Personalized Brain Stimulation Offers New Hope for People with Hard-to-Treat Epilepsy

PITTSBURGH — Doctors and researchers at the University of Pittsburgh and UPMC have developed a new treatment for epilepsy patients who don’t respond to medication and aren’t candidates for surgery. Their approach, published today in Nature Communications, uses deep brain stimulation (DBS) that is tailored to each patient’s unique brain wiring.

Epilepsy affects more than 50 million people worldwide, and about a third of those do not respond to medication. For some, seizures are generated in parts of the brain that control essential functions – speech, movement or vision – that can’t be safely removed. Brain “pacemakers,” which send small electrical pulses into the center part of the brain called the thalamus, have helped some patients, but have had minimal effect on others.

“The existing FDA-cleared therapy targets only one portion of the thalamus, the anterior nucleus,” said lead author Arianna Damiani, M.Sc., a graduate student researcher at Pitt’s Rehab Neural Engineering Laboratories (RNEL). “We hypothesized that electrical stimulation of the brain would be more effective if we could target the specific area of the thalamus most strongly connected to the seizing areas of the cerebral cortex.”

The research team, whose members are physicians, neuroscientists and bioengineers, created detailed maps of the seizure activity of 41 patients with drug-resistant epilepsy. Using advanced imaging and brain recordings, researchers elucidated the brain connections between seizure-prone regions of patients’ cerebral cortex, the outermost layer of their brain, and various locations on the thalamus, a deep cerebral structure located in the topographic center of the head.

When the team electrically stimulated the area of the thalamus best matched with seizure activity in the cerebral cortex, patients experienced a dramatic decrease in the number and severity of seizures. In a group of patients who received long-term implants, those with personalized targeting had an average seizure reduction of nearly 90%. Some became seizure-free for months at a time.

“This is a major step toward making brain stimulation more effective for people with treatment-resistant epilepsy,” said Damiani. “This isn’t just a treatment, this is your treatment.”

This study was unique in that it combined multiple techniques – electrical stimulation, imaging and clinical assessment – within the same patient cohort. Prior research has largely focused on only one aspect.

“The epilepsy monitoring unit at UPMC Presbyterian is like few others in the world,” said coauthor Jorge Gonzalez-Martinez, M.D., Ph.D., UPMC neurosurgeon and director of the epilepsy surgery service. “This technology allowed us to create a novel framework for collecting and analyzing data that ultimately resulted in hyper-personalized treatments for our patients. The combination of high clinical expertise with cutting edge science is what makes significant clinical advancements possible.”

In the past, the Pitt/UPMC team has used thalamus-targeting DBS to restore arm mobility in patients with partial paralysis due to traumatic brain injury and stroke. Researchers think that this precise targeting approach could potentially be used to treat other conditions, including psychiatric disorders, such as depression or addiction. 

“We’re understanding more and more about the common mechanisms underlying many conditions that originate in the brain,” said co-senior author Elvira Pirondini, Ph.D., also with RNEL. “With both stroke and epilepsy, we targeted an area deep in the brain that is connected to the motor cortex. The difference was whether we wanted to potentiate activity or suppress it.”

Additional co-authors include Sirisha Nouduri, Jonathan C. Ho, M.D., Steve Salazar, Aude Jegou, Jiahao Jay Chen, Eliza Reedy, Naoki Ikegaya, and Thandar Aung, M.D., all of Pitt, and Sridevi Sarma, Ph.D., of Johns Hopkins University.

This research received financial support from National Institutes of Health grants 1R01NS122927-01A1 and 1R01NS131428-01A1.

PHOTO DETAILS: click images for high-res versions

Top left

Caption: Arianna Damiani, M.Sc., a graduate student researcher at the University of Pittsburgh Rehab Neural Engineering Laboratories

Credit: Arianna Damiani

Right

Caption: Jorge Gonzalez-Martinez, M.D., Ph.D., UPMC neurosurgeon and director of the epilepsy surgery service.

Credit: UPMC

Bottom left

Caption: Elvira Pirondini, Ph.D., assistant professor, University of Pittsburgh Rehab Neural Engineering Laboratories

Credit: UPMC