Resetting brain circuits

Amber Bodeur was 7 when she was overcome by fear that her father wouldn’t return from an overseas trip unless she flipped a light switch in a specific pattern. It was her first memory of obsessive-compulsive disorder (OCD), but it wouldn’t be her last. In the following years, the disorder hijacked her every thought. “OCD was this monster in my head. It never left me alone,” recalled Bodeur, now 28.

She tried every possible treatment: evidence-based behavioral therapy, ketamine therapy, transcranial magnetic stimulation (TMS), and more than two dozen medications. Nothing controlled the intrusive urges. Unable to work or attend school, she lived in an apartment her parents provided, close to their home in Arizona. “I was confined to my house, having OCD compulsions from the moment I woke up to the moment I went to sleep,” she said.

Then her father read about a clinical trial at Penn Medicine, where researchers were using deep brain stimulation (DBS) to treat OCD. DBS, long used to treat movement disorders, involves surgically implanting electrodes into the brain to stimulate brain circuits causing dysfunction. “A neurosurgery? It sounded so crazy,” Bodeur said. “But I thought, what did I have to lose?” That decision was the first step toward a life she never dreamed possible.

Three decades after neurosurgeons began treating Parkinson’s disease with DBS, the field of brain stimulation continues to break new ground. Today, less-invasive tools like TMS and focused ultrasound offer the promise of resetting glitching brain circuits without implanting electrodes directly into the brain.

Historically, disorders of the brain were treated with medications, psychiatric therapy, or surgery. Neuromodulation offers an entirely new way to intervene—and in the process, it’s breaking down old-fashioned beliefs about the brain.

“We’ve recognized there aren’t these crisp diagnostic boundaries across conditions,” said Katherine Scangos, MD, PhD, the principal investigator of the DBS clinical trial through which Bodeur was treated. “Over the last 20 years we’ve started to link symptoms to circuits—and now, to modulate those circuits” with neurostimulation, said Scangos, an associate professor of Psychiatry and Neurosurgery, and director of the Brain Circuit Therapeutics Clinic at Penn Medicine.

Penn Medicine is playing a leading role in this rapid evolution of neuromodulation research and clinical care. Advances in brain stimulation are opening the door to treating more patients with neurological and psychiatric conditions. And this work is changing the way experts view—and treat—disorders of the brain.

Deep brain stimulation

Neuromodulation technologies like DBS and TMS target brain-based symptoms at their source. In the case of Parkinson’s disease, that’s the basal ganglia—structures near the center of the brain that coordinate muscle movements. “DBS works tremendously well for tremor, and it can be dramatically beneficial for patients’ stiffness and shuffling walk,” said Meredith Spindler, MD, a professor of Clinical Neurology and medical director of the Deep Brain Stimulation Program at Penn’s Parkinson’s Disease and Movement Disorders Center.

Penn was an early adopter and remains one of the highest-volume centers in the world using DBS to treat movement disorders. After thousands of procedures and a wealth of published research identifying new targets in the brain, DBS is becoming even more effective. “DBS technology has changed dramatically in the last 10 years,” Spindler said. “It’s been a very exciting time to be working in this field.”

Neurosurgeons can now target the brain regions responsible for Parkinson’s disease tremors with extreme precision. “We’re doing it five times as fast and getting patients feeling better much faster,” said Casey Halpern, MD, division head of Functional and Stereotactic Neurosurgery, and the neurosurgeon who performed Bodeur’s surgery at Pennsylvania Hospital.

Still, Penn Medicine experts are working to make DBS even more effective. Penn Medicine recently started offering a system called closed-loop DBS, also known as adaptive DBS, that was FDA approved in 2025. Instead of delivering steady stimulation, the system records electrical signals from the brain and adjusts stimulation accordingly. “It’s an exciting development because Parkinson’s doesn’t stay static. It waxes and wanes in the intensity of symptoms,” Spindler explained.

Lauren Hammer, MD, PhD, an assistant professor of Neurology and a lead faculty member in the Center for Neuroengineering and Therapeutics, is driving much of this work forward. A leader in the field of adaptive DBS for Parkinson’s, prior to joining Penn she was a co-investigator on the pivotal adaptive DBS trial that led to its FDA approval. Her work has identified a novel brain signal that could be an even better marker of brain activity in Parkinson’s. With colleagues in engineering and industry, she’s now developing a new adaptive DBS system and planning a pilot study to compare it to the FDA-approved version. She’s also looking beyond the basal ganglia to study brain circuits in the cerebellum, which are linked to essential tremor and cerebellar ataxia.

“Essential tremor is very understudied compared to Parkinson’s disease, but it’s the most common movement disorder in the world—and it often doesn’t respond to medication very well,” Hammer said. She hopes that a better understanding of those cerebellar circuits will lead to new DBS targets for patients with those movement disorders.

Penn Medicine experts are also involved in clinical trials to use DBS in disorders such as depression, OCD, and binge eating disorder. Early attempts to extend the treatment to psychiatric conditions had mixed results. But advances in understanding exactly where to place the electrodes, and what stimulation protocols to use, have led to a new wave of interest—and encouraging results.

In late 2023, Bodeur had the first of two surgeries as part of the ongoing OCD study. Halpern and his colleagues surgically implanted stereoEEG leads into Bodeur’s brain. For two weeks, she remained in the hospital while the leads recorded information about her brain, capturing the precise locations involved in her OCD. The following spring, Halpern implanted permanent electrodes into those regions of her brain. After a month of recovery, the team switched on the device. “Immediate relief is what I felt—immediate relief,” she said.

Not everyone has such a transformative response, though most people experience some improvement, Halpern said. He believes that people who don’t respond just haven’t had the right area (or, perhaps, multiple areas) of the brain stimulated. Finding those targets is only a matter of time, he predicts. “I’m a believer that everybody can respond once we figure out where their sweet spot is,” he said. And in conditions like depression or OCD, DBS might even offer a functional cure, he added. “It can be profound.”

“You can temporarily modify the functionality of a region of the brain and see how the person behaves. And you can take the same tool and push on those areas over and over again—as in, say, depression treatment—to create an enduring change in the pattern of brain activity,” he said.

Hamilton and other Penn researchers are also exploring transcranial direct current stimulation (tDCS), which similarly uses an external device to deliver electrical signals into the brain, but at a lower intensity. Unlike TMS, which carries a very small risk of seizures, risks associated with tDCS, are “virtually nil,” Hamilton said. It’s more portable and requires less training—a benefit that could make neurostimulation more accessible to more people. Indeed, an at-home tDCS device was recently approved to treat depression.

One drawback of tDCS and most TMS devices, however, is that they can reach only into the outer layers of the brain.

“Penn is a leader in the use of non-invasive, high-intensity ultrasonic therapy,” noted William C. Welch, MD, the Frederick A. Simeone Professor in Neurosurgery and chair of Neurosurgery at Pennsylvania Hospital. “These treatments penetrate deeper structures of the brain without surgery. By focusing the beams, cells that generate abnormal electrical signals can be disabled.”

Focused ultrasound is an increasingly popular treatment for motor symptoms in Parkinson’s disease, Halpern added, because it delivers similar results to DBS without surgery. But because it’s irreversible, it’s best suited to disorders, like Parkinson’s, for which the errant brain regions have been mapped with high precision.

Yet that could soon change. Penn Medicine physician-scientists are working with colleagues in Penn Engineering to develop low-intensity focused ultrasound, which can target deep structures without permanently destroying neurons. The technique holds great promise, but there’s a lot to learn about how best to apply the technology for therapeutic purposes. How many times should patients be treated? Should a single session last 5 minutes, or 55? Charles Palmer, MD, an assistant professor of Neurology dually trained in psychiatry and neurology, aims to answer such basic questions in his lab. “I think focused ultrasound will be the next big thing, but it’s still in very early stages,” Palmer said.

Big-picture brain science

Neuromodulation is an approach that falls at the intersection of expertise in neurosurgery, neurology, and psychiatry. And as it evolves, it is helping to break down the boundaries between those disciplines.

“These distinctions between our subspecialties of the brain are so artificial. Those barriers are breaking in the world of neuromodulation,” Hamilton said. “Neuromodulation is where things get reintegrated and resynthesized.”

Mood symptoms, for example, are common among diagnoses that typically fall within psychiatry—such as depression or PTSD—as well as those traditionally classified as neurological—such as Parkinson’s and Huntington’s disease.

“What’s exciting about neuromodulation and the mapping of brain networks is getting a sense of how these disorders actually interrelate. We can take a step back and think more holistically about brain function,” Hammer said.

That more inclusive view may even be changing the way medicine is practiced—and Penn Medicine is at the forefront of those efforts, working with experts in interventional psychiatry and functional neurosurgery from across the U.S. to create a dedicated neuromodulation subspecialty. The fellowship training program would ensure basic standards are met and trainees receive the same instruction, whatever medical specialty they’ve previously trained in.

Parallel to those efforts, Hamilton created the BrainSTIM Center to serve as a hub for neuromodulation research and education, bringing together researchers and clinicians across Penn Medicine. “It’s a community of faculty and trainees who are united by their interest and passion for neuromodulation,” he said.

As that community continues to push the boundaries of neuromodulation, its efforts are already reshaping what’s possible for patients with severe neurological and psychiatric disorders like Bodeur. Two years after her surgery, her life has done a 180. She’s fallen in love with Pennsylvania, where she relocated permanently to be near her care team, including Scangos, who she sees every three months to fine-tune the settings on her DBS device. She lives on her own in a bright, art-filled space, and is close to completing a degree in graphic design.

“I tried so many things. [Without this trial,] I don’t think I would have been given a chance to ever get better,” she said. “I’m so grateful.”