Brain Mechanisms for Autonomic Outflow and Nausea in Cyclic Vomiting Syndrome

描述（由申请人提供）：虽然恶心的感觉在人类体验中是普遍的，但这种知觉状态下的大脑活动尚未得到很好的理解。恶心的典型表现为上腹不适伴呕吐冲动，自主神经系统（ANS）外流以交感神经为主。恶心是周期性呕吐综合征（CVS， ROME III定义）患者的特别衰弱症状。CVS患者会出现极度恶心和呕吐，交替出现相对无症状的时期。虽然CVS的病理生理尚不清楚，但交感迷走神经功能障碍和脑生理改变被认为在其中起着重要作用。我们的研究小组已经成功地引入了功能磁共振成像（fMRI）测量静息或内在大脑连通性的指标，作为慢性疼痛患者疼痛的客观神经生物学相关指标。我们的目标是扩展我们的方法，以更好地表征一种不同的厌恶的主观感觉-恶心。我们最近在健康成人中进行的研究，结合视觉诱导的免疫接种，同时进行功能磁共振成像和自主神经监测，表明恶心背后的大脑回路包括已知处理内感受的区域，以及大脑边缘和前额叶皮层的高级区域。晕车时，这些区域与视觉运动处理区域的连通性更强。我们的初步数据还表明，来自前额叶和边缘皮质脑区的fMRI信号，服务于恶心的认知和情感成分，与晕动病期间的自主神经调节更相关。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人晕车期间相同的内感受、情感和认知处理区域之间的静息大脑连通性增加。这种增强的连通性可能使这些患者对中枢催吐信号反应过度。我们的总体目标是通过对比CVS患者和健康成人在休息和运动病引起的恶心状态下的内在大脑连通性来评估支持恶心的脑回路。我们的目的是评估与健康成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优势的关系。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成像生物标志物，这些生物标志物可用于CVS和其他慢性恶心患者的亚表型，并为开发新疗法的纵向试验确定结果指标。

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.