Brain Mechanisms for Autonomic Outflow and Nausea in Cyclic Vomiting Syndrome

周期性呕吐综合征自主神经流出和恶心的脑机制

• 批准号: 8427958
• 负责人: Braden Kuo
• 金额: $ 26.11万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-20 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8427958
• 关键词: Adult; Affective; Area; Autonomic nervous system; Biological Markers; Brain; Brain region; Chronic; Cognitive; Data; Development; Electrocardiogram; Emetics; Emotions; Epigastric; Esthesia; Exhibits; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Galvanic Skin Response; Goals; Human; Hypothalamic structure; Imaging Techniques; Insula of Reil; Lateral; Link; Magnetic Resonance Imaging; Measures; Medial; Metric; Monitor; Motion; Motion Sickness; Nausea; Nausea and Vomiting; Neurobiology; Outcome Measure; Pain; Patients; Phenotype; Physiology; Play; Prefrontal Cortex; Process; Relative (related person); Rest; Role; Scanning; Signal Transduction; Symptoms; Syndrome; Visual; Visual Motion; Vomiting; chronic pain; cingulate cortex; experience; heart rate variability; indexing; neuroimaging; novel; response

DESCRIPTION (provided by applicant): While the sensation of nausea is universal in the human experience, the brain activity underlying this perceptual state is not well understood. Nausea is typified by epigastric discomfort with the urge to vomit, and autonomic nervous system (ANS) outflow characterized by sympathetic dominance. Nausea is a particularly debilitating symptom for patients with Cyclic Vomiting Syndrome (CVS, ROME III definition). CVS patients suffer from episodes of extreme nausea and vomiting, alternating with relatively symptom-free periods. While the pathophysiology of CVS is poorly understood, sympathovagal dysfunction and altered brain physiology have been proposed to play a significant role. Our group has successfully introduced metrics derived from functional MRI (fMRI) measures of resting, or intrinsic, brain connectivity as objective neurobiological correlates of pain in chroni pain patients. Our goal is to extend our approach to better characterize a different aversive subjective sensation - nausea. Our recent studies in healthy adults using combined visually-induced vection with concurrent fMRI and autonomic monitoring has suggested that the brain circuitry underlying nausea includes areas known to process interoception, as well as limbic and higher prefrontal cortical brain regions. These regions demonstrate greater connectivity to visual motion processing regions during motion sickness. Our preliminary data also suggests that fMRI signal from prefrontal and limbic cortical brain regions subserving the cognitive and affective components of nausea is more correlated with autonomic modulation during motion sickness. Hence, we hypothesize that CVS patients, even during their inter-episodic state, will demonstrate increased resting brain connectivity between the same interoceptive, affective, and cognitive processing regions identified during motion sickness in healthy adults. Such enhanced connectivity may predispose these patients to be hyper-responsive to central emetic signaling. Our overall goal is to evaluate the brain circuitry supporting nausea by contrasting intrinsic brai connectivity in CVS patients with that of healthy adults, both at rest and during a motion sickness-induced nausea state. Our Aims will evaluate functional brain connectivity associated with motion sickness-induced nausea in healthy adults, and investigate altered resting brain connectivity in CVS and its relationship to sympathetic dominance. Once completed, our long-term goal is to use the characterization of brain circuitry underlying nausea and CVS to establish objective neuroimaging biomarkers, which can be used to sub-phenotype CVS and other chronic nausea patients, and to define outcome measures for longitudinal trials in the development of novel therapies. PUBLIC HEALTH RELEVANCE: The goals of this project are to examine the brain circuitry of nausea in both healthy adults and patients with Cyclic Vomiting Syndrome. We will relate this circuitry with activity in the autonomic nervous system. This study will apply state of the art functional magnetic resonance imaging techniques to better understand brain response to motion sickness, comparing our findings with those of patients with chronic nausea.

描述（由申请人提供）：虽然恶心的感觉在人类经验中是普遍的，但这种感知状态下的大脑活动尚未得到很好的理解。恶心的典型症状是上腹部不适，伴有呕吐冲动，以及以交感神经支配为特征的自主神经系统（ANS）流出。恶心是周期性呕吐综合征（CVS，罗马III定义）患者的一种特别衰弱的症状。CVS患者遭受极端恶心和呕吐的发作，与相对无恶心的时期交替。虽然CVS的病理生理学知之甚少，但交感迷走神经功能障碍和脑生理学改变已被提出发挥重要作用。我们的小组已经成功地引入了来自功能性MRI（fMRI）的指标，作为慢性疼痛患者疼痛的客观神经生物学相关性的休息，或内在，大脑连接的措施。我们的目标是扩展我们的方法，以更好地描述一种不同的令人厌恶的主观感觉-恶心。我们最近在健康成年人中使用视觉诱导向量与同时进行的功能磁共振成像和自主监测相结合的研究表明，恶心的脑回路包括已知处理内感受的区域，以及边缘系统和更高的前额叶皮层脑区域。这些区域在晕动病期间表现出与视觉运动处理区域更大的连通性。我们的初步数据还表明，功能性磁共振成像信号从前额叶和边缘皮质脑区subserving恶心的认知和情感成分与自主调制在晕动病。因此，我们假设CVS患者，即使在他们的间歇状态下，也会表现出在健康成年人晕动病期间确定的相同内感受，情感和认知处理区域之间的静息脑连接增加。这种增强的连接性可能使这些患者对中枢呕吐信号过度反应。我们的总体目标是通过对比CVS患者与健康成年人的内在脑连接来评估支持恶心的脑回路，无论是在休息时还是在运动性疾病引起的恶心状态下。我们的目标将评估与健康成年人运动病引起的恶心相关的功能性脑连接，并研究CVS中静息脑连接的改变及其与交感神经优势的关系。一旦完成，我们的长期目标是使用恶心和CVS相关脑回路的表征来建立客观的神经影像学生物标志物，其可用于CVS和其他慢性恶心患者的亚表型，并定义新疗法开发中纵向试验的结局指标。 公共卫生关系：这个项目的目标是检查健康成人和周期性呕吐综合征患者恶心的脑回路。我们将把这个回路与自主神经系统的活动联系起来。这项研究将应用最先进的功能磁共振成像技术，以更好地了解大脑对运动病的反应，将我们的研究结果与慢性恶心患者的研究结果进行比较。