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

颞叶癫痫活动期间目标导向行为和记忆的实验研究

• 批准号: 10153120
• 负责人: Josef Parvizi
• 金额: $ 19.7万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10153120
• 关键词: Address; Adult; Adverse effects; Affect; Amnesia; Anatomy; Behavior; Behavioral; Brain; Chronic; Clinical; Cognition; Cognitive; Cognitive deficits; Data; Devices; Dimensions; Electrodes; Electroencephalography; Epilepsy; Evaluation; Event; Face; Focal Seizure; Frequencies; Future; Goals; High Frequency Oscillation; Hippocampus (Brain); Human; Impact Seizures; Impaired cognition; Impairment; Implant; Individual; Injury; Intervention; Investigation; Knowledge; Life; Measures; Medial; Medical; Memory; Memory Loss; Memory impairment; Methodology; Methods; Mind; Mission; Nature; Neurosciences; Operative Surgical Procedures; Partial Epilepsies; Pathologic; Patients; Performance; Physiological; Problem behavior; Process; Public Health; Publishing; Reaction Time; Refractory; Research; Research Personnel; Retrograde amnesia; Sampling; Science; Seizures; Severities; Site; Stimulus; Structure; Task Performances; Temporal Lobe; Temporal Lobe Epilepsy; Testing; Time; Tissues; United States National Institutes of Health; Work; base; behavioral impairment; clinical phenotype; clinical practice; design; experience; experimental study; implantable device; innovation; memory consolidation; memory encoding; memory process; memory recognition; memory retrieval; millisecond; neural correlate; neurophysiology; neuroregulation; novel; novel strategies; prevent; relating to nervous system; response; social; therapy design; treatment strategy

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.

项目摘要 临床神经科学的一个广泛而总体的目标是开发神经元过程的机理说明 在特定的解剖功能网络中，解释了特定的临床表型。有一个基本 理解癫痫发作和癫痫病理活性的差距（即不仅癫痫发作，而且还 诸如高频振荡之类的活动）会影响患者的认知。人类认知的核心部分是 能够记住的能力。而记忆功能的机制及其与内侧临时叶的关系 已经详细研究了结构，并且有大量有关记忆功能障碍的信息 暂时的叶癫痫，尚不清楚记忆功能如何影响癫痫发射和 癫痫发作。焦点临时叶的癫痫发作是否能够损害目标的任务，这也尚不清楚 表现。在临床实践中，我们根据患者是否记住事件或 没有，但是我们对癫痫发作期间患者记忆的情况没有机械理解 以及癫痫发作如何影响前面和后续经历的记忆。同样，我们对 邮政状态下认知定义的性质。拟议项目的目标是克服方法论 MTL癫痫患者的局限性和测试目标指导的行为和记忆。这里的目的是 表征癫痫活动与面向目标的任务性能与内存之间的关系 加工。该项目的中心假设是MTL中的癫痫活动不仅会影响记忆 在发生时进行处理，但也会通过干扰的巩固来产生逆行效应 在发生癫痫病理活性之前出现的记忆项，它们也将具有 对记忆项目消失后编码，合并和检索的顺行持久影响。 该概念框架基于最新发布的初步数据。概念框架结合了 通过我们的新方法，提出了一个创新的平台，以解决现有的知识差距。提议 研究之所以重要，是因为它将作为系统投资，以提供有关 MTL中癫痫活性引起的记忆障碍的性质。这将指导未来的设计 干预措施以减少使用新颖的病理癫痫活性的有害影响 神经调节方法。我们的长期野心是，在植入慢性神经调节的患者中 我们使用证据来设计新型手段，我们不仅可以控制癫痫发作，而且更重要的是 扭转认知缺陷，甚至通过沉默持续的癫痫组织的储量功能增强的储备功能 我们确认对人类认知有毒的病理癫痫排放。