Acoustic stimulation has been shown to enhance slow wave sleep and in turn, cognition, and now cardiac outcomes in young adults. With the emergence of commercial acoustic devices in the home, we sought to examine the impact of an acoustic, slow wave enhancing device on heart rate variability in healthy, middle-aged males (n = 24, 39.92 ± 4.15 years). Under highly controlled conditions, the participants were randomised to receive closed-loop brain state-dependent stimulation in the form of auditory tones (STIM), or no tones (SHAM), in a crossover design, separated by a 1 week washout period. STIM and SHAM were compared on measures of heart rate variability for the whole night and over the first three sleep cycles. We found an increase in slow wave activity following STIM compared with SHAM. There was a significant increase in high frequency power and standard deviation of the normalised RR-intervals (SDNN) during the STIM condition compared with SHAM (p < 0.05), due to changes observed specifically during N3. In conclusion, heart rate variability appears to improve following acoustic slow wave sleep enhancement.

Study Objectives: As slow-wave activity (SWA) is critical for cognition, SWA-enhancing technologies provide an exciting opportunity to improve cognitive function.

We focus on improving cognitive function beyond sleep-dependent memory consolidation, using an automated device, and in middle-aged adults, who have depleted SWA yet a critical need for maximal cognitive capacity in work environments.

Conclusions: Our study suggests that (1) an automated acoustic device enhances SWA; (2) SWA enhancement improves executive function; (3) SWA enhancement in middle-aged men may be an important therapeutic target for enhancing cognitive function; and (4) there is a need to examine interindividual responses to acoustic stimulation and its effect on subsequent cognitive function.

Sleep is essential for health. Slow wave sleep (SWS), the deepest sleep stage hallmarked by electroencephalographic slow oscillations (SOs), appears of particular relevance here. SWS is associated with a unique endocrine milieu comprising minimum cortisol and high aldosterone, growth hormone (GH), and prolactin levels, thereby presumably fostering efficient adaptive immune responses. Yet, whether SWS causes these changes is unclear. Here we enhance SOs in men by auditory closed-loop stimulation, i.e., by delivering tones in synchrony with endogenous SOs. Stimulation intensifies the hormonal milieu characterizing SWS (mainly by further reducing cortisol and increasing aldosterone levels) and reduces T and B cell counts, likely reflecting a redistribution of these cells to lymphoid tissues. GH remains unchanged. In conclusion, closed-loop stimulation of SOs is an easy-to-use tool for probing SWS functions, and might also bear the potential to ameliorate conditions like depression and aging, where disturbed sleep coalesces with specific hormonal and immunological dysregulations.

The recovery function of sleep is essential. In case of insufficient recovery, we are tired and suffer from well-documented cognitive impairments, such as lapses in attention and reduced vigilance. Insufficient recovery during sleep can be caused by sleep disorders and other pathologies but can also be the result of curtailed sleep in healthy individuals (Van Dongen and Dinges, 2003).

According to the two-process model of sleep regulation, sleep is regulated by a circadian and a homeostatic process. While the circadian process depends on the time of the day and provides the ideal window for sleep, the homeostatic process depends on the duration of wake and sleep and reflects the build-up of sleep pressure (i.e., sleepiness) during the day and dissipation of sleep pressure (i.e., recovery) during sleep (Borbély et al., 1981; Dijk et al., 1990; Achermann and Borbély, 2003).

Slow-wave activity [SWA, power in delta frequency range (1–4 Hz) recorded by electroencephalography (EEG)] during non-rapid eye movement (NREM) sleep is a well-established electrophysiological correlate of the homeostatic regulation of sleep. As expected from such a correlate, (1) SWA is highest at the beginning of a night and this initial level is regulated in a dose-dependent way: The longer an individual is awake, the higher SWA is during sleep the following night and (2) SWA exponentially decreases throughout the night, reflecting the dissipation of sleep pressure, i.e., recovery during sleep. Consequently, (1) sleep restriction and sleep deprivation lead to increased levels of SWA associated with an initially faster dissipation of sleep pressure (Borbély, 1982) and (2) suppression of SWA during sleep by keeping participants in light sleep, slows down the dissipation of sleep pressure and thus hinders recovery during sleep with negative consequences on daytime sleepiness and cognitive processes (Gillberg and Åkerstedt, 1994; Dijk et al., 2006).

Brain activity oscillates at different frequencies, reflecting synchronized activity that organizes information processing and communication in neuronal cortical networks in a state-dependent manner (Buzsáki and Draguhn, 2004; Varela et al., 2001). The <1 Hz slow oscillation (SO) represents the most distinct of these oscillations that hallmark the electroencephalogram (EEG) during slow-wave sleep (SWS) (Steriade, 2006; Timofeev, 2011). The SO is generated in cortical and thalamic networks and reflects global synchronous neural activity alternating between up states of membrane depolarization and increased excitability and down states of hyperpolarization and widespread neuronal quiescence, which spreads across the neocortex, also capturing subcortical structures like the hippocampus (Isomura et al., 2006; Massimini et al., 2004). Importantly, the SO critically contributes to information processing during sleep: apart from an involvement in synaptic downscaling and homeostasis (Tononi and Cirelli, 2006), SOs play a causal role for the consolidation of memory (Chauvette et al., 2012; Diekelmann and Born, 2010; Marshall et al., 2006). For this consolidating function, the synchronization of fast-spindle activity (12–15 Hz) together with hippocampal ripples to the depolarizing up state appears to be critical (Mölle et al., 2011; Mölle and Born, 2011).

The obvious functional importance has stimulated attempts to induce synchronized cortical SO activity through external stimulation, mainly by rhythmic electrical, transmagnetic, and auditory stimulation in humans and rats (Marshall et al., 2006; Massimini et al., 2007; Tononi et al., 2010; Vyazovskiy et al., 2009). Importantly, such studies imposed rhythms on the brain disregarding the phase of ongoing endogenous oscillating activity, which might explain the overall limited functional enhancement in memory retention accompanying SO induction. Here, we utilized the ongoing oscillatory EEG activity to apply, in a closed-loop feedback system, auditory stimulation in synchrony with the brain’s own rhythm, thereby enhancing and extending trains of SOs during sleep.