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; Frederic L.W.V.J. Schaper

doi:10.1038/s41467-025-57392-7

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. ArcherRichard 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^*, Frederic L.W.V.J. Schaper^*

^*Corresponding author for this work

Basic and Clinical Neuroscience

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	2783
Journal	Nature communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-57392-7
Publication status	Published - Dec 2025

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Ji, G. J., Fox, M. D., Morton-Dutton, M., Wang, Y., Sun, J., Hu, P., Chen, X., Jiang, Y., Zhu, C., Tian, Y., Zhang, Z., Akkad, H., Nordberg, J., Joutsa, J., Torres Diaz, C. V., Groppa, S., Gonzalez-Escamilla, G., Toledo, M. D., Dalic, L. J., ... Schaper, F. L. W. V. J. (2025). A generalized epilepsy network derived from brain abnormalities and deep brain stimulation. Nature communications, 16(1), Article 2783. https://doi.org/10.1038/s41467-025-57392-7

@article{6c7772f9561549ee96eb263a4d4c407b,

title = "A generalized epilepsy network derived from brain abnormalities and deep brain stimulation",

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.",

author = "Ji, {Gong Jun} and Fox, {Michael D.} and Mae Morton-Dutton and Yingru Wang and Jinmei Sun and Panpan Hu and Xingui Chen and Yubao Jiang and Chunyan Zhu and Yanghua Tian and Zhiqiang Zhang and Haya Akkad and Janne Nordberg and Juho Joutsa and {Torres Diaz}, {Cristina V.} and Sergiu Groppa and Gabriel Gonzalez-Escamilla and Toledo, {Maria de} and Dalic, {Linda J.} and Archer, {John S.} and Richard Selway and Ioannis Stavropoulos and Antonio Valentin and Jimmy Yang and Faical Isbaine and Gross, {Robert E.} and Sihyeong Park and Gregg, {Nicholas M.} and Arthur Cukiert and Middlebrooks, {Erik H.} and Dosenbach, {Nico U.F.} and Joseph Turner and Warren, {Aaron E.L.} and Chua, {Melissa M.J.} and Cohen, {Alexander L.} and Sara Larivi{\`e}re and Clemens Neudorfer and Andreas Horn and Sarkis, {Rani A.} and Bubrick, {Ellen J.} and Fisher, {Robert S.} and Rolston, {John D.} and Kai Wang and Schaper, {Frederic L.W.V.J.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = dec,

doi = "10.1038/s41467-025-57392-7",

language = "English",

volume = "16",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

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Ji, GJ, Fox, MD, Morton-Dutton, M, Wang, Y, Sun, J, Hu, P, Chen, X, Jiang, Y, Zhu, C, Tian, Y, Zhang, Z, Akkad, H, Nordberg, J, Joutsa, J, Torres Diaz, CV, Groppa, S, Gonzalez-Escamilla, G, Toledo, MD, Dalic, LJ, Archer, JS, Selway, R, Stavropoulos, I , Valentin, A, Yang, J, Isbaine, F, Gross, RE, Park, S, Gregg, NM, Cukiert, A, Middlebrooks, EH, Dosenbach, NUF, Turner, J, Warren, AEL, Chua, MMJ, Cohen, AL, Larivière, S, Neudorfer, C, Horn, A, Sarkis, RA, Bubrick, EJ, Fisher, RS, Rolston, JD, Wang, K & Schaper, FLWVJ 2025, 'A generalized epilepsy network derived from brain abnormalities and deep brain stimulation', Nature communications, vol. 16, no. 1, 2783. https://doi.org/10.1038/s41467-025-57392-7

TY - JOUR

T1 - A generalized epilepsy network derived from brain abnormalities and deep brain stimulation

AU - Ji, Gong Jun

AU - Fox, Michael D.

AU - Morton-Dutton, Mae

AU - Wang, Yingru

AU - Sun, Jinmei

AU - Hu, Panpan

AU - Chen, Xingui

AU - Jiang, Yubao

AU - Zhu, Chunyan

AU - Tian, Yanghua

AU - Zhang, Zhiqiang

AU - Akkad, Haya

AU - Nordberg, Janne

AU - Joutsa, Juho

AU - Torres Diaz, Cristina V.

AU - Groppa, Sergiu

AU - Gonzalez-Escamilla, Gabriel

AU - Toledo, Maria de

AU - Dalic, Linda J.

AU - Archer, John S.

AU - Selway, Richard

AU - Stavropoulos, Ioannis

AU - Valentin, Antonio

AU - Yang, Jimmy

AU - Isbaine, Faical

AU - Gross, Robert E.

AU - Park, Sihyeong

AU - Gregg, Nicholas M.

AU - Cukiert, Arthur

AU - Middlebrooks, Erik H.

AU - Dosenbach, Nico U.F.

AU - Turner, Joseph

AU - Warren, Aaron E.L.

AU - Chua, Melissa M.J.

AU - Cohen, Alexander L.

AU - Larivière, Sara

AU - Neudorfer, Clemens

AU - Horn, Andreas

AU - Sarkis, Rani A.

AU - Bubrick, Ellen J.

AU - Fisher, Robert S.

AU - Rolston, John D.

AU - Wang, Kai

AU - Schaper, Frederic L.W.V.J.

PY - 2025/12

Y1 - 2025/12

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-025-57392-7

DO - 10.1038/s41467-025-57392-7

M3 - Article

AN - SCOPUS:105000715014

SN - 2041-1723

VL - 16

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 2783

ER -

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

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