Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression

• Type of Material: Article
• Authors: Sara Lariviere, McGill University; Jessica Royer, McGill University; Raúl Rodriguez-Cruces, McGill University; Casey Paquola, Forschungszentrum Julich; Maria Eugenia Caligiuri, Magna Graecia University of Catanzaro; Antonio Gambardella, Magna Graecia University of Catanzaro; Luis Concha, Universidad Nacional Autónoma de México; Simon S Keller, University of Liverpool; Fernando Cendes, University of Campinas–UNICAMP; Clarissa L Yasuda, University of Campinas–UNICAMP; Leonardo Bonilha, Emory University; Ezequiel Gleichgerrcht, Medical University of South Carolina; Niels K Focke, University of Medicine Göttingen; Marrtin Domin, University Medicine Greifswald; Flexis von Podewills, University Medicine Greifswald; Soenke Langner, University Medicine Greifswald; Christian Rummel, University Hospital of Bern; Roland Wiest, University Hospital of Bern; Pascal Martin, University of Tübingen; Raviteja Kotikalapudi, University of Tübingen; Terence J O'Brien, Monash University; Benjamin Sinclair, Monash University; Lucy Vivash, Monash University; Paticia M Desmond, University of Melbourne; Elaine Lui, University of Melbourne; Anna Elisabeth Vaudano, Azienda Ospedaliera-Universitaria; Stefano Meletti, Azienda Ospedaliera-Universitaria; Manuela Tondelli, University of Modena and Reggio Emilia; Saud Alhusaini, The Royal College of Surgeons in Ireland; Colin P Doherty, St James Hospital; Gianpiero L Cavalleri, The Royal College of Surgeons in Ireland; Norman Delanty, The Royal College of Surgeons in Ireland; Reetta Kälviäinen, Kuopio University Hospital; Graeme aD Jackson, University of Melbourne; Magdalena Kowalczyk, University of Melbourne; Mario Mascalchi, University of Florence; Mira Semmelroch, University of Melbourne; Rhys H Thomas, Newcastle University; Hamid Soltanian-Zadeh, University of Tehran; Esmaeil Davoodi-Bojd, Henry Ford Health System; Junsong Zhang, Xiamen University; Gavin P Winston, Queens University; Aoife Griffin, Queens University Belfast; Aditi Singh, Queens University Belfast; Vijay K Tiwari, Queens University Belfast; Barbara AK Kreilkamp, University of Medicine Göttingen; Matteo Lenge, University of Florence; Renzo Guerrini, University of Florence; Khalid Hamandi, University Hospital of Whales; Sonya Foley, Cardiff University; Theodor Ruber, University of Bonn; Bernd Weber, University Hospital Bonn; Chantal Depondt, Université Libre de Bruxelles; Julie Absil, Université Libre de Bruxelles; Sarah JA Carr, King’s College London; Eugenio Abela, King’s College London; Mark P Richardson, King’s College London; Orrin Devinsky, NYU GrossmanSch Med; Mariasavina Severino, IRCCS Istituto Giannina Gaslini; Pasquale Striano, IRCCS Istituto Giannina Gaslini; Domenico Tortora, University of Genoa; Erik Kaestner, University of California San Diego; Sean N Hatton, University of California San Diego; Sjoerd B Vos, UCL Institute of Neurology; Lorenzo Caciagli, UCL Institute of Neurology; John S Duncan, UCL Institute of Neurology; Christopher D Whelan, The Royal College of Surgeons in Ireland; Paul M Thompson, University of Southern California; Sanjay M Sisodiya, UCL Institute of Neurology; Andrea Bernasconi, McGill University; Angelo Labate, University of Messina; Carrie R McDonald, University of California San Diego; Neda Bernasconi, McGill University; Boris C Bernhardt, McGill University
• Language: English
• Date: 2022-07-27
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-022-31730-5
• Title of Journal or Parent Work: NATURE COMMUNICATIONS
• Volume: 13
• Issue: 1
• Start Page: 4320
• End Page: 4320
• Grant/Funding Information: P.M.T. is funded in part by a research grant from Biogen, Inc. for work unrelated to the current manuscript.
• Keywords: TEMPORAL-LOBE EPILEPSY; COVARIANCE; GRAPH-THEORETICAL ANALYSIS; COMMON EPILEPSIES; ABNORMALITIES; Multidisciplinary Sciences; MATTER LOSS; ILAE COMMISSION; CORTICAL THICKNESS; Science & Technology; CEREBRAL-CORTEX; Science & Technology - Other Topics; ABERRANT TOPOLOGICAL PATTERNS
• Research Categories: Health Sciences, Mental Health; Health Sciences, Medicine and Surgery; Health Sciences, Radiology

Abstract

Epilepsy 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.