TMS Measured Effects of VNS on Cortical Excitability: Current Knowledge and Future Perspectives

J Clin Neurophysiol. 2026 Nov 13. doi: 10.1097/WNP.0000000000001313. Online ahead of print.

ABSTRACT

Vagus nerve stimulation (VNS) is a neuromodulation technique approved for treating neurologic and psychiatric conditions. However, objective measures that reliably reflect VNS effects on cortical excitability are lacking. Transcranial magnetic stimulation (TMS) can provide clinically meaningful indicators of vagal pathway activation, potentially improving VNS effectiveness by guiding optimal stimulation adjustments. The aim of this study was to evaluate whether previous studies provide evidence that VNS induces changes in cortical excitability captured by TMS measures, and to compare the effects of implanted VNS (iVNS) and transcutaneous VNS (tcVNS). A comprehensive literature search of PubMed and bioRxiv was conducted for human studies combining VNS and TMS. The 14-item Kmet checklist assessed risk of bias in included studies. Two studies in patients with iVNS and 10 studies in healthy participants using tcVNS were identified and reviewed. Across 11 studies, 15 TMS measures reflecting inhibitory circuits were reported: eight showed increases, and seven showed no change. Short-interval intracortical inhibition (SICI) frequently showed increases after both iVNS in patients and tcVNS in healthy participants, suggesting potentially overlapping mechanisms. Facilitatory circuits were less affected, with one study reporting a decrease and four showing no change. TMS measures can capture VNS-induced modulation of cortical excitability. Overall, VNS tends to enhance inhibitory cortical circuits with partially overlapping effects of iVNS and tcVNS. SICI emerges as a promising candidate for further investigation as a marker of VNS target engagement.

PMID:43024692 | DOI:10.1097/WNP.0000000000001313