Preconditioning Stimulus Intensity Alters Paired-Pulse TMS Evoked Potentials

Abstract

Motor cortex (M1) paired-pulse TMS (ppTMS) probes excitatory and inhibitory intracortical dynamics by measurement of motor-evoked potentials (MEPs). However, MEPs reflect cortical and spinal excitabilities and therefore cannot isolate cortical function. Concurrent TMS-EEG has the ability to measure cortical function, while limiting peripheral confounds; TMS stimulates M1, whilst EEG acts as the readout: the TMS-evoked potential (TEP). Whilst varying preconditioning stimulus intensity influences intracortical inhibition measured by MEPs, the effects on TEPs is undefined. TMS was delivered to the left M1 using single-pulse and three, ppTMS paradigms, each using a different preconditioning stimulus: 70%, 80% or 90% of resting motor threshold. Corticospinal inhibition was present in all three ppTMS conditions. ppTMS TEP peaks were reduced predominantly under the ppTMS 70 protocol but less so for ppTMS 80 and not at all for ppTMS 90. There was a significant negative correlation between MEPs and N45 TEP peak for ppTMS 70 reaching statistical trends for ppTMS 80 and 90. Whilst ppTMS MEPs show inhibition across a range of preconditioning stimulus intensities, ppTMS TEPs do not. TEPs after M1 ppTMS vary as a function of preconditioning stimulus intensity: smaller preconditioning stimulus intensities result in better discriminability between conditioned and unconditioned TEPs. We recommend that preconditioning stimulus intensity should be minimized when using ppTMS to probe intracortical inhibition.

Evaluation of GABAAR-mediated inhibition in the human brain using TMS-evoked potentials

“…Our observations of TEP SICI are only in partial agreement with previous studies. These mostly reported a suppression of P60 but also found a decrease of P30 [30-32], and a decrease [30] or an increase of N45 [28, 31, 32]. In a very recent publication, Rawji et al additionally showed a suppression of N15 (here N17) and P180 [28].…”

“…These mostly reported a suppression of P60 but also found a decrease of P30 [30-32], and a decrease [30] or an increase of N45 [28, 31, 32]. In a very recent publication, Rawji et al additionally showed a suppression of N15 (here N17) and P180 [28]. Contrary to all above-mentioned studies, the early study of Paus et al reported no effect of SICI in TEPs [91], whereas two more recent studies only found a reduction of late TEP components N100 and P180/P300 [29, 33].…”

“…As compared to the amplitude of the MEP elicited by a single supra-threshold TMS pulse, the amplitude of the MEP elicited by paired pulses is markedly reduced, and this effect has been attributed to the triggering of GABAAR-mediated short-latency intracortical inhibition (SICI) [26,27]. More recently, several groups described SICI also in M1 TEPs, yet their findings were highly variable as well as the methodology they used [28][29][30][31][32][33].…”

Modulating Frontal Networks’ Timing-Dependent-Like Plasticity With Paired Associative Stimulation Protocols: Recent Advances and Future Perspectives

“…Another undisclosed methodological issue that deserves further investigation is related to the influence of TMS intensity (either of the first and the second pulse) on the effectiveness of PAS, notwithstanding the recent evidence of its crucial role, especially in paired-pulse TMS paradigms or when frontal TEPs are measured (e.g., Bäumer et al, 2009;Zanon et al, 2018;Rawji et al, 2021). For future studies aiming to develop novel frontal PAS, we suggest to carefully consider these methodological works on the importance of TMS intensity, thus to select the better parameters to stimulate (and modulate) the target cortical areas.…”

Motor potentials evoked by transcranial magnetic stimulation: interpreting a simple measure of a complex system

“…In addition, EEG responses due to direct activation of cutaneous afferent fibres by TMS are very small when somatosensory input is mimicked by electrical stimulation of the scalp or even absent when the TMS pulse is considered (Gosseries et al, 2015;Sarasso et al, 2020). Even if responses caused by indirect brain activation due to sensory input are present, they are represented by stereotypical vertex potentials in the 100-200 ms range, irrespective of the stimulation site, compatible with saliency-related multimodal responses (Mouraux & Iannetti, 2009;; these show marked topographical differences compared to TEPs, the latter being characterized by maximal activity at the stimulation site and by the larger amplitude of signals of <100 ms (Belardinelli et al, 2019;Mancuso et al, 2021;Rawji et al, 2021). Beyond these issues, there is no general agreement on the preprocessing pipeline for removing early TMS-locked artifacts (i.e.…”