Closed-Loop Targeted Memory Reactivation During Sleep Spindles Enhances Motor Memory Consolidation

Sleep spindles are thought to facilitate motor memory consolidation by reactivating recently acquired memory traces during non-rapid eye movement (NREM) sleep, yet most human evidence is correlational. Using a closed-loop targeted memory reactivation (CL-TMR) protocol, this study tested whether auditory cueing time-locked to spindles enhances the consolidation of a newly acquired motor sequence. Twenty-six young adults practiced two eight-element, explicitly known, sequences of finger movements, each paired with a distinct auditory cue. During subsequent NREM Stage 2 and 3 nighttime sleep, a portable deep-learning-based EEG device (Portiloop) detected spindles online and selectively replayed the cue associated with one sequence (TMR condition), while the other served as a within-subject non-reactivated control (non-TMR) condition. Behavioural performance was assessed before and after sleep. Greater overnight improvements in performance were observed for the reactivated as compared to the non-reactivated condition, hence demonstrating enhanced consolidation following spindle-locked CL-TMR. The magnitude of this TMR benefit was positively correlated with the percentage of stimulations delivered during true spindles. Furthermore, a higher percentage of stimulations occurring during spindle trains (i.e., two or more spindles separated by < 6 s) was associated with larger TMR-induced gains, whereas a higher percentage during isolated spindles (> 6 s apart) was associated with reduced gains. These findings provide further evidence that spindle-timed reactivation supports motor memory consolidation in humans and suggest that spindle trains may represent a favourable physiological window for closed-loop interventions.