Targeted Memory Reactivation during Sleep Elicits Neural Signals Related to Learning Content

Retrieval of learning-related neural activity patterns is thought to drive memory stabilization. However, finding reliable, noninvasive, content-specific indicators of memory retrieval remains a central challenge. Here, we attempted to decode the content of retrieved memories in the EEG during sleep. During encoding, male and female human subjects learned to associate spatial locations of visual objects with left- or right-hand movements, and each object was accompanied by an inherently related sound. During subsequent slow-wave sleep within an afternoon nap, we presented half of the sound cues that were associated (during wake) with left- and right-hand movements before bringing subjects back for a final postnap test. We trained a classifier on sleep EEG data (focusing on lateralized EEG features that discriminated left- vs right-sided trials during wake) to predict learning content when we cued the memories during sleep. Discrimination performance was significantly above chance and predicted subsequent memory, supporting the idea that retrieval leads to memory stabilization. Moreover, these lateralized signals increased with postcue sleep spindle power, demonstrating that retrieval has a strong relationship with spindles. These results show that lateralized activity related to individual memories can be decoded from sleep EEG, providing an effective indicator of offline retrieval.SIGNIFICANCE STATEMENT Memories are thought to be retrieved during sleep, leading to their long-term stabilization. However, there has been relatively little work in humans linking neural measures of retrieval of individual memories during sleep to subsequent memory performance. This work leverages the prominent electrophysiological signal triggered by lateralized movements to robustly demonstrate the retrieval of specific cued memories during sleep. Moreover, these signals predict subsequent memory and are correlated with sleep spindles, neural oscillations that have previously been implicated in memory stabilization. Together, these findings link memory retrieval to stabilization and provide a powerful tool for investigating memory in a wide range of learning contexts and human populations.