Topographic Divergence of Atypical Cortical Asymmetry and Regional Atrophy Patterns in Temporal Lobe Epilepsy: A Worldwide ENIGMA Study
Authors: Park Bo-yong , Larivière Sara , Rodríguez-Cruces Raul , Royer Jessica , Tavakol Shahin , Wang Yezhou , Caciagli Lorenzo , Caligiuri Maria Eugenia , Gambardella Antonio , Concha Luis , Keller Simon S. , Cendes Fernando , Alvim Marina K. M. , Yasuda Clarissa , Bonilha Leonardo , Gleichgerrcht Ezequiel , Focke Niels K. , Kreilkamp Barbara A. K. , Domin Martin , von Podewils Felix , Langner Soenke , Rummel Christian , Rebsamen Michael , Wiest Roland , Martin Pascal , Kotikalapudi Raviteja , Bender Benjamin , O’Brien Terence J. , Law Meng , Sinclair Benjamin , Vivash Lucy , Desmond Patricia M. , Malpas Charles B. , Lui Elaine , 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 , Lenge Matteo , Guerrini Renzo , Bartolini Emanuele , Hamandi Khalid , Foley Sonya , Weber Bernd , Depondt Chantal , Absil Julie , Carr Sarah J. A. , Abela Eugenio , Richardson Mark P. , Devinsky Orrin , Severino Mariasavina , Striano Pasquale , Parodi Costanza , Tortora Domenico , Hatton Sean N. , Vos Sjoerd B. , Duncan John S. , Galovic Marian , Whelan Christopher D. , Bargalló Núria , Pariente Jose , Conde Estefania , Vaudano Anna Elisabetta , Tondelli Manuela , Meletti Stefano , Kong Xiang-Zhen , Francks Clyde , Fisher Simon E. , Labate Angelo , Sisodiya Sanjay M. , Thompson Paul M. , McDonald Carrie R. , Bernasconi Andrea , Bernasconi Neda , Bernhardt Boris C. 
Published: April 2021

Abstract

Temporal lobe epilepsy (TLE), a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided anin vivowindow into whole-brain grey matter pathology in TLE 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 multi-site ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 TLE patients and 1,418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in TLE, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity, 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 TLE-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 TLE and may inform future discovery and validation of complementary MRI biomarkers in TLE.