Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression
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Published:2022-07-27
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Larivière SaraORCID, Royer JessicaORCID, Rodríguez-Cruces RaúlORCID, Paquola Casey, Caligiuri Maria Eugenia, Gambardella AntonioORCID, Concha LuisORCID, Keller Simon S., Cendes Fernando, Yasuda Clarissa L.ORCID, Bonilha LeonardoORCID, Gleichgerrcht Ezequiel, Focke Niels K.ORCID, Domin MartinORCID, von Podewills Felix, Langner Soenke, Rummel Christian, Wiest RolandORCID, Martin Pascal, Kotikalapudi Raviteja, O’Brien Terence J., Sinclair Benjamin, Vivash Lucy, Desmond Patricia M., Lui Elaine, Vaudano Anna Elisabetta, Meletti Stefano, Tondelli Manuela, Alhusaini Saud, Doherty Colin P., Cavalleri Gianpiero L., Delanty Norman, Kälviäinen Reetta, Jackson Graeme D., Kowalczyk Magdalena, Mascalchi Mario, Semmelroch Mira, Thomas Rhys H., Soltanian-Zadeh HamidORCID, Davoodi-Bojd Esmaeil, Zhang Junsong, Winston Gavin P., Griffin AoifeORCID, Singh Aditi, Tiwari Vijay K.ORCID, Kreilkamp Barbara A. K., Lenge MatteoORCID, Guerrini Renzo, Hamandi Khalid, Foley SonyaORCID, Rüber TheodorORCID, Weber Bernd, Depondt Chantal, Absil Julie, Carr Sarah J. A., Abela Eugenio, Richardson Mark P., Devinsky OrrinORCID, Severino Mariasavina, Striano PasqualeORCID, Tortora Domenico, Kaestner Erik, Hatton Sean N.ORCID, Vos Sjoerd B.ORCID, Caciagli Lorenzo, Duncan John S.ORCID, Whelan Christopher D., Thompson Paul M., Sisodiya Sanjay M., Bernasconi Andrea, Labate AngeloORCID, McDonald Carrie R., Bernasconi Neda, Bernhardt Boris C.ORCID
Abstract
AbstractEpilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.
Funder
Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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