Thalamic interictal epileptic and non-epileptic events during NREM sleep in patients with focal epilepsy: a...

Thalamic 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 characterised interictal epileptic and non-epileptic events during non-rapid eye movement (NREM) sleep across multiple thalamic nuclei and examined their associations to seizure outcomes.

We analysed 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: favourable, unfavourable, and surgically non-remediable. Rates of thalamic spikes, high-frequency oscillations (HFOs), spike-fast activity, and sleep spindles were analysed and compared across nuclei and outcomes.

Recordings 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 unfavourable 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.

This study provides a comprehensive characterisation of thalamic interictal events during NREM sleep, enriching our understanding of thalamic pathophysiology and highlighting the value of thalamic recordings in presurgical evaluation.

Start-up funding of Duke University; National Natural Science Foundation of China (82471469, 82301636); Zhejiang Provincial Natural Science Foundation (LD24H090003); Canadian Institutes of Health Research funding (PJT-175056).