Casey Halpern uses science and surgery to address mental health—starting with cravings

The associate professor of neurosurgery at the Perelman School of Medicine has found that deep brain stimulation senses craving and upcoming loss of control in brain cells and delivers stimulation to restore the stop signal that patients need.

Binge eating disorder is most common eating disorder and is associated with people frequently losing control over their eating. But it’s not hunger that drives them; it’s the craving. And, similar to other compulsions, they can’t stop.

A Penn Medicine study made national headlines recently, showing early promise that what the brain can’t self-regulate in loss of control while eating, smart deep brain stimulation (DBS) can.

“The DBS is smart,” says Casey Halpern, an associate professor of neurosurgery at the Perelman School of Medicine and director of Stereotactic and Functional Neurosurgery at Pennsylvania Hospital. “It senses the craving and upcoming loss of control and then delivers the stimulation at those most vulnerable times.”

Casey Halpern.
Casey Halpern, associate professor of neurosurgery at the Perelman School of Medicine. (Image: Courtesy of Penn Medicine News)

Halpern has focused his career on neurological research since he was an undergraduate at Penn, throughout medical school at Penn Medicine, and as a neurosurgical resident at the Hospital of the University of Pennsylvania. His decision to focus on image-guided neurosurgery stems from the first DBS he saw, which eliminated the tremors in a patient with Parkinson’s disease. In DBS—which Halpern describes as a “pacemaker for the brain”—electrodes are implanted in specific regions of the brain where the uncontrolled behavior is located. In this case, the electrodes disrupted the tremor-related signal. When Halpern observed the surgery, he watched as the stimulator turn on and the tremor “just disappeared,” he recalls.

“The patient did so well I never wanted to do anything else,” Halpern says.

Halpern knew early on that he wanted to apply DBS to diseases beyond Parkinson’s and other neurologic disorders. Obesity and related disorders became his focus.

There wasn’t yet enough preclinical evidence to justify doing these kinds of studies in human trials back in 2007. However, Halpern discovered a research lab on the Penn campus, led by Tracy Bale, formerly at Penn, that was using animal models to study binge-eating behavior and reached out. In 2020, Halpern received FDA approval to proceed with the first clinical trial on humans using DBS to control loss-of-control eating. The implanted electrodes sensed signals that predicted a binge; neutral pictures got no reaction. The electrodes then stimulated the lit-up areas in the nucleus accumbens, disrupting the craving-related signals. “That gave us the confidence that we were in the part of the brain we wanted to modulate, and that led to success in this early clinical trial,” he says.

He hopes to expand his research beyond obesity disorders, to other forms of compulsive behavior that occur in the nucleus accumbens. “The dysregulation of the dopamine system seen in obsessive compulsive disorder [OCD] and in addiction also converge in that region of the brain.”

He is also working with researchers from neurology, psychiatry and engineering to develop noninvasive strategies to control these behaviors. They have been able to detect the same signal predicting a craving on the scalp, which may help develop methods that don’t require brain surgery to intervene. One such possibility may be to use transcranial magnetic stimulation, which has already been approved for depression and OCD.

This story is by Sally Sapega. Read more at Penn Medicine News.