Higher order cognition depends critically on the ability to form and retrieve lasting memories for events, or episodic long-term memory (LTM). The prefrontal cortex (PFC) is thought to play a critical role in the implementation of cognitive control processes that guide LTM formation and retrieval, and dysfunction of the prefrontal cortex (PFC) in neurological (e.g., traumatic brain injury) and psychiatric (e.g., schizophrenia) disorders has been linked to deficits in LTM. Research clarifying the nature of cognitive control processes implemented by specific PFC subregions and their relationship to LTM can provide a relevant foundation for new diagnostic and therapeutic approaches to such conditions. The current project will utilize converging evidence from event-related functional magnetic resonance imaging (fMRI) and event-related brain potential (ERP) experiments to test predictions generated from a novel theory of prefrontal organization. The first specific aim is to specify how different lateral PFC regions contribute to LTM formation. Four event-related fMRI experiments will test the hypothesis that ventrolateral regions of PFC modulate LTM formation through the selection and maintenance of goal-relevant item representations, whereas dorsolateral PFC regions through the formation and manipulation of relations between multiple items that are active in memory. The second specific aim is to specify how anterior PFC contributes to LTM retrieval. I will test the hypothesis that anterior PFC is critical for specifying the kinds of information that will be used to make a memory decision. This hypothesis makes specific predictions about both the timing and the functional characteristics of anterior PFC recruitment during retrieval. This hypothesis will be contrasted against competing accounts in three fMRI and three ERP studies that will separately examine PFC activity during the selection and maintenance of memory decision criteria and during successful memory retrieval. Results from these studies will enable the development of a theory that characterizes, both cognitively and neurally, the processes implemented by specific prefrontal regions that relate to memory.
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