Brain effect of transcutaneous vagal nerve stimulation: A meta-analysis of neuroimaging evidence

Dysfunction in the autonomic nervous system is common throughout many functional gastrointestinal diseases (FGIDs) that have been historically difficult to treat. In recent years, transcutaneous vagal nerve stimulation (tVNS) has shown promise for improving FGID symptoms. However, the brain effects of tVNS remain unclear, which we investigated by neuroimaging meta-analysis.

A total of 157 studies were identified, 4 of which were appropriate for inclusion, encompassing 60 healthy human participants. Using activation likelihood analysis estimation, we statistically quantified functional brain activity changes across three domains: (1) tVNS vs. null stimulation, (2) tVNS vs. sham stimulation, and (3) sham stimulation vs. null stimulation.

tVNS significantly increased activity in the insula, anterior cingulate, inferior and superior frontal gyri, caudate and putamen, and reduced activity in the hippocampi, occipital fusiform gyri, temporal pole, and middle temporal gyri, when compared to null stimulation (all corrected p < 0.005). tVNS increased activity in the anterior cingulate gyrus, left thalamus, caudate, and paracingulate gyrus and reduced activity in right thalamus, posterior cingulate cortex, and temporal fusiform cortex, when compared to sham stimulation (all corrected p < 0.005). Sham stimulation significantly increased activity in the insula and reduced activity in the posterior cingulate and paracingulate gyrus (all corrected p < 0.001), when contrasted to null stimulation.

Brain effects of tVNS localize to regions associated with both physiological autonomic regulation and regions whose activity is modulated across numerous FGIDs, which may provide a neural basis for efficacy of this treatment. Functional activity differences between sham and null stimulation illustrate the importance of robust control procedures for future trials.