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). .

Public Health Relevance

The proposed research investigates how development of hippocampus and prefrontal cortex the human brain supports memory and reasoning during childhood, adolescence, and adulthood. A growing body of empirical work has shown that difficulties with memory and reasoning in development are associated with poor academic outcomes, as well as with several mental health disorders with developmental onsets, including autism, depression, Fragile X, and schizophrenia. Isolating the neural mechanisms that underlie changes in memory and reasoning ability from childhood to adulthood may thus help identify markers of atypical development and contribute to interventions that may improve both cognitive and academic outcomes.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Buhring, Bettina D
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University of Texas Austin
Schools of Arts and Sciences
United States
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Spalding, Kelsey N; Schlichting, Margaret L; Zeithamova, Dagmar et al. (2018) Ventromedial Prefrontal Cortex Is Necessary for Normal Associative Inference and Memory Integration. J Neurosci 38:3767-3775
Zeithamova, Dagmar; Gelman, Bernard D; Frank, Lea et al. (2018) Abstract Representation of Prospective Reward in the Hippocampus. J Neurosci 38:10093-10101
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Schlichting, Margaret L; Preston, Alison R (2016) Hippocampal-medial prefrontal circuit supports memory updating during learning and post-encoding rest. Neurobiol Learn Mem 134 Pt A:91-106
Zeithamova, Dagmar; Manthuruthil, Christine; Preston, Alison R (2016) Repetition suppression in the medial temporal lobe and midbrain is altered by event overlap. Hippocampus 26:1464-1477
Mack, Michael L; Preston, Alison R (2016) Decisions about the past are guided by reinstatement of specific memories in the hippocampus and perirhinal cortex. Neuroimage 127:144-157

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