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.

项目概要 临床神经科学的一个广泛而总体的目标是开发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内存在一个基本原理。 在理解癫痫发作和癫痫病理活动（即不仅是癫痫发作而且还包括癫痫发作）方面存在差距 高频振荡等活动）会影响患者的认知。人类认知的核心部分是认知。 记忆能力及其与内侧颞叶的关系。 结构已被详细研究，并且有大量关于记忆功能障碍的信息 颞叶癫痫，目前尚不清楚癫痫放电和记忆功能如何受到影响 局灶性颞叶癫痫发作是否会损害目标导向的任务仍不清楚。 在临床实践中，我们根据患者是否记得事件或对癫痫发作进行分类。 不是，但我们对癫痫发作期间患者的记忆会发生什么变化还没有机制上的了解 同样，我们对癫痫发作如何影响之前和之后经历的记忆知之甚少。 发作后状态期间认知缺陷的本质 该项目的目标是克服方法论。 MTL 癫痫患者的局限性并测试目标导向行为和记忆。 表征癫痫活动与目标导向的任务表现和记忆之间的关系 该项目的中心假设是 MTL 中的癫痫活动不仅会影响记忆。 在其发生时进行处理，但也会通过扰乱整合而产生逆行效应 癫痫病理活动发生前出现的记忆项目，也会有 顺行对记忆项目消失后的编码、巩固和检索产生持久影响。 该概念框架基于最近发布的初步数据。 我们的新颖方法提供了一个创新平台来解决现有的知识差距。 研究意义重大，因为它将作为一项系统调查，为有关问题提供明确的证据。 MTL 中癫痫活动引起的记忆障碍的本质这将指导未来的设计工作。 使用新颖的干预措施来减少病理性癫痫活动的有害影响 我们的长期目标是在患者中植入慢性神经调节方法。 我们使用我们的证据来设计新颖的设备，通过这些设备我们不仅可以控制癫痫发作，更重要的是 通过沉默正在进行的过程来逆转认知缺陷，甚至增强癫痫组织的储备功能 我们确认对人类认知具有毒性的病理性癫痫放电。