Phasic spike-timing-dependent plasticity of human motor cortex during walking.

Research into mechanisms for inducing long-lasting increases in human motor system excitability holds great promise for two prime reasons. First, the research may provide a better understanding of the role of cortex in human movement. Second, an induced increase in the excitability of the motor system during walking re-training following neural injury may emerge as a valuable therapeutic adjunct. The present study applied paired associative stimulation (PAS) to healthy humans during walking. PAS is based on the principles of spike-timing-dependent plasticity. Our hypothesis predicted that PAS applied to tibialis anterior (TA) during walking would facilitate TA motor system excitability, would not be cycle-phase-specific and would not modulate motor system excitability of other lower limb muscles. Common peroneal nerve (CPN) stimulation paired with transcranial magnetic stimulation (TMS) at 0.2 Hz with an inter-spike interval chosen to achieve a long-lasting facilitation of TMS-induced responses in TA was delivered during the early swing, late swing and stance phases of the step cycle in three separate sessions. The amplitude of TMS-induced motor-evoked potentials was taken as a measure of motor system excitability. The PAS protocol increased the amplitude of TA responses to 130% of baseline in the late swing phase. A subsequent experiment conducted in two sessions revealed that this facilitation could be reversed to suppression if stimulus pairs with the same inter-spike interval were delivered in mid-swing. These novel findings demonstrate that spike-timing-dependent protocols modulate lower limb cortical circuitry during walking in a phasic manner.