Reply to "Revisiting the accuracy of motor evoked potential determination: The overlooked role of surface electrode montage"

Abstract

Reply to "Revisiting the accuracy of motor evoked potential determination: The overlooked role of surface electrode montage" We have read with great interest the letter to the editor by (Garcia and Nogueira-Campos, 2025), which responds to our recent article on factors influencing the number of trials required for reliable motor-evoked potential (MEP) estimates following transcranial magnetic stimulation (TMS) (Nuyts et al., 2025). We thank the authors for their thoughtful feedback and for highlighting the importance of electromy-ography (EMG) electrode montages in recording MEPs following TMS. Our study showed that several factors impact the number of trials needed to achieve reliable MEP estimates, including relative TMS intensity , baseline resting motor threshold (rMT), and the handling of out-liers. Based on these findings, we developed an accessible framework and an accompanying online tool (https://nopt-prediction-fxpc.onrender. com/) to support TMS users in determining an appropriate trial count. (Garcia and Nogueira-Campos, 2025) note that EMG montage can substantially alter absolute MEP amplitudes and, consequently, rMT estimates. We agree that electrode configuration is an important determinant of MEP amplitude, however, as outlined in our limitations, it represents one of several methodological factors that were beyond the scope of our study (cf., (Numssen et al., 2024) and (Spampinato et al., 2023) for relevant reviews). Beyond montage specifically, EMG acquisition includes several additional sources of variation across TMS protocols, including differences in amplifier hardware, the use of line noise eliminators, handling of pre-stimulus EMG activity, and choice of target muscle. Along these other methodological factors, our study did not include EMG montage as our aim was to quantify how naturally varying personal and experimental factors contribute to trial-to-trial MEP variability and, consequently, to reliability metrics. Within this framework, we focused on variables that (1) vary meaningfully across individuals or protocols, (2) have been linked to MEP variability, and (3) can be incorporated into an equation that remains practical for routine TMS use in both research and clinics. Importantly, while electrode montage clearly affects absolute MEP amplitude, its influence on trial-to-trial variability, and thus on the number of TMS pulses needed for reliable estimation (i.e., n opt in our manuscript) remains unclear. Clarifying the potential role of montage on MEP variability requires examining the evidence base on which the current claims are founded. Much of the work cited in the letter has been conducted in proximal upper-limb muscles (e.g., biceps brachii) and modest sample sizes, reflecting the practical constraints of those investigations. As a result, the generalizability of montage-related effects to distal hand muscles, among the most frequent TMS targets, remains to be established. Anatomy and morphology vary substantially across individuals and across muscles, with distal muscles likely interacting differently with electrode configurations than the previously studied proximal muscles. In light of these considerations, and the practical demands associated with advanced EMG configurations, a necessary next step is to determine if variability in electrode placement meaningfully affects MEP reliability metrics when using EMG montages commonly employed in TMS practice. Adequately powered, cross-muscle studies will help clarify which methodological factors warrant strict standardization and which we can reasonably treat as fixed constraints in routine TMS practice. We appreciate the authors for opening this scientific dialogue and for contributing to ongoing efforts to further refine and standardize TMS-based MEP assessment.