Body Region Specificity for Neuromodulation of the Gut-Brain Axis in Functional Dyspepsia

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PROJECT SUMMARY/ABSTRACT The candidate is an accomplished bioengineer with formal training in human brain-body imaging and neuromodulation, and a commitment to a career in translational research in the study of integrative medicine and neurogastroenterology. The candidate’s long-term career goal is to develop a translational research program in integrative medicine approaches for gut-brain modulation. The candidate’s short-term career goals are to 1) transition towards independence through mentored training focused on integrative medicine, placebo research, and neurogastroenterology; 2) weave new research skills into her technical imaging background, with potential for longitudinal studies evaluating non-pharmacological therapies; 3) produce the data and publications necessary to transition into a successful R01 application. This application outlines the institutional commitment, research plan, career development activities, and key mentors involved to ensure the candidate accomplishes these goals. In recently published work, the candidate has demonstrated the feasibility of using dynamic cine- MRI for non-invasive characterization of multiple aspects of gastric function in healthy subjects and patients with functional dyspepsia (FD). In this proposal, the candidate seeks to apply MRI-based tools to compare the impact of stimulation at different acupoint locations on brainstem neurocircuitry and gastric motility in patients with FD, as well as the interaction between treatment and expectancy manipulation. The specific goals of this study are to 1) evaluate the underlying brainstem neurocircuitry of transcutaneous electrical acupoint stimulation (TEAS) in FD; 2) compare the effect of leg (acupoint ST36) versus abdomen (acupoint ST25) TEAS on gastric motility in FD; 3) evaluate the effect of expectancy manipulation on meal- evoked symptoms and physiological outcomes. As an integral part of this proposal, the candidate’s career development will be complemented by participation in advanced coursework to develop expertise in placebo research, integrative medicine, gastroenterology, and conduct of clinical trials. A formal mentorship committee, consisting of multidisciplinary experts in placebo research, neurogastroenterology, neuroimaging, acupuncture, and integrative medicine, will provide supervision, guidance, and assistance for the candidate to achieve her goals. The research environment, which includes the Spaulding Rehabilitation Hospital, the Athinoula A. Martinos Center for Biomedical Imaging, the Center for Integrative Pain Neuroimaging (CiPNI), the Gastrointestinal Unit and MGH Center for Neurointestinal Health, and the Harvard Medical School will provide a rich, collaborative, and intellectually stimulating atmosphere to ensure the candidate’s success. Through this award, the candidate will emerge as an independent investigator by contributing to our understanding of the brain-gut mechanisms supporting acupoint-specific effects in patients with a disorder of gut-brain interactions.