Representation and Binding of Spatial and Temporal Episodic Memories in Human Hip

描述（由申请人提供）：该项目的目标是利用高分辨率功能性磁共振成像（fMRI）和颅内脑电图（iEEG）的创新组合来确定人类情景记忆的神经基础。情景记忆涉及到知道一个事件相对于其他事件发生的地点和时间，这两者都主要取决于海马体。然而，海马体究竟如何以及以何种方式编码情景记忆的空间和时间方面仍不清楚，研究也不充分，特别是在人类中，研究的主要焦点一直是口头情景记忆。使用我们实验室新开发的实验范式，我们将研究情景记忆的空间和时间组成部分，重点关注这些组成部分的两个关键过程：表征和绑定。为了将这些映射到海马体回路，我们使用了高分辨率的功能磁共振成像。与之前在啮齿动物中开发的一些模型相反，我们假设时空表征是海马亚区共享的功能，但亚区CA3/DG在解析上下文元素以表示情节方面起着独特的作用。基于其独特的连通性，我们进一步假设海马亚区CA1在时空结合中发挥核心作用，这与之前关注CA3/DG的模型形成了对比。与两家不同医院的神经学家和神经外科医生合作，我们还将在接受癫痫监测的患者中使用脑电图。这种互补的方法将使我们能够确定情景记忆的一个独立但重要的组成部分：海马体中的协调神经活动是如何作为时空记忆的表征和结合的基础的？海马体长期以来与啮齿动物的空间导航有关，但在人类中尚未得到充分研究。总的来说，我们提出的实验将为情景记忆的神经基础提供新的见解，因为它们在范式和方法上采取了新的方法来解决这个问题，并允许我们测试几种不同的海马功能模型，包括我们的模型。神经退行性疾病，如中风、癫痫和精神分裂症，影响海马体亚区功能和那里的协调神经活动，通常导致患有这些疾病的患者出现空间定向障碍和时间混乱的症状。因此，我们的方法也将对影响海马体的神经疾病产生重大影响。

DESCRIPTION (provided by applicant): The goal of this project is to determine the neural basis of human episodic memory using an innovative combination of high-resolution functional magnetic resonance imaging (fMRI) and intracranial EEG (iEEG). Episodic memory involves knowing where and when an event occurred relative to other events, both of which depend critically on the hippocampus. Yet exactly how and in what manner the hippocampus codes spatial and temporal aspects of episodic memory remains unclear and understudied, particularly in humans where the primary focus of research has been on verbal episodic memory. Using a newly developed experimental paradigm from our lab, we will study the spatial and temporal components of episodic memory, focusing on two critical processes underlying these components: representation and binding. To map these onto the hippocampal circuit, we employ high-resolution fMRI. In contrast to some previous models developed in the rodent, we hypothesize that spatio-temporal representation is a function shared across hippocampal subregions but that subregion CA3/DG plays a distinct role in parsing elements of context to represent an episode. We further hypothesize a central role for hippocampal subregion CA1 in spatio-temporal binding based on its unique connectivity, in contrast to previous models that have focused on CA3/DG. Collaborating with a team of neurologists and neurosurgeons at two different hospitals, we will also employ iEEG in patients undergoing seizure monitoring. This complementary approach will allow us to determine a separate yet critical component of episodic memory: how does coordinated neural activity in the hippocampus, long linked with spatial navigation in the rodent but understudied in humans, underlie representation and binding of spatio-temporal memory? Overall, our proposed experiments will provide novel insight into the neural basis of episodic memory as they take a new approach to this issue paradigmatically and methodologically and allow us to test several different models of hippocampal function, including our model. Neurodegenerative diseases such as stroke, epilepsy, and schizophrenia impact hippocampal subregion function and coordinated neural activity there, often resulting in symptoms of spatial disorientation and temporal confusion in patients afflicted with these conditions. Our approach thus will also have significant implications for neural diseases that affect the hippocampus. PUBLIC HEALTH RELEVANCE: The hippocampus is critical for episodic memory, particularly in coding where and when events occurred. Neurodegenerative diseases such as stroke, epilepsy, and schizophrenia often impact hippocampal function and result in impairments to spatio-temporal episodic memory. Determining how and in what manner the human hippocampus represents space and time will advance our understanding of how damage to this area affects episodic memory.