The Effect of HD-tDCS With Task-Oriented Upper-Limb Training After Stroke: A Randomized Sham-Controlled Trial

Background High-definition transcranial direct current stimulation (HD-tDCS) may provide more focal neuromodulation than conventional tDCS, but its incremental benefit when paired with upper-limb training after chronic stroke remains uncertain. Methods In this multicenter, randomized, double-blind, sham-controlled trial, adults (19–80 years) with unilateral ischemic or hemorrhagic stroke ≥ 3 months and upper-limb impairment (FMA-UE 25–58) received 10 sessions (2–3/week for 4 weeks) of personalized multichannel HD-tDCS or sham using the same montage, each paired with standardized task-oriented upper-limb training. Outcomes assessed at baseline and week 4 included the FMA-UE total score and subdomain scores, dexterity (Box and Block Test), grip and pinch strength, sequential finger tapping, and task-evoked fNIRS metrics (ipsilesional M1 and aIPS activation, M1–aIPS functional connectivity). Between-group effects were estimated using analysis of covariance (ANCOVA) adjusting for baseline values. Safety outcomes included adverse events/adverse device effects and vital signs. Results Fifty-five participants were included in the efficacy analyses (real HD-tDCS n = 27; sham n = 28). Adherence was high and comparable between groups. Both groups improved in FMA-UE total score over 4 weeks; the adjusted between-group difference favored real stimulation but was not statistically significant (adjusted difference 2.09 [95% CI − 0.43 to 4.61], P = 0.1014). However, the FMA-UE wrist subdomain showed a significant between-group difference favoring real HD-tDCS (adjusted difference 1.26 [95% CI 0.26 to 2.26], P = 0.0142). Other FMA-UE subdomains, dexterity, strength, sequential finger tapping, and fNIRS activation/connectivity metrics did not differ significantly between groups. No serious adverse events occurred. Conclusion Personalized multichannel HD-tDCS paired with task-oriented upper-limb training was feasible and safe and showed a significant between-group benefit in the FMA-UE wrist subdomain favoring real stimulation, although the overall FMA-UE total score did not reach statistical significance. These findings suggest that focal HD-tDCS may preferentially modulate distal motor recovery and warrant confirmation in adequately powered trials.