Dataset Information

Functional connectivity of the brain in older women with urgency urinary incontinence.

ABSTRACT:

Background

The brain's role in continence is critical but poorly understood. Although regions activated during bladder stimulation have been identified, little is known about the interaction between regions. In this secondary analysis we evaluate resting state and effective connectivity in older women treated for urgency urinary incontinence (UUI).

Method

54 women ≥60 years old with UUI and 10 continent women underwent fMRI scanning during provocation of urinary urgency, both before and after therapy. Response was defined by >50% reduction in leaks on bladder diary. Regions of interest (RoIs) were selected a priori: right insula, medial prefrontal cortex, and dorsal anterior cingulate cortex. Generalized psycho-physiological interaction (gPPI) was used to calculate "effective connectivity" between RoIs during urgency. We performed a one-way ANOVA pre-treatment between groups (continent/responders/non-responders), as well as a two-way mixed ANOVA between group and time (responders/non-responders; pre-/post-therapy) using false discovery rate (FDR) correction. Principal component analysis was used to assess the variance within RoIs. Exploratory voxel-wise connectivity analyses were conducted between each RoI and the rest of the brain.

Results

RoI-RoI connectivity analysis showed connectivity differences between controls, responders, and non-responders, although statistical significance was lost after extensive correction. Principal component analysis confirmed appropriate RoI selection. Voxel-wise analyses showed that connectivity in responders became more like that of controls after therapy (cluster-wise correction P < 0.05). In non-responders, no consistent changes were seen.

Conclusion

These data support the postulate that responders and non-responders to therapy may represent different subsets of UUI, one with more of a central etiology, and one without.

SUBMITTER: Clarkson BD

PROVIDER: S-EPMC6469490 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Functional connectivity of the brain in older women with urgency urinary incontinence.

Clarkson Becky D BD Karim Helmet T HT Griffiths Derek J DJ Resnick Neil M NM

Neurourology and urodynamics 20180727 8

<h4>Background</h4>The brain's role in continence is critical but poorly understood. Although regions activated during bladder stimulation have been identified, little is known about the interaction between regions. In this secondary analysis we evaluate resting state and effective connectivity in older women treated for urgency urinary incontinence (UUI).<h4>Method</h4>54 women ≥60 years old with UUI and 10 continent women underwent fMRI scanning during provocation of urinary urgency, both befo ...[more]

PMID: 30054930

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Project description:BackgroundPrior study of patients with urgency urinary incontinence by functional magnetic resonance imaging showed altered function in areas of the brain associated with interoception and salience and with attention. Our randomized controlled trial of hypnotherapy for urgency urinary incontinence demonstrated marked improvement in urgency urinary incontinence symptoms at 2 months. A subsample of these women with urgency urinary incontinence underwent functional magnetic resonance imaging before and after treatment.ObjectiveThis study aimed to determine if hypnotherapy treatment of urgency urinary incontinence compared with pharmacotherapy was associated with altered brain activation or resting connectivity on functional magnetic resonance imaging.Study designA subsample of women participating in a randomized controlled trial comparing hypnotherapy vs pharmacotherapy for treatment of urgency urinary incontinence was evaluated with functional magnetic resonance imaging. Scans were obtained pretreatment and 8 to 12 weeks after treatment initiation. Brain activation during bladder filling and resting functional connectivity with an empty and partially filled bladder were assessed. Brain regions of interest were derived from those previously showing differences between healthy controls and participants with untreated urgency urinary incontinence in our prior work and included regions in the interoceptive and salience, ventral attentional, and dorsal attentional networks.ResultsAfter treatment, participants in both groups demonstrated marked improvement in incontinence episodes (P<.001). Bladder-filling task functional magnetic resonance imaging data from the combined groups (n=64, 30 hypnotherapy, 34 pharmacotherapy) demonstrated decreased activation of the left temporoparietal junction, a component of the ventral attentional network (P<.01) compared with baseline. Resting functional connectivity differed only with the bladder partially filled (n=54). Compared with pharmacotherapy, hypnotherapy participants manifested increased functional connectivity between the anterior cingulate cortex and the left dorsolateral prefrontal cortex, a component of the dorsal attentional network (P<.001).ConclusionSuccessful treatment of urgency urinary incontinence with both pharmacotherapy and hypnotherapy was associated with decreased activation of the ventral (bottom-up) attentional network during bladder filling. This may be attributable to decreased afferent stimuli arising from the bladder in the pharmacotherapy group. In contrast, decreased ventral attentional network activation associated with hypnotherapy may be mediated by the counterbalancing effects of the dorsal (top-down) attentional network.

Project description:Bacterial DNA and live bacteria have been detected in human urine in the absence of clinical infection, challenging the prevailing dogma that urine is normally sterile. Urgency urinary incontinence (UUI) is a poorly understood urinary condition characterized by symptoms that overlap urinary infection, including urinary urgency and increased frequency with urinary incontinence. The recent discovery of the urinary microbiome warrants investigation into whether bacteria contribute to UUI. In this study, we used 16S rRNA gene sequencing to classify bacterial DNA and expanded quantitative urine culture (EQUC) techniques to isolate live bacteria in urine collected by using a transurethral catheter from women with UUI and, in comparison, a cohort without UUI. For these cohorts, we demonstrated that the UUI and non-UUI urinary microbiomes differ by group based on both sequence and culture evidences. Compared to the non-UUI microbiome, sequencing experiments revealed that the UUI microbiome was composed of increased Gardnerella and decreased Lactobacillus. Nine genera (Actinobaculum, Actinomyces, Aerococcus, Arthrobacter, Corynebacterium, Gardnerella, Oligella, Staphylococcus, and Streptococcus) were more frequently cultured from the UUI cohort. Although Lactobacillus was isolated from both cohorts, distinctions existed at the species level, with Lactobacillus gasseri detected more frequently in the UUI cohort and Lactobacillus crispatus most frequently detected in controls. Combined, these data suggest that potentially important differences exist in the urinary microbiomes of women with and without UUI, which have strong implications in prevention, diagnosis, or treatment of UUI. Importance: New evidence indicates that the human urinary tract contains microbial communities; however, the role of these communities in urinary health remains to be elucidated. Urgency urinary incontinence (UUI) is a highly prevalent yet poorly understood urinary condition characterized by urgency, frequency, and urinary incontinence. Given the significant overlap of UUI symptoms with those of urinary tract infections, it is possible that UUI may have a microbial component. We compared the urinary microbiomes of women affected by UUI to those of a comparison group without UUI, using both high-throughput sequencing and extended culture techniques. We identified statistically significant differences in the frequency and abundance of bacteria present. These differences suggest a potential role for the urinary microbiome in female urinary health.

Project description:PurposeWe characterize patients with urinary urgency with vs without urgency urinary incontinence who presented to clinics actively seeking treatment for their symptoms.Materials and methodsParticipants who enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network were categorized into urinary urgency with vs without urgency urinary incontinence. Participants were followed for 1 year; their urinary symptoms, urological pain, psychosocial factors, bowel function, sleep disturbance, physical activity levels, physical function, and quality of life were compared. Mixed effects linear regression models were used to examine the relationships between urgency urinary incontinence and these factors.ResultsAmong 683 participants with urinary urgency at baseline, two-thirds (n=453) also had urgency urinary incontinence; one-third (n=230) had urinary urgency-only without urgency urinary incontinence. No differences were detected in urological pain between urinary urgency-only and urgency urinary incontinence. Those with urgency urinary incontinence had more severe urgency and frequency symptoms, higher depression, anxiety, perceived stress scores, more severe bowel dysfunction and sleep disturbance, lower physical activity levels, lower physical function, and worse quality of life than those with urinary urgency-only. Among those with urinary urgency-only at baseline, 40% continued to have urinary urgency-only, 15% progressed to urgency urinary incontinence, and 45% had no urgency at 12 months. Fifty-eight percent with urgency urinary incontinence at baseline continued to report urgency urinary incontinence at 12 months, while 15% improved to urinary urgency-only, and 27% had no urgency.ConclusionsPatients with urgency urinary incontinence have severe storage symptoms, more psychosocial symptoms, poorer physical functioning, and worse quality of life. Our data suggested urgency urinary incontinence may be a more severe manifestation of urinary urgency, rather than urinary urgency and urgency urinary incontinence being distinct entities.

Project description:BackgroundLimited epidemiological data exist describing how patients engage with various treatments for overactive bladder (OAB). To improve care for patients with OAB, it is essential to gain a better understanding of how patients interface with OAB treatments longitudinally, that is, how often patients change treatments and the pattern of this treatment change in terms of escalation and de-escalation.ObjectivesTo describe treatment patterns for women with bothersome urinary urgency (UU) and/or urgency urinary incontinence (UUI) presenting to specialty care over 1 year.Study designThe Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) study enrolled adult women with bothersome UU and/or UUI seeking care for lower urinary tract symptoms (LUTS) between January 2015 and September 2016. An ordinal logistic regression model was fitted to describe the probabilities of escalating or de-escalating level of treatment during 1-year follow-up.ResultsAmong 349 women, 281 reported UUI and 68 reported UU at baseline. At the end of 1 year of treatment by a urologist or urogynecologist, the highest level of treatment received by participants was 5% expectant management, 36% behavioral treatments (BT), 26% physical therapy (PT), 26% OAB medications, 1% percutaneous tibial nerve stimulation, 3% intradetrusor onabotulinum toxin A injection, and 3% sacral neuromodulation. Participants using BT or PT at baseline were more likely to be de-escalated to no treatment than participants on OAB medications at baseline, who tended to stay on medications. Predictors of the highest level of treatment included starting level of treatment, hypertension, UUI severity, stress urinary incontinence, and anticholinergic burden score.ConclusionsTreatment patterns for UU and UUI are diverse. Even for patients with significant bother from OAB presenting to specialty clinics, further treatment often only involves conservative or medical therapies. This study highlights the need for improved treatment algorithms to escalate patients with persistent symptoms, or to adjust care in those who have been unsuccessfully treated.

Project description: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.

Dataset Information

Functional connectivity of the brain in older women with urgency urinary incontinence.

Background

Method

Results

Conclusion

Publications

Functional connectivity of the brain in older women with urgency urinary incontinence.

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