The effects of low- and high-frequency repetitive TMS on the input/output properties of the human corticospinal pathway

The objective of this study was to characterize the effects of various parameters (notably the frequency and intensity) of repetitive transcranial magnetic stimulation (rTMS) applied over the primary motor (M1) and premotor (PMC) cortices on the excitability of the first dorsalis interosseus (FDI) corticospinal pathway. To this end, we applied a comprehensive input-output analysis after fitting the experimental results to a sigmoidal function. Twenty-six healthy subjects participated in the experiments. Repetitive TMS was applied either over M1 or PMC at 1 Hz (LF) for 30 min (1,800 pulses) or at 20 Hz (HF) for 20 min (1,600 pulses). In the HF condition, the TMS intensity was set to 90% (HF90) of the FDI's resting motor threshold (RMT). In the LF condition, the TMS intensity was set to either 90% (LF90) or 115% (LF115) of the RMT. The FDI input/output (I/O) curve was measured on both sides of the body before rTMS (the Pre session) and then during two Post sessions. For each subject, the I/O curves (i.e., the integral of the FDI motor-evoked potential (MEP) vs. stimulus intensity) were fitted using a Boltzmann sigmoidal function. The graph's maximum slope, S-50 and plateau value were then compared between Pre and Post sessions. LF115 over M1 increased the slope of the FDI I/O curve but did not change the S-50 and plateau value. This also suggested an increase in the RMT. HF90 led to a more complex effect, with an increase in the slope and a decrease in the S-50 and plateau value. We did not see a cross effect on the homologous FDI corticospinal pathway, and only PMC LF90 had an effect on ipsilateral corticospinal excitability. Our results suggest that rTMS may exert a more complex influence on cortical network excitability than is usually reported (i.e. simple inhibitory or facilitatory effects). Analysis of the fitted stimulus response curve indicates a dichotomous influence of both low- and high-frequency rTMS on M1 cortical excitability; this may reflect intermingled effects on excitatory and inhibitory cortical networks.