MAPPING THE BRAIN AND ITS FUNCTIONS

INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH

Constance M. Pechura and Joseph B. Martin, Editors

Committee on a National Neural Circuitry Database

Division of Health Sciences Policy

Division of Biobehavioral Sciences and Mental Disorders

INSTITUTE OF MEDICINE

NATIONAL ACADEMY PRESS
Washington, D.C.
1991



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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH MAPPING THE BRAIN AND ITS FUNCTIONS INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH Constance M. Pechura and Joseph B. Martin, Editors Committee on a National Neural Circuitry Database Division of Health Sciences Policy Division of Biobehavioral Sciences and Mental Disorders INSTITUTE OF MEDICINE NATIONAL ACADEMY PRESS Washington, D.C. 1991

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W. Washington, DC 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The Institute of Medicine was chartered in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy's 1863 congressional charter responsibility to be an advisor to the federal government and its own initiative in identifying issues of medical care, research, and education. The work on which this publication is based was performed pursuant to Contract No. 278-89-003 with the National Institute of Mental Health, Public Health Service, Department of Health and Human Services. Funds for this contract were provided by the National Institute of Mental Health, the National Institute of Drug Abuse, and the National Science Foundation (under NSF Agreement No. BNS-8913554). Library of Congress Cataloging-in-Publication Data Institute of Medicine (U.S.). Committee on a National Neural Circuitry Database. Mapping the brain and its functions: integrating enabling technologies into neuroscience research / Committee on a National Neural Circuitry Database, Division of Health Sciences Policy, Division of Biobehavioral Sciences and Mental Health, Institute of Medicine; Constance M. Pechura and Joseph D. Martin, editors. p. cm. — (Publication ; no. IOM-91-08) Includes bibliographical references and index. ISBN0-309-04497-9 1. Brain—Research—Data processing—Congresses. 2. Brain mapping—Congresses. I. Pechura, Constance M. II. Martin, Joseph B., 1938-. III. Title. IV. Series: IOM publication ; 91-08. [DNLM: 1. Brain—physiology. 2. Brain Mapping. 3. Medical Informatics. 4. Neurosciences. 5. Research. WL 335 I59m] QP376.I516 1991 612.8′2—dc20 DNLM/DLC for Library of Congress 91-4832 CIP Copyright ©1991 by the National Academy of Sciences No part of this book may be reproduced by any mechanical, photographic, or electronic process, or in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted, or otherwise copied for public or private use, without written permission from the publisher, except for the purpose of official use by the United States Government. Printed in the United States of America The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatlichemuseen in Berlin.

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH Committee on a National Neural Circuitry Database JOSEPH B. MARTIN (Chair), * Dean, School of Medicine, University of California, San Francisco KAREN J. BERKLEY, McKenzie Professor, Department of Psychology, Florida State University, Tallahassee VINTON CERF, Vice President, Corporation for National Research Initiatives, Reston, Virginia W. MAXWELL COWAN, † Vice President and Chief Scientific Officer, Howard Hughes Medical Institute, Bethesda, Maryland JEROME R. COX, * Welge Professor and Chairman, Department of Computer Science, Washington University, St. Louis, Missouri JOSEPH T. COYLE, * Distinguished Service Professor of Child Psychiatry, Director, Division of Child Psychiatry, Professor of Psychiatry, Neuroscience, Pharmacology, and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland RHETAUGH G. DUMAS, * Dean and Professor, University of Michigan School of Nursing, Ann Arbor JON H. KAAS, Centennial Professor of Psychology, Vanderbilt University, Nashville, Tennessee JAMES KAJIYA, Associate Professor of Computer Science, Department of Computer Science, California Institute of Technology, Pasadena RICHARD LUCIER, Director, Laboratory for Applied Research in Academic Information, Welch Medical Library, Johns Hopkins University, Baltimore, Maryland MARCUS E. RAICHLE, Professor of Neurology, Washington University School of Medicine, St. Louis, Missouri GORDON M. SHEPHERD, Professor of Neuroanatomy, Yale University School of Medicine, New Haven, Connecticut DIANE C.P. SMITH, Chief Scientist, Xerox Advanced Information Technology, Xerox Corporation, Cambridge, Massachusetts LARRY W. SWANSON, Professor of Biological Sciences and Psychology, University of Southern California, Los Angeles DAVID VAN ESSEN, Professor of Neurobiology, Division of Biology, California Institute of Technology, Pasadena DONALD J. WOODWARD, Professor of Cell Biology and Neuroscience, University of Texas Health Science Center at Dallas

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH Institute of Medicine Staff Ruth Ellen Bulger, Director, Division of Health Sciences Policy Constance M. Pechura, Study Director Charles E. Vela, Staff Officer ‡ Elizabeth E. Meyer, Research Associate Shelley A. Myers, Project Assistant April E. Powers, Project Assistant * Member, Institute of Medicine. † Member, Institute of Medicine and National Academy of Sciences. ‡ From September 1989 to May 1990.

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH Preface The Committee on a National Neural Circuitry Database was convened in October 1989 to formulate a position concerning the feasibility and utility of incorporating computer technology into the basic and clinical neurosciences in order to enhance research progress. The committee was comprised of experts from the fields of neuroscience and computer and information sciences. Each group was, in general, unaccustomed to the other area of endeavor, and considerable effort was required in the beginning to identify the problems confronting neuroscience and to learn more about the electronic and digital applications that might be relevant. To carry the analysis forward, the committee commissioned four task forces to examine the issues in more detail, organized three symposia and open hearings, and sought advice and counsel from leaders of the neuroscience community and from those with experience in database development and computer systems design. This report summarizes the committee's findings and offers advice regarding the opportunity to facilitate neuroscience research and to maximize the benefits of that research. It was not altogether clear at the outset of the study how the recommendations would unfold. Several members of the committee were skeptical that the time was ripe to apply new technologies to the gathering and dissemination of neuroscience data. The enthusiasm that emerges in the report for new approaches to these issues arose from much deliberation, numerous discussions, and careful assessment of the technological opportunities that currently exist and which are expected to expand rapidly in the future. Throughout the study

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH the committee confronted some of the same challenges that will eventually be faced by those who may be charged with implementing its recommendations. One challenge was to find effective means of communication across the diverse disciplines of neuroscience (basic and clinical) and computer science and informatics (encompassing digital graphics, database technology, and electronic networks). Beyond the expected difficulties of language (i.e., certain words mean one thing to neuroscientists and something entirely different to computer scientists), there were often fundamental differences in the perceptual frameworks used by the two groups. In educating each other the members of the committee came to the end of the study with a much greater understanding of how each discipline approaches its work and how these approaches can and should be melded in a common effort. A second challenge was to balance creativity with practicality in order to forge a reasonable plan for application of electronic and digital technologies to the neurosciences. Such a balance had to be achieved largely in the absence of immediately applicable models from other areas of biomedical science. The committee evaluated the existing biomedical databases and found substantial disparity in their development, funding, and structures. This disparity was particularly characteristic of the genome and protein sequence databases. The committee also discovered that the federal infrastructure for support of biomedical science has not yet developed a clear, integrated set of guidelines and policies to facilitate the incorporation of technological advances. Nevertheless, technology has made major inroads in most of the physical and biological sciences. A third challenge the committee faced was the recognition that its deliberations were being held during a time of serious biomedical research funding constraints. Indeed, the question of funding was at the core of the most vigorous objections to the proposed brain mapping initiative: some neuroscientists feared the initiative would produce large-scale efforts that would undermine the traditional investigator-initiated research enterprise. The committee took these concerns seriously and the prospect of allocating already scarce resources to possible new initiatives led the committee to attempt to assess the probable costs and benefits of its recommendations. In addressing this issue there emerged a recurring theme of the advantages of investment now, as a protection against costly corrections later. The recommendations offered in the report reflect the committee' s attention to the possible dangers, as well as the possible benefits that neuroscience can derive from computer and information technology. Notwithstanding the difficulties presented by these challenges, great

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH enthusiasm emerged from the committee's deliberations. The committee believes that the more than 150 neuroscientists who served on the committee, participated in task force groups, attended open hearings, or responded to written solicitations of opinions were representative of the diverse neuroscience community. Some were already in favor of the proposals being discussed and expressed strong views that the proposals should proceed. This group tended to be comprised of the most experienced in the use of computer and information technology. Some participants had strong reservations about the proposals. Of the remaining participants, many held no clear position in the beginning. In the end, however, some of the greatest excitement could be found among this group as they considered the capabilities of the various technologies shown in demonstrations and presentations and how these capabilities could be applied to data collection and analysis, as well as to rapid communication of research results. The recommendations that resulted from the committee's deliberations and activities address certain key issues. The first is that a proper base of hands-on experience must be built before any large-scale effort can begin. Thus, the committee has proposed a two-phase initiative. Phase 1 would consist of pilot projects that would allow neuroscientists and computer scientists to work together to construct usable resource prototypes and address a variety of technological and sociological challenges as described in the report. To realize the greatest benefit from these pilot projects, however, a strong central coordinating body must be in place. Thus, the committee has recommended that an advisory panel be charged with certain responsibilities, including the facilitation of information exchange among the projects, the establishment of editorial and training functions, the development of policies to protect confidentiality and intellectual property, and the definition of the overall direction of the program. The committee 's recommendations further outline the possible funding structures that might be used and the need for additional appropriations to support the proposed projects. Despite the need for program stability and central authority, the committee did not assign responsibility for the proposed initiative to any single agency or institute but instead outlined two possible structures. In one, a lead agency would have authority over the implementation of the initiative and responsibility for its funding. Alternatively, multiple agencies could share funding responsibility, but central authority would be maintained by formal agreements between two or more agencies or institutes. Because neuroscience research is funded through a wide variety of sources, the committee felt that strict definition of a structure might limit resources available to the proposed

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH initiatives. Similarly, a detailed plan for the second phase of the initiative is not offered in the committee's recommendations. The more global second phase of development and integration of electronic and digital resources must proceed from the experience gained in the pilot projects, a requirement which limited the committee's ability to define a precise structure for the future. The increasing use of many of the technologies discussed in this report is beginning to change the way research is conducted and an integral role for such technologies in biomedical science in general, and neuroscience in particular, is inevitable. In the absence of clear priorities and policies to support these technologies, the process of change will occur in a scattered, disparate, and costly manner. It is the committee's hope that this report will underscore the importance of a new focus on the role of computer and information technology in the conduct of neuroscience research. Such a focus would help bring neuroscience to an unprecedented level of discovery and, in a broader sense, provide a model for technological integration that would benefit all of biomedical science. In that spirit, this report is aimed primarily toward policymakers in the Congress, the Public Health Service, and other federal agencies who are responsible for the support and direction of the biomedical research enterprise. The report will also be of interest to basic and clinical neuroscientists, computer scientists, systems developers, and information scientists. Beyond these groups, other individuals interested in the broad issues of technological change may find certain aspects of the report useful. Therefore, the committee attempted to respond to the needs of a wide audience in constructing this report. Chapter 1 and Chapter 2 emphasize certain key aspects of neuroscience research, including already achieved and potential benefits; the chapters further describe how computer and information technology might enhance the acquisition of more information about the brain than is available today. Chapter 3 is an overview of some of the methods and concepts of neuroscience. This chapter is specifically intended to give those readers not familiar with neuroscience a greater appreciation of the field's complexity, a factor that makes the integration of computer and information technology especially challenging. Chapter 4 provides a fictional scenario of how a laboratory of the future might use electronic and digital resources, followed by descriptions and specific examples of how computer and information technologies are now in greater use in biomedical science. A summary of the input received by the committee through its various activities is contained in Chapter 5 . This chapter covers a broad range of topics that were discussed at task force meetings and open hearings and that

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH provided a strong base of knowledge for crafting specific recommendations. Finally, Chapter 6 contains the committee's formal recommendations. In completing this study, the committee was aided in many valuable ways. Of particular benefit were the efforts of the task force participants (see Appendix A ). These neuroscientists, computer scientists, and information scientists gave generously of their time and expertise to provide the committee with creative and in many cases indispensable suggestions. Another important source of input was those individuals in the neuroscience community who responded to the committee's requests for opinions. These responses kept the committee in touch with the variety of viewpoints existing in the field. The committee also appreciated the help given by the speakers and demonstrators at each of the three symposia and open hearings (see Appendix C ), as well as the insightful, honest input provided by all the participants of these meetings. Finally, the committee wishes to thank the Fidia Pharmaceutical Corporation and the Fidia Research Foundation for their support of the symposia and hearings, and Barry Peterson and Sandra Hicks from the Department of Physiology at Northwestern University for their help in arranging the hearing held in Chicago. During the course of the study, other individuals provided helpful information and necessary background materials. These included Stephen Koslow and Ronald Schoenfeld, the study's project officers from the National Institute of Mental Health; Lana Skirboll from the Alcohol, Drug Abuse, and Mental Health Administration; Lawrence Sellin from the National Science Foundation; Daniel Masys from the National Library of Medicine; Eugene Streicher from the National Institute of Neurological Disorders and Stroke; and Bruce Waxman from the Defense Mapping Agency. The committee is also grateful for the work of the seven individuals who reviewed the report and provided many thoughtful, carefully crafted suggestions and commentaries, which greatly strengthened the final product. The committee's charge could not have been met without the dedication and expertise of the staff of the Institute of Medicine. Special thanks are owed to staff editor Leah Mazade for her careful work in polishing the report. The committee also wishes to thank the director of the Division of Health Sciences Policy, Ruth Bulger, for her consistent interest and excellent suggestions. Shelley Myers, the project assistant, made the many meetings in and out of Washington as comfortable for the participants as possible and provided excellent secretarial support. April Powers became the project assistant toward the end of the study, when a thousand details, in ever-changing report drafts, require attention. She dealt with these pressures with singular com-

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH mitment and a calming sense of humor. The numerous contributions made by Elizabeth Meyer, the study's research associate, would be difficult to list here. To each task she was assigned, from planning figures and illustrations to writing summaries of the many meetings and designing the fliers for open hearings, Elizabeth brought a quiet competence and an unfailing willingness to help. Before leaving the study to accept a position in industry, Charles Vela, staff officer and assistant study director, provided valuable assistance as a liaison to the computer and information scientists of the committee and key information regarding the funding and organization of other scientific databases. Lastly, and most importantly, I wish to acknowledge the extraordinary efforts of Constance Pechura, the study director, in shepherding the committee through its difficult task. Joseph B. Martin, Chairman Committee on National Neural Circuitry Database

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH Contents     List of Boxes, Color Plates, Figures, and Tables   xiii     SUMMARY   1      Advancing Neuroscience in the Decade of the Brain,   2      Examples of the Value of Integrating Knowledge to Solve Problems,   4      The Growth of Neuroscience,   7      Computer and Information Technology in Biomedical and Neuroscience Research,   8      Building Consensus, Identifying Needs,   10      The Brain Mapping Initiative: Committee Recommendations,   13      Conclusion,   19  1   INTRODUCTION   21  2   ADVANCING NEUROSCIENCE IN THE DECADE OF THE BRAIN   25      Complexity and the Need for Information Management,   26      Examples of the Value of Integrating Knowledge to Solve Problems,   31      The Growth of Neuroscience,   41      References,   46

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH  3   OVERVIEW OF NEUROSCIENCE RESEARCH: A CLOSER LOOK AT THE NEURAL HIERARCHY   48      References and Bibliography,   65  4   COMPUTER AND INFORMATION TECHNOLOGY IN BIOMEDICAL AND NEUROSCIENCE RESEARCH   66      Critical Breakthroughs, Important Opportunities,   69      Conclusion,   88      References,   89  5   BUILDING CONSENSUS, IDENTIFYING NEEDS   91      Building a Useful Resource Complex,   93      The Challenges Ahead,   99      Strategies for Building a Base of Experience,   107      References,   111  6   THE BRAIN MAPPING INITIATIVE: COMMITTEE CONCLUSIONS AND RECOMMENDATIONS   113      The Long-Range Goal,   113     Phase 1: Implementation,   116     Phase 2: Long-Term Integration and Its Potential Benefits,   125      Summary of Recommendations,   127       References,   129     APPENDIXES       A  Task Force Topics and Rosters   133     B  Samples of Requests for Opinions   136     C  Lists of Speakers and Demonstrators in Symposia and Open Hearings   139     INDEX   143

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH List of Boxes, Color Plates, Figures, and Tables BOXES  2-1   The Gene for Neurofibromatosis 1,   30  2-2   Sometimes the Brain Learns to Ignore Visual Input,   32  3-1   Not All Neuroscience Research Is Concerned with Neurons,   56  3-2   The Genetics of Color Vision,   64  4-1   Relational Databases Versus Object-Oriented Databases,   77 COLOR PLATES  2-1   The visual processing region of the monkey cerebral cortex    2-2   Autoradiogram of opiate receptors in the spinal cord    2-3   Infrared thermograph of chronic pain patient    3-1   Computerized PET images    3-2   Loss of dopaminergic neurons in Parkinson's disease    3-3   Voltage and ion sensitive dyes: microfluorometric image    3-4   Computer-enhanced image illustrating in situ hybridization    3-5   Aging and loss of dendritic spines    4-1   The HIV-1 protease    4-2   Computer-assisted reconstruction of EEG activity    4-3   Three-dimensional reconstruction of a monkey brain   FIGURES  2-1   Magnetic resonance images of identical twins, one with schizophrenia and the other without,   39  3-1   The neural hierarchy,   49  3-2   An action potential tracing,   59  3-3   The synthesis of cyclic adenosine monophosphate,   61  3-4   The acetylcholine receptor,   63  4-1   The decreasing cost of computer memory,   71  4-2   Computer-assisted neuronal reconstruction,   75  4-3   Growth of on-line searches of word-oriented databases,   78  4-4   Brain Browser,   83 TABLES  2-1   Prevalence of Selected Neurological Disorders, Mental Illnesses, and Alcohol and Drug Abuse,   42  2-2a   Investment in Neuroscience Research by the National Institutes of Health,   45  2-2b   Investment in Neuroscience Research by the Alcohol, Drug Abuse, and Mental Health Administration,   45  2-3   U.S. Investment in Neuroscience and Mental Health Research: Sponsoring Agencies and Foundations,   46  4-1   Text Versus Image Data: Byte Requirements,   72  4-2   Selected Genome and Scientific Databases,   80

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MAPPING THE BRAIN AND ITS FUNCTIONS: INTEGRATING ENABLING TECHNOLOGIES INTO NEUROSCIENCE RESEARCH MAPPING THE BRAIN AND ITS FUNCTIONS

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