A generalized epilepsy network derived from brain abnormalities and deep brain stimulation

Gong-Jun Ji, Michael D. Fox, Mae Morton-Dutton, Yingru Wang, Jinmei Sun, Panpan Hu, Xingui Chen, Yubao Jiang, Chunyan Zhu, Yanghua Tian, Zhiqiang Zhang, Haya Akkad, Janne Nordberg, Juho Joutsa, Cristina V. Torres Diaz, Sergiu Groppa, Gabriel Gonzalez-Escamilla, Maria de Toledo, Linda J. Dalic, John S. Archer, Richard Selway, Ioannis Stavropoulos, Antonio Valentin, Jimmy Yang, Faical Isbaine, Robert E. Gross, Sihyeong Park, Nicholas M. Gregg, Arthur Cukiert, Erik H. Middlebrooks, Nico U. F. Dosenbach, 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, Robert S. Fisher, John D. Rolston, Kai Wang () and Frederic L. W. V. J. Schaper ()
Additional contact information
Gong-Jun Ji: The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
Michael D. Fox: Harvard Medical School
Mae Morton-Dutton: Harvard Medical School
Yingru Wang: Anhui Medical University
Jinmei Sun: The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
Panpan Hu: The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
Xingui Chen: The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
Yubao Jiang: The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
Chunyan Zhu: Anhui Medical University
Yanghua Tian: The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University
Zhiqiang Zhang: Southern Medical University
Haya Akkad: Harvard Medical School
Janne Nordberg: Turku University Hospital
Juho Joutsa: Turku University Hospital
Cristina V. Torres Diaz: Universidad Autónoma de Madrid
Sergiu Groppa: Rhine Main Neuroscience Network (rmn2)
Gabriel Gonzalez-Escamilla: Rhine Main Neuroscience Network (rmn2)
Maria de Toledo: Universidad Autónoma de Madrid
Linda J. Dalic: The University of Melbourne
John S. Archer: Harvard Medical School
Richard Selway: King’s College Hospital NHS Foundation Trust
Ioannis Stavropoulos: Psychology and Neuroscience
Antonio Valentin: Psychology and Neuroscience
Jimmy Yang: The Ohio State University College of Medicine
Faical Isbaine: Emory University School of Medicine
Robert E. Gross: Rutgers University
Sihyeong Park: Mayo Clinic
Nicholas M. Gregg: Mayo Clinic
Arthur Cukiert: Department of Neurosurgery
Erik H. Middlebrooks: Mayo Clinic
Nico U. F. Dosenbach: Washington University School of Medicine
Joseph Turner: Harvard Medical School
Aaron E. L. Warren: Harvard Medical School
Melissa M. J. Chua: Harvard Medical School
Alexander L. Cohen: Harvard Medical School
Sara Larivière: Harvard Medical School
Clemens Neudorfer: Harvard Medical School
Andreas Horn: Harvard Medical School
Rani A. Sarkis: Harvard Medical School
Ellen J. Bubrick: Harvard Medical School
Robert S. Fisher: Palo Alto
John D. Rolston: Harvard Medical School
Kai Wang: The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
Frederic L. W. V. J. Schaper: Harvard Medical School

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-57392-7

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