Sleep Spindle-Locked Targeted Memory Reactivation Enhances Declarative Memory Consolidation

Study ObjectivesSleep spindles are implicated in memory consolidation. Yet direct evidence linking spindle dynamics to declarative memory outcomes remains limited. We thus tested whether targeted memory reactivation (TMR) time-locked to sleep spindles enhances declarative memory, and whether the temporal organization of stimulated spindles-trains versus isolated events-is selectively associated with distinct memory outcomes. MethodsTwenty-eight healthy young adults learned image locations from two categories (animals, clothing) in a grid, each paired with a distinct auditory cue. During overnight NREM sleep, one cue was replayed time-locked to spindles detected in real-time using a closed-loop system (TMR condition); the other served as the non-reactivated control (No-TMR condition). Category-cue assignment was counterbalanced. Post-sleep recall, recognition accuracy, and movement time were assessed. ResultsRecall accuracy was significantly higher in the TMR than the No-TMR condition (93.96% vs. 90.61%, p = .024), whereas recognition accuracy (p = .139) and movement time (p = .651) did not differ. Stimulation intensity within spindle trains correlated with the TMR effect on recall (Spearman {rho} = .531, p = .004), whereas the proportion of isolated spindle stimulations correlated with the TMR effect on recognition ({rho} = .563, p = .002). Cross-associations were not significant. ConclusionsSpindle-locked TMR enhances recall-based declarative memory retention. The selective association between spindle temporal clustering and memory outcomes suggests that train-embedded and isolated spindles support different aspects of memory consolidation, highlighting spindle temporal context as a functionally relevant dimension of sleep-dependent memory processing.