Behavioral relevance of hippocampal pattern separation and completion processes

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DESCRIPTION (provided by applicant): Two key processes thought to be critical for memory function are pattern separation, or the ability to create distinct memories for similar events and pattern completion, or the process of retrieving previously learned information when presented with a slightly different version of the information. A large body of previous work stresses that the hippocampus is ideally suited to perform both of these crucial functions pertaining to storing and retrieving distinct memories. However, it is currently unknown how pattern separation and pattern completion processes are related to behavior. It is critical to understand how these core hippocampal processes are indeed relevant for human memory in order to fully understand the basic mechanisms of hippocampal function as well as mental health diseases associated with hippocampal dysfunction. This proposal uses high-resolution functional magnetic resonance imaging (fMRI) to investigate how responses in regions of the human hippocampus are related to pattern separation and completion processes and measures of behavioral memory. In Aim 1, we will ask if pattern separation and completion in the hippocampus are associated with implicit, behavioral memory judgments. In addition to this basic research question, we will engage in translational research in Aim 1 by comparing our results to single neuron recordings currently being collected in a parallel behavioral paradigm. This will allow for the comparison of hippocampal network function between humans and animal models to directly evaluate the contributions of animal models for understanding memory formation in humans. Aim 2 will address the question of whether pattern separation and completion processes are manifested at the level of distributed patterns of activity across the entire human hippocampus. The relationship between distributed hippocampal activity patterns and explicit behavioral categorizations will be assessed to ask if these activity patterns are important for behavioral decisions. In sum, this proposal will address important questions of how human hippocampal function is related to behavior by performing high-resolution fMRI during implicit and explicit behavioral memory tasks. This work is essential for understanding basic mechanisms of human hippocampal function and how these mechanisms go awry in disease states. PUBLIC HEALTH RELEVANCE: This proposal is relevant to public health as our goal is to describe the core mechanisms underlying our ability store and retrieve distinct memories and ask how these mechanisms are related to subjective memory experiences in humans. It is important to examine mechanisms of human memory formation in conjunction with behavior in order to understand how processes of memory formation are relevant for diseases in which memory function is impaired, such as autism, schizophrenia, and depression.