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

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 Bonilha, Ezequiel Gleichgerrcht, Niels K. Focke, Martin Domin, Felix von Podewills, Soenke Langner, Christian Rummel, Roland Wiest, Pascal Martin, Raviteja KotikalapudiTerence J. O’Brien, Benjamin Sinclair, Lucy Vivash, Patricia M. Desmond, Elaine Lui, Anna Elisabetta Vaudano, Stefano Meletti, Manuela Tondelli, Saud Alhusaini, Colin P. Doherty, Gianpiero L. Cavalleri, Norman Delanty, Reetta Kälviäinen, Graeme D. Jackson, Magdalena Kowalczyk, Mario Mascalchi, Mira Semmelroch, Rhys H. Thomas, Hamid Soltanian-Zadeh, Esmaeil Davoodi-Bojd, Junsong Zhang, Gavin P. Winston, Aoife Griffin, Aditi Singh, Vijay K. Tiwari, Barbara A.K. Kreilkamp, Matteo Lenge, Renzo Guerrini, Khalid Hamandi, Sonya Foley, Theodor Rüber, Bernd Weber, Chantal Depondt, Julie Absil, Sarah J.A. Carr, Eugenio Abela, Mark P. Richardson, Orrin Devinsky, Mariasavina Severino, Pasquale Striano, Domenico Tortora, Erik Kaestner, Sean N. Hatton, Sjoerd B. Vos, Lorenzo Caciagli, John S. Duncan, Christopher D. Whelan, Paul M. Thompson, Sanjay M. Sisodiya, Andrea Bernasconi, Angelo Labate, Carrie R. McDonald, Neda Bernasconi, Boris C. Bernhardt

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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.

Original languageEnglish
Article number4320
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - Dec 2022
Externally publishedYes

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