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

G Gong-Jun Ji M Michael D. Fox M Mae Morton-Dutton Y Yingru Wang J Jinmei Sun P Panpan Hu X Xingui Chen Y Yubao Jiang C Chunyan Zhu (Frontiers Science Center for New Organic Matter, Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), State Key Laboratory of Advanced Chemical Power Sources, College of Chemistry) Y Yanghua Tian Z Zhiqiang Zhang H Haya Akkad J Janne Nordberg J Juho Joutsa C Cristina V. Torres Diaz S Sergiu Groppa G Gabriel Gonzalez-Escamilla M Maria de Toledo L Linda J. Dalic J John S. Archer R Richard Selway I Ioannis Stavropoulos A Antonio Valentin J Jimmy Yang F Faical Isbaine R Robert E. Gross S Sihyeong Park N Nicholas M. Gregg (Department of Neurology, Mayo Clinic) A Arthur Cukiert E Erik H. Middlebrooks N Nico U. F. Dosenbach J Joseph Turner A Aaron E. L. Warren M Melissa M. J. Chua A Alexander L. Cohen S Sara Larivière C Clemens Neudorfer (Center for Brain Circuit Therapeutics, Department of Neurology, Brigham & Women’s Hospital, Harvard Medical School) A Andreas Horn R Rani A. Sarkis E Ellen J. Bubrick R Robert S. Fisher J John D. Rolston K Kai Wang F Frederic L. W. V. J. Schaper

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.

Article Details

Volume / Issue Vol. 16, Issue 1
Published March 24, 2025
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (44)

G

Gong-Jun Ji

M

Michael D. Fox

M

Mae Morton-Dutton

Y

Yingru Wang

J

Jinmei Sun

P

Panpan Hu

X

Xingui Chen

Y

Yubao Jiang

C

Chunyan Zhu

Frontiers Science Center for New Organic Matter, Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), State Key Laboratory of Advanced Chemical Power Sources, College of Chemistry

Y

Yanghua Tian

Z

Zhiqiang Zhang

H

Haya Akkad

J

Janne Nordberg

J

Juho Joutsa

C

Cristina V. Torres Diaz

S

Sergiu Groppa

G

Gabriel Gonzalez-Escamilla

M

Maria de Toledo

L

Linda J. Dalic

J

John S. Archer

R

Richard Selway

I

Ioannis Stavropoulos

A

Antonio Valentin

J

Jimmy Yang

F

Faical Isbaine

R

Robert E. Gross

S

Sihyeong Park

N

Nicholas M. Gregg

Department of Neurology, Mayo Clinic

A

Arthur Cukiert

E

Erik H. Middlebrooks

N

Nico U. F. Dosenbach

J

Joseph Turner

A

Aaron E. L. Warren

M

Melissa M. J. Chua

A

Alexander L. Cohen

S

Sara Larivière

C

Clemens Neudorfer

Center for Brain Circuit Therapeutics, Department of Neurology, Brigham & Women’s Hospital, Harvard Medical School

A

Andreas Horn

R

Rani A. Sarkis

E

Ellen J. Bubrick

R

Robert S. Fisher

J

John D. Rolston

K

Kai Wang

F

Frederic L. W. V. J. Schaper