TMS Neuromodulation of Brain-to-Stomach Circuits in Chronic Nausea

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

Investigators

Linked publications, trials & patents

Abstract

Project Summary: Chronic nausea vomiting syndrome (CNVS) is a common, debilitating condition impacting about 1% of the adult population. It is well established that bidirectional neural interactions between the cerebral cortex and the stomach shape gastric function. Indeed, CNVS is viewed as a disorder of such gut- brain interaction (DGBI). Gastric physiology can be monitored non-invasively via electrogastrogram (EGG) recording of slow waves -- electrical potentials that propagate within the enteric nervous system. Slow wave amplitude and frequency reflect the continual, summative influence from central nervous system inputs to the stomach and drives various patterns of gastric smooth muscle contraction. Transitions to the state of nausea are accompanied by disruption of normal EGG patterns, and patients with CNVS exhibit both abnormal baseline and meal-induced EGG amplitudes and frequencies. The emerging understanding of baseline and pathological roles of gastric neurophysiology and the role of the CNS influence on this system has led to the possibility that neuromodulation of the brain-gut axis could be harnessed to treat CNVS. We recently developed a non-invasive, transcranial magnetic stimulation (TMS)-based method to stimulate and monitor descending cerebral cortical-to-stomach neural circuitry via gastric motor evoked potentials (GMEPs). In this project, we seek to locate and prioritize cortical regions that most readily impact gastric electrical function in normal subjects. We will map stomach representations in motor and premotor cortical regions by using TMS to elicit GMEPs from both left and right hemispheres (Aim 1). We will then use stimulatory (10Hz or iTBS) and inhibitory (1Hz or cTBS) modes of repetitive TMS (rTMS) neuromodulation, directed to GMEP hotspots in a M1 premotor cortical area and M1, comparing the effect of rTMS on water load-induced EGG amplitude and dominant frequency in normal subjects (Aim 2). Finally, we will reveal neurophysiological biomarkers of CNVS using TMS mapping and rTMS neuromodulation to determine differences in the topography and function of cortical-to-stomach neural circuitry that operate in those with CNVS compared to healthy control subjects (Aim 3). Successful completion of the proposed work will produce significant impact at various levels: 1) a unique and novel technical approach to precisely map cortical gastric representation in both healthy and CNVS subjects; 2) cortical modulation of neural circuits that control the stomach, revealing biomarkers of brain-gut axis pathology; and 3) a novel technique with translational potential as a next-level non-pharmacological intervention to alter the clinical course of CNVS and other DBGIs.