Short Interval Intracortical Inhibition Responses to Low-Frequency Repetitive Transcranial Magnetic Stimulation Under Multiple Interstimulus Intervals and Conditioning Intensities

Background: The extent to which short interval intracortical inhibition (SICI) responds to low-frequency repetitive transcranial magnetic stimulation (rTMS) remains inconclusive with reports of increased, decreased and unchanged response following modulation. The aim of this study was to systematically investigate if the variability of SICI following rTMS is explained by the interstimulus interval (ISI) and/or the conditioning stimulus intensity (CSI). Methods: Two experiments with pretesting/posttesting and an rTMS session (1 Hz, 90% RMT, 900 pulses) were done. Experiment I (N = 15): SICI with multiple ISIs (1.0–4.0 msec, 0.2 msec increment). Experiment II (N = 15): SICI with CSIs (50–95% of RMT, 5% increment). In both experiments, the cortical silent period (cSP) was also collected. Results: After low-frequency rTMS, no significant change (p > 0.10) in SICI at any specific ISI or CSI was observed, nor did the optimal ISI or CSI change. However, a significant decrease was observed in SICI responses when assessed under the range of ISIs (p = 0.0001), but not CSIs. cSP inhibition increased significantly (p < 0.0015) for both experiments. Conclusions: The optimal ISI or CSI did not shift or reveal SICI changes after inhibitory rTMS. However, when the whole curve of SICI responses were evaluated from a wide range of ISIs, a decrease in inhibition was found. The contrast between the results of individual ISI tests and the wide range of ISI assessment may be due to higher intersubject variability of SICI and/or sample size, rendering traditional SICI testing methods ineffective for measuring changes in inhibition. Further, it is possible that rTMS modulates GABA_A and GABA_B mediated inhibitory processes differently, which would explain the conflicting results for SICI and cSP.