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Randomized Controlled Trial
. 2019 May 1;42(5):zsz036.
doi: 10.1093/sleep/zsz036.

Strengthening sleep-autonomic interaction via acoustic enhancement of slow oscillations

Daniela Grimaldi  1 , Nelly A Papalambros  1 , Kathryn J Reid  1 , Sabra M Abbott  1 , Roneil G Malkani  1 , Maged Gendy  1 , Marta Iwanaszko  2 , Rosemary I Braun  2   3 , Daniel J Sanchez  4 , Ken A Paller  5 , Phyllis C Zee  1
Affiliations
Randomized Controlled Trial

Strengthening sleep-autonomic interaction via acoustic enhancement of slow oscillations

Daniela Grimaldi et al. Sleep. .

Abstract

Slow-wave sleep (SWS) is important for overall health since it affects many physiological processes including cardio-metabolic function. Sleep and autonomic nervous system (ANS) activity are closely coupled at anatomical and physiological levels. Sleep-related changes in autonomic function are likely the main pathway through which SWS affects many systems within the body. There are characteristic changes in ANS activity across sleep stages. Notably, in non-rapid eye-movement sleep, the progression into SWS is characterized by increased parasympathetic activity, an important measure of cardiovascular health. Experimental manipulations that enhance slow-wave activity (SWA, 0.5-4 Hz) can improve sleep-mediated memory and immune function. However, effects of SWA enhancement on autonomic regulation have not been investigated. Here, we employed an adaptive algorithm to deliver 50 ms sounds phase-locked to slow-waves, with regular pauses in stimulation (~5 s ON/~5 s OFF), in healthy young adults. We sought to determine whether acoustic enhancement of SWA altered parasympathetic activity during SWS assessed with heart rate variability (HRV), and evening-to-morning changes in HRV, plasma cortisol, and blood pressure. Stimulation, compared with a sham condition, increased SWA during ON versus OFF intervals. This ON/OFF SWA enhancement was associated with a reduction in evening-to-morning change of cortisol levels and indices of sympathetic activity. Furthermore, the enhancement of SWA in ON intervals during sleep cycles 2-3 was accompanied by an increase in parasympathetic activity (high-frequency, HRV). Together these findings suggest that acoustic enhancement of SWA has a positive effect on autonomic function in sleep. Approaches to strengthen brain-heart interaction during sleep could have important implications for cardiovascular health.

Keywords: acoustic stimulation; autonomic nervous system; parasympathetic activity; sleep; slow wave activity.

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Figures

Figure 1.
Figure 1.
Inpatient study timeline. Participants completed two 2-night inpatient visits, each with one night of adaptation and one intervention night. Heart rate variability (red dots) measurements were assessed 30 min before lights out (10 min assessment), overnight during the first three cycles of sleep (5 min assessment), and immediately after lights on (10 min assessment). In the morning, a 5 five-min orthostatic test followed the supine HRV measurement. Blood pressure (blue dots) was measured 15 min before lights out and 30 min after lights on. Cortisol (green dots) samples were collected 10 min before lights out and 30 min after lights on.
Figure 2.
Figure 2.
Examples of EEG data for phase-locked loop pulse delivery using a block design with ON and OFF intervals. Figures are representative of acoustic stimulation delivered in the first (left panel) and fifth (right panel) sleep cycle in one subject. Red dots indicate 50 ms pulses of pink noise.
Figure 3.
Figure 3.
Spectral power during ON/OFF intervals and NREM sleep. The figure shows log-transformed average spectral power in different frequency bands. The analysis was conducted on the average spectral power in ON and OFF intervals normalized to the total power for each frequency band. (A) Spectral power in the SWA, theta, alpha, and sigma bands increased during STIM in ON vs OFF intervals, compared with SHAM. (B) Spectral power during NREM across the entire sleep period was similar between STIM and SHAM nights. Asterisks indicate p < 0.05 (Wilcoxon signed-rank test) following Bonferroni adjustment for multiple comparisons. Error bars represent standard error of the mean.
Figure 4.
Figure 4.
Changes in SWA during ON, OFF, and ON/OFF intervals through the cycles of sleep. The amount of SWA (Fpz, 0.5–4 Hz) in ON and OFF intervals during each cycle was calculated and normalized to the amount of SWA in all intervals (ON and OFF for entire night). (A) In ON intervals, the amount of SWA was higher during STIM compared with SHAM, mainly evident in cycle 2 and 4. (B) In OFF intervals, the amount of SWA was reduced in STIM compared with SHAM mainly during the first cycle of sleep. (C) Change in SWA between ON/OFF intervals was significantly higher during STIM compared to SHAM from the first until the fourth cycle of sleep. Asterisks indicate p < 0.05 (Wilcoxon signed-rank test) following Bonferroni adjustment for multiple comparisons. Error bars represents standard error of the mean.
Figure 5.
Figure 5.
HRV high-frequency relative power (HF%) in the evening assessment before sleep (presleep) and during SWS in the first three cycles of sleep where ~80% of acoustic stimulation occurred. HF% in the presleep assessment was similar in STIM and SHAM. During sleep, HF% was significantly higher during cycles 2 and 3 in the STIM night. One subject was excluded from HRV analysis due to the presence of sinus arrhythmia. Asterisks indicate p <0.05 (Wilcoxon signed-rank test) following Bonferroni adjustment for multiple comparisons. Error bars represents standard error of the mean.
Figure 6.
Figure 6.
Nonparametric correlations between percent change in SWA in ON/OFF intervals and evening-to-morning change in LF:HF and cortisol during acoustic stimulation. Evening-to-morning changes were calculated as postsleep − presleep. (A) A larger reduction in evening-to-morning change of LF:HF was significantly associated with an increase in SWA in the STIM night during ON versus OFF intervals. (B) A significant association was present between the increase in SWA during ON versus OFF intervals and the reduction in evening-to-morning rise in cortisol plasma levels.
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