Memory reactivation during rest supports upcoming learning of related content

Although a number of studies have highlighted the importance of offline processes for memory, how these mechanisms influence future learning remains unknown. Participants with established memories for a set of initial face–object associations were scanned during passive rest and during encoding of new related and unrelated pairs of objects. Spontaneous reactivation of established memories and enhanced hippocampal–neocortical functional connectivity during rest was related to better subsequent learning, specifically of related content. Moreover, the degree of functional coupling during rest was predictive of neural engagement during the new learning experience itself. These results suggest that through rest-phase reactivation and hippocampal–neocortical interactions, existing memories may come to facilitate encoding during subsequent related episodes.Numerous empirical studies (1–4) and theoretical accounts (5, 6) highlight the importance of offline processes—such as reinstatement of recent experience and enhanced interregional communication—for episodic memory. It has been proposed that through hippocampal (HPC)–neocortical interactions (6, 7), memories are reactivated during periods of sleep and awake rest. Such reactivation (or “replay”) is thought to support the strengthening and transfer of memory traces from the HPC to neocortical regions for long-term storage, a process termed “consolidation.” The functional significance of reactivation of recent experience for memory has been demonstrated during awake rest using neurophysiological techniques in rodents (2) and, more recently, in humans using pattern information analysis of functional magnetic resonance imaging (fMRI) data (1, 3). For instance, more delay period reactivation has been observed for stimuli that were remembered, relative to those that were forgotten in a subsequent test (3). Moreover, studies have shown that the degree of HPC–neocortical functional coupling during rest periods following learning relates to later memory for the learned content (4).This existing body of work demonstrates that rest-phase neural signatures relate to memory for prior experiences. However, one important quality of memory is that it is inherently prospective (8); that is, memories are formed for maximal utility in future situations. Whereas research shows that rest-phase reactivation impacts memory for the reactivated content itself (1, 3), how this mechanism might be prospectively advantageous remains unknown. In the present study, we turn our attention to this question: How does spontaneous reactivation of established memories and enhanced HPC–neocortical connectivity during rest affect learning during subsequent related episodes?A number of theories underscore the highly interactive nature of episodic memories (9, 10). One prominent view, “interference theory,” highlights that existing knowledge may impair learning of related content. A host of studies confirm this intuition; that is, people often have worse memory for information that is related to their existing memories relative to unrelated information, a phenomenon termed “proactive interference” (11–13). However, this impairment is not universally observed, even in the classic literature; on the contrary, prior knowledge can also be beneficial to new learning under some circumstances (14). For example, one study showed a memory advantage for new responses paired with well-learned old stimuli (i.e., stimuli previously learned with a different response), a phenomenon known as “associative facilitation” (11). Such facilitation may also extend to novel judgments that require the simultaneous consideration of multiple memories (e.g., inferences).Whereas these data and others (15) suggest that strong prior knowledge may facilitate new learning, the neural mechanisms supporting such associative facilitation are not well understood. One possible explanation stems from a perspective known as “integrative encoding,” which describes how new memories are created in relation to existing knowledge (16, 17). Mechanistically, it has been proposed that when newly encountered content overlaps with one’s stored memory representations, the neural patterns associated with that preexisting knowledge may be reactivated in the brain during new learning (18–20). New episodes may then be encoded in the context of these internally generated representations, connecting these related memories. A recent fMRI study suggests that reactivation of existing knowledge during encoding of new, overlapping events may strengthen preexisting memory traces, making the prior knowledge itself less susceptible to interference (18). Reactivation during learning has also been shown to support novel judgments that span experiences (20), consistent with the notion that this mechanism enables the linking of related memories. However, the potential impact of encoding-phase reactivation on the new learning itself has not been addressed. That is, although reactivation has been shown to strengthen both established memories and the connections among discrete experiences, it is as yet undetermined whether this process also facilitates memory formation for the new, related events through integration.We propose that the degree to which memory processes are engaged during offline periods influences whether prior knowledge interferes with or facilitates new encoding. Importantly, interference theory and integrative encoding make opposing predictions for the impact of rest-phase processes on subsequent learning of related events. Both perspectives might predict that memories are strengthened during offline periods; and that stronger memories are more likely to be reactivated during learning of new, related events. However, these perspectives diverge in their predictions for the consequences of that reactivation on new learning. Although interference theory would suggest that rest-phase strengthening of the initially acquired information might lead to more “competition” and thus worse memory for new, related content (21), integrative encoding predicts the opposite. Because stronger memories are more readily reinstated, they are also more likely to be “updated” with new information during subsequent experiences. For this reason, more engagement of rest-phase memory processing might facilitate both the later encoding of related events and novel judgments that span episodes. We sought to adjudicate between these perspectives by investigating the impact of offline reactivation and functional coupling on subsequent encoding of distinct but related experiences.We used a classic interference paradigm (11, 13) in which adult human participants with prior knowledge encoded new, overlapping pairs. We first trained participants (n = 35) on a set of face–object associations (hereafter AB pairs, where “AB” denotes a studied A_face–B_object association) across four study–test repetitions (Fig. 1A, Experimental Procedures, and SI Methods and Results, Memory Task). We then collected fMRI data while participants engaged in passive rest and encoding of both new overlapping (BC) object–object pairs and nonoverlapping (i.e., unrelated; XY) object–object pairs in a single exposure. Importantly, the order of BC and XY learning was counterbalanced across participants. After scanning, participants completed a cued recall test for studied associations (BC and XY) and a surprise test of inferential (AC) relationships. The AC inference test required participants to recall the A_face item that was indirectly related to the C_object cue through their common association with B_object, indexing each individual’s ability to combine remembered associations across episodes. This paradigm enables investigation of the neural mechanisms that modulate how existing memories (AB) impact future learning (BC) and inference (AC), thus improving our fundamental understanding of the interactive nature of real-world memory.Open in a separate windowFig. 1.Experimental procedure and performance. (A) Participants encoded AB pairs in four alternating study–test repetitions during the pretraining phase (blue). Participants then studied new overlapping (BC; orange) and nonoverlapping (XY; green) pairs during fMRI scanning. BC and XY study blocks were interleaved with rest scans (yellow); the encoding order of BC vs. XY was counterbalanced across participants. After scanning, memory for BC and XY pairs (intermixed; orange/green) and AC inferences (pink) was tested using cued recall. (B) AB memory performance as proportion correct on each test block. Line represents the group mean; points show individual participants. (C) Performance for nonoverlapping XY pairs (green), overlapping BC pairs (orange), and AC inferences (pink). Bar heights represent group means; points show individual participants. See also Fig. S1.