Slow-Wave Activity Enhancement to Improve Cognition

Abstract

Slow-wave activity (SWA), and its coupling with other sleep features, reorganizes cortical circuitry, supporting cognition. This raises the question: can cognition be improved through SWA enhancement? SWA enhancement techniques range from behavioral interventions (such as exercise), which have high feasibility but low specificity, to laboratory-based techniques (such as transcranial stimulation), which have high specificity but are less feasible for widespread use. In this review we describe the pathways through which SWA is enhanced. Pathways encompass enhanced neural activity, increased energy metabolism, and endocrine signaling during wakefulness; also direct enhancement during sleep. We evaluate the robustness and practicality of SWA-enhancement techniques, discuss approaches for determining a causal role of SWA on cognition, and present questions to clarify the mechanisms of SWA-dependent cognitive improvements.

Reduced sleep pressure in young children with autism

“…Moreover, the magnitude of this reduction was associated with individual severity of sleep disturbances and particularly with sleep-onset difficulties. A variety of existing behavioral and pharmacological interventions are available for enhancing sleep pressure (i.e., increasing sleep depth) 54 including mild interventions such as increased exercise 62 . Since improving sleep quality is likely to reduce aberrant behaviors [18][19][20][21] in children with ASD and reduce parental stress 53 , the initiation of clinical trials with these interventions is highly warranted.…”

“…Contemporary sleep research highlights the importance of SWS for regulating the strength (i.e., the number and efficacy) of cortical synapses 36,38,57,58 , which is critical for proper cognitive function including learning and memory consolidation 34,38,[59][60][61] . In typically developing individuals, the amplitude of SWS (i.e.…”

Individual slow wave morphology is a marker of ageing

“…While the translational potential of slow wave research to clinical practice is limited at the moment, some evidence suggests that cognitive functioning in wakefulness can be improved by artificially increasing slow wave activity in NREM sleep through heating, auditory or electrical stimulation, including in old age (Ladenbauer et al, 2017; Papalambros et al, 2017; Wilckens et al, 2018). Therefore, the significance of the present study is to demonstrate that age-related changes in slow wave morphology possibly underlying the age-related reduction of cognitive function are specific, not fully captured by gross parameters and they especially include the rapidness of phase transitions, in line with previous findings about the additional predictive value of slopes over amplitude towards age (Carrier et al, 2011).…”

The frequency-dependent effect of electrical fields on the mobility of intracellular vesicles in astrocytes

“…First, the rate of βamyloid (Aβ) clearance in mice is improved during sleep and this improvement is associated with an increase in the prevalence of slow waves in sleep (5); Second, the Aβ/tau levels in the cerebrospinal fluid (CSF) are inversely correlated with SWA or the percentage of SWS in total sleep time (9,10); Third, the Aβ/tau levels in the interstitial fluid (ISF) significantly increase during sleep deprivation (SD) versus sleep and the more SWA disruption causes the greater increase of CSF Aβ levels (7,(11)(12)(13); Lastly, slow waves are coupled to blood oxygen leveldependent signals and pulsatile CSF oscillations during NREM sleep (4), and the pulsatile CSF oscillations increase brain fluid mixing and diffusion in the fluid. Thus the SWS brain state defined by SWA shows improved clearance of brain waste products (14)(15)(16)(17)(18) and is also important in memory consolidation (19,20). On the other hand, low-frequency EEG oscillations in SWS reflect the underlying transitions between cortical up and down states (21).…”

“…Here, we utilized total internal reflection fluorescence microscopy (TIRFM) to study the frequency-dependent effect on the mobility of astrocytic intracellular vesicles. We applied electrical stimulation within a range of frequency (2,20,200Hz) on cultured rat astrocytes expressing GFP-labelled membrane protein (VAMP3 or CD63), and found that the mobility of intracellular vesicles in both directional and non-directional movement increased more than 20% under 2 Hz electrical stimulation, but remained unchanged under higher frequencies (20 Hz or 200 Hz) of electrical stimulation. This finding indicates that only slow waves elevate the intracellular activity of astrocytes, suggesting a novel glial mechanism of electrical brain activity that the functionality of astrocytes in brain homeostasis and memory formation can be directly modulated by electrical signals embedded in endogenous low-frequency brainwaves during SWS.…”