Efficacy and safety of high-definition transcranial direct current stimulation combined with digital rehabilitation on upper limb function in stroke patients: study protocol for a randomized, double-blind, sham-controlled confirmatory trial

Background: Stroke remains a leading cause of long-term disability worldwide, with a significant proportion of survivors suffering from persistent upper limb impairments despite conventional rehabilitation. High-definition transcranial direct current stimulation (HD-tDCS) has emerged as a promising neuromodulation technique capable of precise cortical targeting, potentially enhancing motor recovery when combined with structured rehabilitation. This study aims to confirm the efficacy and safety of HD-tDCS combined with digital upper limb rehabilitation in improving upper limb motor function among stroke survivors. Methods: This multicenter, randomized, parallel-group, double-blind, sham-controlled superiority trial will enroll 64 participants with chronic unilateral stroke who will be randomized to receive either active HD-tDCS or sham stimulation, both combined with standardized digital upper limb rehabilitation. The intervention will consist of 10 sessions over 4 weeks (40 min per session). Each session will include 10 min of HD-tDCS at rest targeting the ipsilesional primary motor cortex and anterior intraparietal sulcus, followed by 20 min of task-based digital rehabilitation with concurrent HD-tDCS, and a final 10 min of digital rehabilitation alone. The primary outcome will be the postintervention change in the Fugl–Meyer Assessment of Upper Extremity score from baseline. Secondary outcomes will include grip and pinch strength, 9-Hole Pegboard Test, Box and Block Test, finger-tapping performance, Short Form–36, and cortical activation measured via integrated functional near-infrared spectroscopy (fNIRS). fNIRS will help characterize task-related cortical hemodynamic responses in the stimulated area, which are associated with motor recovery. Discussion: This trial provides promising exploratory findings and is designed to rigorously assess both behavioral and hemodynamic brain responses. By integrating real-time brain monitoring, this study seeks to contribute to existing evidence on the mechanisms underlying HD-tDCS-enhanced neuroplasticity and inform the development of future precision neurorehabilitation strategies. Trial registration: This trial has been registered at the Clinical Research Information Service (Registration number: KCT0010556). Registration date: May 28, 2025.