Department of Biomedical Engineering, University of California Davis, Davis, CA 95616, United States of America.
Department of Neurological Surgery, University of California Davis, Sacramento, CA 95817, United States of America; Center for Neuroscience, University of California Davis, Davis, CA 95618, United States of America.
Neurobiol Dis. 2019 Sep;129:169-181. doi: 10.1016/j.nbd.2019.02.009. Epub 2019 Feb 21.
Despite decades of research, our understanding of epilepsy, including how seizures are generated and propagate, is incomplete. However, there is growing recognition that epilepsy is more than just the occurrence of seizures, with patients often experiencing comorbid deficits in cognition that are poorly understood. In addition, the available therapies for treatment of epilepsy, from pharmaceutical treatment to surgical resection and seizure prevention devices, often exacerbate deficits in cognitive function. In this review, we discuss the hypothesis that seizure generation and cognitive deficits have a similar pathological source characterized by, but not limited to, deficits in theta oscillations and their influence on interneurons. We present a new framework that describes oscillatory states in epilepsy as alternating between hyper- and hypo-synchrony rather than solely the spontaneous transition to hyper-excitability characterized by the seizures. This framework suggests that as neural oscillations, specifically in the theta range, vary their tempo from a slowed almost adagio tempo during interictal periods to faster, more rhythmic allegretto tempo preictally, they impact the function of interneurons, modulating their ability to control seizures and their role in cognitive processing. This slow wave oscillatory framework may help explain why current therapies that work to reduce hyper-excitability do not completely eliminate seizures and often lead to exacerbated cognitive deficits.
尽管已经进行了几十年的研究，但我们对癫痫的理解，包括癫痫发作的产生和传播方式，仍不完整。然而，人们越来越认识到，癫痫不仅仅是发作的发生，患者经常经历认知功能的合并缺陷，而这些缺陷还没有得到很好的理解。此外，癫痫的治疗方法，从药物治疗到手术切除和预防癫痫发作的设备，往往会加重认知功能的缺陷。在这篇综述中，我们讨论了这样一个假设，即癫痫发作的产生和认知缺陷具有相似的病理来源，其特征不仅限于θ 振荡的缺陷及其对中间神经元的影响。我们提出了一个新的框架，将癫痫中的振荡状态描述为在超同步和低同步之间交替，而不仅仅是由癫痫发作所表现出的自发向高兴奋性的转变。这个框架表明，神经振荡，特别是在θ 范围内，其节奏从发作间期的缓慢几乎是行板节奏变化到发作前更快、更有节奏的小快板节奏，它们会影响中间神经元的功能，调节它们控制癫痫发作的能力及其在认知处理中的作用。这个慢波振荡框架可以帮助解释为什么目前那些旨在降低过度兴奋的治疗方法不能完全消除癫痫发作，并且经常导致认知缺陷的恶化。
