Transcranial stimulation (TCS) O-TS002. Combining SICF and ICF with QPS boosts excitability increase in the primary motor cortex

Introduction. After-effects induced by repetitive transcranial magnetic stimulation (rTMS) at the primary motor cortex (M1) are usually indexed by the amplitude of the motor evoked potential (MEP). They depend on various parameters, in particular on the temporal pattern. Quadripulse stimulation (QPS; high-frequency train of four pulses delivered every-five seconds for 30 min) was originally invented based on a repetitive paired-pulse TMS (ppTMS) protocol, which utilized short-interval intracortical facilitation (SICF) as a building block. Here, we tried to test whether after-effects of QPS can be increased by integrating either SICF, intracortical facilitation (ICF) or long-interval intracortical inhibition (LICI). Methods. Three conditions were compared using a cross-over design in 23 healthy volunteers. The three conditions were SICF + ICF, SICF + LICI, and QPS-like. In SICF + ICF, two pulses with a 1.5 ms inter-stimulus interval (ISI) were repeated twice, separated by 10 ms (ICF). Likewise, in SICF + LICI two pulses with a 1.5 ms interval were repeated at 100-ms interval (LICI). In the QPS-like condition, the four pulses were evenly delivered at 5-ms intervals. In all three conditions the four pulses were repeated every-five seconds for 10 minutes. Amplitude of MEP elicited by single pulse TMS was measured before the intervention, and up to 60 minutes after it. The MEP amplitudes were normalized to the baseline and served as the main outcome. Results. The combination of two facilitatory ppTMS, SICF + ICF, resulted in significantly increased MEP amplitudes over time whereas combining the facilitatory SICF with the inhibitory LICI tended to decrease the MEP amplitude. QPS with 10-minute intervention time had no effect in contrast to the 3-times longer original QPS paradigm. Conclusion. The efficacy of the original QPS can be maintained with one third of stimulation time when differently organized in time along with optimal values for SICF + ICF.