Ongoing cumulative effects of single TMS pulses on corticospinal excitability: An intra- and inter-block investigation

OBJECTIVE To evaluate the effects of several single TMS pulses, delivered at two different inter-trial intervals (ITIs), on corticospinal excitability. METHODS Twelve healthy volunteers participated in two experimental sessions, during which TMS pulses were delivered at random or at fixed ITIs. The TMS single pulse-induced modulation of corticospinal output (motor evoked potential amplitude - MEP) was evaluated on-line. Each session began with a baseline block, followed by 10 blocks, with 20 TMS pulses each. Intra- and inter-block effects were valuated using an ANOVA model, through nested random effect on subjects considering the subject-specific variability. RESULTS The delivery of successive TMS pulses significantly changed both intra-block and inter-block cortical excitability, as demonstrated by an increase in the amplitude of MEPs (p<0.001) and supported through trend analyses, showing a perfect linear trend for inter-block levels (R(2)=1) and nearly linear trend for intra-block levels (R(2)=0.97). The MEPs significantly increased when the TMS pulses were delivered at both random and fixed ITIs. CONCLUSIONS Single TMS pulses induce cumulative changes in neural activity during the same stimulation, resulting in a motor cortical excitability increase. SIGNIFICANCE Particular attention should be taken when several single TMS pulses are delivered in research and clinical settings for diagnostic and therapeutic purposes.