1 McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada. ke.xie@mail.mcgill.ca.
2 McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.
3 Sherbrooke Laboratory for Integrative Connectomics, Centre de Recherche du CHUS, Université de Sherbrooke, Sherbrooke, QC, Canada.
4 Department of Neurology, Inselspital, Sleep-Wake-Epilepsy-Center, Bern University Hospital, University of Bern, Bern, Switzerland.
5 Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.
6 Division of Neurosurgery, Department of Surgery, Sainte-Justine University Hospital Centre, Montreal, QC, Canada.
7 Multimodal Functional Imaging Lab, Department of Physics and Concordia School of Health, Concordia University, Montreal, QC, Canada.
8 Multimodal Functional Imaging Lab, Department of Biomedical Engineering, McGill University, Montreal, QC, Canada.
9 Department of Neurology, Department of Biomedical Engineering, Duke University, Durham, NC, USA.
10 British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.
11 Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
12 Institute of Neurobiology, Universidad Nacional Autónoma de Mexico, Queretaro, Mexico.
13 McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada. boris.bernhardt@mcgill.ca.

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.