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历中是普遍存在的，但这种感知状态背后的大脑活动尚不清楚。恶心的典型特征是上腹不适并伴有呕吐的冲动，以及以交感神经支配为特征的自主神经系统（ANS）流出。对于周期性呕吐综合征（CVS，ROME III 定义）患者来说，恶心是一种特别令人衰弱的症状。 CVS 患者会出现极度恶心和呕吐的症状，与相对无症状的时期交替出现。虽然人们对 CVS 的病理生理学知之甚少，但交感迷走神经功能障碍和大脑生理学改变已被认为发挥了重要作用。我们的团队成功引入了源自功能性 MRI (fMRI) 静息或内在大脑连接测量的指标，作为慢性疼痛患者疼痛的客观神经生物学相关因素。我们的目标是扩展我们的方法，以更好地描述不同的厌恶性主观感觉——恶心。我们最近对健康成年人进行的研究表明，恶心的大脑回路包括已知的处理内感受的区域，以及边缘系统和较高的前额皮质大脑区域。在晕动病期间，这些区域与视觉运动处理区域表现出更大的连接性。我们的初步数据还表明，来自前额叶和边缘皮质大脑区域的功能磁共振成像信号有助于恶心的认知和情感成分，与晕动病期间的自主调节更相关。因此，我们假设 CVS 患者，即使在发作间期状态下，也会表现出健康成人晕动病期间发现的相同内感受、情感和认知处理区域之间的静息大脑连接性增加。这种增强的连通性可能会使这些患者对中枢催吐信号产生过度反应。我们的总体目标是通过对比 CVS 患者与健康成年人在休息时和晕动病引起的恶心状态下的内在脑连接，来评估支持恶心的大脑回路。我们的目标将评估健康成年人与晕动病引起的恶心相关的功能性大脑连接，并研究 CVS 中静息大脑连接的改变及其与交感神经支配的关系。一旦完成，我们的长期目标是利用恶心和 CVS 背后的脑回路特征来建立客观的神经影像生物标志物，可用于对 CVS 和其他慢性恶心患者进行亚表型分析，并定义纵向试验的结果测量新疗法的开发。 公共健康相关性：该项目的目标是检查健康成人和周期性呕吐综合症患者恶心的大脑回路。我们将把这个电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来更好地了解大脑对晕动病的反应，并将我们的研究结果与慢性恶心患者的研究结果进行比较。