OBJECTIVE: Evaluate if closed-loop auditory stimulation during sleep evokes memory mediating oscillations and improves memory

BACKGROUND: Sleep-dependent memory consolidation relies on the temporal coordination of sleep oscillations, including cortical slow oscillations (SOs) and thalamic spindles, during non-rapid-eye-movement (NREM) sleep. In schizophrenia, healthy aging, and neurodegenerative diseases, reduced sleep spindles correlate with impaired sleep-dependent memory consolidation. Yet treatments that improve memory impairments are lacking. Auditory stimulation, time-locked to the SO upstate, is a promising potential treatment. In healthy adults it evokes SOs and spindles, and improves declarative memory. We investigated whether auditory stimulation can evoke coupled SO-spindle events and improve procedural memory.

DESIGN/METHODS: 20 healthy adults participated in two afternoon nap sessions (pink noise stimulation during the SO upstate and SO detection only) with polysomnography. Participants trained on the finger tapping Motor Sequence Task at the start of each session and were tested after the nap. The percent improvement in correct trials from the end of training to the start of testing indexes sleep-dependent memory consolidation. SOs and spindles were detected during NREM sleep using validated automated detectors.

RESULTS: Auditory stimulation evoked more coupled SO-spindle events than detection only in a fronto-central cluster of electrodes (clustered t-stat=49.6, p<.05). While there was no significant effect of condition on memory, the higher the stimulation rate (#/min), the greater the memory improvement in the stimulation (r=.52 , p<.05), but not detection (r=.32, p=.16 ) condition, although these relations did not differ significantly. Additionally, coupled SO-spindle density (#/min) in a centro-parietal cluster significantly correlated with memory improvement (r2=.29, p=.05).
CONCLUSIONS: Auditory stimulation evokes coordinated spindle-SO events that mediate memory consolidation. The higher the rate of stimulation, the greater sleep-dependent memory consolidation, suggesting a dose-dependent effect. This motivates the investigation of auditory stimulation as a non-invasive and potentially scalable treatment for sleep-dependent memory deficits in patients with abnormal NREM oscillations.