Hippocampal and prefrontal contributions to memory integration

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PROJECT SUMMARY/ABSTRACT Hippocampus (HPC) and prefrontal cortex (PFC) structure and connectivity continue to develop through childhood and adolescence, developmental periods that are associated with substantial gains in memory and cognitive ability. While such structural changes are well documented, we know little about the functions that HPC and PFC development confer, fundamentally limiting our understanding of the mechanisms of cognitive development. The overarching goal of this proposal is to test the hypothesis that the representational capacity of the HPC—PFC memory circuit transforms across development from a system that stores individual memories in childhood to a mature system in adulthood wherein cognitive maps represent the relationships among multiple episodes. Cognitive maps allow memory to extend beyond direct experience by coding unobserved relationships among multiple events. In the absence of a mature HPC—PFC system, such knowledge extension through cognitive map formation may be limited in children and adolescents, and therefore result in development differences in learning, decision making, and reasoning behaviors that require consideration of the relationships among multiple events. Moreover, the differential time course of HPC and PFC development, in which mature HPC function may emerge earlier than that of PFC, suggests there may be distinct patterns of memory representation and behavior in adolescence that differ from both childhood and adulthood. To answer these open questions, the proposed studies use a combination of high-resolution functional magnetic resonance imaging (fMRI) and sophisticated multivariate pattern analyses in children (7-9 years), younger adolescents (10-12 years), older adolescents (13-15 years), and adults (25-30 years). Using these methods, we will quantify: (1) age-related differences in HPC—PFC memory integration and separation strategies that support cognitive map formation and (2) how developmental differences in neural representation impact temporal (Aim 1), spatial (Aim 2), and event memory (Aim 3). Collectively, the results from this project will provide a key test of fundamental theories of cognitive development and substantially advance our knowledge of the representational capacities of the HPC—PFC memory system at different ages. In doing so, the findings have the potential to inform interventions designed to enhance memory and reasoning abilities that rely on cognitive maps, including in individuals diagnosed with mental health or neurodevelopmental disorders associated with memory deficits (e.g., autism, depression, Fragile X, or schizophrenia). .