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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-C (02))
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Osborn, Bettina D
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University of California Davis
Schools of Arts and Sciences
United States
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Jenkins, Lucas J; Ranganath, Charan (2016) Distinct neural mechanisms for remembering when an event occurred. Hippocampus 26:554-9
Addante, Richard James (2015) A critical role of the human hippocampus in an electrophysiological measure of implicit memory. Neuroimage 109:515-28
Hsieh, Liang-Tien; Ranganath, Charan (2015) Cortical and subcortical contributions to sequence retrieval: Schematic coding of temporal context in the neocortical recollection network. Neuroimage 121:78-90
Libby, Laura A; Hannula, Deborah E; Ranganath, Charan (2014) Medial temporal lobe coding of item and spatial information during relational binding in working memory. J Neurosci 34:14233-42
Flegal, Kristin E; Marín-Gutiérrez, Alejandro; Ragland, J Daniel et al. (2014) Brain mechanisms of successful recognition through retrieval of semantic context. J Cogn Neurosci 26:1694-704
Hsieh, Liang-Tien; Gruber, Matthias J; Jenkins, Lucas J et al. (2014) Hippocampal activity patterns carry information about objects in temporal context. Neuron 81:1165-78
Hsieh, Liang-Tien; Ranganath, Charan (2014) Frontal midline theta oscillations during working memory maintenance and episodic encoding and retrieval. Neuroimage 85 Pt 2:721-9
Gruber, Matthias J; Watrous, Andrew J; Ekstrom, Arne D et al. (2013) Expected reward modulates encoding-related theta activity before an event. Neuroimage 64:68-74
Roberts, Brooke M; Hsieh, Liang-Tien; Ranganath, Charan (2013) Oscillatory activity during maintenance of spatial and temporal information in working memory. Neuropsychologia 51:349-57
Gold, James M; Barch, Deanna M; Carter, Cameron S et al. (2012) Clinical, functional, and intertask correlations of measures developed by the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia Consortium. Schizophr Bull 38:144-52

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