Topographic divergence of atypical cortical asymmetry and regional atrophy patterns in temporal lobe epilepsy: a worldwide ENIGMA study
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 an in vivo window 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.
Funding
Canadian Institutes of Health Research (CIHR)
Fonds de la Recherche du Québec – Santé (FRQ-S)
Canadian Open Neuroscience Platform (CONP) fellowship and CIHR
Berkeley Fellowship jointly awarded by UCL and Gonville and Caius College, Cambridge
UNAM-DGAPA (IB201712, IG200117)
Conacyt (181508 and Programa de Laboratorios Nacionales)
UK Medical Research Council grant MR/K013998/1
National Science and Engineering Research Council of Canada (NSERC Discovery-1304413)
CIHR (FDN-154298, PJT-174995)
SickKids Foundation (NI17-039)
Azrieli Center for Autism Research (ACAR-TACC)
BrainCanada
FRQ-S
Tier- 2 Canada Research Chairs program
São Paulo Research Foundation (FAPESP), Grant # 2013/07559-3 (BRAINN - Brazilian Institute of Neuroscience and Neurotechnology)
Ministry of Health (MOH), grant # NET-2013-02355313
ENIGMA-R21 (NIH/NINDS R21NS107739)
History
Comments
The original article is available at https://www.biorxiv.org Published version is available in Brain https://doi.org/10.1093/brain/awab417 and RCSI repository https://hdl.handle.net/10779/rcsi.24512854.v1Published Citation
Park BY. et al. Topographic divergence of atypical cortical asymmetry and regional atrophy patterns in temporal lobe epilepsy: a worldwide ENIGMA study. bioRxiv. 2021Publication Date
30 April 2021External DOI
Department/Unit
- Beaumont Hospital
- FutureNeuro Centre
- School of Pharmacy and Biomolecular Sciences
Publisher
Cold Spring Harbor LaboratoryVersion
- Submitted Version (Preprint)