Neuronal mechanisms of human episodic memory

人类情景记忆的神经机制

• 批准号: 9765420
• 负责人: Adam Nathaniel Mamelak
• 金额: $ 114.12万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765420
• 关键词: Amygdaloid structure; Animal Model; Area; Attention; BRAIN initiative; Behavior; Brain; Cells; Child; Clip; Cognition; Complex; Computer Analysis; Computer Simulation; Decision Making; Development; Disease; Drug resistance; Electric Stimulation; Electrodes; Epilepsy; Episodic memory; Etiology; Event; Eye Movements; Goals; Hippocampus (Brain); Human; Implant; Implanted Electrodes; Investigation; Judgment; Knowledge; Learning; Link; Maintenance; Medial; Memory; Memory Disorders; Methods; Modeling; Nervous system structure; Neurons; Neurosciences; Ocular Physiology; Outcome; Outcomes Research; Patients; Pattern; Physiology; Process; Property; Research; Retrieval; Role; Short-Term Memory; Signal Transduction; Site; Stimulus; Structure; Supporting Cell; System; Techniques; Temporal Lobe; Testing; Time; Translating; Work; awake; base; experience; experimental study; flexibility; frontal lobe; in vivo; innovation; insight; long term memory; memory recall; memory recognition; memory retrieval; metacognition; movie; multidisciplinary; neural patterning; neuromechanism; programs; relating to nervous system; response; spatiotemporal

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 assemble a multi-institutional (Cedars-Sinai/Caltech, Johns Hopkins, U Toronto, Children’s/Harvard), 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 hypothesis on the mechanisms of episodic memory. First, we will test the prediction that stimulus-specific persistent activity is essential for memory formation (Aim 1). Second, we will determine whether neurons accumulate memory-derived evidence to inform retrieval decisions and/or the confidence (a type of metacognition) about retrieval decisions (Aim 2). Third, we will test the hypothesis that visually-and memory selective cells emerge gradually during temporally extended episodes of experience to gradually create and solidify memories (Aim 3). The expected outcomes of this research are an unprecedented characterization of how declarative memories are formed and used in the human brain. This work is significant because we move beyond a “parts list” of neurons and brain areas by testing circuit-based hypothesis 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 due to their unclear relevance to human memory and its diseases. 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对人类至关重要 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 癫痫总体目标是组建一个多机构（雪松西奈/加州理工学院，约翰霍普金斯，美国 多伦多，儿童/哈佛），综合，多学科的团队。我们共同拥有专业知识和耐心 卷测试人类记忆的神经基板上的关键预测。我们将结合使用（i）在- 在清醒行为的人类中通过置信度等级评估记忆强度的体内记录，（ii）局部 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 技术来研究情节记忆机制的三个总体假设。一是 测试刺激特异性持续活动对记忆形成至关重要的预测（目标1）。第二、 我们将确定神经元是否积累记忆来源的证据，以告知检索决策和/或 关于检索决策的信心（一种元认知）（目标2）。第三，我们将检验假设， 视觉和记忆选择性细胞在时间延长的经验片段中逐渐出现， 逐步创造和巩固记忆（目标3）。这项研究的预期成果是前所未有的 陈述性记忆是如何在人脑中形成和使用的。这项工作意义重大 因为我们超越了神经元和大脑区域的“零件清单”， 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。 人类也没有动物模型，因为它们与人类记忆及其疾病的相关性尚不清楚。这一综合 多学科结合的人类在体单神经元生理学，行为，和建模将有助于 这对我们理解产生人类记忆的神经活动的回路和模式有着重要意义， 这是人类神经科学的核心目标，特别是大脑计划。

项目成果

LITTLE MEMORY EDITORS LIVING INSIDE YOUR BRAIN.

生活在您大脑中的小记忆编辑器。

• DOI: 10.3389/frym.2023.968856
• 发表时间: 2023
• 期刊: Frontiers for young minds
• 作者: Zheng,Jie;Chen,Gordon;Kreiman,Gabriel;Rutishauser,Ueli
• 通讯作者: Rutishauser,Ueli

Volitional control of individual neurons in the human brain.

人脑中单个神经元的意志控制。

• DOI: 10.1093/brain/awab370
• 发表时间: 2021
• 期刊: Brain : a journal of neurology
• 作者: Patel,Kramay;Katz,ChaimN;Kalia,SuneilK;Popovic,MilosR;Valiante,TaufikA
• 通讯作者: Valiante,TaufikA

Electrocorticography During Deep Brain Stimulation Surgery: Safety Experience From 4 Centers Within the National Institute of Neurological Disorders and Stroke Research Opportunities in Human Consortium.

深部脑刺激手术期间的皮质电图：来自人类联盟国家神经疾病和中风研究机会研究所内 4 个中心的安全经验。

• DOI: 10.1093/neuros/nyaa592
• 发表时间: 2021
• 期刊: Neurosurgery
• 影响因子: 4.8
• 作者: Sisterson,NathanielD;Carlson,AprilA;Rutishauser,Ueli;Mamelak,AdamN;Flagg,Mitchell;Pouratian,Nader;Salimpour,Yousef;Anderson,WilliamS;Richardson,RMark
• 通讯作者: Richardson,RMark

Distinct roles of dorsal and ventral subthalamic neurons in action selection and cancellation.

• DOI: 10.1016/j.neuron.2020.12.025
• 发表时间: 2021-03-03
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Mosher CP;Mamelak AN;Malekmohammadi M;Pouratian N;Rutishauser U
• 通讯作者: Rutishauser U