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 (R2 = 1) and nearly linear trend for intra-block levels (R2 = 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.