Transcutaneous auricular vagus nerve stimulation influences gastric motility: A randomized, double-blind trial in healthy individuals

Abstract

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated regarding its therapeutic properties in several several conditions such as epilepsy, migraine and major depressive disorder and was shown to access similar neural pathways as invasive vagus nerve stimulation. While the vagus nerve's role in gut motility is physiologically established, the effect of taVNS has scarcely been investigated in humans and yielded conflicting results. Real-time gastric magnetic resonance imaging (rtMRI) is an established reproducible method to investigate gastric motility non-invasively. Objective: To investigate the influence of taVNS on gastric motility of healthy participants using rtMRI. Methods: We conducted a randomized, double-blind study using high-frequency (HF) stimulation at 25Hz or low-frequency (LF) taVNS at 1Hz after ingestions of a standardized meal in 57 healthy participants. The gastric motility index (GMI) was determined by measuring the amplitude and velocity of the peristaltic waves using rtMRI. Results: After HF taVNS, GMI was significantly higher than after LF stimulation (p ¼ 0.005), which was mainly attributable to a higher amplitude of the peristaltic waves (p ¼ 0.003). Conclusion:We provide evidence that 4-h of taVNS influences gastric motility in healthy human participants for the first time using rtMRI. HF stimulation is associated with higher amplitudes of peristaltic waves in the gastric antrum compared to LF stimulation. Further studies are needed to investigate the effect of different frequencies of taVNS and its therapeutic properties in conditions with impaired gastric motility.

Vagus nerve stimulation increases stomach-brain coupling via a vagal afferent pathway

“…The NTS is a crucial part of the gastric-vagal reflex: vagal afferents delivering interoceptive information from the stomach reach the NTS, get integrated and projected to the dorsal vagal motor nucleus, which then sends J o u r n a l P r e -p r o o f efferent commands back to the stomach [45,[47][48][49]. Previous findings also suggest the involvement of this pathway in the efferent modulation of gastric frequency following vagal stimulation in humans [33][34][35]. Although the anatomical pathways mediating the integration of gastric signals in the brain are not fully resolved [50], it is known that the NTS projects to the parabrachial nuclei and the thalamus which acts as a relay station to cortical regions of the gastric network [18,51].…”

“…taVNS has been shown to afferently increase activity in the NTS [23][24][25][26] and improve motivation [27], memory [28][29][30], and mood [31,32]. Crucially, gastric motility was also modulated via an efferent vago-vagal pathway [33][34][35]. To assess the effect of vagal afferent activation on stomach-brain coupling in healthy individuals, we used taVNS with concurrent electrogastrography (EGG) and fMRI (Fig.…”

Vagus nerve stimulation increases stomach-brain coupling via a vagal afferent pathway

“…The NTS is a crucial part of the gastric-vagal reflex: vagal afferents delivering interoceptive information (e.g., mechanical, hormonal, chemical) from the stomach reach the NTS, get integrated and projected to the dorsal vagal motor nucleus, which then sends efferent commands back to the stomach (Berthoud and Neuhuber, 2000;Neuhuber and Berthoud, 2021;Shapiro and Miselis, 1985;Waise et al, 2018). Previous findings also suggest the involvement of this pathway in the efferent modulation of gastric frequency following vagal stimulation in humans (Hong et al, 2019;Steidel et al, 2021;Teckentrup et al, 2020). Although the anatomical pathways mediating the integration of gastric signals in the brain are not fully resolved (Azzalini et al, 2019), it is known that the NTS projects to the parabrachial nuclei (PBN), where vagal and spinal afferents are integrated.…”

“…Our design used a duration of 10 min for each experimental phase (baseline vs. stimulation) as it is comparable to the baseline measurements of stomach-brain coupling by Rebollo et al (2018). However, longer taVNS periods might elicit different changes in stomach-brain coupling as they may evoke effects on gastric frequency and motility which have mostly been demonstrated after longer stimulation periods (Steidel et al, 2021;Teckentrup et al, 2020;. Second, it is not known whether left-vs. right-sided stimulation leads to comparable effects on the gastric network, as lateralization differences between visceral fibers of the vagus nerve might play a role (Wang et al, 2021).…”

“…Transcutaneous auricular vagus nerve stimulation (taVNS) has been shown to afferently increase activity in the NTS (Frangos et al, 2015;Sclocco et al, 2019;Teckentrup et al, 2021;Yakunina et al, 2017) and improve motivation (Neuser et al, 2020), memory (Giraudier et al, 2020;Jacobs et al, 2015;Vazquez-Oliver et al, 2020), and mood (Ferstl et al, 2021;Kraus et al, 2007). Vice versa, gastric motility was modulated by manipulations of an efferent vago-vagal pathway (Hong et al, 2019;Steidel et al, 2021;Teckentrup et al, 2020). Here, we used taVNS with concurrent electrogastrography (EGG) and fMRI to assess the effect of vagal afferent activation on stomach-brain coupling in healthy individuals (Fig.…”