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

描述(由申请人提供)： 虽然有一种快速发展的技术来评估肠易激综合征(IBS)的中枢和自主神经系统活动，使用功能磁共振成像和惊跳反射调制等技术，但产生的大型和复杂的数据集使得传统统计方法的适用性有限，并增加了对更复杂分析策略的需求。经过该领域实质性知识培训的研究科学家，以及用于数据分析的最新和新兴统计技术的应用和开发，对于功能性胃肠道疾病(GI)科学的成功进步至关重要。目前，很少有功能性胃肠功能障碍的研究人员接受过这种双重训练。这个指导临床科学家奖的目标是开发一个研究计划，将最先进的分析和设计技术应用于功能性胃肠道疾病的脑功能成像和心理生理学研究。一种新兴的IBS生物-心理-社会疾病模型假设了与压力和恐惧有关的中枢神经系统机制的潜在变化。这项研究的主要目的是通过更好的统计分析和网络建模，特别是功能磁共振成像和实验性心理生理学研究(包括惊厥范式和诱发反应电位)，提高对功能性胃肠道疾病的中心过程的理解。研究的重点是将神经网络建模方法应用于通过不同的脑成像技术获得的复杂数据集，并将这些结果与同时获得的心理、行为、自主测量相关联。培训计划涉及获取、开发和应用新的量化方法，如功能磁共振成像和心理生理学数据的有效连接建模和混合效果建模，并包括神经科学、脑-肠道相互作用的神经生物学、高级生物统计学、神经工程学和IBS临床研究的课程作业和指导培训。拟议的研究计划包括对广泛的现有和正在进行的研究数据库的新分析，以及两项新的神经心理生理学研究，将为候选人提供一个机会，调查在健康和疾病中观察到的认知、行为、情感和生理变化的神经解剖学和病理生理学基础，这些变化对IBS和相关功能障碍具有重大影响。

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.