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
- Boris C. Bernhardt
2025-11-19
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.