For more than a decade, research teams at UC San Francisco (UCSF) have advanced the use of deep brain stimulation (DBS), with support from the National Institutes of Health (NIH). DBS uses targeted electrical currents delivered through electrodes implanted in the brain to interrupt abnormal activity associated with neurological and psychiatric conditions.
Historically, continuous DBS has been used to manage movement disorders such as Parkinson’s disease. However, traditional systems were not able to adapt to changes in patient symptoms over time and showed limited effectiveness for other disorders.
Professors Philip Starr, MD, PhD, and Edward Chang, MD, from UCSF Neurological Surgery have developed new surgical and brain mapping methods that enable personalized DBS. These approaches deliver electrical stimulation only when abnormal brain activity linked to symptoms is detected—activity that is unique for each patient. The work was made possible by funding from the NIH BRAIN Initiative.
In recent years, UCSF scientists have demonstrated four major ways personalized DBS may impact care:
Parkinson’s Disease
Shawn Connolly was diagnosed with Parkinson’s disease at age 39. As his symptoms progressed, he found that existing DBS technology did not provide adequate relief. In 2021, Connolly joined a clinical trial testing an adaptive DBS system developed by Starr and Simon Little, MBBS, PhD. This next-generation device used an algorithm to detect developing symptoms and provided stimulation only as needed.
The Food and Drug Administration approved two adaptive DBS algorithms in February—including one based on Little’s work—enabling the first adaptive DBS system for people with Parkinson’s disease.
“It’s definitely changed my life,” Connolly said in 2024. “I can just go through the whole day feeling good.”
Starr and Chang are also working on less invasive techniques informed by their insights into brain mapping. Their early adoption of electrocorticography allowed them to record signals inside the brain; this led to advances such as implanting multi-site recording devices in patients beginning in 2013.
Chronic Pain
About one-quarter of Americans experience chronic pain lasting three months or longer. Early attempts at continuous DBS for pain showed temporary results before pain returned—a phenomenon thought to be due to the brain adapting to constant stimulation.
In 2023, Prasad Shirvalkar, MD, PhD at UCSF identified individual pain biomarkers by correlating recorded brain activity with patient-reported pain levels. Artificial intelligence helped predict when patients would feel pain based on these signals. This enabled clinical trials using personalized DBS systems that activate only when pain markers are detected.
Depression
A significant portion of those diagnosed with major depressive disorder live with treatment-resistant depression. Sarah participated in a clinical trial after meeting Edward Chang at UCSF while experiencing severe depression.
“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.”
By using advanced brain mapping techniques developed at UCSF, Chang’s team identified mood-related patterns of electrical activity and new areas for stimulation. In 2020 they provided Sarah with a personalized device that alleviated her symptoms.
“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.”
Sarah described how combined talk therapy and DBS helped control intrusive thoughts: “Those thoughts still come up, but it’s just … poof … the cycle stops.”
Professor Andrew D. Krystal now leads a federally funded trial studying this approach further.
Obsessive-Compulsive Disorder (OCD) and Other Conditions
UCSF is among about twelve hospitals offering continuous DBS for severe OCD cases under FDA regulations limiting its use to patients who do not respond to other treatments. Andrew Moses Lee directs UCSF’s OCD Program and is leading efforts alongside Krystal to identify biomarkers related to OCD symptoms and test future applications of personalized stimulation.
Edward Chang suggested these tailored treatments might eventually extend beyond current indications: “Tailoring these treatments to the person’s neural signature is really the key that allows DBS to be effective across many conditions,” he said.
