J. A.S. Kelso - US grants

Our long term goal is to understand how the nervous system orchestrates its very many degrees of freedom in the service of behavioral function. We view this as a problem or coordination which is a fundamental feature of all living things. We pursue the hypothesis that principles of coordination lie at the level of patterns, defined as stable and reproducible relations among the components of a behavioral or neural system on a chosen level of description. Pattern formation, stability and change are studied both in breadth (different experimental model systems, different kinds of patterns, different levels of description) and depth (especially higher brain functions such as sensorimotor coordination, perception and learning). The research program depends upon a continual interchange between experiment, theory and computation and involves a direct on-site multidisciplinary collaboration between neuroscience, psychology and theoretical physics. The physics combines concepts of self- organization and pattern formation in nonequilibrium systems (collective variables, control parameters, fluctuations, time scales) with the mathematical tools of nonlinear dynamical systems. The psychology concerns the experimental study of how people control voluntary movements, perceive and categorize information, and learn relationships between what they see and what they do. The neuroscience aims at analyzing the spatiotemporally distributed patterns of neural activity generated by the brain when people produce these meaningful behaviors. A strategic focus of the research is around phase transitions or bifurcations where dynamical processes underlying pattern formation, switching, instability and intermittency can be studied in detail and predictions tested. Critical points are crucial because they allow the clear demarcation of patterns enabling the identification of collective variables and their dynamics (equations of motion). Although the same coordination phenomena may be seen at different levels of description, our goal is to find dynamic laws within a given level. The benefits of discovering these (intrinsically nonlinear) dynamic pattern laws are obvious for understanding normal behavior; less obvious is that they also hold the key to understanding abnormal behavior. Where a given system "lives" in the parameter space of its law(s) defines how stable or flexible, normal or aberrant, its behavior may be.

health science research support;

biomedical equipment purchase;

9511360 KELSO The ability of animals to learn from experience reaches its highest form in human beings. Yet, despite extensive work in various fields of scientific inquiry, fundamental questions still remain to be answered: What is learning? What processes underlie the ability of humans to learn new skills? What is the nature of change? What factors determine generalization of one skill to another? What makes one task easy to learn and others difficult? This research is part of a broad program addressing these questions through studies of perceptual-motor coordination in tasks not unlike learning to play a musical instrument, but simple enough to be measured. The approach employs novel methods that allow a quantitative evaluation of the learner's existing capabilities before the introduction of a novel task. Nobody is a blank slate. The individual learner possesses his/her own "signature" (dependent on previous experiences, inherited traits, etc.) that influences the learning process. This research is based on the hypothesis that the rate of the learning process and the form that it takes is depend on the interplay between preexisting capabilities and the task to be learned. Since both can be expressed in terms of the same variables and the rates of change of these variables, dynamical laws of learning become accessible. This research will investigate how learning causes changes, not just in the representation of what has been learned, but in the entire layout of the learner's dynamics. Preliminary studies have shown that what is learned (relevant information) is quite independent of the particular system that practices the task. Thus, the ability to transfer knowledge from one domain to another appears to rest heavily on finding out what the relevant information is. A further direction of the research stems from a conceptualization of memory which assumes that its strength depends on the stability of the learned state and can be precisely quant ified using dynamical measures (e.g., fluctuations, time to relax from perturbations). Moreover, future plans include an evaluation of human brain activity patterns corresponding to behaviorally observed changes in learning and memory. Although the research is basic, aimed at understanding the psychological and neuronal mechanisms of human learning, it has the potential to spawn both implications and applications. In particular, the focus on individual constraints on learning and the need to structure the learning situation in the context of such constraints have significant implications for education. Avenues for applications exist in human-machine interface design, prosthetics, and rehabilitation following strokes, as well as in recovery from the numerous brain diseases that afflict human beings. ***

9512266 Jordan The proposed project is to provide a central, high-performance, and network-based computational facility with high-quality graphics, visualization and animation capabilities for the needs of faculty and graduate students in sciences. The facility supports a large number of diverse research projects in scientific and mathematical disciplines. Four general types of research are identified, namely; (1) compute-intensive, (2) algorithm development and applications, (3) data analysis, visualization and animation, and (4) modelling simulation. The computational environment encourages an interdisciplinary approach which brings together the common elements of research projects in the Departments of Physics, Chemistry, Mathematics, Geology and the multi-disciplinary Center for Complex Systems. An important consequence of the proposed project is that it will not only enhance the current faculty and student research and education but that it will act as a catalyst for new collaborations with the College of Science. ***

This is a request for an ADAMHA Senior Scientist Award (KO5). The broad objective of my experimental and theoretical work is to understand how the nervous system orchestrates its many degrees of freedom in the service of behavioral function. The work is focused on illustrating the mechanisms and principles of coordination within the human brain, and between the brain and behavior, using a carefully selected set of paradigms. The approach is three pronged, combining: 1) theoretical concepts and tools of self-organization; 2) experimental model systems in which bifurcations feature prominently; and 3) advanced technologies that enable the analysis of the brain's spatiotemporal activity. To this end I am fortunate to have access to a full-head, neuromagnetic imaging device at CTF Systems, Vancouver, functional and conventional MRI facilities in Boca Raton, and direct contact with eminent theoreticians who share my interests. The RSA will release me from teaching and administrative duties and allow me to spend the time needed to collect and analyze experimental data. The RSA will also enable me to enhance my understanding of neuroscience, modeling and computational physics, in order to gain deeper insight into the connection between brain structure and function. I expect these research and scientific enhancement activities will consume at least 85% of my time. With the RSA, I also plan to continue my active role in mentoring and science education. l shall continue to lead our NIMH Training Program in Complex Systems and Brain Sciences and to provide research experience and mentoring to predoctoral and postdoctoral students. Finally, I intend to remain active in the South Florida community, promoting science and articulating its goals to the general public, particularly as it relates to the human brain-behavior relation.

This proposal seeks continuation of a multi-disciplinary research effort at F.A..U.~s Center for Complex Systems between neuroscience, psychology and physics that seeks to uncover the basic organizational principles and mechanisms underlying higher brain function. In particular, questions asked are how human beings coordinate their actions with environment, how they perceive and categorize the world around them, and how they learn new skills. The principal hypothesis guiding the research, which embraces theory, computation and experiment, is that brain and behavior are self-organized, governed by coupled dynamical rules on several scales of observation. Such dynamics determine the collective activity of the nervous system, generating the time course of coordination states on a given level of description. Three major experimental sections are proposed to test predicted features of specific dynamical models in the context of the theory of self- organization. In each case, detailed hypotheses are made regarding the neural structures involved and their selective, task-specific engagement over time (to be obtained through a synergism of high density electrode, SquID arrays and fMRI). This information in turn will be used for two purposes: first, to meet the much needed demand for image analysis, compression and visualization that preserves the real-time dynamics of the brain; and, second, to develop theoretical models of global brain function that are based on realistic neuroanatomical and neurophysiological considerations. In addition, a number of new paradigms are proposed aimed at exposing novel dynamical processes that will promote further theoretical developments. Identifying key quantities for collective activity at both brain and behavioral levels and the dynamical rules by which self-organization occurs, should put us in a much better position to understand functional brain disorders. Since the relevant information will be known at the macroscopic level, this knowledge will place constraints on which microscopic processes and variables are relevant and which are not.

DESCRIPTION (provided by applicant): This application seeks continued support for The PhD Program in Complex Systems and Brain Sciences initiated in 1995 under the joint auspices of NIMH and Florida Atlantic University. The need for such a program was recognized by a previous review and may be paraphrased as follows: "As neuroscientists learn more and more about the subcellular and biophysical properties of the nervous system, the complex systems approach seeks to characterize the behavior of integrated units, including neural networks, intact and isolated portions of the spinal cord, whole brain functioning and behavior. The approach is truly interdisciplinary. . . [and] the time is ripe for a fully integrated Training Program in this area." Among the reasons why this Training Program warrants continued support are the following developments that have occurred in the last budget period: 1) The number of well qualified applicants has grown, and far outstretches the number of fellowships available (a ratio of about 10:1); 2) The number of outstanding Core Faculty recruited specifically for this PhD Program has increased by four in the last 3 years alone, enhancing both the depth and breadth of the curriculum; 3) The level of research productivity of past and current fellows is outstanding, and reflects an unusual degree of collaboration between both faculty and students, many of whom come originally from different disciplines; 4) Ten PhDs have been awarded with two more scheduled to finish before September 2001; 5) Graduates of this Program now occupy excellent positions in Universities and other institutions, attesting to the broad range of skills and high level of training provided; 6) A new 20,000 sq. ft. facility to house the Training Program has been constructed that, due to a special collaboration with the private and corporate sector, includes capabilities for cutting-edge, real-time imaging of the human brain (fMRI); 7) The level of University support for this Program -the only one of its kind on campus- is considerable, and includes tuition waivers for both in-state and out-of state fellows, and the provision of at least a matching number of assistantships; and 8) the assignment of a new endowed Chair in Complex Systems and Brain Sciences to this Training Program, which, along with commitments to make a number of junior hires will further enhance training opportunities for pre-and postdoctoral fellows.

DESCRIPTION (provided by applicant): Although several mechanisms have been proposed to underlie observed neuropsychological deficits and subsequent recovery of function following Mild Traumatic Brain Injury (MTBI), to date the link between alterations in axonal morphology, large scale neural functioning and behavioral recovery has not been established. This proposal represents an integrated approach to establishing a connection between structural damage resulting from MTBI, consequent deficits in neural functioning and the outward manifestations of cognitive and behavioral symptoms. The approach is both discovery-based and hypothesis driven, in which animal models of neural reorganization and regeneration, as well as possible cognitive compensatory processes are subject to empirical test. The accessibility to pre-injury baseline measures in athletes makes concussion an ideal entry point into the prospective study of MTBI and recovery of function. Over five consecutive years, pre-season baseline measures will be collected from FAU football players (N=80/year) on a Comprehensive Imaging Protocol for the Assessment of Concussion (CIPAC). The CIPAC will employ a combination of: a) functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), b) a Web-based neurocognitive assessment battery designed specifically for prospective testing (Concussion Resolution Index, Headminder Inc.), c) the NeuroCom(R) sensory organization test and d) self reported symptoms. Players identified as suffering a concussion during the course of the season will enter a post-concussion recording schedule in which they will be tested within 24 hours following injury and at regular intervals during recovery and during follow-up at 1 and 3 months. In this prospective approach, pre-injury levels of behavioral and neural functioning acquired during baseline testing will be used to evaluate post-concussion deficits independently for each individual. Particular focus will be on questions concerning: 1) the morphological, physiological and behavioral consequences of (multiple) concussions; 2) mechanisms of plasticity and recovery of function following MTBI; 3) the relationship between deficits in neural functioning and standardized behavioral measures of concussion; and 4) the implications for current assessment techniques and return to play guidelines. This individualized approach should provide important insights into the structural and dynamic mechanisms underlying recovery of function in the human brain.

[unreadable] DESCRIPTION (provided by applicant): This application addresses a fundamental question of significance to understanding human nature and the entire field of social neuroscience: "What distinguishes a true social interaction between human beings from other perceptuo-motor interactions?" Understanding how coordination occurs both within the human brain and between human brains is vital to the basic and clinical neuroscience mission of NIMH, The reason is that disruptions of coordinative interactions among cortical and subcortical areas and the breakdown of neural integration are thought to lie at the heart of major neuropsychiatric disorders such as schizophrenia and autism. We aim to 1) identify the neurobehavioral mechanisms underlying how brain regions couple and decouple both within an individual brain and between brains engaged in social settings and 2) clarify the nature of the informational coupling between individuals engaged in social behavioral interactions. The work will be carried out by a dedicated interdisciplinary team of researchers whose expertise spans cognitive neuroscience, psychology and physics. It builds upon and explores in depth our recent discovery of an oscillatory complex in the brain that may act as a specific neuromarker of social behavior. The proposed research uses behavioral methods and sophisticated computational analyses in combination with dual high density EEG electrode arrays developed for the simultaneous recording of brain activity from interacting pairs of people to uncover where social signals are processed in the brain and how they become coupled dynamically between individuals. The novel conceptual and analytic framework of coordination dynamics is used to explore cognitive (within brain) and social (shared between-brain) neural representations hypothesized to underlie social coordination. Coordination dynamics provides theoretical concepts, methods and ecologically valid paradigms to attack the outstanding question of how large scale integration in the brain and across brains is accomplished. The research represents a first attempt to incorporate dynamical systems analysis into the study of socially-mediated neurophysiological activity in conscious, interacting humans. Uncovering the neurobiological mechanisms that underlie coordinated human behavior in an individual during social interactions constitutes a major step toward understanding neuropsychiatric disorders and is likely to result in the development of more effective pharmacological and behaviorally relevant treatments. [unreadable] [unreadable] [unreadable]

On an ordinary day, people perform actions that affect other people's behavior resulting in outcomes that affect both. Such social interactions are dynamic, far ranging, and usually require an exchange of information between the parties involved. A simple example is two persons modifying their approach to an elevator to accommodate each other's passage through the narrow space. More complex situations involve a teacher providing guidance to a pupil based on the pupil's own actions or training foreign military personnel to accomplish some function that depends on the latter's previous experiences. How are such social interactions to be quantified and understood? What goes on in a person's brain when they interact with another and what principles and mechanisms govern the coordination between brains? The investigators of this project constitute an interdisciplinary team whose expertise spans physics, cognitive science and neuroscience. They use the concepts, methods and tools of coordination dynamics, the science of coordination, to investigate both the behavioral and neural underpinnings of social behavioral interactions. The basic experimental paradigm involves coordination of movements between two people or between an individual and a computer avatar endowed with human-like capabilities. Pairs of people perform simple actions in front of each other and the investigators monitor key behavioral and neural variables that reveal how strongly each affects the other. By testing specific predictions of a mathematical model of coupled dynamical systems, the investigators aim to understand how social coordination evolves in time and to determine the respective strength of one person's influence on another.

Modern technology is always seeking to enhance human experience and productivity. The notion of 'others' has been expanded to include not only real human beings but also cyber-individuals, as evident in the increasing roles played by robotics and virtual environments in everyday human transactions. In crucial experiments, a human subject interacts with a virtual partner, an avatar driven by the investigators' mathematical model of coupled dynamical systems, thereby allowing the investigators to manipulate parameters (the 'personality' or 'attitude' of the virtual partner) that are not normally accessible in studies of live interactions. Thus the present project may not only uncover rules of ordinary social coordination but also offer a principled approach to human-machine interaction. In addition, the project will disseminate knowledge about complex systems and dynamical approaches to human social behavior. The investigators will train undergraduate and graduate students in advanced methods and analysis techniques that cut across the behavioral and social sciences, the physics and mathematics of coupled dynamical systems, and neuroscience and brain imaging. The development of new measuring instruments that may apply to any arbitrary social interaction is a target. Such training aims to bring forth a new generation of interdisciplinary scientist who will be equipped to integrate studies of brain, behavior and social function within a much needed dynamical framework.

DESCRIPTION (provided by applicant): The goal of this project is to discover the dynamical principles and mechanisms at play both within and between human brains during real-time social interaction. The research plan employs a three-pronged approach that combines (1) experimental manipulations to test specific hypotheses regarding key issues in the neurophysiology of social neuroscience (2) sophisticated measurement and analysis tools from the theory of dynamical systems, including virtual partner interaction (behavioral dynamic clamp of reciprocally coupled humans and model-partners) and (3) multiscale neurocomputational modeling of both structure and function in order to advance our understanding of how individual behavior and the interaction of individuals drives basic forms of social behavior. In our previous research, we established a comprehensive framework to tackle real- time interactions between people in simple, well-defined experimental paradigms in which pairs of participants simultaneously performed and perceived each other's movements. The research program led to the discovery of the phi complex, a neuromarker of social coordination. Also clarified were the contributions of other neuromarkers, especially alpha and mu, to different phases and facets of social behavior. What is most needed now -and what we seek support for in the present Competing Renewal- is to understand the dynamical orchestration of identified neuromarkers over the course of social behavior. The experimental thread works hand-in-hand with neurocomputational modeling of social behavior, theoretical models informing experiments and vice-versa. The aims of this research program-still very much in its infancy-- are (1) to elucidate the neuromarker choreography, that is, to determine when each neuromarker is recruited and disengaged, which neuromarkers originate from which brain areas and how neuromarkers interact with each other in transient networks during the course of social behavior. All of the proposed work is geared to the prediction of efficient or deficient outcomes as assessed by detailed single trial analysis of real-time social behavior; (2) to construct a human dynamic clamp that allows for direct manipulation of the interaction between human participants and virtual partners endowed with human appearance and coordinative capacities. This new paradigm opens up the detailed parametric exploration of social behavior; and (3) to integrate the findings in a multiscale neuro- computational model of social behavior, a platform that will enable understanding of basic mechanisms of interpersonal interactions at combined neural, behavioral and social levels. Successful achievement of this program will specify the neurobehavioral routes leading to improved social function. Given the vast number of pathologies with etiological or symptomatic ties to social behavior, such information will afford many translational opportunities for the compensation or remediation of deficits in diseases such as autism, schizophrenia, depression and dementia to name just a few.