Neuronal mechanisms of human episodic memory

人类情景记忆的神经机制

• 批准号: 10268196
• 负责人: Adam Nathaniel Mamelak
• 金额: $ 155.95万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10268196
• 关键词: Animal Model; Area; Attention; BRAIN initiative; Behavior; Behavioral; Behavioral Model; Binding; Brain; Cells; Child; Clip; Cognition; Cognitive; Communities; Computer Analysis; Computer Models; Data; Data Set; Decision Making; Detection; Development; Disease; Electric Stimulation; Electrodes; Epilepsy; Episodic memory; Ethics; Etiology; Event; Fostering; Foundations; Goals; Human; Implant; Implanted Electrodes; Infrastructure; Intractable Epilepsy; Investigation; Knowledge; Light; Link; Maintenance; Medial; Memory; Memory Disorders; Methods; Modeling; Nervous system structure; Neurons; Neurosciences; Ocular Physiology; Operative Surgical Procedures; Outcome; Patients; Physiology; Procedures; Process; Property; Research; Retrieval; Role; Short-Term Memory; Signal Transduction; Site; Source Code; Standardization; Stimulus; Structure; System; Techniques; Temporal Lobe; Testing; Time; TimeLine; Translating; Work; awake; base; design; experience; experimental study; flexibility; in vivo; innovation; insight; long term memory; meetings; memory recall; memory recognition; memory retrieval; movie; multidisciplinary; neural patterning; neuromechanism; neurophysiology; novel; programs; relating to nervous system; response; visual tracking

Project Summary The rapid formation of new memories and the recall of old memories to inform decisions is essential for human cognition, but the underlying neural mechanisms remain poorly understood. The long-term goal of this research is a circuit-level understanding of human memory to enable the development of new treatments for the devastating effects of memory disorders. Our experiments utilize the rare opportunity to record in-vivo from human single neurons simultaneously in multiple brain areas in patients undergoing treatment for drug resistant epilepsy. The overall objective is to continue and expand a multi-institutional (Cedars-Sinai/Caltech, Johns Hopkins, U Toronto, Children's/Harvard, UC Denver, UCSB), integrated, and multi-disciplinary team. Jointly, we have the expertise and patient volume to test key predictions on the neural substrate of human memory. We will utilize a combination of (i) in-vivo recordings in awake behaving humans assessing memory strength through confidence ratings, (ii) focal electrical stimulation to test causality, and (iii) computational analysis and modeling. We will apply these techniques to investigate three overarching hypotheses on the mechanisms of episodic memory. First, we will determine the role of persistent neuronal activity in translating working memories into long- term declarative memories (Aim 1). Second, we will determine how declarative memories are translated into decisions (Aim 2). Third, we will investigate how event segmentation, temporal binding and reinstatement during temporally extended experience facilitate episodic memory. The expected outcomes of this work are an unprecedented characterization of how episodic memories are formed, retrieved and used for decisions, and how temporally extended experiences are segmented to form distinct but linked episodes. This work is significant because we move beyond a “parts list” of neurons and brain areas by testing circuit-based hypotheses by simultaneously recording single-neurons from multiple frontal cortical and subcortical temporal lobe areas in humans who are forming, declaring and describing their memories. The proposed work is unusually innovative because we combine single-neuron recordings in multiple areas in behaving humans, develop new methods for non-invasive localization of implanted electrodes and electrical stimulation and directly test long-standing theoretical predictions on the role of evidence accumulation in memory retrieval. A second significant innovation is our team, which combines the patient volume and expertise of several major centers to maximally utilize the rare neurosurgical opportunities available to directly study the human nervous system. This innovative approach permits us to investigate circuit-level mechanisms of human memory that cannot be studied non-invasively in humans nor in animal models. This integrated multi-disciplinary combination of human in-vivo single-neuron physiology, behavior, and modeling will contribute significantly to our understanding of the circuits and patterns of neural activity that give rise to human memory, which is a central goal of human neuroscience in general and the BRAIN initiative in particular.

项目摘要 新记忆的快速形成和旧记忆的回忆以指导决策对于人类来说至关重要 认知，但潜在的神经机制仍然知之甚少。本研究的长期目标 是对人类记忆的电路级理解，以开发新的治疗方法， 记忆障碍的毁灭性影响。我们的实验利用难得的机会记录体内从 在接受耐药治疗的患者中同时在多个脑区域中的人类单个神经元 癫痫总体目标是继续和扩大一个多机构（雪松西奈/加州理工学院，约翰 霍普金斯，U多伦多，儿童/哈佛，加州大学丹佛分校，UCSB），综合，多学科团队。我们共同 有专业知识和病人数量来测试人类记忆神经基质的关键预测。我们将 利用以下的组合：（i）在清醒行为的人类中的体内记录， 置信度评级，（ii）局灶性电刺激以测试因果关系，以及（iii）计算分析和建模。 我们将应用这些技术来研究三个总体假设的机制，情节 记忆首先，我们将确定持续的神经元活动在将工作记忆转化为长期记忆中的作用， 术语陈述性记忆（目标1）。其次，我们将确定陈述性记忆如何被翻译成 决策（目标2）。第三，我们将研究事件分割，时间绑定和恢复过程中， 时间延长经验促进情景记忆。这项工作的预期成果是 对情景记忆是如何形成、检索和用于决策的前所未有的描述， 时间上延伸的经历是如何被分割成不同但又相互关联的片段的。这项工作意义重大 因为我们通过测试基于电路的假设， 同时记录来自多个额叶皮质和皮质下颞叶区域的单个神经元， 那些正在形成、声明和描述他们记忆的人。拟议中的工作具有不同寻常的创新性 因为我们将联合收割机在人类行为的多个区域的单神经元记录结合起来，开发了新的方法， 无创定位植入电极和电刺激，直接测试长期 证据积累在记忆提取中的作用的理论预测。第二个重大创新 是我们的团队，它结合了几个主要中心的患者数量和专业知识，最大限度地利用 罕见的神经外科机会，可直接研究人类神经系统。这种创新方法 使我们能够研究人类记忆的电路级机制，这些机制无法在非侵入性的情况下进行研究。 人类也不是动物模型。这种综合多学科结合的人体在体单神经元 生理学、行为学和建模将极大地有助于我们对电路和模式的理解 这是人类神经科学的核心目标， 特别是Brain的倡议。