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

Abstract

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.

Keywords: Event-related potentials; Healthy volunteers; Locus coeruleus; Norepinephrine; P3b; Transcutaneous auricular vagus nerve stimulation.