The hippocampus is believed to reduce memory interference by disambiguating neural representations of similar events. However, there is limited empirical evidence linking representational overlap in the hippocampus to memory interference. Likewise, it is not fully understood how learning influences overlap among hippocampal representations. Using pattern-based fMRI analyses, we tested for a bidirectional relationship between memory overlap in the human hippocampus and learning. First, we show that learning drives hippocampal representations of similar events apart from one another. These changes are not explained by task demands to discriminate similar stimuli and are fully absent in visual cortical areas that feed into the hippocampus. Second, we show that lower representational overlap in the hippocampus benefits subsequent learning by preventing interference between similar memories. These findings reveal targeted experience-dependent changes in hippocampal representations of similar events and provide a critical link between memory overlap in the hippocampus and behavioural expressions of memory interference.

Summary Across the domains of spatial navigation and episodic memory, the hippocampus is thought to play a critical role in disambiguating (pattern separating) representations of overlapping events. However, it is not fully understood how and why hippocampal patterns become separated. Here, we test the idea that event overlap triggers a ‘repulsion’ among hippocampal representations that develops over the course of learning. Using a naturalistic route-learning paradigm and spatiotemporal pattern analysis of human fMRI data, we found that hippocampal representations of overlapping routes gradually diverged with learning to the point that they became less similar than representations of non-overlapping events. In other words, the hippocampus not only disambiguated overlapping events, but formed representations that ‘reversed’ the objective similarity among routes. This finding, which was selective to the hippocampus, is not predicted by standard theoretical accounts of pattern separation. Critically, because the overlapping route stimuli that we used ultimately diverged (so that each route contained overlapping and non-overlapping segments), we were able to test whether the reversal effect was selective to the overlapping segments. Indeed, once overlapping routes diverged (eliminating spatial and visual similarity), hippocampal representations paradoxically became relatively more similar. Finally, using a novel analysis approach, we show that the degree to which individual hippocampal voxels were initially shared across route representations was predictive of the magnitude of learning-related separation. Collectively, these findings indicate that event overlap triggers a repulsion of hippocampal representations—a finding that provides critical mechanistic insight into how and why hippocampal representations become separated.

The hippocampal memory system is thought to alternate between two opposing processing states: encoding and retrieval. When present experience overlaps with past experience, this creates a potential tradeoff between encoding the present and retrieving the past. This tradeoff may be resolved by memory integration—that is, by forming a mnemonic representation that links present experience with overlapping past experience. Here, we used fMRI decoding analyses to predict when—and establish how—past and present experiences become integrated in memory. In an initial experiment, we alternately instructed subjects to adopt encoding, retrieval or integration states during overlapping learning. We then trained across-subject pattern classifiers to ‘read out’ the instructed processing states from fMRI activity patterns. We show that an integration state was clearly dissociable from encoding or retrieval states. Moreover, trial-by-trial fluctuations in decoded evidence for an integration state during learning reliably predicted behavioral expressions of successful memory integration. Strikingly, the decoding algorithm also successfully predicted specific instances of spontaneous memory integration in an entirely independent sample of subjects for whom processing state instructions were not administered. Finally, we show that medial prefrontal cortex and hippocampus differentially contribute to encoding, retrieval, and integration states: whereas hippocampus signals the tradeoff between encoding vs. retrieval states, medial prefrontal cortex actively represents past experience in relation to new learning.

SUMMARYAcross the domains of spatial navigation and episodic memory, the hippocampus is thought to play a critical role in disambiguating (pattern separating) representations of overlapping events. However, the mechanisms underlying hippocampal pattern separation are not fully understood. Here, using a naturalistic route-learning paradigm and spatiotemporal pattern analysis of human fMRI data, we found that hippocampal representations of overlapping routes gradually diverged with learning to the point that they became less similar than representations of non-overlapping events. This representational 'reversal' of the objective route similarity (a) was selective to the hippocampus, (b) only occurred for the specific route segments that were shared across routes, and (c) was predicted by the degree to which individual hippocampal voxels were initially shared across route representations. These findings indicate that event overlap triggers a repulsion of hippocampal representations-a finding that provides critical mechanistic insight into how and why hippocampal representations become separated.peer-reviewed)

One of the primary contributors to forgetting is interference from overlapping memories. Intuitively, this suggests—and prominent theoretical models argue—that memory interference is best avoided by encoding overlapping memories as if they were unrelated. It is therefore surprising that reactivation of older memories during new encoding has been associated with reduced memory interference. Critically, however, prior studies have not directly established why reactivation reduces interference. Here, we first developed a behavioral paradigm that isolates the negative influence that overlapping memories exert during memory retrieval. We then show that reactivating older memories during the encoding of new memories dramatically reduces this interference cost at retrieval. Finally, leveraging multiple fMRI decoding approaches, we show that spontaneous reactivation of older memories during new encoding leads to integration of overlapping memories and, critically, that integration during encoding specifically reduces interference between overlapping, and otherwise competing, memories during retrieval.