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

Author

Listed:
  • Gong-Jun Ji

    (The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
    The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University
    Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders
    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
    Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders)

  • Panpan Hu

    (The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
    Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders)

  • Xingui Chen

    (The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
    Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders)

  • Yubao Jiang

    (The First Affiliated Hospital of Anhui Medical University, Anhui Medical University
    Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders)

  • Chunyan Zhu

    (Anhui Medical University)

  • Yanghua Tian

    (The Second Affiliated Hospital of Anhui Medical University, Anhui Medical University
    Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders
    Anhui Medical University)

  • Zhiqiang Zhang

    (Southern Medical University)

  • Haya Akkad

    (Harvard Medical School
    University College London)

  • Janne Nordberg

    (Turku University Hospital
    University of Turku)

  • Juho Joutsa

    (Turku University Hospital
    University of Turku)

  • 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
    King’s College Hospital NHS Foundation Trust)

  • Antonio Valentin

    (Psychology and Neuroscience
    King’s College Hospital NHS Foundation Trust
    Alder Hey Children’s Hospital Trust)

  • Jimmy Yang

    (The Ohio State University College of Medicine
    Suite B6200)

  • 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
    Washington University School of Medicine
    Washington University in St. Louis)

  • 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
    Harvard Medical School)

  • Sara Larivière

    (Harvard Medical School)

  • Clemens Neudorfer

    (Harvard Medical School
    Harvard Medical School)

  • Andreas Horn

    (Harvard Medical School
    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
    Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders
    Anhui Medical University
    Anhui Institute of Translational Medicine)

  • Frederic L. W. V. J. Schaper

    (Harvard Medical School)

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.

Suggested Citation

  • 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 J, 2025. "A generalized epilepsy network derived from brain abnormalities and deep brain stimulation," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57392-7
    DOI: 10.1038/s41467-025-57392-7
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    References listed on IDEAS

    as
    1. Guo Bin & Tianfu Wang & Hongwu Zeng & Xiaoming He & Feng Li & Jian Zhang & Bingsheng Huang, 2017. "Patterns of Gray Matter Abnormalities in Idiopathic Generalized Epilepsy: A Meta-Analysis of Voxel-Based Morphology Studies," PLOS ONE, Public Library of Science, vol. 12(1), pages 1-11, January.
    2. Shan H. Siddiqi & Frederic L. W. V. J. Schaper & Andreas Horn & Joey Hsu & Jaya L. Padmanabhan & Amy Brodtmann & Robin F. H. Cash & Maurizio Corbetta & Ki Sueng Choi & Darin D. Dougherty & Natalia Ego, 2021. "Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease," Nature Human Behaviour, Nature, vol. 5(12), pages 1707-1716, December.
    3. Joseph J. Taylor & Christopher Lin & Daniel Talmasov & Michael A. Ferguson & Frederic L. W. V. J. Schaper & Jing Jiang & Madeleine Goodkind & Jordan Grafman & Amit Etkin & Shan H. Siddiqi & Michael D., 2023. "A transdiagnostic network for psychiatric illness derived from atrophy and lesions," Nature Human Behaviour, Nature, vol. 7(3), pages 420-429, March.
    4. Evan M. Gordon & Roselyne J. Chauvin & Andrew N. Van & Aishwarya Rajesh & Ashley Nielsen & Dillan J. Newbold & Charles J. Lynch & Nicole A. Seider & Samuel R. Krimmel & Kristen M. Scheidter & Julia Mo, 2023. "A somato-cognitive action network alternates with effector regions in motor cortex," Nature, Nature, vol. 617(7960), pages 351-359, May.
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