Sleep deprivation, vigilant attention, and brain function: a review

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.

Fig. 1

Effects of acute total sleep deprivation and recovery sleep on vigilant attention. Twenty-six healthy young adults were randomized to a total sleep deprivation condition (n = 13) or a control condition (n = 13) in a laboratory study. Subjects in the sleep deprivation condition had two baseline days with 10-h sleep opportunities, a 62-h period of total sleep deprivation, and two recovery days with 10-h sleep opportunities. Subjects in the control condition had 10-h sleep opportunities every night. A 10-min PVT was administered repeatedly during scheduled waking periods to measure vigilant attention. Data show the mean (± standard error) number of lapses (defined as response times greater than 500 ms) on the PVT. Performance was stable across days in the control group (blue line). In contrast, during the 62-h sleep deprivation period, subjects had significantly impaired performance, with deficits increasing across days of total sleep deprivation—modulated by circadian rhythmicity, such that the number of lapses was highest during the morning hours; and performance was quickly recuperated following recovery sleep (red line). Tall gray bars represent sleep opportunities (22:00–08:00) in both conditions; short gray bars represent sleep opportunities in the control condition only. Figure adapted from Whitney et al. [122] with permission

Fig. 2

Vigilant attention and self-reported sleepiness under conditions of sustained sleep restriction. Forty-eight healthy young adults were assigned to 3 days of acute total sleep deprivation (0 h time in bed [TIB]; n = 13; black) or 14 days of sustained sleep restriction with randomization to 4 h TIB per day (n = 13; red), 6 h TIB per day (n = 13; yellow), or 8 h TIB per day (n = 9; green), in the laboratory. The 10-min PVT and the Stanford Sleepiness Scale (SSS) [123] were administered repeatedly during scheduled waking periods to measure vigilant attention and subjective sleepiness, respectively. Data show the daily means (±standard error) for the number of lapses (defined as response times >500 ms) on the PVT and the self-reported sleepiness score on the SSS, relative to baseline. The horizontal gray bands represent the mean (±standard error) in the total sleep deprivation condition following 1 night and 2 nights with 0 h TIB. In the 8-h TIB condition, lapses of attention were relatively rare and subjective sleepiness was stable and low across the study duration. In the 6 and 4-h TIB conditions, there was a steady build-up of vigilant attention deficits on the PVT across the 14 days of sleep restriction, in a sleep dose–response manner—such that impairment in the 4-h TIB condition reached levels equivalent to 2–3 days of acute total sleep deprivation. However, there was no steady build-up of self-reported sleepiness on the SSS, and no systematic dose–response effect—such that subjective sleepiness in the 4 and 6 h TIB conditions stabilized at a much lower level than seen in the total sleep deprivation condition. Figure adapted from Van Dongen et al. [35] with permission

Fig. 3

Vigilant attention deficits after sustained sleep restriction as a function of sleep dose and time of day. In a laboratory study, 90 healthy adults were randomized to one of 18 sustained nocturnal sleep restriction conditions with or without daytime naps of various durations, with the total sleep opportunity ranging from 4.2 to 8.2 h per day. A 10-min PVT was administered repeatedly during scheduled waking periods to measure vigilant attention. Data show the estimated means for the number of PVT lapses (defined as response times >500 ms) after 8 days of sleep restriction, relative to baseline, for daily total time in bed (TIB) of 4.2 h (red), 5.2 h (orange), 6.2 h (yellow), and 8.2 h (green). The data reveal that the dose–response effect of sleep restriction is most pronounced in the morning hours, while the circadian drive for wakefulness provides a degree of protected against vigilant attention deficits in the afternoon (the “wake maintenance zone” [124]). Figure adapted from Mollicone et al. [39] with permission

Fig. 4

Effects of sustained sleep restriction and prior wake extension on vigilant attention. In a laboratory study, 24 healthy young adults were assigned to 7 days of sustained sleep restriction to 3 h time in bed (TIB) per day (SR1–7), followed by 5 days of recovery sleep at 8 h TIB per day (R1–5). In the days prior to the laboratory study, they were randomized to a week of sleep extension to 10 h TIB per day (n = 12; black) or keeping their habitual sleep schedule (n = 12; red). A 5-min PVT was administered repeatedly during scheduled waking periods in the laboratory to measure vigilant attention. Data show the daily means (±standard error) for the number of PVT lapses (defined as response times >500 ms). In the prior habitual sleep condition, there was a steady build-up of vigilant attention deficits across days of sleep restriction, and a gradual recuperation across recovery days. In the prior sleep extension condition, however, the build-up of deficits across days of sleep restriction was attenuated, and recuperation across recovery days was accelerated. These results show long-term effects of sleep restriction and extension indicative of an allostatic process modulating the setpoint of the sleep homeostatic process. Figure adapted from Rupp et al. [40] with permission

Fig. 5

Inter-individual differences in vigilant attention deficits during periods of total sleep deprivation following two different conditions for prior sleep/wake history. Twenty-one healthy young adults were each exposed to 36 h of acute total sleep deprivation in the laboratory on three separate occasions. In the week prior to each laboratory sleep deprivation session, subjects were randomized to a week of sleep restriction to 6 h time in bed (TIB) per day (one session) or sleep extension to 12 h TIB per day (two sessions). A 20-min PVT was administered repeatedly during scheduled waking periods in the laboratory to measure vigilant attention. Data show mean (±standard error) lapses of attention (response times ≥500 ms), averaged across the final 24 h of each 36-h sleep deprivation period. While the effect of prior sleep restriction was evident (red), and consistent with the idea of a shifting homeostatic setpoint due to prior sleep/wake history, the effect was small compared to idiosyncratic, trait inter-individual differences in vulnerability to sleep deprivation (green; 95% range). Trait inter-individual differences in vulnerability to vigilant impairment due to sleep deprivation dominated the data set, explaining 67.5% of the variance [41]

Fig. 6

Effect of sleep deprivation on the PVT response time distribution. Sixteen healthy young adults were each exposed to 38 h of acute total sleep deprivation in the laboratory. A 10-min PVT was administered repeatedly during the sleep deprivation period to measure vigilant attention. A histogram of the response times, in bins of 10 ms each, is shown for daytime performance test times at baseline (blue) and for the same daytime performance test times 24 h later during sleep deprivation (red). The data show that the main effect of sleep deprivation is a skewing of the response time distribution to the right, such that many more response times end up in the right tail of the distribution. The dashed line denotes the commonly used threshold defining lapses of attention (i.e., response times >500 ms). The graph illustrates that the skewing of the distribution due to sleep deprivation lengthens the slowest response times and increases the number of lapses considerably. In contrast, the effects of sleep deprivation on the peak of the distribution and the fastest response times is much more modest, and the majority of responses remains in the baseline range (~200–300 ms for well-rested, healthy young adults). Figure adapted from Grant et al. [90] with permission

Fig. 7

Effect of sustained sleep restriction on the time-on-task effect. Following a baseline period, 66 healthy young adults were assigned to 7 days of sustained sleep restriction or extension, with daily time in bed (TIB) randomized to 3 h (n = 18; red), 5 h (n = 16; orange), 7 h (n = 16; green), or 9 h (n = 16; blue), which was followed by 3 days of recovery sleep at 8 h TIB daily. A 10-min PVT was administered repeatedly during scheduled waking periods to measure vigilant attention. Data show average response times per 1-min bin (not drawn to scale on the time axis) during a baseline day (BL), during the 7 days of experimental sleep restriction or extension (E1–7), and during the 3 recovery days (R1–3). In each of the conditions, there was a general increase of the 1-min average response time across the 10-min task duration, which was reset by the rest breaks between the test bouts. This time-on-task effect was exacerbated as a function of consecutive days of sleep restriction, with shorter sleep durations corresponding to greater time-on-task effects in a dose–response manner. The time-on-task effect was diminished across consecutive recovery days. Figure adapted from Van Dongen et al. [19] with permission

Fig. 8

Conceptual model pertaining to the effects of sleep deprivation on vigilant attention. Left: The ascending arousal system (AAS) promotes global arousal throughout the cortex by means of wide-ranging projections (red pathways). These projections originate from cholinergic structures in the brainstem (PPT, pedunculopontine tegmental nucleus; LDT, laterodorsal tegmental nucleus) and basal forebrain (BF), monoaminergic structures in the BF and hypothalamus (e.g., LC locus coeruleus; TMN tuberomammillary nucleus; raphe nuclei), and orexinergic/hypocretinergic neurons in the lateral hypothalamus (LH), modulated by circadian rhythmicity generated in the suprachiasmatic nucleus (SCN). The strength of arousal from these projections, through interaction between cortical glutamatergic excitatory neurons, and GABAergic inhibitory neurons in the cortex (not shown), instantiates the homeostatic and circadian processes reflecting prior wakefulness and time of day and mediates the propensity for local sleep at the level of neuronal/glial assemblies. This propensity is manifested as a consequence of intense neuronal use in support of information processing during vigilant attention task performance, in task-activated cortical areas such as the precuneus (magnifying glass). Right: Information processing in a neuronal/glial assembly triggers a series of biochemical processes that induce the local sleep state. Synaptic transmission is associated with increased local metabolic activity and energy transfer and release of adenosine triphosphate (ATP) from presynaptic neurons and glial cells into the extracellular space. Breakdown of extracellular ATP to recover the energy captured in the phosphoryl groups results in use-dependent accumulation of adenosine. Binding of adenosine at postsynaptic adenosine receptors (P1R purine type 1 receptors) promotes local sleep, thereby fundamentally altering the neuronal assembly’s synaptic transmission. As a consequence, the fidelity of task-relevant information processing is degraded in a use-dependent manner, modulated by the strength of subcortical arousal from the AAS. This gives rise to the time-on-task effect (vigilance decrement) in interaction with the homeostatic and circadian processes. A rest break (or switching to a task that does not intensively use the same neuronal/glial assemblies) allows adenosine levels to decay (e.g., through the enzymatic action of ADA, adenosine deaminase), thereby resetting the time-on-task effect. Binding of ATP, prior to breakdown, to purine type 2X7 receptors (P2X7R) leads to release of a cascade of sleep regulatory substances (SRSs), such as interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), and brain-derived neurotrophic factor (BDNF). Sustained wakefulness allows SRSs to accumulate and, via their receptors and nuclear factor κB (NF-κB), causes the density of postsynaptic adenosine receptors to increase. This leads to a build-up of the propensity for use-dependent local sleep across consecutive days of wake extension. Across days of recovery sleep, adenosine receptors downregulate and the baseline propensity for local sleep is gradually restored. Left and right: Through mechanisms yet to be elucidated, accumulation of SRSs across the cortex reflecting the collective states of neuronal/glial assemblies is signaled to subcortical circuits (transparent downward arrows), influencing in particular the ventrolateral preoptic nucleus (VLPO). In response, the VLPO blocks the AAS and induces local sleep across the whole cortex (i.e., global sleep), which enables restoration of baseline SRS concentrations and allows recuperation from prior information processing deficits across neuronal/glial assemblies. Figure adapted from a schematic in Van Dongen et al. [19], with visual elements derived from Saper et al. [79] and Davis et al. [125]