2 weeks Ago
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.
Frederic L.W.V.
J. Schaper, MD, Ph.D.
, 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 titled "A generalized epilepsy network derived from brain abnormalities and deep brain stimulation ." In the study, the researchers 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. The team were fascinated by a paradox between classical clinical teaching and results from recent large brain imaging studies in generalized epilepsy.
Clinical experience shows 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, the team believed these brain abnormalities could give 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 the published studies on the topic, suddenly a pattern seemed to emerge, and the team asked themselves the question: could these abnormalities map to a brain network? Using methods developed at the Center for Brain Circuit Therapeutics, the researchers 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, they identified the brain network connected to cortical atrophy locations in patients with idiopathic generalized epilepsy.
The team 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, the results point to a circuit target that could potentially improve DBS and help design new noninvasive brain stimulation treatments for generalized seizures.
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, the team is 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? More information: Ji, G et al.
A generalized epilepsy network derived from brain abnormalities and deep brain stimulation, Nature Communications (2025). DOI: 10.1038/s41467-025-57392-7.
