Accurate detection of acute sleep deprivation using a metabolomic biomarker-A machine learning approach.

Sleep deprivation enhances risk for serious injury and fatality on the roads and in workplaces. To facilitate future management of these risks through advanced detection, we developed and validated a metabolomic biomarker of sleep deprivation in healthy, young participants, across three experiments. Bi-hourly plasma samples from 2 × 40-hour extended wake protocols (for train/test models) and 1 × 40-hour protocol with an 8-hour overnight sleep interval were analyzed by untargeted liquid chromatography-mass spectrometry. Using a knowledge-based machine learning approach, five consistently important variables were used to build predictive models. Sleep deprivation (24 to 38 hours awake) was predicted accurately in classification models [versus well-rested (0 to 16 hours)] (accuracy = 94.7%/AUC 99.2%, 79.3%/AUC 89.1%) and to a lesser extent in regression (R2 = 86.1 and 47.8%) models for within- and between-participant models, respectively. Metabolites were identified for replicability/future deployment. This approach for detecting acute sleep deprivation offers potential to reduce accidents through "fitness for duty" or "post-accident analysis" assessments.

Circadian adaptation to night shift work is associated with higher REM sleep duration.

OBJECTIVE: To investigate the influence of the degree of circadian adaptation to night work on sleep architecture following night shift. METHODS: Thirty four night workers (11 females; 33.8 ± 10.1years) completed a simulated night shift following 2-7 typical night shifts. Participants completed a laboratory-based simulated night shift (21:00-07:00 hours), followed by a recovery sleep opportunity (∼09:00-17:00 hours), recorded using polysomnography. Urinary 6-sulphatoxymelatonin (aMT6s) rhythm acrophase was used as a marker of circadian phase. Sleep duration and architecture were compared between individuals with aMT6s acrophase before (unadapted group, n = 22) or after (partially adapted group, n = 12) bedtime. RESULTS: Bedtime occurred on average 2.16 hours before aMT6s acrophase in the partially adapted group and 3.91 hours after acrophase in the unadapted group. The partially adapted group had more sleep during the week before the simulated night than the unadapted group (6.47 ± 1.02 vs. 5.26 ± 1.48 hours, p = .02). After the simulated night shift, both groups had similar total sleep time (partially adapted: 6.68 ± 0.80 hours, unadapted: 6.63 ± 0.88 hours, p > .05). The partially adapted group had longer total rapid eye movement sleep duration than the unadapted group (106.79 ± 32.05 minutes vs. 77.90 ± 28.86 minutes, p = .01). After 5-hours, rapid eye movement sleep accumulation was higher in the partially adapted compared to the unadapted group (p = .02). Sleep latency and other stages were not affected by circadian adaptation. DISCUSSION: Partial circadian adaptation to night shift was associated with longer rapid eye movement sleep duration during daytime sleep, highlighting the influence of entrainment between the sleep-wake cycle and the circadian pacemaker in night workers. The findings have important implications for sleep and subsequent alertness associated with shift work.

Heart rate variability increases following automated acoustic slow wave sleep enhancement.

Acoustic stimulation has been shown to enhance slow wave sleep and in turn, cognition, and now cardiac outcomes in young adults. With the emergence of commercial acoustic devices in the home, we sought to examine the impact of an acoustic, slow wave enhancing device on heart rate variability in healthy, middle-aged males (n = 24, 39.92 ± 4.15 years). Under highly controlled conditions, the participants were randomised to receive closed-loop brain state-dependent stimulation in the form of auditory tones (STIM), or no tones (SHAM), in a crossover design, separated by a 1 week washout period. STIM and SHAM were compared on measures of heart rate variability for the whole night and over the first three sleep cycles. We found an increase in slow wave activity following STIM compared with SHAM. There was a significant increase in high frequency power and standard deviation of the normalised RR-intervals (SDNN) during the STIM condition compared with SHAM (p < 0.05), due to changes observed specifically during N3. In conclusion, heart rate variability appears to improve following acoustic slow wave sleep enhancement.

The regulation of circadian entrainment in mice by the adenosine the A 2A /A 1 receptor antagonist CT1500.

Circadian entrainment in mice relies primarily on photic cues that trigger the transcription of the core clock genes Period1/2 in the suprachiasmatic nucleus (SCN), thus aligning the phase of the clock with the dawn/dusk cycle. It has been shown previously that this pathway is directly regulated by adenosine signalling and that adenosine A2A/A1 receptor antagonists can both enhance photic entrainment and phase shift circadian rhythms of wheel-running behaviour in mice. In this study, we tested the ability of CT1500, a clinically safe adenosine A2A/A1 receptor antagonist to effect circadian entrainment. We show that CT1500 lengthens circadian period in SCN ex vivo preparations. Furthermore, we show in vivo that a single dose of CT1500 enhances re-entrainment to a shifted light dark cycle in a dose-dependent manner in mice and also phase shifts the circadian clock under constant dark with a clear time-of-day related pattern. The phase response curve shows CT1500 causes phase advances during the day and phase delays at dusk. Finally, we show that daily timed administration of CT1500 can entrain the circadian clock to a 24 h rhythm in free-running mice. Collectively, these data support the use of CT1500 in the treatment of disorders of circadian entrainment.

Dementia in military and veteran populations: a review of risk factors-traumatic brain injury, post-traumatic stress disorder, deployment, and sleep.

The military population face a unique set of risk factors that may increase the risk of being diagnosed with dementia. Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) have a higher prevalence in this group in comparison to the civilian population. By delving into the individual relationships between TBI and dementia, and PTSD and dementia, we are able to better explore dementia in the military and veteran populations. While there are some inconsistencies in results, the TBI-dementia association has become more widely accepted. Moderate-to-severe TBI has been found to increase the risk of being diagnosed with Alzheimer's disease. A correlation between PTSD and dementia has been established, however, whether or not it is a causal relationship remains unclear. Factors such as blast, combat and chemical exposure may occur during a deployment, along with TBI and/or PTSD diagnosis, and can impact the risk of dementia. However, there is a lack of literature exploring the direct effects of deployment on dementia risk. Sleep problems have been observed to occur in those following TBI, PTSD and deployment. Poor sleep has been associated with possible dementia risk. Although limited studies have focused on the link between sleep and dementia in military and veteran populations, sleep is a valuable factor to study due to its association and interconnection with other military/veteran factors. This review aims to inform of various risk factors to the cognitive health of military members and veterans: TBI, PTSD, deployment, and sleep.

Eye blink parameters to indicate drowsiness during naturalistic driving in participants with obstructive sleep apnea: A pilot study.

OBJECTIVES: To determine whether continuous eye blink measures could identify drowsiness in patients with obstructive sleep apnea (OSA) during a week of naturalistic driving. DESIGN: Observational study comparing OSA patients and healthy controls. SETTING: Regular naturalistic driving across one week. PARTICIPANTS: Fifteen untreated moderate to severe OSA patients and 15 age (± 5 years) and sex (female = 6) matched healthy controls. MEASUREMENTS: Participants wore an eye blink drowsiness recording device during their regular driving for one week. RESULTS: During regular driving, the duration of time with no ocular movements (quiescence), was elevated in the OSA group by 43% relative to the control group (mean [95% CI] 0.20[0.17, 0.25] vs 0.14[0.12, 0.18] secs, P = .011). During long drives only, the Johns Drowsiness Scale was also elevated and increased by 62% in the OSA group relative to the control group (1.05 [0.76, 1.33] vs 0.65 [0.36, 0.93], P = .0495). Across all drives, critical drowsiness events (defined by a Johns Drowsiness Scale score ≥2.6) were twice as frequent in the OSA group than the control group (rate ratio [95% CI] =1.93 [1.65, 2.25], P ≤ .001). CONCLUSIONS: OSA patients were drowsier than healthy controls according to some of the continuous real time eye blink drowsiness measures. The findings of this pilot study suggest that there is potential for eye blink measures to be utilized to assess fitness to drive in OSA patients. Future work should assess larger samples, as well as the relationship of eye blink measures to conventional fitness to drive assessments and crash risk.

The impact of the wake maintenance zone on attentional capacity, physiological drowsiness, and subjective task demands during sleep deprivation.

We aimed to investigate the impact of the Wake Maintenance Zone (WMZ) on measures of drowsiness, attention, and subjective performance under rested and sleep deprived conditions. We studied 23 healthy young adults (18 males; mean age = 25.41 ± 5.73 years) during 40 hr of total sleep deprivation under constant routine conditions. Participants completed assessments of physiological drowsiness (EEG-scored slow eye movements and microsleeps), sustained attention (PVT), and subjective task demands every two hours, and four-hourly ocular motor assessment of inhibitory control (inhibition of reflexive saccades on an anti-saccade task). Tests were analyzed relative to dim light melatonin onset (DLMO); the WMZ was defined as the 3 hr prior to DLMO, and the preceding 3 hr window was deemed the pre-WMZ. The WMZ did not mitigate the adverse impact of ~37 hr sleep deprivation on drowsiness, sustained attention, response inhibition, and self-rated concentration and difficulty, relative to rested WMZ performance (~13 hr of wakefulness). Compared to the pre-WMZ, though, the WMZ improved measures of sustained attention, and subjective concentration and task difficulty, during sleep deprivation. Cumulatively, these results expand on previous work by characterizing the beneficial effects of the WMZ on operationally-relevant indices of drowsiness, inhibitory attention control, and self-rated concentration and task difficulty relative to the pre-WMZ during sleep deprivation. These results may inform scheduling safety-critical tasks at more optimal circadian times to improve workplace performance and safety.

The acute effects of sleep restriction therapy for insomnia on circadian timing and vigilance.

Sleep-restriction therapy (SRT) has been shown to improve insomnia symptoms by restricting sleep opportunity. Curtailment of time in bed affects the duration and consolidation of sleep, but also its timing. While recent work suggests that people with insomnia are characterised by misalignment between circadian and behavioural timing of sleep, no study has investigated if SRT modifies this relationship. The primary aim of the present study was to examine change in phase angle after 2 weeks of SRT. As a secondary aim, we also sought to assess the effect of SRT on psychomotor vigilance. Following a 1-week baseline phase, participants implemented SRT for 2 consecutive weeks. Phase angle was derived from the difference between the decimal clock time of dim light melatonin onset (DLMO) and attempted sleep time. Secondary outcomes included vigilance (assessed via hourly measurement during the DLMO laboratory protocol), sleep continuity (assessed via sleep diary and actigraphy), and insomnia severity. Eighteen participants meeting insomnia criteria (mean [SD] age 37.06 [8.99] years) took part in the study. Consistent with previous research, participants showed robust improvements in subjective and objective sleep continuity, as well as reductions in insomnia severity. The primary outcome (phase angle) was measurable in 15 participants and revealed an increase of 34.8 min (~0.58 hr; 95% confidence interval [CI] 0.01-1.15) from baseline to post-treatment (mean [SD] 2.27 [0.94] versus 2.85 [1.25] hr). DLMO remained relatively stable (20:49 versus 21:01 hours), while attempted sleep was 46.8 min later (~0.78 hr; 95%CI 0.41-1.15; 23:05 versus 23:52 hours). For psychomotor vigilance, reaction time was delayed (by 52.71 ms, 95% CI 34.44-70.97) and number of lapses increased (by 5.84, 95% CI 3.93-7.75) after SRT. We show that SRT increases phase angle during treatment, principally by delaying the timing of sleep attempt. Future studies are needed to test if an increase in phase angle is linked to clinical improvement. Finally, reduction in vigilance after SRT appears to be of similar magnitude to normal sleepers undergoing experimental sleep restriction, reinforcing the importance of appropriate safety advice during implementation.

The Impact of COVID-19 on Sleep Quality in People Living With Disabilities.

Background: Research exploring the impact of the COVID-19 pandemic on sleep in people with disabilities has been scarce. This study provides a preliminary assessment of sleep in people with disabilities, across two timepoints during the pandemic, with a focus on those with visual impairment (VI). Methods: Two online surveys were conducted between April 2020 and March 2021 to explore sleep quality using the Pittsburgh Sleep Quality Index (PSQI). A convenience sample of 602 participants completed the first survey and 160 completed the follow-up survey. Results: Across both timepoints, participants with disabilities reported significantly poorer global sleep quality and higher levels of sleep disturbance, use of sleep medication and daytime dysfunction than those with no disabilities. Participants with VI reported significantly higher levels of sleep disturbance and use of sleep medication at both timepoints, poorer global sleep quality, sleep duration and latency at time 1, and daytime dysfunction at time 2, than those with no disabilities. Global sleep quality, sleep duration, sleep efficiency, and self-rated sleep quality deteriorated significantly in participants with no disabilities, but daytime dysfunction increased in all three groups. Disability and state anxiety were significant predictors of sleep quality across both surveys. Conclusion: While sleep was consistently poorer in people with disabilities such as VI, it appears that the COVID-19 pandemic has had a greater impact on sleep in people with no disabilities. State anxiety and, to a lesser extent, disability, were significant predictors of sleep across both surveys, suggesting the need to address anxiety in interventions targeted toward improving sleep.

The impact of structured sleep schedules prior to an in-laboratory study: Individual differences in sleep and circadian timing.

INTRODUCTION: Many sleep and circadian studies require participants to adhere to structured sleep-wake schedules designed to stabilize sleep outcomes and circadian phase prior to in-laboratory testing. The effectiveness of this approach has not been rigorously evaluated, however. We therefore investigated the differences between participants' unstructured and structured sleep over a three-week interval. METHODS: Twenty-three healthy young adults completed three weeks of sleep monitoring, including one week of unstructured sleep and two weeks of structured sleep with consistent bed and wake times. Circadian phase was assessed via salivary dim light melatonin onset (DLMO) during both the unstructured and structured sleep episodes. RESULTS: Compared to their unstructured sleep schedule, participants' bed- and wake times were significantly earlier in their structured sleep, by 34 ± 44 mins (M ± SD) and 44 ± 41 mins, respectively. During structured sleep, circadian phase was earlier in 65% of participants (40 ± 32 mins) and was later in 35% (41 ± 25 mins) compared to unstructured sleep but did not change at the group level. While structured sleep reduced night-to-night variability in sleep timing and sleep duration, and improved the alignment (phase angle) between sleep onset and circadian phase in the most poorly aligned individuals (DLMO < 1h or > 3h before sleep onset time; 25% of our sample), sleep duration and quality were unchanged. CONCLUSION: Our results show adherence to a structured sleep schedule results in more regular sleep timing, and improved alignment between sleep and circadian timing for those individuals who previously had poorer alignment. Our findings support the use of structured sleep schedules prior to in-laboratory sleep and circadian studies to stabilize sleep and circadian timing in healthy volunteers.

Differential Impact of Sleep Deprivation and Circadian Timing on Reflexive Versus Inhibitory Control of Attention.

In a visually stimulating environment with competing stimuli, we continually choose where to allocate attention, and what to ignore. Wake and circadian-dependent modulation of attentional control and resolution of conflict is poorly understood. Twenty-two participants (17males; 25.6 ± 5.6 years) completed ocular motor tasks throughout 40 hours of sleep deprivation under constant routine conditions. A prosaccade task required a reflexive saccade toward a stimulus (no conflict), while an antisaccade task required inhibiting a reflexive saccade to the peripheral stimulus, and looking in the mirror opposite instead (conflict resolution). Antisaccade inhibitory errors showed circadian modulation, being highest in the morning, progressively decreasing until melatonin onset, before returning to the prior morning's peak throughout the biological night. This diurnal rhythm was blunted by sleep loss (>24 hours), with inhibitory control remaining impaired across the second biological day. For prosaccade, responses slowed down during the biological night. Taken together, we provide evidence for a circadian modulation of attentional bias: the morning being biased toward reflexive responding, and the evening toward higher inhibitory control. Our data show that sleep loss and circadian timing differentially impact attention, depending on whether a response conflict is present (antisaccade) or absent (prosaccade).

Acoustic slow wave sleep enhancement via a novel, automated device improves executive function in middle-aged men.

STUDY OBJECTIVES: As slow-wave activity (SWA) is critical for cognition, SWA-enhancing technologies provide an exciting opportunity to improve cognitive function. We focus on improving cognitive function beyond sleep-dependent memory consolidation, using an automated device, and in middle-aged adults, who have depleted SWA yet a critical need for maximal cognitive capacity in work environments. METHODS: Twenty-four healthy adult males aged 35-48 years participated in a randomized, double-blind, cross-over study. Participants wore an automated acoustic stimulation device that monitored real-time sleep EEG. Following an adaptation night, participants were exposed to either acoustic tones delivered on the up phase of the slow-wave (STIM) or inaudible "tones" during equivalent periods of stimulation (SHAM). An executive function test battery was administered after the experimental night. RESULTS: STIM resulted in an increase in delta (0.5-4 Hz) activity across the full-night spectra, with enhancement being maximal at 1 Hz. SWA was higher for STIM relative to SHAM. Although no group differences were observed in any cognitive outcomes, due to large individual differences in SWA enhancement, higher SWA responders showed significantly improved verbal fluency and working memory compared with nonresponders. Significant positive associations were found between SWA enhancement and improvement in these executive function outcomes. CONCLUSIONS: Our study suggests that (1) an automated acoustic device enhances SWA; (2) SWA enhancement improves executive function; (3) SWA enhancement in middle-aged men may be an important therapeutic target for enhancing cognitive function; and (4) there is a need to examine interindividual responses to acoustic stimulation and its effect on subsequent cognitive function. CLINICAL TRIAL REGISTRATION: This study has been registered with the Australian New Zealand Clinical Trials Registry. "The efficacy of acoustic tones in slow-wave sleep enhancement and cognitive function in healthy adult males". https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371548&isReview=true. REGISTRATION: ACTRN12617000399392.

Generalizability of A Neural Network Model for Circadian Phase Prediction in Real-World Conditions.

A neural network model was previously developed to predict melatonin rhythms accurately from blue light and skin temperature recordings in individuals on a fixed sleep schedule. This study aimed to test the generalizability of the model to other sleep schedules, including rotating shift work. Ambulatory wrist blue light irradiance and skin temperature data were collected in 16 healthy individuals on fixed and habitual sleep schedules, and 28 rotating shift workers. Artificial neural network models were trained to predict the circadian rhythm of (i) salivary melatonin on a fixed sleep schedule; (ii) urinary aMT6s on both fixed and habitual sleep schedules, including shift workers on a diurnal schedule; and (iii) urinary aMT6s in rotating shift workers on a night shift schedule. To determine predicted circadian phase, center of gravity of the fitted bimodal skewed baseline cosine curve was used for melatonin, and acrophase of the cosine curve for aMT6s. On a fixed sleep schedule, the model predicted melatonin phase to within ± 1 hour in 67% and ± 1.5 hours in 100% of participants, with mean absolute error of 41 ± 32 minutes. On diurnal schedules, including shift workers, the model predicted aMT6s acrophase to within ± 1 hour in 66% and ± 2 hours in 87% of participants, with mean absolute error of 63 ± 67 minutes. On night shift schedules, the model predicted aMT6s acrophase to within ± 1 hour in 42% and ± 2 hours in 53% of participants, with mean absolute error of 143 ± 155 minutes. Prediction accuracy was similar when using either 1 (wrist) or 11 skin temperature sensor inputs. These findings demonstrate that the model can predict circadian timing to within ± 2 hours for the vast majority of individuals on diurnal schedules, using blue light and a single temperature sensor. However, this approach did not generalize to night shift conditions.

Circadian and wake-dependent changes in human plasma polar metabolites during prolonged wakefulness: A preliminary analysis.

Establishing circadian and wake-dependent changes in the human metabolome are critical for understanding and treating human diseases due to circadian misalignment or extended wake. Here, we assessed endogenous circadian rhythms and wake-dependent changes in plasma metabolites in 13 participants (4 females) studied during 40-hours of wakefulness. Four-hourly plasma samples were analyzed by hydrophilic interaction liquid chromatography (HILIC)-LC-MS for 1,740 metabolite signals. Group-averaged (relative to DLMO) and individual participant metabolite profiles were fitted with a combined cosinor and linear regression model. In group-level analyses, 22% of metabolites were rhythmic and 8% were linear, whereas in individual-level analyses, 14% of profiles were rhythmic and 4% were linear. We observed metabolites that were significant at the group-level but not significant in a single individual, and metabolites that were significant in approximately half of individuals but not group-significant. Of the group-rhythmic and group-linear metabolites, only 7% and 12% were also significantly rhythmic or linear, respectively, in ≥50% of participants. Owing to large inter-individual variation in rhythm timing and the magnitude and direction of linear change, acrophase and slope estimates also differed between group- and individual-level analyses. These preliminary findings have important implications for biomarker development and understanding of sleep and circadian regulation of metabolism.

The wake maintenance zone shows task dependent changes in cognitive function following one night without sleep.

Study Objectives: The interaction between homeostatic sleep pressure and circadian timing modulates the impact of sleep deprivation on cognition. We aimed to investigate how this interaction affects different cognitive functions. Methods: Twenty-three healthy volunteers (18 males; mean age = 25.4 ± 5.7 years) underwent 40 hours of sleep deprivation under constant routine conditions. Performance on the Psychomotor Vigilance Test and a cognitive battery assessing vigilant attention, complex attention, recognition memory, and working memory was assessed in the morning (27 hours awake) and evening (37 hours awake) during sleep deprivation and compared to well-rested performance 24 hours earlier. Circadian phase assessments confirmed evening tests occurred in the wake maintenance zone (WMZ). Results: Increased time awake significantly impacted performance on all measures except recognition memory. Post hoc analyses found performance on all measures was significantly impaired in the morning following 27 hours of sleep deprivation compared to well-rested performance 24 hours earlier. In contrast, complex attention and working memory were preserved in the WMZ after 37 hours awake compared to 24 hours earlier, while vigilant attention and PVT performance were significantly impaired. During sleep deprivation, composite scores of speed and accuracy were both impaired in the morning, while only speed was impaired during the WMZ. Conclusions: We observed task- and time-dependent effects of sleep deprivation, such that vigilant attention was significantly impaired after both 27 hours and 37 hours awake (compared to when well-rested at the same circadian clock time). In contrast, complex attention and working memory were impaired at 27 hours awake, but preserved in the WMZ despite increased homeostatic sleep pressure (37 hours awake).

Self-reported Drowsiness and Safety Outcomes While Driving After an Extended Duration Work Shift in Trainee Physicians.

STUDY OBJECTIVES: Extended duration (≥24 hours) work shifts (EDWSs) are associated with increased risk of motor vehicle crashes, and awareness of any impairment has important implications on legal accountability for any adverse driving outcome. The extent to which adverse driving events were preceded by predrive self-reported sleepiness was evaluated in medical residents after an EDWS. METHODS: Sixteen resident physicians (10 females; 29.2 ± 2.0 years) working EDWS were monitored when driving on their commute to and from the hospital (438 drives). Sleep and work hours were obtained from daily logs, and adverse driving outcomes were captured from a driving log completed at the end of each drive. Self-reported sleepiness (Karolinska Sleepiness Scale; KSS) and objective drowsiness were captured using a time-stamped, hand-held device and infra-red reflectance oculography. RESULTS: Self-reported sleepiness and objective indices of drowsiness were positively correlated, and both were elevated following EDWSs. Compared with the commute to work, EDWSs were associated with more than double the self-reported adverse outcomes when driving home, significantly higher than drives to or from the day shift at comparable times of day. EDWSs more than tripled the odds of reporting sleep-related, inattentive, hazardous, or violation-driving events. The number and type of adverse event was predicted by the predrive KSS level and in a dose-dependent manner. CONCLUSIONS: Driving after an EDWS puts resident physicians/drivers and other road users at avoidable and unnecessary risk. Demonstrating self-reported sleepiness at the beginning of the drive is associated with adverse outcomes has serious implications on the legal accountability for driving when drowsy.

Randomised controlled trial of the efficacy of a blue-enriched light intervention to improve alertness and performance in night shift workers.

OBJECTIVES: Night workers often experience high levels of sleepiness due to misalignment of the sleep-wake cycle from the circadian pacemaker, in addition to acute and chronic sleep loss. Exposure to light, in particular short wavelength light, can improve alertness and neurobehavioural performance. This randomised controlled trial examined the efficacy of blue-enriched polychromatic light to improve alertness and neurobehavioural performance in night workers. DESIGN: Participants were 71 night shift workers (42 males; 32.8±10.5 years) who worked at least 6 hours between 22:00 and 08:00 hours. Sleep-wake logs and wrist actigraphy were collected for 1-3 weeks, followed by 48-hour urine collection to measure the circadian 6-sulphatoxymelatonin (aMT6s) rhythm. On the night following at least two consecutive night shifts, workers attended a simulated night shift in the laboratory which included subjective and objective assessments of sleepiness and performance. Workers were randomly assigned for exposure to one of two treatment conditions from 23:00 hours to 07:00 hours: blue-enriched white light (17 000 K, 89 lux; n=36) or standard white light (4000 K, 84 lux; n=35). RESULTS: Subjective and objective sleepiness increased during the night shift in both light conditions (p<0.05, ηp2=0.06-0.31), but no significant effects of light condition were observed. The 17 000 K light, however, did improve subjective sleepiness relative to the 4000 K condition when light exposure coincided with the time of the aMT6s peak (p<0.05, d=0.41-0.60). CONCLUSION: This study suggests that, while blue-enriched light has potential to improve subjective sleepiness in night shift workers, further research is needed in the selection of light properties to maximise the benefits. TRIAL REGISTRATION NUMBER: The Australian New Zealand Clinical Trials Registry ACTRN12610000097044 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=320845&isReview=true).

Ocular Measures of Sleepiness Are Increased in Night Shift Workers Undergoing a Simulated Night Shift Near the Peak Time of the 6-Sulfatoxymelatonin Rhythm.

STUDY OBJECTIVE: The study examined the relationship between the circadian rhythm of 6-sulphatoxymelatonin (aMT6s) and ocular measures of sleepiness and neurobehavioral performance in shift workers undergoing a simulated night shift. METHODS: Twenty-two shift workers (mean age 33.4, SD 11.8 years) were tested at approximately the beginning (20:00) and the end (05:55) of a simulated night shift in the laboratory. At the time point corresponding to the end of the simulated shift, 14 participants were classified as being within range of 6-sulphatoxymelatonin (aMT6s) acrophase--defined as 3 hours before or after aMT6s peak--and 8 were classified as outside aMT6s acrophase range. Participants completed the Karolinska Sleepiness Scale (KSS) and the auditory psychomotor vigilance task (aPVT). Waking electroencephalography (EEG) was recorded and infrared reflectance oculography was used to collect ocular measures of sleepiness: positive and negative amplitude/velocity ratio (PosAVR, NegAVR), mean blink total duration (BTD), the percentage of eye closure (%TEC), and a composite score of sleepiness levels (Johns Drowsiness Scale; JDS). RESULTS: Participants who were tested within aMT6s acrophase range displayed higher levels of sleepiness on ocular measures (%TEC, BTD, PosAVR, JDS), objective sleepiness (EEG delta power frequency band), subjective ratings of sleepiness, and neurobehavioral performance, compared to those who were outside aMT6s acrophase range. CONCLUSIONS: The study demonstrated that objective ocular measures of sleepiness are sensitive to circadian rhythm misalignment in shift workers.

Temporal dynamics of ocular indicators of sleepiness across sleep restriction.

The current study characterized the temporal dynamics of ocular indicators of sleepiness during extended sleep restriction. Ten male participants (mean age ± SD = 23.3 ± 1.6 years) underwent 40 h of continuous wakefulness under constant routine (CR) conditions; they completed the Karolinska Sleepiness Scale (KSS) and a 10-min auditory psychomotor vigilance task (aPVT) hourly. Waking electroencephalography (EEG) and ocular measures were recorded continuously throughout the CR. Infrared-reflectance oculography was used to collect the ocular measures positive and negative amplitude-velocity ratio, mean blink duration, the percentage of eye closure, and a composite score of sleepiness levels (Johns Drowsiness Scale). All ocular measures, except blink duration, displayed homeostatic and circadian properties. Only circadian effects were detected in blink duration. Significant, phase-locked cross-correlations (p < 0.05) were detected between ocular measures and aPVT reaction time (RT), aPVT lapses, KSS, and EEG delta-theta (0.5-5.5 Hz), theta-alpha (5.0-9.0 Hz), and beta (13.0-20.0 Hz) activity. Receiver operating characteristic curve analysis demonstrated reasonable sensitivity and specificity of ocular measures in correctly classifying aPVT lapses above individual baseline thresholds (initial 16 h of wakefulness). Under conditions of sleep restriction, ocular indicators of sleepiness paralleled performance impairment and self-rated sleepiness levels, and demonstrated their potential to detect sleepiness-related attentional lapses. These findings, if reproduced in a larger sample, will have implications for the use of ocular-based sleepiness-warning systems in operational settings.

Objective and subjective measures of sleepiness, and their associations with on-road driving events in shift workers.

To assess the relationships between sleepiness and the incidence of adverse driving events in nurses commuting to and from night and rotating shifts, 27 rotating and permanent night shift-working nurses were asked to complete daily sleep and duty logs, and wear wrist-activity monitors for 2 weeks (369 driving sessions). During all commutes, ocular measures of drowsiness, including the Johns Drowsiness Scale score, were assessed using the Optalert™ system. Participants self-reported their subjective sleepiness at the beginning and end of each drive, and any events that occurred during the drive. Rotating shift nurses reported higher levels of sleepiness compared with permanent night shift nurses. In both shift-working groups, self-reported sleepiness, drowsiness and drive events were significantly higher during commutes following night shifts compared with commutes before night shifts. Strong associations were found between objective drowsiness and increased odds of driving events during commutes following night shifts. Maximum total blink duration (mean = 7.96 s) during the drive and pre-drive Karolinska Sleepiness Scale (mean = 5.0) were associated with greater incidence of sleep-related events [OR, 5.35 (95% CI, 1.32, 21.60), OR, 1.69 (95% CI, 1.04, 2.73), respectively]. Inattention was strongly associated with a Johns Drowsiness Scale score equal to or above 4.5 [OR, 4.58 (95% CI, 1.26-16.69)]. Hazardous driving events were more likely to occur when drivers had been awake for 16 h or more [OR, 4.50 (95% CI, 1.81, 11.16)]. Under real-world driving conditions, shift-working nurses experience high levels of drowsiness as indicated by ocular measures, which are associated with impaired driving performance following night shift work.