Urgency urinary incontinence and the interoceptive network: a functional magnetic resonance imaging study

Abstract

Background: Treatment of urgency urinary incontinence has focused on pharmacologically treating detrusor overactivity. Recent recognition that altered perception of internal stimuli (interoception) plays a role in urgency urinary incontinence suggests that exploration of abnormalities of brain function in this disorder could lead to better understanding of urgency incontinence and its treatment.

Objective: We sought to: (1) evaluate the relationship between bladder filling, perceived urgency, and activation at brain sites within the interoceptive network in urgency urinary incontinence; (2) identify coactivation of other brain networks that could affect interoception during bladder filling in urgency incontinence; and (3) demonstrate interaction between these sites prior to bladder filling by evaluating their resting-state connectivity.

Study design: We performed an observational cohort study using functional magnetic resonance imaging to compare brain function in 53 women with urgency urinary incontinence and 20 controls. Whole-brain voxelwise analyses of covariance were performed to examine differences in functional brain activation between groups during a task consisting of bladder filling, hold (static volume), and withdrawal phases. The task was performed at 3 previously established levels of baseline bladder volume, the highest exceeding strong desire to void volume. All women continuously rated their urge on a 0- to 10-point Likert scale throughout the task and a mixed measures analysis of variance was used to test for differences in urge ratings. Empirically derived regions of interest from analysis of activation during the task were used as seeds for examining group differences in resting-state functional connectivity.

Results: In both urgency urinary incontinent participants and controls, changes in urge ratings were greatest during bladder filling initiated from a high baseline bladder volume and urgency incontinent participants' rating changes were greater than controls. During this bladder-filling phase urgency incontinent participant's activation of the interoceptive network was greater than controls, including in the left insula and the anterior and middle cingulate cortex. Urgency incontinent participant's activation was also greater than controls at sites in the ventral attention network and posterior default mode network. Urgency incontinent participant's connectivity was greater than controls between a middle cingulate seed point and the dorsal attention network, a "top-down" attentional network. Control connectivity was greater between the midcingulate seed point and the ventral attention network, a "bottom-up" attentional network.

Conclusion: Increasing urge was associated with greater urgency incontinent participant than control activation of the interoceptive network and activation in networks that are determinants of self-awareness (default mode network) and of response to unexpected external stimuli (ventral attention network). Differences in connectivity between interoceptive networks and opposing attentional networks (ventral attention network vs dorsal attention network) were present even before bladder filling (in the resting state). These findings are strong evidence for a central nervous system component of urgency urinary incontinence that could be mediated by brain-directed therapies.

Keywords: attentional and interoceptive networks; brain activation and networks; functional magnetic resonance imaging; resting-state functional connectivity; urgency urinary incontinence in women.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Figure 1

Panel A presents differences in activation between patients with urinary urgency incontinence (UUI) and Controls during the infuse phase of the high fill volume. The magnitude of p-values is denoted using dark blue (p < 0.005) and light blue (p < 0.001) coloring. Sagittal (X) and axial (Z) slice locations are given according to the Talaraich atlas. Percent signal change data for selected regions of interest (ROI) from the dorsal anterior [dACC], middle [MCC] cingulate cortex, anterior insula [aINS]/ventrolateral prefrontal cortex [VLPFC], VLPFC, temporal gyrus [TPJ] posterior medial cortex [PMC] (not pictured on these representative sections), premotor cortex [PMOT], visual cortex [Vis], posterior insula [pINS] and parahippocampal gyrus [PHpc] are presented in Panel B. Box-and-whiskers plots for Controls (red) and UUI (blue) represent total PSC from the infuse phase

Figure 2

Functional connectivity analyses were performed with selected regions from the bladder distention task (Figure 2) that included the left (L) anterior insula/ventrolateral prefrontal cortex (aINS/VLPFC), right (R) VLPFC, and the middle cingulate cortex (MCC). Each panel is color coded to display regions of increased (p < 0.005: dark blue; p < 0.001: light blue) or decreased (p < 0.005: red; p < 0.001: yellow) connectivity for patients with urinary urgency incontinence (UUI) relative to Controls. Locations of the sagittal (X) and axial (Z) slices are given according to the Talairach atlas for the left (L) and right (R) hemispheres. The left inferior parietal lobe (IPL; Panel A) and left paracentral lobule (PCL; Panel B) exhibited significant group differences for the L aINS/VLPFC and R VLPFC seeds, respectively. The MCC seed (Panel C) resulted in group differences for both the left dorsolateral prefrontal cortex (DLPFC) and the right VLPFC. Fisher’s z transformed correlation values are presented in box-and-whisker plots for Controls (red) and UUI (blue) for all regions.