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bioRxiv · 10.1101/2023.04.17.537191

Human thalamic recordings reveal that epileptic spikes block sleep spindle production during non-rapid eye movement sleep

Wodeyar, A.·Chinappen, D.·Mylonas, D.·Baxter, B.·Manoach, D. S.·Eden, U. T.·Kramer, M. A.·Chu, C. J.
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Abstract

In severe epileptic encephalopathies, epileptic activity contributes to progressive cognitive dysfunction. Several epileptic encephalopathies share the trait of spike-wave activation during non-rapid eye movement sleep (EE-SWAS), a state dominated by sleep oscillations known to coordinate offline memory consolidation. How epileptic activity impacts these thalamocortical sleep oscillations has not been directly observed in humans. Using a unique dataset of simultaneous human thalamic and cortical recordings in subjects with and without EE-SWAS, we reconcile prior conflicting observations about how epileptic spikes coordinate with sleep oscillations and provide direct evidence for epileptic spike interference of sleep spindle production. We find that slow oscillations facilitate both epileptic spikes and sleep spindles during stage 2 sleep (N2) at different phases of the slow oscillation. We show that sleep activated cortical epileptic spikes propagate to the thalamus (thalamic spike rate is increased after a cortical spike, p[~]0). Thalamic spikes increase the spindle refractory period (p<1.5e-21). In patients with EE-SWAS, the abundance of thalamic spikes result in downregulation of spindles for 30 seconds after each thalamic spike (p=3.4e-11) and decreased overall spindle rate across N2 (p=2e-7). These direct human thalamocortical observations identify a novel mechanism through which epileptiform spikes could impact cognitive function, wherein sleep-activated epileptic spikes inhibit thalamic sleep spindles in epileptic encephalopathy.

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Wodeyar, A., Chinappen, D., Mylonas, D., Baxter, B., Manoach, D. S., Eden, U. T., Kramer, M. A., Chu, C. J.. 2023-04-17. Human thalamic recordings reveal that epileptic spikes block sleep spindle production during non-rapid eye movement sleep. https://doi.org/10.1101/2023.04.17.537191

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