Clinical and neurophysiological effects of rTMS combined with soft robotic glove training on upper-limb recovery after subacute stroke: a three-arm randomized controlled trial

Persistent wrist-hand motor impairment is common after stroke. Whether combining repetitive transcranial magnetic stimulation (rTMS) with task-oriented soft robotic glove (SRG) training provides additional clinical benefit remains uncertain. This study evaluated the effects of rTMS combined with SRG training on upper-limb motor recovery after subacute stroke and explored associated changes in cortical connectivity and corticomuscular information transfer. In this single-center, assessor-blinded, three-arm randomized controlled trial, 87 participants with subacute stroke were randomly assigned (1:1:1) to rTMS + SRG group, sham rTMS + SRG group, or rTMS combined with time-matched conventional occupational therapy, in addition to standardized background rehabilitation, for 2 weeks, and followed for 1 month. The primary outcome was the Fugl-Meyer Assessment for the Upper Extremity (FMA-UE). Secondary outcomes included FMA upper-arm and wrist-hand subscores, Action Research Arm Test, and Modified Barthel Index. Resting-state functional near-infrared spectroscopy (fNIRS) assessed functional connectivity. Task-based fNIRS and surface electromyography were used to calculate transfer entropy. A total of 79 participants completed all interventions and assessments. Baseline demographic and clinical characteristics were comparable among the three groups. Significant group-by-time interactions were observed for the primary and secondary clinical outcomes ( P ˂0.05). FMA-UE improvement was greater in the rTMS + SRG group than in the sham rTMS + SRG and rTMS + OT groups (mean improvement, 7.07, 4.77, and 4.65 points, respectively; Dunn-adjusted P = 0.0027 and 0.0005 for pairwise comparisons with the rTMS + SRG group). This advantage remained evident at 1-month follow-up. Improvements were most pronounced in the FMA wrist-hand subscore, with greater gains in the rTMS + SRG group than in both comparator groups during the intervention period (Dunn-adjusted P = 0.0067 and < 0.001). Resting-state fNIRS revealed greater increases in motor-related functional connectivity in the rTMS + SRG group. Transfer entropy also showed greater increases in the rTMS + SRG group than in both comparator groups (Dunn-adjusted P = 0.026 and 0.048). rTMS combined with task-oriented SRG training was associated with greater improvement in upper-limb motor impairment after subacute stroke, particularly in distal wrist-hand impairment. Changes in cortical connectivity and task-related corticomuscular information transfer provide exploratory neurophysiological insights, but their mechanistic relevance to clinical recovery requires further investigation. Trial registration Chinese Clinical Trial Registry, ChiCTR2400090007.