Abstract

Study Objectives: Sleep 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. Methods: Twenty-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. Results: Recall 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. Conclusions: Spindle-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. Keywords: sleep spindles, spindle trains, declarative memory consolidation, closed-loop targeted memory reactivation. ### Competing Interest Statement The authors have declared no competing interest. Canadian Institutes of Health Research, https://ror.org/01gavpb45, 254572