Research spotlight: A generalized epilepsy network derived from brain abnormalities and deep brain stimulation

(Press-News.org) Frederic L.W.V.J. Schaper, MD, PhD, director of Epilepsy Network Mapping at the Center for Brain Circuit Therapeutics at Brigham and Women’s Hospital and an instructor of neurology at Harvard Medical School, is the senior author of a paper published in Nature Communications, “A generalized epilepsy network derived from brain abnormalities and deep brain stimulation.”

How would you summarize your study for a lay audience?

Generalized epilepsy has traditionally been considered a seizure of the ‘whole brain.’ However, new research has challenged this longstanding idea, since carefully targeting specific brain areas through deep brain stimulation (DBS) can help reduce generalized seizures. Generalized epilepsy is now increasingly recognized as a brain network disease, but the location of this network and its potential therapeutic role remain unidentified.

In this study, we identified a generalized epilepsy network using locations of subtle brain abnormalities and DBS, a promising surgical treatment option for patients with severe generalized seizures that cannot be helped with antiseizure drugs alone.

What question were you investigating?

We were fascinated by a paradox between classical clinical teaching and results from recent large brain imaging studies in generalized epilepsy.

Clinical experience teaches us that the brain MRI of patients with idiopathic generalized epilepsy is ‘normal,’ while research studies have shown that subtle brain abnormalities can be identified when compared to a healthy person’s brain. These subtle brain abnormalities, also called cortical atrophy, are typically considered harmless.

However, we believed these brain abnormalities could give us crucial clues about where the generalized seizure starts or travels to in the brain.

At first, these spots seemed scattered all over without any clear pattern. After collecting all published studies on the topic, suddenly a pattern seemed to emerge, and we asked ourselves the question: could these abnormalities map to a brain network?

What methods or approach did you use?

Using methods developed at the Center for Brain Circuit Therapeutics, we combined the locations of cortical atrophy in patients with idiopathic generalized seizures with a ‘wiring diagram’ of the human brain, also called a connectome.

With the help of this connectome, we identified the brain network connected to cortical atrophy locations in patients with idiopathic generalized epilepsy.

What did you find?

We found these subtle brain abnormalities map to a common brain network that generalized seizures seem to ‘hijack.’ Serendipitously, a peak of this circuit is located exactly in the region where neurosurgeons place their DBS electrodes to treat generalized seizures (i.e. the centromedian thalamus).

These findings could therefore help explain why DBS of this region is effective in alleviating generalized seizures in some patients. Moreover, our results point to a circuit target that could potentially improve DBS and help design new non-invasive brain stimulation treatments for generalized seizures.
 
What are the next steps?

Clinically, next steps include testing whether this generalized epilepsy network could be used to guide current or develop new brain stimulation therapies for patients. Clinical trials will need to be designed and carried out to assess safety and efficacy.

On the research side, we are looking to externally validate these results and dig deeper using patient-specific data. The current study was a meta-analysis of published locations of brain atrophy which has inherent limitations. A lot remains unknown. Is this network the same for patients with different generalized seizure types? How can we best target this network? Is it safe to modulate this network and will it result in better outcomes?

We are always searching for collaborators to work with us on answering any of these questions and to move closer to our overarching goal to improve the treatment of patient with epilepsy by identifying and modulating brain circuits.

Authorship: In addition to Schaper, Mass General Brigham authors include Michael D. Fox, Mae Morton-Dutton, Joseph Turner, Aaron E.L. Warren, Melissa M.J. Chua, Alexander L. Cohen, Sara Larivière, Clemens Neudorfer, Andreas Horn, Rani A. Sarkis, Ellen J. Bubrick, and John D. Rolston.

Paper cited: Ji, G et al. “A generalized epilepsy network derived from brain abnormalities and deep brain stimulation” Nature Communications DOI: 10.1038/s41467-025-57392-7

Funding: American Epilepsy Society, National Institutes of Health

Disclosures: Fox serves as inventor on an active patent (US010137307B2) by Beth Israel Deaconess Medical Center that covers use of brain connectivity imaging to guide brain stimulation issued with no royalties and an active patent (US11666219B2) by Beth Israel Deaconess Medical Center that covers lesion network mapping issued with no royalties.

END