Bladder control depends on an extensive network of brain regions. Dysfunction in various parts may contribute to urge incontinence, suggesting that there are different phenotypes requiring different treatments.

Aim: To identify age-related changes in the normal brain/bladder control system, and differences between urge incontinence in younger and older women, as shown by brain responses to bladder filling; and to use age, bladder volume, urge incontinence and detrusor overactivity (DO) as probes to reveal control-system function. Functional MRI was used to examine regional brain responses to bladder infusion in 21 females (26 -85 years): 11 "cases" with urge incontinence and DO (proven previously) and 10 normal "controls". Responses and their age dependence were determined at small and large bladder volumes, in whole brain and in regions of interest representing right insula and anterior cingulate (ACG). In "controls", increasing bladder volume/sensation led to increasing insular responses; with increasing age, insular responses became weaker. In younger "cases", ACG responded abnormally strongly at large bladder volumes/strong sensation. Elderly "cases" showed strong ACG responses even at small bladder volume, but more moderate responses at larger volumes; if DO occurred, pontine micturition center (PMC) activation did not increase. Conclusion:Among normal "controls", increasing age leads to decreased responses in brain regions involved in bladder control, including right insula, consistent with its role in mapping normal bladder sensations. Strong ACG activation occurs in urge-incontinent "cases" and may be a sign of urgency, indicating recruitment of alternative pathways when loss of bladder control is feared. Easier ACG provocation in older "cases" reflects lack of physiological reserve or different etiology. ACG responses seem associated with PMC inhibition: reduced ACG activity accompanies failure of inhibition (DO).

Purpose Urge urinary incontinence is a major problem, especially in the elderly, and to our knowledge the underlying mechanisms of disease and therapy are unknown. We used biofeedback assisted pelvic floor muscle training and functional brain imaging (functional magnetic resonance imaging) to investigate cerebral mechanisms, aiming to improve the understanding of brain-bladder control and therapy. Materials and Methods Before receiving biofeedback assisted pelvic floor muscle training functionally intact, older community dwelling women with urge urinary incontinence as well as normal controls underwent comprehensive clinical and bladder diary evaluation, urodynamic testing and brain functional magnetic resonance imaging. Evaluation was repeated after pelvic floor muscle training in those with urge urinary incontinence. Functional magnetic resonance imaging was done to determine the brain reaction to rapid bladder filling with urgency. Results Of 65 subjects with urge urinary incontinence 28 responded to biofeedback assisted pelvic floor muscle training with 50% or greater improvement of urge urinary incontinence frequency on diary. However, responders and nonresponders displayed 2 patterns of brain reaction. In pattern 1 in responders before pelvic floor muscle training the dorsal anterior cingulate cortex and the adjacent supplementary motor area were activated as well as the insula. After the training dorsal anterior cingulate cortex/supplementary motor area activation diminished and there was a trend toward medial prefrontal cortex deactivation. In pattern 2 in nonresponders before pelvic floor muscle training the medial prefrontal cortex was deactivated, which changed little after the training. Conclusions In older women with urge urinary incontinence there appears to be 2 patterns of brain reaction to bladder filling and they seem to predict the response and nonresponse to biofeedback assisted pelvic floor muscle training. Moreover, decreased cingulate activation appears to be a consequence of the improvement in urge urinary incontinence induced by training while prefrontal deactivation may be a mechanism contributing to the success of training. In nonresponders the latter mechanism is unavailable, which may explain why another form of therapy is required.

Evidence from longitudinal studies in community-dwelling elderly links complaints of urgency and urinary incontinence with structural white matter changes known as white matter hyperintensities (WMH). How WMH might lead to incontinence remains unknown, since information about how they relate to neural circuits involved in continence control is lacking. The aim of this study was to investigate the role of WMH in altered brain activity in older women with urgency incontinence. In a cross-sectional study, we measured WMH, globally and in specific white matter tracts, and correlated them with regional brain activity measured by fMRI (combined with simultaneous urodynamic monitoring) during bladder filling and reported 'urgency'. We postulated that increase in global WMH burden would be associated with changes (either attenuation or reinforcement) in responses to bladder filling in brain regions involved in bladder control. Secondly, we proposed that such apparent effects of global WMH burden might be specifically related to the burden in a few critical white matter pathways. The results showed that regional activations (e.g. medial/superior frontal gyrus adjacent to dorsal ACG) and deactivations (e.g. perigenual ACG adjacent to ventromedial prefrontal cortex) became more prominent with increased global WMH burden, suggesting that activity aimed at suppressing urgency was augmented. Secondary analyses confirmed that the apparent effect of global WMH burden might reflect the presence of WMH in specific pathways (anterior thalamic radiation and superior longitudinal fasciculus), thus affecting connections between key regions and suggesting possible mechanisms involved in continence control.

AimsTo identify, in subjects with overactive bladder (OAB), differences in brain activity between those who maintained and those who lost bladder control during functional magnetic resonance imaging (fMRI) of the brain with simultaneous urodynamics.MethodsSecondary analysis of a cohort of older women (aged >60) with proven urgency urinary incontinence, who, in the scanner, either developed detrusor overactivity and incontinence (the “DO group”) or did not (the “no DO” group). A priori hypothesis: during urgency provoked by bladder filling, without DO, activity in regions related to continence control is diminished in the DO group; specifically (1a) less activation in supplementary motor area (SMA) and (1b) less deactivation in prefrontal cortex (PFC) and parahippocampal complex (PH). We also explored phenotypic (clinical and urodynamic) differences between the groups.ResultsDuring urgency preceding DO, the DO group showed stronger activation in SMA and adjacent regions (hypothesis 1a rejected), and less deactivation in PH but no significant difference in PFC (hypothesis 1b partially accepted). These subjects were older, with more changes in brain's white matter, decreased tolerance of bladder filling and greater burden of incontinence.Conclusions(1) In older women with OAB, brain activity in the SMA is greater among those with more easily elicitable DO, suggesting a compensatory response to failure of control elsewhere. (2) OAB is heterogeneous; one possible phenotype shows severe functional impairment attributable partly to age‐related white matter changes. (3) Functional brain imaging coupled with urodynamics may provide CNS markers of impaired continence control in subjects with OAB. Neurourol. Urodynam. 31:652–658, 2012. © 2012 Wiley Periodicals, Inc.

The regions of the supraspinal network that controls urinary bladder behavior are well known, but little is known about their interconnections. We tested the feasibility of using physiophysiological interaction to explore the effective connections of the network and to seek disease-related differences in connectivity. This was a secondary analysis of fMRI data obtained from women aged 26 -85 years, 11 with urge urinary incontinence and 10 with normal bladder function. In each subject, fMRI BOLD images were obtained during a period with full bladder and strong bladder sensation (without detrusor overactivity) while repeatedly infusing and withdrawing a small amount of liquid in and out of the bladder. Regions of interest included right insula (RI) and anterior cingulate gyrus (ACG), both consistently involved in bladder control. Other regions effectively connected to them were identified by significant correlation between their fMRI signal and the interaction RIxACG. Among normal subjects, many regions involved in bladder control were effectively connected with RI/ACG, including frontotemporal and sensorimotor cortex, forebrain, midbrain and pontine regions. The sign of the correlation with RIxACG was near-uniformly positive, perhaps suggesting mainly inhibitory connections. Among urge-incontinent subjects the effective connectivity was shifted to a parietotemporal complex, while the sign of the correlation was predominantly negative, perhaps consistent with excitation (recruitment) of accessory pathways in an attempt to maintain bladder control. Thus, physiophysiological interaction yields potentially important information about the connectivity of the bladder control network and its changes in disease.

Loss of bladder control (urge incontinence) is common in elderly; the cause is usually unknown. Functional imaging has revealed the brain network controlling responses to bladder filling. Age-related changes in this network might predispose to urge incontinence. We sought such changes in 10 continent, healthy women aged 30 – 79 years who underwent fMRI while fluid (20 ml) was repeatedly infused into and withdrawn from the bladder. Data were collected in 4 measurement blocks with progressively increasing bladder volumes and were analyzed by SPM2, using the contrast infuse-withdraw to quantify response to bladder infusion. Effective connectivity was examined by physiophysiological interaction (PhPI; see interpretation in Supplementary Material), with right insula (RI) and dorsal anterior cingulate cortex (dACC) as seed regions. Dependence on age and bladder volume (=block number) was assessed. Bladder infusion evoked expected activations. Activation decreased with age in bilateral insula and dACC. PhPI revealed connectivity with RI and dACC in regions that included bilateral putamen and R pontine micturition center. Interaction (connectivity) tended to increase with age in regions including L insula, L paracentral lobule and PAG. Consistent with a special role in maintaining continence, medial prefrontal cortex (mPFC) showed a trend to deactivation on bladder infusion that became more prominent in old age, and a trend to negative interaction (connectivity) that weakened significantly with age. Thus, with increasing age, weaker signals in the bladder control network as a whole and/or changes in mPFC function or connecting pathways may be responsible for the development of urge incontinence.

Purpose-To investigate the relationship between experimental neuroimaging and self-reported measures of urinary incontinence.Materials and Methods-We evaluated 14 functionally independent, community-dwelling older women (> 60 years) who had moderate to severe urgency urinary incontinence. All underwent detailed clinical assessment (3-day bladder diary, 24-hour pad test, and quality of life assessment), urodynamic testing, and functional brain scanning. Brain activity during reported urgency was assessed using a method that combines fMRI with simultaneous urodynamic monitoring during repeated cycles of bladder filling/emptying. We used SPM2, a statistical parametric mapping program, to correlate brain activity with relevant clinical covariates, including number of urgency incontinent episodes, amount of urine leakage, and psychological burden as assessed by the Urge Impact Scale (URIS-24) questionnaire.Results-Activity in rostral and subgenual anterior cingulate gyrus, insula, inferior frontal gyrus, orbitofrontal cortex, dorsal and posterior cingulate gyrus, parahippocampus, cuneus and parts of parieto-temporal lobe correlated positively with daytime incontinence frequency and urine loss. Different brain regions correlated with the psychological burden, and the associations were inverse: precuneus/cuneus and posterior cingulate gyrus, superior temporal, supramarginal, and transverse gyrus.Conclusions-Regional brain activity in the setting of self-reported urgency, as provoked by bladder filling, correlates significantly with the severity of incontinence in daily life as well as the associated psychological burden. Thus, observations made under experimental conditions correlate with patients' real-life experience and suggest neural correlates of urgency incontinence symptoms that could be used as potential targets for future investigations.