A generalized epilepsy network derived from brain abnormalities and deep brain stimulation
Idiopathic generalized epilepsy (IGE) is a brain network disease, but the location of this network and its relevance for treatment remain unclear. We combine the locations of brain abnormalities in IGE (131 coordinates from 21 studies) with the human connectome to identify an IGE network. We validate this network by showing alignment with structural brain abnormalities previously identified in IGE and brain areas activated by generalized epileptiform discharges in simultaneous electroencephalogram-functional magnetic resonance imaging. The topography of the IGE network aligns with brain networks involved in motor control and loss of consciousness consistent with generalized seizure semiology. To investigate therapeutic relevance, we analyze data from 21 patients with IGE treated with deep brain stimulation (DBS) for generalized seizures. Seizure frequency reduced a median 90% after DBS and stimulation sites intersect an IGE network peak in the centromedian nucleus of the thalamus. Together, this study helps unify prior findings in IGE and identify a brain network target that can be tested in clinical trials of brain stimulation to control generalized seizures.
Authors
- Clemens Neudorfer (ORCID: https://orcid.org/0000-0002-3153-1045)
- Xingui Chen (ORCID: https://orcid.org/0000-0001-8861-8101)
- Aaron E. L. Warren (ORCID: https://orcid.org/0000-0001-6534-2800)
- Zhiqiang Zhang (ORCID: https://orcid.org/0000-0002-3993-7330)
- Gabriel González‐Escamilla (ORCID: https://orcid.org/0000-0002-7209-1736)
- Antonio Valentı́n (ORCID: https://orcid.org/0000-0003-0449-5234)
- Faiçal Isbaine (ORCID: https://orcid.org/0000-0002-4159-420X)
- Sergiu Groppa (ORCID: https://orcid.org/0000-0002-2551-5655)
- John S. Archer (ORCID: https://orcid.org/0000-0002-3939-3847)
- Gong‐Jun Ji (ORCID: https://orcid.org/0000-0002-7073-5534)
- Nico U.F. Dosenbach (ORCID: https://orcid.org/0000-0002-6876-7078)
- Sihyeong Park (ORCID: https://orcid.org/0000-0002-6371-265X)
- Arthur Cukiert (ORCID: https://orcid.org/0000-0002-6563-4149)
- Jimmy C. Yang (ORCID: https://orcid.org/0000-0003-1995-5926)
- Erik H. Middlebrooks (ORCID: https://orcid.org/0000-0002-4418-9605)
- Janne Nordberg (ORCID: https://orcid.org/0000-0002-2917-4341)
- Rani A. Sarkis (ORCID: https://orcid.org/0000-0001-8291-7864)
- Nicholas M. Gregg (ORCID: https://orcid.org/0000-0002-6151-043X)
- Haya Akkad (ORCID: https://orcid.org/0000-0002-5621-3318)
- Yanghua Tian (ORCID: https://orcid.org/0000-0001-5038-0599)
- Andreas Horn (ORCID: https://orcid.org/0000-0002-0695-6025)
- Robert S. Fisher (ORCID: https://orcid.org/0000-0003-0287-613X)
- Ioannis Stavropoulos (ORCID: https://orcid.org/0000-0002-6920-1826)
- Robert E. Gross (ORCID: https://orcid.org/0000-0003-1847-9227)
- Linda J. Dalic (ORCID: https://orcid.org/0000-0001-8335-1348)
- Melissa Chua (ORCID: https://orcid.org/0000-0002-2832-4002)
- Alexander L. Cohen (ORCID: https://orcid.org/0000-0001-6557-5866)
- Sara Larivière (ORCID: https://orcid.org/0000-0001-5701-1307)
- John D. Rolston (ORCID: https://orcid.org/0000-0002-8843-5468)
- Yingru Wang (ORCID: https://orcid.org/0000-0002-0725-9571)
- María de Toledo (ORCID: https://orcid.org/0000-0003-0447-3422)
- Frédéric Schaper (ORCID: https://orcid.org/0000-0001-5487-0923)
- Juho Joutsa (ORCID: https://orcid.org/0000-0002-3457-9415)
- Cristina V. Torres (ORCID: https://orcid.org/0000-0002-3420-0786)
- Jinmei Sun (ORCID: https://orcid.org/0000-0002-8397-9773)
- Ellen J. Bubrick (ORCID: https://orcid.org/0000-0003-1949-1180)
- Richard Selway
- Michael Fox (ORCID: https://orcid.org/0000-0001-8848-6399)
- Mae Morton-Dutton
- Kai Wang (ORCID: https://orcid.org/0000-0002-6197-914X)
- Panpan Hu (ORCID: https://orcid.org/0000-0002-1683-2739)
- Chunyan Zhu (ORCID: https://orcid.org/0000-0002-3434-2581)
- Joseph I. Turner
- Yubao Jiang
Institutions
- Rutgers, The State University of New Jersey (US)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- University of Liverpool (GB)
- Emory University (US)
- University of Turku (FI)
- The University of Melbourne (AU)
- Queen Mary University of London (GB)
- King's College London (GB)
- Johannes Gutenberg University Mainz (DE)
- Anhui Medical University (CN)
- Washington University in St. Louis (US)
- Nanjing General Hospital of Nanjing Military Command (CN)
- Turku University Hospital (FI)
- Johnson University (US)
- WinnMed (US)
- Massachusetts General Hospital (US)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Alder Hey Children's NHS Foundation Trust (GB)
- Circuit Therapeutics (United States) (US)
- Mallinckrodt (United States) (US)
- Center for Neuro-Oncology (US)
- King's College Hospital NHS Foundation Trust (GB)
- Anhui Transport Consulting & Design Institute (China) (CN)
- Mayo Clinic in Arizona (US)
- Hospital Universitario de La Princesa (ES)
- First Affiliated Hospital of Anhui Medical University (CN)
- National Science Centre (PL)
- Mayo Clinic in Florida (US)
- Second Affiliated Hospital of Anhui Medical University (CN)
- Anhui Mental Health Center (CN)
- Alder Hey Children's Hospital (GB)
- Neurological Surgery (US)
- Austin Health (AU)
- University College London (GB)
- The Ohio State University (US)
- Southern Medical University (CN)
- Universidad Autónoma de Madrid (ES)
- Stanford University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-03-24
- DOI
- https://doi.org/10.1038/s41467-025-57392-7
- Citations
- 16
- Primary Topic
- Functional Brain Connectivity Studies
- Type
- article
- Field-Weighted Citation Impact
- 22.90