Scalp Topography of Lower Urinary Tract Sensory Evoked Potentials

Impaired lower urinary tract (LUT) afferents often cause LUT symptoms. Assessment of LUT afferent pathways is possible using bipolar cortical sensory evoked potential (SEP) recordings with the active electrode at the vertex during electrical stimulation in the LUT. This study aimed to investigate the topographical distribution and microstates of lower urinary tract sensory evoked potentials (LUTSEPs) using different stimulation frequencies. Ninety healthy subjects (18–36 years old, 40 women) were randomly assigned to one of five stimulation locations [bladder dome; trigone; proximal, membranous (men only) or distal urethra]. Cycles of 0.5 Hz/1.1 Hz/1.6 Hz electrical stimulation were applied using a custom-made catheter. Cortical activity was recorded from 64 surface electrodes. Marker setting was performed manually on an individual subject-level for the P1, N1, and P2 components of vertex recordings. N1 and P2 topographies presented with central negativities and positivities around the vertex. Regarding topographical distribution, Randomization Graphical User interface (RAGU) analyses revealed consistent frequency effects and microstates for N1/P2. Higher stimulation frequencies resulted in decreasing map strength for P1, N1, and P2. LUTSEP topographies suggest central generators in the somatosensory cortex, which are not detectable in a bipolar set-up. The observed frequency effect indicates fiber refractoriness at higher frequencies. The multichannel approach allows more comprehensive assessment of LUTSEPs and might therefore be sensitive to pathological changes. Examinations in patients with LUT symptoms are needed to further investigate this biomarker. Electronic supplementary material The online version of this article (10.1007/s10548-020-00796-z) contains supplementary material, which is available to authorized users.

Electrooculogram was recorded by two electrodes placed 1cm behind and below the outer canthus of each eye in addition to electrocardiogram (Fig. 2a).

Fig. ESM1
Butterfly plots and time courses of EEG topographies for the location trigone. Butterfly plots (-100 to 600ms) are shown for non-baseline corrected (a-c) and baseline corrected data (d-f) of the three stimulation frequencies (0.5Hz: left, 1.1Hz: middle, 1.6Hz: right, for all: average of 20 subjects). The recordings from Cz-Fz are indicated by the black dashed line and from Cz-AvgRef by the red line. Time courses of topographical maps are shown at 15ms time intervals from -85 to 380ms (average of 20 subjects) for non-baseline corrected data and baseline corrected data of the three stimulation frequencies (g-i). The maps are subdivided into three sections: -85 to 65ms (includes pre-stimulus, P1) framed in light green; 80 to 170ms (N1) framed in light blue; 185 to 380ms (P2) framed in orange. The time point of the stimulus is indicated by an orange dotted line. The last map represents the mean topography of the baseline time window (-53 to -3ms) for non-baseline and baseline corrected data

Fig. ESM2
Butterfly plots and time courses of EEG topographies for the location proximal urethra. Butterfly plots (-100 to 600ms) are shown for non-baseline corrected (a-c) and baseline corrected data (d-f) of the three stimulation frequencies (0.5Hz: left, 1.1Hz: middle, 1.6Hz: right, for all: average of 20 subjects). The recordings from Cz-Fz are indicated by the black dashed line and from Cz-AvgRef by the red line. Time courses of topographical maps are shown at 15ms time intervals from -85 to 380ms (average of 20 subjects) for non-baseline corrected data and baseline corrected data of the three stimulation frequencies (g-i). The maps are subdivided into three sections: -85 to 65ms (includes pre-stimulus, P1) framed in light green; 80 to 170ms (N1) framed in light blue; 185 to 380ms (P2) framed in orange. The time point of the stimulus is indicated by an orange dotted line. The last map represents the mean topography of the baseline time window (-53 to -3ms) for non-baseline and baseline corrected data

Fig. ESM5
Topographic location comparisons of LUTSEPs. Location effects are shown separately for all stimulation frequencies and the three LUTSEP peaks. Scales of the corresponding topographic maps in t-values (scale from: -8 to +8). Please note that t-values of second color grade represent a statistical trend or significance. BD: bladder dome; dUR: distal urethra; mUR: membranous urethra; pUR: proximal urethra; TG: trigone

Pudendal SEP Results:
Single channel analyses revealed for pudendal nerve stimulation significant differences between the two marker sets for the negative component N50 (Table 2 & 3).
LMMs revealed a significant gender effect with men showing longer pudendal SEP latencies compared to women. Hence, we performed a gender-specific analysis of the pudendal SEP data. Body height had no significant effect on latencies, while positive relationship between BMI and P40/N50 latencies were shown.
Butterfly plots and topographical maps of the pudendal nerve stimulation along the entire segment are shown in supplementary Fig. 6.
Statistical analyses showed consistent neural activation along the entire pudendal SEP segment (-100-200ms, except between -50 and -30ms) and for all marker positions (P40, N50, P65, N85) of Cz-Fz and Cz-AvgRef recordings. TANOVA revealed that different sources were active between women and men in the time period of about 45ms to 90ms after stimulus, while no significant differences in map strength were shown along the entire segment (supplementary Fig. 7a).
The topographic pattern analysis on the between-subject factor gender yielded six representative topographic scalp maps (supplementary Fig. 7b). The remaining analyses were consequently based on 6 (1-6) microstate classes, respectively. Their temporal occurrences are shown in supplementary Fig. 7c accompanied by the corresponding SEP grand averages (supplementary Fig. 7d).
The results of the time-locked components in the entire SEP segment were confirmed by the individually set marker positions, showing different brain function states between women and men for the N50, P65, N85 marker (supplementary Fig. 7e). The topographical maps including the t-maps illustrating these differences between women and men are shown in supplementary Fig. 7f.

Fig. ESM7
Results of the topographical analysis obtained from non-baseline-corrected pudendal data and the corresponding wave shapes. a TANOVA (left) and GFP results (right, n=83; factor: gender) are shown along the entire segment (-100 to 200ms). The black line marks the p-value as a function of time (x-axis). Grey areas indicate non-significant time intervals while the white areas indicate significant periods between topographic maps of the factor gender. b The six microstate maps obtained from the cross-validation procedure are labelled from 1 to 6 and displayed in sequence of occurrence from left to right (n=83; orientation: nose up, right is right). Different colors are attributed to different microstate classes. c The time course of each microstates map is shown as a function of GFP for the women and men. Below, results of the topographic consistency test are shown (grey: not significant; white: p<0.05). d Grand average cortical SEPs derived from Cz-Fz in response to pudendal nerve stimulation. e TANOVA (left) and GFP (right, n=83; factors: gender) are shown for the four Cz-Fz marker positions. The black line marks the p-value for P40, N50, P65 and N85 peak amplitudes (x-axis). Grey areas indicate non-significant time intervals while the white areas indicate significant periods between topographic maps of the factor gender. f Mean topographical maps are displayed for women (n=35) and men (n=48) for P40, N50, P65, N85 based on the individually set Cz-Fz markers. T-maps illustrating gender effects are shown based on the individually set Cz-Fz marker positions. Scales of the corresponding topographic maps in μV/t-values, respectively. Second color grade represents significance. GFP: global-field power; m: men; SEP: sensory evoked potential; w: women