Modeling the adenosine system as a modulator of cognitive performance and sleep patterns during sleep restriction and recovery

Andrew J K Phillips, Elizabeth B Klerman and James P Butler

PLOS Computational Biology, 2017, vol. 13, issue 10, 1-21

Abstract: Sleep loss causes profound cognitive impairments and increases the concentrations of adenosine and adenosine A1 receptors in specific regions of the brain. Time courses for performance impairment and recovery differ between acute and chronic sleep loss, but the physiological basis for these time courses is unknown. Adenosine has been implicated in pathways that generate sleepiness and cognitive impairments, but existing mathematical models of sleep and cognitive performance do not explicitly include adenosine. Here, we developed a novel receptor-ligand model of the adenosine system to test the hypothesis that changes in both adenosine and A1 receptor concentrations can capture changes in cognitive performance during acute sleep deprivation (one prolonged wake episode), chronic sleep restriction (multiple nights with insufficient sleep), and subsequent recovery. Parameter values were estimated using biochemical data and reaction time performance on the psychomotor vigilance test (PVT). The model closely fit group-average PVT data during acute sleep deprivation, chronic sleep restriction, and recovery. We tested the model’s ability to reproduce timing and duration of sleep in a separate experiment where individuals were permitted to sleep for up to 14 hours per day for 28 days. The model accurately reproduced these data, and also correctly predicted the possible emergence of a split sleep pattern (two distinct sleep episodes) under these experimental conditions. Our findings provide a physiologically plausible explanation for observed changes in cognitive performance and sleep during sleep loss and recovery, as well as a new approach for predicting sleep and cognitive performance under planned schedules.Author summary: Sleep loss is known to cause significant decrements in cognitive performance, but the physiological mechanisms responsible for this response are not well understood. Computational models have been developed to predict how individuals will cognitively perform under acute or chronic sleep loss, but they currently lack an explicit physiological foundation, and do not specifically predict sleep timing. Adenosine is hypothesized to be an important mediator in the effects of sleep loss, as it is a sleep-promoting substance that accumulates in the brain during wakefulness. We developed a mathematical model of the adenosine system in the brain and showed that it can parsimoniously account for not only changes in cognitive performance during acute sleep deprivation, chronic sleep restriction, and recovery, but also changes in sleep patterns during long-term recovery. The model thus provides a quantitative link between complex whole-organism behaviors and underlying molecular and physiologic mechanisms.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1005759

DOI: 10.1371/journal.pcbi.1005759

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