Bower Mark R
Department of Neurology, Yale University, New Haven, CT, United States.
Front Netw Physiol. 2024 Aug 22;4:1430934. doi: 10.3389/fnetp.2024.1430934. eCollection 2024.
Epilepsy is a complex, multifaceted disease that affects patients in several ways in addition to seizures, including psychological, social, and quality of life issues, but epilepsy is also known to interact with sleep. Seizures often occur at the boundary between sleep and wake, patients with epilepsy often experience disrupted sleep, and the rate of inter-ictal epileptiform discharges increases during non-REM sleep. The Network Theory of Epilepsy did not address a role for sleep, but recent emphasis on the interaction between epilepsy and sleep suggests that post-seizure sleep may also be involved in the process by which seizures arise and become more severe with time ("epileptogenesis") by co-opting processes related to the formation of long-term memories. While it is generally acknowledged that recurrent seizures arise from the aberrant function of neural circuits, it is possible that the progression of epilepsy is aided by normal, physiological function of neural circuits during sleep that are driven by pathological signals. Studies recording multiple, single neurons prior to spontaneous seizures have shown that neural assemblies activated prior to the start of seizures were reactivated during post-seizure sleep, similar to the reactivation of behavioral neural assemblies, which is thought to be involved in the formation of long-term memories, a process known as Memory Consolidation. The reactivation of seizure-related neural assemblies during sleep was thus described as being a component of Seizure-Related Consolidation (SRC). These results further suggest that SRC may viewed as a network-related aspect of epilepsy, even in those seizures that have anatomically restricted neuroanatomical origins. As suggested by the Network Theory of Epilepsy as a means of interfering with ictogenesis, therapies that interfered with SRC may provide some anti-epileptogenic therapeutic benefit, even if the interference targeted structures that were not involved originally in the seizure. Here, we show how the Network Theory of Epilepsy can be expanded to include neural plasticity mechanisms associated with learning by providing an overview of Memory Consolidation, the mechanisms thought to underlie MC, their relation to Seizure-Related Consolidation, and suggesting novel, anti-epileptogenic therapies targeting interference with network activation in epilepsy following seizures during post-seizure sleep.
癫痫是一种复杂、多层面的疾病，除了发作之外，还会在多个方面影响患者，包括心理、社会和生活质量问题，但癫痫也与睡眠相互作用。发作常常发生在睡眠和清醒的边界，癫痫患者经常经历睡眠中断，并且在非快速眼动睡眠期间发作间期癫痫样放电的频率会增加。癫痫的网络理论并未涉及睡眠的作用，但最近对癫痫与睡眠之间相互作用的强调表明，发作后的睡眠可能也参与了癫痫发作随着时间推移而出现并变得更加严重的过程（“癫痫发生”），这是通过利用与长期记忆形成相关的过程来实现的。虽然人们普遍认为反复发作是由神经回路的异常功能引起的，但癫痫的进展有可能是由睡眠期间受病理信号驱动的神经回路的正常生理功能所促进的。在自发性发作之前记录多个单个神经元的研究表明，在发作开始前被激活的神经集合在发作后的睡眠中会再次被激活，这类似于行为神经集合的重新激活，后者被认为与长期记忆的形成有关，这一过程被称为记忆巩固。因此，睡眠期间与发作相关的神经集合的重新激活被描述为发作相关巩固（SRC）的一个组成部分。这些结果进一步表明，即使在那些具有解剖学上局限的神经解剖学起源的发作中，SRC也可被视为癫痫的一个与网络相关的方面。正如癫痫网络理论所提出的作为一种干扰发作产生的手段，干扰SRC的疗法可能会提供一些抗癫痫发生的治疗益处，即使这种干扰针对的是最初不参与发作的结构。在此，我们通过概述记忆巩固、被认为是记忆巩固基础的机制、它们与发作相关巩固的关系，并提出针对发作后睡眠期间癫痫发作后干扰网络激活的新型抗癫痫发生疗法，展示了癫痫网络理论如何能够扩展到包括与学习相关的神经可塑性机制。
