SPARC: Respiratory‐Gated Transcutaneous Vagus Nerve Stimulation Modulates Gastric Function in Functional Dyspepsia

Abstract

The vagus nerve plays an important role in both sensory and motor aspects of gastric physiology. Both animal and human studies suggest that accommodation reflex consists of a vagovagal reflex pathway. Thus, modulating vagal efference may be promising to increase gastric hypomotility for gastroparesis or functional dyspepsia.Transcutaneous vagus nerve stimulation (tVNS) of the auricular branch of the vagus nerve is a promising non‐invasive neuromodulatory therapy for numerous disorders. We have demonstrated that tVNS targets nucleus tractus solitarii, and medullary efferent parasympathetic (vagal) nuclei (Sclocco et al. 2019). Our group showed that neural target‐engagement can be enhanced by gating stimulation to the exhalation phase of respiration, via Respiratory‐gated Auricular Vagal Afferent Nerve Stimulation (RAVANS).In this ongoing study, we evaluate nine (9) functional dyspepsia (FD) patients with both brain fMRI and 4D cine MRI of the stomach during a test meal challenge and concurrent RAVANS or Sham tVNS, to investigate effects on gastric emptying. MRI examinations were performed immediately following ingestion of a food‐based MRI contrast test meal (470ml, pineapple‐based with high manganese content), using 4D cine MRI. Each subject was scanned 15, 65, and 80 minutes post‐meal (T0, T1, T2), while experiencing active RAVANS (300μs pulse width, 1.5s stimulation trains delivered at 100Hz in the cymba concha of the left ear) or Sham (no current) on two different visits (randomized order). Abdominal MRI images were segmented to isolate the stomach, meal and air contents (semi‐automated, based on image contrast) for each subject and post‐meal time point, and volumetric indices of gastric accommodation and emptying were calculated.In FD patients, the ratio between total gastric volume and ingested volume – a proxy for gastric accommodation – was significantly higher during RAVANS compared to Sham (RAVANS: 1.46 ± 0.45, mean ± SD; Sham: 1.18 ± 0.34; p‐val = 0.024). Furthermore, the percent reduction in meal volumes during RAVANS were significantly higher compared to Sham from T0 to T1 (RAVANS: −18.18 ± 11.70%; Sham: −10.40 ± 7.47%; p‐val = 0.032), and from T0 to T2 (RAVANS: −32.68 ± 10.56%; Sham: −24.24 ± 13.63%; p‐val = 0.047).These results support the hypothesis that RAVANS can successfully modulate gastric accommodation and emptying in FD patients. Future investigations will link fMRI response to RAVANS with gut motility to investigate the brain‐gut axis underlying tVNS‐modulated gastric physiology.Support or Funding InformationWe thank the following organizations for funding support: US National Institutes of Health (NIH), Office Of The Director (OT2‐OD023867); National Institute of Biomedical Imaging and Bioengineering (R21‐EB024701); National Center for Complementary and Integrative Health, NIH (R61‐AT009306, P01‐AT006663, R01‐AT007550); National Institute of Diabetes and Digestive and Kidney Diseases (R21‐DK116029).(a) Mosaic image of abdominal 3D MRI data with air (yellow) and meal (red) segmentations; (b) 3D reconstruction of the gastric volume; (c) 3D gastric reconstruction mapping the average displacement on the stomach surface.Figure 1