A biomathematical model of the restoring effects of caffeine on cognitive performance during sleep deprivation

作者：Ramakrishnan Sridhar; Rajaraman Srinivasan; Laxminarayan Srinivas; Wesensten Nancy J; Kamimori Gary H; Balkin Thomas J; Reifman Jaques^*

来源：Journal of Theoretical Biology, 2013, 319: 23-33.

DOI：10.1016/j.jtbi.2012.11.015

• Caffeine model
• Sleep loss
• PVT
• Individualized modeling
• Pharmacokinetic-pharmacodynamic model

Rationale: While caffeine is widely used as a countermeasure to sleep loss, mathematical models are lacking.
Objective: Develop a biomathematical model for the performance-restoring effects of caffeine in sleep-deprived subjects.
Methods: We hypothesized that caffeine has a multiplicative effect on performance during sleep loss. Accordingly, we first used a phenomenological two-process model of sleep regulation to estimate performance in the absence of caffeine, and then multiplied a caffeine-effect factor, which relates the pharmacokinetic-pharmacodynamic effects through the Hill equation, to estimate the performance-restoring effects of caffeine.
Results: We validated the model on psychomotor vigilance test data from two studies involving 12 subjects each: (1) single caffeine dose of 600 mg after 64.5 h of wakefulness and (2) repeated doses of 200 mg after 20, 22, and 24 h of wakefulness. Individualized caffeine models produced overall errors that were 19% and 42% lower than their population-average counterparts for the two studies. Had we not accounted for the effects of caffeine, the individualized model errors would have been 117% and 201% larger, respectively.
Conclusions: The presented model captured the performance-enhancing effects of caffeine for most subjects in the single- and repeated-dose studies, suggesting that the proposed multiplicative factor is a feasible solution.

• 出版日期2013-2-21