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Personalized biomarkers of multiscale functional alterations in temporal lobe epilepsy

Author

Listed:
  • 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
    McGill University, Multimodal Functional Imaging Lab, Department of Biomedical Engineering)

  • 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)

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.

Suggested Citation

  • 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, 2025. "Personalized biomarkers of multiscale functional alterations in temporal lobe epilepsy," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65042-1
    DOI: 10.1038/s41467-025-65042-1
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    1. Evelyn Tang & Chad Giusti & Graham L. Baum & Shi Gu & Eli Pollock & Ari E. Kahn & David R. Roalf & Tyler M. Moore & Kosha Ruparel & Ruben C. Gur & Raquel E. Gur & Theodore D. Satterthwaite & Danielle , 2017. "Developmental increases in white matter network controllability support a growing diversity of brain dynamics," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    2. Yuchao Jiang & Wei Li & Jinmei Li & Xiuli Li & Heng Zhang & Xiutian Sima & Luying Li & Kang Wang & Qifu Li & Jiajia Fang & Lu Jin & Qiyong Gong & Dezhong Yao & Dong Zhou & Cheng Luo & Dongmei An, 2024. "Identification of four biotypes in temporal lobe epilepsy via machine learning on brain images," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Matthew F. Glasser & Timothy S. Coalson & Emma C. Robinson & Carl D. Hacker & John Harwell & Essa Yacoub & Kamil Ugurbil & Jesper Andersson & Christian F. Beckmann & Mark Jenkinson & Stephen M. Smith , 2016. "A multi-modal parcellation of human cerebral cortex," Nature, Nature, vol. 536(7615), pages 171-178, August.
    4. Justine Y. Hansen & Golia Shafiei & Jacob W. Vogel & Kelly Smart & Carrie E. Bearden & Martine Hoogman & Barbara Franke & Daan Rooij & Jan Buitelaar & Carrie R. McDonald & Sanjay M. Sisodiya & Lianne , 2022. "Local molecular and global connectomic contributions to cross-disorder cortical abnormalities," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
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