Enhancement of sleep slow waves: underlying mechanisms and practical consequences

Abstract

Even modest sleep restriction, especially the loss of sleep slow wave activity (SWA), is invariably associated with slower electroencephalogram (EEG) activity during wake, the occurrence of local sleep in an otherwise awake brain, and impaired performance due to cognitive and memory deficits. Recent studies not only confirm the beneficial role of sleep in memory consolidation, but also point to a specific role for sleep slow waves. Thus, the implementation of methods to enhance sleep slow waves without unwanted arousals or lightening of sleep could have significant practical implications. Here we first review the evidence that it is possible to enhance sleep slow waves in humans using transcranial direct-current stimulation (tDCS) and transcranial magnetic stimulation. Since these methods are currently impractical and their safety is questionable, especially for chronic long-term exposure, we then discuss novel data suggesting that it is possible to enhance slow waves using sensory stimuli. We consider the physiology of the K-complex (KC), a peripheral evoked slow wave, and show that, among different sensory modalities, acoustic stimulation is the most effective in increasing the magnitude of slow waves, likely through the activation of non-lemniscal ascending pathways to the thalamo-cortical system. In addition, we discuss how intensity and frequency of the acoustic stimuli, as well as exact timing and pattern of stimulation, affect sleep enhancement. Finally, we discuss automated algorithms that read the EEG and, in real-time, adjust the stimulation parameters in a closed-loop manner to obtain an increase in sleep slow waves and avoid undesirable arousals. In conclusion, while discussing the mechanisms that underlie the generation of sleep slow waves, we review the converging evidence showing that acoustic stimulation is safe and represents an ideal tool for slow wave sleep (SWS) enhancement.

Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aβ42 Levels in Cognitively Normal Elderly

“…In older subjects with SDB, treatment with CPAP improves sleep architecture including SWS. 41 In older subjects without SDB, transcranial magnetic stimulation 42 and existing medications 43,44 may increase or trigger SWS and reduce Aβ42 production. Whether such interventions affect Aβ42 metabolism and/or disease progression remains to be tested, but our current findings support further investigation.…”

Modafinil and sleep architecture in an inpatient–outpatient treatment study of cocaine dependence

“…Deficits in slow-wave sleep are particularly troubling as slow-wave sleep time is typically preserved despite significant sleep restriction (Van Dongen et al, 2003). Furthermore, such deficits are associated both with clinical disorders and impairments in a wide range of cognitive functions including sensory, motor, and declarative learning, as well as executive function and alertness (e.g., Bellesi et al, 2014; Roth et al, 2010). Unfortunately, most pharmacological interventions that target sleep do not affect slow-wave sleep, or actually diminish slow-wave sleep while increasing the time spent in lighter sleep (e.g., Achermann and Borbely, 1987).…”

Occipital long-interval paired pulse TMS leads to slow wave components in NREM sleep

“…Triggering slow waves can also deepen the sleep (Huber et al, 2008) and the amount of slow waves is positively correlated with post-sleep performance improvement (Huber, Ghilardi, Massimini, & Tononi, 2004). Enhancing slow waves might be beneficial in many patient groups with decreased slow wave sleep, for instance patients with chronic sleep restriction and insomnia (Bellesi, Riedner, Garcia-Molina, Cirelli, & Tononi, 2014;Massimini et al, 2007). The present paired-pulse paradigm elicited slow waves by stimulation of a brain area that is normally not involved in the generation of slow wave activity (Murphy et al, 2009).…”