Fractionating Prefrontal Contributions to Memory

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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.