Abstract

Abstract Introduction The nesting of electroencephalographic (EEG) sleep slow oscillations (SOs) to spindles has been shown to be important for sleep-dependent memory consolidation. However, recent evidence indicates that a higher proportion of SOs nested to spindles, relative to δ waves, might be even more critical for sleep-dependent memory consolidation. Acoustic stimulation during slow wave sleep has been shown to be effective in improving memory consolidation. Here, we examined the contribution of SOs nested to spindles relative to δ waves on sleep-dependent declarative memory consolidation associated with acoustic stimulation. Methods Twenty subjects (18-35 years, 75% females) participated in a randomized cross-over study. At each visit participants received either stimulation (stim) or sham following an adaption night. Stim occurred in blocks of 5 pulses (ON intervals) followed by a period of equal length with no stimulation (OFF intervals). Participants learned 40 Arabic-English word pairs and were tested before sleep and after sleep in the morning and again in the afternoon. Detection of SOs (< 2 Hz), δ waves (2-4 Hz), spindles (11-16Hz), and the ratio (%) of spindles nested to SO over δ waves (SO/δ Nesting Index) were calculated during ON intervals for stim and sham conditions. Results Overnight mean (SD) percentage change in word recall between conditions was similar in the morning (stim 6(3)%, sham 4(6)%, p=0.68), but was higher in the afternoon in stim compared to the sham condition (stim 10(4)%, sham 4(6)%, p=0.02). The SO/δ Nesting Index was higher in stim compared to the sham condition (stim 21(13)%, sham 13(10%), p=0.004). Within-subject improvement from sham to stim condition in afternoon memory was associated with a greater change in SO/δ Nesting Index (R=0.63, p=0.03), this association was not observed for spindles nested to SOs (R=0.33, p=0.202) or spindles nested to δ waves (R=-0.18, p=0.811). Conclusion Enhancement of memory consolidation with acoustic stimulation may be dependent on its ability to increase SOs nested to spindles relative to δ waves. Dynamic changes in the relationships between SOs, δ waves and spindles can help inform novel EEG-derived markers and targets to enhance sleep-dependent memory consolidation. Support (if any) DARPA award W911NF-16- 2-0021

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