Transcutaneous auricular vagus nerve stimulation cannot modulate the P3b event-related potential in healthy volunteers

Objective: The release of cortical norepinephrine is one of the possible mechanisms of action of vagus nerve stimulation (VNS), a neuromodulatory treatment currently under investigation for cognitive impairment. Transcutaneous auricular VNS (taVNS) may be able to activate vagal nerve branches ending in the brainstem's locus coeruleus (LC) non-invasively. The aim was to investigate if acute taVNS can modulate the P3b, a cognitive event-related potential (ERP) reflecting noradrenergic brain activation under control of the LC. Methods: Thirty-nine healthy volunteers performed an auditory oddball task during no stimulation, sham stimulation and taVNS in a randomized order. P3b amplitude, latency and behavioral outcome parameters were compared between conditions using linear mixed models. Results: P3b amplitude and latency during taVNS did not differ significantly from sham or control. Reaction time shortened and P3b latency prolonged with repetition of the oddball task. Conclusions: We were unable to modulate cognitive ERPs by means of acute taVNS in a large group of healthy volunteers. Significance: Targeting vagal nerve fibres via a transcutaneous approach did not alter the P3b in healthy participants. The stimulation parameters used and transient delivery of taVNS might be insufficient to adequately modulate the LC. Also, a disbalanced locus coeruleus - norepinephrine system in patients may be more prone for improvement. (C) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Automated summary

The aim of this study was to investigate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the brainstem's locus coeruleus (LC). However, acute taVNS did not significantly modulate cognitive event-related potentials (ERPs) in healthy volunteers, possibly due to insufficient stimulation parameters and delivery. Additionally, patients with an imbalanced LC-norepinephrine system may be more likely to benefit from taVNS.