Study objectives: Memories are strengthened during sleep. The benefits of sleep for memory can be enhanced by re-exposing the sleeping brain to auditory cues; a technique known as targeted memory reactivation (TMR). Prior studies have not assessed the nature of the retrieval mechanisms underpinning TMR: the matching process between auditory stimuli encountered during sleep and previously encoded memories. We carried out two experiments to address this issue.

Methods: In Experiment 1, participants associated words with verbal and nonverbal auditory stimuli before an overnight interval in which subsets of these stimuli were replayed in slow-wave sleep. We repeated this paradigm in Experiment 2 with the single difference that the gender of the verbal auditory stimuli was switched between learning and sleep.

Results: In Experiment 1, forgetting of cued (vs. noncued) associations was reduced by TMR with verbal and nonverbal cues to similar extents. In Experiment 2, TMR with identical nonverbal cues reduced forgetting of cued (vs. noncued) associations, replicating Experiment 1. However, TMR with nonidentical verbal cues reduced forgetting of both cued and noncued associations.

Conclusions: These experiments suggest that the memory effects of TMR are influenced by the acoustic overlap between stimuli delivered at training and sleep. Our findings hint at the existence of two processing routes for memory retrieval during sleep. Whereas TMR with acoustically identical cues may reactivate individual associations via simple episodic matching, TMR with nonidentical verbal cues may utilize linguistic decoding mechanisms, resulting in widespread reactivation across a broad category of memories.