Personalized biomarkers of multiscale functional alterations in temporal lobe epilepsy

Ke Xie (), Ella Sahlas, Alexander Ngo, Judy Chen, Thaera Arafat, Jessica Royer, Yigu Zhou, Raúl Rodríguez-Cruces, Arielle Dascal, Benoit Caldairou, Fatemeh Fadaie, Alexander Barnett, Samantha Audrain, Sara Larivière, Lorenzo Caciagli, Raluca Pana, Alexander G. Weil, Christophe Grova, Birgit Frauscher, Dewi V. Schrader, Zhiqiang Zhang, Luis Concha, Andrea Bernasconi, Neda Bernasconi and Boris C. Bernhardt ()
Additional contact information
Ke Xie: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Ella Sahlas: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Alexander Ngo: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Judy Chen: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Thaera Arafat: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Jessica Royer: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Yigu Zhou: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Raúl Rodríguez-Cruces: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Arielle Dascal: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Benoit Caldairou: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Fatemeh Fadaie: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Alexander Barnett: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Samantha Audrain: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Sara Larivière: Université de Sherbrooke, Sherbrooke Laboratory for Integrative Connectomics, Centre de Recherche du CHUS
Lorenzo Caciagli: University of Bern, Department of Neurology, Inselspital, Sleep-Wake-Epilepsy-Center, Bern University Hospital
Raluca Pana: McGill University, Montreal Neurological Institute and Hospital
Alexander G. Weil: Sainte-Justine University Hospital Centre, Division of Neurosurgery, Department of Surgery
Christophe Grova: Concordia University, Multimodal Functional Imaging Lab, Department of Physics and Concordia School of Health
Birgit Frauscher: Duke University, Department of Neurology, Department of Biomedical Engineering
Dewi V. Schrader: University of British Columbia, British Columbia Children’s Hospital
Zhiqiang Zhang: Nanjing University School of Medicine, Department of Medical Imaging, Jinling Hospital
Luis Concha: Universidad Nacional Autónoma de Mexico, Institute of Neurobiology
Andrea Bernasconi: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Neda Bernasconi: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital
Boris C. Bernhardt: McGill University, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Temporal lobe epilepsy (TLE) is the most common pharmacoresistant epilepsy in adults, yet few patients receive curative surgery due to diagnostic and prognostic uncertainty. In a multicenter cohort, we analyzed multimodal MRI and clinical data from 282 TLE patients, 298 healthy controls, and 45 disease controls. Patient-specific deviations from typical lifespan trajectories of intrinsic brain function were mapped using normative modeling. Regional functional alterations were heterogeneous but overlapped most in the mesiotemporal cortex. Connectome-based simulations revealed abnormality spread followed structural network architecture, highlighting the hippocampus as well as paralimbic and medial default-mode regions as epicenters. Multimodal integration implicated superficial white-matter microstructural alterations as a key contributor. Supervised models achieved AUCs of 0.77 for distinguishing TLE from disease controls, 0.74 for lateralizing seizure focus, and 0.64 for predicting postsurgical seizure freedom; greater contralateral temporal deviations predicted poorer outcomes. These findings support individualized functional biomarkers for precision presurgical care in focal epilepsy.

Date: 2025
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DOI: 10.1038/s41467-025-65042-1

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