Central and Peripheral Autonomic Responses in Irritable Bowel Syndrome

肠易激综合症的中枢和外周自主反应

• 批准号: 7586745
• 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/7586745
• 关键词: Address; Affect; Amygdaloid structure; Anatomy; Anterior; Area; Autonomic nervous system; Aversive Stimulus; Award; Blood flow; Brain; Brain Stem; Brain imaging; Brain region; Cell Nucleus; Chronic; Clinical; Clinical Skills; Colon; Complex; Data; Databases; Development; Disease; Distal; Dorsal; Emotional; Employee Strikes; Evaluation; Female; Frequencies; Functional Gastrointestinal Disorders; Functional Magnetic Resonance Imaging; Functional disorder; Galvanic Skin Response; Gastroenterology; Grant; Habits; Human; Hypersensitivity; Hypothalamic structure; Image; Imagery; Imaging Techniques; Insula of Reil; Intestines; Irritable Bowel Syndrome; Knowledge; Left; Link; Magnetic Resonance Imaging; Measurement; Measures; Medial; Medical; Mentors; Nervous System Physiology; Nervous system structure; Non-Visceral; Nucleus solitarius; Pain; Pathway interactions; Patients; Perception; Peripheral; Phase; Physiological; Pilot Projects; Population; Positron-Emission Tomography; Prefrontal Cortex; Process; Psychological Stress; Public Health; Reflex action; Regulation; Resolution; Role; Science; Series; Sex Characteristics; Sigmoid colon; Signal Transduction; Societies; Stimulus; Stress; Structure; Surrogate Markers; Sympathetic Nervous System; Symptoms; Syndrome; Systems Analysis; Techniques; Testing; Time; Training; Translational Research; United States; Valsalva Maneuver; Viscera; Visceral; Woman; Women' s Health; Work; base; biological adaptation to stress; career development; cell motility; cingulate cortex; depressed; design; gastrointestinal; heart rate variability; immune function; insight; locus ceruleus structure; male; men; midbrain central gray substance; neuroimaging; novel; parabrachial nucleus; prospective; psychologic; psychological stressor; response; sex; skill acquisition; skills; stem; stressor; tool; treatment strategy

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/parasympatheticbalance 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.

肠易激综合征（IBS）是最常见的功能性胃肠道疾病，导致显着 对患者和社会的影响。红衣主教IBS疼痛，不适和肠子改变的症状 习惯可能是由自主神经系统（ANS）的压力调节改变的结合而产生的 肠道的调节和内脏刺激的感知改变。中央压力网络在此中的作用 神经影像数据支持过程。这个指导的职业发展建议是 旨在为候选人提供技能，以整合迅速新兴的神经影像技术， ANS分析以及胃肠病学的临床技能，以执行尖端转化研究 功能性胃肠道疾病。这些技能的获取将在一系列的工作期间发生 假设驱动了该领域专家以及教学培训的临床项目。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 假设IBS患者的交感/副交感神经平衡增加，尤其是 男性。与对照组相比，IBS患者中参与ANS反应的中央网络将是 划定的差异和基于性别的差异。第二阶段通过研究继续候选人的发展 ANS对心理压力的反应，假设IBS患者将具有更大的ANS 激活。首先，在实验压力源期间乙状结肠张力的变化将被测试为肠道特异性ANS 替代度量和与皮肤电导和心率变异性相关。其次，与成像 FMRI将用于确定使用分析的中央ANS电路参与情绪反应 功能有效连接的工具。 IBS患者的ANS反射将通过时间课程进行测试 高分辨率fMRI期间对Valsalva操纵的中央和周围响应分析 评估广义ANS功能障碍。将强调对ANS依据中的性别差异的评估， 鉴于在这种功能障碍和许多其他功能障碍中，女性占主导地位。 相关性：肠易激综合症影响多达15％的美国人口，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套新颖的技能 用于调查IBS的潜在原因并制定新的治疗策略。