For more than a decade, physician-scientists at UC San Francisco (UCSF) have worked to improve deep brain stimulation (DBS), a treatment that uses electrical currents delivered through electrodes implanted in the brain. This approach, similar to how a cardiac pacemaker works, interrupts problematic brain activity and has been used for years to treat movement disorders such as Parkinson’s disease.
Historically, DBS was limited by its continuous delivery of stimulation, which did not adapt well to patients’ changing symptoms and showed inconsistent results when tested for other conditions. Professors Philip Starr, MD, PhD, and Edward Chang, MD, at UCSF have advanced surgical and brain mapping techniques to develop personalized DBS. In this new method—partly developed at UCSF—stimulation is only delivered when abnormal brain activity linked to symptoms is detected.
This progress was supported by funding from the National Institutes of Health (NIH) Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) initiative.
In the case of Parkinson’s disease, Shawn Connolly participated in a clinical trial testing an adaptive DBS system created by Starr and Simon Little, MBBS, PhD. The technology uses an algorithm that identifies signals indicating symptom onset and delivers targeted stimulation only as needed. Unlike earlier versions that were always active, this system responds in real time.
In February 2024, the Food and Drug Administration approved two adaptive DBS algorithms based on research including Little’s work. These approvals enabled the first adaptive DBS system for people with Parkinson’s.
“It’s definitely changed my life,” Connolly said in 2024. “I can just go through the whole day feeling good.”
Starr and Chang’s work also involves less invasive ways to achieve personalized DBS outcomes without surgery. Their efforts were made possible by NIH support for electrocorticography—a monitoring technique allowing researchers to record signals inside the brain—which led Starr to implant the first multi-site recording device in a Parkinson’s patient in 2013.
Chronic pain affects nearly one-quarter of Americans. In 1972, UCSF professors John E. Adams, MD, and Yoshio Hosobuchi, MD tested continuous DBS for chronic pain but found that its effects faded over time as the brain adapted. In 2023 at UCSF, Prasad Shirvalkar, MD, PhD identified individual pain biomarkers using data from implanted electrodes matched with patient logs and applied artificial intelligence to predict pain episodes based on these signals. This discovery allowed clinical trials of personalized DBS systems that deliver stimulation only when pain markers appear.
For depression treatment-resistant cases affect nearly one-third of those diagnosed with major depressive disorder in the U.S.—Chang’s team mapped patterns of electrical activity associated with mood states using advanced techniques developed at UCSF. In 2020 they provided Sarah—a participant whose depression had been severe—with a personalized DBS device that alleviated her symptoms.
“I was at the end of the line. I was severely depressed. I could not see myself continuing … if I could never move beyond this,” she told UCSF in 2021. “It was not a life worth living.”
“In the early few months, the lessening of the depression was so abrupt, and I wasn’t sure if it would last,” she remembered. “But it has lasted. And I’ve come to realize that the device really augments the therapy and self-care I’ve learned while being a patient here at UCSF.” She added: “Those thoughts still come up but it’s just … poof …the cycle stops.”
UCSF Psychiatry Professor Andrew D. Krystal runs a federally funded trial studying DBS for depression; success could make this technology available more widely.
NIH funding has also helped establish UCSF as one of about twelve hospitals offering continuous DBS as psychiatric care for severe obsessive-compulsive disorder (OCD). Andrew Moses Lee directs UCSF’s OCD Program and leads clinical trials aiming to identify biomarkers for future personalized treatments; together with Krystal he is evaluating personalized approaches for OCD.
Chang said: “Tailoring these treatments to the person’s neural signature is really the key that allows DBS to be effective across many conditions.”
