PT - JOURNAL ARTICLE AU - Anna C. Schapiro AU - Elizabeth A. McDevitt AU - Timothy T. Rogers AU - Sara C. Mednick AU - Kenneth A. Norman TI - Human hippocampal replay during rest prioritizes weakly-learned information and predicts memory performance AID - 10.1101/173021 DP - 2017 Jan 01 TA - bioRxiv PG - 173021 4099 - http://biorxiv.org/content/early/2017/08/06/173021.short 4100 - http://biorxiv.org/content/early/2017/08/06/173021.full AB - There is now extensive evidence that the hippocampus replays experiences during quiet rest periods, and that this replay benefits subsequent memory. A critical open question is how memories are prioritized for replay during these offline periods. We addressed this question in an experiment in which participants learned the features of 15 objects and then underwent fMRI scanning to track item-level replay in the hippocampus using pattern analysis during a rest period. Objects that were remembered less well were replayed more during the subsequent rest period, suggesting a prioritization process in which weaker memories—memories most vulnerable to forgetting—are selected for wake replay. Participants came back for a second session, either after a night of sleep or a day awake, and underwent another scanned rest period followed by a second memory test. In the second session, more hippocampal replay of a satellite during the rest period predicted better subsequent memory for that satellite. Only in the group with intervening sleep did rest replay predict improvement from the first to second session. Our results provide the first evidence that replay of individual memories occurs during rest in the human hippocampus and that this replay prioritizes weakly learned information, predicts subsequent memory performance, and relates to memory improvement across a delay with sleep.