In severe epileptic encephalopathies, epileptic activity contributes to progressive cognitive dysfunction. Epileptic encephalopathies share the trait of spike-wave activation during non-rapid eye movement sleep (EE-SWAS), a sleep stage dominated by sleep spindles, brain oscillations known to coordinate offline memory consolidation. Epileptic activity has been proposed to hijack the circuits driving these thalamocortical oscillations, thereby contributing to cognitive impairment. Using a unique dataset of simultaneous human thalamic and cortical recordings in subjects with and without EE-SWAS, we provide evidence for epileptic spike interference of thalamic sleep spindle production in patients with EE-SWAS. First, we show that epileptic spikes and sleep spindles are both predicted by slow oscillations during stage two sleep (N2), but at different phases of the slow oscillation. Next, we demonstrate that sleep activated cortical epileptic spikes propagate to the thalamus (thalamic spike rate increases after a cortical spike, p≈0). We then show that epileptic spikes in the thalamus increase the thalamic spindle refractory period (p≈0). Finally, we show that in three patients with EE-SWAS, there is a downregulation of sleep spindles for 30 seconds after each thalamic spike (p<0.01). These direct human thalamocortical observations support a proposed mechanism for epileptiform activity to impact cognitive function, wherein epileptic spikes inhibit thalamic sleep spindles in epileptic encephalopathy with spike and wave activation during sleep.

中文翻译：

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丘脑癫痫尖峰扰乱癫痫性脑病患者的睡眠纺锤波

在严重的癫痫性脑病中，癫痫活动会导致进行性认知功能障碍。癫痫性脑病具有非快速眼动睡眠 (EE-SWAS) 期间棘波激活的特征，这是一个以睡眠纺锤波为主的睡眠阶段，已知大脑振荡可以协调离线记忆巩固。有人提出，癫痫活动会劫持驱动这些丘脑皮质振荡的回路，从而导致认知障碍。使用具有和不具有 EE-SWAS 的受试者的同时人类丘脑和皮质记录的独特数据集，我们提供了 EE-SWAS 患者丘脑睡眠纺锤体产生的癫痫尖峰干扰的证据。首先，我们表明癫痫尖峰和睡眠纺锤波都是通过第二阶段睡眠（N2）期间的慢振荡来预测的，但在慢振荡的不同阶段。接下来，我们证明睡眠激活的皮质癫痫尖峰传播到丘脑（皮质尖峰后丘脑尖峰率增加，p≈0）。然后我们发现丘脑中的癫痫尖峰会增加丘脑纺锤体不应期（p≈0）。最后，我们发现，在三名 EE-SWAS 患者中，每个丘脑尖峰后睡眠纺锤波下调 30 秒（p<0.01）。这些直接的人类丘脑皮质观察结果支持了癫痫样活动影响认知功能的拟议机制，其中癫痫尖峰抑制癫痫性脑病中的丘脑睡眠纺锤体，并在睡眠期间激活尖峰和波。