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at 2200 h compared with 1600 h, indicative of diurnal variation. Vimal and
colleague s 233 showed significantly increased BOLD activation in response to
light stimuli in the suprachiasmatic nucleus at night compared with midday,
while Peres and colleagues 234 demonstrated systematic BOLD signal differ-
ences across the day in the motor areas during a self-paced finger-tapping
task. Significant time-of-day effects were also observed in the brain orienting
attentional system including the inferior parietal and frontal eye field regions
during a Stroop-like task, suggesting that bottom-up attention orientation
may be vulnerable to circadian factors. 235
Importantly, a few recent BOLD fMRI studies have demonstrated sig-
nificant interindividual differences in circadian variation of brain activation
and the complex interactions between sleep homeostasis, circadian phase,
and genotype. For example, using an auditory 3-back working memory task,
Vandewalle and colleagues 236 showed no changes in brain responses during
the normal sleep-wake cycle for the putatively less-vulnerable PER3
4/4
genotype, while reduced activation in the posterior prefrontal area was
found in the putatively vulnerable PER3
5/5
genotype when comparing eve-
ning and morning activation during a normal sleep-wake cycle. These
authors also reported that blue light increased brain responses in the
frontoparietal regions only in PER3
4/4 individuals in the morning after
one night of normal sleep, while blue light increased brain responses in
the thalamic and frontoparietal regions only in PER3
5/5 individuals in the
morning after one night of total sleep deprivation. 237 In addition, Schmidt
and colleagues 238 showed that morning and evening chronotypes differed in
brain activation in the suprachiasmatic area at night during PVT perfor-
mance. They further found that brain activation associated with conflict
processing and inhibition function were maintained or increased in evening
chronotypes from the subjective morning to the subjective evening but
decreased in morning chronotypes under the same conditions. 239
While the above findings are informative, one major limitation of task-
related BOLD fMRI is that it can only measure relative signal changes and
lacks absolute quantification of brain activity. Therefore, it is difficult to
determine whether the observed BOLD activation changes are due to
changes at baseline or changes during performance of specific tasks, or both.
It is also difficult for task-related BOLD fMRI to dissociate the effects of
sleep loss, time-of-day, or circadian phase on brain function per se and on behav-
ioral performance that subsequently confounds brain activation. In contrast to
BOLD, arterial spin-labeled (ASL) perfusion fMRI—a relatively new imaging
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