Multifocal Theta-Burst Stimulation to Enhance Upper Limb Motor Recovery After Stroke (INSPIRE)

Stroke is one of the leading causes of long-term disability worldwide. Many individuals who survive a stroke continue to experience weakness and reduced control of one arm, even months or years after the event. These motor impairments significantly affect independence, daily activities, and quality of life. Despite rehabilitation efforts, recovery of upper limb function remains incomplete for many patients. Motor recovery after stroke depends on the brain's ability to reorganize itself, a process known as neuroplasticity. Recent research suggests that motor learning and brain recovery are influenced not only by activity in the primary motor cortex (M1), but also by its functional connectivity with other brain regions, particularly the parietal cortex (PC). Strengthening communication between these regions may enhance motor recovery. This study aims to investigate a novel, non-invasive brain stimulation approach called intermittent theta-burst stimulation (iTBS). Unlike traditional stimulation methods that target a single brain region, this study uses a multifocal stimulation protocol targeting both the primary motor cortex and the parietal cortex. The stimulation is combined with structured motor training using an interactive tablet-based rehabilitation device (REAtouch®Lite 2), designed to improve arm movement through goal-directed reaching tasks. The study is a single-center, randomized, sham-controlled, triple-blind clinical trial with parallel groups. Thirty-six individuals with chronic stroke-related upper limb impairment will be randomly assigned to receive either active multifocal iTBS or sham (placebo) stimulation. Both groups will complete identical motor training sessions. In addition, ten healthy participants will complete the same motor training protocol (without brain stimulation) to provide reference data. Participants will attend six visits over approximately 10 days. Assessments will include motor performance tests using the interactive tablet, a standardized clinical motor scale (Fugl-Meyer Assessment for Upper Extremity), and resting-state electroencephalography (EEG) to measure brain connectivity changes. The primary outcome is improvement in motor performance between baseline and one week after the intervention. Secondary outcomes include short-term motor improvements, retention of learning, changes in movement quality, and changes in brain functional connectivity. This study seeks to determine whether combining multifocal brain stimulation with targeted motor training can enhance motor learning and promote better recovery of arm function after stroke. If effective, this approach could contribute to the development of more precise, network-based neurorehabilitation strategies.