Brain State-dependent Repetitive Transcranial Magnetic Stimulation for Motor Stroke Rehabilitation: A Proof of Concept Randomized Controlled Trial

BackgroundIn healthy subjects, repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1) demonstrated plasticity effects contingent on electroencephalography (EEG)-derived excitability states, defined by the phase of the ongoing sensorimotor μ-oscillation. The therapeutic potential of brain state-dependent rTMS in the rehabilitation of upper limb motor impairment post-stroke remains unexplored.ObjectiveProof-of-concept trial to assess the efficacy of rTMS, synchronized to the sensorimotor μ-oscillation, in improving motor impairment and reducing upper-limb spasticity in stroke patients.MethodsWe conducted a parallel group, randomized double-blind controlled trial in 30 chronic stroke patients (clinical trial registration number: NCT05005780). The experimental intervention group received EEG-triggered rTMS of the ipsilesional M1 [1,200 pulses; 0.33 Hz; 100% of the resting motor threshold (RMT)], while the control group received low-frequency rTMS of the contralesional motor cortex (1,200 pulses; 1 Hz, 115% RMT), i.e., an established treatment protocol. Both groups received 12 rTMS sessions (20 min, 3× per week, 4 weeks) followed by 50 min of physiotherapy. The primary outcome measure was the change in upper-extremity Fugl-Meyer assessment (FMA-UE) scores between baseline, immediately post-treatment and 3 months’ follow-up.ResultsBoth groups showed significant improvement in the primary outcome measure (FMA-UE) and the secondary outcome measures. This included the reduction in spasticity, measured objectively using the hand-held dynamometer, and enhanced motor function as measured by the Wolf Motor Function Test (WMFT). There were no significant differences between the groups in any of the outcome measures.ConclusionThe application of brain state-dependent rTMS for rehabilitation in chronic stroke patients is feasible. This pilot study demonstrated that the brain oscillation-synchronized rTMS protocol produced beneficial effects on motor impairment, motor function and spasticity that were comparable to those observed with an established therapeutic rTMS protocol.Clinical Trial RegistrationClinicalTrials.gov, identifier [NCT05005780].