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

AbstractBackgroundIn 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 function and reducing upper-limb spasticity in stroke patients.MethodsWe conducted a parallel group, randomized double-blind controlled trial in 30 chronic stroke patients. The experimental intervention group received EEG-triggered rTMS of the ipsilesional M1 (1,200 pulses; 0.33 Hz; 90% 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, 3x 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 FMA-UE improvement and spasticity reduction (clinical and objective measures). There were no significant differences between the groups in any of the outcome measures.ConclusionsThe 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 disability and spasticity that were comparable to those observed with an established therapeutic rTMS protocol.