USC researchers reveal brain activity behind post stroke urinary incontinence

A new USC-led study using functional magnetic resonance imaging (fMRI) reveals the neural mechanisms that contribute to urinary incontinence, a common condition affecting stroke survivors that has a significant impact on their quality of life.

The research, just published in Stroke, was conducted by a multidisciplinary team of urologists, neurosurgeons, and imaging experts from the Keck School of Medicine of USC, Keck Medicine of USC, the Rancho Los Amigos National Rehabilitation Center, and the Shirley Ryan Ability Lab. The team discovered significant differences in brain activity during voluntary versus involuntary bladder contractions, presenting potential pathways for targeted therapies.

Urinary incontinence affects up to 79% of patients in the immediate aftermath and persists in nearly 40% of survivors one year later. It typically arises from uncontrolled bladder contractions and involuntary urine expulsion, leaving patients with debilitating symptoms such as urinary urgency, frequency, and leakage. Although common, it is often undertreated. This condition also predicts poorer long-term outcomes, including higher mortality rates and increased disability.

The brain plays a crucial role in regulating the bladder, allowing people to sense bladder fullness and giving them the ability to delay urination until it is socially appropriate or initiate it at will. In contrast, stroke survivors often struggle to suppress unwanted bladder contractions and may even lose bladder sensation and awareness entirely. Since a stroke impacts the brain, it disrupts the normal pathways that govern bladder control. Nevertheless, the precise neurological foundations of this dysfunction have remained poorly understood until recently."

Evgeniy Kreydin, MD, adjunct assistant professor of clinical urology and lead author of the study

This research played a key role in Kreydin receiving the McGuire-Zimskind Award from the Society of Urodynamics, Female Pelvic Medicine, and Urogenital Reconstruction (SUFU). The award honors early-career professionals within ten years of completing residency or fellowship who have made significant contributions to the field through basic and clinical research. The study utilized an innovative method of repeated bladder filling and voiding while participants were inside the MRI, during which their brain function was measured.

"In contrast to previous studies where participants using a catheter entered the scanner with a full bladder and voided on command, our study enabled us to observe filling and voiding repeatedly. The simultaneous recording of bladder pressure allowed us to identify both voluntary and involuntary bladder emptying. This allowed us to detect differences in brain activity during involuntary emptying for the first time," said Kay Jann, PhD, of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute at the Keck School of Medicine. Jann develops analytical tools and clinical translations of functional MRI technology and served as the imaging expert for the study.

During voluntary bladder emptying, when participants consciously decided when to empty the bladder, both healthy individuals and stroke survivors showed significant activation in brain regions associated with sensorimotor control and executive decision-making. In contrast, involuntary or incontinent bladder emptying in stroke survivors was marked by minimal cortical activation, suggesting a failure to engage key brain networks necessary for urinary control.

In both healthy individuals and stroke survivors, bladder filling before voluntary urination triggered activity in a collection of brain regions known as the salience network. These brain regions work together to evaluate the importance of internal or external stimuli and coordinate the brain's response to those stimuli. However, during bladder filling that preceded involuntary urination, this network remained inactive for stroke survivors with incontinence. These findings suggest the inability to engage the salience network may be a core mechanism underlying post-stroke urinary incontinence.

These findings open doors for novel interventions aimed at restoring bladder control in stroke patients. Potential therapeutic approaches could include:

• Using non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) or direct current stimulation (tDCS), to target the salience network
• Developing medications that enhance neural activation in critical continence control regions
• Cognitive training and biofeedback therapies designed to improve bladder awareness and voluntary control

While the study represents a significant advancement in understanding post-stroke incontinence, the researchers emphasize the need for further investigation. Future studies could explore how different types of strokes affect urinary control and whether early intervention targeting the salience network might help prevent chronic incontinence in stroke survivors.

Charles Liu, PhD, MD, director of the USC Neurorestoration Center, senior author of the study, and coordinator of all the collaborators, is hopeful for further discovery as this important research is built upon. "The neurological basis of urination is still poorly understood, and additional research will be crucial for the neurorestoration of the urinary and reproductive systems," said Liu, who is also a professor of clinical neurological surgery, surgery, psychiatry and the behavioral sciences, and biomedical engineering at the Keck School of Medicine. "This work not only deepens our understanding of a common post-stroke complication but also provides hope for a better quality of life for millions of stroke survivors globally."

This study was funded by a grant from the Urology Care Foundation to Evgeniy Kreydin. The authors include Evgeniy I. Kreydin, MD, Aidin Abedi, MD, Luis Morales, MD, Stefania Montero, MD, Priya Kohli, BS, Nhi Ha, BS, David Chapman, MD, Armita Abedi, MD, David Ginsberg, MD, Kay Jann, PhD, Richard L. Harvey, MD, and Charles Y. Liu, MD, PhD.