Fractionating Prefrontal Contributions to Memory

描述（由申请人提供）： 记忆过去事件的能力，或“情景记忆”，几乎是日常生活中每一个行为的基础。可悲的是，情节记忆在精神病患者中受到严重破坏（例如，精神分裂症）和神经学（例如，创伤性脑损伤）病症，并且患有记忆障碍的患者经常不能独立工作或生活。本项目的目的是研究人类大脑中时间记忆（“何时记忆”）的神经机制。现有证据表明，前额叶皮层（prefrontalcortex，PFC）对时间记忆有一定的作用，但目前尚不清楚PFC在时间记忆中的作用时间和作用方式，也不清楚不同的PFC亚区在时间记忆中是否发挥着不同的作用。因此，我们提出了4个重要的和相互关联的问题：（1）PFC是否支持记忆的时间顺序，即使它是偶然的或任务无关？我们将使用功能性磁共振成像（FMRI）和脑电图（EEG）数据的时频分析来检验这一假设，即PFC有助于记忆的时间背景信息，即使它是偶然的或无关的编码或检索意图。(2)前额叶皮层是否对时间信息的工作记忆和长时记忆都有贡献？我们将使用功能磁共振成像和脑电图来测试是否PFC既支持WM的时间顺序信息的保留和LTM的时间信息的编码和检索。(3)前额叶皮层在基于时间顺序的联想记忆中的作用与它在其他类型联想记忆中的作用之间有什么关系？我们将使用功能磁共振成像来测试在何种程度上相似或不同的PFC亚区可能参与形成基于时间顺序，语义相关性，或空间邻接的协会。(4)PFC中是否存在时序信息的层次表示？我们将使用功能磁共振成像来测试是否在PFC逐步吻区可能参与编码和维护的时间背景信息在越来越广泛的时间尺度。问题1和2侧重于确定条件下，前额叶皮层有助于记忆的时间顺序，而问题3和4测试预测的相对参与不同的前额叶皮层次区域的时间记忆。总的来说，拟议的研究全面调查了人类大脑中的时间记忆机制。这些研究的结果将使我们第一次开发出一个详细的模型，来研究前额叶皮层和其他大脑区域如何支持时间背景的记忆。阐明PFC如何支持记忆过程的基础研究可以为记忆障碍的新诊断和治疗方法提供基础。 公共卫生相关性： 我们将使用最先进的技术来识别大脑中允许人们记住过去事件发生时间的区域。对支持记忆的大脑机制的基础研究至关重要，因为记忆受到精神分裂症等精神疾病和创伤性脑损伤等神经系统疾病的严重影响。这项拟议中的研究可以为诊断和治疗记忆障碍提供新的方法。

DESCRIPTION (provided by applicant): The ability to remember a past event, or "episodic memory" is fundamental to almost every act of daily living. Tragically, episodic memory is severely disrupted in psychiatric (e.g., Schizophrenia) and neurological (e.g., traumatic brain injury) conditions, and patients with memory disorders are frequently unable to work or live independently. The goal of the present project is to investigate the neural mechanisms of temporal memory ("memory for when") in the human brain. The available evidence indicates that the prefrontal cortex (PFC) contributes to temporal memory, but it is unclear when or how the PFC contributes and it is also unclear whether different PFC subregions play different roles in temporal memory. We therefore propose to address 4 important and inter-related questions: (1) does the PFC support memory for temporal order even when it is incidental or task-irrelevant? We will use functional magnetic resonance imaging (FMRI) and time frequency analyses of electroencephalography (EEG) data to test the hypothesis that the PFC contributes to memory for temporal context information even when it is incidental or irrelevant to encoding or retrieval intentions. (2) Does the PFC contribute to both working memory (WM) and long-term memory (LTM) for temporal information? We will use FMRI and EEG to test whether the PFC supports both retention of temporal order information in WM and the encoding and retrieval of temporal information in LTM. (3) What is the relationship between the role of the PFC in memory for associations based on temporal order and its role in memory for other kinds of associations? We will use FMRI to test the extent to which similar or different PFC subregions may be involved in forming associations based on temporal order, semantic relatedness, or spatial contiguity. (4) Is there a hierarchical representation of temporal order information in PFC? We will use FMRI to test whether progressively rostral areas in PFC may be involved in encoding and maintenance of temporal context information at increasingly broad timescales. Questions 1 & 2 focus on identifying the conditions under which the PFC contributes to memory for temporal order, whereas questions 3 & 4 test predictions about the relative involvement of different PFC subregions in temporal memory. Collectively, the proposed studies comprehensively investigate the mechanisms for temporal memory in the human brain. Results from these studies will allow us, for the first time, to develop a detailed model of how the PFC and other brain areas support memory for temporal context. Basic research clarifying how the PFC supports memory processes can provide a foundation for new diagnostic and therapeutic approaches to memory disorders. PUBLIC HEALTH RELEVANCE: We will use state of the art techniques to identify the regions in the brain that allow people to remember when a past event occurred. Basic research on the brain mechanisms that support memory is critically important because memory is seriously affected by psychiatric disorders such as schizophrenia and neurological conditions such as traumatic brain injury are associated. The proposed research can lead to new approaches to the diagnosis and treatment of memory disorders.