Effective connectivity of central response to Irritable Bowel Syndrome (IBS)

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DESCRIPTION (provided by applicant): Although there is a rapidly expanding technology for assessing central and autonomic nervous system activity in irritable bowel syndrome (IBS) using techniques such as fMRI and modulation of the startle reflex, large and complex data sets are generated that render conventional statistical approaches of limited applicability and have increased the need for more sophisticated analytic strategies. Research scientists trained in both the substantive knowledge in the field as well as the application and development of state-of-the-art and emerging statistical techniques for data analysis are essential to successful advancements in the science of functional gastrointestinal (GI) disorders. Currently, few functional GI disorder researchers have this dual training. The goal of this Mentored Clinical Scientist Award is to develop a research program applying state of the art analysis and design techniques to functional brain imaging and psychophysiological studies in functional GI disorders. An emerging biopsychosocial disease model for IBS posits underlying alterations in central nervous system mechanisms involved in stress and fear. The primary aim of the research is to improve understanding of central processes in functional GI disorders through better statistical analysis and network modeling with particular attention toward fMRI and experimental psychophysiological studies (including startle paradigms and evoked-response potentials). The research focus is on the application of neural network modeling approaches to complex data sets obtained with different brain imaging techniques, and to relate these results to simultaneously obtained psychological, behavioral, autonomic measures. The training plan involves the acquisition, development and application of novel quantitative methods such as effective connectivity modeling and mixed-effects modeling for fMRI and psychophysiological data and includes coursework and mentored training in neuroscience, neurobiology of brain-gut interactions, advanced biostatistics, neuroengineering, and clinical research in IBS. The proposed research plan which includes new analyses of extensive existing and ongoing study databases,and two new neuropsychophysiological studies will provide the candidate an opportunity to investigate the neuroanatomical and pathophysiologic substrates of the cognitive, behavioral, affective and physiologic alterations observed in health and disease with major implications for IBS and related functional disorders.