Abstract
Sleep deprivation impairs cognitive performance and reliably alters brain activation in wakefulness and sleep. Nevertheless, the molecular regulators of prolonged wakefulness remain poorly understood. Evidence from genetic, behavioral, pharmacologic and imaging studies suggest that dopaminergic signaling contributes to the behavioral and electroencephalographic (EEG) consequences of sleep loss, although direct human evidence thereof is missing. We tested whether dopamine neurotransmission regulate sustained attention and evolution of EEG power during prolonged wakefulness. Here, we studied the effects of functional genetic variation in the dopamine transporter (DAT1) and the dopamine D2 receptor (DRD2) genes, on psychomotor performance and standardized waking EEG oscillations during 40 hours of wakefulness in 64 to 82 healthy volunteers. Sleep deprivation consistently enhanced sleepiness, lapses of attention and the theta-to-alpha power ratio (TAR) in the waking EEG. Importantly, DAT1 and DRD2 genotypes distinctly modulated sleep loss-induced changes in subjective sleepiness, PVT lapses and TAR, according to inverted U-shaped relationships. Together, the data suggest that genetically determined differences in DAT1 and DRD2 expression modulate functional consequences of sleep deprivation, supporting the hypothesis that striato-thalamo-cortical dopaminergic pathways modulate the neurobehavioral and neurophysiological consequences of sleep loss in humans.
Highlights
Sleep deprivation enhances sleepiness, impairs performance and alters electrical brain activity in a highly predictable fashion[1,2,3,4]
The present study revealed that functional polymorphisms of DAT1 and DRD2 together modulate the neurobehavioral, subjective and neurophysiological consequences of sleep deprivation
Functional magnetic resonance imaging data suggested that activation of the striatum in a monetary reward paradigm depends on genetic variants of both DAT1 and DRD2 genes
Summary
Impairs performance and alters electrical brain activity in a highly predictable fashion[1,2,3,4]. Consistent with a genetic contribution, the impact of sleep loss on distinct subjective, PVT, and neurophysiological markers of alertness, is trait-like and highly robust within individuals These variables don’t typically show a clear association with each other, but rather develop seemingly independently[13,14]. Based on the evidence presented above, we aimed at investigating the impacts of functional DAT1 and DRD2 polymorphisms on sleep deprivation-induced changes in subjective sleepiness, attentional lapses and the waking EEG in humans. We hypothesized that these genetic variants impact individual consequences of sleep loss and expected that they interact to modulate vigilant attention and EEG power during prolonged wakefulness according to U-shaped relationships
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