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 Podewils
Soenke 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, Henry Ford HealthFollow
Esmaeil Davoodi-Bojd, Henry Ford HealthFollow
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

Document Type


Publication Date


Publication Title

Brain : a journal of neurology


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.

Medical Subject Headings

Adult; Atrophy; Connectome; Epilepsy, Temporal Lobe; Hippocampus; Humans; Magnetic Resonance Imaging

PubMed ID






First Page


Last Page