Temporal Summation of Subthreshold Stimuli in Human Motor Axons: Implications for Intraoperative Neuromonitoring

Abstract Objectives To examine how stimulus amplitude and pulse width influence the properties of peripheral axons and the phenomenon of subthreshold superexcitability. The objective was to determine whether specific stimulus parameter combinations could minimize the likelihood of CMAP generation in response to subthreshold pulse trains, to inform safer settings for intraoperative corticobulbar MEP monitoring. Methods Fifteen healthy participants (convenience sample) received median nerve stimulation under nine conditions combining three amplitudes (80%, 85%, and 90% of threshold) and three pulse widths (0.1 ms, 0.5 ms, 1.0 ms). Trains of 1–7 subthreshold pulses (2 ms interstimulus interval) were delivered 10 times per condition. The number of CMAPs (>100 µV) per train length were recorded from the APB, and mean response probability was calculated as the primary outcome. A latent addition test estimated persistent sodium current contributions, via LAh to subthreshold superexcitability in each participant. Results Higher pulse amplitudes and wider pulse widths significantly increased CMAP probability, with a significant interaction between them (F(4,56) = 4.853, p = .002, partial η² = .257). All pairwise comparisons were significant (p ≤ .023). When controlling for rheobase, LAh was positively correlated with response probability (r partial (12) = .539, p = .047) Conclusions Subthreshold stimulus trains can directly activate motor axons, and this effect was quantified across pulse amplitudes and widths. A setting of 80% threshold and 0.1 ms pulse width yielded a low response probability (1.6%), suggesting it may reduce peripheral activation and improve the specificity of intraoperative corticobulbar MEP neuromonitoring.