Daniela Grimaldi, Christian Mikutta, Kathryn J Reid, Roneil Malkani, Sabra M Abbott, Nelly Papalambros, Alexandra C Ritger, Ken A Paller, Phyllis C Zee
The interplay between sleep slow oscillations (SOs), spindles, and autonomic activity is thought to be crucial for sleep-dependent memory consolidation, yet the precise mechanisms remain unclear. In this randomized, single-blind, crossover study of 20 healthy young adults (25 ± 4 years, 75% female), we investigated whether one night of closed-loop acoustic stimulation of sleep slow waves during non-rapid eye movement sleep stages 2 and 3 enhanced memory retention at a paired word-associates task by modulating these neural and autonomic processes, compared to a sham condition. We found that memory enhancement was associated with two tightly coupled mechanisms: increased spindle nesting with SOs (0.5 - 1.5 Hz) relative to delta waves (δ, >1.5 - 4 Hz), and elevated parasympathetic activity measured by heart rate variability during SWS. Critically, the SO/δ-spindle nesting ratio, not absolute SO-spindle nesting, predicted memory performance, suggesting that an optimized relative balance between SO and δ wave influences on spindle activity drives consolidation. Both the SO/δ-spindle nesting ratio and parasympathetic activity predicted memory retention and were strongly correlated, pointing to a potential mechanistic link. Findings suggest that acoustic stimulation may enhance memory consolidation by optimizing the coordination between sleep oscillatory networks and autonomic activity.