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

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 dilatation to date. Here, we synthesize the existing evidence and compare conventional continuous and pulsed stimulation protocols using 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 continuous or pulsed stimulation protocols. Across studies, we found anecdotal evidence for the alternative hypothesis that tVNS increases pupil size (g = 0.14, 95% CI = [0.001, 0.29], BF01 = 2.5). Separating studies according to continuous vs. pulsed protocols revealed that results were driven by studies using pulsed taVNS (strong evidence for the alternative hypothesis: g = 0.34, 95% CI = [0.15, 0.53], BF10 = 14.15) while continuous tVNS provided strong evidence for the null hypothesis (g = 0.01, CI = [-0.15, 0.16], BF01= 20.7). In conclusion, our meta-analysis highlights differential effects of continuous and pulsed tVNS protocols on pupil dilation. These findings underscore the relevance of tVNS protocols in optimizing its use for specific applications that may require modulation of tonic vs. phasic monoaminergic responses.