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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

Larivière, Sara, Royer, Jessica, Rodríguez-Cruces, Raúl, Paquola, Casey, Caligiuri, Maria Eugenia, Gambardella, Antonio, Concha, Luis, Keller, Simon S., Cendes, Fernando, Yasuda, Clarissa L., Bonilha, Leonardo, Gleichgerrcht, Ezequiel, Focke, Niels K., Domin, Martin, von Podewills, Felix, Langner, Soenke, Rummel, Christian, Wiest, Roland, 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, Hamid, Davoodi-Bojd, Esmaeil, Zhang, Junsong, Winston, Gavin P., Griffin, Aoife, Singh, Aditi, Tiwari, Vijay K., Kreilkamp, Barbara A. K., Lenge, Matteo, Guerrini, Renzo, Hamandi, Khalid, Foley, Sonya, Rüber, Theodor, Weber, Bernd, Depondt, Chantal, Absil, Julie, Carr, Sarah J. A., Abela, Eugenio, Richardson, Mark P., Devinsky, Orrin, Severino, Mariasavina, Striano, Pasquale, Tortora, Domenico, Kaestner, Erik, Hatton, Sean N., Vos, Sjoerd B., Caciagli, Lorenzo, Duncan, John S., Whelan, Christopher D., Thompson, Paul M., Sisodiya, Sanjay M., Bernasconi, Andrea, Labate, Angelo, McDonald, Carrie R., Bernasconi, Neda and Bernhardt, Boris C. 2022. Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression. Nature Communications 13 (1) , 4320. 10.1038/s41467-022-31730-5

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Abstract

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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Psychology
Additional Information: License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher: Nature Research
Date of First Compliant Deposit: 28 July 2022
Date of Acceptance: 30 June 2022
Last Modified: 28 Jul 2022 09:15
URI: https://orca.cardiff.ac.uk/id/eprint/151526

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