When memories relate: medial temporal and prefrontal contributions to memory integration and inference
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Memory is of immeasurable importance to the human experience. It has been known for decades that memory for individual events is supported by the medial temporal lobes (MTL), which include the hippocampus and adjacent cortex. Emerging research suggests that by retrieving related prior experiences during new learning, connections can also be formed among memories to create knowledge that spans events. Such integration mechanisms might be further influenced by memory models stored in medial prefrontal cortex (PFC), which serve to guide learning-phase retrieval and integrate across related memories. In contrast, lateral PFC might maintain separate representations for related events, consistent with its role in resolving interference. This dissertation used functional magnetic resonance imaging (fMRI) in humans to investigate the MTL and PFC mechanisms that link content across episodes. The first experiment investigated the contributions of hippocampal subfields to this encoding mechanism. Consistent with its hypothesized role in detecting inconsistencies and integrating across memories, integration signatures were isolated to the hippocampal CA1 subfield. The second experiment interrogated two aspects of offline processes that promote integration. First, neural evidence for reinstatement of initially learned content and enhanced hippocampal communication with content-specific visual regions during rest was associated with a behavioral index of integration. Moreover, enhanced functional connectivity between hippocampus and medial PFC both during and immediately following learning of related information was associated with better integration. This relationship was mirrored in hippocampal-medial PFC white matter integrity. The third experiment interrogated the nature of the hippocampal and prefrontal representations that underlie memory integration. Results revealed dissociable integration and separation signatures in hippocampus and PFC, highlighting how neural representations of memory elements can simultaneously promote integration across related events and protect from interference. In line with computational theory, these effects were also modulated by the manner in which events were experienced. Taken together, these studies provide insight into the neural mechanisms supporting the dynamic interactions among related memories. More broadly, this dissertation represents an important shift in the scientific study of memory, from exploring memory for individual events to investigating how memories may be derived across experiences to support appropriate action in novel situations.