|Julian Lim and David F. Dinges (2007), Scholarpedia, 2(8):2433.||doi:10.4249/scholarpedia.2433||revision #137223 [link to/cite this article]|
Sleep deprivation is the restriction of sleep below the level of basal sleep need; this can be both acute (a single period of extended wakefulness), or chronic (the accumulation of sleep debt over multiple nights of sleep restriction). The basal sleep need of an organism is its habitual sleep duration in the absence of pre-existing sleep debt, with sleep debt defined as the duration of sleep below which waking deficits can be observed. In human beings, these deficits can be seen across a spectrum of neurocognitive domains from basic attentional processes to high-level executive function.
Under unrestricted sleep conditions, endogenous circadian and homeostatic processes interact to promote periods of stable sleep and wakefulness, with relatively abrupt transitions from one state to the other. Sleep deprivation leads to a breakdown in this stability, beginning with transient and involuntary intrusions of sleep into periods of wakefulness. These intrusions can be observed through a number of neurobehavioral phenomena, including microsleeps, sleep attacks, slow eyelid closures, voluntary naps, and slow rolling eye movements.
Apart from these directly-observable phenomena, the effects of sleep deprivation on human beings fall into two main categories: objective (which can be physiological or cognitive), and subjective.
- Sleep propensity: The classic paradigms used to measure sleep propensity are the multiple sleep latency test (MSLT) (Carskadon and Dement, 1975) and the maintenance of wakefulness test (MWT) (Mitler et al., 1982). The MSLT measures time to sleep onset when subjects are instructed to fall asleep while lying supine in a sleep-conducive environment. In contrast, the MWT measures a subject’s ability to remain awake while sitting upright in a quiet, darkened room. Sleep latency on both of these tests has an inverse relationship with the number of hours a subject has been sleep deprived.
- Endocrine changes are regularly observed in experiments of total sleep deprivation, including a reduction in levels of growth hormone (Radomski et al., 1992; Seifritz et al., 1995) and in levels of leptin in both rodents (Everson and Crowley, 2004) and humans (Mullington et al., 2003) Increases have been observed in levels of thyroid axis hormones (Allan and Czeisler, 1994; Gary et al., 1996), prolactin, luteinizing hormone and estradiol during partial sleep deprivation (Baumgartner et al., 1993). Cortisol levels, which normally follow a circadian/ultradian cycle, are altered following periods of sleep deprivation. These changes are somewhat dependent on the time of measurement post-SD; there is a rebound increase of cortisol before sleep onset after a night without sleep, (Leproult et al. 1997; Mullington et al. 1996; Weitzman et al. 1983), but decreased levels directly after the deprivation period, or when integrated over the course of the subsequent night. (Akerstedt et al. 1980; Dinges et al. 1994; Vgontzas et al. 1999a; Frey et al. 2007). Certain investigators have also found no significant change in levels of this hormone. (Gary et al. 1996; Gonzalez-Ortiz et al. 2000; Haack et al. 2002).
- Immune system/inflammatory response: Sleep deprivation has effects on the immune system, including changes in natural killer cell activity (Irwin et al., 1994; Irwin et al., 1996), interleukin-6 (Redwine et al., 2000; Shearer et al., 2001), soluble tumor necrosis factor-alpha receptor 1 (Shearer et al., 2001) and cell adhesion molecules (Frey et al., 2007). Chronic sleep deprivation in shift workers and nurses is associated with increased cardiovascular risk, possibly mediated by inflammatory markers such as C-reactive protein (Ayas et al., 2003).
- Neurogenesis: There is evidence that sleep deprivation inhibits adult neurogenesis in the dentate gyrus of the hippocampus of rodents via the action of elevated levels of circulating glucocorticoids (Hairston et al., 2005; Mirescu et al., 2006).
- Electrophysiological markers: Sleep deprivation alters the signatures of brain electrophysiology. Increasing homeostatic sleep pressure is associated with increases in spectral power in the theta band (4 -8 Hz), and decreases in the alpha band (9.25 – 10 Hz) as measured by electroencephalography (EEG). EEG changes also manifest in recovery sleep after periods of sleep deprivation, with rebound increases in slow wave activity (0.5 – 4 Hz) reported during recovery nights (Brunner et al., 1993; Van Dongen et al., 2003). It has been suggested that this EEG slow wave activity rebound, which is assumed to involve the restorative aspects of sleep, may also reflect synaptic potentiation (Tononi and Cirelli, 2003).
- Functional magnetic resonance imaging (fMRI) markers: Subjects have been tested on a variety of tasks after sleep deprivation while undergoing functional magnetic resonance imaging (fMRI). Compared to baseline, blood oxygenation level dependent (BOLD) contrast typically reveals hypoactivation in inferior parietal regions after SD (Bell-McGinty et al., 2004; Chee and Choo, 2004; Chee et al., 2006). Given that this phenomenon has been observed across a wide range of cognitive tasks, it has been suggested that parietal hypoactivation after sleep deprivation is associated with a decrease in attentional resources. However, compensatory increases in cerebral activation during sleep deprivation have also been observed during task performance (Drummond et al., 2000; Drummond et al., 2005).
- Fundamental processes: Speed of processing, as measured by neuropsychological tests such as the Digit Symbol Substitution Task, decreases with increasing time awake (Leproult et al., 1997). Additionally, tonic, sustained attention becomes increasingly labile during periods of sleep deprivation, leading to increased variability in reaction times, as well as a greater number of performance lapses on the Psychomotor Vigilance Test (PVT) and other tests of attention (Dinges et al., 1997). The time-on-task effect in sustained attention tasks is also more pronounced in the sleep-deprived state.
- Higher cognitive functions: The effects of sleep deprivation on tasks of higher cognitive function are less well known, and experimental results have been mixed. Numerous studies (Linde et al., 1999; Harrison and Horne, 2000) have shown that subjects are able to recruit compensatory resources and temporarily perform at a level comparable to that of rested controls when performing relatively more complex and engaging tasks. This is more apparent in convergent tasks (e.g. tasks of critical thinking and rule-based deduction), and less true of divergent ones (e.g. assimilation of changing information, updating strategies based on new information, lateral thinking, risk assessment, insight and temporal memory skills). Sleep loss also adversely affects working memory function, defined as the ability to encode, manipulate and retrieve information, in one or more sensory modalities (Chee and Choo, 2004). One unifying hypothesis arising from these results is that sleep deprivation differentially affects prefrontal-cortex-related functions while leaving executive ability associated with other brain regions relatively intact.
- For a more complete review of the neurocognitive consequences of sleep deprivation, refer to Durmer and Dinges (2005).
- Emotion and mood: In comparison to the effects of sleep deprivation on cognition and performance, relatively little is known about the effects of sleep deprivation on emotional processes, with the exception of subjective mood states (Dinges et al., 1997). Experimental data have shown that nearly all forms of sleep deprivation result in increased negative mood states, especially feelings of fatigue, loss of vigor, sleepiness, and confusion. These data are limited however in that they were obtained without systematic mood induction procedures or other experimental probes designed to influence mood. It is not yet known if there are systematic differences in how specific events influence mood in sleepy vs. rested subjects.
Sleep deprivation is also widely believed to be associated with impaired emotional functioning. Field studies of sleep deprivation in medical personnel (Asken and Raham, 1983; Orton and Gruzeller, 1989) have found that reduced sleep is associated with increased negative and decreased positive emotional responses to specific events, but the uncontrolled nature of these studies allows for alternative interpretations of these results. Other than simple subjective self-report measures of affect, there are few laboratory-based studies on affective reactions in sleep-deprived humans.
Interest in understanding the patterns of sleep intrusions and the other detrimental effects of sleep deprivation have led to the use and modification of existing biomathematical models of sleep-wake regulation. In particular, the two-process model of sleep regulation, first proposed by Alexander Borbély (1982), is the leading paradigm used to predict the effects of sleep and sleep deprivation on human cognition and performance. This model consists of a circadian oscillator with a period of slightly over 24 hours, as well as a homeostatic process (reflecting sleep pressure) that builds exponentially during periods of wakefulness and dissipates exponentially during periods of sleep (Figure 1). These two processes interact to promote alertness in the day and sleep during the night. It has been suggested that waking cognitive function can be mathematically modeled as the difference between the quantitative states of the circadian and homeostatic processes (Mallis, 2004).
Numerous refinements have since been proposed to improve the predictive validity of the two-process model. Adjustments have been made for environmental variables (such as light levels, and location), sleep variables (such as length and quality), and the level of cognitive workload during waking periods. In particular, including sleep inertia as an input factor improves the predictive power of the two-process model significantly. Seven leading biomathematical models of human fatigue and performance have emerged from modifications to the two-process model; these are reviewed and discussed by Mallis et al. (2004) and Dinges (2004).
Lapse and wake-state instability hypotheses
Early attempts to understand the effects of sleep deprivation focused on the “lapse hypothesis” (Dinges and Kribbs, 1991). This theory suggested that baseline levels of functioning are identical in rested and sleep-deprived states, but that sleep-deprived individuals experience transient phases of low arousal during which sleep intrusions and performance lapses occur. Although the hypothesis has some measure of explanatory power, evidence from experiments of chronic sleep restriction (Dinges et al., 1997) suggests that it is insufficient to account for the changes in neurobehavioral functioning that occur over time. For example, the increasing variability of reaction times on the Psychomotor Vigilance Test as the number of hours of sleep loss increases would not be predicted by the lapse hypothesis alone.
An alternative hypothesis is the “wake-state instability” theory, which posits that waking-state function degrades after sleep deprivation both because of lapses in attention and a decrease in tonic aspects of functioning. These global deficits in cognitive functioning account for the increased variability in performance, as well as the observed slowing of fastest or optimal responses.
- Biologically, the stability of wakefulness and sleep is controlled and modulated by a set of complex neurochemical pathways, and there is currently no singular unifying theory describing their interactions. The ascending cholinergic reticulothalamocortical pathway, which originates in the upper pons, pedunculopontine, and lateral dorsal tegmental nuclei, and activates the thalamus and cerebral cortex, is primarily responsible for maintaining arousal and wakefulness. Conversely, the ventrolateral preoptic nucleus (VLPO), an area rich in galanin- and GABA-containing neurons, is active during sleep, and is a highly accurate real-time marker of sleep duration. The ascending cholinergic pathway and VLPO are mutually inhibitory, thus forming a “flip-flop” switch with these features:
- A pathway, once active, will tend to stay active, because it both inhibits the opposing pathway as well as the other pathway’s inhibitory effect on itself.
- A small perturbation in the system may lead to a sudden change in the pathway whose activity is dominant.
- There is strong evidence that the orexin-hypocretins are responsible for both stabilizing the sleep switch and altering its equilibrium point (from promoting wakefulness to promoting sleep and vice versa). These molecules interact directly with the arousal system, but not the VLPO, suggesting that that their action inhibits unwanted lapses into sleep (Mignot, 2004).
For a more complete review of the VLPO and its function as a sleep switch, see Saper et al. (2005).
- The biology of sleep regulation informs our understanding of the consequences of sleep deprivation, and suggests a neurobiological basis for wake-state instability. Again, a number of explanatory hypotheses have been suggested. Among these:
- Adenosine has been proposed as an endogenous marker of homeostatic sleep drive. As the number of hours awake increases, brain glycogen reserves and ATP levels are depleted, with ATP degraded into ADP, AMP, and finally adenosine, which accumulates in the basal forebrain (Porkka-Heiskanen et al., 2000). Adenosine A2a receptor agonists incite VLPO neurons to express Fos protein, and also promote sleep in rats; these, and other lines of evidence (Strecker et al., 2000) point to adenosine as the driver of the negative feedback loop of sleep propensity.
- The circadian sleep-wake cycle is temporally regulated at the molecular level by the suprachiasmatic nucleus (SCN). The regulation occurs via a cyclical, 24-hour transcriptional-translational feedback loop phase set by retinal inputs that carry information about environmental light, as well as melatonin secretion from the pineal gland.
Individual differences in response
Comparisons of inter- and intra-individual variability in vulnerability to sleep deprivation have demonstrated that the former are substantially larger than the latter. Van Dongen et al. (2004) measured the intra-class coefficients (ICC) of subjective sleepiness and cognitive performance of participants undergoing three 36-hour periods of sleep deprivation. ICCs were high, with between-subject variance an order of magnitude greater than within-subject variance. These findings indicate that behavioral response to sleep deprivation is trait-like and stable over time. Leproult et al. (2003) also found that subjective and objective (EEG) measures of vulnerability to sleep deprivation were consistent when measured during separate experimental sessions.
Causes and costs
Lack of sleep, both chronic and acute, is a prevalent problem in modern society. For example, of 1.1 million Americans surveyed, as many as 20% indicated that they sleep 6.5 hours or less each night. In its extreme form, pathological levels of sleep deprivation are classified by the International Classification of Diseases (ICD) as insufficient sleep syndrome (ICD #307.49-4). Sleep deprivation can result from physiological deficits (e.g. obstructive sleep apnea), psychological problems (e.g. secondary insomnia), or simply reflect a lifestyle choice. Regardless of the source, it remains an under-treated symptom compared to its dramatic and often overlooked costs. For example, the cost of accidents involving sleep-deprived operators has been estimated at $43-56 billion, with almost 20% of serious motor-vehicles crashes occurring because of drowsy drivers. Sleep deprivation has also been implicated with increased risk of on-the-job errors, personal conflicts, health complaints, poorer academic performance in adolescents and increased drug use, to name just a few of its multitudinous consequences. (IOM, 2006).
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