High-Frequency Repetitive Transcranial Magnetic Stimulation Effects on Motor Intracortical Neurophysiology: A Sham-Controlled Investigation

Purpose:The purpose of this study was to investigate the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) versus sham stimulation on intracortical inhibition (ICI) and intracortical facilitation within the motor cortex. Such data are needed to better understand the presumed neurophysiologic effects of rTMS.Methods:The authors hypothesized that, compared with sham stimulation, 20 Hz rTMS will decrease ICI and increase intracortical facilitation in healthy volunteers. Using single-pulse and paired-pulse TMS, the authors evaluated prestimulation and poststimulation effects on motor cortex neurophysiology in neurologically healthy volunteers who received 2,000 stimuli of either 20 Hz rTMS (n = 11) or sham rTMS (n = 8). Primary outcomes were changes in ICI and intracortical facilitation and secondary outcomes were changes in motor threshold and motor evoked potential amplitude, and both were assessed using separate 2 x 2 (group x time) repeated-measures analysis of variance.Results:For ICI, there were main effects of time (P = 0.002) and group (P < 0.001) with a significant group-by-time interaction (P < 0.01). Intracortical inhibition decreased after rTMS, but was unchanged by sham rTMS. Intracortical facilitation results revealed a main effect of group (P = 0.02) and a significant group-by-time interaction (P = 0.048). Intracortical facilitation increased after rTMS and was slightly reduced after sham rTMS. The group-by-time interactions for motor threshold and motor evoked potential amplitude were not significant.Conclusions:High-frequency rTMS significantly influences the excitatory and inhibitory outputs of motor intracortical networks, specifically increasing intracortical facilitation and reducing ICI as compared with sham stimulation. Such changes were observed despite no significant changes in broader measures of motor cortex activation, that is, motor threshold and motor evoked potential amplitude.