Psychiatry and Clinical Neuroscience

322 Pages·2011·2.584 MB·English

by  Charles Zorumski and Eugene Rubin

Psychiatry and
Clinical Neuroscience
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Psychiatry and
Clinical Neuroscience
A Primer
Charles F. Zorumski , MD
Samuel B. Guze Professor and Head of Psychiatry
Professor of Neurobiology
Chief of Psychiatry, Barnes–Jewish Hospital
Director of the McDonnell Center for Cellular and Molecular Neurobiology
Washington University in St. Louis–School of Medicine
Eugene H. Rubin , MD, PhD
Professor of Psychiatry
Vice-Chair for Education, Department of Psychiatry
Professor of Psychology
Director of Geriatric Psychiatry, Barnes–Jewish Hospital
Washington University in St. Louis–School of Medicine
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1

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Library of Congress Cataloging-in-Publication Data
Zorumski, Charles F.
Psychiatry and clinical neuroscience: a primer/Charles F. Zorumski, Eugene H. Rubin.
p.; cm.
Includes bibliographical references and index.
ISBN 978-0-19-976876-9
1. Psychiatry. 2. Neurology. I. Rubin, Eugene H. II. Title.
[DNLM: 1. Mental Disorders—physiopathology. 2. Brain—physiology. 3. Diagnostic Techniques, Neurological.
4. Neurosciences—trends. 5. Psychiatry—trends. WM 140]
RC321.Z67 2011
616.89—dc22 2010042933
______________________________________________
9 8 7 6 5 4 3 2 1
Printed in the United States of America on acid-free paper
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In anticipation of remarkable scientifi c advances
leading to cures for psychiatric disorders
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Foreword
In the minds of many, understanding how the brain works represents the last great
scientifi c frontier in biology, if not science in general. While a fascination with this
agenda can be related to brains large and small, the ultimate goal is to understand the
workings of the human brain. For herein lies not only the potential to understand
and ultimately treat, rationally and eff ectively, some of the most important diseases
affl icting mankind, but also to address social problems that continue to vex scien-
tists and scholars in fi elds as diverse as anthropology, political science, psychology,
sociology, and economics.
Understanding psychiatric diseases must form a cornerstone of any agenda prob-
ing the functions of the human brain. In this wonderful new book, Zorumski and
Rubin have seized the opportunity to think anew about the brain mechanisms
underlying psychiatric disorders and their treatment. Th is opportunity arose, in
part, through developments in cognitive neuroscience that are worth recalling1.
Th e term cognitive neuroscience was coined by Michael Gazzaniga and George
Miller while riding together in a taxi cab in New York City sometime in the late
1980s (personal communication). Th eir concept was that understanding human
brain function would be enriched signifi cantly if individuals with expertise in the
quantitative description of human behaviors (e.g., cognitive psychologists) could be
encouraged to join forces with scientists capable of monitoring the functions of the
human brain. Th eir view echoed a plea made almost 80 years before by Sir Charles
Sherrington when he suggested that “. . . physiology and psychology, instead of pros-
ecuting their studies, as some now recommend, more strictly apart one from another
than at present, will fi nd it serviceable for each to give to the results achieved by the
other even closer heed than has been customary hitherto.”2 In this book, Zorumski
and Rubin persuasively argue for a much closer relationship between psychiatry and
neuroscience.
As a result of the advocacy of Gazzaniga and Miller that was fueled by the rapid
emergence of techniques for human functional brain imaging, the James S.
McDonnell Foundation and the Pew Charitable Trusts jointly sponsored a program
of training and research that created the fi eld of cognitive neuroscience. Th is pro-
gram, one of the most successful of its kind ever, has made cognitive neuroscientists
an essential component of departments of psychology, psychiatry, neurology, and
neurobiology to name just a few of the most active participants. Brain imaging in the
hands of cognitive neuroscientists has become the medium for much of the discus-
sion as well as an important means of integrating studies of the human brain into
mainstream neuroscience. Th ese developments have appealed to a universal thirst
vii
for information about human brain function in health and disease among brain
scientists as well as the lay public.
Until recently, work in cognitive neuroscience followed a long tradition in neuro-
science of studying responses to stimuli and task performance. In this work, the role
of bott om-up versus top-down or feed-forward versus feed-back causality has fre-
quently been discussed, refl ecting a debate extending back a century or more on the
relative importance of intrinsic and evoked activity in brain function. Recent unex-
pected discoveries in functional brain imaging research have entered this discussion
and will likely be important in shaping future research. Th ese discoveries are impor-
tant to the ideas put forth by Zorumski and Rubin concerning the role of intrinsic
connectivity networks or ICNs in psychiatric diseases. Some historical background
to this work will likely enhance the reading of their book.
Since the 19th century and possibly longer, two views of brain function have
existed3. One view, pioneered by the early work of Sir Charles Sherrington, posits
that the brain is primarily refl exive, driven by the momentary demands of the envi-
ronment. Th e other view is that the brain’s operations are mainly intrinsic, involving
the acquisition and maintenance of information for interpreting, responding to,
and even predicting environmental demands, a view introduced by a disciple of
Sherrington, T. Graham Brown. Th e former has motivated most neuroscience
research including that with functional neuroimaging. Th is is not surprising because
experiments designed to measure brain responses to various stimuli and carefully
designed tasks can be rigorously controlled whereas evaluating the behavioral rele-
vance of intrinsic activity4 can be an elusive enterprise. How do we adjudicate the
relative importance of these two views in terms of their impact on brain function?
One means of adjudicating the relative importance of evoked and intrinsic activ-
ity is to examine their cost in terms of brain energy consumption. Most know that in
the average adult human, the brain represents about 2% of the total body weight yet
it accounts for 20% of all the energy consumed, 10 times that predicted by its weight
alone. However, far fewer realize that relative to this very high rate of ongoing or
‘basal’ energy consumption in the resting state5, the additional energy consumption
associated with evoked changes in brain activity is remarkably small, oft en less than
5%. From these data it is clear that the brain’s enormous energy consumption is litt le
aff ected by task performance. Furthermore, an increasing body of evidence suggests
that the majority of brain energy consumption is devoted to functionally signifi cant
signaling processes such as glutamate cycling. Th e challenge is how to study these
intrinsic brain processes. Functional brain imaging has provided some intriguing
new insights.
A prominent feature of fMRI is the apparent noisiness of the raw blood oxygen
dependent or BOLD signal that, for many years, prompted researchers to average
their data to increase its signal-to-noise ratio. As fi rst shown by Bharat Biswal and
colleagues at the Medical College of Wisconsin, this noise in the BOLD signal
exhibits striking patt erns of spatial coherence delineating all cortical systems in
the human brain and their subcortical connections. Th is highly organized ongoing
activity has been dubbed a default mode of brain function.
viii Foreword
Not only do spatial patt erns of coherence exist within brain systems but also
among systems organized around a hierarchical system of hubs. Th is satisfi es the
need to integrate information among systems for the brain to function properly. Of
particular interest is that one system in the brain seems to reside at the top of this
hierarchical organization. Th is is a group of cortical areas along the brain’s midline in
parietal and prefrontal cortices and in lateral parietal and medial temporal cortices
as well. Th is has come to be known as the brain’s default mode network because it is
most active in the resting state and oft en decreases its activity during the perfor-
mance of goal-directed tasks. It has been the focus of much att ention with regard to
psychiatric conditions because of the self-referential nature of its putative functions,
as Zorumski and Rubin discuss in detail in their book.
Furthermore, this highly organized ongoing activity appears to transcend
levels of consciousness, being present under anesthesia and during sleep. Th ese
observations make it unlikely that the patt erns of coherence and the intrinsic
activity they represent are primarily the result of unconstrained, conscious cogni-
tion (i.e., mind-wandering or day dreaming). Rather, they likely represent a funda-
mental level of functional brain organization adjudicating the delicate balance
between maintaining homeostasis yet allowing fl exibility needed for learning and
memory.
Th us, from resting-state fMRI data, investigators can now interrogate the integ-
rity of the brain’s large scale functional organization within and among systems at
a level of analysis commensurate with the complex signs and symptoms of psychiat-
ric illness. Remarkably, this can now be done without necessarily resorting to the
performance of tasks, a great advantage when comparing patients with diseases
impairing performance to normal control subjects.
Th e recent discovery of the electrical correlates of the fMRI BOLD signal have
further expanded our understanding of its importance in brain organization.
Emerging from this work is the fact that the BOLD signal represents the lowest end
of the brain’s electrical frequency spectrum (i.e., frequencies in the range of 0.001 to
0.1 Hz, which are traditionally referred to as slow cortical potentials or SCPs).
Knowing that SCPs and spontaneous fl uctuations in the BOLD signal are related
provides a bridge to a highly relevant, rich and diverse neurophysiologic literature
on low frequency oscillations/fl uctuations. For example, current evidence suggests
that SCPs represent highly organized fl uctuations in cortical excitability whose
phase aff ects both evoked responses and behavioral performance. Entrainment of
SCPs (and fMRI BOLD signals) to expected, predictable stimuli is an att ractive
means of matching predictions instantiated in intrinsic activity with the natural
regularities of the environment.
Also, SCPs exhibit a remarkable relationship with other elements of the
frequency spectrum of brain electrical activity, including the spiking activity of
neurons. Th ese relationships are likely mediated through variations in cortical excit-
ability. Th is cross-frequency coupling (i.e., nesting) with SCPs serving an overarch-
ing coordinating role within and across systems provides a basis for the integration
functions in both space and time.
Foreword ix