RT Journal Article SR Electronic T1 Functional Magnetic Resonance Imaging-Assessed Brain Responses during an Executive Task Depend on Interaction of Sleep Homeostasis, Circadian Phase, and PER3 Genotype JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 7948 OP 7956 DO 10.1523/JNEUROSCI.0229-09.2009 VO 29 IS 25 A1 Gilles Vandewalle A1 Simon N. Archer A1 Catherine Wuillaume A1 Evelyne Balteau A1 Christian Degueldre A1 André Luxen A1 Pierre Maquet A1 Derk-Jan Dijk YR 2009 UL http://www.jneurosci.org/content/29/25/7948.abstract AB Cognition is regulated across the 24 h sleep-wake cycle by circadian rhythmicity and sleep homeostasis through unknown brain mechanisms. We investigated these mechanisms in a functional magnetic resonance imaging study of executive function using a working memory 3-back task during a normal sleep-wake cycle and during sleep loss. The study population was stratified according to homozygosity for a variable-number (4 or 5) tandem-repeat polymorphism in the coding region of the clock gene PERIOD3. This polymorphism confers vulnerability to sleep loss and circadian misalignment through its effects on sleep homeostasis. In the less-vulnerable genotype, no changes were observed in brain responses during the normal-sleep wake cycle. During sleep loss, these individuals recruited supplemental anterior frontal, temporal and subcortical regions, while executive function was maintained. In contrast, in the vulnerable genotype, activation in a posterior prefrontal area was already reduced when comparing the evening to the morning during a normal sleep-wake cycle. Furthermore, in the morning after a night of sleep loss, widespread reductions in activation in prefrontal, temporal, parietal and occipital areas were observed in this genotype. These differences occurred in the absence of genotype-dependent differences in circadian phase. The data show that dynamic changes in brain responses to an executive task evolve across the sleep-wake and circadian cycles in a regionally specific manner that is determined by a polymorphism which affects sleep homeostasis. The findings support a model of individual differences in executive control, in which the allocation of prefrontal resources is constrained by sleep pressure and circadian phase.