Sleep Spindle-Locked Targeted Memory Reactivation Enhances Declarative Memory Consolidation

Mutreja, V.; Gupta, P.; Lungu, O.; Lazzouni, L.; Gabitov, E.; Benali, H.; Jourde, H.; Beltrame, G.; Coffey, E. B.; Lina, J.-M.; Albouy, G.; King, B.; Boutin, A.; Carrier, J.; Doyon, J.

doi:10.64898/2026.05.08.723823

bioRxiv · 10.64898/2026.05.08.723823

Sleep Spindle-Locked Targeted Memory Reactivation Enhances Declarative Memory Consolidation

Mutreja, V.·Gupta, P.·Lungu, O.·Lazzouni, L.·Gabitov, E.·Benali, H.·Jourde, H.·Beltrame, G.·Coffey, E. B.·Lina, J.-M.·Albouy, G.·King, B.·Boutin, A.·Carrier, J.·Doyon, J.

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Abstract

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.

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Mutreja, V., Gupta, P., Lungu, O., Lazzouni, L., Gabitov, E., Benali, H., Jourde, H., Beltrame, G., Coffey, E. B., Lina, J.-M., Albouy, G., King, B., Boutin, A., Carrier, J., Doyon, J.. 2026-05-12. Sleep Spindle-Locked Targeted Memory Reactivation Enhances Declarative Memory Consolidation. https://doi.org/10.64898/2026.05.08.723823

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