Hippocampal Representations of Targeted Memory Reactivation and Reactivated Temporal Sequences

Abstract

Why are some memories easy to retrieve, while others are more difficult to access? Here, we tested whether we could bias memory replay, a process whereby newly learned information is reinforced by reinstating the neuronal patterns of activation that were present during learning, towards particular memory traces. The goal of this biasing is to strengthen some memory traces, making them more easily retrieved. To test this, participants were scanned during interleaved periods of encoding and rest. Throughout the encoding runs, participants learned triplets of images that were paired with semantically related sound cues. During two of the three rest periods, novel, irrelevant sounds were played. During one critical rest period, however, the sound cues learned in the preceding encoding period were played in an effort to preferentially increase reactivation of the associated visual images, a manipulation known as targeted memory reactivation. Representational similarity analyses were used to compare multi-voxel patterns of hippocampal activation across encoding and rest periods. Our index of reactivation was selectively enhanced for memory traces that were targeted for preferential reactivation during offline rest, both compared to information that was not targeted for preferential reactivation and compared to a baseline rest period. Importantly, this neural effect of targeted reactivation was related to the difference in delayed order memory for information that was cued versus uncued, suggesting that preferential replay may be a mechanism by which specific memory traces can be selectively strengthened for enhanced subsequent memory retrieval. We also found partial evidence of discrimination of unique temporal sequences within the hippocampus. Over time, multi-voxel patterns associated with a given triplet sequence became more dissimilar to the patterns associated with the other sequences. Furthermore, this neural marker of sequence preservation was correlated with the difference in delayed order memory for cued versus uncued triplets, signifying that the ability to reactivate particular temporal sequences within the hippocampus may be related to enhanced temporal order memory for the cued information. Taken together, these findings support the claim that awake replay can be biased towards preferential reactivation of particular memory traces and also suggest that this preferential reactivation, as well as representations of reactivated temporal sequences, can be detected within patterns of hippocampal activation.