The Effect of taVNS on the Cerebello-Thalamo-Cortical Pathway: a TMS Study

Abstract

fMRI studies show activation of cerebellum during transcutaneous auricular vagal nerve stimulation (taVNS); however, there is no evidence whether taVNS induced activation of the cerebellum translates to the cerebellar closed loops involved in motor functions. We assessed the propensity of taVNS at 25 Hz (taVNS25) and 100 Hz (taVNS100) to modulate cerebello-thalamo-cortical pathways using transcranial magnetic stimulation. In our double blind within-subjects study thirty-two participants completed one visit during which cerebellar brain inhibition (CBI) was assessed at baseline (no stimulation) and in a randomized order during taVNS100, taVNS25, and sham taVNS (xVNS). Generalized linear mixed models with gamma distribution were built to assess the effect of taVNS on CBI. The estimated marginal means of linear trends during each taVNS condition were computed and compared in a pairwise fashion with Benjamini-Hochberg correction for multiple comparisons. CBI significantly increased during taVNS100 compared to taVNS25 and xVNS (p = 0.0003 and p = 0.0465, respectively). The taVNS current intensity and CBI conditioning stimulus intensity had no significant effect on CBI. taVNS has a frequency dependent propensity to modulate the cerebello-thalamo-cortical pathway. The cerebellum participates in closed-loop circuits involved in motor, cognitive, and affective operations and may serve as an entry for modulating effects of taVNS.