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

Abstract

Adenosine and functional A 1 adenosine receptor (A 1 AR) availability are supposed to mediate sleep-wake regulation and cognitive performance. We hypothesized that cerebral A 1 AR availability after an extended wake period decreases to a well-rested state after recovery sleep. [ 18 F]CPFPX positron emission tomography was used to quantify A 1 AR availability in 15 healthy male adults after 52 h of sleep deprivation and following 14 h of recovery sleep. Data were additionally compared with A 1 AR values after 8 h of baseline sleep from an earlier dataset. Polysomnography, cognitive performance, and sleepiness were monitored. Recovery from sleep deprivation was associated with a decrease in A 1 AR availability in several brain regions, ranging from 11% (insula) to 14% (striatum). A 1 AR availabilities after recovery did not differ from baseline sleep in the control group. The degree of performance impairment, sleepiness, and homeostatic sleep-pressure response to sleep deprivation correlated negatively with the decrease in A 1 AR availability. Sleep deprivation resulted in a higher A 1 AR availability in the human brain. The increase that was observed after 52 h of wakefulness was restored to control levels during a 14-h recovery sleep episode. Individuals with a large increase in A 1 AR availability were more resilient to sleep-loss effects than those with a subtle increase. This pattern implies that differences in endogenous adenosine and A 1 AR availability might be causal for individual responses to sleep loss.S leep loss is known to impair almost every aspect of cognition, such as learning (1), long-term memory consolidation (2), attention and psychomotor vigilance (PVT) (3), and executive functions (4), including decision making (5) and emotional control (6). Sleep deprivation further typically alters the frequency distribution of the waking electroencephalogram (EEG) as an indicator of alertness corresponding to cognitive performance (7). However, large interindividual differences exist in the degree of cognitive performance decline during sleep deprivation (3). In a trait-like process, some individuals keep high-level performance during sustained wakefulness, whereas others suffer from severe performance loss (3). The neuro-molecular mechanisms in the brain responsible for these different vulnerabilities are still largely unknown. Caffeine, commonly consumed for fighting fatigue, promotes wakefulness via adenosine receptor antagonism. It seems likely that the adenosinergic system is a neurochemical link between performance and sleep (8). Adenosine is contributing to the homeostatic process of sleep-wake regulation (for review, see refs. 9-12). As has been shown in cats and rats, extracellular adenosine concentration fluctuates rhythmically in many brain regions, such as the basal forebrain, increasing during wakefulness and decreasing during sleep: it thereby induces sleep after wake extension and is in turn restored to baseline levels after recovery sleep (13). For additional information on adenosine, see...

Cognitive impairments by alcohol and sleep deprivation indicate trait characteristics and a potential role for adenosine A 1 receptors

“…Individual differences in caffeine sensitivity have been linked to genetic variations in the adenosine system (39,40). In a recent study using PET, we found that the degree of an individual's performance impairment after extended time awake was related to cerebral A 1 AR availability (29). Taken together, the adenosine system appears to be subject to individual variations that in turn contribute to the differences in the vulnerability to sleep loss.…”

“…The present study also reveals that acute ethanol administration is accompanied by a rapid increase in A 1 AR availability in the human brain and that the subjective sedating effects as assessed by the BAES correlate strongly with cerebral A 1 AR availability. Given the previously observed up-regulation of A 1 AR availability with extended time awake (28,29), the cerebral adenosine system might therefore represent a common pathway for both ethanol and sleep deprivation effects on performance. Behavioral studies have established a link between both stressors, providing evidence for additive or even synergistic detrimental effects on cognitive performance (30)(31)(32)(33).…”

Reestablishment of individual sleep structure during a single 14‐h recovery sleep episode after 58 h of wakefulness

“…The study design was described elsewhere (Elmenhorst et al ., ). In brief, participants came to the laboratory for one adaptation night and one baseline night (23:00–07:00 hours) before being sleep deprived for 58 h. Finally, participants had a 14‐h recovery night (17:00–07:00 hours).…”

Impact of acute sleep deprivation on dynamic functional connectivity states

“…Study procedures and neuropsychological tests were documented in detail in a previous publication (Elmenhorst et al, 2017). Study procedures and neuropsychological tests were documented in detail in a previous publication (Elmenhorst et al, 2017).…”

“…In this study, we enrolled 14 young males (age: 28.21 ± 5.21 years, mean body mass index: 24.39 ± 3.58). Study procedures and neuropsychological tests were documented in detail in a previous publication (Elmenhorst et al, 2017). In brief, the participants were requested to maintain their regular sleep habits (time in bed: 23:00 hr to 7:00 hr), to refrain from caffeine and wear a wrist-actigraph during 1 week, 5 days, and 3 days before coming to the sleep research lab, respectively.…”