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Abstract
Vigilant attention is a major component of a wide range of cognitive performance tasks.
Vigilant attention is impaired by sleep deprivation and restored after rest breaks
and (more enduringly) after sleep. The temporal dynamics of vigilant attention deficits
across hours and days are driven by physiologic, sleep regulatory processes—a sleep
homeostatic process and a circadian process. There is also evidence of a slower, allostatic
process, which modulates the sleep homeostatic setpoint across days and weeks and
is responsible for cumulative deficits in vigilant attention across consecutive days
of sleep restriction. There are large inter-individual differences in vulnerability
to sleep loss, and these inter-individual differences constitute a pronounced human
phenotype. However, this phenotype is multi-dimensional; vulnerability in terms of
vigilant attention impairment can be dissociated from vulnerability in terms of other
cognitive processes such as attentional control. The vigilance decrement, or time-on-task
effect—a decline in performance across the duration of a vigilant attention task—is
characterized by progressively increasing response variability, which is exacerbated
by sleep loss. This variability, while crucial to understanding the impact of sleep
deprivation on performance in safety-critical tasks, is not well explained by top-down
regulatory mechanisms, such as the homeostatic and circadian processes. A bottom-up,
neuronal pathway-dependent mechanism involving use-dependent, local sleep may be the
main driver of response variability. This bottom-up mechanism may also explain the
dissociation between cognitive processes with regard to trait vulnerability to sleep
loss.
Genome-wide association studies have greatly improved our understanding of the genetic basis of disease risk. The fact that they tend not to identify more than a fraction of the specific causal loci has led to divergence of opinion over whether most of the variance is hidden as numerous rare variants of large effect or as common variants of very small effect. Here I review 20 arguments for and against each of these models of the genetic basis of complex traits and conclude that both classes of effect can be readily reconciled.
To determine whether a cumulative sleep debt (in a range commonly experienced) would result in cumulative changes in measures of waking neurobehavioral alertness, 16 healthy young adults had their sleep restricted 33% below habitual sleep duration, to an average 4.98 hours per night [standard deviation (SD) = 0.57] for seven consecutive nights. Subjects slept in the laboratory, and sleep and waking were monitored by staff and actigraphy. Three times each day (1000, 1600, and 2200 hours) subjects were assessed for subjective sleepiness (SSS) and mood (POMS) and were evaluated on a brief performance battery that included psychomotor vigilance (PVT), probed memory (PRM), and serial-addition testing, Once each day they completed a series of visual analog scales (VAS) and reported sleepiness and somatic and cognitive/emotional problems. Sleep restriction resulted in statistically robust cumulative effects on waking functions. SSS ratings, subscale scores for fatigue, confusion, tension, and total mood disturbance from the POMS and VAS ratings of mental exhaustion and stress were evaluated across days of restricted sleep (p = 0.009 to p = 0.0001). PVT performance parameters, including the frequency and duration of lapses, were also significantly increased by restriction (p = 0.018 to p = 0.0001). Significant time-of-day effects were evident in SSS and PVT data, but time-of-day did not interact with the effects of sleep restriction across days. The temporal profiles of cumulative changes in neurobehavioral measures of alertness as a function of sleep restriction were generally consistent. Subjective changes tended to precede performance changes by 1 day, but overall changes in both classes of measure were greatest during the first 2 days (P1, P2) and last 2 days (P6, P7) of sleep restriction. Data from subsets of subjects also showed: 1) that significant decreases in the MSLT occurred during sleep restriction, 2) that the elevated sleepiness and performance deficits continued beyond day 7 of restriction, and 3) that recovery from these deficits appeared to require two full nights of sleep. The cumulative increase in performance lapses across days of sleep restriction correlated closely with MSLT results (r = -0.95) from an earlier comparable experiment by Carskadon and Dement (1). These findings suggest that cumulative nocturnal sleep debt had a dynamic and escalating analog in cumulative daytime sleepiness and that asymptotic or steady-state sleepiness was not achieved in response to sleep restriction.
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