Synchronized application of closed-loop NMES and precision tACS in post-stroke hand rehabilitation: a protocol of neurorehabilitation trial.

Background: Severe upper extremity paresis due to stroke is a significant clinical sequela. Neuromuscular electrical stimulation (NMES)-based rehabilitation has demonstrated promising results along with cortical plasticity. Transcranial alternating current stimulation (tACS) has gained attention due to its unique ability to entrain endogenous oscillatory brain rhythms with injected AC frequency, offering the potential for modifying brain conditions to enhance rehabilitative interventions. Because repetitive motor execution in rehabilitation training requires a smooth transition of the brain state despite often being impaired secondary to stroke, combining NMES and tACS may offer better treatment efficacy.

Aim: This study proposes a phase I/II trial of an outpatient comprehensive rehabilitative treatment combining the integrated volitional-control electrical stimulation (IVES), a closed-loop NMES, and the timing-specified focal tACS in individualized beta frequency (dynamic-precision tACS) targeting severe hand paresis in patients with chronic stroke, aiming to demonstrate the feasibility of combination treatment.

Design: Double-blind randomized cross-over trial.

Methods: The repetitive facilitative finger extension training utilizing closed-loop NMES is combined with dynamic-precision tACS on the primary motor cortex to assist post-movement beta-rebound. Together with regular occupational therapy, we propose a comprehensive outpatient neurorehabilitative regimen. Here, a total of 10 sessions will be conducted using a cross-over design using real and sham tACS.

Analysis: The perception and fatigue from stimulation will be investigated as the primary outcomes. The efficacy of improving sensorimotor function and their background physiological mechanisms will be evaluated as the secondary outcomes.

Discussion: This phase I/II trial will be the first to combine tACS and neurorehabilitation using functional electrical stimulation. A weekly outpatient protocol with cheap devices may offer a new treatment paradigm toward functional recovery for chronic stroke patients with severe upper extremity paresis.

Ethics and trial registration: This study was approved by the Ethics Committee of Kyorin University Faculty of Medicine (814-01). The trial was registered in a public database: UMIN000048274.