Utilization of EEG brain state-dependent TMS for treatment of motor impairment in chronic stroke patients: a proof-of-principle trial

Background: The size and direction of plasticity effects induced by transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) have been demonstrated to depend on EEG‐derived excitability states, which are defined by the ongoing sensorimotor mu‐alpha oscillation. The successful utilization of this technology in healthy participants suggests substantial potential for its application in personalized and effective therapy. However, as for now, EEG brain state‐dependent TMS has not been evaluated for the treatment of upper limb motor impairment in chronic stroke patients. Objective: Test the therapeutic efficacy of EEG brain state‐dependent TMS in direct comparison to conventional repetitive TMS (rTMS) therapy in a proof‐of‐principal trial for upper limb motor rehabilitation in chronic stroke patients. Methods: The study was designed as a parallel‐group, double‐blind randomized controlled trial. 30 chronic stroke patients (> 6 months post‐stroke) were recruited and randomly assigned to one of the two study groups. Each patient received 12 TMS therapy sessions (20 min, 3x week, over 4 weeks) directly followed by 50 min of upper limb physiotherapy. The experimental group received 400 ipsilesional TMS triple bursts (100 Hz, inter‐burst interval 3 s) triggered at the trough of sensorimotor mu‐rhythm. The control group received 1200 single pulses of conventional 1 Hz rTMS over the contralesional M1. The primary outcome parameter was the change in Fugl‐Meyer assessment upper‐extremity (FM‐UE). Outcome parameters were recorded pre‐treatment, post‐treatment, and in a 3‐month follow‐up session. Results: Both groups significantly improved in FM‐UE (p < 0.001), the experimental group from 37.6 ± 3.7 to 41.6 ± 3.9 and the control group from 40.8 ± 3.9 to 45.8 ± 4.9. There was no difference between the groups (p = 0.73). Significant gains were present from pre‐ to post‐treatment (p < 0.001), but not from post‐treatment to follow up (p = 0.49). The average phase error for targeting the mu‐alpha trough in the experimental group was ‐18.9° ± 72.6° (mean ± angdev) over all patients and sessions. Conclusion: Both, EEG brain state‐dependent TMS and conventional rTMS therapy combined with physiotherapy significantly improved FM‐UE from pre‐ to post‐treatment. Phase targeting accuracy in chronic stroke patients was comparable to values obtained in healthy participants in earlier studies.