Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy

Bo-Yong Park, Sara Larivière, Raul Rodríguez-Cruces, Jessica Royer, Shahin Tavakol, Yezhou Wang, Lorenzo Caciagli, Maria Eugenia Caligiuri, Antonio Gambardella, Luis Concha, Simon S Keller, Fernando Cendes, Marina K M Alvim, Clarissa Yasuda, Leonardo Bonilha, Ezequiel Gleichgerrcht, Niels K Focke, Barbara A K Kreilkamp, Martin Domin, Felix von PodewilsSoenke Langner, Christian Rummel, Michael Rebsamen, Roland Wiest, Pascal Martin, Raviteja Kotikalapudi, Benjamin Bender, Terence J O'Brien, Meng Law, Benjamin Sinclair, Lucy Vivash, Patrick Kwan, Patricia M Desmond, Charles B Malpas, Elaine Lui, 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, Costanza Parodi, Domenico Tortora, Sean N Hatton, Sjoerd B Vos, John S Duncan, Marian Galovic, Christopher D Whelan, Núria Bargalló, Jose Pariente, Estefania Conde-Blanco, Anna Elisabetta Vaudano, Manuela Tondelli, Stefano Meletti, Xiang-Zhen Kong, Clyde Francks, Simon E Fisher, Benoit Caldairou, Mina Ryten, Angelo Labate, Sanjay M Sisodiya, Paul M Thompson, Carrie R McDonald, Andrea Bernasconi, Neda Bernasconi, Boris C Bernhardt

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy.

Original languageEnglish
Article numberawab417
Pages (from-to)1285-1298
Number of pages14
JournalBrain: a journal of neurology
Issue number4
Early online dateMar 2022
Publication statusPublished - 1 Apr 2022
Externally publishedYes


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