Brain Imaging plus Urodynamics to Investigate the Brain's Control of the Bladder

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DESCRIPTION (provided by applicant): Overactive bladder (OAB) and urge urinary incontinence (UUI) are common, morbid, and costly. Yet, treat- ment has improved little in 50 years, impeded by poor understanding of their etiology, especially of the cerebral factors. Recently, positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have identified key brain areas involved in bladder control. Such imaging has enabled us to devise a working model of the normal brain-bladder control system, in which the insula records bladder sensations, the dorsal anterior cingulate cortex (dACC) provides the motivation to void and motor output, and regions of the prefrontal cortex govern bladder control. By contrast, when patients with UUI are challenged with a large bladder volume and strong desire to void, responses in the dACC, associated supplementary motor area, and dorsolateral prefrontal cortex become exaggerated, representing the neural correlate of "urgency"; in addition, there is deactivation of the medial prefrontal cortex, a crucial element of bladder control. These exciting data suggest that further study of the brain's role in UUI may lead to new therapeutic insights. The promise is dimmed, however, by the limitations inherent in current PET and fMRI technology, which prevent simultaneous study of brain and bladder/sphincter changes and exclude evaluation of many subjects entirely. Functional near-infrared spectroscopy (fNIRS) is a new method that may not only overcome these limitations, but also enable investigation of brain-bladder/sphincter control in individuals (vs. only a group), in real time, during voiding, and in ambulatory settings. Thus, fNIRS could become a powerful complement to urodynamic and neuroimaging techniques, allowing investigators to better study central and peripheral factors that contribute to OAB and UUI. Moreover, exciting new preliminary data confirm that bladder/sphincter related changes in activation can be recorded from key regions in our model. Despite its substantial promise, however, NIRS' potential benefit remains largely unexplored. To address this, the proposed study will evaluate fNIRS' feasibility, reproducibility, and relevance for investigation of bladder/sphincter function associated with UUI: 25 patients with UUI and 15 age-matched controls will undergo urodynamics with concurrent fNIRS. fNIRS responses in key brain regions will be recorded during filling, voiding, and spontaneous bladder events. Responses in patients and controls will be compared to determine whether: (a) NIRS can record reproducible responses in brain regions known from fMRI to be relevant for bladder function; (b) NIRS and fMRI responses are consistent; and (c) new information can be obtained about dynamic changes in bladder/sphincter activation. The proposed study will set the stage for a larger clinical study. fNIRS, a newly developed methodology could become a powerful new tool for investigation of bladder problems and identification of new therapeutic targets. It also could facilitate development of more effective behavioral interventions for both UUI and OAB. PUBLIC HEALTH RELEVANCE: In older adults, loss of bladder control is common, devastating, and costly (>$60 billion in 2007), yet treatment has improved little in decades because the causes are often unknown and therapeutic targets unclear. Recent studies suggest that brain abnormalities may play a major role, but limitations of current brain imaging hinder further insights. The proposed study will investigate the potential role of a new technique which, if proven effective, may not only advance our understanding but also lead to development of more effective treatment.