Sleep and Human Performance

Sleep deprivation consistently decreases vigilant attention, which can lead to difficulty in performing a variety of cognitive tasks. However, sleep-deprived individuals may be able to compensate for degraded vigilant attention by means of top-down attentional control. We employed a novel task to measure the degree to which individuals overcome impairments in vigilant attention by using top-down attentional control, the Flexible Attentional Control Task (FACT). The FACT is a two-choice task that has trials with valid, invalid, and neutral cues, along with an unexpected switch in the probability of cue validity about halfway in the task. The task provides indices that isolate performance components reflecting vigilant attention and top-down attentional control. Twelve healthy young adults completed an in-laboratory study. After a baseline day, the subjects underwent 39 hours of total sleep deprivation (TSD), followed by a recovery day. The FACT was administered at 03:00, 11:00, and 19:00 during sleep deprivation (TSD condition) and at 11:00 and 19:00 after baseline sleep and at 11:00 after recovery sleep (rested condition). When rested, the subjects demonstrated both facilitation and interference effects on cued trials. While sleep deprived, the subjects showed vigilant attention deficits on neutral cue trials, and an impaired ability to reduce these deficits by using predictive contextual cues. Our results indicate that the FACT can dissociate vigilant attention from top-down attentional control. Furthermore, they show that during sleep deprivation, contextual cues help individuals to compensate partially for impairments in vigilant attention, but the effectiveness of top-down attentional control is diminished.

Altered attentional control strategies but spared executive functioning in chronic cannabis users

Objectives: Memory decline caused by insufficient sleep is a critical public health issues and currently lacks effective treatments. This study objective was to explore alleviative effect of melatonin on sleep deprivation (SD)-induced deficiencies in learning and memory.Materials and Methods: A continuous 72 h SD mouse model, with or without melatonin or Fer-1 supplementation were established. The changes of cognitive function, iron homeostasis, lipid peroxidation and intracellular signal pathways in mice were detected by Morris water maze, antioxidant assay, immunohistochemistry, western blot, RT-PCR and Prussian blue staining. In vitro, we treated HT-22 cells with ferroptosis inducer (Erastin) to further explore the specific mechanism of melatonin in ferroptosis.Results: Mice subjected to SD had significantly elevated latency and path length to reach hidden platform, as well as a decrease in number of entries and time spent in the target zone when the hidden platform was removed (p < 0.05). Nevertheless, supplementation with ferroptosis inhibitor (Fer-1) mitigated the memory impairment associated with SD. Further evaluation revealed an up-regulation of intracellular iron accumulation, transferrin receptor 1 and divalent metal transporter 1 expression and ROS and MDA production, and a down-regulation of ferroportin and antioxidant enzyme (GPX4 and SOD) expression in SD mice. SD decreased expression of MT2 receptor rather than of MT1, and inhibited ERK/Nrf2 signaling activation in the hippocampus (p < 0.05). In contrast, the aforementioned SD-inductions were reversed by supplementation using 20 and 40 mg/kg melatonin in SD mice. In vitro, melatonin pretreatment reversed Erastin-induced ferroptosis, abnormalities in iron transporter protein and antioxidant enzyme expression and suppression of ERK/Nrf2 signaling in HT-22 cells, however this protective effect of melatonin was blocked by MT2-, ERK- and Nrf2-specific antagonists (p < 0.05).Conclusion: Our finding suggested SD may induce ferroptosis, in turn leading to cognitive deficits. Melatonin alleviated memory loss and hippocampal ferroptosis caused by acute SD through binding to the MT2 receptor to activate ERK/Nrf2 signaling.

BackgroundThe combined effects of increased life expectancy and the considerable number of persons reaching old age will magnify the dementia epidemic in the USA. Demonstration that subclinical atherosclerosis precedes and is associated with cognitive impairment suggests a modifiable risk factor for age-associated cognitive impairment and dementia. The purpose of this study is to determine whether subclinical atherosclerosis as measured by carotid artery intima-media thickness (CIMT) is associated with changes in cognitive function over time in older adults.MethodsThis study combined longitudinal data from three clinical trials conducted between 2000 and 2013: the B-Vitamin Atherosclerosis Intervention Trial (BVAIT), the Women’s Isoflavone Soy Health (WISH) trial, and the Early versus Late Intervention Trial with Estradiol (ELITE). Participants were recruited from the general population in the Greater Los Angeles area and were free of cardiovascular disease and diabetes; no cognitive or psychiatric exclusion criteria were specified. The same standardized protocol for ultrasound image acquisition and measurement of CIMT was used in all trials. CIMT measurements performed at baseline and 2.5 years were used in these analyses. Cognitive function was assessed at baseline and 2.5 years using a battery of 14 standardized cognitive tests. All clinical trials were conducted at the University of Southern California Atherosclerosis Research Unit, Los Angeles, and had at least 2.5 years of cognitive follow-up.ResultsA total of 308 men and 1187 women, mean age of 61 years, were included in the combined longitudinal dataset for the primary analysis. No associations were found between CIMT and cognitive function at baseline or at 2.5 years. There was a weak inverse association between CIMT measured at baseline and change in global cognition assessed over 2.5 years (β (SE) = − 0.056 (0.028) units per 0.1 mm CIMT, 95% CI − 0.110, − 0.001, p = 0.046). No associations between CIMT at baseline and changes in executive function, verbal memory, or visual memory were found.ConclusionsIn this sample of healthy older adults, our findings suggest an association between subclinical atherosclerosis and change in global cognitive function over 2.5 years. Stronger associations were observed longitudinally over 2.5 years than cross-sectionally. When analysis was stratified by age group (<65 and ≥65 years old), the inverse association remained statistically significant for participants in the older age group. Subclinical atherosclerosis of the carotid artery may be a modifiable correlate of cognitive decline in middle and older age.Trial registrationBVAIT, NCT00114400. WISH, NCT00118846. ELITE, NCT00114517.

ABSTRACTCognitive processes are crucial for human performance. Basic cognitive processes, such as attention, working memory, and executive functions, show homeostatic (time awake, sleep deprivation) and circadian (time of day) variations. Each of these cognitive processes includes several components, which contribute sequentially to the homeostatic and circadian modulation of performance. Sudden (lapses) and gradual changes in cognitive performance occur with sleep deprivation or with time of day. The time course of human cognitive processes throughout the day is relevant to the programming of different human activities. The lowest level of cognitive performance occurs during nighttime and early in the morning, a better level occurs around noon, and even higher levels occur during afternoon and evening hours. However, this time course can be modulated by conditions such as chronotype, sleep deprivation, sleep disorders or medication that affects the central nervous system.

Previous forced desynchrony studies have highlighted the close relationship between the circadian rhythms of core body temperature (CBT) and sleep propensity. In particular, these studies have shown that a “forbidden zone” for sleep exists on the rising limb of the CBT rhythm. In these previous studies, the length of the experimental day was either ultrashort (90 min), short (20 h), or long (28 h), and the ratio of sleep to wake was normal (i.e., 1:2). The aim of the current study was to examine the relative effects of the circadian and homeostatic processes on sleep propensity using a 28-h forced desynchrony protocol in which the ratio of sleep to wake was substantially lower than normal (i.e., 1:5). Twenty-seven healthy males lived in a time-isolation sleep laboratory for 11 consecutive days. Participants completed either a control (n = 13) or sleep restriction (n = 14) condition. In both conditions, the protocol consisted of 2 × 24-h baseline days followed by 8 × 28-h forced desynchrony days. On forced desynchrony days, the control group had 9.3 h in bed and 18.7 h of wake, and the sleep restriction group had 4.7 h in bed and 23.3 h of wake. For all participants, each 30-s epoch of time in bed was scored as sleep or wake based on standard polysomnography recordings, and was also assigned a circadian phase (360° = 24 h) based on a cosine equation fitted to continuously recorded CBT data. For each circadian phase (i.e., 72 × 5° bins), sleep propensity was calculated as the percentage of epochs spent in bed scored as sleep. For the control group, there was a clear circadian rhythm in sleep propensity, with a peak of 98.5% at 5° (∼05:20 h), a trough of 64.9% at 245° (∼21:20 h), and an average of 82.3%. In contrast, sleep propensity for the sleep restriction group was relatively high at all circadian phases, with an average of 96.7%. For this group, the highest sleep propensity (99.0%) occurred at 60° (∼09:00 h), and the lowest sleep propensity (91.3%) occurred at 265° (∼22:40 h). As has been shown previously, these current data indicate that with a normal sleep-to-wake ratio, the effect of the circadian process on sleep propensity is pronounced, such that a forbidden zone for sleep exists at a phase equivalent to evening time for a normally entrained individual. However, these current data also indicate that when the ratio of sleep to wake is substantially lower than normal, this circadian effect is masked. In particular, sleep propensity is very high at all circadian phases, including those that coincide with the forbidden zone for sleep. This finding suggests that if the homeostatic pressure for sleep is sufficiently high, then the circadian drive for wakefulness can be overridden. In future studies, it will be important to determine whether or not this masking effect occurs with less severe sleep restriction, e.g., with a sleep-to-wake ratio of 1:3. (Author correspondence: charli.sargent@cqu.edu.au)

Experimental and epidemiological research has shown that human sleepiness is determined especially by the circadian and homeostatic processes. The present field study examined which work-related factors airline pilots perceive as causing on-duty sleepiness during short-haul and long-haul flights. In addition, the association between the perceived reasons for sleepiness and actual sleepiness levels was examined, as well as the association between reporting inadequate sleep causing sleepiness and actual sleep-wake history. The study sample consisted of 29 long-haul (LH) pilots, 28 short-haul (SH) pilots, and 29 mixed fleet pilots (flying both SH and LH flights), each of whom participated in a 2-month field measurement period, yielding a total of 765 SH and 494 LH flight duty periods (FDPs) for analyses (FDP, a period between the start of a duty and the end of the last flight of that duty). The self-reports of sleepiness inducers were collected at the end of each FDP by an electronic select menu. On-duty sleepiness was rated at each flight phase by the Karolinska Sleepiness Scale (KSS). The sleep-wake data was collected by a diary and actigraph. The results showed that “FDP timing” and “inadequate sleep” were the most frequently reported reasons for on-duty sleepiness out of the seven options provided, regardless of FDP type (SH, LH). Reporting these reasons significantly increased the odds of increased on-duty sleepiness (KSS ≥ 7), except for reporting “inadequate sleep” during LH FDPs. Reporting “inadequate sleep” was also associated with increased odds of a reduced sleep-wake ratio (total sleep time/amount of wakefulness ≤ 0.33). Both “FDP timing” and “inadequate sleep” were most frequently reported during early morning and night FDPs, whereas the other options showed no such phenomenon. The present study suggests that airline pilots’ perceptions of work-related factors that make them sleepy at work are in line with the previous experimental and epidemiological studies of sleepiness regulation.

This laboratory study of 90 healthy adults investigates human performance impairments resulting from sleep restriction in order to examine whether splitting sleep into a shortened nocturnal sleep period and a diurnal nap results in less impairment than a consolidated sleep period of the same total daily duration. This research is directly relevant to space operations in which high-level sustained neurobehavioral performance demands are coupled with constrained mission schedules as there is evidence that even modest sleep restriction results in impairments that reduce productivity and increase the risk of catastrophic accidents due to fatigue-related human error. Recent research has led to my hypothesis that split-sleep schedules with reduced total daily sleep time could result in increased total wake time while preventing cumulative reductions in waking cognitive function. To test this hypothesis, quantitative measurements of neurobehavioral performance were studied in a ground-based, laboratory experiment that included N=90 subjects, each assigned to one of 18 split-sleep regimens during 10 days of sleep restriction. The main result was that across a range of chronic nocturnal sleep restriction conditions, with and without diurnal naps, neurobehavioral performance was primarily a function of total time in bed (TIB) per 24h. A secondary result was that there are circadian-phase dependent, sleep-dose dependent interactions between circadian and long-term homeostatic processes that build across days of sleep restriction. These results provide direct evidence that reductions in total daily sleep cause an accumulation of impairment regardless of whether sleep is scheduled as a consolidated nocturnal sleep period or split into a nocturnal anchor sleep period and a diurnal nap. Further, these impairments manifest as a function of circadian phase and sleep-dose across days of sleep restriction. In conclusion, split-sleep schedules provide no additional recovery benefits compared to schedules that include consolidated sleep of same total daily duration. Split-sleep, however, is operationally feasible if used to enhance the flexibility of sleep/work schedules for space operations involving restricted nocturnal sleep due to mission-critical task scheduling. These results are not only important for space exploration but are generally applicable to any continuous industrial operation that involves sleep restriction, night operations, and shift work.

Ultradian rhythms that modulate daytime human behavior and cognitive performance exist. However, their subtleness may make them susceptible to masking effects from heightened arousal, attention, and motivation. Experimental designs using sleep attenuation and total sleep-deprivation appear to unmask certain ultradian rhythms. This chapter reviews the few studies designed to evaluate rhythms in waking EEG and task performances during sleep deprivation. Some EEG studies demonstrate an approximate 90-min rhythm in arousal. No confirmation has been reached for an underlying common basic rest-activity cycle (BRAC) that ties the phases of the nightly 90-min NREM-REM sleep cyclicity to those of any ensuing similar-period wake time alertness and performance rhythms. Studies have also found a slower 4-h rhythm. Other arousal and performance rhythms shorter than 90 min and longer than 4h have been suggested, but are not as well substantiated. The 90-min and 4-h rhythms seem to dominate the morning and early afternoon circadian rhythm portion during wakefulness, but are attenuated later by the rising circadian rhythm, or perhaps other slower ultradian cycles. Ultradian rhythm expression appears related to a greater susceptibility for reduced arousal and sleepiness. Impairment of cognitive-behavioral performance occurs at times of low circadian influences and increased ultradian fluctuations. These effects, in combination with any amount of sleep deprivation, raise concerns about naturally occurring potentially widespread performance decrements. Concern stems from the widespread increase in chronic partial-sleep loss in cultures deliberately abridging adequate nightly sleep in favor of attempting to maintain a 24/7 mode of existence.

Objective, rapid evaluation of cognitive function is critical for identifying situational impairment due to sleep deprivation. The present study used brain vital sign monitoring to evaluate acute changes in cognitive function for healthy adults. Thirty (30) participants were scanned using portable electroencephalography before and after either a night of regular sleep or a night of total sleep deprivation. Brain vital signs were extracted from three established event-related potential components: (1) the N100 (Auditory sensation); (2) the P300 (Basic attention); and (3) the N400 (Cognitive processing) for all time points. As predicted, the P300 amplitude was significantly reduced in the sleep deprivation group. The findings indicate that it is possible to detect situational cognitive impairment due to sleep deprivation using objective, rapid brain vital sign monitoring.

A frontoparietal network has long been implicated in top-down control of attention. Recent studies have suggested that this network might communicate through coherence in the alpha band. Here we aimed to test the effect of coherent alpha (8–12 Hz) stimulation on the frontoparietal network. To this end, we recorded behavioral performance and electroencephalography (EEG) data while participants were engaged in a spatial attention task. Furthermore, participants received transcranial alternating current stimulation (tACS) over the right frontal and parietal cortex, which oscillated coherently in-phase within the alpha band. Compared to a group of participants that received sham stimulation, we found that coherent frontoparietal alpha band stimulation altered a behavioral spatial attention bias. Neurally, the groups showed hemispheric-specific differences in alpha coherence between the frontal and parietal-occipital cortex. These results provide preliminary evidence that alpha coherence in the frontoparietal network might play a role in top-down control of spatial attention.

Over the past decade, emerging evidence has shed light on the role of the gut microbiota in the interface between diet and brain health. Olive oil, particularly virgin olive oil, a key component and major fat source in the Mediterranean diet, has exhibited widespread healthful benefits, including improvements in gut microbiota and cognitive health. Despite insights from preclinical studies into the relationship between virgin olive oil consumption, gut microbiota, and cognitive function, human research in this area remains limited. Therefore, our study aims to investigate the interplay between total olive oil consumption and its subtypes, gut microbiota, and changes in cognitive function in older adults who were cognitively healthy at baseline but at high risk of cognitive decline. In this prospective cohort study, we assessed a total of 656 participants aged 55 to 75y (mean age 65.0 ± 4.9y, 47.9% women) with overweight/obesity and metabolic syndrome who provided stool samples and completed a validated semi-quantitative food frequency questionnaire at baseline and a comprehensive battery of neuropsychological tests at baseline and at a 2-y follow-up. Results from the multivariable linear regression models showed that higher consumption of virgin olive oil was associated with improved cognitive function over a 2-y follow-up, and a more diverse gut microbiota overall structure at baseline. Conversely, increased consumption of common olive oil is linked to lower alpha diversity of the microbial communities, and accelerated cognitive decline. Mediation analysis suggests that gut microbiota and particularly the Adlercreutzia, may serve as a mediator taxon in the association between virgin olive oil consumption and positive changes in general cognitive function. Higher consumption of virgin olive oil was associated with cognitive preservation, possibly mediated by favorable alterations in gut microbiota composition. Our study provides novel insights into the complex interplay between different types of olive oil consumption, gut microbiota, and changes in cognitive function. These findings underscore the potential of microbiota-targeted dietary strategies to promote cognitive health in aging populations, though further high-quality and clinical cohort studies are required. Video Abstract.

Association between change in brain gray matter volume, cognition, and depression severity: Pre- and post- antidepressant pharmacotherapy for late-life depression

The photopigment melanopsin plays an important role in all three processes known to regulate sleep: the circadian and homeostatic processes and the direct effects of light - results mainly relying on electrophysiological analysis. We therefore examined mRNA expression levels of melanopsin (Opn4) and retinal pituitary adenylate cyclase activating polypeptide (PACAP), a neurotransmitter of the retinohypothalamic tract, which is thought to relay the melanopsin mediated signals to the brain. MRNA expression levels were determined in dependence of light, darkness and circadian and homeostatic processes in nocturnal and diurnal rodents using RT-qPCR. My results show that melanopsin mRNA concentrations follow a circadian rhythm in nocturnal (C57BL/6 mouse and albino Wistar rat) and diurnal species (Arvicanthis ansorgei). In mice, the PACAP mRNA expression was similarly affected and a comparable tendency was observed in Arvicanthis ansorgei. The phase relationship between both circadian rhythms - Opn4 and PACAP - suggests that PACAP is involved in conveying melanopsin-based photic input to the brain. In all species studied, the respective peaks of Opn4 and PACAP occurred in the activity phases of each animal. In the mouse, the highest melanopsin mRNA expression level was at the end of its activity phase (ZT21) whereas in Arvicanthis ansorgei the peak level occurred at the beginning of the same (ZT0-3). Arvicanthis ansorgei´s melanopsin expression levels were inverted when compared to the albino Wistar rat. Here, the peak was detected at the light-dark transition which is likewise considered as the beginning of its activity. In addition, I could show that melanopsin mRNA levels increased under sleep deprivation in mice and Arvicanthis ansorgei, returning to control values during recovery sleep. Again, the same pattern could be demonstrated for retinal PACAP mRNA concentration in Arvicanthis ansorgei. Thus, melanopsin could be established as a sleep homeostatic factor, providing a new concept in the field of sleep research. Finally, I could show that continuous exposure to light or darkness for three days does not influence melanopsin expression in mice or Arvicanthis ansorgei. The findings suggest that Opn4 expression is not regulated by light and dark in these animal models. These results are in contrast to results obtained in albino rats. However, the absence or presence of pigments might have an unrecognized impact. The current work improves our understanding of the mechanisms regulating melanopsin expression and provides significant clues to further understand the effect of light on sleep, alertness and associated behaviors.

In the context of geriatric research, a growing body of evidence links normal age-related changes in sleep with many adverse health outcomes, especially a decline in cognition in older adults. The most important sleep alterations that continue to worsen after 60 years involve sleep timing, (especially early wake time, phase advance), sleep maintenance (continuity of sleep interrupted by numerous awakenings) and reduced amount of sigma activity (during non-rapid eye movement (NREM) sleep) associated with modifications of sleep spindle characteristics (density, amplitude, frequency) and spindle–Slow Wave coupling. After 60 years, there is a very clear gender-dependent deterioration in sleep. Even if there are degradations of sleep after 60 years, daytime wake level and especially daytime sleepiness is not modified with age. On the other hand, under sleep deprivation condition, older adults show smaller cognitive impairments than younger adults, suggesting an age-related lower vulnerability to extended wakefulness. These sleep and cognitive age-related modifications would be due to a reduced homeostatic drive and consequently a reduced sleep need, an attenuation of circadian drive (reduction of sleep forbidden zone in late afternoon and wake forbidden zone in early morning), a modification of the interaction of the circadian and homeostatic processes and/or an alteration of subcortical structures involved in generation of circadian and homeostatic drive, or connections to the cerebral cortex with age. The modifications and interactions of these two processes with age are still uncertain, and still require further investigation. The understanding of the respective contribution of circadian and homeostatic processes in the regulation of neurobehavioral function with aging present a challenge for improving health, management of cognitive decline and potential early chronobiological or sleep-wake interventions.