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

Transcutaneous auricular vagus nerve stimulation (taVNS) is emerging as a promising non-invasive neuromodulation technique to augment neurorehabilitation, yet its mechanisms in humans remain poorly understood. Animal studies suggest that VNS delivered during motor skill practice drives task-specific plasticity in the primary motor cortex (M1), but direct evidence in humans has been lacking. Here, we provide the first demonstration that taVNS paired with motor skill practice selectively enhances cortical plasticity without boosting motor performance beyond practice alone during short-term training. Thirty-one healthy right-handed adults practiced a novel implicit motor task, rotating two balls with the non-dominant hand for 15 minutes. Participants were randomized to receive taVNS to the left tragus or sham stimulation during practice. Motor performance, M1 hand representation (TMS mapping), and spinal excitability (F-wave) were assessed pre- and post-practice, while pupil diameter was continuously monitored as an index of noradrenergic activity. 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 only in the sham group, suggesting that taVNS-driven plasticity was restricted to cortical circuits. Moreover, taVNS uniquely elicited pupil dilation during practice, consistent with noradrenergic system engagement. These findings reveal that taVNS can promote task-specific cortical reorganization in humans independent of immediate behavioral improvement. By linking taVNS-induced plasticity to noradrenergic modulation and dissociating cortical from spinal effects, this study provides novel mechanistic insight into how taVNS may lay the neural groundwork for enhanced motor recovery, with critical implications for neurorehabilitation. Significance StatementMotor recovery after stroke depends on the brains ability to reorganize motor circuits. Vagus nerve stimulation (VNS) has been proposed as a powerful approach to enhance such plasticity, but the underlying mechanisms in humans remain unclear. Here we show that non-invasive transcutaneous auricular VNS (taVNS), when paired with motor practice, selectively enhances reorganization of the primary motor cortex without additional behavioral improvement. Importantly, these effects were observed after only 15 minutes of practice, demonstrating that taVNS can induce rapid plastic changes. This provides the first evidence in humans that taVNS promotes task-specific cortical plasticity, underscoring its promise as a neuromodulatory tool for neurorehabilitation.