Long-latency somatosensory evoked potentials (LL-SEPs) offer critical insights into central mechanism governing neuromodulation in neurogenic lower urinary tract dysfunction (NLUTD). The aim of this study was to characterize LL-SEPs following tibial and pudendal nerve stimulation in healthy participants using a prolonged interstimulus interval. Effects of stimulation frequency and sex were investigated with hypothesis that prolonged interstimulus interval would allow clearer identification of LL-SEP components with increased amplitudes compared to higher stimulation frequency.

SEPs were recorded in 32 healthy participants (age range 20–73 years), with 27 included in final analyses following exclusions for technical reasons. Cortical activity was recorded from 64 surface electrodes during tibial and pudendal nerve stimulation (3.1Hz and 1.1Hz; pulse width: 0.2 ms). SEP components were classified as short-latency (SL: P40, N50, P65, N85) and long-latency (LL: P100, N120/N140, P200, P300) using the Cz′–Fz channel. Analyses comprised response rates (criteria: identifiable and replicable across odd and even SEP averages), latencies, and amplitudes at the single-subject level. Right and left legs were compared as an internal validity check. Linear mixed models (LMM) were calculated with body height, stimulation frequency, and sex as predictors. Source localization was performed using standardized low-resolution brain electromagnetic tomography (sLORETA) for SEP components at peak latency.

Response rates were 100% for tibial SL-SEPs, and >90% for pudendal ones. LL responses were component specific: tibial P100 and P200 ~ 67%, P300 ~48%, N140 ~19%; pudendal P100 30%, P200 70%, P300 33%, and N120 27%. LMM revealed that tibial SL-SEPs latencies increased with height, and faster stimulation shortened N50 but prolonged P65 latencies. Tibial SL amplitudes (P40N50 and P65N85) were significantly higher at slower stimulation compared to faster stimulation. Tibial LL-SEPs were stable across sex, height and body side. Pudendal SL-SEPs were influenced by multiple factors: P40 latency increased with height; faster stimulation prolonged P40 and P65 latencies and reduced amplitudes (P40N50 and P65N85); females had shorter N50 latencies with higher P65N50 amplitudes. Pudendal LL-SEPs were stable across all factors. sLORETA revealed sources primarily in primary somatosensory cortex (S1) and supplementary motor area (SMA) for most of the SEP components (Fig 1).

Our findings validate that LL-SEPs can be elicited using prolonged interstimulus intervals, though they exhibit greater physiological inter-subject variability than SL components. While slower stimulation frequency revealed higher SL amplitudes for tibial SEPs, the classic W-shaped pudendal wave was significantly influenced by an interaction of sex and stimulation frequency; specifically, slower stimulation reduced pudendal P65N50 amplitudes—an effect primarily driven by males—alongside prolonged N50 latencies observed in males (Fig 1). This conduction delay in males is consistent with previous literature highlighting sex-dependent differences in anatomical conduction pathway lengths (1,2). In contrast, LL-SEPs remained robust across all factors. Furthermore, while sLORETA broadly confirmed physiologically plausible generators in S1 and the SMA, the pudendal P40 component at faster stimulation additionally revealed occipital sources (BA 18). This occipital activation is consistent with previously reported bladder-filling-related pathways during pudendal neuromodulation (3).

Prolonged inter-stimulus interval successfully revealed LL-SEPs with physiologically plausible generators confirmed in S1 and the SMA. While some LL-SEPs are less consistently elicited than SL components, the P200 emerged as a highly dominant and robust component. Our normative data demonstrates that, when present, LL-SEPs remain highly stable and largely independent of demographic variables. By defining these foundational reference values and methodological constraints, this study supports that the LL-SEPs may serve as a potential central biomarker for assessing neuromodulation efficacy in patients with NLUTD.

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Continence 19S (2026) 102775
DOI: 10.1016/j.cont.2026.102775