Experimental Study of Goal-Directed Behavior and Memory During Temporal Lobe Epileptic Activity

项目摘要 临床神经科学的一个广泛和首要的目标是发展神经过程的机械解释 在解释特定临床表型的特定解剖功能网络中。有一个根本 在理解癫痫发作和癫痫病理活动（即，不仅是癫痫， 例如高频振荡的活动）影响患者的认知。人类认知的核心部分是 记忆的能力。记忆功能的机制及其与内侧颞叶的关系 已经详细研究了结构，并且有大量关于记忆功能障碍的信息， 颞叶癫痫，尚不清楚癫痫放电期间记忆功能如何受到影响， 癫痫发作局灶性颞叶癫痫发作是否能够损害目标导向任务， 性能在临床实践中，我们根据患者是否记得事件或 但我们对癫痫发作时病人的记忆发生了什么并没有机械的理解 以及癫痫发作如何影响之前和之后的记忆。同样，我们对 癫痫发作后认知缺陷的性质。拟议项目的目标是克服方法上的困难， 限制和测试目标导向的行为和记忆的MTL癫痫患者。我们的目标是 描述癫痫活动与目标导向任务表现和记忆之间的关系 处理.该项目的中心假设是，MTL中的癫痫活动不仅会影响记忆， 在其发生时处理，但也将通过干扰的巩固倒退的影响， 癫痫病理活动发生前的记忆项目，他们也将有一个 在记忆项目消失后，对记忆项目的编码、巩固和提取的顺行性持续影响。 这一概念框架基于最近公布的初步数据。概念框架结合 我们的创新方法提供了一个创新平台，以解决现有的知识差距。拟议 研究是重要的，因为它将作为一个系统的调查，以提供明确的证据， MTL中癫痫活动引起的记忆障碍的性质。这将指导今后的工作， 为了减少病理性癫痫活动的有害影响， 神经调节方法。我们的长期目标是在植入慢性神经调节的患者中 我们使用我们的证据来设计新的手段，我们不仅控制癫痫发作，更重要的是， 逆转认知缺陷，甚至通过沉默持续的癫痫组织来增强癫痫组织的储备功能， 病理性癫痫放电，我们确认对人类认知有毒性。

PROJECT SUMMARY A broad and overarching goal of clinical neurosciences is to develop a mechanistic account of neural processes within a specific anatomical functional network that explains a specific clinical phenotype. There is a fundamental gap in understanding how seizures and epileptic pathological activity (i.e., not only seizures but also epileptic activity such as high frequency oscillations) affect a patient’s cognition. A core part of human cognition is the ability to remember. While the mechanisms of memory functions and their relationship with medial temporal lobe structures have been investigated in detail, and there is a wealth of information on memory dysfunction in temporal lobe epilepsy, it is yet to be known how memory functions are affected during epileptic discharges and seizures. It also remains unknown whether focal temporal lobe seizures are able to impair goal-oriented task performance. In clinical practice, we classify seizures based on whether the patient remembers the events or not, and yet we have no mechanistic understanding of what happens to the patient’s memory during seizures and how seizures impact memory for preceding and subsequent experiences. Likewise, we know little about the nature of cognitive deficits during postictal state. The goal of the proposed project is to overcome methodological limitations and test goal-directed behavior and memory in patients with MTL epilepsy. The objective here is to characterize the relationship between epileptic activities and goal-oriented task performance and memory processing. The central hypothesis of the project is that epileptic activities in the MTL will not only affect memory processing at the time of their occurrence but will also have retrograde effects by disturbing the consolidation of memory items presented before the occurrence of epileptic pathological activity and they will also have an anterograde lasting effect on encoding, consolidation and retrieval of memory items after they have disappeared. This conceptual framework is based on recent published preliminary data. The conceptual framework combined with our novel approach present an innovative platform to address the existing gap of knowledge. The proposed research is significant because it will serve as a systematic investigation to provide clear evidence about the nature of memory impairments caused by epileptic activity in the MTL. This will guide future work to design interventions in order to reduce the deleterious effects of pathological epileptic activity using novel neuromodulation methods. Our long-term ambition is that in patients implanted with chronic neuromodulation devices we use our evidence to design novel means by which we not only control seizures but more importantly reverse the cognitive deficits or even enhance the reserve functions of the epileptic tissue by silencing ongoing pathological epileptic discharges that we confirm to be toxic to human cognition.