title: Functional magnetic resonance imaging-assessed brain responses during an executive task depend on interaction of sleep homeostasis, circadian phase, and PER3 genotype.
abstract: 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.
authors: Cyclotron Research Centre, University of Liège, B-4000 Liège, Belgium.
authors: Gilles
authors: G
authors: Vandewalle
authors: Simon N
authors: SN
authors: Archer
authors: Catherine
authors: C
authors: Wuillaume
authors: Evelyne
authors: E
authors: Balteau
authors: Christian
authors: C
authors: Degueldre
authors: André
authors: A
authors: Luxen
authors: Pierre
authors: P
authors: Maquet
authors: Derk-Jan
authors: DJ
authors: Dijk
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000502:physiology*; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D005260:Female; D005625:Frontal Lobe / Q000502:physiology; D005838:Genotype; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D009687:Nuclear Proteins / Q000235:genetics*; D009778:Occipital Lobe / Q000502:physiology; D010296:Parietal Lobe / Q000502:physiology; D056950:Period Circadian Proteins; D020641:Polymorphism, Single Nucleotide; D017397:Prefrontal Cortex / Q000502:physiology; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D012892:Sleep Deprivation / Q000235:genetics / Q000503:physiopathology; D020080:Tandem Repeat Sequences; D013702:Temporal Lobe / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D014851:Wakefulness / Q000235:genetics / Q000502:physiology; D055815:Young Adult
chemical_list: D009687:Nuclear Proteins; C512644:PER3 protein, human; D056950:Period Circadian Proteins; D014157:Transcription Factors