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

Author

Listed:
  • Sara Larivière

    (McGill University)

  • Jessica Royer

    (McGill University)

  • Raúl Rodríguez-Cruces

    (McGill University)

  • Casey Paquola

    (Forschungszentrum Jülich)

  • Maria Eugenia Caligiuri

    (University Magna Græcia)

  • Antonio Gambardella

    (University Magna Græcia
    University Magna Græcia)

  • Luis Concha

    (Universidad Nacional Autónoma de México)

  • Simon S. Keller

    (University of Liverpool
    Walton Centre NHS Foundation Trust)

  • Fernando Cendes

    (University of Campinas–UNICAMP, Campinas)

  • Clarissa L. Yasuda

    (University of Campinas–UNICAMP, Campinas)

  • Leonardo Bonilha

    (Emory University)

  • Ezequiel Gleichgerrcht

    (Medical University of South Carolina)

  • Niels K. Focke

    (University of Medicine Göttingen)

  • Martin Domin

    (Functional Imaging Unit, University Medicine Greifswald)

  • Felix Podewills

    (University Medicine Greifswald)

  • Soenke Langner

    (University Medicine Greifswald)

  • Christian Rummel

    (University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern)

  • Roland Wiest

    (University Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern)

  • Pascal Martin

    (Hertie Institute for Clinical Brain Research, University of Tübingen)

  • Raviteja Kotikalapudi

    (Hertie Institute for Clinical Brain Research, University of Tübingen)

  • Terence J. O’Brien

    (Monash University, Melbourne
    The University of Melbourne)

  • Benjamin Sinclair

    (Monash University, Melbourne
    The University of Melbourne)

  • Lucy Vivash

    (Monash University, Melbourne
    The University of Melbourne)

  • Patricia M. Desmond

    (The University of Melbourne)

  • Elaine Lui

    (The University of Melbourne)

  • Anna Elisabetta Vaudano

    (Azienda Ospedaliera-Universitaria
    University of Modena and Reggio Emilia)

  • Stefano Meletti

    (Azienda Ospedaliera-Universitaria
    University of Modena and Reggio Emilia)

  • Manuela Tondelli

    (University of Modena and Reggio Emilia
    Azienda Sanitaria Locale di Modena)

  • Saud Alhusaini

    (The Royal College of Surgeons in Ireland
    Yale University School of Medicine)

  • Colin P. Doherty

    (St James’ Hospital
    FutureNeuro SFI Research Centre)

  • Gianpiero L. Cavalleri

    (The Royal College of Surgeons in Ireland
    FutureNeuro SFI Research Centre)

  • Norman Delanty

    (The Royal College of Surgeons in Ireland
    FutureNeuro SFI Research Centre)

  • Reetta Kälviäinen

    (Kuopio University Hospital, Member of the European Reference Network for Rare and Complex Epilepsies EpiCARE
    University of Eastern Finland)

  • Graeme D. 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
    Henry Ford Health System)

  • Esmaeil Davoodi-Bojd

    (Henry Ford Health System)

  • Junsong Zhang

    (Xiamen University)

  • Gavin P. Winston

    (Queen’s University
    UCL Institute of Neurology
    Chalfont Centre for Epilepsy)

  • Aoife Griffin

    (Queens University Belfast)

  • Aditi Singh

    (Queens University Belfast)

  • Vijay K. Tiwari

    (Queens University Belfast)

  • Barbara A. K. Kreilkamp

    (University of Medicine Göttingen)

  • Matteo Lenge

    (Children’s Hospital A. Meyer-University of Florence
    Children’s Hospital A. Meyer-University of Florence)

  • Renzo Guerrini

    (Children’s Hospital A. Meyer-University of Florence)

  • Khalid Hamandi

    (University Hospital of Whales
    Cardiff University Brain Research Imaging Centre (CUBRIC), College of Biomedical Sciences, Cardiff University)

  • Sonya Foley

    (Cardiff University Brain Research Imaging Centre (CUBRIC), College of Biomedical Sciences, Cardiff University)

  • Theodor Rüber

    (University of Bonn Medical Center
    Goethe-University Frankfurt
    Goethe-University Frankfurt)

  • Bernd Weber

    (University Hospital Bonn)

  • Chantal Depondt

    (Université Libre de Bruxelles)

  • Julie Absil

    (Université Libre de Bruxelles)

  • Sarah J. A. Carr

    (King’s College London)

  • Eugenio Abela

    (King’s College London)

  • Mark P. Richardson

    (King’s College London)

  • Orrin Devinsky

    (NYU Grossman School of Medicine)

  • Mariasavina Severino

    (IRCCS Istituto Giannina Gaslini)

  • Pasquale Striano

    (IRCCS Istituto Giannina Gaslini
    University of Genova)

  • Domenico Tortora

    (University of Genova)

  • Erik Kaestner

    (University of California San Diego)

  • Sean N. Hatton

    (University of California San Diego)

  • Sjoerd B. Vos

    (UCL Institute of Neurology
    Chalfont Centre for Epilepsy
    University College London)

  • Lorenzo Caciagli

    (UCL Institute of Neurology
    Chalfont Centre for Epilepsy)

  • John S. Duncan

    (UCL Institute of Neurology
    Chalfont Centre for Epilepsy)

  • Christopher D. Whelan

    (The Royal College of Surgeons in Ireland)

  • Paul M. Thompson

    (University of Southern California)

  • Sanjay M. Sisodiya

    (UCL Institute of Neurology
    Chalfont Centre for Epilepsy)

  • 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)

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.

Suggested Citation

  • Sara Larivière & Jessica Royer & Raúl Rodríguez-Cruces & Casey Paquola & Maria Eugenia Caligiuri & Antonio Gambardella & Luis Concha & Simon S. Keller & Fernando Cendes & Clarissa L. Yasuda & Leonardo, 2022. "Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31730-5
    DOI: 10.1038/s41467-022-31730-5
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