Enhancing Slow Oscillations and Increasing N3 Sleep Proportion with Supervised, Non-Phase-Locked Pink Noise and Other Non-Standard Auditory Stimulation During NREM Sleep

Abstract

Purpose: In non-rapid eye movement (NREM) stage 3 sleep (N3), phase-locked pink noise auditory stimulation can amplify slow oscillatory activity (0.5-1 Hz). Open-loop pink noise auditory stimulation can amplify slow oscillatory and delta frequency activity (0.5-4 Hz). We assessed the ability of pink noise and other sounds to elicit delta power, slow oscillatory power, and N3 sleep.

Participants and methods: Participants (n = 8) underwent four consecutive inpatient nights in a within-participants design, starting with a habituation night. A registered polysomnographic technologist live-scored sleep stage and administered stimuli on randomized counterbalanced Enhancing and Disruptive nights, with a preceding Habituation night (night 1) and an intervening Sham night (night 3). A variety of non-phase-locked pink noise stimuli were used on Enhancing night during NREM; on Disruptive night, environmental sounds were used throughout sleep to induce frequent auditory-evoked arousals.

Results: Total sleep time did not differ between conditions. Percentage of N3 was higher in the Enhancing condition, and lower in the Disruptive condition, versus Sham. Standard 0.8 Hz pink noise elicited low-frequency power more effectively than other pink noise, but was not the most effective stimulus. Both pink noise on the "Enhancing" night and sounds intended to Disrupt sleep administered on the "Disruptive" night increased momentary delta and slow-wave activity (ie, during stimulation versus the immediate pre-stimulation period). Disruptive auditory stimulation degraded sleep with frequent arousals and increased next-day vigilance lapses versus Sham despite preserved sleep duration and momentary increases in delta and slow-wave activity.

Conclusion: These findings emphasize sound features of interest in ecologically valid, translational auditory intervention to increase restorative sleep. Preserving sleep continuity should be a primary consideration if auditory stimulation is used to enhance slow-wave activity.

Keywords: delta power; electroencephalographic spectral analysis; neurobehavioral performance; sleep fragmentation; slow oscillation; slow-wave sleep.

Figure 1

Study protocol. Abbreviations; TIB (time in bed).

Figure 2

(A and B) Mean log₁₀ delta (0.5–4 Hz; A) and mean log₁₀ slow-oscillation (0.5–1 Hz; B) power spectral density (PSD) within the 5-sec pre-stimulus baseline and 10-sec post-stimulus period, separately for auditory stimulation delivered within the Disruptive and Enhancing conditions. Auditory stimulations were included in analyses if delivered out of stages N2 and N3, did not lead to an arousal, and were not ended early by the experimenter. Within each condition, log₁₀ delta and slow-oscillation PSD in the post-stimulus period were significantly increased relative to the pre-stimulus period. In addition, during both the 5-sec baseline and the 10-sec stimulation period, log₁₀ delta and slow-oscillation PSD in the Enhancing condition were greater than log₁₀ PSD in the Disruptive condition. Error bars represent standard error of the mean. *p < .05, **p < .005.

Figure 3

Mean change in delta (0.5–4 Hz) and slow oscillatory (0.5–1 Hz) frequency power spectral density between baseline (5 sec preceding stimulation) and auditory stimulation (10 sec during stimulation; y-axes) for stimuli initiated during N2 and N3 sleep that did not result in sleep disturbance. Participants must have had at least 2 qualifying instances of a stimulus (panels) at a given dBA level (x-axes) to contribute to each data point average. Averages across fewer than 3 participants are not presented; however, all data were included in the linear mixed model analysis. PSD, power spectral density; dBA: decibel.

Figure 4

(A) Mean time (in minutes, y-axis) and percentage of TST (data labels) spent in each sleep stage on the Disruptive and Enhancing condition nights relative to Sham night across eight participants. The ordinate is in 1-hr (60-min) intervals. Error bars represent standard deviation. Participants spent significantly less time in N3 on the Disruptive night than Sham that included a significant Condition*Order interaction. N1 time was significantly greater on the Disruptive night than on Sham. **p < .005, ^†p < .100 (marginally significant), in comparisons of stage percentage. (B) Mean percent difference in N3 sleep between the Disruptive and Enhancing condition nights versus the Sham night, with markers indicating individual participant differences. Filled markers represent participants randomized to the Enhancing condition on Night 2 (two nights prior to Disruptive) and open or letter markers represent participants randomized to the Disruptive condition on Night 2 (two nights prior to Enhancing). Error bars represent standard deviation. Percent N3 was greater in the Enhancing condition than Sham only when Sham did not coincide with a rebound effect following a Disruptive night (ie, only when Enhancing was presented on Night 2, two nights prior to Disruptive).

Figure 5

Mean arousal index (arousals out of a given sleep stage per hour of that sleep stage) in each study condition (Disruptive night, Sham night, or Enhancing night), split by arousal association with sound presentation (spontaneous or associated with auditory stimulation). Sounds were not played during sleep on Sham night; therefore, only spontaneous arousals (empty bars) are indicated in that condition (center column). Arousals associated with auditory stimulation (occurring up to 15 sec after sound presentation onset; shaded bars) are shown for Disruptive and Enhancing nights, with data labels indicating the percentage of arousals in a condition and sleep stage temporally related to stimulation and temporally independent of stimulation (“spontaneous”). Error bars represent standard error of the mean. N3 arousal index n = 7 due to one outlying value that was excluded. Despite the presence of auditory-associated arousals in the Enhancing condition, total arousal indices in stages N2, N3, and REM were similar to arousal indices on Sham night. Arousals were significantly more frequent in the Disruptive condition relative to Sham, except for during REM sleep. ***p < .001 in a comparison of overall arousal indices.

Figure 6

Mean difference in lapse sum (estimated marginal means) across the 10-min PVT after the Disruptive and Enhancing conditions (vs after Sham). Error bars represent standard error of the mean. Lapse count per administration was significantly higher after the Disruptive night than after the Sham night (p < .001); there was no difference in lapses between Enhancing and Sham. ***p < .001 compared to Sham.

Figure 7

Panel of figures summarizing the mean difference in subjective sleep measures between the Disruptive or Enhancing condition nights versus Sham night in a morning survey. Number of Recalled Awakenings (A) indicates the number of times a participant reported awakening between sleep onset and their final morning awakening, Perceived Total Sleep Time (TST; B) indicates the total amount of time participants thought they slept (depicted here in minutes), and Perceived Sleep Quality (C), Perceived Residual Sleepiness (that morning; D), and Perceived Restoration (that morning; E) were participant responses to a 7-point Likert scale. Error bars represent standard deviation. For all measures, subjective sleep was rated significantly worse after the Disruptive night compared to Sham. The Enhancing condition did not differ for any sleep rating relative to Sham. ***p < .001, **p < .005, *p < .05.