Neuromodulation of the Brain-Gut Axis by Transcutaneous Vagal Nerve Stimulation in Functional Dyspepsia

摘要 功能性消化不良(FD)是一种常见的功能性胃肠道疾病，影响着数百万美国人 每年都有。症状包括复发性上腹部不适，包括任何一种或一种组合 餐后饱足、早期饱足和/或上腹痛或灼热，在缺乏明确的结构性症状的情况下 病因学。一些FD患者尤其受到餐后饱腹感和早饱的困扰。 餐后窘迫综合征(PDS)亚型的标志。这些症状可能特别 使人虚弱，导致日常功能受损和生活质量下降。尽管有负面影响 这些症状影响了患者的生活，PDS主导型FD(PDS-FD)的发病机制尚不清楚 理解，尽管已经假设大脑-肠轴的失调是由异常 脑干迷走神经回路可能是罪魁祸首。目前治疗PDS-FD的主要方法是 药物干预，充其量是适度有效的。此外，在一些严重的病例中，症状 变得难以治愈，药物导致不想要的副作用和/或患者变得抗拒治疗。 然而，考虑到FD症状和迷走功能受损之间的强烈联系，我们提出了一种非 经皮迷走神经靶向迷走神经耳支的侵入性入路 刺激(TVNS)传递到外耳的Cumba耳甲。因此，耳穴TVNS可提供 调节以PDS为主的FD患者异常脑肠信号的新治疗策略。在 目前的项目，我们使用胃/自主神经测量结合多模式神经成像技术来 询问伴随着脑肠神经调节的外周和中枢神经系统的变化 进餐挑战期间PDS-FD患者耳廓TVNS发出的轴向信号。拟议的研究将 为PDS-FD背后的病理生理学贡献新的见解，以及评估小说的保真度， 非侵入性神经调节技术，如耳穴TVNS，以缓解FD症状。

ABSTRACT Functional Dyspepsia (FD) is a common functional gastrointestinal disorder that affects millions of Americans every year. Symptoms include recurrent epigastric discomfort consisting of any one or a combination of postprandial fullness, early satiation, and/or epigastric pain or burning, in the absence of a clear structural etiology. Some patients with FD are particularly bothered by postprandial fullness and early satiation, a hallmark of the Postprandial Distress Syndrome (PDS) subtype. These symptoms can be particularly debilitating, leading to impaired daily functioning and decreased quality of life. Despite the negative impact these symptoms have on patients' lives, the pathogenesis of PDS-predominant FD (PDS-FD) is not well understood, although it has been postulated that dysregulation of the brain-gut axis driven by abnormal brainstem vagal neurocircuitry is a possible culprit. The current mainstay of treatment for PDS-FD is pharmacological intervention which is, at best, modestly effective. Moreover, in some severe cases, symptoms become intractable, medication causes unwanted side effects and/or patient becomes treatment resistant. However, given the strong link between FD symptoms and compromised vagal function we propose a non- invasive approach that targets the auricular branch of the vagus nerve via transcutaneous vagal nerve stimulation (tVNS) delivered to the cymba conchae of the external ear. Thus, auricular tVNS may provide a novel therapeutic strategy to modulate aberrant brain-gut signaling in PDS-predominant FD. In the current project, we use gastric/autonomic measures combined with multimodal neuroimaging techniques to interrogate the peripheral and central nervous system changes that accompany neuromodulation of brain-gut axis signaling by auricular tVNS in PDS-FD patients during a prandial challenge. The proposed study will contribute new insights into the pathophysiology underlying PDS-FD as well as evaluate the fidelity of novel, non-invasive neuromodulatory techniques such as auricular tVNS to mitigate FD symptoms.