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Brain Imaging in Substance Abuse Research, Clinical, and Forensic Applications Edited by Marc J. Kaufman, PhD Humana Press Brain Imaging in Substance Abuse F O R E N S I C S C I E N C E A N D M E D I C I N E Steven B. Karch, MD, SERIES EDITOR BRAIN IMAGING IN SUBSTANCE ABUSE:Research, Clinical, and Forensic Applications edited byMarc J. Kaufman,2001 TOXICOLOGYAND CLINICAL PHARMACOLOGYOF HERBAL PRODUCTS, edited by Melanie Johns Cupp,2000 A PHYSICIAN'S GUIDE TO CLINICAL FORENSIC MEDICINE, edited byMargaret M. Stark,2000 CRIMINAL POISONING:INVESTIGATIONAL GUIDEFOR LAW ENFORCEMENT, TOXICOLOGISTS, FORENSIC SCIENTISTS,AND ATTORNEYS, byJohn H. Trestrail, III,2000 Brain Imaging in Substance Abuse Research, Clinical, and Forensic Applications Edited by Marc J. Kaufman P D H Harvard Medical School and McLean Hospital, Belmont, MA Foreword by Joseph Frascella PHD National Institute on Drug Abuse, Rockville, MD Humana Press Totowa, New Jersey © 2000 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. The content and opinions expressed in this book are the sole work of the authors and editors, who have warranted due diligence in the creation and issuance of their work. The publisher, editors, and authors are not responsible for errors or omissions or for any consequences arising from the information or opinions presented in this book and make no warranty, express or implied, with respect to its contents. This publication is printed on acid-free paper. (cid:39) ANSI Z39.48-1984 (American Standards Institute) Permanence of Paper for Printed Library Materials. Cover design by Patricia F. Cleary. For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or at any of the following numbers: Tel: 973-256-1699; Fax: 973-256-8341; E-mail: [email protected], or visit our Website at www.humanapress.com Photocopy Authorization Policy: Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Humana Press Inc., provided that the base fee of US $10.00 per copy, plus US $00.25 per page, is paid directly to the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license from the CCC, a separate system of payment has been arranged and is acceptable to Humana Press Inc. The fee code for users of the Transactional Reporting Service is: [0-89603-770-3/00 $10.00 + $00.25]. Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 Library of Congress Cataloging in Publication Data Brain imaging in substance abuse: research, clinical, and forensic applications/edited by Marc J. Kaufman. p.; cm—(Forensic science) Includes bibliographical references and index. ISBN 0-89603-770-3 (alk. paper) 1. Substance abuse—Diagnosis. 2.Brain—Imaging. 3.Brain—Effect of drugs on. 4. Diagnostic imaging. I. Kaufman, Marc J. II.Series. [DNLM: 1.Substance-Related Disorders—diagnosis. 2. Brain—drug effects. 3.Brain—physiology. 4. Diagnostic Imaging. 5. Forensic Medicine. WM 270 B814 2000] RC386.6.D52 B74 2000 616.86'0754—dc21 99-054063 Foreword The last two decades have seen prodigious growth in the application of brain imaging methods to questions of substance abuse and addiction. Despite considerable advances in our understanding of the central effects of drugs provided by preclinical data, relatively little direct evidence was known of how substances of abuse affect the brain and other CNS processes in humans. Brain imaging techniques have allowed access to the human brain and enabled the asking of questions never before imagined. The positron emission tomography (PET) data of Volkow and her colleagues in the late 1980s, showing the uptake and time course of cocaine’s binding in the human brain, revealed for the first time the distinct sites of action of this drug. This work was extremely important because it showed clearly, through imaging a drug in the brain of a living human, that the time course of its action paralleled the behavioral state of “high.” This study marked a turning point in our understanding of drug-brain-behav- ior interactions in humans. Many more investigations of drug effects on the structure and function of the human brain were soon to follow, leading to much better insights into brain systems. Brain imaging allowed for the direct assessment of structural and functional anatomy, biology, and chemistry in substance abusers. The effects of both acute and chronic exposure could be assessed through imaging in the awake, behaving human, and these drug-induced changes in brain processes could be correlated effec- tively with increasingly more complex behavioral states. We now know much more about the subtle as well as distinct ways in which drugs influence brain-behavior interactions. Despite the tremendous advances revealed over the last several years, most of which are described in detail within this book, early applications of brain imaging techniques were met with some skepticism. Questions were raised regarding the large expense of such clinical studies. For example, early PET work was sometimes criti- cized as being a very expensive autoradiographic method that could be done more effectively in preclinical models. Experimenter control was seen as being somewhat compromised because human drug abusers typically are not single-substance abusers; thus, brain imaging findings might not be directly attributable to abuse of one drug. Further, brain changes noted in imaging studies might have represented abnormalities associated with a preexisting condition, rather than resulting from the effects of drug use. Fortunately, clinical imaging researchers addressed these and other issues and persisted through these early times. The field has blossomed to include other imaging v vi Foreword methods, and now includes studies that integrate findings across multiple modalites. The research findings detailed in this book are the product of this perseverance. Brain Imaging in Substance Abuse: Research, Clinical, and Forensic Applica- tionsis an outstanding and in-depth compilation of the state-of-the-science in the clinical neurobiology of substance abuse. This book will be an extremely useful resource to the field and will provide an excellent overview to the more casual reader. The review chapters are comprehensive and include most abused substances for which findings have been obtained. All major brain imaging techniques are covered in this book, and importantly, the methods chapters are written in clear language so that even those with nontechnical backgrounds will understand these highly complex technologies. These methods chapters include discussions of strengths, weaknesses, and future directions of each modality. The review chapters are critical examinations of the meth- ods and findings, and include discussions of experimental design factors that compli- cate clinical substance abuse research. Overall, what makes this book special and sets it apart from the usual text is its organization. A remarkably complete and structured bibliography with over 1350 citations is included. Detailed Tables of Contents and the extensive index facilitate access to topics and findings of interest. Thus, in addition to being a complete collection of critical reviews of the field, this book will serve as a particularly useful reference. Rapid developments in brain imaging technology, as well as the integration of findings from individual brain imaging methods and combinations thereof, will lead us to a much better understanding of the neurobiology of substance abuse and addic- tion. The science presented in this book will form a firm foundation for future suc- cesses in this research endeavor. Joseph Frascella, PHD Chief, Clinical Neurobiology Branch Division of Treatment Research and Development National Institute on Drug Abuse Preface Brain imaging techniques are increasingly being used by clinical researchers, physicians, forensics experts, and lawyers to evaluate mechanisms and consequences of brain changes associated with acute and chronic substance abuse. Because of the technical nature and high costs historically associated with most brain imaging modalities, access to these technologies, and their practical applications in substance abuse research have been limited. However, the number of clinical research sites imple- menting brain imaging modalities is multiplying, and the techniques themselves are becoming less invasive and less expensive. This evolution will ensure expanded use of brain imaging in substance abuse-related research, diagnosis, and litigation. The goal of Brain Imaging in Substance Abuse: Research, Clinical, and Foren- sic Applicationsis to describe the methods and to review the research findings gener- ated by clinical brain imaging modalities most commonly used in the study of substance abuse and dependence. These include electroencephalography, emission tomography, and magnetic resonance. By themselves, each of these powerful techniques has the ability to measure a number of parameters that indicate brain function, including elec- trical activity, metabolism, hemodynamics, receptor and neurotransmitter levels, neu- rochemistry, and structure. It is the consensus of the contributors to this volume that the most comprehensive view of the mechanisms and consequences of drug abuse and dependence will be achieved by those who can understand and synthesize the research findings from all of these brain imaging modalities. Pursuit of an integrated understanding of the literature from all of these fields is by no means a trivial goal, since each modality has numerous technical complexities. This book has been organized to assist in this effort. The first three chapters of the book describe the technical foundations for electroencephalography, emission tomog- raphy, and magnetic resonance. These chapters also discuss the strengths and weak- nesses of each method. Chapters 1–3 are written so that readers with nontechnical backgrounds will be able to appreciate how these technologies work. Chapters 4–6 present comprehensive reviews of the electroencephalographic, emission tomographic, and magnetic resonance research findings in substance abuse, and also discuss the methodological factors that complicate the interpretation of results from studies of chronic substance abusers. These factors include the confounds of polydrug abuse, medical and/or psychiatric comorbidity, premorbid disease, and genetic or sociologic predisposition to substance abuse. A concise, comprehensive list vii viii Preface of the many confounds that confront all clinical brain imaging studies of chronic sub- stance abusers is presented as a part of Chapter 4. Chapter 7 focuses on the neuropsychology of substance abuse. While neuropsy- chological assessment is not strictly a form of brain imaging, it offers standardized and reliable methods for relating neuroimaging findings to higher levels of brain func- tion. Accordingly, it is increasingly being required by peer-review committees, jour- nal referees, and courts, to provide functional context for neuroimaging findings. This chapter reviews the extensive neuropsychology literature in substance abuse, lists and describes the most commonly used neuropsychological tests, and also discusses the strengths and weaknesses of this discipline. There is a nexus between substance abuse and crime, and as a result, it is expected that brain imaging findings will see expanded use (and misuse) in legal contexts. Chapter 8 discusses these issues and proposes guidelines for appropriate use of brain imaging findings in the courtroom. This chapter also contains a discussion of the scientific and legal definitions of “evidence,” and of how differences in these definitions between the professions contribute to problems when science (and scientists) enter the court- room. This chapter is particularly relevant to judges who must render legal decisions based on legal andscientific precedents, because, according to Supreme Court rulings regarding the presentation of scientific evidence, they must serve as “gatekeepers,” scrutinizing the relevance of expert scientific testimony. The last part of the book is a comprehensive bibliography of clinical brain imag- ing and neuropsychological research in substance abuse. The bibliography is struc- tured by technique and by substance abuse topic, and has a detailed table of contents to facilitate rapid access to topics of interest. It is my hope that Brain Imaging in Substance Abuse: Research, Clinical, and Forensic Applicationswill help to foster a more complete understanding of the effects of substance abuse on the human brain, by providing better access to the methods and findings in this field. A CKNOWLEDGMENTS I am grateful to my distinguished colleagues who contributed chapters to this volume, and to the following individuals for their contributions: J. T. Arnold, PHD Linda Chang, MD Bruce M. Cohen, MD, PHD Eileen Connolly, RTR Lyn Dietrich, MSLS, AHIP Kerstin Dostal, BA Richard R. Ernst, PHD Thomas Ernst, PHD Joseph Frascella, PHD Håkan Hall, PHD Arnold R. Kriegstein, MD, PHD Paul C. Lauterbur, PHD Preface ix Edythe D. London, PHD Peter R. Martin, MD Nancy K. Mello, PHD Jack H. Mendelson, MD Rabbi Donald J. Pollock, DAPA John J. Resnik, JD Anne M. Smith, RTR Edith B. Stern Lawrence L. Wald, PHD I would also like to thank the National Institute on Drug Abuse for generous grant support. Additionally, I would like to acknowledge Bertha K. Madras, PHD, for a decade of wonderful mentorship, friendship, and insight. Finally, I am indebted to my wife Rebekah, who spent many hours assisting in the preparation of this volume. My life and work have always benefited from her touch. Marc J. Kaufman, PHD

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Highly experienced clinical researchers from diverse fields describe in detail the use of electroencephalography, emission tomography, magnetic resonance imaging, and neuropsychology to study the neural effects of substance abuse. They extensively review research findings these powerful methods have
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