UC San Francisco researchers have developed a new form of deep brain stimulation (DBS) that adjusts in real time as a person walks, helping improve gait and reduce falls in people with Parkinson's disease.
The study , publishing June 15 in Nature Medicine, demonstrates for the first time that an implanted brain stimulator can detect neural signals associated with each step and automatically adjust stimulation within fractions of a second. Much like a cardiac pacemaker responds to the heart's rhythm, the new system responds to the brain's rhythm of walking.
"Difficulty walking is one of the most disabling symptoms of Parkinson's disease and one of the hardest to treat," said Doris D. Wang , MD, PhD, associate professor of neurological surgery at UCSF and senior author of the study. "Walking is a highly dynamic behavior that requires precise timing across both sides of the body. We developed a system that can recognize those movement patterns and respond in real time, effectively allowing the stimulation to work with the patient as they move."
A Smarter Kind of Brain Stimulation
More than 10 million people worldwide live with Parkinson's disease. While deep brain stimulation can dramatically improve tremor, stiffness, and slowness, many patients continue to struggle with gait impairment, freezing of gait, and falls —symptoms that are among the leading causes of disability and loss of independence.
The UCSF team believed that one reason standard DBS has limited effects on walking is that gait itself is constantly changing. Every step requires rapid coordination between the brain, spinal cord, and muscles. Conventional or continuous DBS, however, delivers a fixed pattern of stimulation regardless of what a person is doing.
To address this challenge, the researchers developed a personalized adaptive DBS (aDBS) system that identifies brain signals associated with movement of the left and right legs. These signals are then embedded directly into the implanted neurostimulator, allowing the device to automatically adjust stimulation during each phase of walking without requiring an external computer.
"The brain contains remarkably rich information about movement," said first author Kenneth H. Louie , PhD, a UCSF post-doctoral scholar. "We found that we could identify neural signatures linked to each step and use them to guide stimulation in real time."
From Constant Therapy to Responsive Therapy
The study enrolled five people with Parkinson's disease who had undergone DBS surgery and were participating in a UCSF research program using an investigational DBS system. In addition to their therapeutic DBS leads implanted deep within the brain, participants had research electrodes placed over movement-related areas of the brain. Together, these devices allowed researchers to identify personalized neural signatures (brain signals) of walking and program the stimulator to automatically adjust therapy in real time.
In laboratory testing, the aDBS system improved measures of gait symmetry and reduced variability in walking patterns, both markers of more stable and efficient gait.
Participants then completed a blinded, multi-day crossover study in their daily lives. During periods when the adaptive system was active, participants experienced fewer falls while maintaining overall control of Parkinson's symptoms. No serious adverse events occurred, and patients tolerated the rapid stimulation adjustments well.
Although larger studies are needed, the findings provide early evidence that timing stimulation to behavior may improve outcomes beyond what is possible with conventional continuous stimulation.
A New Frontier for Personalized Neuromodulation
The work represents a shift in how scientists think about brain stimulation therapies. Most aDBS systems developed to date respond to slowly changing indicators of disease state. The UCSF approach instead responds directly to behavior itself.
"This study is about more than walking," Wang said. "It demonstrates that brain stimulation can adapt to what a person is doing in real time. That opens the door to future therapies that respond dynamically to movement, speech, mood, cognition, and other brain functions."
Researchers envision a future in which implanted devices continuously sense and respond to neural activity, delivering personalized therapy only when and where it is needed.
"This is an important step toward a new generation of brain therapies," said Wang. "Instead of delivering the same stimulation all day long, future devices may continuously listen to the brain and immediately respond to a patient's needs. Just as pacemakers transformed the treatment of heart disease, intelligent neurostimulators may transform how we treat disorders of the brain."
Additional UCSF Authors: Kenneth H. Louie, PhD, Jannine P. Balakid, BS, Jessica E. Bath, DPT, PhD, Seongmi Song, PhD, Hamid Fekri Azgomi, PhD, Jacob H. Marks, BA, Philip A. Starr, MD, PhD.
Additional Authors: Julia T. Choi, PhD, (University of Florida, Gainesville).
Funding: This study was supported by the Michael J Fox Foundation Grant MNS135499A, the UCSF Burroughs Wellcome Fund Career Award for Medical Scientist, and National Institute of Neurological Disorders and Stroke (NIH/NINDS) 1R01NS130183. This study was also partially supported by UCSF Catalyst Grants. All funding above was obtained by D.D.W.
Disclosures: D.D.W. consults for Medtronic, Boston Scientific, and Iota Bioscience, and receives research support from Boston Scientific. P.A.S. receives support from Medtronic and Boston Scientific for fellowship education. K.H.L. is a current employee of Echo Neurotechnologies. This work was completed prior to their employment at Echo Neurotechnologies, and Echo Neurotechnologies had no role in the study design, data collection, analysis, or decision to publish.
About UCSF Health: UCSF Health is recognized worldwide for its innovative patient care, reflecting the latest medical knowledge, advanced technologies and pioneering research. It includes the flagship UCSF Medical Center, which is a highly-ranked hospital, as well as UCSF Benioff Children's Hospitals, with campuses in San Francisco and Oakland; two community hospitals, UCSF Health Stanyan Hospital and UCSF Health Hyde Hospital; Langley Porter Psychiatric Hospital; UCSF Benioff Children's Physicians; and the UCSF Faculty Practice. These hospitals serve as the academic medical center of the University of California, San Francisco, which is world-renowned for its graduate-level health sciences education and biomedical research. UCSF Health has affiliations with hospitals and health organizations throughout the Bay Area. Visit http://www.ucsfhealth.org/ . Follow UCSF Health on Facebook , Threads
