Brieann C. Satterfield

Occupational fatigue, underlying sleep and circadian mechanisms, and approaches to fatigue risk management

In most occupational settings, a primary reason for fatigue is incompatible timing of duty schedules relative to circadian (i.e., 24-hour) rhythm and the need for sleep. This review describes the sleep-related neurobiology of fatigue; factors in the operational environment that contribute to fatigue; and the effects of fatigue on cognitive performance that lead to errors, incidents, and accidents. A range of fatigue countermeasures are reviewed, broadly categorized as preventive countermeasures and operational countermeasures. Fatigue-related optimization of duty schedules and fatigue risk management systems are discussed as comprehensive ways to reduce fatigue and increase safety while maintaining productivity and operational integrity. Occupational fatigue is of significant concern at the individual, organizational, and societal levels, and strategies have been developed to help successfully manage and mitigate fatigue at each level.

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.

Naturalistic field study of the restart break in US commercial motor vehicle drivers: Truck driving, sleep, and fatigue.

Commercial motor vehicle (CMV) drivers in the US may start a new duty cycle after taking a 34-h restart break. A restart break provides an opportunity for sleep recuperation to help prevent the build-up of fatigue across duty cycles. However, the effectiveness of a restart break may depend on its timing, and on how many nighttime opportunities for sleep it contains. For daytime drivers, a 34-h restart break automatically includes two nighttime periods. For nighttime drivers, who are arguably at increased risk of fatigue, a 34-h restart break contains only one nighttime period. To what extent this is relevant for fatigue depends in part on whether nighttime drivers revert back to a nighttime-oriented sleep schedule during the restart break. We conducted a naturalistic field study with 106 CMV drivers working their normal schedules and performing their normal duties. These drivers were studied during two duty cycles and during the intervening restart break. They provided a total of 1260days of data and drove a total of 414,937 miles during the study. Their duty logs were used to identify the periods when they were on duty and when they were driving and to determine their duty cycles and restart breaks. Sleep/wake patterns were measured continuously by means of wrist actigraphy. Fatigue was assessed three times per day by means of a brief psychomotor vigilance test (PVT-B) and a subjective sleepiness scale. Data from a truck-based lane tracking and data acquisition system were used to compute lane deviation (variability in lateral lane position). Statistical analyses focused on 24-h patterns of duty, driving, sleep, PVT-B performance, subjective sleepiness, and lane deviation. Duty cycles preceded by a restart break containing only one nighttime period (defined as 01:00-05:00) were compared with duty cycles preceded by a restart break containing more than one nighttime period. During duty cycles preceded by a restart break with only one nighttime period, drivers showed more nighttime-oriented duty and driving patterns and more daytime-oriented sleep patterns than during duty cycles preceded by a restart break with more than one nighttime period. During duty cycles preceded by a restart break with only one nighttime period, drivers also experienced more lapses of attention on the PVT-B and increased lane deviation at night, and they reported greater subjective sleepiness. Importantly, drivers exhibited a predominantly nighttime-oriented sleep schedule during the restart break, regardless of whether the restart break contained only one or more than one nighttime period. Consistent with findings in laboratory-based studies of the restart break, the results of this naturalistic field study indicate that having at least two nighttime periods in the restart break provides greater opportunity for sleep recuperation and helps to mitigate fatigue.

Fatiguing effect of multiple take-offs and landings in regional airline operations

Fatigue is a risk factor for flight performance and safety in commercial aviation. In US commercial aviation, to help to curb fatigue, the maximum duration of flight duty periods is regulated based on the scheduled start time and the number of flight segments to be flown. There is scientific support for regulating maximum duty duration based on scheduled start time; fatigue is well established to be modulated by circadian rhythms. However, it has not been established scientifically whether the number of flight segments, per se, affects fatigue. To address this science gap, we conducted a randomized, counterbalanced, cross-over study with 24 active-duty regional airline pilots. Objective and subjective fatigue was compared between a 9-hour duty day with multiple take-offs and landings versus a duty day of equal duration with a single take-off and landing. To standardize experimental conditions and isolate the fatiguing effect of the number of segments flown, the entire duty schedules were carried out in a high-fidelity, moving-base, full-flight, regional jet flight simulator. Steps were taken to maintain operational realism, including simulated airplane inspections and acceptance checks, use of realistic dispatch releases and airport charts, real-world air traffic control interactions, etc. During each of the two duty days, 10 fatigue test bouts were administered, which included a 10-minute Psychomotor Vigilance Test (PVT) assessment of objective fatigue and Samn-Perelli (SP) and Karolinska Sleepiness Scale (KSS) assessments of subjective sleepiness/fatigue. Results showed a greater build-up of objective and subjective fatigue in the multi-segment duty day than in the single-segment duty day. With duty start time and duration and other variables that could impact fatigue levels held constant, the greater build-up of fatigue in the multi-segment duty day was attributable specifically to the difference in the number of flight segments flown. Compared to findings in previously published laboratory studies of simulated night shifts and nighttime sleep deprivation, the magnitude of the fatiguing effect of the multiple take-offs and landings was modest. Ratings of flight performance were not significantly reduced for the simulated multi-segment duty day. The US duty and flight time regulations for commercial aviation shorten the maximum duty duration in multi-segment operations by up to 25% depending on the duty start time. The present results represent an important first step in understanding fatigue in multi-segment operations, and provide support for the number of flight segments as a relevant factor in regulating maximum duty duration. Nonetheless, based on our fatigue results, a more moderate reduction in maximum duty duration as a function of the number of flight segments might be considered. However, further research is needed to include investigation of flight safety, and to extend our findings to nighttime operations.

Catechol- O -methyltransferase (COMT) genotype affects cognitive control during total sleep deprivation

Adaptive decision making is profoundly impaired by total sleep deprivation (TSD). This suggests that TSD impacts fronto-striatal pathways involved in cognitive control, where dopamine is a key neuromodulator. In the prefrontal cortex (PFC), dopamine is catabolized by the enzyme catechol-O-methyltransferase (COMT). A functional polymorphism (Val158Met) influences COMTs enzymatic activity, resulting in markedly different levels of prefrontal dopamine. We investigated the effect of this polymorphism on adaptive decision making during TSD. Sixty-six healthy young adults participated in one of two in-laboratory studies. After a baseline day, subjects were randomized to either a TSD group (nxa0=xa032) with 38xa0h or 62xa0h of extended wakefulness or a well-rested control group (nxa0=xa034) with 10xa0h nighttime sleep opportunities. Subjects performed a go/no-go reversal learning (GNGr) task at well-rested baseline and again during TSD or equivalent control. During the task, subjects were required to learn stimulus-response relationships from accuracy feedback. The stimulus-response relationships were reversed halfway through the task, which required subjects to learn the new stimulus-response relationships from accuracy feedback. Performance on the GNGr task was quantified by discriminability (d) between go and no-go stimuli before and after the stimulus-response reversal. GNGr performance did not differ between COMT genotypes when subjects were well-rested. However, TSD exposed a significant vulnerability to adaptive decision making impairment in subjects with the Val allele. Our results indicate that sleep deprivation degrades cognitive control through a fronto-striatal, dopaminergic mechanism.

Sleep Deprivation Diminishes Attentional Control Effectiveness and Impairs Flexible Adaptation to Changing Conditions

Insufficient sleep is a global public health problem resulting in catastrophic accidents, increased mortality, and hundreds of billions of dollars in lost productivity. Yet the effect of sleep deprivation (SD) on decision making and performance is often underestimated by fatigued individuals and is only beginning to be understood by scientists. The deleterious impact of SD is frequently attributed to lapses in vigilant attention, but this account fails to explain many SD-related problems, such as loss of situational awareness and perseveration. Using a laboratory study protocol, we show that SD individuals can maintain information in the focus of attention and anticipate likely correct responses, but their use of such a top-down attentional strategy is less effective at preventing errors caused by competing responses. Moreover, when the task environment requires flexibility, performance under SD suffers dramatically. The impairment in flexible shifting of attentional control we observed is distinct from lapses in vigilant attention, as corroborated by the specificity of the influence of a genetic biomarker, the dopaminergic polymorphism DRD2 C957T. Reduced effectiveness of top-down attentional control under SD, especially when conditions require flexibility, helps to explain maladaptive performance that is not readily explained by lapses in vigilant attention.

Evidence of Actigraphic and Subjective Sleep Disruption Following Mild Traumatic Brain Injury

OBJECTIVE/BACKGROUNDnMild traumatic brain injuries (mTBI) are frequently associated with long-term, self-reported sleep disruption. Objective corroboration of these self-reports is sparse and limited by small sample sizes. The purpose of this study was to report on actigraphically-measured sleep outcomes in individuals with and without a history of recent mTBI in two U.S. cities (Boston, MA and Tucson, AZ).nnnPATIENTS/METHODSnFifty-eight individuals with a recent (within 18 months) mTBI and 35 individuals with no prior mTBI history were recruited for one of four studies across two sites. Participants completed a minimum of one week of actigraphy. Additionally, mTBI participants self-reported daytime sleepiness, sleep disruption, and functional sleep-related outcomes.nnnRESULTSnIn Boston, mTBI participants obtained less average sleep with shorter sleep onset latencies (SOL) than healthy individuals. In Tucson, mTBI participants had greater SOL and less night-to-night SOL variability compared to healthy individuals. Across mTBI participants, SOL was shorter and night-to-night SOL variability was greater in Boston than Tucson. Sleep efficiency (SE) variability was greater in Tucson than Boston across both groups. Only SOL variability was significantly associated with daytime sleepiness (rxa0=xa00.274) in the mTBI group after controlling for location.nnnCONCLUSIONnSleep quality, SOL and SE variability, are likely affected by mTBIs. Between-group differences in each site existed but went in opposite directions. These findings suggest the possibility of multiple, rather than a singular, profiles of sleep disruption following mTBI. Precision medicine models are warranted to determine whether multiple sleep disruption profiles do indeed exist following mTBI and the predisposing conditions that contribute to an individuals experience of sleep disruption.

Chronic sleep restriction affects the association between implicit bias and explicit social decision making

Objectives: Previous work suggests that sleep restriction (SR) reduces cognitive control and may increase negative implicit biases. Here we investigated whether SR might influence decision making on a social‐evaluative task where individuals had to make judgments of threat based on facial photographs. Furthermore, we investigated the effect of changes in negative implicit biases as a result of sleep restriction on this decision‐making task. Design: Fourteen healthy adults underwent two 3‐week counterbalanced in‐laboratory stays (chronic SR and control sleep [CS] conditions). Participants completed the Arab Muslim Names implicit association test (a measure of implicit bias/attitudes toward Arab Muslims) and the Karolinska Airport Task (a measure of explicit decision making). The Karolinska Airport Task requires participants to judge the potential dangerousness of individuals based on facial photographs. Results: After SR, participants were more likely to deem individuals with less positive and more negative facial features as dangerous than after CS. In addition, after SR, those participants showing higher negative implicit bias toward Arab Muslims tended to consider as more dangerous individuals with more quintessentially untrustworthy facial features (r = 0.76, P = .007), whereas this relationship was nonsignificant after CS (r = 0.33, P = .28). Conclusions: These findings show not only that SR may increase implicit biases against a particular minority group but that SR also modifies how individuals make explicit decisions about anothers trustworthiness based on facial features. These findings may have important implications for many occupations where workers who are routinely restricted of sleep are also responsible for making judgments about other peoples trustworthiness (eg, police, security, military personnel).

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

Significance Shift workers, whose schedules are misaligned relative to their suprachiasmatic nuclei (SCN) circadian pacemaker, are at elevated risk of metabolic disorders. In a study of simulated day- versus night-shift work followed by a constant routine, we separated plasma-circulating metabolites according to whether their 24-h rhythms aligned with the central SCN pacemaker or instead reflected externally imposed behavioral schedules. We found that rhythms in many metabolites implicated in food metabolism dissociated from the SCN pacemaker rhythm, with the vast majority aligning with the preceding sleep/wake and feeding/fasting cycles. Our metabolomics study yields insight into the link between prolonged exposure to shift work and the spectrum of associated metabolic disorders by providing a window into peripheral oscillators and the biobehavioral factors that orchestrate them. 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.

Cardiac autonomic activity during simulated shift work

Shift work leads to adverse health outcomes including increased risk of cardiovascular disease. Heart rate (HR) and heart rate variability (HRV) are measures of cardiac autonomic activity and markers of cardiovascular disease and mortality. To investigate the effects of shift work on cardiac autonomic activity, we assessed the influence of simulated night work on HR and HRV, and dissociated the direct effects of circadian misalignment from those of sleep displacement and altered physical activity patterns. A total of 29 subjects each participated in one of two in-laboratory, simulated shift work studies. In both studies, EKG was continuously monitored via Holter monitors to measure HR and the high frequency (HF) component of HRV (HF-HRV). We found endogenous circadian rhythmicity in HR and HF-HRV. Sleep and waking physical activity, both displaced during simulated night work, had more substantial, and opposite, effects on HR and HF-HRV. Our findings show systematic but complex, interacting effects of time of day, sleep/wake state, and physical activity on cardiac autonomic activity. These effects need to be taken into account when evaluating HR and HRV in shift work settings and when interpreting these measures of cardiac autonomic activity as markers of cardiovascular disease.