Precision mapping and molecular contextualization of surgical outcome epicenters in temporal lobe epilepsy

Fadaie, F.; Xie, K.; Lam, J.; Arafat, T.; Sahlas, E.; Chen, J.; Royer, J.; Goodall-Halliwell, I.; Ding, R.; Naish, M.; R.Cruces, R.; Mo, J.; Hall, J.; Weng, Y.; Lariviere, S.; Obaid, S.; Hadjinicolaou, A.; Weil, A.; Pana, R.; Zhang, Z.; Bernasconi, A.; Bernasconi, N.; Bernhardt, B.

doi:10.64898/2026.03.06.710165

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bioRxiv · 10.64898/2026.03.06.710165

Precision mapping and molecular contextualization of surgical outcome epicenters in temporal lobe epilepsy

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Abstract

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy is the most common drug-resistant epilepsy, with surgical resection offering the primary path to seizure freedom. Despite standardized approaches, a substantial proportion of patients experience seizure recurrence, and the neurobiological substrates underlying these divergent outcomes remain unclear. We applied an individualized normative modeling framework to multimodal preoperative MRI data in a group that subsequently underwent surgical resection, to characterize patient-specific structural deviations and identify disease epicenters. Patients who became seizure-free exhibited spatially coherent abnormalities localized to the hippocampus and ipsilateral association regions, anchored in agranular limbic territories and enriched for genes linked to calcium-dependent signaling. Non-seizure-free patients, on the other hand, showed a more heterogeneous and distributed pattern of deviations, consistent with a "temporal-plus" network organization, and broader neuromodulatory dysregulation. Crucially, overlap between resected tissue and network-defined epicenters was closely associated with seizure freedom, independent of total resection volume. These findings provide a multiscale framework for precision surgical planning, shifting the focus from standardized tissue removal to targeted disconnection of patient-specific pathological hubs.

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Fadaie, F., Xie, K., Lam, J., Arafat, T., Sahlas, E., Chen, J., Royer, J., Goodall-Halliwell, I., Ding, R., Naish, M., R.Cruces, R., Mo, J., Hall, J., Weng, Y., Lariviere, S., Obaid, S., Hadjinicolaou, A., Weil, A., Pana, R., Zhang, Z., Bernasconi, A., Bernasconi, N., Bernhardt, B.. 2026-03-10. Precision mapping and molecular contextualization of surgical outcome epicenters in temporal lobe epilepsy. https://doi.org/10.64898/2026.03.06.710165

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