USC Team Maps Spinal Cord 'Address' for Bladder Control, Restoring Voiding in 91.7% of Trials
核心洞察
USC researchers identified the dorsolateral funiculus (搜索) (DLF) as a precise spinal cord region that encodes bladder fullness, with neural firing climbing from 30 Hz to nearly 100 Hz during filling.
Patterned electrical microstimulation at DLF coordinates triggered coordinated voiding in 91.7% of trials in rats, rising to 100% when the bladder was pre-filled to natural activation volume.
The envisioned closed-loop neuroprosthesis, named BLISS (Bladder-Linked Stimulation System), would restore both the sensation of needing to void and the act itself.
Nearly all of the approximately 308,000 people in the United States living with spinal cord injury (搜索) lose bladder control—a devastating consequence that receives far less research attention than motor restoration. Now, a team at the University of Southern California has pinpointed a tiny region of the spinal cord that encodes the sensation of bladder fullness and demonstrated that electrically stimulating it can restore coordinated voiding.
"When you can't control your bladder, that's all you think about," said Dr. Charles Liu, professor of neurological surgery and neurology at the Keck School of Medicine of USC, director of the USC Neurorestoration Center, and co-senior author on the study published in IEEE Transactions on Neural Systems and Rehabilitation Engineering. Liu noted that the problem extends beyond social stigma: "All of my brain-computer interface patients have a severe episode of urosepsis every year. I've known patients who died from this."
The DLF: A Precise Anatomical Address
The team, including co-senior author Vasileios Christopoulos, assistant professor in the Alfred E. Mann Department of Biomedical Engineering at USC Viterbi School of Engineering, and first author Shan Zhong, a postdoctoral researcher at USC Viterbi, focused on the dorsolateral funiculus (搜索) (DLF)—a thin bundle of ascending sensory fibers near the spinal cord's surface.
Normally, as the bladder fills, signals travel up through the DLF to the brain, which registers fullness and sends a coordinated command back down to contract the bladder muscle and relax the sphincter simultaneously. After spinal cord injury (搜索), that loop is severed, and patients lose both voluntary control and the ability to feel the need to void.
Using custom microelectrode arrays developed by Ecate LLC (搜索), a USC-affiliated startup, the researchers mapped neural activity in rats during controlled bladder filling. Most candidate spinal cord regions were silent. But in the DLF, one or two adjacent channels lit up with rhythmic bursting that tracked filling precisely, climbing from 30 Hz with the first drops of saline to nearly 100 Hz just before voiding. Electrodes just 65 micrometers away stayed completely silent. The responsive zone, roughly 100 by 100 micrometers, was consistent enough across animals to serve as a reliable anatomical address.
"The spinal cord is not just a cable," Zhong said. "Bladder control is sparsely distributed in the brain. But here, we can directly target one region and trigger the sense of bladder filling."
Restoring Coordinated Voiding
In a separate animal model group, the team delivered patterned electrical pulses at those same DLF coordinates, timed to mimic the biological signal of a full bladder. Coordinated voiding followed in 91.7% of trials, rising to 100% when the bladder was pre-filled to the volume where natural DLF activity begins. Leg muscle electrodes remained silent throughout, confirming the response was bladder-specific rather than a generalized motor reflex.
The envisioned full system, named BLISS (Bladder-Linked Stimulation System), would pair this sensory interface with a bladder volume sensor and a motor stimulator, creating a closed-loop neuroprosthesis that restores both the sensation and the act of voiding. "The best thing about this," Zhong said, "is that it can actually make people feel that there is a need for voiding, instead of depending on alarm clocks."
Pathway to Patients
Liu estimates that with adequate funding, initial human recordings could begin within 18 months—not in spinal cord injury (搜索) patients first, but piggybacked onto spinal cord tumor surgeries that are already far more invasive. A brief recording during an existing surgery adds minimal risk, while those patients often face bladder complications themselves and have a direct stake in the technology.
Parallel Effort Targets Stroke (搜索)-Related Incontinence
In a related development, researchers from the Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC and Rancho Los Amigos National Rehabilitation Center have received an NIH grant to investigate brain changes responsible for urinary incontinence (搜索) after stroke (搜索).
Led by Evgeniy Kreydin, MD, adjunct assistant professor of clinical urology, the project will combine functional MRI, diffusion MRI, clinical bladder testing, and transcutaneous spinal cord stimulation (TSCS). Bladder symptoms persist in more than 30% of stroke (搜索) survivors, yet current treatments—including medications and bladder injections—primarily address symptoms rather than the disrupted signaling between brain, spinal cord, and bladder.
"Bladder dysfunction after stroke (搜索) can have a profound effect on a person's independence, dignity, and quality of life, yet treatment is often focused on the bladder rather than the neurological injury that caused the problem," Kreydin said.
The study will compare stroke (搜索) survivors with injuries in different brain areas, including the basal ganglia and pons, alongside healthy controls. Participants will undergo fMRI during controlled bladder filling, paired with urodynamic testing. Diffusion MRI and tractography will map white matter pathways connecting key bladder-control regions, revealing how stroke disrupts communication.
Participants will receive 12 weeks of TSCS, with repeat imaging afterward. The goal is to develop imaging biomarkers that predict which patients are most likely to benefit—moving toward personalized neuromodulation rather than a one-size-fits-all approach.
"This project reflects the promise of neuroimaging to connect what we see in the brain with meaningful improvements in patients' lives," said Arthur W. Toga, PhD, director of the Stevens INI.
