Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study

ENIGMA-Epilepsy Working Group, Sara Larivière, Raúl Rodríguez-Cruces, Jessica Royer, Maria Eugenia Caligiuri, Antonio Gambardella, Luis Concha, Simon S Keller, Fernando Cendes, Clarissa 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, 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, Matteo Lenge, Renzo Guerrini, Emanuele Bartolini, Khalid Hamandi, Sonya Foley, Bernd Weber, Chantal Depondt, Julie Absil, Sarah J A Carr, Eugenio Abela, Mark P Richardson, Orrin Devinsky, Mariasavina Severino, Pasquale Striano, Domenico Tortora, Sean N Hatton, Sjoerd B Vos, 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

74 Citations (Scopus)


Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Negative effects of age on atrophy further revealed a strong influence of connectome architecture in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided deeper insights into the macroscale features that shape the pathophysiology of common epilepsies.

Original languageEnglish
Article numbereabc6457
JournalScience Advances
Issue number47
Publication statusPublished - 18 Nov 2020
Externally publishedYes


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