Transcutaneous auricular vagus nerve stimulation during short-term motor practice drives cortical plasticity without...

Transcutaneous auricular vagus nerve stimulation (taVNS) is emerging as a promising non-invasive neuromodulation technique to augment neurorehabilitation; however, its mechanisms in humans remain poorly understood. Animal studies indicate that VNS during motor skill practice drives task-specific plasticity in the primary motor cortex (M1), but direct evidence in humans is limited. Here, we demonstrate that taVNS paired with dexterous motor skill practice selectively enhances cortical plasticity without boosting motor performance during short-term training. Thirty-one healthy adults practiced a two-ball rotation task for 15 min. Participants were randomised to receive taVNS to the left tragus or sham stimulation during practice. Motor performance, M1 representation (transcranial magnetic stimulation mapping) and spinal excitability (F-wave) were assessed pre- and post-practice, while pupil diameter was monitored during practice. Motor performance improved similarly in both groups, whereas cortical map expansion was significantly greater in the taVNS group than in the sham group. F-wave amplitude increased in the sham group but not in the taVNS group, suggesting a relative shift in the expression of practice-related plasticity toward cortical circuits when training was paired with taVNS. This pattern suggests that taVNS may influence the hierarchical expression of motor plasticity. Moreover, taVNS elicited pupil dilation during practice, consistent with noradrenergic engagement. These findings suggest that taVNS facilitates task-specific cortical reorganization in humans independent of immediate behavioural improvement. By relating taVNS-induced plasticity to noradrenergic engagement and revealing differential cortical and spinal responses, this study offers novel mechanistic insights into how pairing taVNS with motor training may establish a neural basis for motor recovery. KEY POINTS: Previous research has shown that transcutaneous auricular vagus nerve stimulation (taVNS) is a promising neuromodulatory method, yet its effects on human motor learning and underlying plasticity mechanisms remain unclear. This study shows that, in healthy adults, taVNS paired with dexterous motor practice enhanced cortical plasticity (increased M1 map size) without immediate behavioural improvement. By contrast, sham stimulation alone increased F-wave amplitude, suggesting that taVNS may promote a relative shift in the expression of plasticity toward cortical circuits. Pupillometric monitoring revealed enhanced noradrenergic activity during taVNS‑paired training, suggesting a neuromodulatory pathway associated with cortical plasticity. These findings highlight the potential of taVNS to modulate central plasticity mechanisms, offering a novel strategy that could be translated into rehabilitation interventions targeting neural recovery in neurological disorders.