Frequency-Specific Effects of Noninvasive Median Nerve Stimulation on Gastric Slow Wave Activity in Humans

Neuromodulation. 2024 Mar 11:S1094-7159(24)00028-X. doi: 10.1016/j.neurom.2023.12.005. Online ahead of print.

Abstract

Objectives: The present study explored the effects of different frequencies of noninvasive median nerve stimulation (nMNS) on two autonomic responses: gastric slow waves under water-loading condition and heart rate variability (HRV). To the best of our knowledge, this is the first study to document the effects of different frequencies of nMNS on gastric slow waves (GSW) in humans under 5-minute water-loading condition.

Materials and methods: Twenty healthy adult participants were fitted with a noninvasive body-surface gastric mapping, electrocardiogram (ECG), and a transcutaneous electrical nerve stimulation device and administered with four different nMNS frequencies (placebo-0 Hz, 40 Hz, 120 Hz, and 200 Hz) on four separate counterbalanced days. After the baseline and stimulation periods, a 5-minute water-load test was applied, and a post-water-load period also is recorded for ECG and GSW activity. Time-domain HRV parameters are analyzed with repeated-measures one-way analysis of variance (ANOVA) and a post hoc Tukey multiple comparison test. Parameters that failed normality tests underwent a Freidman test with a post hoc Dunn multiple comparison test. GSW data are analyzed with repeated-measures mixed-effects ANOVA.

Results: In empty stomach (baseline vs stimulation), only the 40-Hz frequency statistically significantly (p = 0.0129) increased GSW amplitude in comparison with its own baseline. In full (distended) stomach, 40-Hz and 200-Hz stimulations showed a statistically significant difference (post hoc multiple comparison adjusted, p = 0.0016 and p = 0.0183, respectively) in the Gastric Rhythm Index in comparison with the change obtained by placebo stimulation (baseline vs poststimulation periods); 120-Hz nMNS showed a statistically significant difference (p = 0.0300) in the stress index in comparison with the decrease observed in the placebo group. However, 120-Hz nMNS did not induce a statistically significant change in gastric electrical activity compared to placebo stimulation. The nMNS did not follow the linear "dose-response" relationship between nMNS frequency and gastric/HRV parameters.

Conclusions: The 40-Hz and 200-Hz nMNS frequencies showed the most promising results in response to gastric distension, in addition to 40 Hz for an empty stomach. Further research is essential to explore the potential therapeutic effects of these frequencies on gastric diseases such as gastroparesis, gastroesophageal reflux disease, and functional dyspepsia that can be used in wrist wearables.

Keywords: Electrogastrogram; gastric motility; heart rate variability; median nerve stimulation; noninvasive neuromodulation.