Sustaining Executive Functions During Sleep Deprivation: A Comparison of Caffeine, Dextroamphetamine, and Modafinil

Killgore, William D.S.; Kahn-Greene, Ellen T.; Grugle, Nancy L.; Killgore, Desiree B.; Balkin, Thomas J.

doi:10.1093/sleep/32.2.205

Cited by 121 publications

(84 citation statements)

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“…26,27 Also, the effects of caffeine on higher-order complex cognitive capacities (e.g., planning, decision making, and memory) appear to be mixed, suggesting different degrees of performance restoration depending on the particular task in question and caffeine dose amount. 18,28,29 Another potential limitation is that the UMP does not account for chronic caffeine use or withdrawal effects. In other words, it is possible that habitually high caffeine users may require a larger caffeine dose to experience the same benefits as compared to habitually low caffeine users, and may show significant performance impairments due to withdrawal.…”

Section: Discussionmentioning

confidence: 99%

A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine

Ramakrishnan

Wesensten

Kamimori

et al. 2016

Sleep

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Study Objectives: Existing mathematical models of neurobehavioral performance cannot predict the beneficial effects of caffeine across the spectrum of sleep loss conditions, limiting their practical utility. Here, we closed this research gap by integrating a model of caffeine effects with the recently validated unified model of performance (UMP) into a single, unified modeling framework. We then assessed the accuracy of this new UMP in predicting performance across multiple studies. Methods: We hypothesized that the pharmacodynamics of caffeine vary similarly during both wakefulness and sleep, and that caffeine has a multiplicative effect on performance. Accordingly, to represent the effects of caffeine in the UMP, we multiplied a dose-dependent caffeine factor (which accounts for the pharmacokinetics and pharmacodynamics of caffeine) to the performance estimated in the absence of caffeine. We assessed the UMP predictions in 14 distinct laboratory-and field-study conditions, including 7 different sleep-loss schedules (from 5 h of sleep per night to continuous sleep loss for 85 h) and 6 different caffeine doses (from placebo to repeated 200 mg doses to a single dose of 600 mg). Results: The UMP accurately predicted group-average psychomotor vigilance task performance data across the different sleep loss and caffeine conditions (6% < error < 27%), yielding greater accuracy for mild and moderate sleep loss conditions than for more severe cases. Overall, accounting for the effects of caffeine resulted in improved predictions (after caffeine consumption) by up to 70%. Conclusions:The UMP provides the first comprehensive tool for accurate selection of combinations of sleep schedules and caffeine countermeasure strategies to optimize neurobehavioral performance. Keywords: biomathematical model, caffeine model, chronic sleep restriction, PVT, total sleep deprivation Citation: Ramakrishnan S, Wesensten NJ, Kamimori GH, Moon JE, Balkin TJ, Reifman J. A unified model of performance for predicting the effects of sleep and caffeine. SLEEP 2016;39(10):1827-1841. INTRODUCTIONMathematical models that accurately predict the effects of sleep/wake schedules on human neurobehavioral performance are valuable tools for effective management of operational alertness and fatigue. However, to be of practical use, they must also be able to predict the alertness-and performance-enhancing effects of caffeine, the most widely used stimulant compound. Caffeine is available in a wide range of concentrations in myriad foods and beverages, including coffee, tea, soft drinks, and energy drinks, providing a spectrum of performance-improving effects. Nevertheless, the most thoroughly validated predictive models of performance do not account for the effects of caffeine, 1,2 and the few that do have limitations. For example, the models proposed by Benitez et al. 3 and by Ramakrishnan et al.

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Section: Discussionmentioning

confidence: 99%

A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine

Ramakrishnan

Wesensten

Kamimori

et al. 2016

Sleep

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“…Sleep deprivation has been shown to have significant adverse effects on a range of higherorder cognitive processes, including memory encoding, consolidation, and retrieval (Walker 2008), behavioral inhibition (Drummond et al 2006;Harrison et al 2007), judgment (Killgore et al 2007a), planning (Horne 1988;Killgore et al 2009), and divergent thinking capacities (Horne 1988). All such processes are believed to draw heavily upon resources in the prefrontal cortex (Killgore et al 2011).…”

Section: Sleep Deprivation Affects Higher-order Cognitive Processesmentioning

confidence: 99%

“…Some evidence indicates that the effectiveness of stimulants, including caffeine, on executive functions may be task specific, and depend upon the underlying executive function systems targeted by different stimulant (Killgore et al 2009). For instance, participants' performance on a behavioral measure of risk-taking and impulsive responding (the Balloon Analog Risk Task) was relatively resistant to the effects of sleep loss until about 75 hours of continuous wakefulness, at which point there was a clear increase in risky decision making (Killgore et al 2011).…”

Section: Caffeine Has Weak Potency To Improve Impaired Higher-order Amentioning

confidence: 99%

Adenosine, Caffeine, and Performance: From Cognitive Neuroscience of Sleep to Sleep Pharmacogenetics

Urry

Landolt

2014

Current Topics in Behavioral Neurosciences

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An intricate interplay between circadian and sleep-wake homeostatic processes regulate cognitive performance on specific tasks, and individual differences in circadian preference and sleep pressure may contribute to individual differences in distinct neurocognitive functions. Attentional performance appears to be particularly sensitive to time of day modulations and the effects of sleep deprivation. Consistent with the notion that the neuromodulator, adenosine adenosine , plays an important role in regulating sleep pressure, pharmacologic and genetic data in animals and humans demonstrate that differences in adenosinergic tone affect sleepiness, arousal and vigilant attention attention in rested and sleep-deprived states. Caffeine Caffeine -the most often consumed stimulant in the world-blocks adenosine receptors and normally attenuates the consequences of sleep deprivation on arousal, vigilance, and attention. Nevertheless, caffeine cannot substitute for sleep, and is virtually ineffective in mitigating the impact of severe sleep loss on higher-order cognitive functions. Thus, the available evidence suggests that adenosinergic mechanisms, in particular adenosine A2A receptor-mediated signal transduction, contribute to waking-induced impairments of attentional processes, whereas additional mechanisms must be involved in higher-order cognitive consequences of sleep deprivation. Future investigations should further clarify the exact types of cognitive processes affected by inappropriate sleep. This research will aid in the quest to better understand the role of different brain systems (e.g., adenosine and adenosine receptors) in regulating sleep, and sleep-related subjective state, and cognitive processes. Furthermore, it will provide more detail on the underlying mechanisms of the detrimental effects of extended wakefulness, as well as lead to the development of effective, evidence-based countermeasures against the health consequences of circadian misalignment and chronic sleep restriction. In press (accepted): January 14, 2014 Addresses for correspondence:Hans-Peter Landolt, Ph.D.

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“…In zwei Studien wurde an jungen Gesunden der Effekt von 400 mg Modafinil, 20 mg Amphetamin und 600 mg Koffein mittels diverser neuropsychologischer Tests untersucht [20,21]. Hier fanden sich keine wesentlichen Wirkunterschiede.…”

Section: Modafinilunclassified

Pharmakologisches Neuroenhancement und „Hirndoping“

Franke

Lieb

2010

Bundesgesundheitsbl.

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Pharmacological neuroenhancement refers to the use of psychoactive substances by healthy subjects with the purpose of cognitive enhancement, e.g., vigilance, concentration, memory, or mood. "Brain doping", however, refers to the illicit use of a subcategory of these substances such as prescription drugs. This subcategory includes psychostimulants (e.g., amphetamines, methylphenidate), modafinil, antidementia drugs (acetylcholine-esterase inhibitors, memantine), and antidepressants (selective serotonin reuptake inhibitors) which are being prescribed for the treatment of ADHD (attention deficit/hyperactivity disorder), Alzheimer's disease, and depression. Only psychostimulants and modafinil show significant effects on concentration, attentiveness, and vigilance in healthy subjects. However, a general use by healthy persons can not be justified because of relevant side effects and safety risks. Caffeine for pharmacological neuroenhancement can be seen as an equally effective alternative. "Brain doping" raises numerous ethical and social concerns that require a continued discussion. Demands of liberalization should be critically questioned.

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Sustaining Executive Functions During Sleep Deprivation: A Comparison of Caffeine, Dextroamphetamine, and Modafinil

Abstract: Although comparisons across tasks cannot be made due to the different times of administration, within-task comparisons suggest that, at the doses tested here, each stimulant may produce differential advantages depending on the cognitive demands of the task.

Cited by 121 publications

References 67 publications

A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine

A Unified Model of Performance for Predicting the Effects of Sleep and Caffeine

Adenosine, Caffeine, and Performance: From Cognitive Neuroscience of Sleep to Sleep Pharmacogenetics

Pharmakologisches Neuroenhancement und „Hirndoping“

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