ASSOCIATIVE RETRIEVAL AND MISMATCH SIGNALS IN THE CA FIELDS OF HUMAN HIPPOCAMPUS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. While the role of the hippocampus in declarative memory is well established, the mechanisms subserved by component subfields remain underspecified. Within the hippocampuswhich includes dentate gyrus, CA3, CA1, and subiculumit has been hypothesized that CA3 and CA1 differentially support memory-based associative predictions and the detection of associative prediction error. From this perspective, CA3 is posited to encode conjunctive memories that are subsequently "pattern completed" during associative retrieval, in essence making predictions about the present based on associative knowledge acquired in the past. CA3 is thought to pass these predictions to CA1, which is positioned to compare this output from memory with input from entorhinal cortex that transmits the present state of "sensory reality". Specific Aims: We seek to examine the functional contributions of human CA3 and CA1 to associative retrieval and the detection of associative prediction error. Methods and Materials: We used high-resolution fMRI to measure the functional response of MTL corticesperirhinal, parahippocampal, and entorhinaland the subfields of hippocampus. Subjects encoded face-house pairs, and were subsequently scanned at 3T while performing cued-recall followed by a match/mismatch probe decision. On each recall trial, one element of a studied pair served as the retrieval cue, which was followed by a 7.5-s delay during which the subject attempted to retrieve the associate. Following the delay, a probe was presented¿either the correct associate (match) or an incorrect item (mismatch); subjects had 750 ms to respond.