Volitional muscle activity paired with transcranial magnetic stimulation increases corticospinal excitability

Studies of activity-dependent stimulation in non-human primates suggest that pairing each instance of volitional muscle activity with immediate intracortical stimulation causes long-term-potentiation-like effects. This technique holds promise for clinical rehabilitation, yet few investigators have tested activity-dependent stimulation in human subjects. In addition, no one has studied activity-dependent stimulation on the cortical representation for two separate target muscles in human subjects. We hypothesized that 40 min of transcranial magnetic stimulation (TMS) triggered from ballistic muscle activity at a mean repetition rate of 1 Hz would cause greater increases in corticospinal excitability than TMS-cued muscle activity, and that these changes would be specific to the muscle of study. Ten healthy human subjects participated in 4 separate sessions in this crossover study: (1) visually cued volitional activation of the abductor pollicis brevis (APB) muscle triggering TMS (APB-Triggered TMS), (2) volitional activation of APB in response to TMS delivered from a recording of the prior APB-Triggered TMS session (TMS-Cued APB), (3) visually cued volitional activation of the extensor digitorum (ED) triggering TMS (ED-Triggered TMS), and (4) volitional activation of ED in response to TMS delivered from a recording of the prior ED-Triggered TMS session (TMS-Cued ED). Contrary to our hypothesis, we discovered evidence of increased corticospinal excitability for all conditions as measured by change in area of the motor evoked potential. We conclude that single TMS pulses paired either before or after muscle activity may increase corticospinal excitability and that further studies are needed to clarify the optimal time window for inducing neural plasticity with activity-dependent stimulation. These findings will inform the design of future activity-dependent stimulation protocols for clinical rehabilitation.