Cognitive impact of iterictal spikes in temporal lobe epilepsy

癫痫是一种神经系统疾病，影响着全世界数百万人。发作间期棘波是大多数患者的一种常见现象，它是脑电图记录中的短暂异常波形，由癫痫神经元群同步放电产生。发作间期棘波可以影响其起源的大脑区域的内在神经功能;然而，在癫痫的临床管理中几乎从未考虑过它们。海马体是参与复杂学习和记忆功能的大脑区域。它也是颞叶癫痫发作间期棘波的主要来源，尽管它们对其功能的影响尚未得到系统研究。本研究旨在评估发作间期棘波对海马突起的影响。我们已经收集了初步的数据表明，发作间期的尖峰在海马增加的敏感性，在短期记忆任务的错误。此外，我们还观察到这些尖峰的多个一致亚型，它们可能起源于不同的海马回路。我们假设颞叶癫痫发作间期的棘波可能起源于多个海马网络通路，从而通过扰乱神经生理节律损害其内在的认知功能。我们将通过完成以下具体目标来评估这一假设：1）在颞叶癫痫的脑内Campal-Pilocarpine模型中研究发作间期棘波发生和传播的神经回路。2)研究发作间期海马棘波对短期记忆功能和相关电生理振荡的影响。这些实验将在已建立的颞叶癫痫大鼠模型中利用新方法。具体目标1将涉及海马和互连区域中的高空间密度深度电极记录，以评估发作间期尖峰的电路。具体目标2将使用专门涉及海马功能的行为任务，沿着同时进行的深度电极记录，以检查发作间期尖峰对认知和相关神经生理振荡的影响。这项研究将提供新的观点，神经生理和功能的后果，发作间期的棘波在认知加工。公共卫生相关性：我们的研究结果可能具有相当大的临床意义，由于癫痫患者发作间期棘波的丰富。我们的最终目标是辨别发作间期尖峰是否有可能显著影响患者的生活质量，以及因此是否应将其存在纳入临床治疗决策。

Epilepsy is a neurological disorder that affects millions of people worldwide. A common phenomenon in most patients is the appearance of interictal spikes, which are brief abnormal waveforms in electroencephalographic recordings, produced by groups of epileptic neurons discharging synchronously. Interictal spikes can affect intrinsic neural function in the brain region where they originate; however, they are virtually never considered in the clinical management of epilepsy. The hippocampus is a brain region involved in complex learning and memory functions. It is also a major source of interictal spikes in temporal lobe epilepsy, though their impact on its function has not been systematically investigated. This proposal seeks to evaluate the effects of interictal spikes on hippocampal processes. We have gathered preliminary data suggesting that interictal spikes in the hippocampus increase susceptibility to errors in a short-term memory task. In addition, we have observed multiple consistent subtypes of these spikes, which may be originating in divergent hippocampal circuits. We hypothesize that interictal spikes in temporal lobe epilepsy can originate in multiple hippocampal network pathways, consequently impairing their intrinsic cognitive functions by disrupting neurophysiological rhythms. We will evaluate this hypothesis by completing the following Specific Aims: 1) Investigate the neural circuitry of interictal spike genesis and propagation in the intrahippocampal-pilocarpine model of temporal lobe epilepsy. 2) Investigate the impact of interictal spikes in the hippocampus on short-term memory functions and related electro-physiological oscillations. These experiments will utilize novel methods in an established rat model of temporal lobe epilepsy. Specific Aim 1 will involve high spatial-density depth electrode recordings in the hippocampus and interconnected areas to evaluate the circuitry of interictal spikes. Specific Aim 2 will use behavioral tasks that specifically involve hippocampal function, along with simultaneous depth electrode recordings to examine the impact of interictal spikes on cognition and related neurophysiological oscillations. This investigation will provide novel perspectives on the neurophysiological and functional consequences of interictal spikes in cognitive processing. Public Health Relevance: Our results may hold considerable clinical relevance, due to the abundance of interictal spikes in patients with epilepsy. Our ultimate goal is to discern whether interictal spikes have the potential to significantly impact patient quality of life, and consequently if their presence should be factored in to clinical treatment decisions.