Functional and structural brain connectivity alterations in post-stroke lower urinary tract dysfunction - 1 2 project summary 3 stroke impairs more than movement and speech-IT damages the brain…

The National Institute of Diabetes and Digestive and Kidney Diseases awarded Rancho Research Institute $727,810 on June 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to investigate functional and structural brain connectivity alterations in post-stroke lower urinary tract dysfunction and to identify biomarkers predicting response to transcutaneous spinal cord stimulation therapy.

The research combines three integrated aims. Aim 1 uses task-based and resting-state fMRI to map how basal-ganglia, pontine, and occipital strokes differentially disrupt connectivity among key bladder-control hubs—the insula, anterior cingulate cortex, supplementary motor area, and pontine micturition center—and correlate those losses with urodynamic severity. Aim 2 applies diffusion-MRI tractography to define the white-matter pathways anchoring those networks and tests whether tract injury mediates functional disconnection and symptoms. Aim 3 delivers a twelve-week course of transcutaneous spinal cord stimulation to determine whether baseline network and tract integrity, combined with therapy-induced connectivity changes, predict objective clinical improvement and create a prospectively validated biomarker panel.

Work is performed at Rancho Research Institute in Downey, California. The award runs through March 31, 2031. Up to 30 percent of stroke survivors experience chronic urinary incontinence; existing bladder-wall treatments often fail or cause side effects because they do not address upstream neurological injury. This project addresses that gap by linking stroke-induced network injury to treatment outcome, targeting a subset of patients currently unresponsive to therapy and lacking selection biomarkers.

Functional and structural brain connectivity alterations in post-stroke lower urinary tract dysfunction - 1 2 project summary 3 stroke impairs more than movement and speech-IT damages the brain circuits that keep the bladder 4 continent. Up to 30% of survivors live with chronic urinary incontinence, eroding quality of life and increasing 5 caregiver burden. Existing treatments act at the bladder wall and often fail or cause side effects because they 6 do not address the upstream neurological injury. 7 neuromodulation offers a disease-targeted alternative. Our group has piloted transcutaneous spinal cord 8 stimulation (TSCS) - a non-invasive therapy that reduced incontinence in stroke survivors - yet only a subset 9 of patients respond and no biomarkers guide selection. This project will close that GAP by linking stroke-induced 10 network injury to TSCS outcome. 11 aim 1 uses task-based and resting-state fmri to map how basal-ganglia, pontine, and occipital strokes 12 differentially disrupt connectivity among key bladder-control hubs (insula, ACC, SMA, pontine micturition center) 13 and how these losses relate to urodynamic severity. 14 hypothesis: greater loss of connectivity within salience, executive, and sensorimotor networks will correlate with 15 worse urodynamic measures of storage and voiding. 16 aim 2 applies diffusion-MRI tractography to define the white-matter pathways that anchor those networks and 17 tests whether tract injury mediates functional disconnection and symptoms. 18 hypothesis: lower fractional anisotropy and higher diffusivity in these tracts will mediate the functional 19 disconnection identified in aim 1 and independently predict LUT symptom severity. 20 aim 3 delivers a 12-week TSCS course to determine whether baseline network/tract integrity and therapy- 21 induced connectivity changes predict objective clinical improvement, creating a prospectively validated 22 biomarker panel. 23 hypothesis: responders will show better-preserved baseline network and tract integrity and will exhibit TSCS- 24 induced restoration of supraspinal information flow; these imaging signatures will predict clinical improvement 25 with high accuracy. 26 by integrating functional and structural neuroimaging with objective bladder metrics, we will create the first 27 personalized, brain-based framework for treating post-stroke incontinence. The resulting biomarkers will enable 28 precise patient selection, shorten therapeutic trials, and accelerate adoption of TSCS and future 29 neuromodulation approaches in routine stroke care. 30 internal