• Loren H Ketai, Yuko M Komesu, Andrew B Dodd, Rebecca G Rogers, Josef M Ling, and Andrew R Mayer.
• University of New Mexico Health Sciences Center, Albuquerque, NM.
• Am. J. Obstet. Gynecol. 2016 Oct 1; 215 (4): 449.e1-449.e17.

BackgroundTreatment 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.ObjectiveWe 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 DesignWe 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.ResultsIn 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.ConclusionIncreasing 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.Copyright © 2016 Elsevier Inc. All rights reserved.

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