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Background High frequency repetitive transcranial magnetic stimulation (rTMS) elicits plastic effects in excitatory and inhibitory circuits. Inter-train intervals (ITI) were initially incorporated into rTMS paradigms to avoid overheating and for safety considerations. Recent studies have shown that inclusion of ITI, as opposed to continuous stimulation, is essential for eliciting excitatory effects, but the optimal ITI remains unknown. Moreover, if ITI duration has no effect, it may be possible to substantially reduce treatment time for rTMS. Hypothesis ITI duration modulates the excitatory and disinhibitory effects of rTMS. Methods rTMS (20 Hz, 2 s trains, 1200 pulses, 100% RMT) was applied in 14 healthy individuals with ITI of 4s (duration: ∼3 min), 8s (∼5 min), 16s (∼9 min) or 32s (16.5 min) in sessions separated by ≥5 days. Effects on cortical excitability and GABA A receptor mediated short interval intracortical inhibition (SICI) were measured for 75 min following rTMS. Results The time-course of increased cortical excitability following rTMS was independent of ITI duration. There was a striking influence of ITI on SICI, whereby disinhibition increased with shorter ITI duration. Changes in cortical excitability and SICI were independent of each other. Conclusion These findings provide the first evidence to suggest that ITI may be substantially shortened without loss of rTMS effects, and warrant further investigation where rTMS is applied therapeutically. Furthermore, shorter ITIs result in greater disinhibitory effects which may be desirable in some clinical disorders and accelerated treatment paradigms. The tuning of the plasticity of cortical excitatory and inhibitory circuits to rTMS parameters in human cortex are independent. [ABSTRACT FROM AUTHOR]