High-intensity, low-frequency repetitive transcranial magnetic stimulation enhances excitability of the human corticospinal pathway

Paired corticospinal-motoneuronal stimulation (PCMS) is the repeated pairing of transcranial magnetic stimulation (TMS) with peripheral nerve stimulation to modify corticospinal synapses; however, it has yet to be determined whether PCMS modulates cortical excitability in a manner similar to paired-associative stimulation protocols. In this study, we first examined the effects of PCMS on adductor pollicis motor evoked potentials (MEPs). In , on 2 separate days PCMS (repetitive, high-intensity TMS and ulnar nerve stimulation pairs; 1.5-ms interstimulus interval; 0.1 Hz) was compared with control conditioning of repetitive high-intensity TMS-only stimuli (0.1 Hz). Before and after conditioning, adductor pollicis MEPs were elicited using low-intensity TMS in three different coil orientations to preferentially activate corticospinal axons directly (thus bypassing cortical effects) or indirectly (cortical effects present). Unexpectedly, similar MEP increases were seen for all orientations on both PCMS (129 to 136% of baseline) and control days (108 to 129% of baseline). Given the common factor between conditioning protocols was repeated, high-intensity TMS, further experiments were performed to characterize this repetitive TMS (rTMS) protocol. In , an intensity dependence of the rTMS protocol was revealed by a lack of change in MEPs elicited after repetitive low-intensity TMS (0.1 Hz; = 0.37). In , MEP recruitment curve and paired pulse analyses showed that the high-intensity rTMS protocol increased MEPs over a range of stimulus intensities but that effects were not accompanied by changes in intracortical inhibition or facilitation ( > 0.12). These experiments reveal a novel high-intensity, low-frequency rTMS protocol for enhancing corticospinal excitability. In this study, we present a novel, intensity-dependent repetitive transcranial magnetic stimulation (rTMS) protocol that induces lasting, plastic changes within the corticospinal tract. High-intensity rTMS at a frequency of 0.1 Hz induces facilitation of motor evoked potentials (MEPs) lasting at least 35 min. Additionally, these changes are not limited only to small MEPs but occur throughout the recruitment curve. Finally, facilitation of MEPs following high-intensity rTMS does not appear to be due to changes in intracortical inhibition or facilitation.