Spatial activation of motor evoked potentials depends on paired-pulse transcranial magnetic stimulation orientation and intensity

Objective: To investigate how stimulus orientation, intensity, and interstimulus interval (ISI) in paired-pulse transcranial magnetic stimulation (TMS) influence the spatial activation of motor evoked potentials (MEPs) in forearm flexor muscles. Methods: Paired-pulse paradigms were applied to the motor cortex using multi-coil TMS (mTMS) to control the stimulus parameters electronically without coil repositioning. MEP spatial activation was recorded with a highdensity surface electromyography (HDsEMG) grid over the forearm muscles. Conditioning stimuli (CS) were delivered at anterior-to-medial (0 degrees) and posterior-to-medial (90 degrees) orientations and 70-90 % of resting motor threshold (rMT), followed by test stimuli (TS) at 0 degrees and 110 % rMT. ISIs of 0.5 and 8 ms probed neuronal refractoriness and intracortical facilitation, respectively. Results: MEPs were facilitated at 8-ms and suppressed at 0.5-ms ISI. At 0.5 ms, changing CS orientation from 0 degrees to 90 degrees reduced suppression. Increasing CS intensity shifted activation centroids medially in most cases. Centroids were more medial at 8 ms and more lateral at 0.5 ms. Conclusions: TMS pulse orientation, intensity, and ISI systematically affect the magnitude and spatial activation of forearm muscles. Significance: Our findings highlight the utility of mTMS-HDsEMG in probing neurophysiological mechanisms of corticomotor control with important diagnostic and therapeutic clinical implications.