Identification of age and SEX dependent contributions to supraspinal mechanisms involved in underactive bladder - the lower urinary tract (LUT) functions by switching between storage and voiding…

The National Institute on Aging awarded The Methodist Hospital Research Institute $665,617 on September 15, 2026, under the Aging Research program (CFDA 93.866) to identify age and sex-dependent contributions to supraspinal mechanisms involved in underactive bladder dysfunction. The research addresses the poorly understood neurological underpinnings of underactive bladder (UAB), which presents with symptoms including slow urinary stream, hesitancy, and incomplete emptying. UAB predominantly affects older adults and, if untreated, increases risks of recurrent urinary tract infection, renal failure, and bladder stones; current therapies including catheterization have limited efficacy and poor compliance. The project will investigate altered supraspinal neural network activity during the bladder filling and storage-voiding cycle using functional magnetic resonance imaging to identify brain regions of interest that may serve as targets for supraspinal neuromodulation, building on evidence that such abnormal activity is a hallmark of aging-associated lower urinary tract symptoms. Performance of work occurs in Houston, Texas, with a period of performance extending through May 31, 2031. The Methodist Hospital Research Institute, a nonprofit biomedical research organization and division of The Methodist Hospital, serves as the recipient organization.

Identification of age and SEX dependent contributions to supraspinal mechanisms involved in underactive bladder - the lower urinary tract (LUT) functions by switching between storage and voiding phases and is intricately regulated by spinal and supraspinal (brain, cerebellum, brainstem) neural control. In dysfunctional states across the LUT storage-voiding cycle, patients experience LUT symptoms (luts), which negatively impact their quality of life. Luts syndromes such as overactive bladder (OAB) and bladder pain are well characterized and have multiple effective treatments. In contrast, the mechanisms underlying underactive bladder (UAB) remain poorly is characterized by symptoms such as slow urinary stream, hesitancy, and straining to void, with or without a feeling of incomplete bladder emptying and, in some cases, accompanied by storage symptoms. If untreated, incomplete bladder emptying increases the risks of recurrent urinary tract infection, renal failure, and bladder stones. Understood, and effective therapies are lacking. UAB UAB is most prevalent in older adults and imposes substantial quality of life and financial burdens. Currently, available therapies have limited efficacy. Catheterization, the most commonly used treatment, is often uncomfortable, leading to poor compliance. Altered supraspinal network activity during bladder filling, as seen in functional magnetic resonance imaging (fmri), is a hallmark of aging-associated luts such as OAB. Region of interest (rois) with abnormal activity serve as targets for supraspinal neuromodulation in both non-urologic disorders and in LUT syndromes, including OAB, voiding dysfunction, and bladder pain. However, the supraspinal rois involved in UAB remain unknown and detrusor muscle weakening. T lies in the essential role of supraspinal activity in regulating the LUT storage/voiding cycle. Understanding supraspinal control of the LUT in UAB and healthy aging adults is critical to advancing treatment options. May be influenced by aging-related structural and physiologic changes in the LUT, such as he significance of this study the overall objective of this study is to characterize neural activity and structure in adults with UAB using a high-resolution fmri platform. We hypothesize that aging-related degeneration of structure and function associated with UAB contributes to supraspinal activity during the LUT storage/voiding cycle and WM microstructural organization which deviates from similarly aged HCS. We will test our hypothesis with these specific aims: aim 1: identify and characterize supraspinal activity and functional connectivity (FC) in adults with UAB in regions involved in the LUT storage/voiding cycle. Aim 2: elucidate changes in supraspinal activity, FC and white matter (WM) microstructural differences in UAB versus similar aged healthy controls. Aim 3: characterize contributions of aging and SEX to supraspinal activity, FC, and WM microstructural differences. This will be the first study to define supraspinal networks in UAB while also addressing the physiological changes of aging and SEX differences. This interdisciplinary research fosters fundamental discovery of the supraspinal mechanism for UAB and contributions of age and SEX using an innovative strategy which aligns with the parent R01 grant mechanism.