CRCNS Research Proposal: US-German Collaboration: Roles of place and grid cells and phase precession in human spatial and episodic memory

CRCNS 研究提案：美德合作：位置和网格细胞以及相位进动在人类空间和情景记忆中的作用

• 批准号: 1724243
• 负责人: Joshua Jacobs
• 金额: $ 61.68万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-11-01 至 2021-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1724243&HistoricalAwards=false
• 关键词: CRCNS; Research; Proposal; US; German

A fundamental issue that affects everyone's life is how the brain represents memories and how this process sometimes experiences dysfunction. To examine this topic, our research project uses direct human brain recordings to characterize the brain signals that represent aspects of individual memories. A key question is understanding how the brain supports tasks such as answering "Where did I leave my keys this morning"? In this project, we will test how memory-related spatial information is represented by the activity of individual cells in the human brain. We perform this work by examining direct human brain recordings, working with patients who are undergoing neurosurgery to map their epilepsy. While the brain signals are recorded, patients play a video game that involves spatial navigation and memory. We measure patterns of electrical activity that show how the brain stores memories for individual spatial locations and well as for events in time. In particular, we focus on measuring the role in memory of a particular cell type, the "grid cell", that is known to play a role in spatial navigation, to test whether the brain's navigation network also supports memory storage. By revealing the neural basis of memory, this work has implications for developing treatments for memory and navigation disorders such as Alzheimer's Disease. In addition to these scientific objectives, there is a direct educational component to our work. Through performing our research, we will train students at various levels, including graduate, undergraduate, and post-doctoral fellows, on the methods used for studying the human brain and its involvement in memory. We also will develop curriculum material for K-12 and undergraduate students to learn about how the brain supports memory and spatial cognition.Scientifically, the goal of this work is characterize the neural basis of episodic memory by identifying how the rate and timing of the activations of human grid and place cells support the storage of spatial memories. By examining these cells' activations as patients perform our hybrid spatial-episodic memory task, we test the broad hypothesis that there is a fundamental link between how the brain represents the location and timing of when events occur. Our main hypothesis is that the activity of grid cells during memory retrieval represents the spatial location where an event occurred. We also test the role of grid cells in memory retrieval based on cues (Aim 1) as well as self-initiated recalls from memory search (Aim 2). Finally, will also evaluate whether temporal ordering of memories is stored via a rhythmic process in the brain, called theta-band phase precession. Our findings are likely to expand our understanding of how the human entorhinal cortex and hippocampus support a range of cognitive and behavioral processes. A companion project is being funded by the Federal Ministry of Education and Research, Germany (BMBF).

影响每个人生活的一个基本问题是大脑是如何表达记忆的，以及这个过程有时是如何出现功能障碍的。为了研究这个主题，我们的研究项目使用直接的人类大脑记录来表征代表个人记忆方面的大脑信号。一个关键的问题是理解大脑是如何支持诸如回答“今天早上我把钥匙放在哪里了”这样的任务的？在这个项目中，我们将测试与记忆相关的空间信息是如何通过人类大脑中单个细胞的活动来表示的。我们通过检查直接的人类大脑记录来完成这项工作，与正在接受神经外科手术的患者一起绘制他们的癫痫图。在记录大脑信号的同时，患者玩一个涉及空间导航和记忆的视频游戏。我们测量了脑电活动的模式，这些模式显示了大脑是如何储存个体空间位置和时间事件的记忆的。我们特别关注测量一种特定细胞类型在记忆中的作用，即“网格细胞”，它已知在空间导航中发挥作用，以测试大脑的导航网络是否也支持记忆存储。通过揭示记忆的神经基础，这项工作对开发记忆和导航障碍（如阿尔茨海默病）的治疗方法具有启示意义。除了这些科学目标之外，我们的工作还有一个直接的教育成分。通过开展我们的研究，我们将培养不同层次的学生，包括研究生，本科生和博士后，关于研究人类大脑及其参与记忆的方法。我们还将为K-12和本科生开发课程材料，以了解大脑如何支持记忆和空间认知。从科学上讲，这项工作的目标是通过确定人类网格细胞和位置细胞的激活速度和时间如何支持空间记忆的存储来表征情景记忆的神经基础。当患者执行我们的混合空间-情景记忆任务时，通过检查这些细胞的激活情况，我们验证了一个广泛的假设，即大脑如何表征事件发生的位置和时间之间存在着根本的联系。我们的主要假设是，在记忆检索过程中，网格细胞的活动代表了事件发生的空间位置。我们还测试了网格细胞在基于线索的记忆检索（目的1）以及记忆搜索的自我发起回忆（目的2）中的作用。最后，我们还将评估记忆的时间顺序是否通过大脑中称为θ波段相位进动的有节奏的过程来存储。我们的发现可能会扩展我们对人类内嗅皮层和海马体如何支持一系列认知和行为过程的理解。德国联邦教育和研究部（BMBF）正在资助一个伙伴项目。

项目成果

Hexadirectional Modulation of High-Frequency Electrophysiological Activity in the Human Anterior Medial Temporal Lobe Maps Visual Space

• DOI: 10.1016/j.cub.2018.09.035
• 发表时间: 2018-10
• 期刊: Current Biology
• 影响因子: 9.2
• 作者: T. Staudigl;M. Leszczyński;J. Jacobs;S. Sheth;C. Schroeder;O. Jensen;Christian F. Doeller

Grid-like hexadirectional modulation of human entorhinal theta oscillations

• DOI: 10.1073/pnas.1805007115
• 发表时间: 2018-10-16
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Maidenbaum, Shachar;Miller, Jonathan;Jacobs, Joshua
• 通讯作者: Jacobs, Joshua

Single-Neuron Representations of Spatial Targets in Humans

人类空间目标的单神经元表示

• DOI: 10.1016/j.cub.2019.11.048
• 发表时间: 2020
• 期刊: Current Biology
• 影响因子: 9.2
• 作者: Tsitsiklis, Melina;Miller, Jonathan;Qasim, Salman E.;Inman, Cory S.;Gross, Robert E.;Willie, Jon T.;Smith, Elliot H.;Sheth, Sameer A.;Schevon, Catherine A.;Sperling, Michael R.
• 通讯作者: Sperling, Michael R.