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

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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.