Temporal summation of subthreshold stimuli in human motor axons: Implications for intraoperative neuromonitoring.

Objectives: To examine how stimulus amplitude and width influence subthreshold superexcitability of peripheral axons and to provide evidence-based recommendations for minimizing inadvertent compound muscle action potential (CMAP) generation during intraoperative corticobulbar monitoring. Methods: Fifteen healthy participants 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 interpulse interval) were delivered 10 times per condition. CMAPs were recorded from the abductor pollicis brevis (APB), and the probability of a response exceeding 100 µV (baseline-to-negative-peak) was calculated. Persistent sodium current was estimated using the latent addition test (LAh). Results: Higher pulse amplitudes and wider pulse widths significantly increased CMAP probability, with a significant interaction (F(4,56) = 4.853, p = 0.002, partial η2 = 0.257). All pairwise comparisons were significant (p ≤ 0.023). When controlling for rheobase, LAh was positively correlated with response probability (rpartial(12) = 0.539, p = 0.047). Conclusions & significance: Subthreshold trains activate motor axons in a predictable manner depending on amplitude, width, and train length. These findings challenge current IONM assumptions and highlight the need for threshold-referenced, standardized protocols.