School of Physics, University of Sydney, New South Wales 2006, Australia.
J Theor Biol. 2011 Mar 21;273(1):44-54. doi: 10.1016/j.jtbi.2010.12.018. Epub 2010 Dec 19.
A recent physiologically based model of human sleep is extended to incorporate the effects of caffeine on sleep-wake timing and fatigue. The model includes the sleep-active neurons of the hypothalamic ventrolateral preoptic area (VLPO), the wake-active monoaminergic brainstem populations (MA), their interactions with cholinergic/orexinergic (ACh/Orx) input to MA, and circadian and homeostatic drives. We model two effects of caffeine on the brain due to competitive antagonism of adenosine (Ad): (i) a reduction in the homeostatic drive and (ii) an increase in cholinergic activity. By comparing the model output to experimental data, constraints are determined on the parameters that describe the action of caffeine on the brain. In accord with experiment, the ranges of these parameters imply significant variability in caffeine sensitivity between individuals, with caffeine's effectiveness in reducing fatigue being highly dependent on an individual's tolerance, and past caffeine and sleep history. Although there are wide individual differences in caffeine sensitivity and thus in parameter values, once the model is calibrated for an individual it can be used to make quantitative predictions for that individual. A number of applications of the model are examined, using exemplar parameter values, including: (i) quantitative estimation of the sleep loss and the delay to sleep onset after taking caffeine for various doses and times; (ii) an analysis of the system's stable states showing that the wake state during sleep deprivation is stabilized after taking caffeine; and (iii) comparing model output successfully to experimental values of subjective fatigue reported in a total sleep deprivation study examining the reduction of fatigue with caffeine. This model provides a framework for quantitatively assessing optimal strategies for using caffeine, on an individual basis, to maintain performance during sleep deprivation.
最近提出了一个人类睡眠的生理基础模型，该模型扩展后可以纳入咖啡因对睡眠-觉醒时间和疲劳的影响。该模型包括下丘脑腹外侧视前区（VLPO）的睡眠活性神经元、觉醒活性单胺能脑干群体（MA）、它们与胆碱能/食欲素能（ACh/Orx）输入到 MA 的相互作用，以及昼夜节律和内稳态驱动。我们对咖啡因对大脑的两种作用建模，这是由于咖啡因对腺苷（Ad）的竞争性拮抗作用：（i）内稳态驱动的降低，（ii）胆碱能活性的增加。通过将模型输出与实验数据进行比较，确定了描述咖啡因对大脑作用的参数的约束条件。与实验一致，这些参数的范围意味着个体之间对咖啡因的敏感性存在显著差异，咖啡因减轻疲劳的效果高度依赖于个体的耐受性和过去的咖啡因和睡眠史。尽管咖啡因敏感性存在广泛的个体差异，因此参数值也存在差异，但一旦为个体校准模型，就可以使用该模型对该个体进行定量预测。使用示例参数值检查了该模型的多个应用，包括：（i）定量估计在摄入不同剂量和时间的咖啡因后睡眠损失和入睡延迟；（ii）分析系统的稳定状态，表明摄入咖啡因后睡眠剥夺期间的觉醒状态得到稳定；以及（iii）将模型输出与总睡眠剥夺研究中报告的主观疲劳的实验值进行比较，该研究检查了咖啡因对疲劳的减轻作用。该模型提供了一个框架，可用于根据个体情况定量评估使用咖啡因的最佳策略，以在睡眠剥夺期间保持表现。
