Cognitive impact of iterictal spikes in temporal lobe epilepsy

癫痫是一种影响全世界数百万人的神经系统疾病。大多数患者的一个常见现象是出现间期尖峰，这是脑电图记录中短暂的异常波形，由癫痫神经元群同步放电产生。间期尖峰可以影响其产生的大脑区域的内在神经功能；然而，它们在癫痫的临床管理中几乎从未被考虑过。海马体是一个涉及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尖峰的主要来源，尽管它们对其功能的影响尚未系统研究。本研究旨在评估间隔尖峰对海马过程的影响。我们收集到的初步数据表明，海马体的间歇峰增加了短期记忆任务中对错误的易感性。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。我们假设颞叶癫痫的间歇峰可能起源于多个海马网络通路，从而通过破坏神经生理节律损害其内在认知功能。我们将通过完成以下具体目标来评估这一假设：1)研究颞叶癫痫海马内-匹罗卡品模型中间期尖峰发生和传播的神经回路。2)研究海马间期峰对短期记忆功能和相关电生理振荡的影响。这些实验将利用新的方法建立大鼠颞叶癫痫模型。具体目标1将涉及海马体和相互连接区域的高空间密度深度电极记录，以评估间隔尖峰的电路。具体目标2将使用具体涉及海马功能的行为任务，以及同时深度电极记录来检查间隔尖峰对认知和相关神经生理振荡的影响。这项研究将为认知加工中间歇峰的神经生理和功能后果提供新的视角。公共卫生相关性：我们的研究结果可能具有相当大的临床相关性，因为癫痫患者中有大量的间歇尖峰。我们的最终目标是辨别间隔尖峰是否有可能显著影响患者的生活质量，因此是否应该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.