Abstract
BACKGROUND: Although traditional rehabilitation training can partially improve motor function in patients with post-stroke motor disorders, its impact on neural plasticity remains limited. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive method targeting the auricular branch of the vagus nerve, represents a promising neuromodulatory approach. This prospective study aimed to assess the therapeutic effects of taVNS on functional recovery in this population. METHODS: A total of 147 patients with post-stroke motor disorders were consecutively enrolled between February 2023 and November 2024. After excluding 8 dropouts, 139 patients were randomly assigned via a random number table to either an electrical stimulation group (taVNS group) or a rehabilitation group (conventional training). The taVNS group initially included 73 patients, with 3 dropouts yielding a final sample of 70. The rehabilitation group initially included 74 patients, with 5 dropouts resulting in 69 participants. All participants underwent comprehensive assessments at baseline and following a 4-week intervention period. Outcome measures encompassed neuroelectrophysiological parameters (motor evoked potential latency and amplitude), clinical functional evaluations (Action Research Arm Test, Fugl-Meyer Assessment for Upper Extremity, Modified Barthel Index), serum biomarker levels (brain-derived neurotrophic factor, S100 calcium-binding protein β), and systematic documentation of adverse events. Based on post-treatment Fugl-Meyer Assessment-Upper Extremity (FMA-UE) scores, patients were further categorized into improvement and non-improvement subgroups for additional comparative analysis. Pearson correlation analysis was utilized to examine potential relationships between functional scores, neurophysiological data, and biomarker concentrations. RESULTS: Baseline characteristics were comparable between groups (p > 0.05). Post-intervention, the taVNS group showed significantly superior outcomes: shorter MEP latency (p < 0.05), higher MEP amplitude (p < 0.05), improved scores on ARAT, FMA-UE, and MBI (all p < 0.05), increased levels of BDNF (p < 0.05), and decreased levels of S100-β (p < 0.05). Within-group analysis indicated that MEP latency decreased only in the taVNS group, while amplitude improved in both groups. In the rehabilitation group, post-treatment MEP latency showed no significant difference from baseline (p > 0.05). Both groups exhibited significant post-treatment improvements in ARAT, FMA-UE, and MBI scores. However, the magnitude of improvement in clinical scores and biomarkers was substantially greater in the taVNS group after treatment. The pre-to post-treatment changes in MEP latency and MEP amplitude were larger in the taVNS group compared to the rehabilitation group (p < 0.001). Similarly, the changes in ARAT, FMA-UE, and MBI scores, as well as in BDNF and S100-βlevels, were all greater in the taVNS group than (p < 0.001). Adverse reaction incidence did not differ significantly between groups (taVNS 11.43% vs. rehabilitation 8.70%, p > 0.05). ARAT, FMA-UE, and MBI scores were negatively correlated with MEP latency and S100-β levels, and positively correlated with MEP amplitude and BDNF levels (all p < 0.05). These correlations were consistent for baseline values, post-treatment values, and pre-post change values. CONCLUSION: taVNS is an effective and safe adjunctive therapy for post-stroke motor recovery. It enhances neuroelectrophysiological function, improves motor and daily living abilities, and favorably modulates biomarkers of neural injury and repair. The consistent correlations among functional, neurophysiological, and biochemical outcomes highlight an integrated recovery pathway, supporting the integration of taVNS into standard neurorehabilitation protocols.