Neuronal mechanisms of human episodic memory

人类情景记忆的神经机制

• 批准号: 10452541
• 负责人: Adam Nathaniel Mamelak
• 金额: $ 157.28万
• 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/10452541
• 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为决策提供信息对人类来说是必不可少的 认知，但潜在的神经机制仍然知之甚少。这项研究的长期目标是 是对人类记忆的电路水平的理解，从而能够开发出治疗 记忆障碍的破坏性影响。我们的实验利用难得的机会在体内记录来自 耐药治疗患者多个脑区同时存在单个神经元 癫痫。总体目标是继续和扩大多机构(锡达斯-西奈/加州理工学院，约翰斯 霍普金斯大学，多伦多大学，儿童/哈佛大学，加州大学丹佛分校，UCSB)，集成的多学科团队。共同，我们 拥有专业知识和患者数量来测试人类记忆的神经底物上的关键预测。我们会 利用(I)清醒人类的活体记录的组合来评估记忆强度 可信度评级，(Ii)测试因果关系的焦点电刺激，和(Iii)计算分析和建模。 我们将应用这些技术来研究关于发作机制的三个主要假说 记忆。首先，我们将确定持续神经元活动在将工作记忆转化为长时间记忆中的作用。 术语陈述性记忆(目标1)。其次，我们将确定陈述性记忆是如何被翻译成 决定(目标2)。第三，我们将调查事件分割、时间绑定和恢复在 暂时延长的经验有助于情景记忆。这项工作的预期结果是 史无前例地描述了情节记忆是如何形成、检索和用于决策的，以及 时间延伸的经历是如何被分割成不同但相互关联的情节的。这项工作意义重大 因为我们通过测试基于电路的假说，超越了神经元和大脑区域的“部件清单” 同时记录多个额叶皮质和皮质下颞叶的单个神经元 人类正在形成、宣告和描述他们的记忆。拟议中的工作具有不同寻常的创新性 因为我们结合了人类行为中多个区域的单个神经元记录，开发了新的方法来 植入电极的无创定位和电刺激及直接检测已久 证据积累在记忆提取中作用的理论预测。第二项重大创新 是我们的团队，它结合了几个主要中心的病人数量和专业知识，以最大限度地利用 难得的神经外科机会，可以直接研究人类神经系统。这一创新方法 使我们能够研究人类记忆的电路级机制，而这些机制不能在 在人类或动物模型中也是如此。这种体内单个神经元的多学科综合组合 生理学、行为和建模将大大有助于我们对电路和模式的理解 引起人类记忆的神经活动，这是人类神经科学的中心目标， 尤其是大脑的主动性。