Title : NSF9158 - The NSF in the Decade of the Brain NSF Org : BBS Type : Report Date : June 21, 1991 File : nsf9158 Keywords : 1002030 PT 34 KW 1002030 THE NATIONAL SCIENCE FOUNDATION IN THE DECADE OF THE BRAIN The National Science Foundation continues to play an important catalytic role in the development of research on the brain and behavior. Declaration of the 1990s as the "Decade of the Brain" by the Congress (House Joint Resolution-174, 101st Congress), signed by President George Bush, focused the nation's attention on the importance of brain research for the people and the opportunities for advancing our knowledge of the most complex of human organs. The human brain, the marvelously designed organ that allows us to learn, remember, plan, decide, communicate and do all the things that make us human, and that regulates our physical and mental health, is at last yielding its secrets. The Federal Coordinating Council for Science, Engineering and Technology has issued a report: Maximizing Human Potential: Decade of the Brain. The report, prepared by a committee representing 20 Federal agencies involved in brain research, identifies nine research areas that could form the basis of an integrated research program in the brain and behavioral sciences. A chart summarizing the Federal activities in these nine areas is provided in the report. In addition, three themes that span the nine identified research areas are also discussed: basic research, technology, and international activities. Since 1972, with the establishment of a Neurobiology Program, the National Science Foundation has taken an active role in fostering research in the neurosciences. The brain and behavioral sciences constitute the primary focus of the Foundation's Division of Behavioral and Neural Sciences, established in 1975. While its resources are modest, representing less than five percent of all Federal expenditures on brain and behavioral research, the National Science Foundation's role in the government-wide brain science effort is to support innovative ideas in basic research on the brain and on the behavior that results from brain activity. Basic neuroscience explores the brain and nervous system to discover the fundamental ways in which neurons work, how the nervous system develops, and how the brain has evolved adaptations for appropriate behavior in particular environments. The discoveries are the building blocks needed to answer questions about the brain, behavior, intelligence, and disease. Because the human brain is so complex and still largely inaccessible, the National Science Foundation supports research on comparatively simple biological systems and on ingenious -2- models for extracting information from human behavior. Such simple systems may involve a few neuronal cells in a dish in a totally controlled setting, or invertebrate brains with a few hundred cells, or subsystems in the brains of vertebrates. Among the vertebrates, studies extend from ancient species such as the lamprey through various levels of complexity to human studies. Human studies include research in perception, linguistics, developmental and social psychology, physical and cultural anthropology and the growing area of cognitive science. Cognitive science is an interdisciplinary activity focused on understanding intelligent systems, both biological and artificial. The National Science Foundation is undertaking a Cognitive Science Initiative during the Decade of the Brain to plan and provide the resources needed to assist this field in reaching full maturity. Central to the NSF effort are basic laboratory experiments on how the brain produces behavior, on the ways we use our senses to control movement, the interactions between endocrine and nervous systems, and the study of behavior in many animal species. All of these studies reveal the workings of the brain. Research on the brain and behavior is an exploration as important as any that humans have ever undertaken; more complex than exploring new lands, more compact than exploring space and more meaningful to our everyday lives than ever before. The Decade of the Brain offers an opportunity to concentrate on a massive research effort. Knowledge gained in neuroscience in the last decade has accelerated so fast that opportunities have outstripped the resources to support all the new avenues opened. The results of the Decade of the Brain will provide the foundation to help explain ourselves to ourselves, to give directions for breakthroughs in medicine, substance abuse, and robotics engineering, and to address many problems that we do not know how to handle at present. The Decade of the Brain will point to the future and look at the past, and give a new design for living healthier and wiser in the next century. Three technological developments in the past decade are driving the novel findings of current neuroscience efforts. First, an explosion of new anatomical techniques enables neuroscientists to trace pathways and to identify particular cell types. These include powerful new stains and intracellular dyes for histology, voltage-sensitive dyes for real-time monitoring of whole populations of cells, immunocytochemical techniques to label classes of cells, brain-scan imaging based on physical techniques (PET, MRI, etc.), and confocal microscopy for living tissue. Second, computers are in virtually every lab, allowing real-time -3- data analysis, sophisticated stimulus creation, very high temporal resolution of electrophysiological events, and tremendous data-capture and storage capabilities. In a few cases, major computational efforts using supercomputers or parallel processors have led to development of theories about much more complex systems of model neurons than ever before possible. Third, the tools of molecular genetics are coming into neuroscience, with cDNA libraries, studies of protein expression, normal and abnormal neural structure and function. The National Science Foundation is organized to facilitate an integrated approach to basic research on the nervous system. Programs dealing with molecules involved in the development and functioning of brain cells interact closely with programs dealing with animal behavior and human psychology. The following descriptions of program areas involved in the Decade of the Brain indicate the directions in which the National Science Foundation is fostering research. Division of Behavioral and Neural Sciences NEUROSCIENCE PROGRAM Cellular Neuroscience The cellular units of the nervous system are neurons and glial cells, which process information by a variety of signals, including movement of ions through channels in their membranes and release of intra- and intercellular messenger molecules. Progress in understanding the molecular and cellular level of nervous-system function continues to depend on contributions from biophysics, neurochemistry, neuroanatomy, neurophysiology, and neuropharmacology. In addition to dealing with the intracellular structures and molecules that are involved in excitability and transmitter release, cellular neuroscience also studies the molecular mechanisms that result in the unique spatial arrangements and contacts of neurons. Neurons possess rather elaborate shapes that allow them to function as complex units distributing information in sophisticated processing networks. This information processing is mediated to a large extent by spatial branching and interrelationships between neurons. It is this feature that distinguishes the nervous system from other complicated information-processing networks such as the immune system, which rely largely on chemical specificity rather than spatial relationships. This feature is also what makes the study -4- of the nervous system a specialized discipline compared to other areas of biology: chemical mechanisms cannot be understood without explicitly being related to the unique morphological configurations of neurons. Developmental Neuroscience The development of the brain involves generating many different types of nerve cells that form precise connections with each other. Perturbations in the number of nerve cells generated, the time courses over which cells are generated and the development of neuronal shape and biochemistry can affect neuronal connections both quantitatively and qualitatively, leading to alterations in brain function and behavior. In addition, glial cells, which form the major cellular component of the brain, play crucial roles in neuronal development, maintenance and aging. Although the differentiation of cells in the brain is ultimately controlled by the expression of each cell's genetic information, this expression is vulnerable to the influences of extracellular signals derived from local cell-cell interactions, as well as from peripheral tissues, as in the case of certain hormones. Pivotal questions in developmental neuroscience revolve around identifying the nature of extracellular instructive signals that lead to the formation of specific types of nerve and glial cells, the genetic and cellular mechanisms involved in the action of such signals, and the relationship of developmental mechanisms to processes important to plasticity, aging and regeneration of the nervous system. Synaptic Mechanisms The synapse is the site of functional contact between nerve cells, and represents the key link that allows a set of neurons to function as an information-processing system. Supported research focuses on the synthesis and release of molecules that serve as intercellular messengers (neurotransmitters and neuroregulators), the cell-surface receptors that mediate the postsynaptic response upon binding the intercellular messenger, and the morphological specializations that allow synaptic sites to transfer information from one cell to another in a highly effective and regulated manner. Some of the most active areas of research in synaptic mechanisms are the elucidation of families of genes controlling the synthesis of transmitter receptors, the characterization of multiple subtypes of receptors that mediate spatially restricted responses, and mechanisms underlying the development of contacts between specific presynaptic and postsynaptic elements. -5- Sensory Systems Our various sensory systems (i.e., sight, hearing, taste, smell, touch, balance, and proprioception) deliver all the information about our external and internal environments. A basic property of all sensory systems is stimulus transduction, the process that captures the physical energy of the appropriate stimulus and transforms it into a neural signal. The stimulus energy is often initially captured and concentrated into the cellular receptors by accessory structures that are not themselves neural tissue (such as the lens of the eye, the eardrum and middle-ear bones, or the mucous layer of the olfactory epithelium) but are integrated parts of sophisticated sensory organs. The cellular sensory events may be initiated by microscopic deformation in mechanoreceptors, by molecular binding to membrane sites in chemoreceptors, or by internal molecular changes of photopigments in vision. Often a biochemical second-messenger system within the cell activates proteins modulating transmembrane ion channels, leading to subsequent transmitter release from the receptor cell to the primary afferent neuron. Research at this cellular and subcellular scale is an extremely active front. At the other extreme of the hierarchy, in the complex centers of the brain such as primary sensory cortex, a major new bridging is occurring between classic psychophysical studies of sensory perception and modern techniques of monitoring neural activity by electrophysiology, voltage- sensitive dyes, or whole-brain imaging technology. BIOLOGICAL BASIS OF BEHAVIOR PROGRAM Neural Mechanisms of Behavior The central nervous system controls behavior in living organisms. Studies are underway at all levels of phylogeny from isolated systems of invertebrate neurons to muscle adjustments by humans as they perform discrete motor tasks. Data obtained from simple model systems in invertebrates provide principles that can be generalized to more complex forms of behavior in higher vertebrates. Single unit recordings from large invertebrate neurons can produce fundamental knowledge that will help in understanding the neural circuitry involved in the responses of primates to complex behavioral choices. Supported research focuses on motor systems and integrated behavioral systems. Examples of coordinated motor systems include swimming in lampreys and vocalization in songbirds. The systems can consist of highly repetitive patterns or a complex series of musculoskeletal responses that require constant feedback. The neural basis of integrated behavioral systems -6- refers to studies of homeostatic mechanisms which are under varying degrees of autonomic and voluntary control. The study of the neural regulation of micturition, circadian rhythms, thermoregulation, chemoregulation, sleep, feeding and drinking, hibernation, activity and exercise, aggression, and pain depends on detailed analysis of neural elements in the context of behavioral functioning. Many approaches are used in these studies, including electrophysiological recording in vivo and in vitro, measurements of levels of transmitter substances by neurochemical assays, tracing of anatomical connections by both light and electron microscopy, brain lesions or stimulation by electrical or pharmacological means, and behavioral testing. Technical advances in these areas are constantly challenging our understanding of the way in which the nervous system controls behavior. Cognitive, Computational and Theoretical Neurobiology Cognitive Neurobiology fosters animal (non-human) research in the basic cognitive processes including attention, learning, memory, and perception. These studies apply a neurophysiological and/or anatomical orientation in combination with behavioral methodology. Computational Neurobiology encourages mathematical or computer modeling of biological neural systems. The mathematical interpretation of signal processing by biological neuronal networks will be fostered for those studying known neuronal circuits. Research by neuroscientists working on neural network theory and interfacing with biological tissue is encouraged, as is research on biocontrol by neuronal networks and looking for emergent behavior patterns in complex systems. Theoretical Neurobiology fosters emerging and innovative theoretical ideas regarding biological neural systems. The theoretical bases for understanding the emergence of collective behavior from individual nerve cells and networks is an example. Behavioral Neuroendocrinology Hormones have historically been studied for their influences on various behaviors including sexual behavior, motivation, emotion, and aggression. With the advent of new technologies, the study of behavior is now taking place at the cellular level. Behavioral neuroendocrinology encompasses a large array of research centered on the multifaceted relationships between hormones and the brain. While in the past the endocrine and nervous systems were considered to be separate, although interactive, this distinction has now been challenged, with the finding that hormones, especially the neuropeptides, can serve as neuromodulators. Important questions still remain about the mechanisms of interaction among hormones, the CNS and behavior. -7- We need to know which hormones are involved in particular behavioral functions. We need to know where these hormones are acting. We need to know how the hormones mediate their effects on brain tissue. The development of sophisticated molecular-derived techniques is playing a pivotal role in providing answers to these questions. Three particularly important topics within the field of neuroendocrinology that are receiving increased attention are the sexual differentiation of the brain, the interactions among stress, hormones and the brain, and the relationship between circadian rhythms and neuroendocrine systems. These topics involve endocrine networks that include neuronal systems and peripheral organs that secrete powerful steroid hormones. Animal Behavior Research on animal behavior can provide a valuable comparative perspective on human behavior. It also yields experimental paradigms that are essential for investigating the brain mechanisms of learning, motivation, communication, social behavior, and other complex behavioral processes. A characteristic of many of the most promising research areas is that they are integrative in approach: Investigators pursue multiple levels of causation, they combine experimental and observational techniques, and they integrate several subdisciplines. For example, research in animal learning has been enriched by new approaches from behavioral ecology, cognitive psychology, and neuroscience. Our understanding of the behavioral processes of learning and memory is developing through vigorous research that is providing neuroscientists new challenges for explanation as well as new behavioral tools for analyzing neural mechanisms of learning and memory. Other particularly promising research areas include studies of natural communication systems in a variety of species with an emphasis on examining the cognitive structures underlying communication, the dependence of communication on social organization, the extent to which cognitive abilities may be adapted to individual social needs within groups, biological constraints and rules of learning, the role of learning in behavioral development, and the roles of socialization and social development in learning. Such studies are making vital contributions to our understanding of brain function, cognitive evolution, and the evolution of culture. -8- LANGUAGE, COGNITION, AND SOCIAL BEHAVIOR PROGRAM Human Cognition and Perception Human beings are in contact with the world about them through their senses, but the constancy of their perception of objects, motions, textures, and complex sounds, to give a few examples, goes far beyond the information specified by the energy reaching the receptors of their sense organs. Human beings then use this perceptual information in a myriad of processes we call cognitive, for example memory, learning, making decisions, and solving problems. Another term for this complex of cognitive processes that are in many ways uniquely human is "mind," which is not to be taken as some mystical entity, but rather as a description of the functional properties of our brains that render us human. Thus, the study of human cognition and perception is in a very real sense the study of functional properties of the human brain. It constitutes the central part of cognitive science, the study of the nature of intelligent systems, biological and artificial, which is the subject of NSF's Cognitive Science Initiative, a major component of NSF's Decade of the Brain activity. One aspect of the study of human cognition and perception is the use of various non-invasive techniques, such as PET, MRI, ERP, and MEG, to discover the neural correlates of human cognitive and perceptual activity. The goal here is not reductionistic but rather the use of information about neural activity to inform and constrain theories of cognitive and perceptual function and the use of information about the latter to inform and constrain theories of brain anatomy and physiology. Linguistics An important window on the workings of the human mind and brain is through language--how we use speech to encode meaningful messages, and how we understand and interpret the speech of others. Thus the study of language and its use forms a key component of the burgeoning field of cognitive science. Neurolinguistic research is handicapped by the shortage of effective, non-invasive methodologies for controlled, systematic observation of brain function during the use of language. One important research goal is to refine the methods that are available and to seek out promising new ones. One research technique that has yielded most of the knowledge we now have about the localization of linguistic functioning in the brain is the study of aphasia--deficits in linguistic ability resulting from damage to the brain by trauma or stroke. -9- Another method that has yielded some intriguing results in recent years is study of event-related potentials. Non-invasive sensors attached to the scalp detect intracranial electrical activity. Analysis of the jumbled signal that emerges shows that it is composed of a number of interacting wave-forms. Some of the wave- forms are steady and seemingly unaffected by the sensory environment, but others display characteristic, replicable reactions to sensory events of various sorts. Many of the event- related potentials that have been identified are immediate autonomic reactions, but one especially interesting group appear to be occasioned by the higher-level processes involved in the semantic interpretation of language. Social Psychology Research in social psychology spans all aspects of human social behavior. Since human social interaction is perhaps the highest level of animal interaction known, and since it is the result of the output of the brain, one aspect of the Decade of the Brain is to understand more fully this complex behavior. In recent years, social psychologists have become increasingly interested in studying the physiological concomitants of social behavior. A substantial part of the research now being done by these scientists includes measures of physiological processes. This research is aimed at understanding the relationship between social behavior and biology, with the impact going in either direction. For example, there are studies on the influence of stress on the immune system, as well as studies of the impact of endocrine changes in adolescence on social development. Recent research on dispositional optimism has demonstrated that optimists under stress display lower levels of cardiovascular activity than do pessimists under stress. Among other topics now being studied by social psychologists are brain lateralization in infants, emotion and temperature regulation in the brain, the impact of social factors on immunology and on the aging process, and biological processes accompanying the development of empathy in children. ANTHROPOLOGY PROGRAM Physical Anthropology Physical anthropology provides an evolutionary time depth to analysis of the brain, behavior and cognition. Two lines of endeavor provide this depth: investigations of the fossil record for human evolution and studies of modern non-human primates as -10- models of human ancestors. Fossils provide the direct evidence of past brain structure; the analysis of brain morphology is greatly enhanced by the applications of modern technology. CAT scans and other imaging techniques are being used to provide noninvasive views of brain structure in long-extinct relatives. Traditional approaches too, such as the morphology of endocranial casts and the patterns of arterial supply to the brain, are used to clarify anatomical structure. In conjunction with research on the cultural remains of past populations, the anatomical data help to decipher our evolving behavioral and cognitive skills. Studies of living primates provide data on the relationships between brain anatomy and behavior. Observation of primate behavior, in both captive and wild populations, allows us to assess the range of variation in behavior as well as putting behavior within the context of a social and ecological setting. Such information then provides yardsticks for the further interpretation of the fossil materials. THE SPECIAL NSF ROLE In order to foster innovative and interdisciplinary research on the brain and behavior during the Decade of the Brain, the primary role of the neuroscience programs within NSF is being differentiated from the programs of other agencies. The Foundation will seek to support those projects identified as more risky or innovative, young investigators beginning independent research careers in the neurosciences, and research on model systems not directly related to disease processes. The Foundation will discourage the submission of proposals that duplicate applications pending at other Federal agencies. Investigators should contact the appropriate NSF program officer prior to submitting a proposal. In addition to regular investigator-initiated research projects, investigators should take advantage of other types of support offered by the National Science Foundation. 1. Small Grants for Exploratory Research (SGER). These are high- risk, non-renewable small grants, limited to under $50,000. PIs must discuss a potential project with the appropriate program officer prior to submitting a proposal. Decisions are made by program officers, with Division Director concurrence, but without the normal process of merit review. Up to 5 percent of each program's funds may be used for SGER awards. 2. BBS Research Training Groups. These awards, for which there is one competition per year, provide support (up to $250,000 per year) for interdisciplinary research training, including instrumentation, within a high-quality research setting. -11- 3. Multiuser instrumentation awards provide matching funds for the purchase of major items of research equipment to be used by two or more laboratories. 4. Selected programs are available that target minority, women, and disabled scientists and research conducted in predominantly undergraduate colleges and universities. In summary, the National Science Foundation through its Division of Behavioral and Neural Sciences is experienced in and will continue to support and encourage a wide range of basic-science approaches to brain research. Such basic research may not have immediate applications or be of instant clinical relevance but may develop into the critical scientific steps for the important breakthroughs of tomorrow.