Sleep Deprivation with and Without Stimulant Use Exposesdistinct Dimensions of Cognition

Introduction: Stimulants are commonly used as countermeasures to sleep loss-induced performance impairment in operational settings. People show substantial interindividual variability in vulnerability to sleep loss, and this variability is task-dependent. Limited prior evidence suggests that caffeine and modafinil, stimulants that act through adenosinergic and dopaminergic systems, respectively, may differentially affect interindividual and task-dependent differences. As a first analysis to investigate this, we assessed whether the dimensions of cognition underlying task-dependent performance during total sleep deprivation (TSD) are conserved with caffeine and modafinil during a double-blind, randomized, placebo-controlled TSD in-laboratory study.

Methods: N = 68 healthy adults (25.0 ± 5.0y; 37 males) completed a 3-night/4-day in-laboratory study. During a 38h TSD period (08:00 day 2 to 22:00 day 3), participants received 4 drug administrations beginning at 01:00 on day 3 after randomization to either caffeine (n = 26; 200mg every 4h), modafinil (n = 22; alternating 200mg and placebo every 4h), or placebo (n = 20). On day 3 participants completed an 18min go/no-go task with reversal (GNGr) at 09:30 and a 30min traffic light task in a high-fidelity driving simulator at 12:00. At 13:30, they completed a computerized task battery with the Karolinska Sleepiness Scale (KSS), 10min psychomotor vigilance test (PVT), 4min digit-symbol substitution task (DSST), and Positive and Negative Affect Schedule (PANAS). Performance outcomes included stimulus acquisition and cognitive flexibility measures from pre- and post-reversal discriminability indices on the GNGr; drowsiness and prepotent response inhibition measures from lane deviation and a discriminability index on the traffic light task; subjective sleepiness score on the KSS; vigilant attention assessed by lapses (RT≥500ms) and log signal-to-noise ratio of RTs on the PVT; number correct as a combined measure of vigilant attention and associative learning on the DSST; and positive and negative affect scores on the PANAS. Clustering of interindividual differences in these outcomes was investigated using principal component analysis (PCA) with varimax rotation, controlling for drug condition.

Results: Two distinct factors emerged from the PCA analysis. The first factor captured increased subjective sleepiness and reduced vigilant attention, associative learning, and positive affect. The second factor captured increased drowsiness (lane deviation), negative affect, reduced stimulus acquisition, cognitive flexibility, and prepotent response inhibition. Together, these dimensions of cognitive performance explained 45.8% of the variance in TSD-induced performance impairment.

Conclusion: When controlling for caffeine, modafinil, and placebo drug conditions, cognitive performance impairment during sleep deprivation clustered around two orthogonal dimensions – one predominated by vigilant attention deficits, the other predominated by cognitive control deficits – suggesting distinct underlying neurobiological mechanisms shared across conditions, regardless of the neurobiological mechanisms involved in the actions of caffeine and modafinil. Follow-up analyses will assess the extent to which these stimulants may also have interacted differentially with the task-dependent interindividual differences in vulnerability to sleep deprivation. Support: USAMRDC W81XWH-18–1-0100.

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Artikel online veröffentlicht:
08. Oktober 2025