Low-frequency rTMS promotes use-dependent motor plasticity in chronic stroke: a randomized trial

Objective: To investigate the long-term behavioral and neurophysiological effects of combined time-locked repetitive Transcranial Magnetic Stimulation (rTMS) and physical therapy (PT) intervention in chronic stroke patients with mild motor disabilities. Methods: 30 patients were enrolled in a double-blind, randomized, single-center clinical trial. Patients received 10 daily sessions of 1Hz rTMS over the intact motor cortex. In different groups, stimulation was either real (rTMSR) or sham (rTMSS) and was administered either immediately before or after PT. Outcome measures included dexterity, force, interhemispheric inhibition and corticospinal excitability and were assessed for three months after the end of treatment. Results: Treatment induced cumulative rebalance of excitability in the two hemispheres and a reduction of interhemispheric inhibition in the rTMSR-groups. Use-dependent improvements were detected in all groups. Improvements in trained abilities were small and transitory in rTMSS patients. Greater behavioral and neurophysiological outcomes were found after rTMSR, with the group receiving rTMSR before PT (rTMSR-PT) showing robust and stable improvements and the other group (PT-rTMSR) showing a slight improvements decline over time. Conclusion: Our findings indicate that priming PT with inhibitory rTMS is optimal to boost use-dependent plasticity and rebalance motor excitability and suggest that time-locked rTMS is a valid and promising approach for chronic stroke patients with mild motor impairment. Classification of evidence: This interventional study provides Class I evidence that time-locked repetitive Transcranial Magnetic Stimulation (rTMS) before or after physical therapy improves measures of dexterity and force in the affected limb in patients with chronic deficits more than 6 months post stroke.