A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
A generalized epilepsy network derived from brain abnormalities and deep brain stimulation
Tekijät: Ji, Gong-Jun; Fox, Michael D.; Morton-Dutton, Mae; Wang, Yingru; Sun, Jinmei; Hu, Panpan; Chen, Xingui; Jiang, Yubao; Zhu, Chunyan; Tian, Yanghua; Zhang, Zhiqiang; Akkad, Haya; Nordberg, Janne; Joutsa, Juho; Torres Diaz, Cristina V.; Groppa, Sergiu; Gonzalez-Escamilla, Gabriel; Toledo, Maria de; Dalic, Linda J.; Archer, John S.; Selway, Richard; Stavropoulos, Ioannis; Valentin, Antonio; Yang, Jimmy; Isbaine, Faical; Gross, Robert E.; Park, Sihyeong; Gregg, Nicholas M.; Cukiert, Arthur; Middlebrooks, Erik H.; Dosenbach, Nico U. F.; Turner, Joseph; Warren, Aaron E. L.; Chua, Melissa M. J.; Cohen, Alexander L.; Lariviere, Sara; Neudorfer, Clemens; Horn, Andreas; Sarkis, Rani A.; Bubrick, Ellen J.; Fisher, Robert S.; Rolston, John D.; Wang, Kai; Schaper, Frederic L. W. V. J.
Kustantaja: Springer Science and Business Media LLC
Kustannuspaikka: BERLIN
Julkaisuvuosi: 2025
Journal: Nature Communications
Tietokannassa oleva lehden nimi: Nature Communications
Lehden akronyymi: NAT COMMUN
Artikkelin numero: 2783
Vuosikerta: 16
Numero: 1
Sivujen määrä: 15
eISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-025-57392-7
Verkko-osoite: https://doi.org/10.1038/s41467-025-57392-7
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/491573212
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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Julkaisussa olevat rahoitustiedot:
This study was funded by the National Natural Science Foundation of China, Grant Numbers: 82371507 (G.-J.J.), 32071054 (Y.T.), 82090034 (K.W.), U23A20424 (K.W.), and 31970979 (K.W.); the collaborative innovation project between universities and Hefei Comprehensive National Science Center (GXXT-2022-028, G.-J.J.); Hefei comprehensive national science center Hefei brain project (K.W.); Anhui Province Clinical Medical Research Transformation Special Project (202204295107020006 and 202204295107020028 to K.W.); Anhui Province Outstanding Youth Fund (2024AH020004 to G.-J.J.); Anhui province key research and development project (202104j07020033 to K.W.); the Science Fund for Distinguished Young Scholars of Anhui Province (1808085J23); F.L.W.V.J.S was supported by the American Epilepsy Society (846534) and National Institutes of Health (R01NS127892). L.J.D. and J.S.A. were supported by NHMRC project grants #628725 and #1108881, as were the imaging acquisition and prior analysis of DBS data related to LGS. J.D.R. and A.E.L.W. were supported by an NIH/NINDS grant (UH3NS109557A1). A.L.C. was supported by the NIMH (K23MH120510) and the Simons Foundation Autism Research Initiative. S.L. was funded by the Canadian Institutes of Health Research (CIHR) Banting Postdoctoral Fellowship. A.H. was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, 424778381 – TRR 295), Deutsches Zentrum für Luft- und Raumfahrt (DynaSti grant within the EU Joint Program Neurodegenerative Disease Research, JPND), the National Institutes of Health (R01 13478451, 1R01NS127892-01, 2R01 MH113929, and UM1NS132358) as well as the New Venture Fund (FFOR Seed Grant). M.D.F. was supported by grants from the National Institute of Mental Health, the National Institute on Aging, the Ellison-Baszucki Family Foundation, Kaye Family Research Endowment, and Manley family outside the submitted work. Dr. Fisher receives support from NIH UG3NS114438, the James and Carrie Anderson Fund for Epilepsy, The Steve Chen Epilepsy Research Fund, and the Pilliod Research Fund. J.J. receives support from the Finnish Medical Foundation, Sigrid Juselius Foundation, Instrumentarium Research Foundation, and Turku University Hospital (VTR funds). Genomics Superstruct Project (GSP) data were provided (in part) by the Brain Genomics Superstruct Project of Harvard University and Massachusetts General Hospital (principal investigators: Randy Buckner, Joshua Roffman, and Jordan Smoller), with support from the Center for Brain Science Neuroinformatics Research Group, the Athinoula A. Martinos Center for Biomedical Imaging, and the Center for Human Genetic Research. Twenty individual investigators at Harvard University and Massachusetts General Hospital generously contributed data to the overall project. The preprocessed GSP connectome can be found at: https://doi.org/10.7910/DVN/ILXIKS%27, https://doi.org/10.7910/DVN/ILXIKS. Some of the data used in the preparation of this article were obtained from the ABCD study (https://abcdstudy.org), held in the National Institute of Mental Health Data Archive. This is a multisite, longitudinal study designed to recruit more than 10,000 children aged 9–10 years and follow them over 10 years into early adulthood. The ABCD study is supported by the NIH and additional fed- eral partners under award numbers U01DA041048, U01DA050989, U01DA051016, U01DA041022, U01DA051018, U01DA051037, U01DA050987, U01DA041174, U01DA041106, U01DA041117, U01DA041028, U01DA041134, U01DA050988, U01DA051039, U01DA041156, U01DA041025, U01DA041120, U01DA051038, U01DA041148, U01DA041093, U01DA041089, U24DA041123, and U24DA041147. A full list of supporters is available at https://abcdstudy.org/federal-partners.html. A listing of participating sites and a complete listing of the study investigators can be found at https://abcdstudy.org/scientists/ workgroups/. ABCD consortium investigators designed and implemented the study and/or provided data but did not necessarily participate in the analysis or writing of this report. This article reflects the views of the authors and may not reflect the opinions or views of the NIH or ABCD consortium investigators. The ABCD data repository grows and changes over time. The ABCD data used in this report are listed at: https://nda.nih.gov/study.html?id=1054, https://doi.org/10.15154/1520630. A.H. was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, 424778381 – TRR 295), Deutsches Zentrum für Luft- und Raumfahrt (DynaSti grant within the EU Joint Programme Neurodegenerative Disease Research, JPND), the National Institutes of Health (R01 13478451, 1R01NS127892-01, and 2R01 MH113929) as well as the New Venture Fund (FFOR Seed Grant). E.H.M. reports grant funding from Vigil Neuroscience, Inc. and the National Institutes of Health (U01-DK140734).
