Low-Intensity Paired-Pulse rTMS given to the Primary Motor Cortex at 5Hz Attenuates Intracortical Excitability

Background: Repetitive transcranial magnetic stimulation (rTMS) to the primary motor hand area (M1) at a rate of 5Hz and intensities at or just below active motor threshold can produce changes in paired-pulse intracortical inhibition (SICI) beyond the time of stimulation (Oliviero et al., Exp Brain Res 2003; 149: 107–113; Peinemann et al., Neurosci Lett 2000: 296 (Dec): 21–24). Objective: to examine whether paired-pulse rTMS (pp-rTMS) at a frequency of 5Hz can modify intracortical excitability. Methods: We investigated 10 right-handed healthy subjects. Paired rTMS was applied over the left M1. All participants received either real pp-rTMS (5Hz, 80% of active motor threshold) or sham pp-rTMS (5Hz, 3% of maximum stimulator output) on two separate days in a counterbalanced order. The interstimulus interval (ISI) between paired stimuli was 2 ms. Using the Kujirai paradigm (Kujirai et al., J Physiol 1993; 471: 501–519), we assessed paired-pulse excitability of the conditioned M1 before and two times after pp-rTMS (1–10min and 11–20min after pp-rTMS). The conditioning effects of rTMS on paired-pulse excitability were assessed by measuring the amplitude of motor evoked potentials (MEPs) of the contralateral first dorsal interosseus muscle. Statistical analysis was performed using an ANOVA for repeated measurements (p<0.05). Results: Real pp-rTMS but not sham pp-rTMS caused a lasting suppression of short-interval intracortical inhibition (SICI) at ISIs of 2 and 4 ms and short-interval intracortical facilitation (SICF) at ISIs of 6, 8, 10 and 12 ms without affecting the amplitude of unconditioned MEPs. The time course of changes in SICI and SICF was different. SICI was already reduced during the first ten minutes after pp-rTMS. SICF was initially unchanged showing a delayed suppression only 10–20min after pp-rTMS. Conclusion: Low-intensity pp-rTMS of the M1 provides a promising means to suppress intracortical paired-pulse excitability without affecting the excitability of corticospinal output neurons.