Does transcutaneous auricular vagus nerve stimulation alter pupil dilation? A living Bayesian meta-analysis.

Background: Transcutaneous vagus nerve stimulation (tVNS) has emerged as a promising technique to modulate autonomic functions, and pupil dilation has been recognized as a promising biomarker for tVNS-induced monoaminergic release. Nevertheless, studies on the effectiveness of various tVNS protocols have produced heterogeneous results on pupil dilation to date.

Methods: Here, we synthesize the existing evidence and compare conventional ("continuous") and pulsed stimulation protocols using a Bayesian meta-analysis. To maintain a living version, we developed a Shiny App with the possibility to incorporate newly published studies in the future. Based on a systematic review, we included 18 studies (N = 771) applying either conventional or pulsed stimulation protocols.

Results: Across studies, we found anecdotal evidence for the null hypothesis, showing that taVNS does not increase pupil size (g = 0.15, 95% CI = [0.03, 0.27], BF = 1.0). Separating studies according to conventional vs. pulsed protocols revealed that studies using pulsed taVNS provide strong evidence for the alternative hypothesis(g = 0.36, 95% CI = [0.19, 0.53], BF = 50.8) while conventional taVNS studies provide strong evidence for the null hypothesis (g = 0.002, CI = [-0.14, 0.14], BF= 21.9).

Conclusion: Our meta-analysis highlights differential effects of conventional and pulsed taVNS protocols on pupil dilation. These findings underscore the relevance of taVNS protocols in optimizing its use for specific applications that may require modulation of tonic vs. phasic monoaminergic responses and might also help to gain mechanistic insights into potential therapeutic effects.