Central and Peripheral Autonomic Responses in IBS

IBS 的中枢和外周自主反应

• 批准号: 7019925
• 负责人: KIRSTEN TILLISCH
• 金额: $ 12.5万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7019925
• 关键词: autonomic nervous system; bioimaging /biomedical imaging; clinical research; functional magnetic resonance imaging; gender difference; human data; human subject; irritable bowel syndrome; neuroimaging; neurophysiology; patient oriented research; physiologic stressor; positron emission tomography; psychological stressor

DESCRIPTION (provided by applicant): Irritable Bowel Syndrome (IBS) is the most common functional gastrointestinal disorder, leading to significant impact on both patients and society. The cardinal IBS symptoms of pain, discomfort and altered bowel habits likely arise from a combination of stress modulated alterations in autonomic nervous system (ANS) regulation of the gut and altered perception of visceral stimuli. The role of central stress networks in this process has been supported by neuroimaging data. This Mentored Career Development Proposal is designed to provide the candidate with skills to integrate the rapidly emerging techniques of neuroimaging, ANS analysis, and clinical skills in gastroenterology to perform cutting edge translational research in functional gastrointestinal disorders. Acquisition of these skills will occur during work on a series of hypothesis driven clinical projects with experts in the field, and with didactic training. Phase I of the proposal involves analysis of fMRI, PET, and ANS data collected during aversive visceral stimulation to examine the hypothesis that there is an increased sympathetic/parasympathetic balance among IBS patients, particularly males. The central networks involved in ANS responses among IBS patients compared to controls will be delineated, and sex-based differences examined. Phase II continues the candidate's development via study of ANS responses to psychological stress, with the hypothesis that IBS patients will have greater ANS activation. First, changes in sigmoid tone during an experimental stressor will be tested as gut-specific ANS surrogate measure and correlated with skin conductance and heart rate variability. Second, imaging with fMRI will be used to determine the central ANS circuitry involved in emotional responses using the analytic tools of functional and effective connectivity. ANS reflexes in IBS patients will be tested via time course analysis for central and peripheral responses to the Valsalva maneuver during high resolution fMRI to assess for generalized ANS dysfunction. Evaluation of sex differences in ANS reponse will be emphasized, given the striking female predominance in this and many other functional disorders. Relevance: Irritable Bowel Syndrome affects up to 15% of the United States population, making it an important public health issue. The proposed training will provide the candidate with a novel set of skills to use in investigating the potential causes of IBS, and developing new treatment strategies

描述（由申请人提供）： 肠易激综合征（IBS）是最常见的功能性胃肠道疾病，会对患者和社会产生重大影响。疼痛，不适和肠习惯改变的红衣主教IBS症状可能是由于压力调节的自主神经系统（ANS）调节的肠道刺激和内脏刺激感知改变而产生的。中央应力网络在此过程中的作用得到了神经影像数据的支持。这项指导的职业发展建议旨在为候选人提供技能，以整合胃肠病学的神经影像，ANS分析和临床技能的快速新兴技术，以在功能性胃肠道疾病中进行最先进的转化研究。在一系列假设驱动的临床项目的工作期间，将与该领域的专家以及教义培训进行一系列驱动的临床项目。该提案的第一阶段涉及对厌恶性内脏刺激期间收集的fMRI，PET和ANS数据的分析，以检查IBS患者（尤其是男性）的交感神经/副交感神经平衡的假设。与对照组相比，IBS患者中参与ANS反应的中央网络将被描述，并检查了基于性别的差异。第二阶段通过研究ANS对心理压力的反应，继续候选人的发展，假设IBS患者将具有更大的ANS激活。首先，在实验压力源过程中乙状结肠张力的变化将被测试为肠道特异性ANS替代度量，并与皮肤电导和心率变异性相关。其次，使用fMRI成像将使用功能和有效连通性的分析工具来确定与情绪响应有关的中央ANS电路。 IBS患者中的ANS反射将通过时间课程分析在高分辨率fMRI期间对Valsalva操纵的中央和周围反应进行测试，以评估广泛的ANS功能障碍。鉴于女性在这种功能障碍和其他许多功能障碍中的占主导地位，将强调对ANS回复响应中性别差异的评估。 相关性：肠易激综合症影响多达15％的美国人口，这使其成为重要的公共卫生问题。拟议的培训将为候选人提供一系列新颖的技能，以调查IBS的潜在原因，并制定新的治疗策略