Adenosinergic Mechanisms Contribute to Individual Differences in Sleep Deprivation-Induced Changes in Neurobehavioral Function and Brain Rhythmic Activity

Abstract

Large individual differences characterize the changes induced by sleep deprivation on neurobehavioral functions and rhythmic brain activity. To investigate adenosinergic mechanisms in these differences, we studied the effects of prolonged waking and the adenosine receptor antagonist caffeine on sustained vigilant attention and regional electroencephalogram (EEG) power in the ranges of theta activity (6.25-8.25 Hz) in waking and the slow oscillation (Ͻ1 Hz) in sleep. Activity in these frequencies is functionally related to sleep deprivation. In 12 subjectively caffeine-sensitive and 10 -insensitive young men, psychomotor vigilance task (PVT) performance and EEG were assessed at 3 h intervals before, during, and after one night without sleep. After 11 and 23 h waking, subjects received 200 mg caffeine and placebo in double-blind, cross-over manner. In the placebo condition, sleep deprivation impaired PVT speed more in caffeinesensitive than in caffeine-insensitive men. This difference was counteracted by caffeine. Theta power in waking increased more in a frontal EEG derivation than in a posterior derivation. Caffeine attenuated this power gradient in caffeine sensitive subjects. Sleep loss also differently affected the power distribution Ͻ1 Hz in non-rapid eye movement sleep between caffeine sensitive and insensitive subjects. Also, this difference was mirrored by the action of caffeine. The effects of sleep deprivation and caffeine on sustained attention and regional EEG power in waking and sleep were inversely related. These findings suggest that adenosinergic mechanisms contribute to individual differences in waking-induced impairment of neurobehavioral performance and functional aspects of EEG topography associated with sleep deprivation.

Recovery sleep after extended wakefulness restores elevated A 1 adenosine receptor availability in the human brain

“…However, presumably because of the rather small sample size, we could not detect a significant association here. There was also no relationship between adenosine receptor availability and subjective caffeine sensitivity based on a previously evaluated questionnaire (35). Furthermore, no association was found between the caffeine sensitivity subtype and cognitive performance or sleep parameters.…”

“…From cognitive performance under sleepdeprivation conditions, it is known that the degree of impairment varies highly among individuals (34). Differences in caffeine effects have been linked to sleep-loss-induced performance impairments (35) and to genetic variants of the adenosinergic system (36,37). Along these lines, we defined two subgroups based on the A 1 AR availability decrease, of which one group showed a strong decline in receptor availability, whereas the other revealed only a minor decline.…”

Genotype-Dependent Differences in Sleep, Vigilance, and Response to Stimulants

“…Power in the theta/low-alpha band of the waking EEG increases during prolonged time awake [41,[43][44][45]. The time constant of this increase is similar to that of the wake-dependent increase of low-frequency activity in nonREM sleep [44,45].…”

“…It is widely accepted that EEG delta/theta and spindle frequency activity (SFA) in nonREM sleep serve as physiological markers of sleep homeostasis in humans. The duration of slow wave sleep and initial low-frequency activity rise as a function of time awake, while SFA is typically reduced after sleep deprivation [29,[40][41][42]]. …”

What Keeps Us Awake?—the Role of Clocks and Hourglasses, Light, and Melatonin

“…Furthermore, the adenosine receptor antagonist caffeine has the ability to attenuate electroencephalographic (EEG) markers of NREM sleep homeostasis . Accordingly, caffeine administra tion is effective in counteracting the detrimental performance effects of extended wakefulness (Retey et al, 2006;Wyatt et al, 2004).…”