Biomathematical modeling of fatigue due to sleep inertia.

Biomathematical models of fatigue capture the physiology of sleep/wake regulation and circadian rhythmicity to predict changes in neurobehavioral functioning over time. We used a biomathematical model of fatigue linked to the adenosinergic neuromodulator/receptor system in the brain as a framework to predict sleep inertia, that is, the transient neurobehavioral impairment experienced immediately after awakening. Based on evidence of an adenosinergic basis for sleep inertia, we expanded the biomathematical model with novel differential equations to predict the propensity for sleep inertia during sleep and its manifestation after awakening. Using datasets from large laboratory studies of sleep loss and circadian misalignment, we calibrated the model by fitting just two new parameters and then validated the model's predictions against independent data. The expanded model was found to predict the magnitude and time course of sleep inertia with generally high accuracy. Analysis of the model's dynamics revealed a bifurcation in the predicted manifestation of sleep inertia in sustained sleep restriction paradigms, which reflects the observed escalation of the magnitude of sleep inertia in scenarios with sleep restriction to less than âˆ¼ 4 h per day. Another emergent property of the model involves a rapid increase in the predicted propensity for sleep inertia in the early part of sleep followed by a gradual decline in the later part of the sleep period, which matches what would be expected based on the adenosinergic regulation of non-rapid eye movement (NREM) sleep and its known influence on sleep inertia. These dynamic behaviors provide confidence in the validity of our approach and underscore the predictive potential of the model. The expanded model provides a useful tool for predicting sleep inertia and managing impairment in 24/7 settings where people may need to perform critical tasks immediately after awakening, such as on-demand operations in safety and security, emergency response, and health care.

Long-term influence of sleep/wake history on the dynamic neurobehavioural response to sustained sleep restriction.

Chronic sleep restriction, common in today's 24/7 society, causes cumulative neurobehavioural impairment, but the dynamics of the build-up and dissipation of this impairment have not been fully elucidated. We addressed this knowledge gap in a laboratory study involving two, 5-day periods of sleep restriction to 4 hr per day, separated by a 1-day dose-response intervention sleep opportunity. We measured sleep physiological and waking neurobehavioural responses in 70 healthy adults, each randomized to one of seven dose-response intervention sleep doses ranging from 0 to 12 hr, or a non-sleep-restricted control group. As anticipated, sleep physiological markers showed homeostatic dynamics throughout the study, and waking neurobehavioural impairment accumulated across the two sleep restriction periods. Unexpectedly, there was only a slight and short-lived effect of the 1-day dose-response intervention sleep opportunity. Whether the dose-response intervention sleep opportunity involved extension, further restriction or total deprivation of sleep, neurobehavioural functioning during the subsequent second sleep restriction period was dominated by prior sleep-wake history. Our findings revealed a profound and enduring influence of long-term sleep-wake history as a fundamental aspect of the dynamic regulation of the neurobehavioural response to sleep loss.

Effects of total sleep deprivation on components of top-down attentional control using a flexible attentional control task.

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.

Profiling rhythmicity of bile salt hydrolase activity in the gut lumen with a rapid fluorescence assay.

Diurnal rhythmicity of cellular function is key to survival for most organisms on Earth. Many circadian functions are driven by the brain, but regulation of a separate set of peripheral rhythms remains poorly understood. The gut microbiome is a potential candidate for regulation of host peripheral rhythms, and this study sought to specifically examine the process of microbial bile salt biotransformation. To enable this work, an assay for bile salt hydrolase (BSH) that could work with small quantities of stool samples was necessary. Using a turn-on fluorescence probe, we developed a rapid and inexpensive assay to detect BSH enzyme activity with concentrations as low as 6-25 µM, which is considerably more robust than prior approaches. We successfully applied this rhodamine-based assay to detect BSH activity in a wide range of biological samples such as recombinant protein, whole cells, fecal samples, and gut lumen content from mice. We were able to detect significant BSH activity in small amounts of mouse fecal/gut content (20-50 mg) within 2 h, which illustrates its potential for use in various biological/clinical applications. Using this assay, we investigated the diurnal fluctuations of BSH activity in the large intestine of mice. By using time restricted feeding conditions, we provided direct evidence of 24 h rhythmicity in microbiome BSH activity levels and showed that this rhythmicity is influenced by feeding patterns. Our novel function-centric approach has potential to aid in the discovery of therapeutic, diet, or lifestyle interventions for correction of circadian perturbations linked to bile metabolism.

Night shift schedule causes circadian dysregulation of DNA repair genes and elevated DNA damage in humans.

Circadian disruption has been identified as a risk factor for health disorders such as obesity, cardiovascular disease, and cancer. Although epidemiological studies suggest an increased risk of various cancers associated with circadian misalignment due to night shift work, the underlying mechanisms have yet to be elucidated. We sought to investigate the potential mechanistic role that circadian disruption of cancer hallmark pathway genes may play in the increased cancer risk in shift workers. In a controlled laboratory study, we investigated the circadian transcriptome of cancer hallmark pathway genes and associated biological pathways in circulating leukocytes obtained from healthy young adults during a 24-hour constant routine protocol following 3 days of simulated day shift or night shift. The simulated night shift schedule significantly altered the normal circadian rhythmicity of genes involved in cancer hallmark pathways. A DNA repair pathway showed significant enrichment of rhythmic genes following the simulated day shift schedule, but not following the simulated night shift schedule. In functional assessments, we demonstrated that there was an increased sensitivity to both endogenous and exogenous sources of DNA damage after exposure to simulated night shift. Our results suggest that circadian dysregulation of DNA repair may increase DNA damage and potentiate elevated cancer risk in night shift workers.

Astrocyte expression of the Drosophila TNF-alpha homologue, Eiger, regulates sleep in flies.

Sleep contributes to cognitive functioning and is sufficient to alter brain morphology and function. However, mechanisms underlying sleep regulation remain poorly understood. In mammals, tumor necrosis factor-alpha (TNFα) is known to regulate sleep, and cytokine expression may represent an evolutionarily ancient mechanism in sleep regulation. Here we show that the Drosophila TNFα homologue, Eiger, mediates sleep in flies. We show that knockdown of Eiger in astrocytes, but not in neurons, significantly reduces sleep duration, and total loss-of-function reduces the homeostatic response to sleep loss. In addition, we show that neuronal, but not astrocyte, expression of the TNFα receptor superfamily member, Wengen, is necessary for sleep deprivation-induced homeostatic response and for mediating increases in sleep in response to human TNFα. These data identify a novel astrocyte-to-neuron signaling mechanism in the regulation of sleep homeostasis and show that the Drosophila cytokine, Eiger, represents an evolutionarily conserved mechanism of sleep regulation across phylogeny.

Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism.

Misalignment between internal circadian rhythmicity and externally imposed behavioral schedules, such as occurs in shift workers, has been implicated in elevated risk of metabolic disorders. To determine underlying mechanisms, it is essential to assess whether and how peripheral clocks are disturbed during shift work and to what extent this is linked to the central suprachiasmatic nuclei (SCN) pacemaker and/or misaligned behavioral time cues. Investigating rhythms in circulating metabolites as biomarkers of peripheral clock disturbances may offer new insights. We evaluated the impact of misaligned sleep/wake and feeding/fasting cycles on circulating metabolites using a targeted metabolomics approach. Sequential plasma samples obtained during a 24-h constant routine that followed a 3-d simulated night-shift schedule, compared with a simulated day-shift schedule, were analyzed for 132 circulating metabolites. Nearly half of these metabolites showed a 24-h rhythmicity under constant routine following either or both simulated shift schedules. However, while traditional markers of the circadian clock in the SCN-melatonin, cortisol, and PER3 expression-maintained a stable phase alignment after both schedules, only a few metabolites did the same. Many showed reversed rhythms, lost their rhythms, or showed rhythmicity only under constant routine following the night-shift schedule. Here, 95% of the metabolites with a 24-h rhythmicity showed rhythms that were driven by behavioral time cues externally imposed during the preceding simulated shift schedule rather than being driven by the central SCN circadian clock. Characterization of these metabolite rhythms will provide insight into the underlying mechanisms linking shift work and metabolic disorders.

Fatigue risk management based on self-reported fatigue: Expanding a biomathematical model of fatigue-related performance deficits to also predict subjective sleepiness.

Biomathematical models of fatigue can be used to predict neurobehavioral deficits during sleep/wake or work/rest schedules. Current models make predictions for objective performance deficits and/or subjective sleepiness, but known differences in the temporal dynamics of objective versus subjective outcomes have not been addressed. We expanded a biomathematical model of fatigue previously developed to predict objective performance deficits as measured on the Psychomotor Vigilance Test (PVT) to also predict subjective sleepiness as self-reported on the Karolinska Sleepiness Scale (KSS). Four model parameters were re-estimated to capture the distinct dynamics of the KSS and account for the scale difference between KSS and PVT. Two separate ensembles of datasets - drawn from laboratory studies of sleep deprivation, sleep restriction, simulated night work, napping, and recovery sleep - were used for calibration and subsequent validation of the model for subjective sleepiness. The expanded model was found to exhibit high prediction accuracy for subjective sleepiness, while retaining high prediction accuracy for objective performance deficits. Application of the validated model to an example scenario based on cargo aviation operations revealed divergence between predictions for objective and subjective outcomes, with subjective sleepiness substantially underestimating accumulating objective impairment, which has important real-world implications. In safety-sensitive operations such as commercial aviation, where self-ratings of sleepiness are used as part of fatigue risk management, the systematic differences in the temporal dynamics of objective versus subjective measures of functional impairment point to a potentially significant risk evaluation sensitivity gap. The expanded biomathematical model of fatigue presented here provides a useful quantitative tool to bridge this previously unrecognized gap.

Action plan interrupted: resolution of proactive interference while coordinating execution of multiple action plans during sleep deprivation.

The ability to retain an action plan to execute another is necessary for most complex, goal-directed behavior. Research shows that executing an action plan to an interrupting event can be delayed when it partly overlaps (vs. does not overlap) with the retained action plan. This phenomenon is known as partial repetition costs (PRCs). PRCs reflect proactive interference, which may be resolved by inhibitory, executive control processes. We investigated whether these inhibitory processes are compromised due to one night of sleep deprivation. Participants were randomized to a sleep-deprived group or a well-rested control group. All participants performed an action planning task at baseline after a full night of sleep, and again either after a night of sleep deprivation (sleep-deprived group) or a full night of sleep (control group). In this task, two visual events occurred in a sequence. Participants retained an action plan to the first event in working memory while executing a speeded action to the second (interrupting) event; afterwards, they executed the action to the first event. The two action plans either partly overlapped (required the same hand) or did not (required different hands). Results showed slower responses to the interrupting event during sleep deprivation compared to baseline and the control group. However, the magnitude of the PRCs was no different during sleep deprivation compared to baseline and the control group. Thus, one night of sleep deprivation slowed global responses to the interruption, but inhibitory processes involved in reducing proactive interference while responding to an interrupting event were not compromised. These findings are consistent with other studies that show sleep deprivation degrades global task performance, but does not necessarily degrade performance on isolated, executive control components of cognition. The possibility that our findings involve local as opposed to central inhibition is also discussed.

Circulating Exosomal miRNAs Signal Circadian Misalignment to Peripheral Metabolic Tissues.

Night shift work increases risk of metabolic disorders, particularly obesity and insulin resistance. While the underlying mechanisms are unknown, evidence points to misalignment of peripheral oscillators causing metabolic disturbances. A pathway conveying such misalignment may involve exosome-based intercellular communication. Fourteen volunteers were assigned to a simulated day shift (DS) or night shift (NS) condition. After 3 days on the simulated shift schedule, blood samples were collected during a 24-h constant routine protocol. Exosomes were isolated from the plasma samples from each of the blood draws. Exosomes were added to naïve differentiated adipocytes, and insulin-induced pAkt/Akt expression changes were assessed. ChIP-Seq analyses for BMAL1 protein, mRNA microarrays and exosomal miRNA arrays combined with bioinformatics and functional effects of agomirs and antagomirs targeting miRNAs in NS and DS exosomal cargo were examined. Human adipocytes treated with exosomes from the NS condition showed altered Akt phosphorylation responses to insulin in comparison to those treated with exosomes from the DS condition. BMAL1 ChIP-Seq of exosome-treated adipocytes showed 42,037 binding sites in the DS condition and 5538 sites in the NS condition, with a large proportion of BMAL1 targets including genes encoding for metabolic regulators. A significant and restricted miRNA exosomal signature emerged after exposure to the NS condition. Among the exosomal miRNAs regulated differentially after 3 days of simulated NS versus DS, proof-of-concept validation of circadian misalignment signaling was demonstrated with hsa-mir-3614-5p. Exosomes from the NS condition markedly altered expression of key genes related to circadian rhythm in several cultured cell types, including adipocytes, myocytes, and hepatocytes, along with significant changes in 29 genes and downstream gene network interactions. Our results indicate that a simulated NS schedule leads to changes in exosomal cargo in the circulation. These changes promote reduction of insulin sensitivity of adipocytes in vitro and alter the expression of core clock genes in peripheral tissues. Circulating exosomal miRNAs may play an important role in metabolic dysfunction in NS workers by serving as messengers of circadian misalignment to peripheral tissues.

Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation.

BACKGROUND: Although sleep deprivation is associated with neurobehavioral impairment that may underlie significant risks to performance and safety, there is no reliable biomarker test to detect dangerous levels of impairment from sleep loss in humans. This study employs microarrays and bioinformatics analyses to explore candidate gene expression biomarkers associated with total sleep deprivation (TSD), and more specifically, the phenotype of neurobehavioral impairment from TSD. Healthy adult volunteers were recruited to a sleep laboratory for seven consecutive days (six nights). After two Baseline nights of 10 h time in bed, 11 subjects underwent an Experimental phase of 62 h of continuous wakefulness, followed by two Recovery nights of 10 h time in bed. Another six subjects underwent a well-rested Control condition of 10 h time in bed for all six nights. Blood was drawn for measuring gene expression on days two, four, and six at 4 h intervals from 08:00 to 20:00 h, corresponding to 12 timepoints across one Baseline, one Experimental, and one Recovery day. RESULTS: Altogether 212 genes changed expression in response to the TSD Treatment, with most genes exhibiting down-regulation during TSD. Also, 28 genes were associated with neurobehavioral impairment as measured by the Psychomotor Vigilance Test. The results support previous findings associating TSD with the immune response and ion signaling, and reveal novel candidate biomarkers such as the Speedy/RINGO family of cell cycle regulators. CONCLUSIONS: This study serves as an important step toward understanding gene expression changes during sleep deprivation. In addition to exploring potential biomarkers for TSD, this report presents novel candidate biomarkers associated with lapses of attention during TSD. Although further work is required for biomarker validation, analysis of these genes may aid fundamental understanding of the impact of TSD on neurobehavioral performance.

Does Implementation of Biomathematical Models Mitigate Fatigue and Fatigue-related Risks in Emergency Medical Services Operations? A Systematic Review.

BACKGROUND: Work schedules like those of Emergency Medical Services (EMS) personnel have been associated with increased risk of fatigue-related impairment. Biomathematical modeling is a means of objectively estimating the potential impacts of fatigue on performance, which may be used in the mitigation of fatigue-related safety risks. In the context of EMS operations, our objective was to assess the evidence in the literature regarding the effectiveness of using biomathematical models to help mitigate fatigue and fatigue-related risks. METHODS: A systematic review of the evidence evaluating the use of biomathematical models to manage fatigue in EMS personnel or similar shift workers was performed. Procedures proposed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology were used to summarize and rate the certainty in the evidence. Potential bias attached to retained studies was documented using the Cochrane Collaboration's Risk of Bias tool for experimental studies. RESULTS: The literature search strategy, which focused on both EMS personnel and non-EMS shift workers, yielded n = 2,777 unique records. One paper, which investigated non-EMS shift workers, met inclusion criteria. As part of a larger effort, managers and dispatchers of a trucking operation were provided with monthly biomathematical model analyses of predicted fatigue in the driver workforce, and educated on how they could reduce predicted fatigue by means of schedule adjustments. The intervention showed a significant reduction in the number and cost of vehicular accidents during the period in which biomathematical modeling was used. The overall GRADE assessment of evidence quality was very low due to risk of bias, indirectness, imprecision, and publication bias. CONCLUSIONS: This systematic review identified no studies that investigated the impact of biomathematical models in EMS operations. Findings from one study of non-EMS shift workers were favorable toward use of biomathematical models as a fatigue mitigation scheduling aid, albeit with very low quality of evidence pertaining to EMS operations. We propose three focus areas of research priorities that, if addressed, could help better elucidate the utility and impact of biomathematical models as a fatigue-mitigation tool in the EMS environment.

Proposed Performance Measures and Strategies for Implementation of the Fatigue Risk Management Guidelines for Emergency Medical Services.

BACKGROUND: Performance measures are a key component of implementation, dissemination, and evaluation of evidence-based guidelines (EBGs). We developed performance measures for Emergency Medical Services (EMS) stakeholders to enable the implementation of guidelines for fatigue risk management in the EMS setting. METHODS: Panelists associated with the Fatigue in EMS Project, which was supported by the National Highway Traffic Safety Administration (NHTSA), used an iterative process to develop a draft set of performance measures linked to 5 recommendations for fatigue risk management in EMS. We used a cross-sectional survey design and the Content Validity Index (CVI) to quantify agreement among panelists on the wording and content of draft measures. An anonymous web-based tool was used to solicit the panelists' perceptions of clarity and relevance of draft measures. Panelists rated the clarity and relevance separately for each draft measure on a 4-point scale. CVI scores ≥0.78 for clarity and relevance were specified a priori to signify agreement and completion of measurement development. RESULTS: Panelists judged 5 performance measures for fatigue risk management as clear and relevant. These measures address use of fatigue and/or sleepiness survey instruments, optimal duration of shifts, access to caffeine as a fatigue countermeasure, use of napping during shift work, and the delivery of education and training on fatigue risk management for EMS personnel. Panelists complemented performance measures with suggestions for implementation by EMS agencies. CONCLUSIONS: Performance measures for fatigue risk management in the EMS setting will facilitate the implementation and evaluation of the EBG for Fatigue in EMS.

Evidence-Based Guidelines for Fatigue Risk Management in Emergency Medical Services.

BACKGROUND: Administrators of Emergency Medical Services (EMS) operations lack guidance on how to mitigate workplace fatigue, which affects greater than half of all EMS personnel. The primary objective of the Fatigue in EMS Project was to create an evidence-based guideline for fatigue risk management tailored to EMS operations. METHODS: Systematic searches were conducted from 1980 to September 2016 and guided by seven research questions framed in the Population, Intervention, Comparison, Outcome (PICO) framework. Teams of investigators applied inclusion criteria, which included limiting the retained literature to EMS personnel or similar shift worker groups. The expert panel reviewed summaries of the evidence based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The panel evaluated the quality of evidence for each PICO question separately, considered the balance between benefits and harms, considered the values and preferences of the targeted population, and evaluated the resource requirements/needs. The GRADE Evidence-to-Decision (EtD) Framework was used to prepare draft recommendations based on the evidence, and the Content Validity Index (CVI) was used to quantify the panel's agreement on the relevance and clarity of each recommendation. CVI scores for relevance and clarity were measured separately on a 1-4 scale to indicate consensus/agreement among panel members and conclusion of recommendation development. RESULTS: The EtD framework was applied to all 7 PICO questions, and the panel created 5 recommendations. PICO1: The panel recommends using fatigue/sleepiness survey instruments to measure and monitor fatigue in EMS personnel. PICO2: The panel recommends that EMS personnel work shifts shorter than 24 hours in duration. PICO3: The panel recommends that EMS personnel have access to caffeine as a fatigue countermeasure. PICO4: The panel recommends that, EMS personnel have the opportunity to nap while on duty to mitigate fatigue. PICO5: The panel recommends that EMS personnel receive education and training to mitigate fatigue and fatigue-related risks. The panel referenced insufficient evidence as the reason for making no recommendation linked to 2 PICO questions. CONCLUSIONS: Based on a review of the evidence, the panel developed a guideline with 5 recommendations for fatigue risk management in EMS operations.

Interindividual differences in the dynamics of the homeostatic process are trait-like and distinct for sleep versus wakefulness.

The sleep homeostatic Process S reflects the build-up of sleep pressure during waking and its dissipation during sleep. Process S is modelled as a saturating exponential function during waking and a decreasing exponential function during sleep. Slow wave activity is a physiological marker for non-rapid eye movement (non-REM) sleep intensity and serves as an index of Process S. There is considerable interindividual variability in the sleep homeostatic responses to sleep and sleep deprivation. The aim of this study was to investigate whether interindividual differences in Process S are trait-like. Polysomnographic recordings of 8 nights (12-h sleep opportunities, 22:00-10:00 hours) interspersed with three 36-h periods of sustained wakefulness were performed in 11 healthy young adults. Empirical mean slow wave activity per non-REM sleep episode at episode mid-points were used for parameter estimation. Parameters of Process S were estimated using different combinations of consecutive sleep recordings, resulting in two to three sets of parameters per subject. Intraclass correlation coefficients were calculated to assess whether the parameters were stable across the study protocol and they showed trait-like variability among individuals. We found that the group-average time constants of the build-up and dissipation of Process S were 19.2 and 2.7 h, respectively. Intraclass correlation coefficients ranged from 0.48 to 0.56, which reflects moderate trait variability. The time constants of the build-up and dissipation varied independently among subjects, indicating two distinct traits. We conclude that interindividual differences in the parameters of the dynamics of the sleep homeostatic Process S are trait-like.

3-minute smartphone-based and tablet-based psychomotor vigilance tests for the assessment of reduced alertness due to sleep deprivation.

The psychomotor vigilance test (PVT) is widely used to measure reduced alertness due to sleep loss. Here, two newly developed, 3-min versions of the psychomotor vigilance test, one smartphone-based and the other tablet-based, were validated against a conventional 10-min laptop-based PVT. Sixteen healthy participants (ages 22-40; seven males, nine females) completed a laboratory study, which included a practice and a baseline day, a 38-h total sleep deprivation (TSD) period, and a recovery day, during which they performed the three different versions of the PVT every 3 h. For each version of the PVT, the number of lapses, mean response time (RT), and number of false starts showed statistically significant changes across the sleep deprivation and recovery days. The number of lapses on the laptop was significantly correlated with the numbers of lapses on the smartphone and tablet. The mean RTs were generally faster on the smartphone and tablet than on the laptop. All three versions of the PVT exhibited a time-on-task effect in RTs, modulated by time awake and time of day. False starts were relatively rare on all three PVTs. For the number of lapses, the effect sizes across 38 h of TSD were large for the laptop PVT and medium for the smartphone and tablet PVTs. These results indicate that the 3-min smartphone and tablet PVTs are valid instruments for measuring reduced alertness due to sleep deprivation and restored alertness following recovery sleep. The results also indicate that the loss of sensitivity on the 3-min PVTs may be mitigated by modifying the threshold defining lapses.

TNFα G308A polymorphism is associated with resilience to sleep deprivation-induced psychomotor vigilance performance impairment in healthy young adults.

Cytokines such as TNFα play an integral role in sleep/wake regulation and have recently been hypothesized to be involved in cognitive impairment due to sleep deprivation. We examined the effect of a guanine to adenine substitution at position 308 in the TNFα gene (TNFα G308A) on psychomotor vigilance performance impairment during total sleep deprivation. A total of 88 healthy women and men (ages 22-40) participated in one of five laboratory total sleep deprivation experiments. Performance on a psychomotor vigilance test (PVT) was measured every 2-3h. The TNFα 308A allele, which is less common than the 308G allele, was associated with greater resilience to psychomotor vigilance performance impairment during total sleep deprivation (regardless of time of day), and also provided a small performance benefit at baseline. The effect of genotype on resilience persisted when controlling for between-subjects differences in age, gender, race/ethnicity, and baseline sleep duration. The TNFα G308A polymorphism predicted less than 10% of the overall between-subjects variance in performance impairment during sleep deprivation. Nonetheless, the differential effect of the polymorphism at the peak of performance impairment was more than 50% of median performance impairment at that time, which is sizeable compared to the effects of other genotypes reported in the literature. Our findings provided evidence for a role of TNFα in the effects of sleep deprivation on psychomotor vigilance performance. Furthermore, the TNFα G308A polymorphism may have predictive potential in a biomarker panel for the assessment of resilience to psychomotor vigilance performance impairment due to sleep deprivation.

The spectrum of the non-rapid eye movement sleep electroencephalogram following total sleep deprivation is trait-like.

The sleep electroencephalogram (EEG) spectrum is unique to an individual and stable across multiple baseline recordings. The aim of this study was to examine whether the sleep EEG spectrum exhibits the same stable characteristics after acute total sleep deprivation. Polysomnography (PSG) was recorded in 20 healthy adults across consecutive sleep periods. Three nights of baseline sleep [12 h time in bed (TIB)] following 12 h of wakefulness were interleaved with three nights of recovery sleep (12 h TIB) following 36 h of sustained wakefulness. Spectral analysis of the non-rapid eye movement (NREM) sleep EEG (C3LM derivation) was used to calculate power in 0.25 Hz frequency bins between 0.75 and 16.0 Hz. Intraclass correlation coefficients (ICCs) were calculated to assess stable individual differences for baseline and recovery night spectra separately and combined. ICCs were high across all frequencies for baseline and recovery and for baseline and recovery combined. These results show that the spectrum of the NREM sleep EEG is substantially different among individuals, highly stable within individuals and robust to an experimental challenge (i.e. sleep deprivation) known to have considerable impact on the NREM sleep EEG. These findings indicate that the NREM sleep EEG represents a trait.

Diffusion model for one-choice reaction-time tasks and the cognitive effects of sleep deprivation.

One-choice reaction-time (RT) tasks are used in many domains, including assessments of motor vehicle driving and assessments of the cognitive/behavioral consequences of sleep deprivation. In such tasks, subjects are asked to respond when they detect the onset of a stimulus; the dependent variable is RT. We present a cognitive model for one-choice RT tasks that uses a one-boundary diffusion process to represent the accumulation of stimulus information. When the accumulated evidence reaches a decision criterion, a response is initiated. This model is distinct in accounting for the RT distributions observed for one-choice RT tasks, which can have long tails that have not been accurately captured by earlier cognitive modeling approaches. We show that the model explains performance on a brightness-detection task (a "simple RT task") and on a psychomotor vigilance test. The latter is used extensively to examine the clinical and behavioral effects of sleep deprivation. For the brightness-detection task, the model explains the behavior of RT distributions as a function of brightness. For the psychomotor vigilance test, it accounts for lapses in performance under conditions of sleep deprivation and for changes in the shapes of RT distributions over the course of sleep deprivation. The model also successfully maps the rate of accumulation of stimulus information onto independently derived predictions of alertness. The model is a unified, mechanistic account of one-choice RT under conditions of sleep deprivation.

Sleep restriction and degraded reaction-time performance in Figaro solo sailing races.

In solo offshore sailing races like those of the Solitaire du Figaro, sleep must be obtained in multiple short bouts to maintain competitive performance and safety. Little is known about the amount of sleep restriction experienced at sea and the effects that fatigue from sleep loss have on sailors' performance. Therefore, we assessed sleep in sailors of yachts in the Figaro 2 Beneteau class during races and compared response times on a serial simple reaction-time test before and after races. Twelve men (professional sailors) recorded their sleep and measured their response times during one of the three single-handed races of 150, 300 and 350 nautical miles (nominally 24-50 h in duration). Total estimated sleep duration at sea indicated considerable sleep insufficiency. Response times were slower after races than before. The results suggest that professional sailors incur severe sleep loss and demonstrate marked performance impairment when competing in one- to two-day solo sailing races. Competitive performance could be improved by actively managing sleep during solo offshore sailing races.