Fractionating Prefrontal Contributions to Memory

描述(由申请人提供)： 记忆过去的事件或“情节记忆”的能力几乎是日常生活中每一种行为的基础。可悲的是，情景记忆在精神疾病(如精神分裂症)和神经疾病(如创伤性脑损伤)中受到严重干扰，记忆障碍患者往往无法独立工作或生活。本项目的目标是研究人脑中时间记忆(“何时记忆”)的神经机制。现有证据表明，前额叶皮质(PFC)参与了时间记忆，但PFC的作用时间和方式尚不清楚，不同的PFC亚区在时间记忆中是否发挥不同的作用也不清楚。因此，我们建议解决四个重要且相互关联的问题：(1)PFC是否支持时间顺序记忆，即使它是偶然的或与任务无关的？我们将使用功能磁共振成像(FMRI)和脑电(EEG)数据的时频分析来检验这一假设，即PFC有助于记忆时间背景信息，即使它与编码或提取意图是附带的或无关的。(2)PFC对时间信息的工作记忆(WM)和长时记忆(LTM)是否都有贡献？我们将使用fMRI和EEG来测试PFC是否支持WM中的时序信息保留和LTM中的时序信息的编码和检索。(3)PFC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是什么关系？我们将使用功能磁共振成像来测试相似或不同的PFC亚区可能在多大程度上参与基于时间顺序、语义相关性或空间邻接性形成关联。(4)PFC中是否存在时序信息的层次化表征？我们将使用fMRI来测试PFC中的渐进式喙区域是否可能参与在越来越广泛的时间尺度上对时间背景信息的编码和维护。问题1和2集中于识别PFC对时间顺序记忆的贡献的条件，而问题3和4测试关于不同PFC亚区在时间记忆中的相对参与的预测。总而言之，拟议的研究全面调查了人脑中时间记忆的机制。这些研究的结果将使我们第一次能够开发出一个详细的模型，说明PFC和其他大脑区域是如何支持时间背景记忆的。澄清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障碍的严重影响，与创伤性脑损伤等神经疾病有关。这项拟议的研究可能会带来诊断和治疗记忆障碍的新方法。

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.