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Psychiatry and Clinical Neuroscience PDF

322 Pages·2011·2.584 MB·English
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Psychiatry and Clinical Neuroscience This page intentionally left blank 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 1 1 Oxford University Press, Inc., publishes works that further Oxford University’s objective of excellence in research, scholarship, and education. Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne M exico City Nairobi New Delhi Shanghai Taipei Toronto With offi ces in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan Poland Portugal Singapore South Korea Switzerland Th ailand Turkey Ukraine Vietnam Copyright © 2011 by Oxford University Press, Inc. Published by Oxford University Press, Inc. 198 Madison Avenue, New York, New York 10016 Oxford is a registered trademark of Oxford University Press Oxford University Press is a registered trademark of Oxford University Press, Inc. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitt ed, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of Oxford University Press, Inc. ______________________________________________ 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 Note to Readers Th is material is not intended to be, and should not be considered, a substitute for medical or other professional advice. Treatment for the conditions described in this material is highly dependent on the individual circumstances. And, while this material is designed to off er accurate information with respect to the subject matt er covered and to be current as of the time it was writt en, research and knowledge about medical and health issues is constantly evolving and dose schedules for medications are being revised continually, with new side eff ects recognized and accounted for regularly. Readers must therefore always check the product information and clinical procedures with the most up-to-date published product information and data sheets provided by the manufacturers and the most recent codes of conduct and safety regulation. Th e publisher and the authors make no representations or warranties to readers, express or implied, as to the accuracy or completeness of this material. Without limiting the foregoing, the publisher and the authors make no representations or warranties as to the accuracy or effi cacy of the drug dosages mentioned in the material. Th e authors and the publisher do not accept, and expressly disclaim, any responsibility for any liability, loss or risk that may be claimed or incurred as a consequence of the use and/or application of any of the contents of this material. Y ou may order this or any other Oxford University Press publication by visiting the Oxford University Press website at www.oup.com In anticipation of remarkable scientifi c advances leading to cures for psychiatric disorders This page intentionally left blank 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

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