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The Journal of Neuroscience, October 11, 2006, 26(41):10472-10479; doi:10.1523/JNEUROSCI.1538-06.2006

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Behavioral/Systems/Cognitive
Adenosinergic Mechanisms Contribute to Individual Differences in Sleep Deprivation-Induced Changes in Neurobehavioral Function and Brain Rhythmic Activity

Julia V. Rétey,¹ Martin Adam,¹ Julie M. Gottselig,¹ Ramin Khatami,¹ Roland Dürr,¹ Peter Achermann,^1,2 and Hans-Peter Landolt^1,2

¹Institute of Pharmacology and Toxicology and ²Zürich Center for Integrative Human Physiology, University of Zürich, 8057 Zürich, Switzerland

Correspondence should be addressed to Dr. Hans-Peter Landolt, Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. Email: landolt{at}pharma.unizh.ch

Large individual differences characterize the changes induced by sleep deprivation on neurobehavioral functions and rhythmic brain activity. To investigate adenosinergic mechanisms in these differences, we studied the effects of prolonged waking and the adenosine receptor antagonist caffeine on sustained vigilant attention and regional electroencephalogram (EEG) power in the ranges of theta activity (6.25–8.25 Hz) in waking and the slow oscillation (<1 Hz) in sleep. Activity in these frequencies is functionally related to sleep deprivation. In 12 subjectively caffeine-sensitive and 10 -insensitive young men, psychomotor vigilance task (PVT) performance and EEG were assessed at 3 h intervals before, during, and after one night without sleep. After 11 and 23 h waking, subjects received 200 mg caffeine and placebo in double-blind, cross-over manner. In the placebo condition, sleep deprivation impaired PVT speed more in caffeine-sensitive than in caffeine-insensitive men. This difference was counteracted by caffeine. Theta power in waking increased more in a frontal EEG derivation than in a posterior derivation. Caffeine attenuated this power gradient in caffeine sensitive subjects. Sleep loss also differently affected the power distribution <1 Hz in non-rapid eye movement sleep between caffeine sensitive and insensitive subjects. Also, this difference was mirrored by the action of caffeine. The effects of sleep deprivation and caffeine on sustained attention and regional EEG power in waking and sleep were inversely related. These findings suggest that adenosinergic mechanisms contribute to individual differences in waking-induced impairment of neurobehavioral performance and functional aspects of EEG topography associated with sleep deprivation.

Key words: attention; electroencephalogram; caffeine; human; frontal cortex; circadian

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Received April 10, 2006; revised Aug. 22, 2006; accepted Sept. 4, 2006.

Correspondence should be addressed to Dr. Hans-Peter Landolt, Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. Email: landolt{at}pharma.unizh.ch

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