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bioRxiv · 10.64898/2025.12.11.693651

Thalamic Interictal Epileptic and Non-Epileptic Events during NREM Sleep in Patients with Focal Epilepsy: a Stereo-EEG Study

Ye, H.·Jaber, K.·Ho, A.·Ye, L.·Thomas, J.·Xu, X.·Chen, C.·Chen, Y.·Ren, G.·Moye, M.·Avigdor, T.·Klimes, P.·Parikh, P.·Southwell, D.·Zheng, Z.·Zhu, J.·Wang, S.·Frauscher, B.
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Abstract

BackgroundThalamic recordings are increasingly incorporated into stereo-electroencephalography (SEEG) evaluations of drug-resistant focal epilepsy to guide neuromodulation targeting. Human thalamic electrophysiology, however, is poorly defined, limiting the distinction between pathological and physiological activity. Here, we characterized interictal epileptic and non-epileptic events during non-rapid eye movement (NREM) sleep across multiple thalamic nuclei and examined their relationship to seizure outcomes. MethodsWe analyzed NREM sleep SEEG recordings from 64 patients with drug-resistant focal epilepsy. Electrodes sampled four thalamic nuclei: centromedian (CM), pulvinar (Pu), ventral lateral (VL), and ventral posterolateral (VPL). Patients were classified into three outcome groups: favorable, unfavorable, and surgically non-remediable. Rates of thalamic spikes, high-frequency oscillations (HFOs), spike-fast activity, and sleep spindles were analyzed and compared across nuclei and outcomes. FindingsRecordings of the thalamus revealed both pathological and physiological interictal events. Interictal epileptic events were infrequent. Only [~]0.2% of seizure-onset zone spikes propagated to the thalamus. Thalamic spike-fast activity was indicative of unfavorable surgical outcomes (CM: p = 0.047, d = 0.46) or surgically non-remediable epilepsy (VL: p = 0.002, d = 0.84). In contrast, thalamic sleep spindles were ubiquitous but reduced in surgically non-remediable patients (CM: p = 0.031, d = -0.58; VL: p = 0.005, d = -0.79). Finally, unique thalamic SEEG patterns were identified, including spikes concomitant with spindles, isolated spikes, and physiological fast ripples. InterpretationThis study provides a comprehensive characterization of thalamic interictal events during NREM sleep, enriching our understanding of thalamic pathophysiology and highlighting the value of thalamic recordings in presurgical evaluation.

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Ye, H., Jaber, K., Ho, A., Ye, L., Thomas, J., Xu, X., Chen, C., Chen, Y., Ren, G., Moye, M., Avigdor, T., Klimes, P., Parikh, P., Southwell, D., Zheng, Z., Zhu, J., Wang, S., Frauscher, B.. 2025-12-15. Thalamic Interictal Epileptic and Non-Epileptic Events during NREM Sleep in Patients with Focal Epilepsy: a Stereo-EEG Study. https://doi.org/10.64898/2025.12.11.693651

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