Closed-loop auditory stimulation during sleep shapes cortical responses and memory consolidation depending on spindle timing

Abstract

Sleep spindles contribute to memory consolidation, and acoustic stimulation during sleep can modulate spindle activity. However, it remains unclear whether these effects depend on the timing of stimulation relative to the spindle cycle. Using closed-loop spindle detection, we delivered four variants of pink noise either during ongoing spindles or shortly after spindle offset. In Experiment 1, stimulation delivered during a spindle prolonged its duration, whereas stimulation applied shortly after spindle offset, i.e., within the refractory period, delayed the onset of the subsequent spindle. This pattern was consistent across all sound variants, indicating that the stimulation timing, rather than acoustic properties, drove the observed effects. Experiment 2 examined whether post-spindle stimulation influences memory consolidation. Relative to a no-stimulation nap, post-spindle stimulation reduced post-nap deterioration in motor sequence accuracy but did not significantly affect word-pair recall. EEG analyses revealed that stimulation elicited widespread slow oscillation activity without triggering new spindles, demonstrating that cortical processing of external input persists even during the refractory period. Notably, the motor benefit was greatest in participants with lower spindle density during the baseline adaptation nap. Together, these findings challenge the notion that the post-spindle refractory period is a functionally silent interval. Instead, this period remains receptive to external input, capable of eliciting cortical activity and supporting motor memory consolidation even in the absence of new spindle generation.