain.
NeuroImage, 191, 193–​204. doi:10.1016/​j.neuroimage.2019.01.07
Aru, J., Aru, J., Priesemann, V., Wibral, M., Lana, L., Pipa, G., Singer, W., & Vicente, R. (2015).
Untangling cross-​frequency coupling in neuroscience. Current Opinion in Neurobiology, 31,
51–​61. doi:10.1016/​j.conb.2014.08.002
Aydore, S., Pantazis, D., & Leahy, R. M. (2013). A note on the phase locking value and its
properties. NeuroImage, 74, 231–​244.
Belloy, M. E., Naeyaert, M., Abbas, A., Shah, D., Vanreusel, V., van Audekerke, J., ... Verhoye M
(2018). Dynamic resting state fMRI analysis in mice reveals a set of quasi-​periodic patterns
and illustrates their relationship with the global signal NeuroImage, 180(Pt B), 463–​484.
doi:10.1016/​j.neuroimage.2018.01.075.
Brookes, M. J., Woolrich, M. W., & Barnes, G. R. (2012). Measuring functional connectivity
in MEG: A multivariate approach insensitive to linear source leakage. NeuroImage, 63(2),
910–​920.
Bruns, A. (2004). Fourier-​, Hilbert-​and wavelet-​based signal analysis: Are they really different
approaches? Journal of Neuroscience Methods, 137, 321–​332.
Bullmore, E. & Sporns, O. (2009). Complex brain networks: Graph theoretical analysis of
structural and functional systems. Nature Reviews Neuroscience, 10, 186–​198.
Canolty, R. T. & Knight, R. T. (2010). The functional role of cross-​frequency coupling. Trends in
Cognitive Science, 14(11), 506–​515. doi:10.1016/​j.tics.2010.09.001
Colclough, G. L., Brookes, M. J., Smith, S. M., & Woolrich, M.W. (2015). A symmetric multi-
variate leakage correction for MEG connectomes. NeuroImage, 117, 439–​448. doi:10.1016/​
j.neuroimage.2015.03.071.
Fell, J. & Axmacher, N. (2011). The role of phase synchronization in memory processes. Nature
Reviews Neuroscience, 12(2), 105–​118. doi:10.1038/​nrn2979
Hipp, J. F., Hawellek, D. J., Corbetta, M., Siegel, M., & Engel, A. K. (2012). BOLD fMRI correl-
ation reflects frequency-​specific neuronal correlation. Nature Neuroscience, 15, 884–​889.
Hirvonen, J., Monto, S., Wang, S. H., Palva, J. M., & Palva, S. (2018). Dynamic large-​scale net-
work synchronization from perception to action. Network Neuroscience, 2(4), 442–​463.
https://​doi.org/​10.1162/​netn​_​a_​0​003
Huang, N. E. & Wu, Z. (2008). A review on Hilbert‐Huang transform: Method and its
applications to geophysical studies. Reviews of Geophysics [online], 46, 1–​23.
Kramer, M. A., Tort, A. B. L., & Kopell, N. J. (2008). Sharp edge artifacts and spurious coupling
in EEG frequency comodulation measures. Journal of Neuroscience Methods, 170(2), 352–​357.
doi:10.1016/​j.jneumeth.2008.01.020
Kriegeskorte, N., Simmons, W. K., Bellgowan, P. S., & Baker, C. I. (2009). Circular analysis in
systems neuroscience: The dangers of double dipping. Nature Neuroscience, 12(5), 535–​40.
doi:10.1038/​nn.2303
Jensen, O. & Colgin, L. L. (2007). Cross-​frequency coupling between neuronal oscillations.
Trends in Cognitive Sciences, 11, 267–​269. doi:10.1016/​j.tics.2007.05.003
Lisman, J. E. & Jensen, O. (2013). The theta-​gamma neural code. Neuron, 77, 1002–​1016.
doi:10.1016/​j.neuron.2013.03.007
512    J. MATIAS PALVA and SATU PALVA

Haumann NT, Parkkonen L Kliuchko M, Vuust P , Brattico E Comparing the Performance

of Popular MEG/​EEG Artifact Correction Methods in an Evoked-​Response Study Comput
Intell Neurosci 2016;2016:7489108.
Hyafil, A., Giraud, A. L., Fontolan, L., & Gutkin, B. (2015). Neural cross-​frequency coup-
ling: Connecting architectures, mechanisms, and functions. Trends in Neuroscience, 38, 725–​
740. doi:10.1016/​j.tins.2015.09.001
Lobier, M., Siebenhühner, F., Palva, S., & Palva, J. M. (2014). Phase transfer entropy: A
novel phase-​based measure for directed connectivity in networks coupled by oscillatory
interactions. NeuroImage, 85(Pt 2), 853–​872.
Monto S, Palva S, Voipio J, Palva JM (2008) Very slow EEG fluctuations predict the dy-
namics of stimulus detection and oscillation amplitudes in humans. Journal of Neuroscience
28: 8268–​8272.
Nolte, G., Bai, O., Wheaton, L., Mari, Z., Vorbach, S., & Hallett, M. (2004). Identifying
true brain interaction from EEG data using the imaginary part of coherency. Clinical
Neurophysiology, 115, 2292–​2307.
Nikulin VV, Linkenkaer-​Hansen K, Nolte G, Lemm S, Müller KR, Ilmoniemi RJ, Curio
G. Eur J Neurosci. 2007 A novel mechanism for evoked responses in the human brain. Eur J
Neurosci. 2007 May;25(10):3146–​54.
Palva, J. M. & Palva, S. (2012). Discovering oscillatory interaction networks with MEG/​
EEG: Challenges and breakthroughs. Trends in Cognitive Sciences, 16, 219–​230.
Palva, J. M. & Palva, S. (2017). Functional integration across oscillatory frequencies by cross-​
frequency phase synchronization. European Journal of Neuroscience, 48(7), 2399–​2406.
doi:10.1111/​ejn.13767
Palva, J. M., Palva, S., & Kaila, K. (2005). Phase synchrony among neuronal oscillations in the
human cortex. Journal of Neuroscience, 25, 3962–​3397.
Palva, J. M., Monto, S., Kulashekhar, S., & Palva, S. (2010a). Neuronal synchrony reveals
working memory networks and predicts individual memory capacity. Proceedings of the
National Academy of Science of the United States of America, 107, 7580–​7585.
Palva, J. M., Wang, S. H., Palva, S., Zhigalov, A., Monto, S., Brookes, M. J., Schoffelen, J. M., &
Jerbi, K. (2018) Ghost interactions in MEG/​EEG source space: A note of caution on inter-​
areal coupling measures. NeuroImage, 173, 632–​643. doi:10.1016/​j.neuroimage.2018.02.032
Palva, S., Monto, S., & Palva, J. M. (2010b). Graph properties of synchronized cortical networks
during working memory maintenance. NeuroImage, 49, 3257–​3268.
Palva, S. & Palva, J. M. (2018). Roles of brain criticality and multi-​scale oscillations in temporal
predictions for sensorimotor processing. Trends in Neuroscience, 41(10), 729–​743. https://​
doi.org/​10.1016/​j.tins.2018.08.008
Schroeder, C. E. & Lakatos, P. (2009). Low-​frequency neuronal oscillations as instruments of
sensory selection. Trends in Neuroscience, 32, 9–​18.
Rosenblum, M. G., Pikovsky, A. S., & Kurths, J. (2004). Synchronization approach to analysis
of biological systems. Fluctuation and Noise Letters, 4, 52–​63.
Rubinov, M. & Sporns, O. (2010). Complex network measures of brain connectivity: Uses and
interpretations. NeuroImage, 52, 1059–​1069
Sinkkonen, J., Tiitinen, H., & Näätänen, R. (1995). Gabor filters: An informative way for
analysing event-​related brain activity. Journal of Neuroscience Methods, 56, 99–​104.
Tallon-​Baudry, C., Bertrand, O., Delpuech, C., & Pernier, J. (1996). Stimulus specificity
of phase-​locked and non-​phase-​locked 40 Hz visual responses in human. Journal of
Neuroscience, 16, 4240–​4249.
 BIVARIATE FUNCTIONAL CONNECTIVITY MEASURES    513

Tass, P., Rosenblum, M. G., Weule, J., Kurths, J., Pikovsky, A., Volkmann, J., Schnitzler, A.,
& Freund, H.-​J. (1998). Detection of n:m phase locking from noisy data: Application to
magnetoencephalography. Physics Review Letters, 81, 3291.
Siebenhühner, F., Wang, S. H., Arnulfo, G., Lampinen, A., Nobili, L., Palva, J. M., & Palva,
S. (2020). Resting-​state cross-​frequency coupling networks in human electrophysiological
recordings. PLoS Biology, 18(5), e3000685. https://​doi.org/​10.1371/​jour​nal.pbio.3000​685.
Siebenhühner, F., Wang, S. H., Palva, J. M., & Palva, S. (2016). Cross-​frequency synchroniza-
tion connects networks of fast and slow oscillations during visual working memory main-
tenance. Elife, 5, e13451. doi:10.7554/​eLife.13451
van Driel, J., Cox, R., & Cohen, M. X. (2015). Phase-​clustering bias in phase–​amplitude
cross-​frequency coupling and its removal. Journal of Neuroscience Methods, 254, 60–​72.
doi:10.1016/​j.jneumeth.2015.07.014
Vanhatalo, S., Palva, J. M., Holmes, M. D., Miller, J. W., Voipio, J., & Kaila, K. (2004). Infraslow
oscillations modulate excitability and interictal epileptic activity in the human cortex during
sleep. Proceedings of the National Academy of Science of the United States of America, 101,
5053–​5057.
Vinck, M., Oostenveld, R., van Wingerden, M., Battaglia, F., & Pennartz, C. M. (2011). An
improved index of phase-​synchronization for electrophysiological data in the presence of
volume-​conduction, noise and sample-​size bias. NeuroImage, 55, 1548–​1565.
Vinck, M., van Wingerden, M., Womelsdorf, T., Fries, P., & Pennartz, C. M. (2010). The pair-
wise phase consistency: A bias-​ free measure of rhythmic neuronal synchronization.
NeuroImage, 51, 112–​122.
Zhang, X., Pan, W. J., & Keilholz, S. D. (2020). The relationship between BOLD and neural
activity arises from temporally sparse events. NeuroImage, 207, 116390. doi:10.1016/​
j.neuroimage.2019
Zhigalov, A., Arnulfo, G., Nobili, L., Palva, S., & Palva, J. M. (2017). Modular co-​organization of
functional connectivity and scale-​free dynamics in the human brain. Network Neuroscience,
1(2), 143–​165.
 CHAPTER 21

MULTIVARIAT E MET H OD S
FOR FU NC T I ONA L
C ONNECTIVIT Y A NA LYSI S

SELIN AVIYENTE

21.1  Introduction

Cognition and perception are founded on the coordinated activity of neural

populations communicating among different specialized brain regions (Uhlhaas &
Singer, 2006). Neurons that synchronously oscillate across different frequency bands
provide the fundamental mechanism for information transfer (Bastos & Schoffelen,
2016), allowing coordinated activity in the normally functioning brain (Uhlhaas &
Singer, 2016; Buzsáki & Draguhn, 2004; Fries, 2009). This neural coordination is spatio-​
temporally dynamic (Lakatos et al., 2008), and the oscillatory synchronization among
different regions is dynamically adjusted based on the cognitive task (Uhlhaas & Singer,
2016). Tononi and colleagues (1998, 1994) argue that brain functionality is based on
functional segregation and integration; the former establishes that specialized activity
occurs due to segregated neuronal populations within dedicated brain regions (Rubinov
& Sporns, 2010), while the latter consists of the combination of multiple distributed
regions and serves as the basis for coherent cognition and behavior (Rubinov &
Sporns, 2010).
Methods for quantifying functional connectivity include linear correlation, mu-
tual information, coherence, synchronization likelihood, phase-​locking value (PLV)
(Lachaux et al., 1999; Aviyente et al., 2011), and pairwise phase consistency (Pereda
et al., 2005; Quiroga et al., 2002). In order to quantify both linear and nonlinear
relationships in the brain signals, phase synchronization, as defined in the context of
two chaotic oscillators, has emerged as an alternative method for the assessment of
functional connectivity and is quantified through PLV (Aviyente et al., 2011; Aviyente
 MULTIVARIATE METHODS FOR FUNCTIONAL CONNECTIVITY ANALYSIS    515

& Yener Mutlu, 2011; Dimitriadis et al., 2013). As a measure for functional connect-
ivity, PLV was introduced by Lachaux and colleagues (1999) and it estimates the syn-
chrony between two signals by looking at the circular variance of their phase difference
across trials. In comparison to other linear and nonlinear methods, PLV is more sen-
sitive to nonlinear effects (Jalili et al., 2013). In addition, this metric contributes to the
assessment of brain rhythms and their related cognitive processes, for example, alpha,
beta, delta, and theta in the low-​frequency bands and gamma bands in the higher
frequencies (Pereda et al., 2005; Lachaux et al., 1999; Aydore et al., 2013; Aviyente
et al., 2011).
Although PLV is a promising measure for quantifying functional connectivity, it
is still limited due to its bivariate nature. Specifically, it does not provide information
regarding the integration across multiple regions in the brain. In addition, functional
connectivity results from bivariate measures are difficult to interpret and computation-
ally expensive for systems with large number of regions. In order to overcome these
drawbacks, researchers propose multivariate phase synchrony measures (Stam & Van
Dijk, 2002; Carmeli et al., 2005; Mutlu & Aviyente, 2012; Al-​Khassaweneh et al., 2016).
The two main approaches to quantifying multivariate synchronization are spectral and
graph theoretic methods.
The application of bivariate measures to multivariate data sets with N time-​series
results in an N × N matrix of bivariate indices, which leads to a large amount of mostly
redundant information. Therefore, it is necessary to reduce the complexity of the data
set in such a way to reveal the relevant underlying structures using multivariate ana-
lysis methods. The basic approach used for multivariate phase synchronization is to
trace the observed pairwise correspondences back to a smaller set of direct interactions
using approaches such as partial coherence adapted to phase synchronization (Schelter
et al., 2006). Another complementary way to achieve such a reduction is cluster
analysis—​a separation of the parts of the system into different groups such that the
signal interdependencies within each group tend to be stronger than in between groups
(Newman, 2006a, 2006b). Allefeld and colleagues have proposed two complementary
approaches to identify synchronization clusters and applied their methods to EEG data
(Allefeld & Kurths, 2004; Allefeld et al., 2007; Allefeld et al., 2005; Allefeld & Kurths,
2003). Allefeld and Kurths (2004) present a mean-​field approach that assumes the ex-
istence of a single synchronization cluster that all oscillators contribute to a different ex-
tent. The authors define the to-​cluster synchronization strength of individual oscillators
to identify multivariate synchronization. This method has the disadvantage of assuming
a single cluster and thus cannot identify the underlying clustering structure. Allefeld
and colleagues (2007) introduce an approach that addresses the limitation of the single
cluster approach using methods from random matrix theory. This method is based on
the eigenvalue decomposition of the pairwise bivariate synchronization matrix and
appears to allow identification of multiple clusters. Each eigenvalue greater than 1 is
associated with a synchronization cluster and quantifies its strength within the data set.
The internal structure of each cluster is described by the corresponding eigenvector.
516   SELIN AVIYENTE

Combining the eigenvalues and the eigenvectors, one can define a participation index
for each oscillator and its contribution to different clusters. This method assumes that
the synchrony between systems belonging to different clusters (i.e. between-​cluster
synchronization) is equal to zero and requires an adjustment for proper computation
of the participation indices in the case that there is between-​cluster synchronization.
Despite the usefulness of eigenvalue decomposition for the purposes of cluster iden-
tification, Allefeld and Bialonski (2007) demonstrate that there are important special
cases—​clusters of similar strength that are slightly synchronized to each other—​where
the assumed one-​to-​one correspondence of eigenvectors and clusters is completely lost.
Other alternative measures that quantify multivariate relationships include the directed
transfer function and Granger causality defined for an arbitrary number of channels
(Granger, 1969; Baccala & Sameshima, 2001). Both of these methods have been applied
to study interdependencies and causal relationships, however, are limited to stationary
processes and linear dependencies.
On the other hand, graph theory provides the means for characterizing the
functional connections in the brain using a complex network model (Bullmore &
Sporns, 2009). Functional connectivity networks are constructed by considering
the different brain regions or electrodes/​sensors as nodes and the relationships be-
tween different nodes, quantified by bivariate functional connectivity measures such
as PLV and correlation, as edges. In this manner, functional connectivity networks
can take advantage of the widely available set of techniques for characterizing com-
plex networks. In terms of brain networks, these measures have been grouped as
measures of functional segregation and functional integration (Rubinov & Sporns,
2010). Measures of functional segregation include the clustering coefficient, tran-
sitivity, and modularity (Rubinov & Sporns, 2010; de Vico Fallani et al., 2014). On
the other hand, measures of functional integration include the characteristic path
length and the global efficiency. By computing measures that characterize network
structure, such as the small-​world measure and the degree distribution, it has been
shown that functional connectivity networks exhibit features of complex networks,
including the small-​world network (Bullmore & Sporns, 2009; Bassett & Bullmore,
2017; Bassett & Bullmore, 2006), and both small-​world and scale-​free networks
(van den Heuvel et al., 2008). Although graph theoretic measures have contributed
greatly to the advancements in the study of functional connectivity networks, these
measures present some drawbacks. Measures employed in the characterization of
network structure such as the mean clustering coefficient, the characteristic path
length and the global efficiency may be affected by certain characteristics of the net-
work. Examples include how nodes with low degree affect the clustering coefficient,
and the dependence of the characteristic path length and the global efficiency in the
shortest path between nodes, when networks may rely on other mechanisms than
the shortest path for communication.
This chapter reviews spectral, direct multivariate, and graph theoretic measures for
quantifying multivariate synchrony within a group of oscillators.
 MULTIVARIATE METHODS FOR FUNCTIONAL CONNECTIVITY ANALYSIS    517

21.2  Spectral Methods

for Multivariate Synchronization

The most common approach to quantifying multivariate connectivity is to utilize the

N × N bivariate connectivity matrix, A. Since this matrix usually contains redun-
dant information, tools from dimensionality reduction and random matrix theory are
utilized to extract information from this matrix such as the spectrum of the connectivity
matrix, that is, the distribution of the eigenvalues. There are a variety of methods used to
quantify multivariate synchrony based on the distribution of these eigenvalues.

21.2.1 S-​Estimator
S-​estimator is one of the most commonly used multivariate synchronization metrics. It
quantifies the amount of synchronization within a group of oscillators using the eigen-
value spectrum of the correlation, covariance or functional connectivity matrix:

λ log ( λ i )
N

S = 1+
∑ i =1 i
, (21.1)
log ( N )

where λ i s are the N normalized eigenvalues. This measure is complementary to the en-
tropy of the normalized eigenvalues of the correlation matrix. The more dispersed the
eigenspectrum is the higher the entropy would be. If all of the oscillations in a group are
completely synchronized, that is, the entries of the pairwise functional connectivity ma-
trix are all equal to 1, then all of the eigenvalues except one will be equal to zero, and the
value of S will be equal to 1 indicating perfect multivariate synchrony. This measure can
quantify the amount of synchronization within a group of signals and thus is useful as a
global complexity measure.

21.2.2 Omega Complexity
A variation of S-​estimator is Ω-​complexity. Using the eigenvalues of the correlation ma-
trix as λ i , the omega complexity can be computed as:

 N λ λ
Ω = exp  − ∑ i log i  . (21.2)
 i =1 N N

Ω-​complexity varies between 1 (maximum synchronization) and N (minimum syn-

chrony, i.e., maximum de-​synchronization). In order to scale the above measure
518   SELIN AVIYENTE

between a value close to 0 (for minimum synchrony) and 1 (for maximum synchrony),
one can compute Omega as 1/ Ω.

21.2.3 Global Field Synchronization

A multivariate synchronization can be calculated in frequency domain by means of
global field synchronization (GFS) measure. First, the time-​series are converted to
frequency-​domain using fast Fourier transform. This results in the sine and cosine
coefficients. At a given frequency f, the multivariate signals can be visualized in two-​
dimensional sine-​cosine maps. As the entries are getting more scattered, the phase
synchrony between them worsens. Let λ1 ( f ) and λ 2 ( f ) be the eigenvalues of the co-
variance matrix along these two vectors (coefficients of sine and cosine). GFS at a given
frequency is calculated as

λ1 ( f ) − λ 2 ( f )
GFS ( f ) = . (21.3)
λ1 ( f ) + λ 2 ( f )

If the sine-​cosine clouds lie on a straight line, one of the eigenvalues equals to 0 and
the covariance is completely explained by a single principal component; the GFS takes
a value of 1 for such cases. This corresponds to complete phase synchrony at a given fre-
quency. In a non phase-​synchronized case, the two eigenvalues are close to each other,
leading to GFS values close to 0. In order to obtain GFS values in a certain frequency
range, similar to cross-​coherence, one can get the average of GFS values over that fre-
quency range.

21.3  Direct Measures of

Multivariate Synchronization

Omega complexity and S-​estimator are all based on the computation of the covari-
ance or bivariate connectivity matrix. Therefore, the metrics are not direct measures
quantifying multivariate synchrony and will be influenced by the bias affecting bivariate
measures. A solution to this problem is to use multivariate phase synchrony (MPS)
measure, which is indeed an extension to PLV. Having extracted the instantaneous
phases from the individual time-​series (using the Hilbert transform, for instance), the
MPS is computed as

L N
1
MPS = ∑⋅
LN t =1
∑e
jΦi (t )
(21.4)
i =1
 MULTIVARIATE METHODS FOR FUNCTIONAL CONNECTIVITY ANALYSIS    519

MPS measures the mean phase coherence between the time-​series, averaged over the
observation samples. It ranges from 0 for completely unsynchronized systems to 1 for
completely synchronized systems. However, this measure does not directly quantify
the relationship of phases across oscillators as it relies on the absolute phase rather than
the phase differences. For this reason, in this section we discuss a more recent method
to quantify multivariate phase synchrony directly from the phase differences of the
observed oscillators (Al-​Khassaweneh et al., 2016; Mutlu & Aviyente, 2012).

21.3.1 Hyper-​Spherical Phase Synchrony

Bivariate phase synchrony is based on the circular variance of the two-​dimensional dir-
ection vectors on a unit circle (1-​sphere), obtained by mapping the phase differences
between two oscillators, {Φ1k,2 (t ) = Φ1k (t ) − Φ2k (t )}k =1,2,…, K where K is the total number
of trials, between the two time-​series onto a Cartesian coordinate system. If the cir-
cular variance of these direction vectors is low, the time-​series are said to be locked to
each other. This idea can be extended to the multivariate case by considering the phase
differences across M oscillators. In order to capture global phase information, the phase
difference between the phase of each oscillator and the phase of the resultant vector of
 M 
the remaining oscillators is defined, that is, θik (t ) = Φik (t ) − arg  ∑ exp jΦmk (t ) . ( )
m =1,m ≠ i 
Using the ( M − 1) angular coordinates, a direction vector Γ k (t ) =  γ 1k (t ) ,…, γ kM (t ) can
be formed by mapping the angular coordinates
( θ1 ,..., θ M −1 ) on a unit ( M − 1) -​sphere as:

           γ 1k (t ) = cos θ1k (t ) , ( )

           γ 2k (t ) = sin (θ (t )) × cos (θ (t )) ,
k
1
k
2

γ 3k (t ) = sin (θ (t )) × sin (θ (t )) × cos (θ (t )) ,

k
1
k
2
k
3


γ k
M −1 (t ) = sin (θ (t )) ×…× sin (θkM −2 (t )) × cos (θkM −1 (t )) ,
k
1

and γ kM (t ) = sin (θ1k (t )) ×…× sin (θkM −2 (t )) × sin (θkM −1 (t )) . (21.5)

For example, γ 1k (t ) is the x coordinate of a vector on the unit circle at angular pos-
ition θ1k (t ) , while γ 2k (t ) is the x coordinate of a vector on a circle with radius sin θ1k (t ) ( )
at angular position θ (t ) . Similar analysis applies to the remaining θ (t ) s. Thus, every
k
2
k
i
i −1
γ ik (t ) is just the x coordinate of a vector on a circle with radius rik (t ) = ∏ sin θkj (t ) ,
j =1
( )
520   SELIN AVIYENTE

for i = 2, 3,..., M and with a phase θik (t ) . The equation for ri (t ) shows that as i increases,
γ ik (t ) will have less impact on the overall synchrony. This means that the choice of the
first phase difference, θ1k (t ) , will have a high impact on the measured synchrony.
Equation (21.5) may also be interpreted as follows. Every γ ik (t ) is the x projection of
the y coordinate of the previous γ ik−1 (t ) on the x-​axis with a phase θik (t ) , i.e. define x
and y coordinates of the rotating vector for each trial k as

( )
γ kx1 (t ) = cos θ1k (t ) ,
          

         γ (t ) = sin (θ (t )) ,
k
y1
k
1

         γ (t ) = sin (θ (t )) × cos (θ (t )) ,

k
x2
k
1
k
2

         γ (t ) = sin (θ (t )) × sin (θ (t )) ,

k
y2
k
1
k
2

  γ (t ) = sin (θ (t )) × sin (θ (t )) × cos (θ (t )) ,

k
x3
k
1
k
2
k
3

γ (t ) = sin (θ (t )) × sin (θ (t )) × sin (θ (t )) ,

k
y3
k
1
k
2
k
3


γ k
xM (t ) = sin (θ (t )) ×…× sin (θkM −1 (t )) × cos (θkM (t )) ,
k
1

γ ky M (t ) = sin (θ1k (t )) ×…× sin (θkM −1 (t )) × sin (θkM (t )) , (21.6)

where the superscripts x and y refer to the projection coordinates.
This recursive structure in the definition of the x-​and y-​axis for each oscillator
causes a dependence of the synchrony metric on the order of the phases. To solve this
problem, we consider both the x and y coordinates for all oscillators and normalize these
i −1

( )
coordinates by dik (t ) = rik (t ) = ∏ sin θkj (t ) for i = 2, 3,..., M . This will result in unit
j =1

radius for all i. Therefore, the multivariate phase synchrony measure, hyper-​torus phase
synchrony (HTS), is given by

N
1
HTS (t ) = ∑ D (t ) k
(21.7)
N× M k =1 2

 γ kx (t ) γ ky (t ) γ kx (t ) γ ky M (t ) 
where D k (t ) =  k1 , k1 , …, kM , .
 d1 (t ) d1 (t ) d M (t ) d Mk (t ) 
This HTS metric can also be simplified as
 MULTIVARIATE METHODS FOR FUNCTIONAL CONNECTIVITY ANALYSIS    521

1
HTS (t ) = PLV12 (t ) + …+ PLVM2 (t )
M

1 M
= ∑PLVi2 (t ),  
M i =1
(21.8)

where PLVi quantifies the synchronization of each oscillator with respect to a common
reference angle with θik (t, ω ) as described above and PLVi is given by

N
1
PLVi (t ) =
N
∑ exp ( jθ (t ))
k =1
k
i

= 〈 cosθik (t )〉2 + 〈sinθik (t )〉2 . (21.9)

The maximum value of HTS is 1, when there is complete phase synchronization

among oscillators. On the other hand, HTS is theoretically 0 when the oscillators are
independent.
Some advantages of this formulation with respect to the spectral methods discussed in
the previous section is its computational efficiency and flexibility. First, for N oscillators
this metric requires the computation of N PLV values, whereas the spectral methods re-
quire the computation of N ( N − 1) pairs of PLV values. Second, this metric is directly
applicable for quantifying the synchrony within a group of oscillators, whereas the spec-
tral methods are usually applied to the whole connectivity network.

21.4  Graph Theoretic Metrics

In the last decade, connectivity-​ based methods have had a prominent role in
characterizing normal brain organization as well as alterations due to various brain
disorders. Functional connectivity networks (FCNs) are obtained by recording physio-
logical signals from different brain regions and then computing the pairwise similarity
(Stam & Reijneveld, 2007; Bullmore & Bassett, 2011). In this context, the nodes of the
network correspond to the brain regions and the edges correspond to their functional
connectivity. In the context of synchronization, the N × N bivariate connectivity ma-
trix, A can be treated as the adjacency matrix of the graph.
As with other real-​world connected systems and relational data, studying the top-
ology of interactions in the brain has profound implications in the comprehension of
complex phenomena, such as the emergence of coherent behaviour and cognition or
the capability to functionally reorganize after brain lesions (i.e. brain plasticity) (Sporns,
2018). In practice, graph metrics (or indices) such as clustering coefficient, path length
522   SELIN AVIYENTE

and efficiency measures are often used to characterize the “small-​world” properties of
brain networks. Centrality metrics such as degree, betweenness, closeness, and eigen-
vector centrality are used to identify the crucial areas within the network. Community
structure analysis, which detects the groups of regions more densely connected between
themselves than expected by chance, is also essential for understanding brain network
organization and topology.
The definition of the nodes (or vertices) for brain graphs is modality specific. In
sensor-​based modalities, such as EEG, brain nodes are commonly assigned directly
to sensors or to electrodes. However, volume conduction in EEG causes the signal at
each sensor to be a mixture of blurred activity from different inner cortical sources.
This effect can either be ignored, in which case brain nodes will suffer from a biased
non-​neural dependence, or it can be addressed in several ways, such as using spatial
filters (Kayser & Tenke, 2006), choosing functional connectivity metrics that attenuate
volume conduction (Stam et al., 2007), or using cortical source reconstruction. After
defining brain nodes, assigning links between them is the subsequent crucial modelling
step. In functional neuroimaging, the links of a brain graph are given by evaluating the
similarity between two brain signals, through functional connectivity (FC) measures
such as phase synchrony, Pearson’s correlation or coherence. FC methods fall into
two broad categories: those measuring symmetric mutual interaction (undirected
weighted links) and those measuring asymmetric information propagation (directed
weighted links). FC across N recording sites can be described by an N × N adjacency
matrix A containing all the pairwise FC measures aij corresponding to the weighted
links of the brain graph. Since most of the graph theoretic metrics are defined on
binary (unweighted) graphs, initial efforts on the analysis of brain network topologies
were implemented via the binarization of the weights using some arbitrarily chosen
thresholds with some good success. A simple way of building a graph from a weighted
FC matrix is to apply a threshold τ to each element of the matrix, such that if aij ≥ τ ,
then an edge is drawn between the corresponding nodes, but if aij < τ , no edge is drawn
(Achard et al., 2006). This thresholding operation thus binarizes the weight matrix and
converts the continuously variable edge weights to either 1 or 0. By varying the threshold
τ used to construct a binary graph from a continuous weight matrix, the connection
density of the network is made denser or less dense. If the threshold is low and many
weak weights are added to the graph as edges then the connection density will increase;
if the threshold is high and only the strongest weights are represented as edges, then
the connection density will decrease. Since the choice of τ may be arbitrary, a lot of the
binarization techniques rely on choosing a threshold to achieve a certain graph density.
Moreover, in recent work, instead of choosing a single τ , a range of τ values have been
chosen to generate multiple binary graphs from a single FC network. In this manner, the
topology of the connectivity network can be analyzed across different scales. However,
thresholding poses the problem of over-​simplifying FCNs and, more importantly, there
is no generally accepted criterion to select the threshold (Bassett & Bullmore, 2017; Lee
 MULTIVARIATE METHODS FOR FUNCTIONAL CONNECTIVITY ANALYSIS    523

et al., 2012). Moreover, the size and density of the thresholded network vary based on
the chosen threshold value (Rubinov & Sporns, 2010). Recent studies show that the sig-
nificance of the difference between groups is strongly dependent on the threshold par-
ameter, that is, the power of the statistical analysis varies with the threshold (Langer
et al., 2013). Recently, extensions of graph theoretic measures have been proposed
for weighted networks to address some of these issues (Bolanos et al., 2013; Bassett
et al., 2011). It has also been shown that graph theoretic measures, such as the clustering
measure and the small-​world parameter, are very sensitive to the size of the network,
that is, the number of nodes, and the density of the connections. Thus, comparing two
networks with different edge density may lead to wrong conclusions, making it diffi-
cult to disentangle experimental effects from those introduced by differences in the
average degree (Bassett & Bullmore, 2017; Muldoon et al., 2016). For these reasons, in
this chapter we focus on metrics suitable for undirected and weighted links.
Graphs can be investigated at different levels of scale, and specific measures cap-
ture graph attributes at local (nodal) and global (network-​wide) scales (Kruschwitz
et al., 2015; de Vico Fallani et al., 2014). Nodal measures include simple statistics such
as node degree or strength, while global measures express networkwide attributes
such as the path length or the efficiency. Intermediate scales can be accessed via hier-
archical neighborhoods around single graph elements, or by considering subgraphs
or motifs. Motifs are defined as subsets of network nodes and their mutual edges
whose patterns of connectivity can be classified into distinct motif categories. In em-
pirical networks, these categories often occur in characteristic frequencies that can be
compared with distributions from appropriate (random) null models. Even though a
multitude of graph theoretics have been defined to analyze complex networks, here we
focus on metrics that are particularly useful for characterizing functional connectivity
networks.

21.4.1 Small-​World
Watts and Strogatz (1998) showed that graphs with many local connections and a
few random long distance connections are characterized by a high cluster coefficient
(like ordered networks) and a short path length (like random networks). Such near-​
optimal networks, which are intermediate between ordered and random networks,
are designated as small-​world networks. Many neuroimaging studies have shown that
both structural and functional brain networks shared similar small-​world properties of
short path length and high clustering (Bassett & Bullmore, 2006; Bassett & Bullmore,
2017). Small-​world networks are simultaneously strongly clustered and integrated.
This phenomenon of small-​worldness is captured by the small-​world parameter, which
is the ratio of the normalized clustering coefficient to the normalized path length. For
a weighted network, the small-​world parameter is given as (Rubinov & Sporns, 2010;
Humphries & Gurney, 2008):
524   SELIN AVIYENTE

C w / Crand
w
σw = (21.10)
Lw / Lwrand

where C and Crand are the clustering coefficients of the network and a random network
with the same degree distribution, respectively, and L and Lrand are the characteristic
path lengths of the network and a random network with the same degree distribution,
respectively. In this definition, the clustering coefficient is a measure of segregation and
reflects mainly the fraction of clustered connectivity available around individual nodes.
The clustering coefficient for a weighted network is defined as (Onnela et al., 2005):

1 2tiw
Cw = ∑
N i N ki ( ki − 1)
, (21.11)

where tiw is the weighted geometric mean of the triangles around a node i.
Similarly, the characteristic path length of the network is the average shortest path
length between all pairs of nodes in the network. For a weighted network it is calculated
as (Rubinov & Sporns, 2010):

1 ∑ j N , j ≠i dij (21.12)
w

L = ∑ i N
w
,
N (n − 1)
where dijw is the shortest weighted path length between node i and j.
Even though the small-​world parameter has been widely used to characterize func-
tional brain networks, it has some shortcomings. First, it is not clear in most cases how
the small-​worldness of the brain network relates to biological properties. Second, a
single parameter that summarizes the network topology is not sufficient and does not
tell the whole story about the network structure. Third, the small-​world scalar σ can be
greater than 1 even in cases when the normalized path length is much greater than one;
because it is defined as a ratio, if C >> 1 and L > 1 , the scalar σ > 1 . This means that a
small-​world network will always have σ > 1 , but not all networks with σ > 1 will be
small-​world (some of them may have greater path length than random graphs). Finally,
the measure is strongly driven by the density of the graph, and denser networks will
naturally have smaller values of σ even if they are in fact generated from an identical
small-​world model.

21.4.2  Modularity
Among the most widely encountered and biologically meaningful aspects of brain
networks is their organization into distinct network communities or modules (Meunier,
 MULTIVARIATE METHODS FOR FUNCTIONAL CONNECTIVITY ANALYSIS    525

Lambiotte et al., 2009; Laumann et al., 2015; Chavez et al., 2010; Fair et al., 2009; Ferrarini
et al., 2009; Meunier, Archard et al., 2009; Power et al., 2011). Modules are useful to par-
tition larger networks into basic “building blocks,” that is, internally densely connected
clusters that are more weakly interconnected among each other. Modular partitions have
neurobiological significance as their boundaries separate functionally related neural
elements, define critical bridges and hubs that join communities, channel and restrict the
flow of neural signals and information, and limit the uncontrolled spread of perturbations.
There are numerous computational techniques for extracting communities and
modules from complex networks. One of the most widely used approaches in network
neuroscience is modularity maximization, which aims to divide a given network into a set of
nonoverlapping communities by maximizing a global objective function, the modularity
metric (Newman, 2006a). Originally, this metric was formulated to detect communities
whose internal density of connections is maximal, relative to a degree-​preserving null
model. A good partitioning of a network is expected to have high modularity Q with
( ) (
Q = fraction of edges within communities − expected fraction of such edges , where )
the expected fraction of edges is evaluated for a random graph.
While modularity characterizes the brain network at a finer scale compared to the small-​
world parameter, it still has some shortcomings. First, modularity maximization has some
shortcomings such as coming up with degenerate solutions, that is, numerous partitions
may result in the same value of the modularity metric. Second, modularity optimization
cannot identify modules below a certain size. One way to address these issues and repre-
sent the full multi-​scale structure of brain networks is to perform consensus clustering
across multiple spatial resolutions—​an approach that combines sampling the entire range
of possible spatial resolutions with a hierarchical consensus clustering procedure.

21.4.3  Centrality
Numerous measures quantify the potential of individual nodes and edges to influ-
ence the global state of the network. Many of them allow the identification of network
hubs generally defined as highly central parts of the network (Sporns et al., 2007). The
number of connections maintained by a node (its degree) or the combined weight
of these connections (its strength) often provides a strong indicator of influence or
centrality. Other measures of centrality take advantage of the layout of the shortest
paths within the network and record the number of such paths that pass through a
given node or edge—​a measure called the betweenness. Another way to approach
centrality is by referencing the relation of nodes and edges to a network’s commu-
nity structure. The participation coefficient quantifies the diversity of a given node’s
connections across multiple modules—​high participation indicates that many of
these connections are made across modules, thus linking structurally and function-
ally the distinct communities (Guimera & Nunes Amaral, 2005). This measure is par-
ticularly useful in brain networks as it can be applied to both structural and functional
network data.
526   SELIN AVIYENTE

21.5  Illustrative Example

This section illustrates the differences between the various multivariate metrics
introduced in this chapter. Moran and colleagues (2015) used an EEG dataset from a
previously published cognitive control-​related error processing study. The study was
designed following the experimental protocol approved by the Institutional Review
Board (IRB) of the Michigan State University. The data collection was performed in
accordance with the guidelines and regulation established by this protocol. Written and
informed consent was collected from each participant before data collection.
The experiment consisted of a speeded-​reaction Flanker task (Eriksen & Eriksen,
1974), in which subjects identified the middle letter on a five-​letter string, being con-
gruent (e.g. MMMMM) or incongruent (e.g. MMNMM) with respect to the Flanker
letters. Flanker letters (e.g. MM MM) were shown during the first 35 ms of each trial, and
during the following 100 ms the Flanker and target letters were shown on the screen.
This was followed by an inter-​trial interval of variable duration ranging from 1200 ms
to 1700 ms. A total of six blocks consisting of 80 trials composed the experiment, and
letters were changed between blocks. EEG responses were recorded by the 64 elec-
trode ActiveTwo system (BioSemi, Amsterdam, The Netherlands). The sampling fre-
quency was 512 Hz. Trials containing artifacts were rejected and volume conduction was
reduced through the Current Source Density (CSD) Toolbox (Kayser & Tenke, 2006).
A total of 18 subjects and 58 channels were considered for the analysis, for which the
total number of error trials ranged from 20 to 61. The same number of correct responses
was chosen randomly. In this example, we explore the effectiveness of the different
multivariate measures by applying them to the N × N bivariate functional connectivity
matrices corresponding to error-​related negativity (ERN) and the correct-​related nega-
tivity (CRN). Previous studies have shown that the ERN is associated with increased
synchronization in the theta band (4–​8 Hz) between electrodes in the central and lat-
eral frontal regions (Aviyente et al., 2011). For this reason, an FCN was constructed for
each subject by averaging the PLV over the time window 25–​75 ms and the frequency
bins corresponding to the theta band per subject and response type. This results in two
FCNs of size 58 × 58 per subject, one corresponding to error responses and the other to
correct responses.
Table 21.1 summarizes the results of applying four of the metrics discussed in this
chapter. For the S-​estimator and Omega complexity, in both cases the results indicate
that the FCNs for the correct response have higher levels of synchronization compared
to the error response. However, these measures do not necessarily quantify how this
increased synchronization is distributed across the network and does not reflect the
organization of the network. The graph theoretic metrics, on the other hand, address
this issue. We note that the small-​world measure is slightly higher for error networks
compared to correct ones. In particular, the FCNs constructed from error responses
are small-​world while the ones from correct response are not. This difference between
 MULTIVARIATE METHODS FOR FUNCTIONAL CONNECTIVITY ANALYSIS    527

Table 21.1 Mean ± Standard deviation of the different multivariate metrics

on example FCNs
Metric ERN CRN
S-​estimator 0.2147 ± 0.0282 0.3216 ± 0.01
Omega Complexity 0.8825 ± 0.0017 0.8891 ± 0.0006
Small-​World 1.0078 ± 0.0086 0.9938 ± 0.001
Modularity 0.0329 ± 0.0154 0.0041 ± 0.0019

small-​world parameters is statistically significant using a two-​tailed t-​test ( p < 0.001 ).

This implies that the FCN constructed from the error response is more clustered and has
smaller average path length indicating a better integreated system. Similarly, the modu-
larity values are higher for error network compared to correct FCNs with the difference
being significant ( p < 0.001 ). This difference in modularity shows that the network has
a more modular structure, that is, groups of nodes that are highly integrated, for the
error response.
Next, we illustrate the use of the direct multivariate phase synchrony measure, HTS,
on the same data. Unlike the metrics discussed earlier, HTS does not require the N × N
connectivity matrix and can be directly applied to a group of oscillators or electrodes.
A preliminary analysis shows that HTS yields increased synchronization for the cen-
tral and lateral frontal regions for the error response, whereas there is no topographical
differentiation of synchrony for the correct response. For this reason, we focus on ERN
networks and assess whether the medial and lateral electrodes formed a stronger net-
work than that between medial and occipital electrodes by computing HTS among elec-
trode FCz and the left lateral (F1, F3, F5), right lateral (F2, F4, F6), and occipital (Oz, O1,
O2) electrodes. Table 21.2 shows the multivariate synchrony among these regions, and
as expected, the medial and lateral regions exhibit higher synchrony when compared to
the medial and occipital regions. Moreover, we examined the statistical significance of
the difference in multivariate synchrony of these regions. The multivariate synchrony
among the medial and left and right lateral regions is not significantly different. On the

Table 21.2 Mean ± Standard deviation of HTS for error-​

related negativity networks over different brain
regions
Electrodes HTS
FCz,F1, F3, F5 0.2649 ± 0.049
FCz, F2, F4, F6 0.2845 ± 0.042
FCz, Oz, O1, O2 0.2294 ± 0.036
528   SELIN AVIYENTE

other hand, lateral-​medial synchrony is significantly different than that within the oc-
cipital regions.

21.6  Conclusions

This chapter reviewed different metrics that have been introduced to quantify multi-
variate synchronization in the brain. The first group of methods focus on spectral
properties of the bivariate phase synchrony matrix and as such quantify the spread of
the eigenvalues of this N × N matrix. Even though these measures are successful at
capturing the global synchronization within the brain, they do not pinpoint to the ac-
tual mechanisms underlying the observed global synchrony values. Graph theoretic
metrics, on the other hand, can characterize the network topology across multiple scales
ranging from the micro to the macro-​scale. Thus, they can provide explanations to the
observed synchrony values in terms of different network models such as small-​world
and modular structures. In order to better characterize brain networks, these analyses
need to be performed at the subnetwork level. The recently proposed hyper-​torus phase
synchrony measure addresses this issue by computing the synchronization within a
group of electrodes or a subnetwork. This type of analysis offers the best trade-​off be-
tween bivariate metrics that focus on pairs of electrodes and multivariate metrics that
focus on the whole brain.

REFERENCES
Achard, S., Salvador, R., Whitcher, B., Suckling, J., & Bullmore, E. T. (2006). A resilient, low-​
frequency, small-​world human brain functional network with highly connected association
cortical hubs. Journal of Neuroscience, 26(1), 63–​72.
Al-​Khassaweneh, M., Villafane-​Delgado, M., Yener Mutlu, A., & Aviyente, S. (2016). A measure
of multivariate phase synchrony using hyperdimensional geometry. IEEE Transactions on
Signal Processing, 64(11), 2774–​2787.
Allefeld, C. & Bialonski, S. (2007). Detecting synchronization clusters in multivariate time
series via coarse-​graining of Markov chains. Physical Review E, 76(6), 66207–​66215.
Allefeld, C., Frisch, S., & Schlesewsky, M. (2005). Detection of early cognitive processing by
event-​related phase synchronization analysis. Neuroreport, 16(1), 13–​16.
Allefeld, C. & Kurths, J. (2003). Multivariate phase synchronization analysis of EEG data. IEICE
Transactions on Fundamentals of Electronics, Communications and Computer Sciences,
86(9), 2218–​2221.
Allefeld, C. & Kurths, J. (2004). An approach to multivariate phase synchronization analysis
and its application to event-​related potentials. International Journal of Bifurcation and
Chaos, 14(2), 417–​426.
Allefeld C., Müller, M., & Kurths, J. (2007). Eigenvalue decomposition as a generalized syn-
chronization cluster analysis. International Journal of Bifurcation Chaos, 17, 3493–​3497.
 MULTIVARIATE METHODS FOR FUNCTIONAL CONNECTIVITY ANALYSIS    529

Aviyente, S., Bernat, E. M., Evans, W. S., & Sponheim, S. R. (2011). A phase synchrony measure
for quantifying dynamic functional integration in the brain. Human Brain Mapping,
32(1), 80–​93.
Aviyente, S. & Yener Mutlu, A. (2011). A time-​frequency-​based approach to phase and phase
synchrony estimation. IEEE Transactions on Signal Processing, 59(7), 3086–​3098.
Aydore, S., Pantazis, D., & Leahy, R. M. (2013). A note on the phase locking value and its
properties. Neuroimage, 74, 231–​244.
Baccala, L. A. & Sameshima, K. (2001). Partial directed coherence: A new concept in neural
structure determination. Biological Cybernetics, 84(6), 463–​474.
Bassett D. S. & Bullmore, E. (2006). Small-​world brain networks. The Neuroscientist, 12(6),
512–​523.
Bassett D. S. & Bullmore, E. T. (2017). Small-​world brain networks revisited. The Neuroscientist,
23(5), 499–​516.
Bassett, D. S., Wymbs, N. F., Porter, M. A., Mucha, P. J., Carlson, J. M., & Grafton, S. T. (2011).
Dynamic reconfiguration of human brain networks during learning. Proceedings of the
National Academy of Sciences, 108(18) 7641–​7646.
Bastos, A. M. & Schoffelen, J. M. (2016). A tutorial review of functional connectivity analysis
methods and their interpretational pitfalls. Frontiers in Systems Neuroscience [online],
9, 175.
Bolanos, M., Bernat, E. M., He, B., & Aviyente, S. (2013). A weighted small world network
measure for assessing functional connectivity. Journal of Neuroscience Methods, 212(1),
133–​142.
Bullmore E. T. & Bassett, D. S. (2011). Brain graphs: Graphical models of the human brain
connectome. Annual Review of Clinical Psychology, 7, 113–​140.
Bullmore, E. & Sporns, O. (2009). Complex brain networks: Graph theoretical analysis of
structural and functional systems. Nature Reviews Neuroscience, 10(3), 186–​198.
Buzsáki, G. & Draguhn, A. (2004). Neuronal oscillations in cortical networks. Science,
304(5679), 1926–​1929.
Carmeli, C., Knyazeva, M. G., Innocenti, G. M., & De Feo, O. (2005). Assessment of EEG syn-
chronization based on state-​space analysis. Neuroimage, 25(2), 339–​354.
Chavez, M., Valencia, M., Navarro, V., Latora, V., & Martinerie, J. (2010). Functional modu-
larity of background activities in normal and epileptic brain networks. Physical Review
Letters, 104(11), 118701.
Dimitriadis, S. I., Laskaris, N. A., & Tzelepi, A. (2013). On the quantization of time-​varying
phase synchrony patterns into distinct functional connectivity microstates (fcμstates) in a
multi-​trial visual ERP paradigm. Brain Topography, 26(3), 397–​409.
de Vico Fallani, F., Richiardi, J., Chavez, M., & Achard, S. (2014). Graph analysis of functional
brain networks: Practical issues in translational neuroscience. Philosophical Transactions of
the Royal Society B: Biological Sciences, 369(1653), 20130521.
Eriksen, B. A. & Eriksen, C. W. (1974). Effects of noise letters upon the identification of a target
letter in a nonsearch task. Perception & Psychophysics, 16(1), 143–​149.
Fair, D. A., Cohen, A. L., Power, J. D., Dosenbach, N. U. F., Church, J. A., Miezin, F. M.,
Schlaggar, B. L., & Petersen, S. E. (2009). Functional brain networks develop from a “local to
distributed” organization. PLoS Computational Biology, 5(5), e1000381.
Ferrarini, L., Veer, I. M., Baerends, E., van Tol, M-​J., Renken, R. J., van der Wee, N.
J. A., . . . Milles, J. (2009). Hierarchical functional modularity in the resting-​state human
brain. Human Brain Mapping, 30(7), 2220–​2231.
530   SELIN AVIYENTE

Fries, P. (2009). Neuronal gamma-​band synchronization as a fundamental process in cortical

computation. Annual Review of Neuroscience, 32, 209–​224.
Granger, C. W. J. (1969). Investigating causal relations by econometric models and cross-​
spectral methods. Econometrica, 37(3), 424–​438.
Giulio, T., McIntosh, A. R., Russell, D. P., & Edelman, G. M. (1998). Functional
clustering: Identifying strongly interactive brain regions in neuroimaging data. NeuroImage,
7(2), 133–​149.
Guimera, R. & Nunes Amaral, L. A. (2005). Functional cartography of complex metabolic
networks. Nature, 433(7028), 895–​900.
Humphries, M. D. & Gurney, K. (2008). Network “small-​world-​ness”: A quantitative method
for determining canonical network equivalence. PloS One, 3(4), e0002051.
Jalili, M., Barzegaran, E., & Knyazeva, M. G. (2013). Synchronization of EEG: Bivariate and
multivariate measures. IEEE Transactions on Neural Systems and Rehabilitation Engineering,
22(2), 212–​221.
Kayser J. & Tenke, C. E. (2006). Principal components analysis of Laplacian waveforms as a
generic method for identifying ERP generator patterns: I. evaluation with auditory oddball
tasks. Clinical Neurophysiology, 117(2), 348–​368.
Kruschwitz, J. D., List, D., Waller, L., Rubinov, M., & Walter, H. (2015). Graphvar: A user-​
friendly toolbox for comprehensive graph analyses of functional brain connectivity. Journal
of Neuroscience Methods, 245, 107–​115.
Lachaux, J-​P., Rodriguez, E., Martinerie, J., & Varela, F. J. (1999). Measuring phase synchrony in
brain signals. Human Brain Mapping, 8, 194–​208.
Lakatos, P., Karmos, G., Mehta, A. D., Ulbert, I., & Schroeder, C. E. (2008). Entrainment of
neuronal oscillations as a mechanism of attentional selection. Science, 320(5872), 110–​113.
Langer, N., Pedroni, A., & Jäncke, L. (2013). The problem of thresholding in small-​world net-
work analysis. PloS One, 8(1), e53199.
Laumann, T. O., Gordon, E. M., Adeyemo, B., Snyder, A. Z., Joo, S. J., Chen, M-​Y., . . . Petersen,
S. E. (2015). Functional system and areal organization of a highly sampled individual human
brain. Neuron, 87(3), 657–​670.
Lee, H., Kang, H., Chung, M. K., Kim, B-​N., & Lee, D. S. (2012). Persistent brain network homology
from the perspective of dendrogram. IEEE Transactions on Medical Imaging, 31(12), 2267–​2277.
Meunier, D., Achard, S., Morcom, A., & Bullmore, E. (2009). Age-​related changes in modular
organization of human brain functional networks. NeuroImage, 44(3), 715–​723.
Meunier, D., Lambiotte, R., Fornito, A., Ersche, K., & Bullmore, E. T. (2009). Hierarchical
modularity in human brain functional networks. Frontiers in Neuroinformatics, 3, 37.
Moran, T. P., Bernat, E. M., Aviyente, S., Schroder, H. S., & Moser, J. S., (2015). Sending mixed
signals: Worry is associated with enhanced initial error processing but reduced call for sub-
sequent cognitive control. Social Cognitive and Affective Neuroscience, 10(11), 1548–​1556.
Muldoon, S. F., Bridgeford, E. W., & Bassett, D. S. (2016). Small-​world propensity and weighted
brain networks. Scientific Reports, 6(1) 1–​13.
Newman, M. E. J. (2006a). Finding community structure in networks using the eigenvectors of
matrices. Physical Review E, 74(3), 036104.
Newman, M. E. J. (2006b). Modularity and community structure in networks. Proceedings of
the National Academy of Sciences of the United States of America, 103(23), 8577–​8582.
Onnela, J-​P., Saramäki, J., Kertész, J., & Kaski, K. (2005). Intensity and coherence of motifs in
weighted complex networks. Physical Review E, 71(6), 065103.
Pereda, E., Quiroga, R. Q., & Bhattacharya, J. (2005). Nonlinear multivariate analysis of neuro-
physiological signals. Progress in Neurobiology, 77(1–​2), 1–​37.
 MULTIVARIATE METHODS FOR FUNCTIONAL CONNECTIVITY ANALYSIS    531

Power, J. D., Cohen, A. L., Nelson, S. M., Wig, G. S., Barnes, K. A., Church, J. A., . . . Petersen, S.
E. (2011). Functional network organization of the human brain. Neuron, 72(4), 665–​678.
Quiroga, R. Q., Kraskov, A., Kreuz, T., & Grassberger, P. (2002). Performance of different
synchronization measures in real data: A case study on electroencephalographic signals.
Physical Review E, 65(4), 041903.
Rubinov, M. & Sporns, O. (2010). Complex network measures of brain connectivity: Uses and
interpretations. NeuroImage, 52(3), 1059–​1069.
Schelter, B., Winterhalder, M., Dahlhaus, R., Kurths, J., & Timmer, J. (2006). Partial phase
synchronization for multivariate synchronizing systems. Physical Review Letters, 96(20),
208103.
Sporns, O. (2018). Graph theory methods: Applications in brain networks. Dialogues in Clinical
Neuroscience, 20(2), 111.
Sporns, O., Honey, C. J., & Kötter, R. (2007). Identification and classification of hubs in brain
networks. PloS One, 2(10), e1049.
Stam, C. J., Nolte, G., & Daffertshofer, A. (2007). Phase lag index: Assessment of functional
connectivity from multi-​channel EEG and MEG with diminished bias from common
sources. Human Brain Mapping, 28(11), 1178–​1193.
Stam C. J. & Reijneveld, J. C. (2007). Graph theoretical analysis of complex networks in the
brain. Nonlinear Biomedical Physics, 1(1), 1–​19.
Stam, C. J. & Van Dijk, B. W. (2002). Synchronization likelihood: An unbiased measure of
generalized synchronization in multivariate data sets. Physica D: Nonlinear Phenomena,
163(3–​4), 236–​251.
Tononi, G., Sporns, O., & Edelman, G. M. (1994). A measure for brain complexity: relating
functional segregation and integration in the nervous system. Proceedings of the National
Academy of Sciences of the United States of America, 91(11), 5033–​5037.
Uhlhaas, P. J. & Singer, W. (2006). Neural synchrony in brain disorders: Relevance for cognitive
dysfunctions and pathophysiology. Neuron, 52(1), 155–​168.
Uhlhaas P. J. & Singer, W. (2010). Abnormal neural oscillations and synchrony in schizo-
phrenia. Nature Reviews Neuroscience, 11(2), 100–​113.
van den Heuvel, M. P., Stam, C. J., Boersma, M., & Hulshoff Pol, H. E. (2008). Small-​world and
scale-​free organization of voxel-​based resting-​state functional connectivity in the human
brain. NeuroImage, 43(3), 528–​539.
Watts, D. J. & Strogatz, S. H. (1998). Collective dynamics of “small-​world” networks. Nature,
393(6684), 440–​442.
Yener Mutlu, A. & Aviyente, S. (2012). Hyperspherical phase synchrony for quantifying multi-
variate phase synchronization. 2012 IEEE Statistical Signal Processing Workshop (SSP),
888–​891.
 CHAPTER 22

BRAIN STIM U L AT I ON
APPROAC H E S TO
INVESTIGAT E E E G
OSCILL AT I ONS

FLORIAN H. KASTEN AND

CHRISTOPH S. HERRMANN

22.1  Introduction

Several of the previous chapters in this book laid out the numerous associations be-
tween oscillatory brain activity and various domains of cognitive functioning that have
been discovered over the course of the last century. At the same time, altered patterns of
this oscillatory brain activity have been observed in many neurological and psychiatric
diseases (Herrmann & Demiralp, 2005; Uhlhaas & Singer, 2006, 2012).
The recording of brain signals using electro-​or magnetoencephalography
(EEG/​ MEG) or by means of invasive techniques (e.g., intracortical EEG or
electrocorticography), has strongly contributed to our knowledge in this area, and
will continue to do so. However, as these methods can only provide observational
data, inference about the functional role of brain oscillations for cognitive functions
remains correlational. That is, oscillatory activity is observed as the dependent vari-
able while participants are engaged in different cognitive tasks or task conditions,
which are experimentally manipulated (independent variable, Figure 22.1A). Whether
the observed oscillatory activity has a direct causal influence on the investigated
function, or whether it reflects byproducts of the underlying neural processing,
cannot be resolved by this type of experimental design. In order to demonstrate such
causal relationships, one needs to revert the design and experimentally manipulate
the oscillatory activity in question (independent variable) and measure the resulting
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    533

(a) Manipulate (Independent Variable) (b) Manipulate (Independent Variable)

20
15
A B 10
5
0
5 10 15 20
Frequency [Hz]
20
15
10
5
0
5 10 15 20
Frequency [Hz]

Measure (Dependent Variable) Measure (Dependent Variable)

20
15 100
A 10

Performance [%]
5 80
0
5 10 15 20 60
Frequency [Hz]
20 40
15
B 10 20
5
0 5 0
10 15 20
Frequency [Hz]

Figure 22.1  Experimental designs to investigate brain oscillations. (A) In traditional EEG
experiments participants are exposed to different experimental conditions (e.g. a task free fix-
ation interval and a stimulus). An EEG is recorded and the frequency content of the signal is
compared between task conditions and correlated with task performance. (B) In order to estab-
lish causal relationships between the brain oscillation and the cognitive process, one needs to
revert the design and manipulate a feature of the oscillation of interest (here power around 10 Hz)
by an intervention. If behavioral changes are observed in response to the intervention, this can be
taken as evidence for a causal involvement of the oscillations in the investigated process.

behavioral changes as the dependent variable (Bergmann et al., 2016; Herrmann et al.,
2016b; Figure 22.1B).
In principle, a variety of methods allow researchers to modulate brain oscillations.
However, many of these approaches, such as pharmacological interventions (e.g.,
Kopp et al., 2004), optogenetics (Sohal, 2012), or intracranial electrical stimulation
(Alagapan et al., 2016; Fröhlich & McCormick, 2010), are highly invasive and their ap-
plication mostly restricted to animal models and small groups of patients. For example,
light-​driven activation of fast-​spiking interneurons at 40 Hz has been shown to cause
gamma band increase of local field potentials in mice (Cardin et al., 2009) and low-​
frequency direct cortical stimulation in the alpha range has been shown induce state-​
dependent modulation of oscillatory brain activity in the alpha and theta band in
epilepsy patients (Alagapan et al., 2016). While invasive stimulation offers potential for
more reliable effects due to stronger and more focal perturbation of brain activity, they
require opening of the scalp and skull or even penetration of brain tissue making them
unsuitable for application in healthy human subjects. Other methods like rhythmic
534    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

stimulation with sensory stimuli (e.g., rhythmic visual stimulation with flickering
light causes steady state visual evoked responses) or neurofeedback training have been
shown to modulate oscillatory activity in the brain and can be applied in healthy human
subjects. However, steady-​state responses exhibit their effects on brain oscillations
indirectly via the sensory systems and it is debated whether the observed oscillatory
activity reflects a modulation of brain oscillations or merely a superposition of event-​
related potentials (but see Notbohm et al., 2016). Neurofeedback training can be used
in many different contexts, including studying higher cognitive processes. However, the
intervention is rather time consuming as the training usually requires several sessions
on separate days before its effects can be measured.
During the past decades, a branch of techniques has evolved to noninvasively
modulate brain activity by either applying magnetic pulses via transcranial magnetic
stimulation (Barker et al., 1985; Hallett, 2000), or weak electric currents by means of
transcranial electrical stimulation (tES). The latter is an umbrella term covering sev-
eral electrical stimulation methods including transcranial direct current stimulation
(tDCS), transcranial alternating current stimulation (tACS), and transcranial random
noise stimulation (Woods et al., 2016). Among these methods, the rhythmic, repetitive
application of TMS (rTMS) and tACS are considered particularly promising to study
the functional role of brain oscillations in cognition. The latter works via the application
of an alternating current usually of sinusoidal shape. Although, depending on the spe-
cific limitations of the hardware used for stimulation, almost any type of waveform can
be created (Figure 22.2). For example, recent work applied tACS using the envelope of

tDCS tACS

otDCS sawtooth tACS AM–tACS env–tACS

AM–tACS speech signal
modulating waveform env–tACS

TMS monophasic TMS biphasic

Figure 22.2  Stimulation waveforms used in tES and TMS. Top: Waveforms conventionally
used for tDCS and tACS. Middle: Alternative waveforms used to stimulate oscillatory activity
in the brain. For otDCS, a sinusoidal tACS waveform is combined with a DC offset. TACS using
sawtooth waves cause large power in the spectrum at harmonic frequencies, which makes re-
sidual artifacts easier to detect. In amplitude modulated-​tACS a high-​frequency carrier wave-
form is modulated in amplitude by a low-​frequency waveform at the frequency of the target brain
oscillation. For envelope-​tACS the stimulation waveform is extracted from the envelope of a
speech signal. Bottom: Waveform shapes of mono-​and biphasic TMS pulses.
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    535

human speech signals to improve speech intelligibility (Riecke et al., 2018; Wilsch et al.,
2018). Others administered tACS with sawtooth waves or amplitude modulated sine
waves that are supposed to allow easier removal of stimulation artifacts from concur-
rent electrophysiological recordings (Dowsett & Herrmann, 2016; Kasten et al., 2018b;
Witkowski et al., 2016). Some researchers also applied alternating currents together with
a DC offset, which has been referred to as oscillating transcranial direct current stimu-
lation (otDCS; Marshall et al., 2006; Neuling et al., 2012a). RTMS and tACS are believed
to synchronize/​entrain endogenous brain oscillations to the externally applied driving
force, thus specifically targeting the brain oscillation of interest and probing its causal
role during a particular task (Herrmann et al., 2013; Reato et al., 2013; Thut et al., 2011b,
2011a). In addition, effects outlasting the duration of stimulation by several minutes or
even hours have been observed in many rTMS and tACS studies (Veniero et al., 2015).
These findings give rise to the hope that in the future these methods may offer new
treatment options for psychiatric and neurological conditions by restoring dysfunc-
tional oscillatory activity.

22.2  Mechanisms Underlying

rTMS and tES

TMS exploits the principles of electromagnetic induction of electric fields in the brain
(Barker et al., 1985; Wagner et al., 2009). To this end, strong, transient currents are fed
through a coil of wire placed above the scalp in the proximity of the targeted brain
area. The high-​intensity current creates a magnetic field with magnetic flux passing
perpendicularly to the plane of the coil. The rapidly changing magnetic field in turn
passes through the skull and induces current in the brain tissues underneath the scalp,
flowing in loops parallel to the coil plane (Figure 22.3A; Hallett, 2000; Wagner et al.,
2009). The resulting electric fields cause changes in membrane polarization sufficiently
strong to modulate neural excitability by changing membrane polarization and even
trigger the firing of action potentials (Wagner et al., 2009). Different coil shapes, like
circular, double cone, or figure of eight, are available that vary with respect to their in-
tensity, focality, and the depth of brain areas that can be reached with the stimulation
(Hallett, 2000; Klomjai et al., 2015). TMS can be administered using different stimula-
tion protocols. The application of a single TMS pulse can already elicit effects and im-
pair visual perception (Amassian et al., 1989). Traditionally, low-​frequency rTMS (<1
Hz) is considered to suppress cortical excitability while high-​frequency rTMS (>5Hz)
is considered facilitatory (Klomjai et al., 2015). Variants of rTMS include theta burst
stimulation, where short bursts of high-​frequency stimulation (40 Hz) are repeated at
theta frequency (5 Hz). Besides the overall excitatory and inhibitory effects of rTMS,
the method can also be used to modulate and investigate brain oscillations (Hanslmayr
et al., 2014; Thut et al., 2011b).
536    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

(a) (b) (c) (d)

(e) Stim on (f)

EEG Synchronization
rTMS area

Intensity [a.u.]
oscillation adapts fully synchronized
EEG
tACS

0
∆Frequency [Hz]
(g)
Synchronization
area
Intensity [a.u.]

1:3 1:2 2:3 1:1 3:2 2:1 3:1

Frequency ratio [n:m]

Figure 22.3  Modes and mechanisms of stimulation. (A) Figure-​eight coil TMS and induced
magnetic/​electric field. (B) Simple tACS montage with electrodes placed above Cz and Oz of the
international 10–​20 system to target occipital-​parietal regions. (C & D) Electrode montages to
modulate inter-​hemispheric synchronization. Stimulation between electrode pairs is applied ei-
ther in-​phase (C) or anti-​phase (D). (E) Synchronization of endogenous brain oscillations to ex-
ternal stimulation via rTMS (top) and tACS (bottom). The external driving force causes the brain
oscillation to adapt in frequency and phase to the stimulation. Due to the increased synchronous
neuronal activity, an amplitude increase is expected. Please note that real EEG recordings are
strongly corrupted by artifacts arising from stimulation. (F) The “Arnold tongue” illustrates the
relationship between the intensity of a driving force coupled to an oscillator and their frequency
differences on the resulting synchronization. The farther apart the frequency of the driving
force and the oscillator, the higher the intensity needed to cause the oscillator to synchronize.
If the frequencies of the oscillator and driving force match, very small intensities are needed.
(G) Arnold tongues at different n:m (n perturbations within m oscillatory cycles) frequency
ratios.
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    537

In contrast to TMS, tES methods like tDCS and tACS have much more subtle effects
on neuronal activity. Here, a direct or alternating current is passed through the scalp
by two or more stimulation electrodes (Figure 22.3B–​D). Commonly, saline soaked
sponge electrodes, fixed to the scalp via rubber bands, or electrically conductive rubber
electrodes attached using a conductive, adhesive paste are used for this purpose.
Some systems also make use of Ag/​AgCl electrodes similar to those used in standard
EEG systems. Results from simulations of the current flow through the head, as well
as findings from invasive recordings in animals and human cadavers suggest that a
large proportion of the current is directly shunted through the skin (Miranda et al.,
2006; Neuling et al., 2012b; Opitz et al., 2016; Vöröslakos et al., 2018). However, at the
same time, small amounts of the injected current still reach the target regions in the
brain. In case of tDCS, these currents shift the resting potentials of the stimulated
neurons, resulting in slight depolarization of the cell membrane under the anode and
hyperpolarization under the cathode. While these changes in membrane potentials are
too small to directly elicit neural firing, early work on animal models in vivo and in
vitro suggests that they can alter neuronal excitability by shifting the membrane poten-
tial such that more or less incoming excitatory postsynaptic potentials are required to
reach the cells’ firing threshold (Bikson et al., 2004; Bindman et al., 1964; Creutzfeldt
et al., 1962; Jefferys, 1981).
When an alternating current is applied (e.g., via tACS), the electric field rhythmic-
ally alternates between hyperpolarizing and depolarizing the cell membrane during
the negative and positive half cycles of the sinusoidal stimulation waveform. Computer
simulations as well as in vivo and in vitro recordings demonstrated that these phasic
modulations of membrane polarization temporally align neural firing to the frequency
of the externally applied stimulation (Deans et al., 2007; Fröhlich & McCormick, 2010;
Krause et al., 2019; Ozen et al., 2010; Reato et al., 2010). The electric field strengths neces-
sary to achieve this effect are comparable to the electric fields reaching cortical pyram-
idal cells during tES (Antal & Herrmann, 2016; Opitz et al., 2016).
Although the mechanisms of tACS and rTMS differ in terms of their effects on the
cellular level, both techniques are assumed to cause synchronization/​entrainment of the
endogenous oscillatory brain activity to the external driving force (Thut et al., 2011a).
Synchronization phenomena can be observed everywhere in nature, from chirping of
crickets to the beating of the heart, as well as in human-​made technical systems like pen-
dulum clocks or electric circuits. The basic principles of these phenomena are universal
and can be described using the framework of synchronization theory (Pikovsky et al.,
2003). Synchronization requires the presence of a so-​called self-​sustained oscillator.
Such oscillators are characterized by an internal source of energy, allowing the oscillator
to exhibit some sort of rhythmic activity until the energy source is consumed (Pikovsky
et al., 2003). If two or more oscillators with similar eigenfrequencies (i.e., the frequency
at which a system tends to oscillate in the absence of any external driving force) are
weakly coupled, their rhythmic activity synchronizes; that is, they align their rhythmic
activity in frequency and phase (Pikovsky et al., 2003). Similarly, if coupled to an ex-
ternal driving force, the oscillator synchronizes in frequency and phase to the external
538    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

signal. Importantly, the further apart the frequency of the external force is to the eigen-
frequency of the oscillator, the more energy is needed to synchronize it (Pikovsky et al.,
2003). Driving forces at frequencies too far away from the oscillators’ eigenfrequency
and with too little strength cannot achieve synchronization. In contrast, driving forces
that exactly match the frequency of the oscillator can achieve synchronization even at
very small intensities. When the relationship between frequency difference and driving
force strength on the synchronization strength is visualized in a diagram with synchron-
ization strength coded in color, a triangular shape can be observed, which has been
referred to as the Arnold Tongue (Figure 3G; Pikovsky et al., 2003). Besides 1:1 frequency
matching between oscillator and driving force, synchronization can also occur if the
driving force perturbs the oscillator at harmonic or subharmonic frequencies. Such har-
monic entrainment can occur for any n:m (n perturbations within m oscillatory cycles)
frequency relationship (where n, m ∈ ). For example, an oscillator with a frequency of
10 Hz synchronizes to driving forces with frequencies around 10 Hz, but also to those
with 2.5 Hz, 3.33 Hz, 6.66 Hz, 15 Hz, 20 Hz, and 30 Hz, corresponding to the 1:3, 1:2, 2:3,
3:2, 2:1, and 3:1 Arnold tongues (Figure 22.3G). The strength of synchronization decays
the higher the harmonic frequency of the external driving force is (Pikovsky et al., 2003).
In the human brain, synchronization of oscillatory activity to external driving
forces has been observed in response to flickering light stimulation (Herrmann, 2001;
Notbohm et al., 2016) and rTMS (Herrmann et al., 2016a; Thut et al., 2011b). Further,
the effect of sinusoidal alternating currents on local field potentials and multi-​unit ac-
tivity follows the rules of synchronization theory in computer simulations as well as
in in vivo and in vitro recordings (Fröhlich & McCormick, 2010; Krause et al., 2019;
Negahbani et al., 2018; Ozen et al., 2010; Reato et al., 2010). However, as recordings of M/​
EEG activity during stimulation are contaminated by a strong, electromagnetic artifact,
direct evidence for these mechanisms of actions for tACS effects in humans is largely
missing so far (an overview of approaches for tACS artifact removal in M/​EEG and their
associated problems is reviewed in Kasten & Herrmann, 2019).
These mechanisms describe the general framework currently assumed to underlie
effects of rTMS and tACS during stimulation (also called online effects). A common ob-
servation in brain stimulation experiments is that behavioral and physiological effects
persist after the stimulation is switched off (reviewed in Veniero et al., 2015). These
aftereffects (or offline effects) can last for several minutes or even hours after both rTMS
(Schindler et al., 2008; Schutter et al., 2001) and tACS (Kasten et al., 2016; Neuling et al.,
2013; Wischnewski et al., 2018). After tACS, these outlasting effects tend to be rather fre-
quency specific. The application of rTMS, in contrast, seems to elicit more broadband
aftereffects in all frequency bands irrespective of the stimulation frequency (Veniero
et al., 2015). While the pattern of effects observed during this sustained period may
appear similar to those observed during stimulation, it is important to emphasize that
the underlying mechanisms responsible for those effects may be different. This phe-
nomenon has been well documented for effects of tDCS on motor evoked potentials
(MEPs). Here, the selective, pharmacological blockage of NMDA receptors abolished
the induction of long-​lasting aftereffects, while not affecting online effects of the
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    539

stimulation (Nitsche et al., 2003). In contrast, blockage of calcium and sodium channels
abolished or reduced the enhancing effect of anodal tDCS on MEP size during and after
stimulation (Nitsche et al., 2003). These results indicate that the online effect of tDCS
depends on membrane polarization, modulating the conductance of sodium and cal-
cium channels. Offline effects appear to be caused by NMDA receptor mediated plas-
ticity, although online effects seem to be necessary to induce the offline effect (Nitsche
et al., 2003).
While the mechanism underlying online effects of rTMS and tACS is assumed to be
entrainment, offline effects have been suggested to be caused by entrainment echoes, a
state of sustained synchronization after stimulation is switched off (Hanslmayr et al.,
2014), or processes of spike-​timing dependent plasticity (STDP; Vossen et al., 2015;
Zaehle et al., 2010). STDP relies on the temporal relation of pre-​and postsynaptic
potentials. If a presynaptic potential repeatedly precedes a postsynaptic potential, the
synaptic connection is strengthened, which is referred to as long-​term potentiation
(LTP). If the presynaptic potential repeatedly follows the postsynaptic potential, long-​
term depression (LTD) occurs and the synaptic connection is weakened (Markram
et al., 1997). In a neural circuit that generates an oscillation, pathways exist by which the
activity of a neuron is fed back to its own synaptic input connections via other neurons.
Depending on the length and speed of these connections, each spike requires a certain
time to travel through these circuits, which determines its intrinsic frequency (Zaehle
et al., 2010). Following the principles of STDP, repetitive stimulation (e.g., with rTMS or
tACS) with frequencies slightly below the circuits’ intrinsic frequency should lead to a
strengthening of synaptic connections because stimulation can systematically precede
the circulating action potentials. The application of other frequencies in turn, cannot
cause such effects, as the stimulation does not match the circuits’ intrinsic frequency,
and membrane polarization does not coincide with incoming neural spiking (Vossen
et al., 2015; Zaehle et al., 2010).
Although entrainment echoes may exist during the first few seconds after stimula-
tion, the STDP model seems more suited to explain the long-​lasting changes elicited
by tACS and rTMS, which have been observed for up to an hour (Kasten et al., 2016;
Veniero et al., 2015; Vossen et al., 2015). Wischnewski and colleagues (2018) provided
direct evidence for such involvement of synaptic plasticity in the generation of tACS
aftereffects. In that study, administration of an NMDA receptor antagonist was observed
to abolish aftereffects induced by tACS in the beta range over the primary motor cortex.
This suggests a role of NMDA receptor-​mediated plasticity in the generation of tACS
aftereffects similar to those observed after tDCS (Nitsche et al., 2003).

22.3  Targets for Brain Stimulation

During the design of a brain stimulation experiment a couple of choices have to be made
that can severely impact both the stimulation success and the interpretability of results.
540    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

This section provides an overview of these choices and examples of how different
features of brain oscillations are targeted to investigate their causal role for different
domains of cognitive functioning.
Usually, the design process starts with identifying a brain oscillation that correlates
with a cognitive function, or ideally an output measure of a concrete task (e.g., reac-
tion time or performance). Depending on the kind of association, brain stimulation can
be used to target different features of the oscillation, such as its amplitude, frequency,
or phase. Some relationships may also depend on cross-​frequency interactions (Palva
et al., 2005) or synchronization between distinct brain areas (Siegel et al., 2012). Another
important aspect is related to the stimulation montage. One needs to decide about the
positioning and orientation of the stimulation electrodes or the TMS coil. Usually, the
observed correlations between a cognitive function and a brain oscillation are limited to
specific areas of the brain. Oscillations in the same frequency range may serve different
functions within distinct areas of the brain. Based on neuroimaging results, for ex-
ample, from source localization of oscillatory activity, a target region in the brain is
derived and a montage is chosen that maximizes the electric field strength in this area.
A couple of software tools are available that simulate the expected current flow caused
by transcranial magnetic and electrical stimulation (e.g., ROAST: Huang et al., 2017a;
Simnibs: Thielscher et al., 2015). Recent validation studies using invasive electrophysi-
ology in animals and humans indicate that these models are able to predict the spa-
tial extent of the electric field in the brain quite accurately but tend to overestimate the
strength of the induced electric fields (Huang et al., 2017b; Opitz et al., 2016). Even more
advanced tools are able to automatically optimize electrode montages to target specific
brain areas with specific directions of current flow (Baltus et al., 2018b; Huang et al.,
2018; Saturnino et al., 2019; Wagner et al., 2016).
As soon as a feature of an oscillation and a brain region are selected for stimulation,
appropriate control conditions for the experiment must be established. The choice
of adequate control conditions is not a trivial problem. Stimulation using TMS or
tACS can induce visual and somatosensory perceptions that may confound results if
compared to a stimulation-​free control condition (Schutter, 2016; Turi et al., 2013, 2014).
In addition, one would ideally compare the selected stimulation condition with stimu-
lation of all other possible stimulation frequencies at all possible brain regions in order
to demonstrate frequency and region-​specific effects. However, due to a huge param-
eter space this is practically impossible. Let us consider a very simple case of tACS with
only two electrodes that can be placed on any of the 32 locations of the international
10–​20 system for EEG electrodes. In addition, stimulation frequencies are limited to
only one frequency within each of the five major EEG frequency bands. This param-
eter space already amounts to almost 5,000 possible control conditions. The inclusion
of more fine-​grained electrode locations and stimulation frequencies or stimulating at
different intensities easily increases the number of possible control conditions to sev-
eral million. In practice, stimulation of the target oscillations is thus usually compared
to one or two control frequencies applied to the same region, or the same stimulation
frequency is applied to one or two control regions. Other researchers also compare
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    541

stimulation effects against a sham stimulation. During sham stimulation, stimulation

is usually applied in a way that mimics visual and somatosensory sensations, but that
is considered ineffective in modulating brain activity. The aim is to blind participants
towards their experimental condition and to avoid confounds of behavioral results by
participants’ expectations. The exact choice of appropriate control conditions heavily
depends on the research question and should allow to rule out alternative explanations
how stimulation may have affected the task.
A straightforward target for stimulation, and probably the most popular, is the amp-
litude of a brain oscillation. Several studies demonstrated that tACS and rTMS can
elevate the power of brain oscillations in the range of the stimulated frequency band
(Kasten et al., 2016; Vossen et al., 2015; Wischnewski et al., 2018; Zaehle et al., 2010).
Moreover, both techniques have been shown to also modulate event-​related changes
in oscillatory power (Kasten et al., 2018a; Kasten & Herrmann, 2017; Klimesch et al.,
2003; Wischnewski & Schutter, 2017). While rTMS is frequently used to stimulate os-
cillatory activity during specific periods of a task (Hanslmayr et al., 2014; Klimesch
et al., 2003; Romei et al., 2010), similar protocols using tACS show less-​reliable
effects (Braun et al., 2017; Stonkus et al., 2016), which might be explained by insuffi-
cient stimulation durations or state-​dependent effects (Kasten et al., 2018a; Kasten &
Herrmann, 2017; Strüber et al., 2015). More commonly, tACS is applied in a continuous
manner while participants are engaged in a cognitive task. Such continuous stimula-
tion during tasks that involve induced event-​related oscillations appears to foster the
pre-​existing patterns of event-​related power change (Kasten et al., 2018a; Kasten &
Herrmann, 2017).
Boosting oscillatory activity with rTMS has been used to study the role of posterior
pre-​stimulus alpha oscillations for basic visual perception (Romei et al., 2010), as well
as for higher visual-​spatial processing (Klimesch et al., 2003) and short-​term memory
(Sauseng et al., 2009). Enhancing beta oscillations with rTMS disrupted the encoding
of items in a verbal memory task (Hanslmayr et al., 2014). In these experiments, authors
applied short trains of rTMS in the frequency band of interest to specifically alter the
amplitude of the oscillation during certain time intervals (e.g., before or after stimulus
presentation). To demonstrate that the observed behavioral changes are specific to one
frequency band, the authors also applied stimulation at control frequencies where no
effects were expected (and indeed not found).
As outlined, tACS (and its derivative otDCS) are mostly applied in a continuous
manner. One of the first applications was to increase slow-​wave oscillations during sleep
to probe their role for memory consolidation (Marshall et al., 2006). Here, participants’
memory performance significantly increased after stimulation during overnight sleep
as compared to a control condition. In the awake brain, tACS has been used to study the
role of alpha amplitude in creativity (Lustenberger et al., 2015), visual-​spatial cognitive
performance (Kasten & Herrmann, 2017), attention (Wöstmann et al., 2018, Kasten et al,
2020), and many more cognitive domains (for a recent overview see Klink et al. 2020).
In these experiments, tACS was applied continuously over a brain region during task
execution to increase participants’ alpha amplitude.
542    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

If the frequency of a brain oscillation is of interest, one would try to speed up or slow
the target oscillation by applying stimulation at frequencies slightly above or below its
intrinsic frequency. According to synchronization theory, such stimulation should shift
the intrinsic frequency in the brain towards the frequency of the external driving force
(Pikovsky et al., 2003). This approach has been used, for example, to investigate the causal
role of occipital alpha oscillations in the generation of the sound-​induced double-​flash
illusion (Cecere et al., 2015). The illusion occurs when two sound beeps are presented
within a time window of ~100 ms together with a single visual flash. Participants per-
ceive a second illusory flash in this kind of experiment (Shams et al., 2002). The authors
were able to alter the length of the temporal window during which the illusion occurs by
stimulating participants ± 2 Hz above or below their individual alpha frequency (Cecere
et al., 2015). In another experiment, the perceived frequency of an illusory jitter was
modulated in a similar manner by applying amplitude modulated tACS ± 1 Hz above or
below participants’ individual alpha frequency (Minami & Amano, 2017). In the audi-
tory domain, tACS has been used to test whether the frequency of gamma oscillations
determines the temporal resolution of the auditory system. In that study, participants
were stimulated above or below their individual gamma frequency (Baltus et al., 2018a,
2018b). By accelerating the individual gamma frequency, participants were able to de-
tect smaller gaps in continuous sound streams of noise. However, when the individual
gamma frequency was decelerated, no modulation of gap detection performance was
observed (Baltus et al., 2018a, 2018b). Beyond investigations into basic sensory pro-
cessing, the frequency of brain oscillations had also been modulated in the context of
working memory performance. It is well known that humans can uphold 7 ± 2 items in
their working/​short term memory (Miller, 1956). Later, this capacity has been associated
with individual gamma and theta frequencies. Specifically, it is argued that the number
of gamma cycles that fit into the positive half wave of a theta oscillation determines the
capacity (Lisman & Idiart, 1995; Lisman & Jensen, 2013). Vosskuhl and colleagues (2015)
tested this relationship and demonstrated that slowing down participants’ theta fre-
quency with tACS such that more gamma cycles fit into one theta oscillation increased
working memory capacity in a digit span task.
Investigations into the role of oscillatory phase or phase relationships for cogni-
tion are comparatively challenging as they require precise stimulus timing or complex
stimulation protocols. Neuling and colleagues (2012a) presented brief auditory targets
at specific phases of a 10 Hz otDCS waveform applied to the auditory cortex. In line
with previous correlational evidence (Mathewson et al., 2009), participants’ detection
performance systematically varied depending on the phase of the 10-​Hz stimulation
at which the target was presented. Similar modulations of detection performance with
tACS phase was found for 4-​Hz stimulation in an auditory detection task (Riecke et al.,
2015) and for stimulation of somatosensory cortex at mu frequency in a somatosensory
detection task (Gundlach et al., 2016). In a different type of experiment, authors applied
tACS to two distinct brain regions with the same stimulation waveform applied either
in or out of phase (with 0-​or 180-​degree phase shift, Figure 22.3C,D). This way, stimula-
tion is thought to either increase (in phase) or decrease (out of phase) the synchrony of
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    543

the targeted brain regions within a specific frequency band. Such modulation of inter-​
regional synchrony, when applied in the gamma frequency range, modulates percep-
tion of ambiguous movements (Helfrich et al., 2014a; Strüber et al., 2014). Increasing/​
decreasing fronto-​parietal synchronization in the theta frequency range in the left
hemisphere with in-​phase vs. anti-​phase tACS has been shown to increase/​decrease
reaction times in a visual memory-​matching task (Polanía et al., 2012). Other authors
extended this concept to even target interpersonal synchrony (Novembre et al., 2017;
Szymanski et al., 2017). In one study, tACS in the beta range was simultaneously applied
to the motor cortex of two participants (Novembre et al., 2017). Here, in-​phase stimula-
tion in the beta range increased synchrony in a joint finger tapping task as compared to
anti-​phase stimulation or sham. No such effect was found for stimulation in other fre-
quency bands. In another study, simultaneous tACS with same-​phase same-​frequency
vs. different-​phase different-​frequency in the theta range over fronto-​parietal sites did
not show effects on a synchronous drumming task (Szymanski et al., 2017). An im-
portant concern about in-​phase vs. anti-​phase stimulation protocols has been raised
recently. In order to directly infer a phase dependent relationship of a behavioral
measure and a brain oscillation, it is crucial that the only difference between stimu-
lation conditions is in the phase difference between the stimulated areas. Saturnino
and colleagues (2017) simulated the electric fields created by different stimulation
montages targeting inter-​regional synchrony with in-​phase and anti-​phase stimulation.
Their results demonstrated that the electric field patterns differed during in-​and anti-​
phase stimulation for many of the employed montages, giving rise to the concern that
effects of the stimulation could also originate from differences in field strength or even
differences in the brain regions that have been (co-​)stimulated during the in-​and anti-​
phase stimulation (Saturnino et al., 2017). However, the authors also suggest stimulation
montages that can avoid such confounds. Especially, montages using a stimulation elec-
trode in the center, surrounded by several return electrodes or a large ring electrode, are
recommended to avoid such confounds (Saturnino et al., 2017).
Besides direct targeting of a brain oscillation with stimulation of the same frequency
band, sometimes cross-​frequency interactions are of interest or used to indirectly
modulate an oscillation via stimulation of a different frequency band. For example,
oscillations in the alpha and gamma range are well known to show an antagonistic re-
lationship. When alpha oscillations increase, gamma oscillations are suppressed, and
vice versa (Jensen & Mazaheri, 2010). Some authors therefore applied stimulation in
the gamma frequency range to suppress alpha oscillations (Boyle & Frohlich, 2013). As
increased activity in the alpha band is negatively correlated with vigilance. This antag-
onistic stimulation approach has recently been used to counteract increasing reaction
times in a sustained attention task (Loffler et al., 2018). Along the same lines, rTMS in the
alpha range has been observed to alter alpha-​gamma cross-​frequency coupling during
a visual working memory task (Hamidi et al., 2009). An exceptionally sophisticated
tACS cross-​frequency protocol has been used to study theta-​gamma coupling in a
working memory task. As discussed earlier, short-​term or working memory capacity is
thought to depend on the number of gamma oscillations that fit into the positive half of
544    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

a theta cycle (Lisman and Idiart, 1995; Lisman and Jensen, 2013), and can be increased
by slowing the frequency of fronto-​parietal theta oscillations (Vosskuhl et al., 2015).
To further study the relationship of theta and gamma oscillations in working memory,
Alekseichuk and colleagues (2016) applied tACS using short trains of a high-​frequency
stimulation at different gamma frequencies superimposed on either the positive or the
negative half wave of a slow stimulation waveform in the theta range. In that study, only
gamma stimulation applied during the positive but not during the negative half of the
theta cycle fostered participants’ working memory performance.
The aforementioned studies exemplify how brain stimulation can be used to study
the role of various features of oscillatory brain activity for cognition. Especially tACS
can be used very flexibly. As it allows high control over timing and waveform shapes, it
can be used to study complex phase or cross-​frequency relationships. In contrast, rTMS
protocols allow to stimulate during specific, transient time periods of a cognitive pro-
cess as it induces stronger/​faster effects.

22.4  Combining brain stimulation

and neuroimaging

A major challenge in the context of brain stimulation is the measurement of stimu-

lation effects. Ideally one would like to monitor the changes in brain activity elicited
by stimulation that cause the behavioral effects. This would not only allow validation
of whether a technique induced its effects on brain activity in the expected direction
but also strengthen our knowledge about the general mechanisms of stimulation.
Although there are elaborate theories about the mechanisms underlying stimulation
effects backed up by evidence from animal models and computer simulations, direct
observations into these mechanisms in humans are sparse and difficult to obtain. The
application of strong magnetic fields or electric currents introduces massive distortions
to electrophysiological recordings (e.g., M/​EEG). Naturally, these distortions are several
orders of magnitude larger than the concurrently recorded brain signals and in most
cases spectrally overlap with the brain oscillation of interest (Kasten et al., 2018a).
In recent years, different strategies have been employed to measure effects of
stimulation on human brain activity. A common approach is to discard the artifact-​
contaminated recordings obtained during stimulation and to focus on aftereffects in
M/​EEG. Such aftereffects are commonly observed after rTMS and tACS at different
frequencies (Veniero et al., 2015) and have been related to sustained alterations of be-
havioral measures (Kasten and Herrmann, 2017). On the one hand, these after effects
offer important evidence for the ability of brain stimulation techniques to modulate
brain oscillations. Such sustained changes are of major interest, especially in the con-
text of potential clinical applications. Only if the stimulation can elicit long-​lasting
changes of dysfunctional oscillatory activity can it offer real potential for the treatment
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    545

of neurological or psychiatric disorders. On the other hand, the mechanisms of action

underlying online effects and aftereffects may be different. Online effects of rTMS
and tACS are usually assumed to result from entrainment of the endogenous brain
oscillations, whereas offline effects are likely to result from mechanisms of synaptic
plasticity (Vossen et al., 2015; Wischnewski et al., 2018; Zaehle et al., 2010). While there
might be some relation between online effects and aftereffects (Helfrich et al., 2014b),
inference about online effects from aftereffects is inherently difficult and cannot substi-
tute direct measurements.
Some researchers have recorded brain signals during stimulation using measurement
modalities that are less susceptible to distortions of the stimulation. For example, fMRI
can be recorded during tACS with little to no distortions introduced to the signal (Antal
et al., 2014; Vosskuhl et al., 2016). Initial studies were able to show that stimulation
with tACS at different frequencies can modulate the blood-​oxygen-​level-​dependent
(BOLD) response (Violante et al., 2017; Vosskuhl et al., 2016) and connectivity profiles
(Cabral-​Calderin et al., 2016; Violante et al., 2017; Weinrich et al., 2017). This way, the
authors were able to causally test relationships between brain oscillations and specific
patterns of BOLD-​signal activation previously observed in concurrent EEG-​fMRI (e.g.,
Goldman et al., 2002; Laufs et al., 2003). A major drawback of this approach is, how-
ever, that the hemodynamic response measured in fMRI is a rather indirect measure
to draw conclusions about effects of stimulation on oscillatory activity in the brain. In
order to obtain direct insights to the effects occurring during stimulation, simultan-
eous recordings of electrophysiological signals with EEG and MEG and are ultimately
required. In recent years different strategies have been developed with the ambitious
goal to clean these recordings from the massive stimulation artifacts.
The magnetic fields generated by TMS are too strong to be measured in the MEG, as
the pulses will harm the sensitive electronics of the systems. Concurrent recording of
EEG signals during TMS application is generally feasible, albeit technically challenging.
Each TMS pulse is accompanied by a couple different artifacts that need to be considered
during the conductance of the measurements and data analysis (Ilmoniemi et al., 2015;
Ilmoniemi & Kičić, 2010; Veniero et al., 2009). Although the TMS pulses themselves
only last for less than a millisecond, the strong electromagnetic artifact can induce
eddy currents to EEG leads that can saturate EEG amplifiers for several hundreds of
milliseconds and polarize electrode contacts. Specialized TMS compatible EEG hard-
ware has been developed to handle this strong distortion without saturation. With
such specialized hardware, the duration of intervals contaminated with the TMS arti-
fact can be reduced to ~5 ms (Veniero et al., 2009). In addition to the TMS pulse it-
self, recharging of capacitors in the TMS electronics can induce a second artifact in the
EEG signal. Depending on the stimulation intensity, this artifact can follow the pulse by
some tens of milliseconds (Veniero et al., 2009). Apart from electromagnetic artifacts,
the strong stimulation has the potential to trigger different physiological responses like
eye movements/​blinks and muscle artifacts. Further, the strong magnetic force can
cause vibration of the coil and click sounds which can elicit unwanted somatosensory
or auditory evoked potentials (Ilmoniemi & Kičić, 2010; Rogasch et al., 2017). In order
546    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

to obtain meaningful results from concurrent TMS-​EEG, one needs to account for these
artifacts—​ideally by avoiding/​reducing them when performing the experiment, for ex-
ample, by carefully arranging the EEG cables relative to the coil or by slowing down the
recharging times of the TMS device (Veniero et al., 2009). The remaining distortions in
the signal have to be removed by advanced data processing procedures.
The data segment containing the massive, sharp artifact of the TMS pulse (lasting 10–​
25 ms after the pulse) is commonly removed from the data and subsequently replaced
by a linear or cubic interpolation (Bergmann et al., 2012; Thut et al., 2011b). The same
approach can be used to get rid of the recharger artifact following the pulse (Thut
et al., 2011b). However, here the latency of the artifact has to be carefully identified as
the artifact strongly depends on the TMS intensity (Veniero et al., 2009). To remove
physiological artifacts from eye movements or muscle activity, blind-​source separation
methods such as principle component analysis (PCA), independent component ana-
lysis (ICA), or signal space projection are widely used (Ilmoniemi et al., 2015; Rogasch
et al., 2017).
Transcranial alternating current stimulation can be measured using both EEG and
MEG. Again, the stimulation contaminates the recorded signals with a strong elec-
tromagnetic artifact and recording hardware with sufficient dynamic range is needed
to avoid saturation of the recordings. When combined with EEG, direct connection
of stimulation and recording electrodes via bridges of gel or saline solution should be
avoided. When used in the MEG, stimulation parameters should be carefully tested
on a phantom head to rule out that the electromagnetic artifact imposes harm to the
sensor array. In contrast to the transient stimulation pulses used in TMS, tACS applies
a continuous alternating current. Consequently, recordings will not contain artifact-​
free segments as long as the stimulation is switched on, precluding the use of interpol-
ation methods as with TMS. During the last couple of years different strategies have
been employed aiming to suppress the tACS artifact from M/​EEG recordings (Kasten &
Herrmann, 2019).
In concurrent tACS-​EEG, some authors created a template of the artifact waveform
and subtracted it from the EEG recording (Dowsett & Herrmann, 2016; Helfrich et al.,
2014b; Kohli & Casson, 2015; Voss et al., 2014). The method assumes that the stimulation
artifact has a stable size and shape over time, while signals originating from the brain
fluctuate randomly. To create the template, multiple EEG segments, time-​locked to the
same phase of the artifact waveform (e.g., the zero-​crossing of the signal), are averaged.
This way, brain activity represented in the segments averages out, while the shape and
size of the artifact is retained. The subtraction of the template should in turn remove the
artifact from the EEG signal, while leaving the superimposed brain activity intact. As
the approach achieved non-​optimal results, some authors subsequently applied PCA to
remove residual artifacts from the data (Helfrich et al., 2014b).
In the MEG, spatial filtering approaches, such as synthetic aperture magnetom-
etry (Soekadar et al., 2013) and linearly constrained minimum variance (LCMV)
beamforming (Neuling et al., 2015), have been suggested to suppress artifacts from
tACS and tDCS. Beamformers have been designed to separate signals originating from
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    547

different directions and have widespread applications for example in radar and sonar
technologies (Van Veen & Buckley, 1988). In neuroscience, beamformers are used to lo-
calize sources of brain activity seen in M/​EEG signals and can work in both the time (Van
Veen et al., 1997) and the frequency domains (Gross et al., 2001). The filters are designed
to pass signals from a specific location in the brain, while attenuating signals from all
other sources. To obtain a spatial map of brain activation, multiple filters with different
spatial pass-​bands are constructed on a predefined grid of possible source locations
(Van Veen et al., 1997). The crucial feature of the LCMV beamformer in the context of
concurrent tACS-​MEG is its insensitivity to highly correlating sources (Neuling et al.,
2015). The spatial filters of the LCMV beamformer are designed to minimize the vari-
ance of the output signal at each source location (hence the name). If two or more spa-
tially distinct, highly correlating sources are present in the data, the common variance
of the signals cancels to minimize the filter output (Van Veen et al., 1997). Such high
correlations between distinct sources are unlikely to naturally occur in the brain and
the LCMV beamformer is relatively robust to moderate correlations between sources
(Van Veen et al., 1997). During concurrent tACS-​MEG, the massive stimulation arti-
fact propagates to virtually all sensors with high consistency. Thus, the beamformer can
cancel out large proportions of the artifact waveform (Neuling et al., 2015). As a conse-
quence, however, the artifact suppression capabilities of the beamformer are naturally
limited by the degree to which the artifact signals are correlated (or uncorrelated) over
the sensor array (Mäkelä et al., 2017).
Both methods, the template subtraction and the beamformer approach, assume a sta-
tionary, invariant artifact waveform, but this assumption has recently been challenged.
Physiological processes such as heartbeat and respiration can lead to small changes
in body impedance and elicit small head movements that can modify the size of the
recorded artifact waveform compromising the artifact suppression capabilities of these
methods (Noury et al., 2016; Noury & Siegel, 2017). These systematic changes in artifact
size manifest in an amplitude modulation of the tACS waveform that causes side-​bands
around the main stimulation frequency, which survive artifact suppression attempts
(Noury et al., 2016). Additionally, these processes may also affect artifact suppression
performance directly at the stimulation frequency. Variations in artifact strength cannot
be incorporated when constructing a template of the artifact to be subtracted from EEG
data. As a consequence, any deviation of the artifact strength from the averaged tem-
plate remains in the signal as a residual artifact. In a similar manner, artifact suppression
capabilities of LCMV beamforming might be corrupted if the systematic changes re-
duce the signal correlation of the artifact waveform over sensors (Mäkelä et al., 2017).
While the presence of residual tACS artifacts hinders the proper analysis of stimu-
lation effects on spontaneous brain oscillations, some authors argue that the methods
attenuate the stimulation artifact sufficiently to analyze tACS effects on event-​related
oscillations (Kasten et al., 2018a; Neuling et al., 2017; Noury & Siegel, 2018), because the
residual artifact cancels out if two intervals (e.g., a pre-​and a post-​stimulus interval) that
contain a similar residual artifact are contrasted. Importantly, this approach can only
work if the absolute difference of the conditions is computed. Relative measures that
548    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

involve a division of one condition by the other, as done for example to compute event-​
related (de-​) synchronization (Pfurtscheller & Lopes Da Silva, 1999), are vulnerable to
systematic bias by the residual tACS artifact (Kasten et al., 2018a; Kasten & Herrmann,
2019). Further, the subtraction requires that the artifact size is uncorrelated with the
task. Such systematic modulations of the artifact size may arise if a task elicits head
movements or changes in body impedance (e.g., emotional stimuli) and should be ruled
out by appropriate control analyses (Kasten et al., 2018a; Kasten & Herrmann, 2019).
In order to improve the performance of artifact cleaning approaches or to directly
avoid artifact contamination within the frequency range of interest, the use of alterna-
tive stimulation waveforms such as sawtooth waves (Dowsett & Herrmann, 2016) or
stimulation with an amplitude modulated, high frequency waveform (Witkowski et al.,
2016) has been proposed (Figure 22.2 shows examples of both waveforms). Sawtooth
waves contain strong harmonic peaks in the frequency spectrum that allow for easier
detection and rejection of data segments contaminated by residual artifacts (Dowsett
& Herrmann, 2016). Amplitude modulated waveforms consist of a high-​frequency car-
rier signal, which is modulated in amplitude by the lower-​frequency stimulation wave-
form. In principle, such a signal only contains power at the carrier frequency and two
sidebands, but not at the frequency of the modulating waveform itself, thus shifting
the stimulation artifact into higher frequencies and avoiding the spectral overlap be-
tween the brain signal of interest and the artifact (Witkowski et al., 2016). Recently, a
computer simulation demonstrated that a cortical network, oscillating in the alpha fre-
quency range, can be entrained to the modulation frequency of such a signal, although
the effect was substantially weaker as compared to stimulation with a pure sine wave
(Negahbani et al., 2018). Further, there are challenges to the assumption that M/​EEG
recordings of AM-​tACS are completely artifact free in the range of the modulation fre-
quency as nonlinear behavior of the involved hardware has been shown to reintroduce
such artifacts (Kasten et al., 2018a; Minami & Amano, 2017).

22.5  Safety Aspects

In general, the application of rTMS and tACS is considered safe if applied within
normal dosage ranges (intensities and durations) and by trained personnel. Expert
congresses have yielded publications that detail guidelines for TMS and tES safety
(Antal et al., 2017;Rossi et al. 2020). This section provides a brief introduction to safety
aspects associated with rTMS and tACS. For details, the reader is referred to the afore-
mentioned publications.
The most severe adverse effect associated with rTMS is the potential to induce
seizures. Such events are reported extremely rarely and in most cases stimulation
parameters were chosen outside the recommended dosage ranges. However, in some
patient groups or under specific medication the threshold for seizures may be lowered
(Rossi et al., 2020). Dosage limits for rTMS depend on the number of applied pulses,
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    549

stimulation intensity, frequency, and inter-​train intervals. Contraindication for the use
of TMS is the presence of hardware containing metallic parts in the proximity of the
TMS coil (e.g., cochlear implants, pulse generators, or medical pumps). The strong mag-
netic force may cause malfunction of the devices. When combined with EEG, rTMS
can cause heating of the electrodes and an increase in the risk of skin burns. The use of
smaller electrodes (pallet or annulus shaped electrodes), can greatly reduce the amount
of heating (Ilmoniemi & Kičić, 2010).
Transcranial electrical stimulation is generally considered safe within the range of
0–​4 mA stimulation intensity for <60 minutes over a single session (Antal et al., 2017).
For tACS, stimulation durations of up to 45 minutes at 1.5 mA have been used without
severe adverse effects (Laczó et al., 2012). The application of electric currents via scalp
electrodes bears the risk of skin burns, if electrodes are incorrectly applied (e.g., drying
of sponge electrodes or use of tap water instead of saline solution). So far, there are no
confirmed incidence of seizures reported in the context of tES (Antal et al., 2017). In
addition to adverse effects that impose serious safety issues, it should be acknowledged
that both methods can cause discomfort for participants. The application of electric
currents can lead to the sensation of tingling and itching or heating under the electrodes.
Further, parts of the current may polarize cells of the retina and induce a flickering sen-
sation (so-​called phosphenes). The amount of visual and somatosensory sensation
depends on stimulation intensities, frequencies, and electrode montages (Turi et al.,
2013, 2014). Comparatively high intensities may even be painful for some participants.
TMS can induce phosphenes and contractions of scalp muscles in the proximity of the
stimulated brain area. In order to increase participant safety and comfort, standardized
questionnaires are available to screen participants for risk factors (diseases, medica-
tion, etc.) and exclusion criteria (implants) and to evaluate commonly reported adverse
effects (Antal et al., 2017; Brunoni et al., 2011; Rossi et al., 2009).

22.6  Challenges and Future Directions

Probing causal relationships between brain oscillations and cognitive processes by

means of non-​invasive brain stimulation is a rapidly growing and developing field.
Methods to non-​invasively modulate oscillatory activity in the brain offer promising
pathways to advance basic scientific research as well as clinical practice. However, many
of the fundamental mechanisms of the stimulation are still not fully understood and
require further investigation. The development and improvement of measurement and
analysis techniques for electrophysiological signals acquired during stimulation can
strongly contribute to this knowledge.
An important issue concerning all non-​invasive brain stimulation techniques is the
variability of stimulation effects and its potential sources. A recent meta-​analysis found
that effects of tACS on cognitive measures to be in the small to moderate range (Schutter
& Wischnewski, 2016) and several studies failed to induce effects in behavioral or EEG
550    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

measures (e.g., Fekete et al., 2018; Stecher & Herrmann, 2018; Veniero et al., 2017). There
is a wide range of potential factors that may affect stimulation success or even the dir-
ection of effects. For example, there is accumulating evidence that brain stimulation
effects are state dependent (Feurra et al., 2013; Neuling et al., 2013; Ruhnau et al., 2016;
Silvanto et al., 2008), with some brain states being more susceptible to stimulation than
others. For example, when participants close their eyes, alpha oscillations tend to in-
crease strongly. During such a state of strong activity, brain stimulation failed to further
increase power in the alpha band (Neuling et al., 2013; Ruhnau et al., 2016). Nevertheless,
some involvement of the stimulated oscillation in the a given task or stimulation setting
seems necessary to see effects (Feurra et al., 2013). Such results indicate that the overall
context of the stimulation may play a crucial role. Subtle differences in the context,
such as the lightning conditions of the room, may modulate or mask stimulation effects
(Stecher et al., 2017).
Apart from contextual influences, differences between individuals could po-
tentially explain large proportions of effect variability. Of increasing interest are
differences in individual anatomy. Humans differ with respect to skull thickness and
folding of the cortex. Applying stimulation at standard locations (e.g., according to
EEG electrode positions) can result in substantially different electric field patterns in
the brain (Laakso et al., 2015). Recent work has shown that these e-​field differences
can account for a large amount of variability of brain stimulation effects (Antonenko
et al., 2019; Kasten et al., 2019). Utilizing improved modelling software to individu-
alize stimulation montages may increase the reliability of stimulation effects (Huang
et al., 2018; Saturnino et al., 2019; Wagner et al., 2016). In the context of aftereffects,
a long list of factors is known to have the potential to modulate the induction of cor-
tical plasticity by means of non-​invasive brain stimulation. Those factors include
participants’ sex, age, genetics, and use of medication or psychoactive substances
(Ridding & Ziemann, 2010). Unfortunately, most of the work has been done in the
context of tDCS and TMS protocols not targeting brain oscillations. Thus far, direct
investigations into the role of these factors for modulatory effects of rTMS and tACS
on brain oscillations is largely missing and requires more investigation. Individual
factors may not only alter the induction of plasticity dependent aftereffects, but also
influence the brain oscillation of interest. For example, nicotine has been shown to
diminish or abolish the induction of aftereffects in the context of tDCS and TMS
protocols (Grundey et al., 2012; Thirugnanasambandam et al., 2011). At the same
time, nicotine can alter the frequency and amplitudes of brain oscillations in the
alpha and theta range (Domino et al., 2009; Herning et al., 1983). Tobacco smoking
initially reduces power of alpha and theta oscillations, while tobacco withdrawal is
associated with a power increase (Herning et al., 1983). In the context of stimula-
tion protocols targeting alpha or theta oscillations, such effects could severely con-
found experimental results. Strengthening the understanding of determinants of
brain stimulation effects has the potential to reduce the variability of stimulation
outcomes, for example by identifying participant (or patient) groups not responding
to brain stimulation.
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    551

Dysfunctional patterns of oscillatory activity in the brain have been associated with
a wide range of psychiatric and neurological disease (Herrmann & Demiralp, 2005;
Uhlhaas & Singer, 2006, 2012). TACS is seen as an especially promising technique to
restore such dysfunctional oscillations and reduce related symptoms as devices are
small, portable, comparably cheap and relatively easy to apply after short training
(Antal et al., 2017; Bikson et al., 2018). Further, the devices allow high levels of control
over stimulation waveforms, enabling the design of stimulation protocols for very spe-
cific applications. For example, recently two studies applied tACS using the envelope
of human speech to improve speech intelligibility, offering potential to combine brain
stimulation with hearing aids (Riecke et al., 2018; Wilsch et al., 2018). There are also
recent results from a first clinical trial, applying tACS to restore reduced power in the
alpha band in order to reduce auditory hallucinations in patients with schizophrenia
(Ahn et al., 2019; Mellin et al., 2018). While the authors find some indication that tACS
may be capable of inducing long-​term changes to dysfunctional oscillatory activity and
lead to symptom improvement, a lot more research is needed to demonstrate its clin-
ical value.
A disadvantage of rTMS and tACS is that both methods can only target superfi-
cial regions in the brain, but cannot reach areas in the depth of the brain without co-​
stimulating the overlaying cortex. Recently, stimulation with interfering electric fields
(so-​called temporal interference stimulation, TIS) has been proposed as a possible
solution for this (Grossmann et al., 2017). TIS is based on the idea that alternating
currents with slightly different high frequencies are injected to the brain via two pairs
of electrodes. While superficial areas of the brain are stimulated at high frequencies out-
side of the physiological range, stimulation gives rise to an amplitude modulation or
beat-​frequency in regions where the two electric fields overlap (von Conta et al. 2021).
Such amplitude-​modulated stimulation waveforms can in principle interact with neural
oscillations, however, substantially higher stimulation intensities may be required in
comparison to conventional tACS (Negahbani et al. 2018, Esmaipour et al. 2020). While
there is first evidence from computational modelling and from animal models, the
effects of TIS in humans have so far only been demonstrated in one study applying TIS
to superficial areas of the motor cortex (Ma et al. 2022). Overall, TIS has great poten-
tial to offer new applications and stimulation targets for non-​invasive brain stimulation.
However, more research is needed to establish the efficacy of TIS in humans, especially
in targeting deep brain regions, and its underlying mechanisms.

22.7  Conclusions

Non-​invasive stimulation to modulate oscillations in the human brain is increasingly

popular in human neuroscience. This chapter presents approaches that have the poten-
tial to strengthen our knowledge about brain oscillations and their functional role for
cognition, as they allow to probe the of causal relationships between different features of
552    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

oscillatory activity and human cognition. Further, they may offer new pathways to treat
neurological and psychiatric disease. However, more research is needed to explore the
underlying mechanisms of the stimulation and understand the processes and factors
determining stimulation success and the direction of effects. In particular, the improve-
ment of analysis methods for concurrent recordings of brain activity during stimulation
can strongly contribute to our knowledge in this area.

REFERENCES
Ahn, S., Mellin, J. M., Alagapan, S., Alexander, M. L., Gilmore, J. H., Jarskog, L. F., &
Fröhlich, F. (2019). Targeting reduced neural oscillations in patients with schizophrenia
by transcranial alternating current stimulation. NeuroImage, 186, 126–​136. doi:10.1016/​
j.neuroimage.2018.10.056
Alagapan, S., Schmidt, S. L., Lefebvre, J., Hadar, E., Shin, H. W., & Frӧhlich, F. (2016).
Modulation of cortical oscillations by low-​frequency direct cortical stimulation is state-​
dependent. PLOS Biology, 14, e1002424. doi:10.1371/​journal.pbio.1002424
Alekseichuk, I., Turi, Z., Amador de Lara, G., Antal, A., & Paulus, W. (2016). Spatial working
memory in humans depends on theta and high gamma synchronization in the prefrontal
cortex. Current Biology, 26, 1513–​1521. doi:10.1016/​j.cub.2016.04.035
Amassian, V. E., Cracco, R. Q., Maccabee, P. J., Cracco, J. B., Rudell, A., & Eberle, L. (1989).
Suppression of visual perception by magnetic coil stimulation of human occipital
cortex. Electroencephalography and Clinical Neurophysiology, 74, 458–​462. doi:10.1016/​
0168-​5597(89)90036-​1
Antal, A., Alekseichuk, I., Bikson, M., Brockmöller, J., Brunoni, A. R., Chen, R., . . . Paulus,
W. (2017). Low intensity transcranial electric stimulation: Safety, ethical, legal regula-
tory and application guidelines. Clinical Neurophysiology, 128(9), 1774–​1718. doi:10.1016/​
j.clinph.2017.06.001
Antal, A., Bikson, M., Datta, A., Lafon, B., Dechent, P., Parra, L. C., & Paulus, W. (2014).
Imaging artifacts induced by electrical stimulation during conventional fMRI of the brain.
NeuroImage, 85, 1040–​1047. doi:10.1016/​j.neuroimage.2012.10.026
Antal, A. & Herrmann, C. S. (2016). Transcranial alternating current and random noise stimu-
lation: Possible mechanisms. Neural Plasticity, 2016, 3616807. doi:10.1155/​2016/​3616807
Antonenko, D., Thielscher, A., Saturnino, G. B., Aydin, S., Ittermann, B., Grittner, U.,
et al. (2019). Towards precise brain stimulation: Is electric field simulation related to
neuromodulation? Brain Stimulation, 12(5), 1159–​1168. doi:10.1016/​j.brs.2019.03.072
Baltus, A., Vosskuhl, J., Boetzel, C., & Herrmann, C. S. (2018a). Transcranial alternating current
stimulation modulates auditory temporal resolution in elderly people. European Journal of
Neuroscience, 51(5), 1328–​1338. doi:10.1111/​ejn.13940
Baltus, A., Wagner, S., Wolters, C. H., & Herrmann, C. S. (2018b). Optimized auditory
transcranial alternating current stimulation improves individual auditory temporal reso-
lution. Brain Stimulation, 11, 118–​124. doi:10.1016/​j.brs.2017.10.008
Barker, A. T., Jalinous, R., & Freeston, I. L. (1985). Non-​invasive magnetic stimulation of human
motor cortex. The Lancet, 1(8437), 1106–​1107. doi:10.1016/​s0140-​6736(85)92413-​4
Bergmann, T. O., Karabanov, A., Hartwigsen, G., Thielscher, A., & Siebner, H. R. (2016).
Combining non-​ invasive transcranial brain stimulation with neuroimaging and
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    553

electrophysiology: Current approaches and future perspectives. NeuroImage, 140, 4–​19.

doi:10.1016/​j.neuroimage.2016.02.012
Bergmann, T. O., Molle, M., Schmidt, M. A., Lindner, C., Marshall, L., Born, J., & Siebner, H. R.
(2012). EEG-​guided transcranial magnetic stimulation reveals rapid shifts in motor cortical
excitability during the human sleep slow oscillation. Journal of Neuroscience, 32, 243–​253.
doi:10.1523/​JNEUROSCI.4792-​11.2012
Bikson, M., Brunoni, A. R., Charvet, L. E., Clark, V. P., Cohen, L. G., Deng, Z-​D, . . . Lisanby, S.
H. (2018). Rigor and reproducibility in research with transcranial electrical stimulation: An
NIMH-​sponsored workshop. Brain Stimulation, 11, 465–​480. doi:10.1016/​j.brs.2017.12.008
Bikson, M., Inoue, M., Akiyama, H., Deans, J. K., Fox, J. E., Miyakawa, H., & Jefferys, J. G. R.
(2004). Effects of uniform extracellular DC electric fields on excitability in rat hippocampal
slices in vitro. Journal of Physiology, 557, 175–​190. doi:10.1113/​jphysiol.2003.055772
Bindman, L. J., Lippold, O. C. J., & Redfearn, J. W. T. (1964). The action of brief polarizing
currents on the cerebral cortex of the rat (1) during current flow and (2) in the production
of long-​lasting after-​effects. Journal of Physiology, 172, 369–​382. doi:10.1113/​jphysiol.1964.
sp007425
Boyle, M. R. & Frohlich, F. (2013). EEG feedback-​controlled transcranial alternating current
stimulation. In L. S. Colzato (Ed.), 2013 6th International IEEE/​EMBS Conference on Neural
Engineering (NER) (pp. 140–​143). IEEE. doi:10.1109/​NER.2013.6695891
Braun, V., Sokoliuk, R., & Hanslmayr, S. (2017). On the effectiveness of event-​related beta tACS
on episodic memory formation and motor cortex excitability. Brain Stimulation, 10, 910–​
918. doi:10.1016/​j.brs.2017.04.129
Brunoni, A. R., Amadera, J., Berbel, B., Volz, M. S., Rizzerio, B. G., & Fregni, F. (2011). A sys-
tematic review on reporting and assessment of adverse effects associated with transcranial
direct current stimulation. International Journal of Neuropsychopharmacology, 14, 1133–​1145.
doi:10.1017/​S1461145710001690
Cabral-​Calderin, Y., Williams, K. A., Opitz, A., Dechent, P., & Wilke, M. (2016). Transcranial
alternating current stimulation modulates spontaneous low frequency fluctuations as
measured with fMRI. NeuroImage, 141, 88–​107. doi:10.1016/​j.neuroimage.2016.07.005
Cardin, J. A., Carlén, M., Meletis, K., Knoblich, U., Zhang, F., Deisseroth, K., Tsai, L-​H., &
Moore, C. I. (2009). Driving fast-​spiking cells induces gamma rhythm and controls sensory
responses. Nature, 459, 663–​667. doi:10.1038/​nature08002
Cecere, R., Rees, G., and Romei, V. (2015). Individual differences in alpha frequency drive
crossmodal illusory perception. Current Biology, 25, 231–​235. doi:10.1016/​j.cub.2014.11.034
Creutzfeldt, O. D., Fromm, G. H., & Kapp, H. (1962). Influence of transcortical d-​ c
currents on cortical neuronal activity. Experimental Neurology, 5, 436–​452. doi:10.1016/​
0014-​4886(62)90056-​0
Deans, J. K., Powell, A. D., & Jefferys, J. G. R. (2007). Sensitivity of coherent oscillations in
rat hippocampus to AC electric fields. Journal of Physiology, 583, 555–​565. doi:10.1113/​
jphysiol.2007.137711
Domino, E. F., Ni, L., Thompson, M., Zhang, H., Shikata, H., Fukai, H., Sakaki, T., & Ohya,
I. (2009). Tobacco smoking produces widespread dominant brain wave alpha fre-
quency increases. International Journal of Psychophysiology, 74, 192–​ 198. doi:10.1016/​
j.ijpsycho.2009.08.011
Dowsett, J. & Herrmann, C. S. (2016). Transcranial alternating current stimulation with
sawtooth waves: Simultaneous stimulation and EEG recording. Frontiers in Human
Neuroscience, 10, 1–​10. doi:10.3389/​fnhum.2016.00135
554    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

Esmaeilpour, Zeinab, Greg Kronberg, Davide Reato, Lucas C. Parra, and Marom Bikson.
“Temporal Interference Stimulation Targets Deep Brain Regions by Modulating Neural
Oscillations.” Brain Stimulation, 14, no. 1 (January 1, 2021): 55–​65. https://​doi.org/​10.1016/​
j.brs.2020.11.007.
Fekete, T., Nikolaev, A. R., Knijf, F. De, Zharikova, A., & van Leeuwen, C. (2018). Multi-​
electrode alpha tACS during varying background tasks fails to modulate subsequent alpha
power. Frontiers in Neuroscience, 12, 428. doi:10.3389/​fnins.2018.00428
Feurra, M., Pasqualetti, P., Bianco, G., Santarnecchi, E., Rossi, A., & Rossi, S. (2013). State-​
dependent effects of transcranial oscillatory currents on the motor system: What you think
matters. Journal of Neuroscience, 33, 17483–​9. doi:10.1523/​JNEUROSCI.1414-​13.2013
Fröhlich, F. & McCormick, D. A. (2010). Endogenous electric fields may guide neocortical net-
work activity. Neuron, 67, 129–​143. doi:10.1016/​j.neuron.2010.06.005
Goldman, R. I., Stern, J. M., Engel, J., & Cohen, M. S. (2002). Simultaneous EEG and fMRI of
the alpha rhythm. Neuroreport, 13, 2487–​2492. doi:10.1097/​00001756-​200212200-​00022
Gross, J., Kujala, J., Hamalainen, M., Timmermann, L., Schnitzler, A., & Salmelin, R. (2001).
Dynamic imaging of coherent sources: Studying neural interactions in the human brain.
Proceedings of the National Academy of Sciences of the United States of America, 98, 694–​699.
doi:10.1073/​pnas.98.2.694
Grossman, Nir, David Bono, Nina Dedic, Suhasa B. Kodandaramaiah, Andrii Rudenko, Ho-​
Jun Suk, Antonino M. Cassara, et al. “Noninvasive Deep Brain Stimulation via Temporally
Interfering Electric Fields.” Cell, 169, 6 (2017): 1029–​ 1041.e16. https://​
doi.org/​
10.1016/​
j.cell.2017.05.024.
Grundey, J., Thirugnanasambandam, N., Kaminsky, K., Drees, A., Skwirba, A. C., Lang,
N., . . . Nitsche, M. A. (2012). Rapid effect of nicotine intake on neuroplasticity in non-​
smoking humans. Frontiers in Pharmacology, 3, 1–​9. doi:10.3389/​fphar.2012.00186
Gundlach, C., Müller, M. M., Nierhaus, T., Villringer, A., & Sehm, B. (2016). Phasic modulation
of human somatosensory perception by transcranially applied oscillating currents. Brain
Stimulation, 9, 712–​7 19. doi:10.1016/​j.brs.2016.04.014
Hallett, M. (2000). Transcranial magnetic stimulation and the human brain. Nature, 406, 147–​
150. doi:10.1038/​35018000
Hamidi, M., Slagter, H. A., Tononi, G., & Postle, B. R. (2009). Repetitive transcranial mag-
netic stimulation affects behavior by biasing endogenous cortical oscillations. Frontiers in
Integrative Neuroscience, 3, 14. doi:10.3389/​neuro.07.014.2009
Hanslmayr, S., Matuschek, J., & Fellner, M. C. (2014). Entrainment of prefrontal beta
oscillations induces an endogenous echo and impairs memory formation. Current Biology,
24, 904–​909. doi:10.1016/​j.cub.2014.03.007
Helfrich, R. F., Knepper, H., Nolte, G., Strüber, D., Rach, S., Herrmann, C. S., et al. (2014a).
Selective modulation of interhemispheric functional connectivity by HD-​tACS shapes per-
ception. PLoS Biology, 12(12), e1002031. doi:10.1371/​journal.pbio.1002031
Helfrich, R. F., Schneider, T. R., Rach, S., Trautmann-​Lengsfeld, S. A., Engel, A. K., &
Herrmann, C. S. (2014b). Entrainment of brain oscillations by transcranial alternating
current stimulation. Current Biology, 24, 333–​339. doi:10.1016/​j.cub.2013.12.041
Herning, R. I., Jones, R. T., & Bachman, J. (1983). EEG changes during tobacco withdrawal.
Psychophysiology, 20, 507–​512. doi:10.1111/​j.1469-​8986.1983.tb03004.x
Herrmann, C. S. (2001). Human EEG responses to 1–​100 Hz flicker: Resonance phenomena in
visual cortex and their potential correlation to cognitive phenomena. Experimental Brain
Research, 137, 346–​53. doi:10.1007/​s002210100682
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    555

Herrmann, C. S. & Demiralp, T. (2005). Human EEG gamma oscillations in neuropsychiatric

disorders. Clinical Neurophysiology, 116, 2719–​2733. doi:10.1016/​j.clinph.2005.07.007
Herrmann, C. S., Murray, M. M., Ionta, S., Hutt, A., & Lefebvre, J. (2016a). Shaping intrinsic
neural oscillations with periodic stimulation. Journal of Neuroscience. 36, 5328–​5337.
doi:10.1523/​JNEUROSCI.0236-​16.2016
Herrmann, C. S., Rach, S., Neuling, T., and Strüber, D. (2013). Transcranial alternating current
stimulation: A review of the underlying mechanisms and modulation of cognitive processes.
Frontiers in Human Neuroscience, 7, 1–​13. doi:10.3389/​fnhum.2013.00279
Herrmann, C. S., Strüber, D., Helfrich, R. F., & Engel, A. K. (2016b). EEG oscillations: From
correlation to causality. International Journal of Psychophysiology, 103, 12–​21. doi:10.1016/​
j.ijpsycho.2015.02.003
Huang, Y., Datta, A., Bikson, M., & Parra, L. C. (2017a). Realistic vOlumetric-​Approach to
Simulate Transcranial Electric Stimulation –​ROAST –​a fully automated open-​source pipe-
line. bioRxiv [online]. doi:10.1101/​217331
Huang, Y., Liu, A. A., Lafon, B., Friedman, D., Dayan, M., Wang, X., ... Parra, L. C. (2017b).
Measurements and models of electric fields in the in vivo human brain during transcranial
electric stimulation. Elife, 6, e18834. doi:10.7554/​eLife.18834
Huang, Y., Thomas, C., Datta, A., & Parra, L. C. (2018). Optimized tDCS for targeting multiple
brain regions: An integrated implementation. 2018 40th Annual International Conference
of the IEEE Engineering in Medicine and Biology Society (EMBC) (IEEE), 2018, 3545–​3548.
doi:10.1109/​EMBC.2018.8513034
Ilmoniemi, R. J., Hernandez-​Pavon, J. C., Makela, N. N., Metsomaa, J., Mutanen, T. P., Stenroos,
M., & Sarvas, J. (2015). Dealing with artifacts in TMS-​evoked EEG. 2015 37th Annual
International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC),
2015, 230–​233. doi:10.1109/​EMBC.2015.7318342
Ilmoniemi, R. J. & Kičić, D. (2010). Methodology for combined TMS and EEG. Brain
Topography, 22, 233–​248. doi:10.1007/​s10548-​009-​0123-​4
Jefferys, J. G. (1981). Influence of electric fields on the excitability of granule cells in guinea-​pig
hippocampal slices. Journal of Physiology, 319, 143–​52. doi:10.1113/​jphysiol.1981.sp013897
Jensen, O. & Mazaheri, A. (2010). Shaping functional architecture by oscillatory alpha
activity: gating by inhibition. Frontiers in Human Neuroscience, 4, 186. doi:10.3389/​
fnhum.2010.00186
Kasten, F. H., Dowsett, J., & Herrmann, C. S. (2016). Sustained aftereffect of α-​tACS lasts
up to 70 min after stimulation. Frontiers in Human Neuroscience, 10, 245. doi:10.3389/​
fnhum.2016.00245
Kasten, F. H., Duecker, K., Maack, M. C., Meiser, A., & Herrmann, C. S. (2019). Integrating
electric field modeling and neuroimaging to explain inter-​individual variability of tACS
effects. Nature Communications, 10, art. no. 5427. doi:10.1038/​s41467-​019-​13417-​6
Kasten, F. H. & Herrmann, C. S. (2017). Transcranial alternating current stimulation (tACS)
enhances mental rotation performance during and after stimulation. Frontiers in Human
Neuroscience, 11, 1–​16. doi:10.3389/​fnhum.2017.00002
Kasten, F. H. & Herrmann, C. S. (2019). Recovering brain dynamics during concurrent tACS-​
M/​EEG: An overview of analysis approaches and their methodological and interpretational
pitfalls. Brain Topography. doi:10.1007/​s10548-​019-​00727-​7
Kasten, Florian H., Tea Wendeln, Heiko I. Stecher, and Christoph S. Herrmann. “Hemisphere-​
Specific, Differential Effects of Lateralized, Occipital–​ Parietal α-​versus γ-​ TACS on
556    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

Endogenous but Not Exogenous Visual-​Spatial Attention.” Scientific Reports, 10, no. 1
(December 2020): 12270. https://​doi.org/​10.1038/​s41​598-​020-​68992-​2.
Kasten, F. H., Maess, B., & Herrmann, C. S. (2018a). Facilitated event-​ related power
modulations during transcranial alternating current stimulation (tACS) revealed by con-
current tACS-​MEG. eNeuro [online] 5(3). doi:10.1523/​ENEURO.0069-​18.2018
Kasten, F. H., Negahbani, E., Fröhlich, F., & Herrmann, C. S. (2018b). Non-​linear transfer
characteristics of stimulation and recording hardware account for spurious low-​frequency
artifacts during amplitude modulated transcranial alternating current stimulation (AM-​
tACS). NeuroImage, 179, 134–​143. doi:10.1016/​j.neuroimage.2018.05.068
Klimesch, W., Sauseng, P., & Gerloff, C. (2003). Enhancing cognitive performance with re-
petitive transcranial magnetic stimulation at human individual alpha frequency. European
Journal of Neuroscience, 17, 1129–​1133. doi:10.1046/​j.1460-​9568.2003.02517.x
Klink, Katharina, Sven Paßmann, Florian H. Kasten, and Jessica Peter. “The Modulation of
Cognitive Performance with Transcranial Alternating Current Stimulation: A Systematic
Review of Frequency-​Specific Effects.” Brain Sciences, 10, no. 12 (December 2020): 932.
https://​doi.org/​10.3390/​brain​sci1​0120​932.
Klomjai, W., Katz, R., & Lackmy-​Vallée, A. (2015). Basic principles of transcranial magnetic
stimulation (TMS) and repetitive TMS (rTMS). Annals of Physical and Rehabilitation
Medicine, 58, 208–​213. doi:10.1016/​j.rehab.2015.05.005
Kohli, S. & Casson, A. J. (2015). Removal of transcranial a.c. current stimulation artifact from
simultaneous EEG recordings by superposition of moving averages. 2015 37th Annual
International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC),
2015, 3436–​3439. doi:10.1109/​EMBC.2015.7319131
Kopp, C., Rudolph, U., Low, K., & Tobler, I. (2004). Modulation of rhythmic brain activity by di-
azepam: GABAAreceptor subtype and state specificity. Proceedings of the National Academy
of Sciences of the United States of America, 101, 3674–​3679. doi:10.1073/​pnas.0306975101
Krause, M. R., Vieira, P. G., Csorba, B. A., Pilly, P. K., & Pack, C. C. (2019). Transcranial
alternating current stimulation entrains single-​ neuron activity in the primate brain.
Proceedings of the National Academy of Sciences of the United States of America, 116, 5747–​
5755. doi:10.1073/​pnas.1815958116
Laakso, I., Tanaka, S., Koyama, S., De Santis, V., & Hirata, A. (2015). Inter-​subject vari-
ability in electric fields of motor cortical tDCS. Brain Stimulation, 8, 906–​913. doi:10.1016/​
j.brs.2015.05.002
Laczó, B., Antal, A., Niebergall, R., Treue, S., & Paulus, W. (2012). Transcranial alternating
stimulation in a high gamma frequency range applied over V1 improves contrast percep-
tion but does not modulate spatial attention. Brain Stimulation, 5, 484–​491. doi:10.1016/​
j.brs.2011.08.008
Laufs, H., Kleinschmidt, A., Beyerle, A., Eger, E., Salek-​Haddadi, A., Preibisch, C., & Krakow,
K. (2003). EEG-​correlated fMRI of human alpha activity. NeuroImage, 19, 1463–​1476.
doi:10.1016/​S1053-​8119(03)00286-​6
Lisman, J. E. & Idiart, M. A. (1995). Storage of 7+​/-​​2 short-​term memories in oscillatory
subcycles. Science, 267(5203), 1512–​1515. doi:10.1126/​science.7878473
Lisman, J. E. & Jensen, O. (2013). The theta-​gamma neural code. Neuron, 77, 1002–​1016.
doi:10.1016/​j.neuron.2013.03.007
Loffler, B. S., Stecher, H. I., Fudickar, S., de Sordi, D., Otto-​Sobotka, F., Hein, A., & Herrmann,
C. S. (2018). Counteracting the slowdown of reaction times in a vigilance experiment with
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    557

40-​Hz Transcranial alternating current stimulation. EEE Transactions on Neural Systems

and Rehabilitation Engineering, 26(10), 2053–​2061. doi:10.1109/​TNSRE.2018.2869471
Lustenberger, C., Boyle, M. R., Foulser, A. A., Mellin, J. M., & Fröhlich, F. (2015). Functional role
of frontal alpha oscillations in creativity. Cortex, 67, 74–​82. doi:10.1016/​j.cortex.2015.03.012
Ma, R., Xia, X., Zhang, W., Lu, Z., Wu, Q., Cui, J., Song, H., Fan, C., Chen, X., Zha, R., Wei,
J., Ji, G.-​J., Wang, X., Qiu, B., & Zhang, X. (2022). High Gamma and Beta Temporal
Interference Stimulation in the Human Motor Cortex Improves Motor Functions. Frontiers
in Neuroscience, 15. https://​www.fron​tier​sin.org/​arti​cle/​10.3389/​fnins.2021.800​436
Mäkelä, N., Sarvas, J., & Ilmoniemi, R. J. (2017). Proceedings #17. A simple reason why
beamformer may (not) remove the tACS-​induced artifact in MEG. Brain Stimulation, 10,
e66–​e67. doi:10.1016/​j.brs.2017.04.110
Markram, H., Lübke, J., Frotscher, M., & Sakmann, B. (1997). Regulation of synaptic ef-
ficacy by coincidence of postsynaptic APs and EPSPs. Science, 275, 213–​5. doi:10.1126/​
science.275.5297.213
Marshall, L., Helgadóttir, H., Mölle, M., & Born, J. (2006). Boosting slow oscillations during
sleep potentiates memory. Nature, 444, 610–​613. doi:10.1038/​nature05278
Mathewson, K. E., Gratton, G., Fabiani, M., Beck, D. M., & Ro, T. (2009). To see or not to
see: Prestimulus phase predicts visual awareness. Journal of Neuroscience, 29, 2725–​2732.
doi:10.1523/​JNEUROSCI.3963-​08.2009
Mellin, J. M., Alagapan, S., Lustenberger, C., Lugo, C. E., Alexander, M. L., Gilmore, J. H.,
Jarskog, L. F., & Fröhlich, F. (2018). Randomized trial of transcranial alternating current
stimulation for treatment of auditory hallucinations in schizophrenia. European Psychiatry,
51, 25–​33. doi:10.1016/​j.eurpsy.2018.01.004
Miller, G. A. (1956). The magical number seven, plus or minus two: Some limits on our capacity
for processing information. Psychology Review, 63, 81–​97. doi:10.1037/​h0043158
Minami, S. & Amano, K. (2017). Illusory jitter perceived at the frequency of alpha oscillations.
Current Biology, 27, 2344-​2351.e4. doi:10.1016/​j.cub.2017.06.033
Miranda, P. C., Lomarev, M., & Hallett, M. (2006). Modeling the current distribution during
transcranial direct current stimulation. Clinical Neurophysiology, 117, 1623–​1629. doi:10.1016/​
j.clinph.2006.04.009
Negahbani, E., Kasten, F. H., Herrmann, C. S., & Frohlich, F. (2018). Targeting alpha-​band
oscillations in a cortical model with amplitude-​modulated high-​frequency transcranial
electric stimulation. NeuroImage, 173, 3–​12. doi:10.1016/​j.neuroimage.2018.02.005
Neuling, T., Rach, S., & Herrmann, C. S. (2013). Orchestrating neuronal networks: Sustained
after-​effects of transcranial alternating current stimulation depend upon brain states.
Frontiers in Human Neuroscience, 7, 161. doi:10.3389/​fnhum.2013.00161
Neuling, T., Rach, S., Wagner, S., Wolters, C. H., & Herrmann, C. S. (2012a). Good
vibrations: Oscillatory phase shapes perception. NeuroImage, 63, 771–​778. doi:10.1016/​
j.neuroimage.2012.07.024
Neuling, T., Ruhnau, P., Fuscà, M., Demarchi, G., Herrmann, C. S., & Weisz, N. (2015).
Friends, not foes: Magnetoencephalography as a tool to uncover brain dynamics during
transcranial alternating current stimulation. NeuroImage, 118, 406–​ 413. doi:10.1016/​
j.neuroimage.2015.06.026
Neuling, T., Ruhnau, P., Weisz, N., Herrmann, C. S., & Demarchi, G. (2017). Faith and
oscillations recovered: On analyzing EEG/​MEG signals during tACS. NeuroImage, 147,
960–​963. doi:10.1016/​j.neuroimage.2016.11.022
558    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

Neuling, T., Wagner, S., Wolters, C. H., Zaehle, T., & Herrmann, C. S. (2012b). Finite-​element
model predicts current density distribution for clinical applications of tDCS and tACS.
Frontiers in Psychiatry, 3, 1–​10. doi:10.3389/​fpsyt.2012.00083
Nitsche, M. A, Fricke, K., Henschke, U., Schlitterlau, A., Liebetanz, D., Lang, N., et al.
(2003). Pharmacological modulation of cortical excitability shifts induced by transcranial
direct current stimulation in humans. Journal of Physiology, 553, 293–​301. doi:10.1113/​
jphysiol.2003.049916
Notbohm, A., Kurths, J., & Herrmann, C. S. (2016). Modification of brain oscillations via
rhythmic light stimulation provides evidence for entrainment but not for superpos-
ition of event-​related responses. Frontiers in Human Neuroscience, 10, 10. doi:10.3389/​
fnhum.2016.00010
Noury, N., Hipp, J. F., & Siegel, M. (2016). Physiological processes non-​linearly affect electro-
physiological recordings during transcranial electric stimulation. NeuroImage, 140, 99–​109.
doi:10.1016/​j.neuroimage.2016.03.065
Noury, N. & Siegel, M. (2017). Phase properties of transcranial electrical stimulation
artifacts in electrophysiological recordings. NeuroImage, 158, 406–​ 416. doi:10.1016/​
j.neuroimage.2017.07.010
Noury, N. & Siegel, M. (2018). Analyzing EEG and MEG signals recorded during tES, a reply.
NeuroImage, 167, 53–​61. doi:10.1016/​j.neuroimage.2017.11.023
Novembre, G., Knoblich, G., Dunne, L., & Keller, P. E. (2017). Interpersonal synchrony
enhanced through 20 Hz phase-​coupled dual brain stimulation. Social Cognitive and
Affective Neuroscience, 12(4), 662–​670. doi:10.1093/​scan/​nsw172.
Opitz, A., Falchier, A., Yan, C. G., Yeagle, E. M., Linn, G. S., Megevand, P., et al. (2016).
Spatiotemporal structure of intracranial electric fields induced by transcranial electric
stimulation in humans and nonhuman primates. Scientific Reports, 6, 1–​11. doi:10.1038/​
srep31236
Ozen, S., Sirota, A., Belluscio, M. A., Anastassiou, C. A., Stark, E., Koch, C., et al. (2010).
Transcranial electric stimulation entrains cortical neuronal populations in rats. Journal of
Neuroscience, 30, 11476–​11485. doi:10.1523/​JNEUROSCI.5252-​09.2010
Palva, J. M., Palva, S., & Kaila, K. (2005). Phase synchrony among neuronal
oscillations in the human cortex. Journal of Neuroscience, 25, 3962–​72. doi:10.1523/​
JNEUROSCI.4250-​04.2005
Pfurtscheller, G., & Lopes Da Silva, F. H. (1999). Event-​related EEG/​MEG synchronization and
desynchronization: Basic principles. Clinical Neurophysiology, 110, 1842–​1857. doi:10.1016/​
S1388-​2457(99)00141-​8
Pikovsky, A., Rosenblum, M., & Kurths, J. (2003). Synchronization: A Universal concept in
nonlinear sciences. Cambridge University Press. doi:10.1063/​1.1554136
Polanía, R., Nitsche, M. A., Korman, C., Batsikadze, G., & Paulus, W. (2012). The importance
of timing in segregated theta phase-​coupling for cognitive performance. Current Biology, 22,
1314–​1318. doi:10.1016/​j.cub.2012.05.021
Reato, D., Rahman, A., Bikson, M., & Parra, L. C. (2010). Low-​intensity electrical stimula-
tion affects network dynamics by modulating population rate and spike timing. Journal of
Neuroscience, 30, 15067–​15079. doi:10.1523/​JNEUROSCI.2059-​10.2010.
Reato, D., Rahman, A., Bikson, M., & Parra, L. C. (2013). Effects of weak transcranial alternating
current stimulation on brain activity-​a review of known mechanisms from animal studies.
Frontiers in Human Neuroscience, 7, 687. doi:10.3389/​fnhum.2013.00687
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    559

Ridding, M. C. & Ziemann, U. (2010). Determinants of the induction of cortical plasticity by

non-​invasive brain stimulation in healthy subjects. Journal of Physiology, 588, 2291–​304.
doi:10.1113/​jphysiol.2010.190314
Riecke, L., Formisano, E., Herrmann, C. S., & Sack, A. T. (2015). 4-​Hz transcranial alternating
current stimulation phase modulates hearing. Brain Stimulation, 8, 777–​783. doi:10.1016/​
j.brs.2015.04.004
Riecke, L., Formisano, E., Sorger, B., Başkent, D., & Gaudrain, E. (2018). Neural entrainment
to speech modulates speech intelligibility. Current Biology, 28, 161-​169.e5. doi:10.1016/​
j.cub.2017.11.033
Rogasch, N. C., Sullivan, C., Thomson, R. H., Rose, N. S., Bailey, N. W., Fitzgerald,
P. B., et al. (2017). Analysing concurrent transcranial magnetic stimulation and
electroencephalographic data: A review and introduction to the open-​source TESA soft-
ware. NeuroImage, 147, 934–​951. doi:10.1016/​j.neuroimage.2016.10.031
Romei, V., Gross, J., & Thut, G. (2010). On the role of prestimulus alpha rhythms over occipito-​
parietal areas in visual input regulation: Correlation or causation? Journal of Neuroscience,
30, 8692–​8697. doi:10.1523/​JNEUROSCI.0160-​10.2010
Rossi, Simone, Andrea Antal, Sven Bestmann, Marom Bikson, Carmen Brewer, Jürgen
Brockmöller, Linda L. Carpenter, et al. “Safety and Recommendations for TMS Use in
Healthy Subjects and Patient Populations, with Updates on Training, Ethical and Regulatory
Issues: Expert Guidelines.” Clinical Neurophysiology, 132, no. 1 (January 1, 2021): 269–​306.
https://​doi.org/​10.1016/​j.cli​nph.2020.10.003.
Ruhnau, P., Neuling, T., Fuscá, M., Herrmann, C. S., Demarchi, G., & Weisz, N. (2016). Eyes
wide shut: Transcranial alternating current stimulation drives alpha rhythm in a state
dependent manner. Scientific Reports, 6, 27138. doi:10.1038/​srep27138
Saturnino, G. B., Madsen, K. H., Siebner, H. R., & Thielscher, A. (2017). How to target inter-​
regional phase synchronization with dual-​site transcranial alternating current stimulation.
NeuroImage, 163, 68–​80. doi:10.1016/​j.neuroimage.2017.09.024
Saturnino, G. B., Siebner, H. R., Thielscher, A., & Madsen, K. H. (2019). Accessibility of cor-
tical regions to focal TES: Dependence on spatial position, safety, and practical constraints.
NeuroImage, 203, 116–​183. doi:10.1016/​j.neuroimage.2019.116183
Sauseng, P., Klimesch, W., Heise, K. F., Gruber, W. R., Holz, E., Karim, A. A., et al. (2009). Brain
oscillatory substrates of visual short-​term memory capacity. Current Biology, 19, 1846–​1852.
doi:10.1016/​j.cub.2009.08.062
Schindler, K., Nyffeler, T., Wiest, R., Hauf, M., Mathis, J., Hess, C. W., et al. (2008). Theta burst
transcranial magnetic stimulation is associated with increased EEG synchronization in the
stimulated relative to unstimulated cerebral hemisphere. Neuroscience Letters, 436, 31–​34.
doi:10.1016/​j.neulet.2008.02.052
Schutter, D. J. L. G. (2016). Cutaneous retinal activation and neural entrainment in transcranial
alternating current stimulation: A systematic review. NeuroImage, 140, 83–​88. doi:10.1016/​
j.neuroimage.2015.09.067
Schutter, D. J. L. G. & Wischnewski, M. (2016). A meta-​analytic study of exogenous oscilla-
tory electric potentials in neuroenhancement. Neuropsychologia, 86, 110–​118. doi:10.1016/​
j.neuropsychologia.2016.04.011
Schutter, D. J., van Honk, J., D’Alfonso, A. A., Postma, A., & de Haan, E. H. (2001). Effects
of slow rTMS at the right dorsolateral prefrontal cortex on EEG asymmetry and mood.
Neuroreport, 12, 445–​7. doi:10.1097/​00001756-​200103050-​00005
560    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

Shams, L., Kamitani, Y., & Shimojo, S. (2002). Visual illusion induced by sound. Cognitive
Brain Research, 14, 147–​152. doi:10.1016/​S0926-​6410(02)00069-​1
Siegel, M., Donner, T. H., & Engel, A. K. (2012). Spectral fingerprints of large-​scale neuronal
interactions. Nature Reviews Neuroscience, 13, 121–​134. doi:10.1038/​nrn3137
Silvanto, J., Muggleton, N., & Walsh, V. (2008). State-​dependency in brain stimulation
studies of perception and cognition. Trends in Cognitive Sciences, 12, 447–​454. doi:10.1016/​
j.tics.2008.09.004
Soekadar, S. R., Witkowski, M., Cossio, E. G., Birbaumer, N., Robinson, S. E., & Cohen, L. G.
(2013). In vivo assessment of human brain oscillations during application of transcranial
electric currents. Nature Communications, 4, 2032. doi:10.1038/​ncomms3032
Sohal, V. S. (2012). Insights into cortical oscillations arising from optogenetic studies. Biol.
Psychiatry 71, 1039–​1045. doi:10.1016/​j.biopsych.2012.01.024
Stecher, H. I. & Herrmann, C. S. (2018). Absence of alpha-​tACS aftereffects in darkness reveals
importance of taking derivations of stimulation frequency and individual alpha variability
into account. Frontiers in Psychology, 9, 1–​9. doi:10.3389/​fpsyg.2018.00984
Stecher, H. I., Pollok, T. M., Strüber, D., Sobotka, F., & Christoph, S. (2017). Ten minutes of α-​
tACS and ambient illumination independently modulate EEG α-​power. Frontiers in Human
Neuroscience, 11. doi:10.3389/​fnhum.2017.00257
Stonkus, R., Braun, V., Kerlin, J. R., Volberg, G., & Hanslmayr, S. (2016). Probing the causal
role of prestimulus interregional synchrony for perceptual integration via tACS. Scientific
Reports, 6, 32065. doi:10.1038/​srep32065
Strüber, D., Rach, S., Neuling, T., Herrmann, C. S., & Kar, K. (2015). On the possible role of
stimulation duration for after-​ effects of transcranial alternating current stimulation.
Frontiers in Cellular Neuroscience, 9, 311. doi:10.3389/​fnsys.2015.00148
Strüber, D., Rach, S., Trautmann-​Lengsfeld, S. A., Engel, A. K., & Herrmann, C. S. (2014).
Antiphasic 40 Hz oscillatory current stimulation affects bistable motion perception. Brain
Topography, 27, 158–​171. doi:10.1007/​s10548-​013-​0294-​x
Szymanski, C., Müller, V., Brick, T. R., von Oertzen, T., & Lindenberger, U. (2017). Hyper-​
transcranial alternating current stimulation: Experimental manipulation of inter-​brain syn-
chrony. Frontiers in Human Neuroscience, 11, 1–​15. doi:10.3389/​fnhum.2017.00539
Thielscher, A., Antunes, A., & Saturnino, G. B. (2015). Field modeling for transcranial magnetic
stimulation: A useful tool to understand the physiological effects of TMS? 2015 37th Annual
International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC),
2015, 222–​225. doi:10.1109/​EMBC.2015.7318340
Thirugnanasambandam, N., Grundey, J., Adam, K., Drees, A., Skwirba, A. C.,
Lang, N., .  . 
. Nitsche, M. A. (2011). Nicotinergic impact on focal and non-​ focal
neuroplasticity induced by non-​ invasive brain stimulation in non-​ smoking humans.
Neuropsychopharmacology, 36, 879–​86. doi:10.1038/​npp.2010.227
Thut, G., Schyns, P. G., & Gross, J. (2011a). Entrainment of perceptually relevant brain
oscillations by non-​ invasive rhythmic stimulation of the human brain. Frontiers in
Psychology, 2, 1–​10. doi:10.3389/​fpsyg.2011.00170
Thut, G., Veniero, D., Romei, V., Miniussi, C., Schyns, P., & Gross, J. (2011b). Rhythmic TMS
causes local entrainment of natural oscillatory signatures. Current Biology, 21, 1176–​1185.
doi:10.1016/​j.cub.2011.05.049
Turi, Z., Ambrus, G. G., Ho, K.-​A., Sengupta, T., Paulus, W., & Antal, A. (2014). When size
matters: Large electrodes induce greater stimulation-​related cutaneous discomfort than
smaller electrodes at equivalent current density. Brain Stimulation, 7, 460–​467. doi:10.1016/​
j.brs.2014.01.059
 BRAIN STIMULATION APPROACHES TO INVESTIGATE EEG OSCILLATIONS    561

Turi, Z., Ambrus, G. G., Janacsek, K., Emmert, K., Hahn, L., Paulus, W., et al. (2013). Both
the cutaneous sensation and phosphene perception are modulated in a frequency-​specific
manner during transcranial alternating current stimulation. Restorative Neurology and
Neuroscience, 31, 275–​85. doi:10.3233/​RNN-​120297
Uhlhaas, P. J. & Singer, W. (2006). Neural synchrony in brain disorders: Relevance for cognitive
dysfunctions and pathophysiology. Neuron, 52, 155–​168. doi:10.1016/​j.neuron.2006.09.020
Uhlhaas, P. J. & Singer, W. (2012). Neuronal dynamics and neuropsychiatric disorders: Toward
a translational paradigm for dysfunctional large-​scale networks. Neuron, 75, 963–​980.
doi:10.1016/​j.neuron.2012.09.004
Van Veen, B. D. & Buckley, K. M. (1988). Beamforming: A versatile approach to spatial filtering.
IEEE ASSP Magazine, 5, 4–​24. doi:10.1109/​53.665
Van Veen, B. D., Van Drongelen, W., Yuchtman, M., & Suzuki, A. (1997). Localization of
brain electrical activity via linearly constrained minimum variance spatial filtering. IEEE
Transactions in Biomedical Engineering, 44, 867–​880. doi:10.1109/​10.623056
Veniero, D., Benwell, C. S. Y., Ahrens, M. M., & Thut, G. (2017). Inconsistent effects of parietal
α-​tACS on pseudoneglect across two experiments: A failed internal replication. Frontiers in
Psychology, 8, 1–​14. doi:10.3389/​fpsyg.2017.00952
Veniero, D., Bortoletto, M., & Miniussi, C. (2009). TMS-​EEG co-​registration: On TMS-​
induced artifact. Clinical Neurophysiology, 120, 1392–​1399. doi:10.1016/​j.clinph.2009.04.023
Veniero, D., Vossen, A., Gross, J., & Thut, G. (2015). Lasting EEG/​MEG aftereffects of rhythmic
transcranial brain stimulation: Level of control over oscillatory network activity. Frontiers in
Cellular Neuroscience, 9, 477. doi:10.3389/​fncel.2015.00477
Violante, I. R., Li, L. M., Carmichael, D. W., Lorenz, R., Leech, R., Hampshire, A., Rothwell,
J. C., & Sharp, D. J. (2017). Externally induced frontoparietal synchronization modulates
network dynamics and enhances working memory performance. Elife, 6. doi:10.7554/​
eLife.22001
Conta, Jill von, Florian H. Kasten, Branislava Ćurčić-​Blake, André Aleman, Axel Thielscher,
and Christoph S. Herrmann. “Interindividual Variability of Electric Fields during
Transcranial Temporal Interference Stimulation (TTIS).” Scientific Reports, 11, no. 1 (October
13, 2021): 20357. https://​doi.org/​10.1038/​s41​598-​021-​99749-​0.
Vöröslakos, M., Takeuchi, Y., Brinyiczki, K., Zombori, T., Oliva, A., Fernández-​ Ruiz,
A., . . . Berényi, A. (2018). Direct effects of transcranial electric stimulation on brain circuits
in rats and humans. Nature Communications, 9, 483. doi:10.1038/​s41467-​018-​02928-​3
Voss, U., Holzmann, R., Hobson, A., Paulus, W., Koppehele-​Gossel, J., Klimke, A., & Nitsche,
M. A. (2014). Induction of self-​awareness in dreams through frontal low current stimulation
of gamma activity. Nature Neuroscience, 17, 810–​812. doi:10.1038/​nn.3719
Vossen, A., Gross, J., & Thut, G. (2015). Alpha power increase after transcranial alternating
current stimulation at alpha frequency (α-​tACS) reflects plastic changes rather than entrain-
ment. Brain Stimulation, 8, 499–​508. doi:10.1016/​j.brs.2014.12.004
Vosskuhl, J., Huster, R. J., & Herrmann, C. S. (2015). Increase in short-​term memory capacity
induced by down-​regulating individual theta frequency via transcranial alternating current
stimulation. Frontiers in Human Neuroscience, 9, 257. doi:10.3389/​fnhum.2015.00257
Vosskuhl, J., Huster, R. J., & Herrmann, C. S. (2016). BOLD signal effects of transcranial
alternating current stimulation (tACS) in the alpha range: A concurrent tACS–​fMRI study.
NeuroImage, 140, 118–​125. doi:10.1016/​j.neuroimage.2015.10.003
Wagner, S., Burger, M., & Wolters, C. H. (2016). An optimization approach for well-​targeted
transcranial direct current stimulation. SIAM Journal of Applied Mathematics, 76, 2154–​2174.
doi:10.1137/​15M1026481
562    FLORIAN H. KASTEN and CHRISTOPH S. HERRMANN

Wagner, T., Rushmore, J., Eden, U., & Valero-​Cabre, A. (2009). Biophysical foundations
underlying TMS: Setting the stage for an effective use of neurostimulation in the cognitive
neurosciences. Cortex, 45, 1025–​1034. doi:10.1016/​j.cortex.2008.10.002
Weinrich, C. A., Brittain, J. S., Nowak, M., Salimi-​Khorshidi, R., Brown, P., & Stagg, C. J. (2017).
Modulation of long-​ range connectivity patterns via frequency-​ specific stimulation of
human cortex. Current Biology, 27, 3061-​3068.e3. doi:10.1016/​j.cub.2017.08.075
Wilsch, A., Neuling, T., Obleser, J., & Herrmann, C. S. (2018). Transcranial alternating current
stimulation with speech envelopes modulates speech comprehension. NeuroImage, 172,
766–​774. doi:10.1016/​j.neuroimage.2018.01.038
Wischnewski, M., Engelhardt, M., Salehinejad, M. A., Schutter, D. J. L. G., Kuo, M.-​F., &
Nitsche, M. A. (2018). NMDA receptor-​mediated motor cortex plasticity after 20 Hz
transcranial alternating current stimulation. Cerebral Cortex, 29(7), 2924–​2931. doi:10.1093/​
cercor/​bhy160
Wischnewski, M. & Schutter, D. J. L. G. (2017). After-​effects of transcranial alternating current
stimulation on evoked delta and theta power. Clinical Neurophysiology, 128, 2227–​2232.
doi:10.1016/​j.clinph.2017.08.029
Witkowski, M., Garcia-​Cossio, E., Chander, B. S., Braun, C., Birbaumer, N., Robinson, S. E., &
Soekadar, S. R. (2016). Mapping entrained brain oscillations during transcranial alternating
current stimulation (tACS). NeuroImage, 140, 89–​98. doi:10.1016/​j.neuroimage.2015.10.024
Woods, A. J., Antal, A., Bikson, M., Boggio, P. S., Brunoni, A. R., Celnik, P., . . . Nitsche, M. A..
(2016). A technical guide to tDCS, and related non-​invasive brain stimulation tools. Clinical
Neurophysiology. 127, 1031–​1048. doi:10.1016/​j.clinph.2015.11.012
Wöstmann, M., Vosskuhl, J., Obleser, J., & Herrmann, C. S. (2018). Opposite effects of
lateralised transcranial alpha versus gamma stimulation on auditory spatial attention. Brain
Stimulation, 11, 752–​758. doi:10.1016/​j.brs.2018.04.006
Zaehle, T., Rach, S., & Herrmann, C. S. (2010). Transcranial alternating current stimulation
enhances individual alpha activity in human EEG. PLoS One 5, 13766. doi:10.1371/​journal.
pone.0013766
 CHAPTER 23

PAR AM ETERIZI NG NE U RA L
F IELD P OTENTIA L DATA

BRADLEY VOYTEK

23.1  Introduction

The proliferation of large-​scale, single-​unit electrophysiological recording has been a

boon for modern neuroscience, permitting us to record greater numbers of neurons
in more parts of the brain simultaneously (Buzsáki, 2004). These studies provide tre-
mendous insight regarding how neurons translate input into action, perception, and
cognition, and how disease disrupts the normal function of neuronal circuits. While
these forms of recording are direct measures of neuronal activity, they are invasive and
penetrating—​irreparably damaging brain tissue—​and therefore they are performed al-
most exclusively in animals. As opposed to microscale single-​unit recordings, meso-​
and macroscale recordings are aggregated from neuronal populations—​ hereafter
collectively referred to as field potentials. Field potential methods include invasive local
field potentials (LFP) and electrocorticography (ECoG), as well as non-​invasive mag-
neto-​and electroencephalography (M/​EEG) (Buzsáki et al., 2012). M/​EEG is especially
important because it can be performed non-​invasively in humans, with EEG being the
only functional approach that is used clinically.
Field potential recordings are a less direct measure of neural activity than single-​unit
approaches: instead of expressly capturing neuronal spiking of the underlying local
population, field potentials are largely composed of the integrated postsynaptic currents
of the millions of inputs to the region (Buzsáki et al., 2012; Pesaran et al., 2018). These
field potential signals exhibit aperiodic and periodic properties (Miller et al., 2012;
Gao et al., 2017; Donoghue et al., 2020). The periodic signal consists of both tonic and
bursting neural oscillations (Feingold et al., 2015; Jones, 2016; Peterson & Voytek, 2017);
oscillations are widely studied, and are linked to numerous physiological, cognitive, be-
havioral, and disease states (Engel et al., 2001; Buzsáki & Draguhn, 2004; Kopell et al.,
2014; Voytek & Knight, 2015).
564   BRADLEY VOYTEK

There is a growing literature focusing on the fact that oscillations are nonsinusoidal
(Sherman et al., 2016; Cole & Voytek, 2017, 2018, 2019; Cole et al., 2017; Jackson et al.,
2019); specific time-​domain characteristics of their nonsinusoidality potentially capture
dynamics of the underlying neural circuit (Sherman et al., 2016; Cole & Voytek, 2018).
Most analyses of oscillations are conducted on canonically defined frequency bands.
This is often done without consideration of the aperiodic component, which has a 1/​f-​
like characteristic in the power spectrum that likely arises from the double-​exponential
time domain shape of postsynaptic currents (Freeman & Zhai, 2009; Gao et al., 2017).
Because power at any given frequency is a mixture of both periodic and aperiodic ac-
tivity, measuring band-​limited power with the presumption that the resulting numer-
ical power value captures only oscillatory power is problematic (Haller et al., 2020).
First and foremost, this chapter highlights problems regarding the traditional inter-
pretation of field potential data, and then presents recent approaches for minimizing the
damage that our presumptions cause (as related to physiological interpretations of field
potential analyses). For example, because field potentials include a mixture of features—​
aperiodic, periodic, and transients—​one cannot be certain that band-​limited power
values extracted from traditional analyses includes an oscillation at all. Therefore, if
we wish to talk about oscillations and their various functional correlates, we must first
verify—​to the best of our ability—​that an oscillation is present above and beyond the
aperiodic signal.
As an additional caveat, we must also ensure that spectral power above the aperi-
odic signal reflects an oscillation at that frequency, rather than a harmonic of a slower,
nonsinusoidal rhythm (Cole & Voytek, 2017). Finally, because the aperiodic signal of
neural power spectra has received less attention than oscillations, we discuss the origins
of this signal, its possible physiological interpretations, and emerging research regarding
its cognitive and behavioral relevance. I argue that these three features—​oscillations,
nonsinusoidal waveforms, and the aperiodic signal—​simultaneously exist in the same
field potential data, but likely have different physiological interpretations. Without
careful parameterization of all of these features simultaneously, it is easy to misinterpret
their physiological relevance. The goal of this chapter is to help researchers mitigate the
propagation of potential physiological (mis)interpretations of their oscillation results
by encouraging explicit parameterization of field potential data.

23.2  What is an oscillation?

Oscillations are one of the most widely used analytic approaches in human neuro-
science. Part of the excitement about neural oscillations is their ubiquity: they are
conserved across species (Bullock, 1981), correlate with numerous cognitive and be-
havioral processes (Engel et al., 2001; Varela et al., 2001), are disrupted in a variety of
neurological and psychiatric disorders (Voytek & Knight, 2015), and have been causally
linked to neural information routing and the shaping of spiking networks (Varela et al.,
 PARAMETERIZING NEURAL FIELD POTENTIAL DATA    565

2001, 2001; Fries, 2005). Mechanistically, oscillatory networks are said to coordinate
distributed neural ensembles via synchronizing spike-​timing via phase coordination
of spiking (Fries, 2005); that is, oscillations have been argued to be the mechanism by
which brain regions form functional, dynamic communication networks (Fries, 2005;
Voytek et al., 2015a; Helfrich & Knight, 2016).
The vast majority of studies examining neural oscillations assume classic, canonical
bands of interest. These are approximately defined as: delta (1–​4 Hz), theta (4–​8 Hz),
alpha (8–​12 Hz), beta (16–​30 Hz), and low gamma (30–​60 Hz). However, these fre-
quency bands are only loosely related to the underlying physiology; there exists a great
deal of variability across species (Bullock, 1981), age (Obrist, 1954), and cognitive/​be-
havioral state (Klimesch, 1999; Haegens et al., 2014; Samaha et al., 2015). One concern
with such a priori, band-​limited analyses is that they are often performed without first
examining the power spectrum to account for this intra-​and interindividual variability
in, for example, center frequency. This means that predetermined frequency bands may
include nonoscillatory activity from outside the true physiological oscillatory band—​
whose center frequency and bandwidth may not fall exactly within a canonical band—​
thus masking crucial behaviorally and physiologically relevant information.
While there are several methods for identifying individual differences in oscillations,
most are restricted to identifying the frequency at which the power spectrum peaks
within a specific sub-​band (Haegens et al., 2014); additionally, these methods are limited
to finding only one oscillation within a specified band while ignoring other potentially
physiologically relevant oscillations and their inter-​relationships (Donoghue et al.,
2020). Importantly, all of these methods measure total band power, not band power rela-
tive to the aperiodic signal, thus conflating the two processes (Donoghue et al., 2020).
To further complicate matters, oscillations are often not tonic and sustained, but ra-
ther appear in brief, intermittent bursts (Feingold et al., 2015; Jones, 2016; Peterson &
Voytek, 2017). The functional significance of bursting is supported by a rapidly growing
literature, primarily based on cortical LFP recordings from rodents and nonhuman
primates (Feingold et al., 2015; Lundqvist et al., 2016; Sherman et al., 2016). Example
works have shown that oscillatory burst probability increases during a variety of cog-
nitive and behavioral tasks such as working memory (Lundqvist et al., 2016) or motor
control and action completion (Feingold et al., 2015; Sherman et al., 2016). Historically,
the separation between the functional role of bursting and sustained oscillations can
be highlighted by research into the visual alpha rhythm. The earliest EEG studies of
alpha treated it as an idling rhythm (Jasper & Penfield, 1949; Klimesch, 2012), one that is
sustained while at rest and becomes intermittent when awake and attentive. The idling
perspective was complicated by studies revealing that alpha power in posterior (visual)
regions increases with working memory load across many paradigms (Jensen, 2002).
The fact that alpha power increases during active working memory conflicts with higher
alpha power during eyes closed restful states. Thus, the idling hypothesis was updated
to an account where alpha acts to rhythmically inhibit neural gain (Jensen & Mazaheri,
2010). In this updated view, regions not receiving sensory information, or otherwise
engaging in active behavioral responses, were said to be suppressed to avoid introducing
566   BRADLEY VOYTEK

noise into the larger network. When stimulated, task-​relevant regions are disinhibited,
restoring cortical processing. (For an in-​depth perspective on the alpha rhythm, see
Chapter 10.)
Recent computational work from our lab has challenged this classic view of alpha as
a suppression rhythm (Peterson & Voytek, 2017). When alpha oscillations are modeled
specifically as balanced gain modulation, alpha can suppress visual detection. When
suppression acts over long periods (e.g., >1 sec) this strongly reduces the overall gain,
per the standard view. That is, this low-​gain state reflects an “idle” state of activity,
serving to inhibit firing output for any given input. Surprisingly, however, the model
shows that when alpha is in a short, bursting mode (<0.5 sec, or 5 cycles), alpha actu-
ally enhances neuronal firing. That is, modeling and physiological work uncovered an
enticing result: that oscillatory bursts may play a different functional role compared to
sustained oscillations of the same frequency. This result—​that oscillatory bursts may
have a different physiological effect than sustained rhythms—​highlights the import-
ance of parameterizing not just the power of an oscillation, but its short-​time temporal
dynamics.

23.3  Nonsinusoidal oscillations

Neural oscillations are not smoothly varying sinusoids. Rather, they manifest many
different nonsinusoidal characteristics. Across brain regions, species, and frequencies,
there do exist a variety of stereotyped nonsinusoidal shapes such as human motor
cortical beta oscillations (Cole et al., 2017; Jackson et al., 2019), sleep slow oscillations
(Steriade et al., 1993; Amzica & Steriade, 1998), the sensorimotor mu rhythm (Kuhlman,
1978; Arroyo et al., 1993), and especially the rodent hippocampal theta rhythm (Belluscio
et al., 2012; Cole & Voytek, 2018). The nonsinusoidal shape of oscillation waveforms is
an exciting, re-​emerging candidate for potentially indexing circuit-​level physiology,
such as synaptic input synchrony (Sherman et al., 2016). It is becoming increasingly
apparent that nonsinusoidal oscillatory waveform shape carries physiological informa-
tion (Sherman et al., 2016; Cole & Voytek, 2017, 2018). Because there does not seem to
be a theoretical reason why brain oscillations should be sinusoidal, it may be that the
diverse set of neuronal activation and synaptic current dynamics present in different
oscillations determine the waveform shape in the nearby field potential.
Several nonsinusoidal features of an oscillation can be parameterized, such as a
waveform’s symmetry (the ratio between the rise period and the decay period), the
sharpness of each oscillation peak, the rise and decay times for each cycle’s voltage, and so
on. To quantify these features, an oscillation can explicitly be broken up into individual
cycles by identifying the locations of peaks and troughs and then computing features
on the raw voltage time series (Figure 23.1) (Cole & Voytek, 2019). We recently reviewed
studies that have related the waveform shape of brain oscillations to neurophysiology
(Cole & Voytek, 2017). One of the most well-​supported of these relationships shows that
 PARAMETERIZING NEURAL FIELD POTENTIAL DATA    567

(a) Trough duration (samples) for each cycle

400
200
0
Voltage (uV)

–200 51 19 29
26 26
17 22 20 33 23
–400 18 21 24
19 21 26
–600 20
–800 15
–1000
3.0 3.2 3.4 3.6 3.8 4.0
Time (S)

amplitude period time_rise time_trough time_decay time_peak volt_rise volt_trough volt_decay volt_peak
0 27.442521 46 26 18 20 22 77.542938 –18.474257 127.051091 108.576834
1 34.980215 48 37 19 11 21 123.623268 –84.545266 143.613947 59.068681
2 19.290058 40 31 24 9 29 161.573095 –87.419348 126.497350 39.078002
3 18.898692 53 7 31 46 30 113.252293 15.490505 58.663243 74.153747
4 20.070945 29 16 10 13 13 149.175399 31.155748 97.587049 128.742797

(b)
Sharp-peak oscillation
Voltage

Power
0.0 0.5 1.0 0 10 20 30 40 50
Sinusoid-like oscillation
Voltage

Power

0.0 0.5 1.0 0 10 20 30 40 50

Time (s) Frequency (s)

Figure 23.1  Nonsinusoidal oscillations: (A, Top) Example of a time-​domain parameteriza-

tion approach for quantifying nonsinusoidal features of neural oscillations, on a cycle-​by-​cycle
basis. Here, the duration of the trough is annotated directly on each cycle’s trough. (A, Bottom)
For each cycle, features such as amplitude, period, rise-​and decay times, asymmetries, and so on,
are extracted and stored. (B, Left) Two simulated neural time series where the main difference
between the two is the “sharpness” of each waveform peak. The top rhythm is sharper and less si-
nusoidal than the bottom. (B, Right) The power spectral representations of these two time series
are markedly different, such that the sharpness of the waveforms in the top trace are accompanied
by significant harmonic peaks that are absent in the smoother rhythm (horizontal dashed blue
lines at 10, 20, and 30 Hz).

sharper extrema of oscillations relate to higher synchrony of a neuronal population.

This has been shown, for example, for motor cortical beta oscillations (Sherman et al.,
2016) and for alpha oscillations in the rat gustatory cortex (Tort et al., 2010).
While narrowband power above the aperiodic signal is the definition of an oscilla-
tion, even this definition can be misleading due to a natural consequence of the math-
ematics of how nonsinusoidal waveforms are captured by the Fourier transform. This
is critically important, because we showed recently how the harmonic effects that re-
sult from nonsinusoidal waveform shape can also lead to the appearance of strong
568   BRADLEY VOYTEK

cross-​frequency coupling (Cole et al., 2017)—​the statistical interaction between mul-

tiple different oscillatory processes (Canolty et al., 2006; Canolty & Knight, 2010)—​
when in fact no such multiple-​oscillation interaction need exist. Given the role that
cross-​frequency coupling has been argued to play in organizing neural activity across
regions (Canolty & Knight, 2010; Voytek et al., 2013, 2015a), it is imperative that the
physiological nature of any statistical interaction between multiple oscillations is clear.
Such cross-​frequency coupling can take many forms, including phase-​phase coupling
and phase-​amplitude coupling (PAC) (Bruns et al., 2000; Varela et al., 2001; Canolty
& Knight, 2010). The results of experiments leveraging such approaches are often
interpreted as implying mechanism: for example, phase-​phase coupling may suggest
multiplexing of information across different frequencies while PAC may represent the
biasing of population spiking by an oscillation electric field. It has been recently shown
that patients with Parkinson’s disease have significantly higher beta-​to-​high gamma
(70–​150 Hz) PAC in their motor cortices. With the application of subthalamic deep brain
stimulation (DBS), this PAC significantly decreases in a manner that relates to improved
clinical outcomes (de Hemptinne et al., 2015). We recently analyzed those same data
to show that, rather than abolishing pathological multiple-​oscillation cross-​frequency
coupling, DBS effects could more parsimoniously be described by a reduction in the
waveform sharpness of a single beta oscillator (Cole et al., 2017).
The DSB example highlights the practical, clinical importance of considering whether
measured outputs from algorithmic approaches to oscillations analysis, such as PAC, de-
rive multiple rhythmic processes vs. a single non-​sinusoidal oscillator. This point was
elegantly demonstrated in a recent paper that leveraged a large population of intracra-
nial human recordings across the neocortex (2,750 contacts from 33 patients) (Vaz et al.,
2017). This paper showed that in some cases—​often in anterior frontal and ventral tem-
poral regions—​significant PAC arose from coupled oscillations, where two independent
rhythms are truly coupled. In other cases—​mostly in somatosensory regions and lateral
temporal cortex—​significant PAC arose from the nonsinusoidality of a single rhythm.
That is, the PAC metric only informs about the statistical strength of the relationship, not
the physiological or signal-​processing origin that gives rise to the PAC.

23.4  The aperiodic signal

Until recently, the aperiodic signal has been largely referred to as electrophysiological
“noise” or the “background.” There is mounting evidence, however, that this signal
carries physiological information (Gao et al., 2017) and is dynamically altered by cog-
nitive and perceptual states (Waschke et al., 2017; Dave et al., 2018), as well as in aging
(Voytek et al., 2015b; Waschke et al., 2017; Dave et al., 2018) and disease (Peterson et al.,
2018; Robertson et al., 2019; Veerakumar et al., 2019).
This aperiodic signal has previously been referred to as the 1/​f background and/​or
neural noise, because power at any given frequency is inversely related to the frequency
 PARAMETERIZING NEURAL FIELD POTENTIAL DATA    569

itself (1/​f ) and looks like colored (pink or brown) “noise” seen in digital signal pro-
cessing. However, this is likely not just “noise”, because, as noted, field potentials are
dominated by postsynaptic currents across relatively large populations (Buzsáki et al.,
2012; Pesaran et al., 2018). These currents are driven by input from neurons that are
integrated across a large number of neurons and thus can appear noise-​like. However,
we have shown that the 1/​f-​like nature of the signal can arise simply as a consequence
of the nonlinear nature of post-​synaptic currents, and that changes in the exponent—​
or degree—​of the 1/​f drop-​off may reflect the relative balance of excitatory and inhibi-
tory (EI) currents coming in to the region (Gao et al., 2017). For this reason, we refer
to this feature as the aperiodic signal, rather than referring to it as “noise” (Donoghue
et al., 2020).
The prospect that the aperiodic signal may index EI balance is exciting, but much
more work is required to assess the strength and accuracy of this relationship.
Unfortunately, because field potential spectra are a combination of periodic and aperi-
odic components, and because the large-​power periodic oscillatory bumps can easily
lead to mismeasurements of the aperiodic component, a method for carefully and ac-
curately separating and parametrizing those components is critical. This is especially
important given the mounting computational and animal single-​unit evidence that
suggests that EI balance may be the physiological basis for top-​down gain modulation
(Chance et al., 2002) and persistent delay period activity required for working memory
maintenance (Lim & Goldman, 2013).

23.5  Parameterizing neural

field potentials

In order for researchers to state that oscillatory power in frequency X has altered as a
function of task, condition, behavior, or group, they must first demonstrate that such
an oscillation exists in their data, and that the apparent change in oscillatory power is
due to a true reduction in that oscillation as opposed to a change in its center frequency
moving it outside the analyzed band, a shift in its bandwidth, or from a shift in the aperi-
odic signal. Additionally, these oscillations need to be demonstrated to be true rhythms,
and not harmonics caused by nonsinusoidal features of a rhythm at another frequency.
Problematically, standard analytic approaches conflate periodic parameters
(center frequency, power, bandwidth) with aperiodic ones (offset, exponent). This
compromises physiological interpretations. Additionally, separating bursting from
sustained oscillations can be difficult, if not impossible, if just looking at the spectral
representation of the data (Jones, 2016). To further compound the problem, a single
nonsinusoidal, rhythmic process that has “sharp” extrema will manifest, in the power
spectrum, as an oscillatory bump at the frequency of the rhythm as well as exhibiting
smaller bumps at integer harmonics of the rhythm’s primary frequency. This means that
570   BRADLEY VOYTEK

a sharp 10-​Hz oscillation will also appear as a bump at 20 Hz, and possibly at 30 Hz and
beyond. In such a scenario—​one that is common due to the ubiquity of nonsinusoidal
brain rhythms—​a narrowband analysis at, say, 20 Hz, would give the researcher the im-
pression that a 20-​Hz beta oscillation exists in their data in conjunction with the 10-​Hz
alpha, when in fact all that is present is a nonsinusoidal 10-​Hz rhythm. Further, should
this 10-​Hz sharpness change in relation to behavioral state, such as a task-​related reduc-
tion in sharpness resulting in a “smoother” 10-​Hz shape, power in the 20-​Hz harmonic
would concomitantly be reduced. This could easily lead to the results being interpreted
as a task-​related reduction in 20-​Hz beta power, when in fact no such beta oscillation
truly existed in the first place.
There are currently several algorithms for identifying oscillations in specific ways that
have attempted to address some of these concerns individually, but never conjointly. In
particular, an approach called BOSC (Better OSCillation Detector) (Hughes et al., 2012),
begins by fitting a linear regression to the log-​log PSD to estimate the aperiodic signal.
This is used to determine a power threshold, which is then used in combination with a
duration threshold to define oscillations in wavelet-​based decompositions of the time
series data. However, a significant limitation of this and other similar methods is that a
simple linear fit of the background spectrum can be significantly skewed by the presence
of oscillations—​especially large oscillations—​and therefore mischaracterizes the aperi-
odic signal.
Another similar approach is the irregular-​resampling auto-​spectral analysis (IRASA)
method, which seeks to explicitly separate the periodic and aperiodic components
through a resampling procedure (Wen & Liu, 2016). Though conceptually similar, this
resampling method is computationally much more expensive, and may have trouble
separating large amplitude oscillations from the aperiodic signal. Other methods, such
as principle component variants fail to separate periodic and aperiodic features, and re-
quire manual component selection (Miller et al., 2012). Consistent with previous work,
we show that the aperiodic signal is of significant physiological and behavioral interest,
although all of these methods treat it as a nuisance variable, such as correcting for it via
spectral whitening rather than a feature to be explicitly modeled.
To overcome the limitations of traditional narrowband analyses, to reduce the errors
caused by conflating periodic and aperiodic features, and to address the nonsinusoidal
nature of field potential signals, we recently developed several open-​source algorithms
for parameterizing field potential data. The first is a semi-​automated parameterization
of neural power spectra (Donoghue et al., 2020). Spectra are parameterized as a linear
combination of the aperiodic component and putative periodic oscillations (Figure
23.2). This method thus operates upon frequency representations of time-​series field
potential data. The algorithm considers the PSD as the linear sum of an aperiodic signal
upon which there oscillatory “bumps,” or frequency regions of power over and above
this aperiodic signal, can exist. These bumps are considered to be putative oscillations
and modeled individually as Gaussians. Each Gaussian then characterizes the fre-
quency definition of the oscillation, whereby the mean, amplitude, and standard devi-
ation can be interpreted as the center frequency, power, and bandwidth, respectively,
 PARAMETERIZING NEURAL FIELD POTENTIAL DATA    571

(c) (d) multi-Gaussian fit using

fit and remove Gaussians iteration parameters
peak

(a) fit aperiodic signal 2std (g) combine

Gaussian fit
log(power)

fit
iterate
(e) remove Gaussians from
original PSD

10 20 30 40
frequency (Hz)
peak Gaussian fit
(b) 2std (h)
remove aperiodic signal assess goodness of fit

final fit
halt itting at noise floor (f) re-fit aperiodic

fit
peak
2std

Figure 23.2  Parametrization algorithm applied to field potential data. (A) The power spectral
density (PSD) is first fit with an estimated aperiodic signal (blue), defined by two parameters: a
slope and an offset. (B) The estimated aperiodic portion of the signal is subtracted from the raw
PSD, the residuals of which are assumed to be a mix of periodic oscillatory peaks and noise.
(C) The maximum (peak) of the residuals is found. If this peak is above the noise floor (2std; red
dashed line) then a Gaussian (green) is fit around this peak based on the peak’s frequency, ampli-
tude, and estimated bandwidth. The fitted Gaussian is then subtracted, and the process is iterated
until the noise floor is reached (bottom). These values are used as seeds for the multi-​Gaussian
fitting in D. (D) Having identified the number of putative oscillations, based on the number of
peaks above the noise floor, multi-​Gaussian fitting is then performed on the aperiodic-​adjusted
signal from B to account for the joint power contributed by all the putative oscillations, together.
(E) This multi-​Gaussian model is then subtracted from the original PSD from A. (F) This is done
to give a better estimate of the aperiodic signal—​one that is less corrupted by the large oscillations
present in the original PSD. (G) This re-​fit aperiodic signal is combined with the multi-​Gaussian
model to give the final fit. (H) The final fit—​here parameterized as a line (aperiodic signal) and
two Gaussians (putative oscillations)—​captures >99% of the variance of the original PSD. In
this example, the extracted parameters for the aperiodic signal are: broadband offset =​-​21.4 au;
slope =​-​1.12 au/​Hz. Two Gaussians were found, with the parameters: (1) frequency =​10.0 Hz
amplitude =​0.69 au, bandwidth =​3.18 Hz; (2) frequency =​16.3 Hz, amplitude =​0.14 au, band-
width =​7.03 Hz.
This figure appears in https://​doi.org/​10.1038/​s41​593-​020-​00744-​x

of the oscillation. The final outputs of the algorithm are the definition of the fit aperi-
odic signal, and the definitions for N Gaussians, where N is the number of oscillations
found in the PSD. Notably, this algorithm extracts all these parameters together in a
manner that accounts for potentially overlapping oscillations; it also minimizes the
degree to which they are confounded and requires no specification of canonical oscil-
lation bands.
572   BRADLEY VOYTEK

As for waveform shape methods, multiple approaches have been developed. In par-
ticular, instantaneous phase estimation methods for hippocampal theta have been
modified to consider the peak and trough locations in a broadband signal to account
for nonsinusoidal features. Another approach, empirical mode decomposition, has
the theoretical capability of extracting a nonsinusoidal oscillation in a single compo-
nent (Sweeney-​Reed et al., 2018), although in practice on neural signals the rhythms of
interest spread across multiple components, meaning the decomposition does not reli-
ably separate components of interest.
Though there are still many open questions regarding approaches to analyzing wave-
form shape, we have developed a set of available methods that cover critical basics
(Figure 23.1). Our current toolbox for parameterizing cycle-​by-​cycle waveform features
(bycycle) breaks an oscillation up into individual cycles by identifying the locations of
peaks and troughs and then computing features on the raw voltage time-​series. After the
signal is segmented into cycles, each cycle is characterized by a set of parameters. The
amplitude of the cycle is computed as the average voltage difference between the trough
and the two adjacent peaks. The period is defined as the time between the two peaks.
Rise-​decay symmetry is the fraction of the period that was composed of the rise time.
Peak-​trough symmetry is the fraction of the period, encompassing the previous peak
and current trough, that was composed of the peak. The distributions of these features
can be computed across all cycles in a signal in order to compare oscillation properties
in different neural signals.
However, in order to analyze cycle-​by-​cycle features, we must first identify, in the time
domain, whether a signal has an oscillatory cycle or not. After computing features for
each cycle, following the waveform shape algorithm given, an additional step is done to
determine whether each cycle is part of an oscillatory burst. Traditional burst-​detection
methods are relatively simple: bursts are detected by comparing instantaneous, band-​
limited power at each time point to the median power (usually three times median)
in the channel of interest (Feingold et al., 2015). When the amplitude rises above this
threshold, the signal is said to have entered a bursting state; when it falls below another
threshold (e.g., 1.5 times median) it is said to exit the burst state. While this is accept-
able in some cases, for very stable oscillations and very intermittent oscillations, this cri-
terion becomes unreliable because it will often fail to separate a stable oscillation from
brief nonoscillatory segments. Further, this median-​threshold procedure has never
been explicitly tested against ground-​truth simulated neural data. Oscillatory bursts
are identified as time periods in which consecutive cycles in the time-​series had similar
amplitudes, similar periods, and rise and decay flanks that are predominantly mono-
tonic (Cole & Voytek, 2019).
Unlike our approaches, these other methods are not generalizable across the nu-
merous different forms of field potential data, nor are they designed and optimized to
be parallelizable or to run in a cloud environment. Additionally, none are designed to
examine all of the features in concert, which we show is critical for teasing apart the
physiological interpretations of changes to oscillations, the aperiodic signal, and wave-
form shape.
 PARAMETERIZING NEURAL FIELD POTENTIAL DATA    573

23.6  Discussion

The fact that both periodic oscillations and the aperiodic signal are seen in field poten-
tial data hints at the promise for those signals to bridge across those spatial scales. In
studying neural oscillations, the analyses we apply are often very complicated, math-
ematically intensive, and full of assumptions, both explicit and implicit. Therefore,
careful consideration of the methods applied to our data is paramount, as seemingly
arbitrary choices in the hyperparameters of our analysis, such as the minimum number
of spikes required for including a neuron in an analysis or the length and precise cutoff
frequencies of a filter, can have large impacts on the results and ultimate conclusions.
Often, in-​depth knowledge of the techniques is required in order to appropriately
choose hyperparameters and assure the validity of our conclusions. Because consid-
erable effort is required to obtain this knowledge, this means that we will often make
honest mistakes in our analysis and as peer reviewers, because we often miss the statis-
tical confounds that may underlie highly impactful results.
Therefore, we first advocate paying deliberate and careful attention to the raw data to
help gain a maximal understanding of broad features; complicated methods can often
transform our data in ways we do not expect. If we do not understand how we see the
ultimate effect by looking at the raw data, there is reason for concern, or at least further
investigation. It can similarly be useful to apply multiple methods to our data. When it
comes to analyzing neural oscillations, there are several analytic options to choose from
(e.g., in the frequency or time-​domains), and so this choice should be made consciously.
The choice for the analytic method applied can strongly impact the ultimate conclu-
sion. As we showed, phase-​amplitude coupling analysis and sharpness analysis were
capturing the same phenomena in the data. However, the former favored a conclusion
of coupled oscillations, whereas we favored the latter conclusion concerning synchrony
of transmembrane currents. The choice of developing a time-​domain approach to
analyzing neural oscillations was very deliberate: as physical processes, including neural
dynamics, happen over time (as opposed to being generated in the frequency domain),
there are advantages in analyzing signals in this natural domain and directly measuring
and accounting for non-​stationarities in the dynamics.
While it is certainly a biased perspective, we believe that neural oscillations research
would be better positioned if analysis of these rhythms combined time-​domain and
frequency-​domain approaches, using careful parameterization. Time-​domain cycle-​by-​
cycle parameterization offers several advantages over frequency-​domain approaches.
First, it directly quantifies waveform asymmetry, which is only indirectly and ambigu-
ously captured in spectral analysis (i.e., similar harmonic patterns can be generated by
different oscillations that produce diverse waveforms). Second, cycle-​by-​cycle param-
eterization inherently runs an oscillation detection algorithm, so oscillatory features
are only analyzed on appropriate portions of the signal (i.e., where the oscillation is
observable). Third, cycle-​by-​cycle parameterization offers time-​resolved estimates of
574   BRADLEY VOYTEK

oscillatory features with an appropriate degree of temporal resolution: not only is sym-
metry measured for a single cycle, but the estimates of amplitude and frequency are
intuitively measured in terms of peak-​to-​trough voltage and trough-​to-​trough time,
respectively. However, “instantaneous” estimates of amplitude and frequency that are
comparatively used offer amplitude and frequency estimates at every point in time.
We have previously demonstrated that the cycle-​by-​cycle approach can provide more
sensitive measures of amplitude and frequency, compared to more traditional filter-​
and-​Hilbert transform approaches, by better differentiating simulated experimental
conditions (Cole & Voytek, 2019).
One downside of the time-​domain approach outlined is that it can miss relatively
weaker oscillations, and that fine-​tuning of oscillation-​detection hyperparameters can
influence results. For this reason, we advocate including a frequency-​domain param-
eterization approach to help identify which frequencies have power above the aperiodic
signal, during which times. In this way, both parameterization approaches can be used
synergistically.
To date, tens of thousands of studies have been published regarding neural
oscillations, their function, and their behavioral, cognitive, and disease correlates.
Most of these studies have been conducted using traditional approaches that assume
canonical frequency bands—​delta, theta, alpha/​mu, beta, and gamma. Often these os-
cillation bands are described as having roles themselves, such as theta being equated
with memory, and alpha with attention and wakefulness. This approach arises due to
letting predefined bands guide analyses, rather than allowing the data to guide the
analyses. That is, canonical band analyses commit us to tacit acceptance of predefined
oscillatory bands having a functional role, rather than considering the underlying
physiological mechanisms that may generate different spectral features and addressing
inter-​individual differences. With proper parameterization, it is possible to broaden
our perspective, allowing us to take full advantage of the rich variance present in oscil-
latory data. This increases analytical power and can potentially provide greater insight
into physiological mechanisms underlying oscillations and the role that oscillatory
variability may play in explaining individual differences in cognitive functioning in
health, aging, and disease.

ACKNOWLEDGEMENTS
I sincerely thank Scott Cole, Thomas Donoghue, Richard Gao, Matar Haller, Erik Peterson,
Natalie Schaworonkow, Avgusta Shestyuk, Tammy Tran, and Roemer van der Meij for all the
years of hard work, careful thought, and patience with these ideas. My support for this work
came from a Sloan Research Fellowship (FG-​2015-​66057), the Whitehall Foundation (2017-​12-​
73), the National Science Foundation under grant BCS-​1736028, and the National Institute of
General Medical Sciences grant 1R01GM134363-​01. The author declares no competing finan-
cial interests. Portions of this chapter are based on/​informed by Donoghue et al., 2020; Cole &
Voytek, 2018; Peterson & Voytek, 2018.
 PARAMETERIZING NEURAL FIELD POTENTIAL DATA    575

References
Amzica, F. & Steriade, M. (1998). Electrophysiological correlates of sleep delta waves.
Electroencephalography and Clinical Neurophysiology, 107, 69–​83.
Arroyo, S., Lesser, R. P., Gordon, B. , Uematsu, S., Jackson, D., & Webber, R. (1993). Functional
significance of the mu rhythm of human cortex: An electrophysiologic study with subdural
electrodes. Electroencephalography and Clinical Neurophysiology, 87, 76–​87.
Belluscio, M. A., Mizuseki, K., Schmidt, R., Kempter, R., & Buzsáki, G. (2012). Cross-​frequency
phase-​phase coupling between theta and gamma oscillations in the hippocampus. Journal of
Neuroscience, 32, 423–​435.
Bruns, A., Eckhorn, R., Jokeit, H., & Ebner, A. (2000). Amplitude envelope correlation detects
coupling among incoherent brain signals: Neuroreport, 11, 1509–​1514.
Bullock, T. H. (1981). Neuroethology deserves more study of evoked responses. Neuroscience,
6(7), 1203–​1215.
Buzsáki, G. (2004). Large-​scale recording of neuronal ensembles. Nature Neuroscience, 7,
446–​451.
Buzsáki, G., Anastassiou, C. A., & Koch, C. (2012). The origin of extracellular fields and
currents—​EEG, ECoG, LFP and spikes. Nature Reviews Neuroscience, 13, 407–​420.
Buzsáki, G. & Draguhn, A. (2004). Neuronal oscillations in cortical networks. Science, 304,
1926–​1929.
Canolty, R. T., Edwards, E., Dalal, S. S., Soltani, M., Nagarajan, S. S., Kirsch, H. E., . . . Knight,
R. T. (2006). High gamma power is phase-​locked to theta oscillations in human neocortex.
Science, 313, 1626–​1628.
Canolty, R. T. & Knight, R. T. (2010). The functional role of cross-​frequency coupling. Trends in
Cognitive Sciences, 14, 506–​515.
Chance, F. S., Abbott, L. F., & Reyes, A. D. (2002). Gain modulation from background synaptic
input. Neuron, 35, 773–​782.
Cole, S. & Voytek, B. (2019). Cycle-​ by-​ cycle analysis of neural oscillations. Journal of
Neurophysiology, 122(2), 849–​861.
Cole, S. R., van der Meij, R., Peterson, E. J., de Hemptinne, C., Starr, P. A., & Voytek, B. (2017).
Nonsinusoidal beta oscillations reflect cortical pathophysiology in Parkinson’s disease.
Journal of Neuroscience, 37, 4830–​4840.
Cole, S. R. & Voytek, B. (2017). Brain oscillations and the importance of waveform shape.
Trends in Cognitive Sciences, 21, 137–​149.
Cole, S. R. & Voytek, B. (2018). Hippocampal theta bursting and waveform shape reflect CA1
spiking patterns. bioRxiv [online]. http://​bior​xiv.org/​loo​kup/​doi/​10.1101/​452​987
Dave, S., Brothers, T. A., & Swaab, T. Y. (2018). 1/​f neural noise and electrophysiological indices
of contextual prediction in aging. Brain Research, 1691, 34–​43.
de Hemptinne, C., Swann, N. C., Ostrem, J. L., Ryapolova-​Webb, E. S., San Luciano, M.,
Galifianakis, N. B., & Starr, P. A. (2015). Therapeutic deep brain stimulation reduces cortical
phase-​amplitude coupling in Parkinson’s disease. Nature Neuroscience, 18, 779–​786.
Engel, A. K., Fries, P., & Singer, W. (2001). Dynamic predictions: Oscillations and synchrony in
top–​down processing. Nature Reviews Neuroscience, 2, 704–​7 16.
Feingold, J., Gibson, D. J., DePasquale, B., & Graybiel, A. M. (2015). Bursts of beta oscilla-
tion differentiate postperformance activity in the striatum and motor cortex of monkeys
performing movement tasks. Proceedings of the National Academy of Sciences of the United
States of America, 112, 13687–​13692.
576   BRADLEY VOYTEK

Freeman, W. J. & Zhai, J. (2009). Simulated power spectral density (PSD) of background elec-
trocorticogram (ECoG). Cognitive Neurodynamics, 3, 97–​103.
Fries, P. (2005). A mechanism for cognitive dynamics: neuronal communication through
neuronal coherence. Trends in Cognitive Sciences, 9, 474–​480.
Gao, R., Peterson, E. J., & Voytek, B. (2017) Inferring synaptic excitation/​inhibition balance
from field potentials. NeuroImage, 158, 70–​78.
Haegens, S., Cousijn, H., Wallis, G., Harrison, P. J., & Nobre, A. C. (2014). Inter-​and intra-​
individual variability in alpha peak frequency. NeuroImage, 92, 46–​55.
Donoghue, T., Haller, M., Peterson, E., Varma, P., Sebastian, P., Gao, R., . . . Voytek, B. (2020).
Parameterizing neural power spectra into periodic and aperiodic components. Nature
Neuroscience, 23,1655–​1665.
Helfrich, R. F. & Knight, R. T. (2016). Oscillatory dynamics of prefrontal cognitive control.
Trends in Cognitive Sciences, 20, 916–​930.
Hughes, A. M., Whitten, T. A., Caplan, J. B., & Dickson C. T. (2012). BOSC: A better oscilla-
tion detection method, extracts both sustained and transient rhythms from rat hippocampal
recordings. Hippocampus, 22, 1417–​1428.
Jackson, N., Cole, S. R., Voytek, B., & Swann, N. C. (2019). Characteristics of waveform
shape in Parkinson’s disease detected with scalp electroencephalography. eNeuro, 6(3),
ENEURO.0151-​19.2019.
Jasper, H. & Penfield, W. (1949). Electrocorticograms in man: Effect of voluntary movement
upon the electrical activity of the precentral gyrus. Archiv für Psychiatrie & Nervenkrankh,
183, 163–​174.
Jensen, O. (2002). Oscillations in the alpha band (9-​12 Hz) increase with memory load during
retention in a short-​term memory task. Cerebral Cortex, 12, 877–​882.
Jensen, O. & Mazaheri, A. (2010). Shaping functional architecture by oscillatory alpha ac-
tivity: Gating by inhibition. Frontiers in Human Neuroscience, 4, 186. doi:10.3389/​
fnhum.2010.00186
Jones, S. R. (2016). When brain rhythms aren’t ‘rhythmic’: Implication for their mechanisms
and meaning. Current Opinion in Neurobiology, 40, 72–​80.
Klimesch, W. (1999). EEG alpha and theta oscillations reflect cognitive and memory perform-
ance: A review and analysis. Brain Research Reviews, 29, 169–​195.
Klimesch, W. (2012). Alpha-​band oscillations, attention, and controlled access to stored infor-
mation. Trends in Cognitive Sciences, 16, 606–​617.
Kopell, N. J., Gritton, H. J., Whittington, M. A., & Kramer, M. A. (2014). Beyond the
connectome: The dynome. Neuron, 83, 1319–​1328.
Kuhlman, W. N. (1978). Functional topography of the human mu rhythm.
Electroencephalography and Clinical Neurophysiology, 44, 83–​93.
Lim, S. & Goldman, M. S. (2013). Balanced cortical microcircuitry for maintaining informa-
tion in working memory. Nature Neuroscience, 16,1306–​1314.
Lundqvist, M., Rose, J., Herman, P., Brincat, S. L., Buschman, T. J., & Miller, E. K. (2016).
Gamma and beta bursts underlie working memory. Neuron, 90, 152–​164.
Miller, K. J., Hermes, D., Honey, C. J., Hebb, A. O., Ramsey, N. F., Knight, R. T., Ojemann,
J. G., & Fetz, E. E. (2012). Human motor cortical activity is selectively phase-​entrained on
underlying rhythms. PLoS Computational Biology, 8, e1002655.
Obrist, W. D. (1954). The electroencephalogram of normal aged adults. Electroencephalography
and Clinical Neurophysiology, 6, 235–​244.
 PARAMETERIZING NEURAL FIELD POTENTIAL DATA    577

Pesaran, B., Vinck, M., Einevoll, G. T., Sirota, A., Fries, P., Siegel,
M., . . . Srinivasan, R. (2018). Investigating large-​s cale brain dynamics using field po-
tential recordings: analysis and interpretation. Nature Neuroscience, http://​w ww.nat​
ure.com/​artic​les/​s41​593-​018-​0171-​8
Peterson, E. J., Rosen, B. Q., Campbell, A. M., Belger, A., & Voytek, B. (2018). 1/​f neural noise is
a better predictor of schizophrenia than neural oscillations. bioRxiv [online]. http://​bior​xiv.
org/​loo​kup/​doi/​10.1101/​113​449
Peterson, E. J. & Voytek, B. (2017). Alpha oscillations control cortical gain by modulating
excitatory-​inhibitory background activity. bioRxiv [online]. http://​bior​xiv.org/​loo​kup/​doi/​
10.1101/​185​074
Robertson, M. M., Furlong, S., Voytek, B., Donoghue, T., Boettiger, C. A., & Sheridan, M. A.
(2019). EEG power spectral slope differs by ADHD status and stimulant medication ex-
posure in early childhood. Journal of Neurophysiology, 122(6), 2427–​2437. doi:10.1152/​
jn.00388.2019.
Samaha, J., Bauer, P., Cimaroli, S., & Postle, B. R. (2015). Top-​down control of the phase of
alpha-​band oscillations as a mechanism for temporal prediction. Proceedings of the National
Academy of Sciences of the United States of America, 112, 8439–​8444.
Sherman, M. A., Lee, S., Law, R., Haegens, S., Thorn, C. A., Hämäläinen, M. S., Moore, C. I., &
Jones, S. R. (2016). Neural mechanisms of transient neocortical beta rhythms: Converging
evidence from humans, computational modeling, monkeys, and mice. Proceedings of the
National Academy of Sciences of the United States of America, 113, E4885–​E4894.
Steriade, M., Contreras, D., & Curr, F. (1993). The slow (4 Hz) oscillation in reticular thalamic
and thalamocortical neurons: Scenario of sleep rhythm generation in interacting thalamic
and neocortical networks. Journal of Neuroscience, 13(8), 3284–​3299.
Sweeney-​Reed, C. M., Nasuto, S. J., Vieira, M. F., & Andrade, A. O. (2018). Empirical mode de-
composition and its extensions applied to EEG analysis: A review. Advances in Data Science
and Adaptive Analysis, 10(2), 1840001.
Tort, A. B. L., Fontanini, A., Kramer, M. A., Jones-​Lush, L. M., Kopell, N. J., & Katz, D. B. (2010).
Cortical networks produce three distinct 7-​12 Hz rhythms during single sensory responses
in the awake rat. Journal of Neuroscience, 30, 4315–​4324.
Varela, F., Lachaux, J-​P., Rodriguez, E., & Martinerie, J. (2001). The brainweb: Phase synchron-
ization and large-​scale integration. Nature Reviews Neuroscience, 2, 229–​239.
Vaz, A. P., Yaffe, R. B., Wittig, J. H., Inati, S. K., & Zaghloul, K. A. (2017). Dual origins of
measured phase-​amplitude coupling reveal distinct neural mechanisms underlying epi-
sodic memory in the human cortex. NeuroImage, 148, 148–​159.
Veerakumar, A., Tiruvadi, V., Howell, B., Waters, A. C., Crowell, A. L., Voytek, B., . . . Mayberg,
H. S. (2019). Field potential 1/​f activity in the subcallosal cingulate region as a candidate
signal for monitoring deep brain stimulation for treatment-​resistant depression. Journal of
Neurophysiology, 122(3), 1023–​1035.
Voytek, B., D’Esposito, M., Crone, N., & Knight, R. T. (2013). A method for event-​related phase/​
amplitude coupling. NeuroImage, 64, 416–​424.
Voytek, B., Kayser, A. S., Badre, D., Fegen, D., Chang, E. F., Crone, N. E., . . . D’Esposito, M.
(2015a). Oscillatory dynamics coordinating human frontal networks in support of goal
maintenance. Nature Neuroscience, 18, 1318–​1324.
Voytek, B. & Knight, R. T. (2015). Dynamic network communication as a unifying neural basis
for cognition, development, aging, and disease. Biological Psychiatry, 77, 1089–​1097.
578   BRADLEY VOYTEK

Voytek, B., Kramer, M. A., Case, J., Lepage, K. Q., Tempesta, Z. R., Knight, R. T., & Gazzaley, A.
(2015b). Age-​related changes in 1/​f neural electrophysiological noise. Journal of Neuroscience,
35, 13257–​13265.
Waschke, L., Wöstmann, M., & Obleser, J. (2017). States and traits of neural irregularity in
the age-​varying human brain. Scientific Reports, 7, art no. 17381. https://​doi.org/​10.1038/​s41​
598-​017-​17766-​4
Wen, H. & Liu, Z. (2016). Separating fractal and oscillatory components in the power spectrum
of neurophysiological signal. Brain Topography, 29, 13–​26.
 Index

For the benefit of digital users, indexed terms that span two pages (e.g., 52–​53) may, on occasion,
appear on only one of those pages.
Tables and figures are indicated by t and f following the page number

A affective reactions
ACC see anterior cingulate cortex (ACC) see also affective processes, asymmetric
action potentials  23–​24, 46–​47 frontal cortical activity
active inhibition  206–​8 and manipulations of asymmetric frontal
active sensing  51 cortical activity  222–​24
ActiveTwo system  526 neurofeedback 223
adaptive control hypothesis  182 situational 224
adenosine triphosphate (ATP)  410–​11 unilateral hand contractions  223–​24
adolescence and early adulthood negative affect  224
age as discrete or continuous  334–​35 positive affect  224, 226–​27
specific age-​related associations  330–​31 affective valence
time-​frequency activity in  324–​47 and asymmetric frontal cortical
advantages of time-​frequency activity  221–​22
activity  325–​27 defining 221
characterizing the results  339–​42, 340f and motivational direction  221, 227–​28
covariation in patterns of change  342–​45 trait 222
and development  328–​31, 335 age factors
empirical exploration  335–​46 age-​related associations, developmental
extending of findings  338 research  330–​31
methodological issues  333–​34 altered oscillations  270
pubertal stage  334 aperiodic signal  568
research design issues  331–​33 cognitive decline in aging  92–​93, 401–​2
statistical analysis  334–​35 and development  270
task difficulty vs. task demands  333–​34 research design  331–​32
Adrian, E. D.  145–​46 and sleep  402–​3, 408, 413
affective processes Alayrangues, J.  270–​7 1
see also affective reactions algorithms
asymmetric frontal cortical activity artefact correction  34
parenting and child frontal EEG cognitive tasks  44–​45
asymmetry  309–​10 complementary 157
socioemotional outcome  309 data-​driven/​adaptive time frequency
temperament  308–​9 representations  71–​72
differential functions of 6–​9 Hz distributed source modeling  380
activity  310–​11 eye-​tracking data  157
580   Index

algorithms (cont.) compared with mu and beta  262–​63

greedy  71–​72 differential functions of 6–​9 Hz
low-​resolution electromagnetic activity  310–​11
tomography (LORETA)  380 executive processes  304–​7
matching pursuit (MP)  73 frequency development across infancy/​
mathematical  156, 159–​60 childhood  300–​11
MNE 380 action-​perception processes  302–​4
open-​source  570–​7 1 affective processes  307–​10
signal processing  276 central alpha (mu)  297–​98
sLORETA 381 executive processes  304–​7
source models  381 ontogenesis  296–​98
aliasing  37–​38 posterior alpha  297
Allefeld, C.  515–​16 ontogenesis  296–​98
Allen, J. J. B.  4, 224, 240 central alpha (mu)  297–​98
alpha activity posterior alpha  297
see also alpha band (8–​12 Hz); alpha oscillations 45
oscillations; alpha power; alpha sleep, alpha waves during  416–​18
rhythms; alpha waves source localization, cortical  391
and anxiety  465–​69 strength of  352–​53
conflicting findings and anxiety traditional view  262–​63
subtypes  466–​68 alpha-​beta EEG ratios  368
early foundations and the right-​sided alpha/​beta power and oscillations
bias  465–​66 decreases in power  202–​3, 208, 209–​10
methodological heterogeneity and and information  209
ambiguity  468–​69 suppression of oscillations  202–​3
attenuated 405t alpha oscillations  122, 124f, 202–​16, 566
and CDA  126–​27 see also beta oscillations
central  297–​98 amplitude  202–​3
desynchronization  310–​11 decrease in  203–​4
evoked and ongoing  118–​19 decreases in alpha power and information
frontal  296–​97 representation  208–​11
modulations  126, 127 functional interpretation  208
neural sources  468 information sampling and replay, in alpha
ongoing  118–​19, 122–​23, 127 phase  211–​14
posterior  416–​17, 467–​68 linking alpha phase and power  214–​15
pre-​stimulus  124–​26 parameters  204, 205f
and sleep  416–​17, 418 passive idling vs. active inhibition  206–​8
spontaneous  543–​44 pre-​stimulus  127
alpha band (8–​12 Hz)  300–​11 relation to cognition  202–​4
see also beta band (13–​30 Hz); frequency signal properties of alpha
analysis frequency 204
action-​perception processes  302–​4 phase 206
and ADHD  354 power  205–​6
affective processes  307–​10 task-​irrelevant activity, tuning
alpha phase  211–​12 out  207–​8
changes during perception and selective alpha phase  211–​15
attention  52–​53 linking with power  214–​15
 Index   581

alpha power American Academy of Sleep Medicine

see also alpha/​beta power and oscillations (AASM) 404
affective processing  310–​11 AMPA (α-​amino-​3-​hydroxy-​5-​methyl-​4-​
and anxiety  465 isoxazolepropionic acid)  49
asymmetric frontal cortical activity  220, amplitude
222, 223 alpha oscillations  202–​3
and attention  53 amplitude modulation of neuronal
cognitive processing  206–​7, 310–​11 oscillatory activity  121, 122f
in contralateral hemisphere  53 asymmetry see amplitude
and functional connectivity (FC)  468–​69 asymmetry
high  53, 207, 214–​15, 565–​66 beta oscillations  263–​64, 271, 272, 273
increases in  53, 206–​8, 210–​11, 214–​15, 416–​ correct-​related negativity (CRN)  180
17, 565–​66 ERP methodologies  88–​90
and information processing/​ error-​related negativity (ERN)  236
representation  209, 210f, 210–​11 high-​amplitude gamma oscillations  51
ipsilateral sensors  53 high and low  48
left and right regions  220 low-​pass configuration  22
low  52–​53, 207, 214–​15 mismatch negativity (MMN)  92–​93
lowest and highest modulations  122–​23, odor-​specific spatial patterns  145–​46
125f P3  94–​95
and perception  52–​53 phase and amplitude correlations of
in posterior regions  467–​68, 565–​66 oscillations 497
pre-​target  53 phase-​and amplitude-​time series
reduction of  53, 206–​7, 208, 211, 212, 213f, estimation  499–​500
215–​16, 392–​93, 465 referencing 35
topography of  35–​36, 36f in schizophrenia  447
upregulated  207–​8 sleep  408–​9
alpha rhythms  299 sleep spindles  420
central alpha (mu)  262, 296–​97, 298, 303 spatiotemporal 54
attenuation  303–​4 squared, of the wave  3–​4
and mu rhythm  262 theta power  335
occipital  296–​97 amplitude asymmetry
posterior  296–​97 baseline shifts  121
pre-​central  296–​97 and CDA  126–​27
relationship between evoked and ongoing empirical evidence supporting 
activity  118–​19, 120 122–​23
alpha symmetry  468–​69 and ongoing/​evoked activity  127–​28
alpha waves  41–​42, 145, 202–​3, 293–​94, 298, post-​event-​related potentials  123–​26
352–​53 pre-​event oscillatory activity  123–​26
continuous or intermittent  416–​17 amplitude modulated waveforms  548
during sleep  416–​18, 419 amygdala  352, 359
altered oscillations  269–​73 amyloid-​beta protein, abnormal aggregation
development and aging  270 in AD  164
learning  270–​7 1 analog signal processing  24, 37–​38
movement disorders  271–​73 analog-​to-​digital signal conversion  24–​26,
Alzheimer’s dementia (AD)  163 25f
mouse model  164 analog-​to-​digital converter  24, 37–​38
582   Index

anger approach motivation  221, 222

and approach motivation, see also asymmetric frontal cortical activity;
manipulating  229–​31 motivation; motivational direction
and asymmetric frontal cortical and anger  227–​28
activity  227–​31 behavioral activation system (BAS)  225, 238
manipulation of  228–​29 deficiencies of, in depression  239–​40, 245
relative left activity and state anger  229 heightened, in bipolar  242
resting 228 individual differences  225–​26
and avoidance motivation  229 intensity of  225–​26
self-​reported  231 manipulating  229–​31
state 229 and pictures of motivationally significant
trait 228 stimuli  225–​26
withdrawal behavior  231 and positive affect  224–​25, 226–​27
anterior cingulate cortex (ACC)  96, 98, 179 relative left frontal cortical activity  224–​25,
and anxiety  469, 470, 475 227, 232, 236, 237–​38, 245–​46
frontal midline theta (FMT)  179–​80 research aspects  244–​45
and theta-​beta power ratio  352, 360, 362 self-​reported trait  225
antipsychotic medication  437, 443, 448 trait  233–​34, 235
anxiety whole body posture, using to
and alpha  465–​69 manipulate 227
conflicting findings and anxiety artefacts  6–​7
subtypes  466–​68 blink 158
early foundations and the right-​sided components 34
bias  465–​66 correction 34
methodological heterogeneity and EEG signal  32
ambiguity  468–​69 environmental 7
cognitive performance anxiety eye movements  7
(CPA) 364 microsaccade-​induced spike
and cross frequency coupling  474–​77 potential  158–​59
delta-​beta coupling  475–​76 muscle  7, 157, 160
frontal theta/​beta ratio  476–​77 physiological  156–​58
primer on  474–​75 physiological and non-​physiological
and delta-​beta coupling  475–​76 noise 32
frontal asymmetry  241–​42 rejection 33
and frontal midline theta  469–​74 technical  155–​56
FMT-​related ERP components  470–​7 1 associative learning  153–​54, 361
primer on as an index of medial frontal ASSR see auditory steady-​state response
cortex function  469–​70 (ASSR)
generalized anxiety disorder (GAD)  97, asymmetric frontal cortical activity  220–​46
472–​73 see also approach motivation; motivation;
imaging control functions in  464–​82 motivational direction
revised BIS (r-​BIS)  233 additional models  237–​39
self-​reported anxious arousal  467 activation vs. inhibition  238–​39
subtypes  466–​68 bilateral BAS  237–​38
and time-​frequency representations of and affective processes  307–​10
MCC activity  472–​74 parenting and child frontal EEG
aperiodic signal  568–​69, 570 asymmetry  309–​10
 Index   583

socioemotional outcome  309 anticipatory  295–​96

temperament  308–​9 automatic  154–​55
and affective reactions  222–​24 changes in alpha power  53
neurofeedback 223 derived attention index  355–​56
positive and negative affect, situational directed  364–​65
manipulations 224 divided 266
unilateral hand contractions  223–​24 dorsal and ventral  389–​91
and affective valence  221–​22 focused 146
and anger  227–​31 heart-​rate attention model  392–​93
anxiety  241–​42 and inattention  354, 355
behavioral activation system (BAS) infant  295–​96, 389–​91, 392–​93
approach motivation  225, 238 involuntary  92–​93
bilateral model  237–​38 and memory  203–​4, 212
evidence of r-​BIS functioning  234–​37 working memory  127
trait r-​BIS  233–​34 networks  146, 391–​92
bipolar disorder  242–​43 oddball task  94–​95
depression  239–​41 and prefrontal cortex  359
manipulations of regulation 359
and affective reactions  222–​24 and rhythms  392–​93
anger reactions  228–​29 sampling  211–​12
situational see situational manipulations selective  51–​52, 152, 154, 155
below spatial  152, 386–​87, 391
non-​significant associations  243–​45 sustained  127, 184, 211–​12, 295–​96, 386–​88,
psychological concepts, definitions  221 434
and psychopathology  239–​43 in infants  389–​91, 392–​93
relative left visual and auditory  391
approach motivation  224–​25, 227, 232, temporal-​parietal brain activity  94
236, 237–​38, 245–​46 top-​down  155
and state anger  229 visual  297, 304–​5
relative right visuospatial  137–​38, 140
and effortful control  232–​37 and working memory  127
evidence of r-​BIS functioning, frontal attentional control
EEG activity  234–​37 and anxiety  476, 478–​79
trait r-​BIS and frontal EEG and central executive  364–​66
activity  233–​34 increased 365
resting self-​reported  364
and trait affective valence  222 trait 365
and trait anger  228 attentional control theory (ACT), of
and trait motivational direction  225 anxiety  478–​79
reviewed research  243–​45 attention deficit hyperactivity disorder
situational manipulations (ADHD)
of motivation  225–​27 see also theta-​beta power ratio
of positive and negative affect  224 attentional problems  163, 354
attention biomarkers 358
see also attentional control; attention deficit central executive and attentional control
hyperactivity disorder (ADHD) function 364
alpha oscillation during tasks  53 central nervous system  354
584   Index

attention deficit hyperactivity disorder basal forebrain  413

(ADHD) (cont.) Başar, E.  146, 163
diagnostics, theta-​beta power ratio Başar-​Eroğlu, C.  161
in  355–​58 baseline (resting-​state) EEG  222, 244, 367, 446
Glass’ delta  356 see also default mode network (DMN);
Hedges’ delta  356 idling hypothesis
Orwin’s method  357 asymmetric frontal cortical activity
resting-​state theta-​beta power ratio  358 and trait affective valence  222
Rosenberg’s fail-​safe number and trait anger  228
analysis 357 and trait motivational direction  225
sampling error  356 childhood/​infancy  301, 304–​5, 307
sensitivity and specificity scores  355–​56 frontocentral theta activity  353
transition-​frequency  357–​58 “intrinsic” networks  359
distractibility 163 spontaneous oscillations  446
dopaminergic activity, normalization  358 theta-​beta power ratio  358, 361
EEG patterns  354 B-​distribution RID  70–​7 1
features/​symptomology  354, 358–​59, 366 beamformers  546–​47
frontal cortex  358 Beck Depression Inventory (BDI)  239–​40
gamma activity impairment  162–​63 behavior
hypo-​arousal model  354 and neural oscillations
inattentive type  367–​68 examples  41–​42
meta-​analytic perspective  353–​54 oscillations as pacemakers for  58
methylphenidate (Ritalin) for  355, 358, 359 role in behavior  48–​52
mind wandering  366 behavioral activation system (BAS)  236, 238, 475
resting asymmetric frontal cortical approach motivation  225, 238
activity 228 bilateral model  237–​38
scalp recordings  354, 355f bipolar disorder  242
source localization  388 and frontal EEG activity
auditory gamma oscillations  436–​39 evidence of r-​BIS functioning  234–​37
auditory steady-​state response trait r-​BIS  233–​34
(ASSR)  436–​38, 439 questionnaire 225
early auditory-​evoked gamma band revised BIS (r-​BIS)  235
response (EAGBR)  436, 438–​39 state anger and relative left frontal cortical
auditory MMN  92 activity 229
auditory oddball paradigm  328 trait  244–​45
auditory steady-​state response (ASSR)  436, behavioral inhibition/​behavioral activation
447, 450, 451 system (BIS/​BAS)  225
studies  436–​38, 439 see also behavioral activation system (BAS);
autism spectrum disorders (ASD)  162 behavioral inhibition system (BIS)
avoidance motivation  231 BIS/​BAS model of anterior activation
(BBMAA) 239
B behavioral inhibition system (BIS)  225, 236,
Bae, G.-​Y.  127 238
Baker, M. R.  266–​67 and anxiety  477–​79, 480
Baker, S. N.  266–​67 cross-​frequency coupling  474–​75
Balloon Analogue Risk Task (BART)  235, 473 revised BIS (r-​BIS)  232–​33, 246
BAS see behavioral activation system (BAS) trait 233
 Index   585

Bell, M. A.  301 absolute 271

Berger, H.  5–​6, 41–​42, 45, 145, 202–​3, 293–​94, baseline 270
296–​97, 298, 300, 418–​19 and cerebral cortical activity  359
beta activity cortical 266
see also beta band (13–​30 Hz); beta cortico-​spinal coherence  266–​67
oscillations; beta power; beta waves increases in  275
and dopamine  358 local field potentials (LFPs)  264–​65
during sleep  423–​24 sensorimotor system 261f
beta band (13–​30 Hz) spectral  263–​64
see also alpha band (8–​12 Hz); beta activity; beta rhythms  298
beta coherence; beta ERD; beta beta waves  41–​42, 145
oscillations; frequency bands Better OSCillation Detector (BOSC)  570
and ADHD  354 Bialonski, S.  515–​16
compared with alpha and mu  262–​63 bimanual learning  271
modulations  262–​63 binomial kernel  76–​77
ontogenesis  298–​99 bipolar disorder
oscillations 45 frontal asymmetry  242–​43
phase coupling and causality, in gamma ASSR deficit  437
monkeys 139 heightened approach motivation  242
and schizophrenia  440 sleep spindles and cognition  422
traditional view  262–​63 Bivariate EMD (BEMD)  81
beta coherence  267–​68, 268f bivariate functional connectivity (FC)
beta ERD  262–​63, 264, 270, 271, 275 measures  495–​509
movement-​related  275–​76 aperiodic forms of activity  496, 498f
beta ERS  270–​7 1 for within-​and cross-​frequency coupling of
beta oscillations  262–​63, 359, 367–​68, 541 oscillations  495–​509
see also alpha oscillations data-​driven approach for mapping
amplitude  263–​64, 271, 272, 273 oscillatory connectomes  508–​9
band-​pass filtered scalp  354, 355f definition of phase difference as basis for
and bradykinesia  272–​73 range of interaction metrics  500–​2
cortical, entrainment of  263 “ghost” interactions constituting false
cortico-​spinal coherence  266 positives  501–​8
down-​ and up-​regulation  263 periodic activities  496, 497, 498f
entrainment 263 periodic and quasi-​periodic signals  499–​500
excessive 272 phase and amplitude correlations of
macaque monkey  140 oscillations 497
motor cortical  566–​67 phase-​and amplitude-​time series
prokinetic gamma  264–​65 estimation  499–​500
prominent role for  263–​64 phase locking, quantification  502–​3
resting 354 phase-​locking value (PLV)
role  275–​76 and alternative measures  502–​3
sensorimotor system  269 linear mixing inflating  504–​6
and sleep  423 use of for measuring phase synchrony
waveform shape  274 and CFC  504
beta power quasi-​periodic neuronal oscillations  496,
see also alpha/​beta power and oscillations; 497, 498f
alpha power; theta-​beta power ratio scalp EEG  504–​5
586   Index

bivariate parallel process models  339–​42, 341t combining with neuroimaging  544–​48
bivariate phase synchrony  519 computer simulations  537
blood-​oxygen-​level dependent (BOLD) invasive  533–​34
signals 359 safety aspects  548–​49
brain stimulation  545 targets for  539–​44
fMRI  388–​89, 410–​11 transcranial alternating current
sleep  410–​11 stimulation (tACS)  165, 263, 363, 422,
source localization, cortical  388–​89, 391–​92 534–​35, 540–​41, 542–​44, 547, 551
Bonnefond, M.  207–​8 transcranial direct current stimulation
Borkovec, T. D.  467 (tDCS)  534–​35
Born–​Jordan RID  70–​7 1 transcranial electrical stimulation
boundary element method (BEM)  383, 384, (tES)  534–​39, 536f
387 transcranial magnetic stimulation
Bowers, M. E.  100 (TMS) 444
bradykinesia  272–​74 rhythmic repetitive application
brain (rTMS)  534–​39, 536f, 541, 548
see also amygdala; anterior cingulate cortex transcranial random noise
(ACC); brain stimulation; cerebral stimulation  534–​35
cortex; cerebrospinal fluid (CSF); broadband activity  496–​97
frequency analysis; frequency bands; Brodbeck, V.  388
frontal cortex; gray matter (GM); burst-​detection methods  572
hippocampus; hypothalamus; motor Button, K. S.  10–​11
cortex; neuroimaging; prefrontal cortex;
regions of interest (ROIs); thalamus; C
ventral tegmental area (VTA); visual Canali, P.  444
cortex; white matter (WM) capacitance  18, 23, 37–​38
classical views of function  444–​45 capacitors  21–​22
default mode network, regions Carter, W. R.  467
within  392–​93 Carver, C. S.  225
distribution of tissues  384 cat neocortex  146
electrochemical machine  15 cat olfactory bulb  145–​46
experimental human research  359 cat visual cortex  146, 147
functional connectivity (FC), applying EEG causality, in monkeys
source analysis  388–​92 fronto-​parietal network  139
hemispheres see hemispheres, brain sensorimotor systems  134–​35
oscillations see oscillations, neural visual neocortex  136–​38
oscillatory dynamics  434–​51 Cavanagh, J. F.  97, 469–​70
rhythms of  4 CDA see contralateral delay activity
skull-​to-​brain conductivity ratio, (CDA)
uncertainty  384–​85 cell membranes  23
subcortical regions  474 central executive and attentional control
whole-​brain functional connectivity function  364–​66
(FC) 394 cerebral cortex  293–​94, 353
whole-​brain networks  435–​36 cerebrospinal fluid (CSF)  383, 384
brain computer interfaces  275 CFC see cross-​frequency coupling (CFC)
brain stimulation  532–​52 chaos theory  50
challenges/​future directions  549–​51 Chen, R.  263
 Index   587

childhood/​infancy oscillations as pacemakers for  58

EEG frequency across  293–​313 sensorimotor system  274–​75
alpha band  300–​11 sleep spindles  422–​23
broader impact/​future directions  311–​13 theta phase dynamics and cognitive
ontogenesis of EEG bands  294–​300 control  185–​87
heart-​rate attention model  392–​93 time-​frequency activity  329
scalp EEG  424 Cohen, M. X.  43, 182–​83, 387, 391
source localization Cohen’s class, time-​frequency
in frequency analysis  392–​94 decompositions  66, 69–​7 1, 81–​82, 84,
and use of realistic head models  385–​86 91–​92
sustained attention  389–​91, 392–​93 reduced interference distributions see
working memory  389 reduced interference distributions
Cho, R. V.  443 (RIDs)
Choi–​Williams (CW) RID  70–​7 1 Wigner distribution  70
Chorlian, D. B.  335 coherence
cingulate 470 beta  267–​68, 268f
circadian rhythms  402, 404 communication through coherence (CTC)
circatrigintan (circalunar) periodicity  404–​7 hypothesis 154
circuits  18–​19 cortico-​cortical  268–​69
capacitors  20–​21 cortico-​spinal  266–​67
complex, reducing to a simple cortico-​subcortical  267–​68
equivalent  19, 20f frontal alpha  389
equivalent representations  19 frontal intra-​hemisphere  304–​5, 306, 307
Hodgkin–​Huxley model  23–​24 fronto-​parietal gamma band  146
mechanisms underlying functional connectivity (FC)
oscillation abnormalities in measure  265–​69
schizophrenia  448–​50 imaginary part  269
RC (resistors and capacitors) circuits  24 partial  515–​16
resistors  20–​21 phase coherency  44–​45
simple circuit model  23, 24 pre-​stimulus beta-​frequency
simple series and parallel  18, 19f coherence  134, 135f, 136–​37, 137f
water analogy  18 cohort-​sequential designs  332–​33
Classen, J.  268–​69 Cole, S. R.  274
Clementz, B. A.  436, 442 communication
Coan, J. A.  224 oscillatory  51–​52
cognition signals, carriers of  58
and alpha oscillations  202–​4 “top-​down” and “bottom-​up”  65
cognitive control trials  443 communication through coherence (CTC)
cognitive performance anxiety (CPA)  364 hypothesis 154
cognitive tasks and neural Complex EMD  81
oscillations  44–​45 complex PLV (cPLV)  502
differential functions of 6–​9 Hz complex system states, oscillations as
activity  310–​11 organizing principles for  58–​59
EEG source localization in frequency complex system theory  50
analysis  386–​88 component congruence  336–​38
gamma activity see gamma activity computer simulations  537
monkey neocortical local field potential  134 COMT genotype  447
588   Index

conductance 23 Current Source Density (CSD)

conductivity  16–​18, 37–​38 Toolbox 526
conductors  16–​18, 37–​38 cutoff frequency  22, 37–​38
conjugate variables  30, 37–​38 CWT see continuous wavelet transform
continuous wavelet transform (CWT)  68–​69, (CWT)
80, 84 cycle-​by-​cycle waveform features  572, 573–​74
contralateral delay activity (CDA)  126–​27 cyclic alternating pattern (CAP)  411–​12
control parameter  50
convolution  27–​29, 37–​38 D
corpus callosum  220 data collection methods, frequency
correct-​related negativity (CRN)  180, 526 analysis  3–​12
correlation metrics, linear mixing  504–​6 artefacts  6–​7
cortico-​cortical coherence  268–​69 definitions of frequency research  3–​4
cortico-​spinal coherence  266–​67 dual nature of EEG signals  5–​7
cortico-​subcortical coherence  267–​68 and electricity  36–​37
cross correlation measures  496 equipment and recording  5–​6
cross-​frequency coupling (CFC)  274, 312, 480 experimental design  8–​9
and anxiety  474–​77 exploration 12
delta-​beta coupling  475–​76 frequency processing  7–​8
frontal theta/​beta ratio  476–​77 increasing power of studies  10–​11
bivariate functional connectivity (FC) methods, materials and data, making
measures  495–​509 open 11
confounders in local and inter-​areal physiological basis of EEG  4–​5
CFC  509, 510f pre-​register specific hypotheses  9–​10
delta-​beta coupling  475–​76 a priori power calculations,
phase-​locking value (PLV), using to conducting  10–​11
measure 504 replication and expansion  12
primer on  474–​75 reproducibility in electrophysiology  8–​9
cross-​frequency phase synchronization Davidson, R. J.  224, 239–​40, 465
(CFS) 501 Day-​Night task  306
cross-​sectional research deep brain stimulation (DBS)  260–​61, 267,
frequency development across infancy/​ 273, 274, 568
childhood  298, 299, 303–​4, 306 default mode network (DMN)  359, 392–​93
sensorimotor system  270 delayed-​match-​to-​sample paradigm  163
time-​frequency activity in adolescence/​ delta-​alpha power ratio  367–​68
early adulthood  327–​28, 331–​32, 335–​ delta band (1–​4 Hz)
36, 347 feedback negativity (FN)/​reward positivity
Cuevas, K.  389 (RewP)  99–​100
Curham, K. J.  4 ontogenesis 295
current  16–​18, 37–​38 sleep  352, 413–​14
alternating current (AC)  21–​22, 28 social reward processing  104
direct current (DC)  20–​21, 28 delta-​beta coupling  475
low-​pass RC filter 22f, 22 delta-​beta decoupling  475–​76
current-​density re-​construction delta-​beta power ratio  367–​68
(CDR)  381–​82 delta-​theta power ratio  446
current source density (CSD)  35–​36, 36f, delta waves, in sleep  404–​7, 413–​14, 447–​48
381–​82, 468 dementia  163, 164, 422
 Index   589

dendrites Donner, T. H.  182–​83, 274

apical  419–​20 dopamine  33, 358, 443, 447
dendritic trees  47 dopamine depletion rodent model  183–​84
monkey neocortical local field dopaminergic activity/​pathway  358, 359, 360
potential  132–​34 dorsal lateral prefrontal cortex  469
of pyramidal cells  121 down states, slow oscillation  412–​13
recording and characterization of dendritic Durka, P. J.  75–​76
activity 133 dystonia 273
single-​neuron dendritic branch
response 133 E
density, sleep spindles  421 EAGBR see early auditory-​evoked gamma
depression band response (EAGBR)
approach motivation deficiencies  239–​40, early auditory-​evoked gamma band response
245 (EAGBR) 436
error-​related negativity (ERN)  97 studies  438–​39
frontal asymmetry  239–​41 Edgar, J. C.  450
long-​term (LTD)  539 EEG (electroencephalography) see
major depressive disorder  416–​17, 422 electroencephalography (EEG)
maternal  309–​10 Ekman, P.  224
prenatal 309 electric field  18, 37–​38
desynchronization  310–​11 electricity  16–​18, 17f, 37–​38
see also event-​related desynchronization see also circuits; current; electrodes
(ERD) components 18
information-​via-​desynchronization guide to electrical symbols and terminology
hypothesis 209 18t
detrended fluctuation analysis  409–​10 electrocorticography (ECoG)  47, 54, 133–​34,
development 563
and aging  270 combined with fMRI  359
altered oscillations due to  270 sensorimotor system  260–​61
and time-​frequency activity  328–​31 subdural  149–​50
auditory oddball paradigm  328 electrodes
general developmental trends  329–​30 active or passive  6
related to specific psychological and artefact correction  34
cognitive processes  329 deep brain stimulation (DBS)  260–​61
specific age-​related associations  330–​31 EEG signal artefacts  32
diazepam  266–​67 EOG 7
diffusion tensor imaging (DTI)  305 ground 33
digital signal processing  24, 37–​38 placement 6
Dimensional Change Card Sort  306 referencing  34–​35
direct current (DC)  20–​21, 28 wet or dry  6
directed influence asymmetry index electroencephalography (EEG)
(DAI) 138 artefacts see artefacts
directed transfer function  515–​16 desynchronization 294
discrete-​time sampling  24, 25f dual nature of signals  5
distributed source modeling  378, 379–​82 EEG signal artefacts  32, 33
sLORETA algorithm  387–​88 evoked and induced EEG/​MEG
Doesburg, S. M.  391 changes  115–​28
590   Index

electroencephalography (EEG) (cont.) E/​MEG see electro/​magnetoencephalogram

executive processing-​related  306 (E/​MEG)
first recordings  41–​42, 202–​3, 293 empirical mode decomposition (EMD)  66,
frequency research, defining see frequency 72–​73, 77, 78f
analysis EMD-​based phased estimation  80–​81
frontal EEG activity ensemble EMD (EEMD)  73
evidence of r-​BIS functioning  234–​37 enhancement factor  328
trait r-​BIS  233–​34 equipment and recording  5–​6
grounding 33 equivalent current dipole (ECD)  378–​79, 392
measuring 4 ERN see error-​related negativity (ERN)
physiological basis of  4–​5 ERPs (event-​related potentials) see event-​
practical considerations  32–​36 related potentials (ERPs)
“quantitative” analysis  435 error-​related negativity (ERN)
reactivity 294 and anxiety  471
referencing  34–​36 FMT response  180–​81
resting-​state  304–​6 functional connectivity (FC)  526
signals  5, 6 response-​locked  180–​81
single-​trial analysis  106 revised BIS (r-​BIS)  236
surface-​recorded  15 time-​frequency activity
synchronization 294 in ERP methodologies  88–​90, 92,
time-​domain ERPs  100, 102, 470–​7 1 96–​97
topography of alpha power  35–​36, 36f event-​related potential analysis  76, 77
electro/​magnetoencephalogram (E/​ error-​related positivity (Pe)  96–​97
MEG)  115–​16 Espenhahn, S.  271
assumptions and labels  116–​20, 117f essential tremor  272–​73
origin of changes  118 Ethridge, L.  442
relationship between evoked and ongoing event-​related desynchronization (ERD)  116–​
activity  118–​28, 119f 18, 261f, 262
additive and phase-​resetting theories beta ERD  262–​63, 264, 270, 271, 275–​76
119f, 119–​20 time window  263
alpha rhythm  118–​19, 120 event-​related fields (ERF)  116
grand averaged ERP difference 121f event-​related modes (ERMs)  73
model of generation 120f event-​related potentials (ERPs)
signal changes, evoked and induced  115–​28, advantages  91–​92
117f components  9, 88–​91, 89f, 116
electromotive force (EMF)  16–​18, 37–​38 defining 88
electromyography (EMG)  7, 260–​61, 404 findings, linked to FMT response  180–​82
electrons 16 FMT-​related ERP components  470–​7 1
free  16–​18, 37–​38 formation of  119–​20
electro-​oculograms (EOG)  7, 157, 404 grand mean ERP waveforms 326f, 326–​27
microsaccades, detection of  159–​60 limitations  90–​91
vertical and horizontal  338 methodologies, time frequency
vertical electro-​oculogram (VEOG)  158 analyses  88–​107
electro-​or magnetoencephalography (EEG/​ components  88–​90
MEG)  532–​33 error-​related negativity (ERN)  96–​97
electrophysiology  8, 10 feedback negativity (FN)/​reward
EMD see empirical mode decomposition (EMD) positivity (RewP)  98–​101
 Index   591

mismatch negativity (MMN)  92–​93 experimental design  8–​9

P3  92, 94–​96 eye movements
prototypical waveform  88–​90 artefacts 7
social reward processing  101–​6 blinks and saccades  157, 158
task design  88–​90 high-​resolution eye trackers  159–​60
P50  436, 445 eye tracking  157, 159
P300 445 high-​resolution  159–​60
peaks and troughs in waveform  116 Eysenck, M. W.  478
phase-​locked component  182–​83
post-​event-​related potentials  123–​26 F
response-​conflict-​related N2 ERP Fanelli, D.  8–​9
component  182–​83 fast Fourier transform (FFT)  8, 69, 367
slow-​sustained  127 feedback error-​related negativity
studies 9 (fERN)  180–​81
time-​domain ERPs  100, 102, 470–​7 1 feedback negativity (FN)  98, 471
time-​frequency activity  326–​27 Feedback-​P3-​delta  102
and time-​frequency decompositions see feedback-​related FMT  473
time-​frequency decompositions feedback-​related negativity (FN)  92, 180–​81
(TFDs) feedback-​related negativity (FN)/​reward
transient  55–​56 positivity (RewP)  98–​101
whether ERP theta and FMT reflect the social reward processing  103–​4, 104f, 105–​6
same process  182–​83 Ferrarelli, F.  444
event-​related spectral perturbations Fetz, E. E.  269
(ERSP) 346 fibromyalgia syndrome  416–​17
event-​related synchronization (ERS)  116–​18, fidelity-​weighted inverse modeling  508
261f, 262, 271 field potential recordings  563
beta  270–​7 1 fight-​flight-​freeze system (FFFS)  238, 239, 478
gamma 270 filtering 24
ipsilateral gamma  270 digital  26–​28, 27f
post-​movement  270–​7 1 filters  22, 380
time window  263 finite impulse response (FIR) filter  24, 26,
event-​related synchronization and de-​ 27, 37–​38
synchronization (ERS/​ ERD)  205–​6 fine-​grained analysis  325
evoked activity MP (EMP)  75–​76 finger-​tapping  260–​61, 269
evoked gamma activity  150–​51 bimanual  268–​69
exact low-​resolution electromagnetic joint tasks  542–​43
tomography (eLORETA)  380, 381, unimanual 271
391–​92 finite element method (FEM)  383, 384
executive control network (ECN)  365, 366 finite impulse response (FIR) filter  24, 26,
executive function (EF)  304, 306 37–​38
and motivation  368–​69 moving average 27f, 27
executive processes first-​order waves  41–​42
see also central executive Flandrin, P.  73
executive function (EF) Flanker task  526
and resting-​state EEG  304–​6 fMRI see functional magnetic resonance
term 304 imaging (fMRI)
executive processing-​related EEG  306 FMT see frontal midline theta (FMT)
592   Index

Food and Drug Administration (FDA), monkey neocortical local field

US 356 potential  131–​40
forced-​choice reaction task  162–​63 Nyquist frequency  24–​26
Fourier analysis  28, 145 oscillations 91
Fourier series  28 practical considerations for EEG  32–​36
Fourier transform processing  7–​8
ERPs, time-​frequency decompositions and quality of the EEG  6–​7
for  65–​66 sampling rates  24–​26, 25f
fast Fourier transform (FFT)  8, 69, 367 sleep spindles  419
frequency domain  27–​29 source localization, application of  386–​94
frequency processing  7 cognitive functions  386–​88
of local autocorrelation function  69–​70 time-​frequency analysis  30–​32
moving window  91–​92 traditional demarcation of oscillatory
neural field potential data  567–​68 events  45–​46
RID-​based phase estimation  81–​82 windowing  7, 30
short-​time Fourier transform (STFT)  31, frequency bands
67–​68, 84 see also alpha band (8–​12 Hz); beta band
source localization, cortical  389 (13–​30 Hz); delta band (1–​4 Hz);
of time-​domain signal  30 gamma band; rhythms; slow wave
windowing 30 activity (SWA); theta band (4–​8 Hz)
Fox, N. A.  301, 465–​66 difference between alpha, mu and
Foxe, J. J.  378–​79 beta  262–​63
fractals  409–​10 dynamic view of  273–​74
free electrons  16–​18, 37–​38 high-​frequency oscillations 261f, 265
Freeman, W.  50–​51, 54, 145–​46 and neural oscillations  45–​46
frequency analysis ontogenesis  294–​300
see also data collection methods, frequency ontogeny 294
analysis; frequency bands; frequency outline of  4
domain prokinetic gamma  264–​65
analog-​to-​digital signal conversion  24–​26, prominent role for beta oscillations  263–​64
25f sensorimotor system  261
circuits  18–​19 traditional demarcation of oscillatory
cognitive functions, source localization events 45
for  386–​88 traditional view  262–​65
definitions of frequency research  3–​4 frequency domain 29f
digital filtering  26–​28, 27f frequency resolution  67–​68
domain  28–​30 frequency-​specific connectivity  31–​32
EEG development across infancy and frontal asymmetry
childhood see also asymmetric frontal cortical activity
alpha band  300–​11 anxiety  241–​42
broader impact/​future directions  311–​13 bipolar disorder  242–​43
ontogenesis of EEG bands  294–​300 depression  239–​41
EEG source localization in  386–​88 inconsistent patterns  242
pediatric populations  392–​94 and psychopathology  239–​43
electricity  16–​18 frontal cortex
filtering  24, 26–​28, 27f see also prefrontal cortex
logic behind  15–​37 and ADHD  358
 Index   593

left and right regions  221, 236, 363 graph theoretic metrics  521–​25
medial 96 illustrative example  526–​28
structural development  358 spectral methods for multivariate
theta-​band activity  387 synchronization  517–​18
TMS 444 resting-​state  468–​69
VTA projections  359 small-​world parameter  523–​24
frontal eye fields (FEF)  330–​31 whole-​brain  394
frontal midline theta (FMT) functional connectivity networks (FCNs)  521,
activity during Stage 1 and REM sleep  415–​16 526–​27
anterior cingulate cortex (ACC)  179–​80 functional magnetic resonance imaging
and anxiety  469–​74 (fMRI) 212
broader impact/​future directions  188 and anxiety  468–​69
characteristics  179–​83 BOLD response  388–​89, 410–​11
clinical applications  187–​88 brain stimulation  545
conflict-​related  182–​83 combined with electrocorticography  359
and cross-​frequency coupling  479–​80 feedback negativity (FN)/​reward positivity
enhanced 182 (RewP) 100
ERP components  179–​80 resting-​state research  391–​92
ERP findings linked to FMT source localization  378–​79, 388–​89, 394
response  180–​82 EEG inverse solutions  382, 383
error-​related  472–​73 Funder, D. C.  244
feedback-​related  473 fusiform face area (FFA)  378–​79
functional aspects  179–​80
history  178–​79 G
model specimen of cortical theta  178–​88 GABA see gamma-​aminobutyric acid
primer on as an index of medial frontal (GABA)
cortex function  469–​70 Gable, P. A.  232, 233–​34, 235
processes 179 Galambos, R.  44, 146
response-​conflict  182–​83 gamma activity
single-​trial  472–​73 see also prokinetic gamma
translational potential  183–​87 and ADHD  162–​63
whether ERP theta and FMT reflect the and ASD  162
same process  182–​83 clinical relevance  160–​64
frontal-​related negativity (FRN)  360 early studies  146
fronto-​basal ganglia circuits  275 evoked  150–​51, 161
fronto-​parietal network, in monkeys  139 frequencies, in traditional EEG
Fukuda, K.  127 research  149–​50
full-​band EEG  410–​11 high and low gamma  149–​50
functional connectivity (FC) induced (total)  147–​49, 151–​52
bivariate measures  495–​509 and microsaccades  158–​60
clustering coefficient  524 methodological aspects  155–​56
coherence  265–​69 modality-​specific effects  161
EEG source analysis, applying  388–​92, 394 neurofeedback  164–​65
executive control network (ECN)  366 neurophysiological mechanisms  153–​55
multivariate methods  514–​28 oscillatory synchrony  153
direct measures of multivariate phase-​locked early evoked  162
synchronization  518–​21 pyramidal cells  153, 161–​62
594   Index

gamma activity (cont.) evoked 150

representational hypothesis of induced frontal  423–​24
activity 152 frontal and central  299–​300
research history/​background  145–​47 high 446
resting-​state  161–​62 increases in  264–​65
scalp EEG/​scalp recordings  151, 155–​56, 157 induced  158, 442, 443, 447
and schizophrenia  160–​61 modulating  164–​65
sensory and cognitive processing  145–​65 non-​oscillatory  149–​50
during sleep  423–​24 occipital  299–​300
spontaneous  161–​62 resting  299–​300, 446
studies 152 in schizophrenia  443
technical artefacts  156 spontaneous  447, 449–​50
types  147–​50 gamma resonance, hippocampus  146
gamma-​aminobutyric acid (GABA)  443 gamma waves  145
GABA-​ergic interneurons  153, 154, 161–​62, Gao, R.  378–​79, 383
422 Gaussian fields  50–​51
gamma band (60–​80 Hz) Gaussian function/​window function  30, 31,
see also gamma activity 80, 570–​7 1
bursts  138–​39 time-​frequency activity  67–​68, 77
frontal enhancement  152 Gaussian wavelet filtering  499
fronto-​parietal gamma band coherence  146 General Behavior Inventory (GBI)  243
information processing  435–​36 generalized anxiety disorder (GAD)  97,
lower gamma (30–​80 Hz)  4 472–​73
ontogenesis  299–​300 Generalized Morse Wavelet (GMW)  68–​69
and schizophrenia  440 Gestalt perception  439–​41
sensory information  138–​39 GFS see global field synchronization (GFS)
synchronization  138, 154–​55 Ghorashi, S.  440
upper gamma (80–​150 Hz)  4 Gianotti, L. R.  234
gamma oscillations global field synchronization (GFS)  518
abnormal, in ASD  162 go/​no-​go task  330–​31
auditory  436–​39 Goodman, S. N.  8–​9
causal evidence  164–​65 Granger causality  504, 515–​16
cortical 153 Granger prediction  185–​87
evoked and induced activity  147–​49, 148f graph theoretic metrics  516, 521–​25, 526–​27
high-​amplitude  51 centrality 525
in human visual cortex  146 modularity  524–​25
neurodegenerative diseases  163 small-​world  523–​24
neurofeedback training  165 graph theory  394, 509, 516
research history/​background  145–​47 see also graph theoretic metrics
sensory and perceptual, in Grassberger–​Procaccia dimension  50
schizophrenia  435–​42 Grassi, A.  411
during sleep  423–​24 Gray, C. M.  146, 237–​38, 478, 479–​80
slow  273–​74 Gray, J. A.  475
synchronous 146 gray matter (GM)  381–​82, 383, 384
gamma power  391, 423 Grent-​‘t-​Jong, T  441–​42, 446
augmented 152 Griffiths, B.  209
broadband  158–​59, 447, 449–​50 Grützner, C.  440–​42
 Index   595

H hippocampus  52, 360, 413, 449

Haenschel, C.  443 gamma resonance phenomena  146
Hall, J. R.  355 hippocampal neurons  51
Hall, M.  438–​39 hippocampal RSA  415
hallucinations  161–​62, 437 hippocampal theta rhythms  184
Hamming window function  30, 67–​68 ripples 424
hand contractions, unilateral  223–​24 rodent hippocampal theta  183
Hanning window function  67–​68 septo-​hippocampal complex  352, 359, 360
Hann window function  30 theta waves and rhythmic slow
Hanslmayr, S.  209 activity  415–​16
HARKing (hypothesizing after results are Hirano, Y.  447, 450
known)  9–​10 Hirschmann, J.  267
Harmon-​Jones, E.  224, 243 Hirvonen, J.  441
Harrewijn, A.  475–​76 Hodgkin–​Huxley circuit model  23–​24
heart rate variability (HRV)  480–​81 Hofmann, S. G.  467
Hebb, D.  49 homeostasis, sleep (process H)  402–​3, 404
Hebbian cell assemblies and oscillations  49, Horder, J.  156
51–​52 Houweling, S.  271
Hebbian plasticity  53–​54 HTS (multivariate phase synchrony
Hebbian principles of association  54 measure)  527–​28
Heinrichs-​Graham, E.  270 Huang, N. E.  73
Heller, W.  467, 478 Hughes, D. M.  245
hemispheres, brain  207–​8, 268–​69, 310–​11, Huo, X.  270
506–​8 Hwang, K.  330–​31
see also brain; ventrolateral and dorsolateral hyperedge bundling  508
prefrontal cortex of the right hyperpolarization, thalamocortical
hemisphere (VLPFC and DLPFC) neurons 414
contralateral  53, 224, 264–​65 hyper-​spherical phase synchrony  519–​21
frontal intra-​hemisphere coherence  304–​5, hypothalamus 402
306, 307
right and left  6, 135f, 220, 221, 411–​12, 450, I
542–​43 idling hypothesis  206–​8, 565–​66
anxiety, imaging control functions  465, Iemi, L.  124
466, 467 Igarashi, J.  273–​74
childhood/​infancy, frequency imaging control functions in anxiety
development  307, 308–​9 alpha and anxiety  465–​69
sensorimotor function  259–​60, 271–​72 cross frequency coupling  474–​77
Henriques, J. B.  239–​40 frontal midline theta  469–​74
Herrmann, C. S.  146 future directions  480–​81
Heschl’s gyrus  450 theoretical considerations  477–​80
Hewig, J.  234–​35, 237–​38 impedance  21, 33, 37–​38
high-​frequency oscillations (HFOs) 261f, 265, impulse response  24, 37–​38
273–​74 impulsivity  233–​34, 235
Hilbert–​Huang Transform (HHT)  73 in ADHD  354, 361
Hilbert spectral analysis  73, 77 trait  235, 246
Hilbert transform  69, 77, 79–​81, 499–​500, 518 independent component analysis (ICA)  34,
Hillebrand, A.  269 91, 382, 546
596   Index

induced (total) gamma activity  151–​52 invertebrate ganglia

and microsaccades  158–​60 in vitro studies  47
induced activity MP (IMP)  75–​76 Ioannidis, J. P. A.  8–​9
induced waves  145–​46 ionization  37–​38
infancy, EEG frequency across see childhood/​ irregular-​resampling auto-​spectral analysis
infancy (IRASA) 570
inferior frontal gyrus (IFG)  275 ISO see infraslow oscillations in sleep (ISO)
infinite impulse response (IIR)  24, 26
information J
alpha/​beta power and oscillations  209 Jensen, O.  122, 123, 207–​8
and decreases in alpha power  208–​11 Johnson, M. C.  467
information-​via-​desynchronization
hypothesis 209 K
mutual 496 Kanizsa square  439, 440
a priori  382–​83 Kanizsa triangle  151
representation and alpha power  208–​11 K-​complexes  413
sampling and replay, in alpha phase  211–​14 Keil, A.  5
sensory  138–​39 Kemp, A. H.  467
task-​irrelevant  208 kernel function/​regression  70–​7 1, 335
infradian cycles, sleep  404–​7 Kerren, C.  213–​14
infragranular labeled neurons  138 Kim, J.-​ H.  387–​88
infraslow oscillations in sleep (ISO)  410–​12 Kim, S.  450
see also slow oscillation (SO), in sleep Klimesch, W.  45, 207, 312
cyclic alternating pattern (CAP)  411–​12 Knyazev, G. G.  474–​75
slow wave activity and sleep Kolev, V.  328, 329
spindles  411–​12 Krishnan, G. P.  442
insulators  16–​18, 37–​38
inter-​areal phase-​and amplitude L
coupling 508 Lachaux, J. P.  514–​15
inter-​channel phase synchrony (ICPS)  83, language learning  300
472–​73 Lansbergen, M. M.  363
inter-​electrode phase synchrony  439 Laplacian filter  380
internal pallidum (GPi)  260–​61, 267, 272, 273 large-​scale frequency-​following
International Affective Picture System  473 responses  54–​55
interneurons  132–​33, 448–​49 latency  88–​90
inter-​trial phase consistency (ITPC)  329–​30, latent growth curve (LGC)  339
333–​34, 339–​45, 346 lead-​field matrix  378, 379
inter-​trial phase synchrony (ITPS)  83 learning
intracranial EEG (iEEG)  133–​34 active 295
intrinsic mode functions (IMFs)  72, 73, 77, altered oscillations due to  270–​7 1
80–​81 associative  53–​54, 153–​54, 361
inverse model bimanual 271
“inverse problem” with EEG source language 300
analysis  381–​82 machine learning  34, 57, 275
a priori information, as constraints to EEG and memory  52, 53–​54, 164, 359, 424
inverse solution  382–​83 motor 422
procedures 377 motor skill  271
 Index   597

neurofeedback 223 Looney, D.  80–​81

oscillatory activity  271 loss-​related theta (FN)  103–​4
punishment 361 Löwdin orthogonalization  506–​8
reinforcement  181–​82 low-​pass RC filter 22f, 22
reversal  362–​63 low-​resolution electromagnetic tomography
reward 361 (LORETA)  380–​81, 384
sensorimotor 270 Lubar, J.  354
sleep spindles  422 Luck, S. J.  5, 127
trial and error  471 Luria’s Hand game  306
Leicht, G.  438–​39 Lyapunov coefficients  50
Levin, E. A.  475
Lindsley, D. B.  295, 297, 298 M
linearly constrained minimum variance macaque monkey
(LCMV)  546–​47 dendrites  132–​34
linear mixed effects (LME) regression hippocampal theta rhythms  184
models  334–​35 neocortical local field potential
linear mixing  504–​6 and cognition  134
linear time-​frequency decomposition comparisons with human
methods  66–​69 neocortex  131–​32
continuous wavelet transform (CWT)  68–​ frequency analysis  131–​40
69, 80, 84 neocortical oscillations  133–​34
short-​time Fourier transform in prefrontal neocortex  138–​39
(STFT)  67–​68 phase coupling and causality
linked mastoid (LM)  35–​36 in fronto-​parietal network  139
Litvak, V.  267 in sensorimotor systems  134–​35
Liu, Q.  330–​31, 391–​92 in visual neocortex  136–​38
local field potentials (LFPs)  44, 45, 47, 48, 131, prefrontal cortex  131–​32
563 visual cortex  51
see also macaque monkey neocortical local machine learning  34, 57, 275
field potential McNaughton, N.  475, 478, 479–​80
alpha power decreases  210–​11 macroscale 46
beta power  264–​65 magnetic resonance imaging (MRI)  90, 378–​
prefrontal laminar  139 79, 386
sensorimotor system  260–​61 structural 383
synchronized oscillations  269 magnetoencephalography (MEG)  48, 115–​16,
longitudinal research  271, 326–​28, 132–​34, 382, 384
342–​43 developmental research,
ANOVA  334–​35 adolescence  330–​31
design  327–​28, 331–​33, 345 frequency development across infancy/​
frequency development across infancy/​ childhood  298, 299
childhood  297–​98, 299–​300, 301, and schizophrenia  440–​41
303–​4, 308, 311–​12 sensorimotor system  260–​61, 269
models 332 major depressive disorder  416–​17, 422
time-​frequency activity  335–​38 Makeig, S.  65–​66
long-​term memory (LTM)  151 Mallat, S. G.  73
long-​term potentiation (LTP)  539 Malone, S. M.  336, 339
Loomis, A. L.  418–​19, 420 Mangels, J. A.  152
598   Index

Mantini, D.  391–​92 MMP see multichannel matching pursuit (MMP)

Marshall, P. J.  301 modafinil 443
mastoids, referencing  34–​35, 36f mode mixing problem  73
matching pursuit (MP)  66, 71–​72, 73–​75 Moisello, C.  271
with a Gabor dictionary  74–​75, 77, 79f monkey, macaque see macaque monkey
Mazaheri, A.  122, 123, 207 neocortical local field potential;
MCC see midcingulate cortex (MCC) macaque monkey visual cortex
medial-​frontal negativities (MFNs)  98 Mooney faces, upright and inverted  440
mediofrontal negativity (MFN)  180–​81 Morlet wavelet  103, 120f, 499
mediofrontal spikes  183 time-​frequency decomposition (TFDs)
memory methods  68–​69, 76–​77, 80
see also working memory morphology
and attention  203–​4, 212 ERP dynamics  326–​27
encoding and retrieval  179 mismatch negativity (MMN)  92–​93
and learning  52, 53–​54, 164, 359, 424 sleep spindles  419–​20
long-​term  151 motivation
oscillations as substrate of representations see also asymmetric frontal cortical activity;
in 59 motivational direction
short-​term  152 approach see approach motivation
menstrual cycles  404–​7 avoidance 231
mesolimbic pathway  359 and executive function  368–​69
mesoscale 46 facial expressions  226–​27
methylphenidate (Ritalin)  355, 358, 359 intense 230
Meyer, B.  299 and prefrontal cortex  359
Michelmann, S.  214 situational manipulations
microsaccades and asymmetric frontal cortical
defining 158 activity  225–​27
frontally occurring microsaccade-​induced pictures of motivationally significant
saccadic spike potential  158–​59 stimuli  225–​26
and induced gamma activity  158–​60 and positive affect  226
rate 158 whole body posture, use of  227
microscale 46 motivational direction  224–​27
midcingulate cortex (MCC)  179–​80, 470 see also motivation
anxiety and time-​frequency representations and affective valence  221, 227–​28
of activity  472–​74 defining 221
Milioli, G.  411 situational manipulations and asymmetric
Miller, E.  132 frontal cortical responses  225–​27
mind wandering, in ADHD  366 trait 225
minimum norm estimation (MNE)  380–​81 motor cortex  206–​7, 208, 264
Minnesota Center for Twin and Family brain stimulation  542–​43, 551
Research (MCTFR)  335–​36, 338 lesions 276
Minzenberg, M. J.  443 precentral  262–​63
mirror neurons  275 pre-​motor cortex  274
Miskovic, V.  475–​76 primary 261f, 266–​67, 539
mismatch negativity (MMN)  92–​93, 187–​88 in rats  273–​74
missingness by design  332–​33 superficial areas  551
Mizuki, Y.  469–​70 motor evoked potentials (MEPs)  538–​39
 Index   599

movement disorders, altered oscillations due functional  444–​45

to  271–​73 functional connectivity (FC)  523
MP see matching pursuit (MP) neuromodulation  45–​46
mu (central alpha) band neurons
compared with alpha and beta  262–​63 see also interneurons
ontogenesis  297–​98 correlated  210–​11
source localization, cortical  392 GABAergic 422
mu (central alpha) rhythms see alpha rhythm hippocampal 51
multichannel matching pursuit Hodgkin–​Huxley circuit model  23–​24
(MMP)  75–​76 lower-​level  154
multivariate synchronization  514–​28 mirror 275
see also graph theoretic metrics olfactory 54
direct measures  518–​21 open field  4–​5
global field synchronization (GFS)  518 parallel-​oriented cortical  65
hyper-​spherical phase synchrony  519–​21 physiological basis of EEG  4–​5
multivariate methods for functional presynaptic  154, 209
connectivity (FC) analysis  514–​28 pyramidal  4–​5, 15
omega complexity  517–​18 sensorimotor neocortical  134–​35
S-​estimator  517 simple circuit model  23
spectral methods for  517–​18 sodium-​potassium pumps  23
Murthy, V. N.  269 spike trains  435
muscle artefact (electromyography)  7 supragranular and infragranular  138
mutual information  496 task-​irrelevant 210f, 210–​11
thalamic reticular  421
N thalamocortical  414, 421, 447–​48
N170 ERP component  378–​79 neurophysiological mechanisms, gamma
Narayanan, B.  446 activity  153–​55
narrowband analyses  570–​7 1 Neuropsychiatric EEG-​Based Assessment Aid
National Institute of Mental Health (NIMH), Health 356
Research Domain Criteria  187 neurostimulation 45
Neal, L. B.  233–​34, 235 neurotransmitters 4
negative affect, situational manipulations  224 neutrons 16
neural field potential data nicotine 359
defining oscillation  564–​66 Nikulin, V. V.  122
discussions  573–​74 NMDA (N-​Methyl-​D-​Aspartate)  49
parameterizing  563–​74 NMDAR (N-​methyl-​D-​aspartate receptor)
parameterizing neural field potentials  569–​72 hypofunction
neural mirroring  302–​3 brain stimulation  538–​39
neurofeedback 223 and schizophrenia  438, 449–​50
gamma activity  164–​65 no-​interaction null hypothesis  503
neuroimaging non-​deterministic polynomial-​time hard
see also functional magnetic resonance (NP-​hard) problems  73
imaging (fMRI); magnetic resonance nonlinear dynamics  50
imaging (MRI); positron emission non-​rapid eye movement (NREM)
tomography (PET) sleep  401–​2, 411–​13
combining with brain stimulation  544–​48 see also rapid eye movement (REM) sleep;
EEG techniques  90 sleep
600   Index

non-​rapid eye movement (NREM) oscillations, neural  40–​59

sleep (cont.) see also alpha oscillations; beta oscillations
and delta waves  413–​14 amplitude modulation of neuronal
FMT activity during  415–​16 oscillatory activity  121, 122f
infradian cycles  404–​7 aperiodic signal  568–​69
overall picture of sleep EEG  408–​9, 410 auditory gamma  436–​39
positive occipital sharp transients baseline shifts  122, 123f
(POSTs) 418 and behavior
ultradian cycles  404 examples  41–​42
vertex sharp transients  418 oscillations as pacemakers for  58
nonsinusoidal oscillations  566–​68 role in  48–​52
norepinephrine 443 broadband activity  496–​97
Nottage, J. F.  156 as carriers of communication signals  58
NREM sleep see non-​rapid eye movement cognitive tasks context  44–​45
(NREM) sleep in complex systems  40–​41
Nusslock, R.  240–​41, 242–​43, 467 complex system theory  50
Nyquist sampling rate/​frequency  24–​26, conceptual framework, elements of  56–​59
37–​38 coupled oscillator models  46–​47
within-​ and cross-​frequency
O coupling  495–​509
obsessive compulsive disorder (OCD)  97 cyclic and recurrent  42–​43
occipital alpha attenuation  303 defining  40–​41, 204, 564–​66
occipital cortex, right and left  207–​8 at different observation levels  46–​48
occipital face area (OFA)  378–​79 as drivers of plasticity  57–​58
ocular activity  157 as epiphenomena  57
oddball task  94, 157, 326–​27, 332 frequency see frequency analysis
auditory 447 frequency bands  45–​46
Begleiter’s rotated heads  335–​36, 345–​46 gamma
EAGBR  438–​39 auditory  436–​39
novelty 335 sensory and perceptual  435–​42
P3 (ERP component)  94–​96 visual  439–​42
“simple”  333–​34 and Hebbian cell assemblies  49, 51–​52
visual  324, 327, 329 inter-​scale interactions  48
olfactory bulb, animals  145–​46 learning and memory  53–​54
rabbit olfactory system  50–​51, 54, local-​ and inter-​area  52
145–​46 long-​term changes in oscillatory
omega complexity  517–​18 activity  269–​73
ontogenesis of EEG bands  294–​300 development and aging  270
alpha band (alpha family)  296–​98 learning  270–​7 1
delta band  295 movement disorders  271–​73
theta band  295–​96 low-​frequency  445
open field  4–​5 neocortical, in monkeys  133–​34
orbitofrontal cortex (OFC)  475 nonsinusoidal  566–​68, 567f, 572
Orekhova, E. V.  296 oscillatory brain dynamics  434–​51
Oribe, N.  438 oscillatory hierarchies  51
orthogonalized cross correlation oscillatory synchrony  153
(oCC)  506–​8 periodic  40–​41, 573
 Index   601

periodic stimulation, generating Parkinson’s disease (PD)  163, 183–​84, 265, 267, 272
oscillations by  54–​56, 56f and dementia  422
phase and amplitude correlations  497 Parrino, L.  411
pre-​event oscillatory activity  123–​26 partial correlation matrix  506–​8
in prefrontal cortex, of monkeys  138–​39 partial path diagram, bivariate growth
properties 204 model  343–​45, 344f
quantifying and categorizing 42f, 42–​44 parvalbumin-​expressing (PV+​) inhibitory
quasi-​periodic  496, 497, 498f neurons  448–​49
resting state  446 Pascual-​Marqui, R. D.  380–​81
ripples/​HFO oscillations  424 PCA see principal component analysis (PCA)
sensorimotor function see sensorimotor Pearson correlation coefficients  342–​43
system pedunculopontine nucleus (PPN)  267–​68
sensory and perceptual gamma, in Penn State Worry Questionnaire  467
schizophrenia  435–​42 perception
sinusoidal oscillators  184–​85 alpha-​band changes during  52–​53
slow delta and alpha  367–​68 action-​perception processes  302–​4
spatio-​temporal patterns and travelling Gestalt perception  439–​41
waves  50–​51 oscillations as substrate of representations
spontaneous, in schizophrenia  435, 444–​48 in 59
and evoked activity  444–​45 sensory and perceptual gamma
as “noise”  444–​45, 447 oscillations  435–​42
sleep  447–​48 Perez, V. B.  438
during tasks  447 periodicity, sleep spindles  421
subthreshold 47 periodic stimulation, generating oscillations
synchrony and oscillatory by  54–​56, 56f
communication  51–​52 Peterson, E. J.  245
TMS-​evoked  435 PFC see prefrontal cortex (PFC)
traditional demarcation of oscillatory Pfurtscheller, G.  206–​7
events  45–​46 phase-​amplitude coupling (PAC)  501, 568
working memory task, changes during 43f, 43 phase and amplitude correlations of
oscillatory communication  51–​52 oscillations 497
Ozer, D. J.  244 phase-​and amplitude-​time series
estimation  499–​500
P phase coherency  44–​45
P2-​N2-​P3-​Slow Wave complex  95 phase coupling and causality, in monkeys
P2-​RewP-​P3-​Slow Wave complex  102 fronto-​parietal network  139
P3-​related processes sensorimotor systems  134–​35
components 94 visual neocortex  136–​38
ERP methodologies  92, 94–​96 Wiener–​Granger (WG) causality  134–​35,
oddball task  94–​96 137–​38, 139
P3a subcomponent  94 phase-​frequency regression  266–​67
P3b subcomponent  94 phase-​locking
reduced time-​domain P3  95–​96 see also phase-​locking value (PLV)
pallidal activity  273 gamma activity  162
Papenberg, G.  330–​31 indices of  44–​45
paradoxical sleep  404 inter-​trial  55–​56, 56f
parametrization algorithm  570–​7 1, 571f quantification of  42–​43, 502–​3
602   Index

phase locking factor (PLF)  436–​37, 438, 440, potassium ion channels  23–​24
447, 450 potential energy  18, 37–​38
phase-​locking value (PLV) power
and alternative measures  502–​3 see also alpha/​beta power and oscillations;
functional connectivity (FC)  514–​15 alpha power; beta power; gamma
imaginary part (iPLV)  505–​6 power; theta-​beta power ratio
linear mixing inflating  504–​6 baseline-​corrected  336–​38
measurement of phase synchrony and definitions of EEG frequency research  3–​4
CFC 504 enhanced beta/​gamma  423
single trial phase-​locking value (S-​PLV)  83 oscillations 91
phase-​phase coupling  568 peak power, in sleep  409
phase spectrum  28, 29f, 37–​38 a priori calculations, conducting  10–​11
phase synchronization index  82–​83 semi-​automated parameterization  570–​7 1
phase synchrony spectral see spectral power
see also synchrony time-​frequency  336–​38
inter-​regional  391 power spectrum  28, 37–​38, 65–​66
inter-​trial phase synchrony (ITPS)  83 predictive coding  53, 128
measures  82–​83 prefrontal cortex (PFC)  140, 359
phosphenes 549 and amygdala  310
photic stimulation  146 and attention  359
physiological artefacts  156–​58 and cognitive control  470
pictorial dot-​probe paradigm  364–​65 dorsolateral  330–​31, 468–​69
Pivik, R. T.  299–​300 lateral 473
plasticity macaque monkey  131–​32, 138–​39
Hebbian  53–​54 and medial frontal cortex  470
oscillations as drivers of  57–​58 oscillations in  138–​39
spike-​timing dependent plasticity and posterior parietal cortex  139, 140
(STDP) 539 right lateral  234
synaptic  153–​54, 270 schizophrenia, impairments in  311,
PLV see phase-​locking value (PLV) 442–​44
polarity  88–​90 and sleep  412–​13
population coding  264 and TMS-​evoked oscillations  444
positive affect and visual working memory  140
and approach motivation  224–​25, 226–​27 and VTA  359
and asymmetric frontal cortical Prehn-​Kristensen, A.  163
activity  224, 226–​27 “preparing to overcome prepotency” (POP)
positive occipital sharp transients task, 443
(POSTs) 418 pre-​register specific hypotheses  9–​10
positron emission tomography (PET)  378–​79, pre-​stimulus beta-​frequency coherence  134,
382 135f, 136–​37, 137f
raclopride 359 primary motor cortex 261f, 261
Possel, P.  240–​41 principal component analysis (PCA)  34, 35,
posterior alpha band, ontogenesis  297 91, 342–​43, 546
post-​synaptic potentials  4–​5, 47, 205–​6 developmental research, adolescence  336,
post-​synaptic receptor molecules  132–​33 337f, 339, 340f
post-​traumatic stress disorder (PTSD)  241, process H (sleep homeostasis)  402–​3, 404
467–​68 prokinetic gamma  264–​65
 Index   603

punishment-​elicited theta power  101 RID-​based phase estimation  81–​82

Putman, P.  476 time-​frequency decompositions
pyramidal cells  4–​5, 121, 153 (TFDs)  70–​7 1
columnar  381–​82 referencing  34–​36
cortical  450, 537 Regan, D.  146
dendrites of  47, 121 regions of interest (ROIs)  378–​79, 389–​91
excitatory  153, 263–​64, 448–​49 regression analysis
gamma activity  153, 161–​62 see also analysis of variance (ANOVA)
spiking of  263–​64 kernel function  70–​7 1
pyramidal neurons, synchronized  377 linear mixed effects (LME) regression
pyramidal tract neurons (PTNs)  264 models  334–​35
linear regression  34, 345–​46
R nonparametric regression  335
rabbit olfactory system  50–​51, 54, 145–​46 phase-​frequency regression  266–​67
Rabe, S.  467 piecewise linear regression  345–​46
Ramyead, A.  446 reinforcement sensitivity theory (RST)  478
rapid eye movement (REM) sleep  401–​2, relative left asymmetric frontal cortical
410 activity
see also non-​rapid eye movement (NREM) approach motivation  224–​25, 227, 232, 236,
sleep; sleep 237–​38, 245–​46
alpha activity  418 and state anger  229
FMT during NREM Stage 1 and REM relative right asymmetric frontal cortical
sleep  415–​16 activity
hippocampal RSA  415 and effortful control  232–​37
sawtooth waves during  416 frontal EEG activity
ratios evidence of r-​BIS functioning  234–​37
see also theta-​beta power ratio trait r-​BIS and frontal EEG
alpha-​beta EEG ratios  368 activity  233–​34
delta-​alpha power ratio  367–​68 REM sleep see rapid eye movement (REM) sleep
delta-​beta power ratio  367–​68 representational similarity analysis
delta-​theta power ratio  446 (RSA) 209
signal-​to-​noise ratio see signal-​to-​noise reproducibility in electrophysiology  8–​9
ratio research  10–​11
slow-​fast  368 see also data collection methods, frequency
Rayleigh test  503 analysis; research design
RC (resistors and capacitors) circuits approach motivation  244–​45
filters 24 asymmetric frontal cortical activity  243–​45
RC time constant  20–​21, 37–​38 auditory steady-​state response
reactance  21, 37–​38 (ASSR)  436–​38, 439
realistic head models, source analysis confirmatory testing  12
distinction between head tissues  383–​84 cross-​sectional see cross-​sectional research
importance in pediatric populations  385–​86 definitions of frequency research  3–​4
and structural MRI  383–​86 dependent variables  9–​10
uncertainty of the skull-​to-​brain early auditory-​evoked gamma band
conductivity ratio  384–​85 response (EAGBR)  438–​39
reduced interference distributions (RIDs) longitudinal see longitudinal research
developmental research, adolescence  336 neuroscience studies  10–​11
604   Index

research (cont.) multiplicity of, in sleep  402–​10

psychological research labs  6 oscillatory  116, 294–​95, 311–​12, 394
time-​frequency activity and psychological functions  354
characterizing the results  339–​42, 340f resting-​state oscillatory  311–​12
cohort-​sequential designs  332–​33 rhythmic repetitive application
design issues  331–​33 (rTMS)  534–​39, 536f, 541, 548
extending of findings  338 sensorimotor system  302–​4
missingness by design  332–​33 sigma 419
research design source localization  389
experimental  8–​9 Richards, J. E.  5
time-​frequency activity Richter, C. G.  138
cohort-​sequential designs  332–​33 Ridderinkhof, K. R.  391
missingness by design  332–​33 Riddle, C. N.  266–​67
resistance  16–​18, 21, 37–​38 RIDs (reduced interference distributions) see
resistors  21–​22 reduced interference distributions (RIDs)
resting asymmetric frontal cortical activity see Riečanský, I.  442
asymmetric frontal cortical activity right inferior frontal gyrus (rIFG)  233, 235
resting-​state see baseline (resting-​state) EEG right-​parietal activity  479
reticular thalamic nucleus  422 Rihaczek distribution  81–​82
reverse inference error  203–​4 Rodrigues, J.  238
reward-​related delta (RewP-​delta)  101, 102, Rodriguez, E.  439
103–​4 Rolandic fissure  262
rhythmic repetitive application (rTMS)  534–​ Rotation Invariant EMD (RIEMD)  81
35, 541, 544, 548
mechanisms underlying  535–​39, 536f S
rhythmogenesis 422 saccadic spike potential  158, 159, 160, 446
rhythms 4 frequency plot  159–​60
see also alpha rhythms; beta rhythms; microsaccade-​induced  158–​59
frequency analysis; frequency potential 160
bands; mu (central alpha) rhythms; reducing 160
oscillations, neural; rhythmic sampling rates, analog-​to-​digital signal
repetitive application (rTMS); conversion  24, 25f, 26f
rhythmogenesis; theta rhythms Nyquist sampling rate/​frequency  24–​26,
amplitude 275 37–​38
and attention  392–​93 Saturnino, G. B.  542–​43
behavioral 58 Sauseng, P.  387, 391
and BOLD signal  391–​92 Savostyanov, A. N.  475
in children  300, 312–​13 sawtooth waves, REM sleep  416
circadian  402, 404 scalp EEG
coinciding or overlapping  79–​80, 298, bivariate functional connectivity (FC)
311–​12 measures  504–​5
cyclical  40–​41 in children  424
differences between  262–​63 conventional  149–​50
importance in brain function  353 distributed source modeling  379–​80
infradian  404–​7 equipment  178–​79
interactions  311, 312 frontal midline theta (FMT)  178–​79
multiple theta  357, 360 gamma activity  151, 157
 Index   605

realistic head models, source analysis  384 sleep spindles and cognition  422
recordings  419–​20 as a “splitting of the mind”  435–​36
in schizophrenia  444–​45 spontaneous oscillations  435, 444–​48
scalp-​Laplacian  35–​36 resting state oscillations  446
scalp location  35 sleep oscillations  447–​48
scalp recordings  153, 159 during tasks  447
in ADHD  354, 355f transcranial magnetic stimulation
alpha activity  52–​53 (TMS) 444
EEG and MEG  450 unmedicated  161, 437, 438, 443, 446
field dynamics  65 visual evoked and induced gamma  441–​42
frontal midline theta (FMT)  179 working memory  434, 442–​44
gamma activity  147, 155–​56 schizotypal personality disorder  434, 437
potentials  365, 436 Schmeichel, B. J.  236
resting-​state frontocentral theta Schöne, B.  226
activity 353 Schutter, D. J.  475
scalp topography  88–​90, 102 selective attention, alpha-​band changes
theta 296 during  52–​53
Schaffer, C. E.  239–​40 sensorimotor system
schizophrenia cognitive aspects  274–​75
see also antipsychotic medication coherence
auditory gamma oscillations  436–​39 cortico-​cortical  268–​69
auditory steady-​state response cortico-​spinal  266–​67
(ASSR)  436–​38, 439 cortico-​subcortical  267–​68
early auditory-​evoked gamma band as a measure of functional connectivity
response (EAGBR)  436, 438–​39 (FC)  265–​69
auditory hallucinations  434 frequency bands see frequency bands
chronic  161, 437, 443, 446 long-​term changes in oscillatory
circuit mechanisms underlying oscillation activity  269–​73
abnormalities  448–​50 development and aging  270
NMDAR (N-​methyl-​D-​aspartate learning  270–​7 1
receptor) hypofunction  438, 449–​50 movement disorders  271–​73
reduced synaptic connectivity  450 movement-​related time-​frequency spectra
delusions 434 for primary motor cortex 261f, 261
early-​onset  434 oscillatory activity  259–​76
first-​episode  437, 438, 443 phase coupling and causality, in
future directions  451 monkeys  134–​35
and gamma activity  160–​61 understanding  259–​61
hallucinations 437 sensory and perceptual gamma oscillations
oscillatory brain dynamics  434–​51 auditory  436–​39
PFC impairments  311, 442–​44 auditory steady-​state response
psychotic symptoms  434, 437 (ASSR)  436–​38, 439
scalp EEG  444–​45 early auditory-​evoked gamma band
sensory and perceptual gamma response (EAGBR)  436, 438–​39
oscillations  435–​42 visual  439–​42
auditory  436–​39 Gestalt perception  439–​41
visual  439–​42 visual evoked and induced
Singer and Eckhorn labs  435 gamma  441–​42
606   Index

sensory processing slow oscillations (SO)  412–​13

gamma activity see gamma activity overall picture of sleep EEG  408–​10
septo-​hippocampal complex  352, 359, 360 paradoxical 404
S-​estimator  517, 526–​27 peak power  409
Shannon entropy  82–​83 polygraphic features  404, 405t
Sheer, D. E.  146 polysomnographic signal characteristics of
Sherman, M. A.  273 stages  404, 406f
short-​time Fourier transform (STFT)  31, positive occipital sharp transients
67–​68, 84 (POSTs) 418
sigma rhythm  419 rapid eye movement (REM)  401–​2, 410
signal-​to-​noise ratio  57–​58, 437, 447, 504 FMT during NREM Stage 1 and REM
decreased 447 sleep  415–​16
high 437 hippocampal RSA  415
low  106, 132 sawtooth waves during  416
poor 265 sleep to wake transition  403
superior  149–​50 slow oscillation (SO)  412–​13, 421
simulations 47 two-​process model 403f, 403
Singer, W.  146 ultradian cycles  404
single-​sweep wave index (SSWI)  328, 329 vertex sharp transients  418
single trial phase-​locking value (S-​PLV)  83 sleep spindles  418–​23
situational manipulations see asymmetric amplitude 420
frontal cortical activity; motivation, and cognition  422–​23
situational manipulations density and periodicity  421
sleep duration 420
see also sleep spindles fast 421
age factors  402–​3, 408, 413 frequency 419
alpha power/​waves  416–​18, 419 morphology  419–​20
amplitude  408–​9, 420 rhythmogenesis 422
beta and gamma activity during  423–​24 ripples/​HFO oscillations  424
circadian rhythms  402, 404 sharp negative-​positive waves  419–​20
consecutive cycles  404 smooth surface negative waves  419–​20
cycle of NREM and REM  404 topography 421
delta waves  352, 413–​14 Slobodskaya, H. R.  474–​75
detrended fluctuation analysis  409–​10 slow oscillation (SO), in sleep  412–​13, 421
EEG features  402–​10 see also infraslow oscillations in sleep (ISO)
frequency characteristics  401–​24, 407t slow wave activity (SWA)  354, 402–​3, 404,
frontal midline theta during NREM Stage 1 405t
and REM sleep  415–​16 see also P2-​N2-​P3-​Slow Wave complex; P2-​
homeostasis (process H)  402–​3, 404 RewP-​P3-​Slow Wave complex
infradian rhythms  404–​7 and delta waves  413–​14
multiplicity of rhythms  402–​7 and sleep spindles  411–​12
non-​rapid eye movement (NREM) see non-​ slow oscillation (SO)  412–​13
rapid eye movement (NREM) sleep slow wave sleep (SWS)  404, 405t, 408–​9, 410,
oscillations  447–​48 412–​14
infraslow oscillations in sleep EEG amplitude  408
(ISO)  410–​12 Snyder, S. M.  355
ripples/​HFO oscillations  424 social reward processing  101–​6
 Index   607

reward-​related delta (RewP-​delta)  101, 102, ssVEPs see steady-​state visual evoked
103–​4 potentials (ssVEPs)
Society of Psychophysiological Research  301 standardized low-​resolution brain
sodium ion channels  23–​24 electromagnetic tomography
source analysis studies  475 (sLORETA)  233, 380–​81, 387–​88, 392
source localization, cortical  377–​94 State-​Trait Anger Expression
see also inverse model Questionnaire  231, 234–​35
application of, in frequency steady-​state evoked potentials  146
analysis  386–​94 steady-​state responses  533–​34
clinical applications  388 steady-​state visual evoked potentials
forward and inverse model  377 (ssVEPs)  54–​56, 149f
frequency analysis  386–​88 Steriade, M.  412–​13
frequency bands  262–​63 Sternberg paradigm  443
functional brain connectivity, applying EEG Stewart, J. L.  240
source analysis  388–​92 STFT see short-​time Fourier transform
pediatric populations  385–​86, 392–​94 (STFT)
procedures 377 stimulus evoked responses  444–​45
realistic models and structural Stroganova, T. A.  297, 311–​12
MRI  383–​86 Strogatz, S. H.  523
techniques/​approaches  378–​83 Stroop-​like tasks  306
applying a priori information as structural equation model (SEM)  339
constraints to inverse solution  382–​83 structural MRI  383
distributed source modeling  378, 379–​82 and realistic models see realistic head
equivalent current dipole (ECD)  378–​79 models, source analysis
“inverse problem” with EEG source substance use disorder (SUD)  97
analysis  381–​82 subthalamic deep brain stimulation  568
source space  379 subthalamic nucleus (STN)  260–​61, 261f, 267,
spatial filtering  546–​47 272f, 272, 275–​76
spatio-​temporal patterns  50–​51 Summerfield, C.  152
spectral plots  301, 302f Sun, L.  441–​42
spectral power  106, 564 superior temporal gyrus (STG)  450
averaging 273 suprachiasmatic nucleus (SCN)  402
band-​limited relative  410 supragranular labeled neurons (SLN)  138
changes in  271 supragranular layers  138
distributions  354, 355f surface negative deflection  412–​13
and oscillations  43, 44–​45, 54–​55 Sutton, S. K.  94
overall 157 SWA see slow wave activity (SWA)
sensorimotor system 261f, 261, 271–​72, 272f SWS see slow wave sleep (SWS)
sleep 410 synchronization  294, 310–​11
task-​related  157 see also desynchronization; event-​related
spectrogram 104 synchronization (ERS); multivariate
spectrum of spectra approach  411–​12 synchronization
Spencer, K. M.  439, 440, 441–​42, 447 global field synchronization (GFS)  518
spike timing  47, 134–​35, 153–​54, 497 phase synchronization index  82–​83
coordination of  185, 360, 564–​65 synchrony
spike-​timing dependent plasticity (STDP)  539 see also phase synchrony; time-​frequency-​
spike trains  45, 46–​47, 48 based phase synchrony analysis
608   Index

synchrony (cont.) low  353, 364–​65

hyper-​spherical phase synchrony  519–​21 methodological issues  367
inter-​electrode  439 neuro-​anatomic framework 366f, 366
medio-​lateral  187 and other ratios  367–​68
medio-​motor  185–​87 resting-​state, in ADHD  358, 361
medio-​occipital  185–​87 reward and punishment sensitivity  361–​63
and oscillatory communication  51–​52 theta phase dynamics, translational
phase synchrony, using PLV for potential  183–​87, 186f
measuring 504 and cognitive control  185–​87
time-​frequency analyses  66 and decision integration  184–​85
synthetic aperture magnetometry  546–​47 theta power  93, 97, 100–​1, 335, 391, 472f, 473
see also theta-​beta power ratio
T and age  330–​31, 335, 342–​43
Tal, N.  160 and BOLD signal  359
Talairach, J.  179 and delta-​beta  446, 449
Tan, H.  270–​7 1 increases in  102, 295–​96, 346, 392–​93
task difficulty vs. task demands  333–​34 and ITPC  339–​43, 342f
technical artefacts  155–​56 punishment-​elicited  101
temperament, affective processes  308–​9 sex differences  335
TFDs see time-​frequency decomposition topographic distribution  339
(TFDs) methods theta rhythms  127–​28, 295, 357, 360
thalamic gating mechanism  52–​53 and frontal midline theta (FMT)  178, 183,
thalamocortical neurons  414, 421, 447–​48 184–​85
thalamus  4–​5, 352–​53 multiple theta  357, 360
schizophrenia  447–​48, 449 theta waves  93, 363
sensorimotor system  259–​60, 260f see also theta-​beta power ratio; theta power;
sleep  413, 422–​23 theta rhythms
ventrolateral  267, 272–​73, 275–​76 and rhythmic hippocampal slow
theta band (4–​8 Hz) activity  415–​16
and ADHD  354 Thigpen, N. N.  5
feedback negativity (FN)/​reward positivity Thorndike’s law of effect  362
(RewP)  99–​100 rhythmic slow activity (RSA)  415
Granger prediction  185–​87 Tierney, A.  299–​300
limbic areas  352 time-​domain feedback-​P3 104
ontogenesis  295–​96 time-​domain studies  93
phase coupling and causality, in time-​frequency activity
monkeys 138 see also time-​frequency decomposition
source localization, cortical  387 (TFDs) methods
theta-​beta power ratio  352–​69, 476 in adolescence and early adulthood  324–​47
see also beta power; theta band (4–​8 Hz); advantages of time-​frequency
theta power; theta rhythms; theta waves activity  325–​27
in ADHD see attention deficit hyperactivity characterizing the results  339–​42, 340f
disorder (ADHD) covariation in patterns of change  342–​45
central executive and attentional control and development  328–​31
function  364–​66 developmental change  335
functional correlates  358–​61 empirical exploration  335–​46
high  353, 360, 362, 363, 364–​65 extending of findings  338
 Index   609

methodological issues  333–​34 EMD-​based phased estimation  80–​81

pubertal stage  334 measures of phase synchrony  82–​83
research design issues  331–​33 RID-​based phase estimation  81–​82
statistical analysis  334–​35 wavelet-​based phase estimation  80
task difficulty vs. task demands  333–​34 time-​frequency decomposition (TFDs)
advantages of developmental study methods  65–​84
advantages  325–​27 see also time-​frequency activity; time-​
ERP dynamics  326–​27 frequency-​based phase synchrony
fine-​grained analysis  325 analysis
stability of time-​frequency measures  325 continuous wavelet transform (CWT)  68–​
tracking developmental change  325 69, 80, 84
analysis  30–​32 data-​driven/​adaptive  71–​76
in the auditory oddball paradigm  328 empirical mode decomposition
and development  328–​31 (EMD)  72–​73, 77, 78f
auditory oddball paradigm  328 matching pursuit (MP)  73–​75
general developmental trends  329–​30 multichannel matching pursuit
related to specific psychological and (MMP)  75–​76
cognitive processes  329 discrete-​time  71
specific age-​related associations  330–​31 illustration 76f, 76–​77
energy, derivation of  336 linear  66–​69
in ERP methodologies  88–​107 logic behind EEG frequency analysis  31–​32
advantages  91–​92 non-​linear (Cohen’s class)  69–​7 1
error-​related negativity (ERN)  96–​97 quadratic  81–​82
feedback negativity (FN)/​reward short-​time Fourier transform (STFT)  31,
positivity (RewP)  98–​101 67–​68, 84
limitations  90–​91 time resolution  67–​68
mismatch negativity (MMN)  92–​93 TMS see transcranial magnetic stimulation
P3  92, 94–​96 (TMS)
social reward processing  101–​6 topography
methodological issues  333–​34 of alpha power  35–​36, 36f
overlapping signals  92 sleep spindles  421
related to specific psychological and trait affective valence  222
cognitive processes  329 trait anger  228
research trait anxiety  469–​70
characterizing the results  339–​42, 340f trait impulsivity  235, 246
design issues  331–​33 trait motivational direction  225
extending of findings  338 transcranial alternating current stimulation
single-​trial EEG signals  65–​66 (tACS)  165, 263, 363, 422, 534–​35, 540–​
stability of time-​frequency measures  325 41, 542–​44, 551
statistical analysis  334–​35 transcranial direct current stimulation
wavelet time-​frequency resolution trade-​off (tDCS)  534–​35
31f, 31 transcranial electrical stimulation
time-​frequency-​based phase synchrony (tES)  534–​35
analysis  79–​83 transcranial magnetic stimulation (TMS)
see also time-​frequency activity; time-​ coil  540, 548–​49
frequency decomposition (TFDs) evoked oscillations  444
methods pulses  545–​46
610   Index

transcranial magnetic stimulation behavioral context  138

(TMS) (cont.) beta band coherence  268–​69
repetitive  207–​8 in cats  146, 147
rhythmic repetitive application deep layers  155
(rTMS)  534–​39, 536f, 544 deprivation of sensory input  352–​53
in schizophrenia  435 frequency bands  140
targets for brain stimulation  540–​41, 544 gamma oscillations  146, 164–​65
traditional demarcation of oscillatory high-​frequency oscillations (HFOs)  441
events  45–​46 macaque monkey  51
transcranial random noise in mice  164
stimulation  534–​35 oscillatory field responses  54–​55
transmembrane ionic currents  132–​33 phase coupling and causality, in
travelling waves  50–​51 monkeys  136–​37
trial-​averaged component  98–​99 “prime”  136–​37
Tucker congruence coefficients  336 source localization, cortical  391
twin studies  335–​36, 438–​39 spike trains of neurons in  435
visual neocortex, in monkeys  51, 54–​55
U phase coupling and causality in  136–​38
Uhlhaas, P. J.  440–​41 visual steady-​state response (VSSR)  442, 447
ultradian cycles, sleep  404 Volkow, N. D.  359
uncertainty principle  67–​68 volt  37–​38
Unified Parkinson’s Disease Rating voltage  16–​18, 37–​38
Scale 272 fluctuations 88
univariate EMD  81 von Bülow, U.  41–​42
UPPS-​P scale  233–​34 Vorwerk, J.  384
UPPS-​P Behavioral Impulsivity Scale  235 Voytek, B.  4

V W
Van Dijk, B. W.  126 waking EEG  297
Van Honk, J.  475 Watts, D. J.  523
Van Peer, J. M.  475 wavelet analysis
van Tricht, M. J.  446 continuous wavelet transform (CWT)  68–​
Van Wijk, M.  266 69, 80, 84
ventral lateral thalamus  267, 275–​76 Morlet wavelet  103, 120f, 499
ventral tegmental area (VTA)  359, 360 time-​frequency decomposition (TFDs)
ventrolateral and dorsolateral prefrontal methods  68–​69, 76–​77, 80
cortex of the right hemisphere quantifying and categorizing brain
(VLPFC and DLPFC)  330–​31 oscillations 43
vertex centrality  509 wavelet-​based phase estimation  80
vertex sharp transients  418 wavelet time-​frequency resolution trade-​off
vertical electro-​oculogram (VEOG)  158 31f, 31
vigilance, effective and affective facets of  179 wavelet transforms  91–​92
visual cortex Webb, C.  101
see also macaque monkey weighted phase-​lag index (wPLI)  389–​91,
alpha oscillations  206–​7 505–​6
attentional influences on  154–​55 White, T. L.  225
 Index   611

white matter (WM)  383, 384 related to working memory

Whitham, E. M.  147 processes  442–​44
wide band analysis  301 oscillatory changes during task 43f, 43
Wiener–​Granger (WG) causality  134–​35, oscillatory hierarchies  51
137–​38, 139 P3  94–​95
Wigner distribution  70, 74 prefrontal neocortical oscillatory
Williams syndrome  422 activity  131–​32
windowing  7, 30 schizophrenia  434, 442–​44
fixed time-​window size  500 Wu, Z.  73
moving window Fourier transforms  31, Wynn, J. K.  440
91–​92
sliding window approach  66 X
time-​frequency trade-​off  31 Xie, W.  5, 389–​91, 394
window functions  30
Winterer, G.  447 Y
working memory Yordanova, J.  96–​97, 162, 328, 329
cognitive processing  133 Yuval-​Greenberg, S.  147, 158, 159, 160
infants 389
macaque monkeys and humans  131–​32 Z
oscillations Zhang, Z.  73
changes in during task 43f, 43 Zhao–​Atlas–​Marks RID  70–​7 1