Suppression of EMG activity by subthreshold paired-pulse transcranial magnetic stimulation to the leg motor cortex

Cortical activity driving a voluntary muscle contraction is inhibited by very low-intensity transcranial magnetic stimulation (TMS) and is reflected in the suppression of the average rectified EMG. This approach offers a method to test the contribution of cortical neurons actively involved in a motor task, but requires a large number of stimuli (~100) to suitably depress the average EMG. Here, we investigated whether two pulses of subthreshold TMS at interstimulus intervals (ISIs) ranging between 1 and 12 ms could enhance the amount of EMG suppression in the tibialis anterior muscle compared to a single pulse. Pairs of subthreshold TMS at an ISI of 7 ms produced the maximum EMG suppression that was 42% more than the inhibition elicited using a single pulse. In addition, the signal-to-noise ratio of the TMS-induced suppression was further increased by a second pulse, delivered 7 ms later. The reduction in the EMG at the 7 ms paired-pulse interval occurred without any short-latency excitation suggesting that the two stimuli increased the activation of cortical inhibitory neurons. Subthreshold paired-pulse TMS at ISIs of 1-3 ms was prone to EMG excitation in the period that immediately preceded the inhibition and is consistent with the recruitment of short-interval intracortical facilitation (SICF). We propose that pairs of subthreshold TMS outside the range of SICF with an inter-pulse interval of 7 ms is optimal to inhibit ongoing cortical activity during human motor movement.