Effects of modafinil on working memory processes in humans

Abstract

Rationale

Modafinil is a well-tolerated psychostimulant drug with low addictive potential that is used to treat patients with narcolepsy or attention deficit disorders and to enhance vigilance in sleep-deprived military personal. So far, understanding of the cognitive enhancing effects of modafinil and the relevant neurobiological mechanisms are incomplete.

Objectives

The aim of this study was to investigate the effects of modafinil on working memory processes in humans and how they are related to noradrenergic stimulation of the prefrontal cortex.

Methods

Sixteen healthy volunteers (aged 20–29 years) received either modafinil 200 mg or placebo using a double blind crossover design. Two computerized working memory tasks were administered, a numeric manipulation task that requires short-term maintenance of digit-sequences and different degrees of manipulation as well as delayed matching task that assesses maintenance of visuo-spatial information over varying delay lengths. The battery was supplemented by standardized paper pencil tasks of attentional functions.

Results

Modafinil significantly reduced error rates in the long delay condition of the visuo-spatial task and in the manipulation conditions, but not in the maintenance condition of the numeric task. Analyses of reaction times showed no speed-accuracy trade-off. Attentional control tasks (letter cancellation, trail-making, catch trials) were not affected by modafinil.

Conclusions

In healthy volunteers without sleep deprivation modafinil has subtle stimulating effects on maintenance and manipulation processes in relatively difficult and monotonous working memory tasks, especially in lower performing subjects. Overlapping attentional and working memory processes have to be considered when studying the noradrenergic modulation of the prefrontal cortex.

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Acknowledgements

The authors are indebted to Dr. Luke Clark and an anonymous reviewer for comments on an earlier version of this paper, to Sandra Brattge and Bettina Johst for programming the delayed matching task, to Anke Pitzmaus for laboratory assistance and to all volunteers for participation. The study was supported by the Max Planck Society and the Alexander von Humboldt-Foundation (Feodor Lynen-Fellowship awarded to U.M.).

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Correspondence to Ulrich Müller.

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Müller, U., Steffenhagen, N., Regenthal, R. et al. Effects of modafinil on working memory processes in humans. Psychopharmacology 177, 161–169 (2004). https://doi.org/10.1007/s00213-004-1926-3

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Keywords

  • Human
  • Modafinil
  • Noradrenaline
  • Prefrontal
  • Working memory