Translating a Preclinically Tested 15 Hz rTMS Protocol to Humans With Chronic Spinal Cord Injury: A Safety and Feasibility Study

Objectives Repetitive transcranial magnetic stimulation (rTMS) is a non‐invasive brain stimulation strategy with a demonstrated potential to reinforce the residual pathways after a spinal cord injury (SCI). A preclinically tested high‐frequency (15 Hz) rTMS (15 Hz rTMS) protocol was shown to induce corticospinal tract axon regeneration growth and sprouting, resulting in improved voluntary motor control and performance. In a translational perspective, we aimed to investigate the safety and feasibility of the 15 Hz rTMS paradigm as an adjunct therapeutic intervention in individuals with chronic SCI. Method We thus investigated the effects of a 15‐day repeated protocol consisting of 15 Hz rTMS followed by task‐specific hand motor training in 7 individuals with chronic cervical SCI. 15 Hz rTMS targeted the weaker wrist extensor muscle, based on participant‐ and day‐specific resting motor threshold, motor responses, and maximum tolerability. Safety, feasibility, neurophysiological, and clinical functional outcomes were measured at different times of the therapeutic protocol. Results The therapeutic stimulation protocol was delivered mostly as designed except with regard to stimulation intensity and duration and was overall tolerable without major serious effects. Preliminary neuroplastic and functional benefits revealed by corticospinal excitability and intracortical inhibition modulation and clinical improvements were noted and were still observable at follow‐up times. Interpretation This study confirms that an intervention combining 15 Hz rTMS and task‐specific motor training is feasible, tolerable, and has the potential to induce neuroplastic changes and improve function in individuals with chronic cervical SCI. This feasibility study, in parallel with previous reports in able‐bodied individuals, warrants further investigation of the adapted 15 Hz rTMS protocol in individuals at an earlier stage post‐injury and to confirm efficacy in a larger and controlled study trial.