Circadian Rhythms, Sleep Deprivation, and Human Performance - Progress in Molecular Biology and Translational Science - page 173

different sleep-restriction paradigms than that of Goel et al. , 148 claimed that
the PER3 VNTR polymorphism was related to individual differences in
neurobehavioral responses to chronic sleep restriction. Notably, one of
these 184 failed to include subjects from the critical PER3

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putatively vul-
nerable genotype, and thus its findings must be interpreted cautiously and
replicated in the appropriately inclusive genotypes. As another example,
we found that the catechol-O-methyltransferase Val158Met polymorphism
predicted individual differences in sleep homeostatic responses to chronic
sleep restriction, 173 but such prediction has not been shown to acute total
sleep deprivation. 185 Clearly, more studies are warranted to investigate
potential genotypic markers of phenotypic vulnerability to sleep loss and
the differential role they might play in response to different types of
sleep loss.

6.2. Neuroimaging of sleep deprivation and circadian
variations in brain metabolism and neural activity
With few exceptions, the influences of sleep deprivation and circadian var-
iations on brain metabolism and neural activity have been studied separately
in the past two decades using various neuroimaging methods, particularly
positron emission tomography (PET) and functional magnetic resonance
imaging (fMRI).
PET studies of sleep deprivation have consistently reported significant
reductions in metabolic rates in the thalamic, parietal, and prefrontal regions
after sleep loss, which correlated with declines of cognitive performance and
alertness. 186-189 An early PET study examined the effects of time of day (a
surrogate for circadian phase) on the cerebral metabolic rate of glucose and
observed a trend toward increased whole brain glucose metabolism from
the morning to the afternoon scans. 190 A more recent PET study found
increased relative glucose metabolism in the brainstem and hypothalamic
arousal systems and decreased relative metabolism in the posterior cortical
regions during evening wakefulness compared with morning wakeful-
ness. 191 Moreover, variations in regional brain glucose metabolism have
been reported to differ across morning and evening scans in depressed
and healthy adult subjects. 192 New PET studies on neurotransmitter recep-
tors have shown downregulation of striatal dopamine receptor s 193 but
increases in cerebral serotonin receptor binding with sleep loss, 194 which
may reflect a complex adaptive brain response to sleep deprivation. How-
ever, due to its invasiveness and the rapid decay of radioactive tracers, further