Sleep deficiency in spaceflight is associated with degraded neurobehavioral functions and elevated stress in astronauts on six-month missions aboard the International Space Station

Astronauts are required to maintain optimal neurobehavioral functioning despite chronic exposure to the stressors and challenges of spaceflight. Sleep of adequate quality and duration is fundamental to neurobehavioral functioning, however astronauts commonly experience short sleep durations in spaceflight (<6 h). As humans embark on long-duration space exploration missions, there is an outstanding need to identify the consequences of sleep deficiency in spaceflight on neurobehavioral functions. Therefore, we conducted a longitudinal study that examined the sleep-wake behaviors, neurobehavioral functions, and ratings of stress and workload of N=24 astronauts before, during, and after 6-month missions aboard the International Space Station (ISS). The computerized, Reaction SelfTest (RST), gathered astronaut report of sleep-wake behaviors, stress, workload, and somatic behavioral states; the RST also objectively assessed vigilant attention (i.e., Psychomotor Vigilance Test-Brief). Data collection began 180 days before launch, continued every 4 days in-flight aboard the ISS, and up to 90 days post-landing, which produced N=2,856 RSTs. Consistent with previous ISS studies, astronauts reported sleeping ~6.5 h in-flight. The adverse consequences of short sleep were observed across neurobehavioral functions, where sleep durations <6 h were associated with significant reductions in psychomotor response speed, elevated stress, and higher workload. Sleep durations <5 h were associated with elevated negative somatic behavioral states. Furthermore, longer sleep durations had beneficial effects on astronaut neurobehavioral functions. Taken together, our findings highlight the importance of sleep for the maintenance of neurobehavioral functioning and as with humans on Earth, astronauts would likely benefit from interventions that promote sleep duration and quality.

Temporal Dynamics of Subjective and Objective Alertness During Exposure to Bright Light in the Afternoon for 5 h

Light can induce an alertness response in humans. The effects of exposure to bright light vs. dim light on the levels of alertness during the day, especially in the afternoon, as reported in the literature, are inconsistent. This study employed a multiple measurement strategy to explore the temporal variations in the effects of exposure to bright light vs. regular office light (1,200 lx vs. 200 lx at eye level, 6,500 K) on the alertness of participants for 5 h in the afternoon. In this study, 20 healthy adults (11 female; mean age 23.25 ± 2.3 years) underwent the Karolinska sleepiness scale (KSS), the auditory psychomotor vigilance test (PVT), and the waking electroencephalogram (EEG) test for two levels of light intervention. The results yielded a relatively lower relative delta power and a relatively higher beta power for the 1,200 lx condition in comparison with the 200 lx condition. However, the light conditions elicited no statistically significant differences in the KSS scores and performance with respect to the PVT. The results suggested that exposure to bright light for 5 h in the afternoon could enhance physiological arousal while exerting insignificant effects on subjective feelings and performance abilities relating to the alertness of the participants.

Predictors of interindividual differences in vulnerability to neurobehavioral consequences of chronic partial sleep restriction

Interindividual differences in the neurobehavioral response to sleep loss are largely unexplained and phenotypic in nature. Numerous factors have been examined as predictors of differential response to sleep loss, but none have yielded a comprehensive view of the phenomenon. The present study examines the impact of baseline factors, habitual sleep–wake patterns, and homeostatic response to sleep loss on accrued deficits in psychomotor vigilance during chronic partial sleep restriction (SR), in a total of 306 healthy adults that participated in one of three independent laboratory studies. Findings indicate no significant impact of personality, academic intelligence, subjective reports of chronotype, sleepiness and fatigue, performance on working memory, and demographic factors such as sex, ethnicity, and body mass index, on neurobehavioral vulnerability to the negative effects of sleep loss. Only superior baseline performance on the psychomotor vigilance test and ability to sustain wakefulness on the maintenance of wakefulness test were associated with relative resilience to decrements in vigilant attention during SR. Interindividual differences in vulnerability to the effects of sleep loss were not accounted for by prior sleep history, habitual sleep patterns outside of the laboratory, baseline sleep architecture, or homeostatic sleep response during chronic partial SR. A recent theoretical model proposed that sleep–wake modulation may be influenced by competing internal and external demands which may promote wakefulness despite homeostatic and circadian signals for sleep under the right circumstances. Further research is warranted to examine the possibility of interindividual differences in the ability to prioritize external demands for wakefulness in the face of mounting pressure to sleep.

Genetics and Cognitive Vulnerability to Sleep Deprivation in Healthy Subjects: Interaction of ADORA2A, TNF-α and COMT Polymorphisms

Several genetic polymorphisms differentiate between healthy individuals who are more cognitively vulnerable or resistant during total sleep deprivation (TSD). Common metrics of cognitive functioning for classifying vulnerable and resilient individuals include the Psychomotor Vigilance Test (PVT), Go/noGo executive inhibition task, and subjective daytime sleepiness. We evaluated the influence of 14 single-nucleotide polymorphisms (SNPs) on cognitive responses during total sleep deprivation (continuous wakefulness for 38 h) in 47 healthy subjects (age 37.0 ± 1.1 years). SNPs selected after a literature review included SNPs of the adenosine-A2A receptor gene (including the most studied rs5751876), pro-inflammatory cytokines (TNF-α, IL1-β, IL-6), catechol-O-methyl-transferase (COMT), and PER3. Subjects performed a psychomotor vigilance test (PVT) and a Go/noGo-inhibition task, and completed the Karolinska Sleepiness Scale (KSS) every 6 h during TSD. For PVT lapses (reaction time >500 ms), an interaction between SNP and SDT (p < 0.05) was observed for ADORA2A (rs5751862 and rs2236624) and TNF-α (rs1800629). During TSD, carriers of the A allele for ADORA2A (rs5751862) and TNF-α were significantly more impaired for cognitive responses than their respective ancestral G/G genotypes. Carriers of the ancestral G/G genotype of ADORA2A rs5751862 were found to be very similar to the most resilient subjects for PVT lapses and Go/noGo commission errors. Carriers of the ancestral G/G genotype of COMT were close to the most vulnerable subjects. ADORA2A (rs5751862) was significantly associated with COMT (rs4680) (p = 0.001). In conclusion, we show that genetic polymorphisms in ADORA2A (rs5751862), TNF-α (rs1800629), and COMT (rs4680) are involved in creating profiles of high vulnerability or high resilience to sleep deprivation. (NCT03859882).

Concordance of multiple methods to define resiliency and vulnerability to sleep loss depends on Psychomotor Vigilance Test metric

Study Objectives Sleep restriction (SR) and total sleep deprivation (TSD) reveal well-established individual differences in Psychomotor Vigilance Test (PVT) performance. While prior studies have used different methods to categorize such resiliency/vulnerability, none have systematically investigated whether these methods categorize individuals similarly. Methods 41 adults participated in a 13-day laboratory study consisting of 2 baseline, 5 SR, 4 recovery, and one 36h TSD night. The PVT was administered every 2h during wakefulness. Three approaches (Raw Score [average SR performance], Change from Baseline [average SR minus average baseline performance], and Variance [intraindividual variance of SR performance]), and within each approach, six thresholds (±1 standard deviation and the best/worst performing 12.5%, 20%, 25%, 33%, and 50%) classified Resilient/Vulnerable groups. Kendall’s tau-b correlations examined the concordance of group categorizations of approaches within and between PVT lapses and 1/reaction time (RT). Bias-corrected and accelerated bootstrapped t-tests compared group performance. Results Correlations comparing the approaches ranged from moderate to perfect for lapses and zero to moderate for 1/RT. Defined by all approaches, the Resilient groups had significantly fewer lapses on nearly all study days. Defined by the Raw Score approach only, the Resilient groups had significantly faster 1/RT on all study days. Between-measures comparisons revealed significant correlations between the Raw Score approach for 1/RT and all approaches for lapses. Conclusion The three approaches defining vigilant attention resiliency/vulnerability to sleep loss resulted in groups comprised of similar individuals for PVT lapses but not for 1/RT. Thus, both method and metric selection for defining vigilant attention resiliency/vulnerability to sleep loss is critical.

O034 Rockabye sailor: investigating the impact of simulated motion on sleep and cognitive performance

Background Many naval vessels are designed with sleeping berths orientated in a fore/aft direction. Reorientating the berths changes the rocking from side-to-side to head-to-foot. It is unknown what effect rocking orientation may have on sleep. Aim This study aimed to investigate the impact of a simulated fore/aft orientation (side-to-side motion) with a simulated athwartships berth orientation (head-to-foot motion), on sleep quality and quantity, and cognitive performance. Method 21 participants (13M/8F; 24.0±4.8 years; BMI 21.1±2.5) slept in berths on a motion platform replicating vessel motion. In a repeated measures design, each participant slept under three conditions in randomised order: 1) no motion, 2) fore/aft orientation (side-to-side motion), and 3) athwartships orientation (head-to-foot motion). Measurements of sleep (ambulatory polysomnography), sleepiness (Karolinska Sleepiness Scale: KSS), and vigilance (Psychomotor Vigilance Test: PVT) were analysed using Mixed Effects ANOVA. Results Participants’ total sleep time was shorter (p&lt;0.001), sleep efficiency was reduced (p&lt;0.001), they woke more frequently (p&lt;0.001), and their sleep contained less REM (p&lt;0.001) in the athwartships orientation (head-to-foot motion) compared to the no motion, and fore/aft orientation (side-to-side motion) conditions. Participants’ also reported significantly higher sleepiness on KSS (p=0.006), poorer subjective sleep quality (p&lt;0.001), and displayed worse vigilant attention on PVT (p=0.03) following the athwartships orientation compared to the two other conditions. Discussion The simulated athwartships bunk orientation (head-to-foot motion) negatively impacted sleep and cognitive performance. These results may have implications for crew wellbeing. The data also gives unique theoretical insight into the effects of different types of rhythmic movement on sleep. Funding DSTG

P106 Evaluating the correlation between objective daytime sleepiness, daytime functioning and subjective sleepiness

Introduction Daytime sleepiness is typically assessed in clinical settings with the Multiple Sleep Latency Test (MSLT) and Maintenance of Wakefulness Test (MWT). However, these tests do not necessarily assess daytime functioning. This study aimed to assess the correlation between a 10-min Psychomotor Vigilance Test (PVT), as a measure of daytime functioning, and excessive daytime sleepiness as measured with the MSLT or MWT. Methods Patients attending the sleep clinic for assessments of daytime sleepiness underwent overnight polysomnography (PSG) and completed the Epworth Sleepiness Scale (ESS). The following day, patients completed four test sessions every 2h starting 1.5h after waking. Testing sessions included the Stanford Sleepiness Scale (SSS), PVT, MWT or MSLT. PVT lapses (reaction time &gt;500ms), SSS score and sleep latencies (MSLT and MWT) were averaged within participants across sessions and regression analyses performed to assess the relationship between PVT lapses and sleepiness measures. Results A total of 41 patients (BMI: 33.7±8.7kg/m²; aged 44.8±17.8 years) completed the study. Of these, 22 (19 F) underwent the MSLT and 19 (2 F) underwent the MWT. PVT lapses correlated with MWT mean sleep latency (r²=0.62; p&lt;0.001), ESS (r²= 0.19; p&lt;0.01) and SSS (r²= 0.12; p&lt;0.05) but not MSLT mean sleep latency (r²= 0.02; p = 0.50). Discussion In clinical practice, MWT and ESS are often used in conjunction to assess daytime functioning. Results suggest that the PVT could be used alongside MWT to aid clinical judgments around an individuals’ daytime functioning.

Multimodal Analysis of Eye Movements and Fatigue in a Simulated Glass Cockpit Environment

Pilot fatigue is a critical reason for aviation accidents related to human errors. Human-related accidents might be reduced if the pilots’ eye movement measures can be leveraged to predict fatigue. Eye tracking can be a non-intrusive viable approach that does not require the pilots to pause their current task, and the device does not need to be in direct contact with the pilots. In this study, the positive or negative correlations among the psychomotor vigilance test (PVT) measures (i.e., reaction times, number of false alarms, and number of lapses) and eye movement measures (i.e., pupil size, eye fixation number, eye fixation duration, visual entropy) were investigated. Then, fatigue predictive models were developed to predict fatigue using eye movement measures identified through forward and backward stepwise regressions. The proposed approach was implemented in a simulated short-haul multiphase flight mission involving novice and expert pilots. The results showed that the correlations among the measures were different based on expertise (i.e., novices vs. experts); thus, two predictive models were developed accordingly. In addition, the results from the regressions showed that either a single or a subset of the eye movement measures might be sufficient to predict fatigue. The results show the promise of using non-intrusive eye movements as an indicator for fatigue prediction and provides a foundation that can lead us closer to developing a near real-time warning system to prevent critical accidents.

Altered Hypothalamic Functional Connectivity Following Total Sleep Deprivation in Young Adult Males

Background: Sleep deprivation can markedly influence vigilant attention that is essential to complex cognitive processes. The hypothalamus plays a critical role in arousal and attention regulation. However, the functional involvement of the hypothalamus in attentional impairments after total sleep deprivation (TSD) remains unclear. The purpose of this study is to investigate the alterations in hypothalamic functional connectivity and its association with the attentional performance following TSD.Methods: Thirty healthy adult males were recruited in the study. Participants underwent two resting-state functional magnetic resonance imaging (rs-fMRI) scans, once in rested wakefulness (RW) and once after 36 h of TSD. Seed-based functional connectivity analysis was performed using rs-fMRI for the left and right hypothalamus. Vigilant attention was measured using a psychomotor vigilance test (PVT). Furthermore, Pearson correlation analysis was conducted to investigate the relationship between altered hypothalamic functional connectivity and PVT performance after TSD.Results: After TSD, enhanced functional connectivity was observed between the left hypothalamus and bilateral thalamus, bilateral anterior cingulate cortex, right amygdala, and right insula, while reduced functional connectivity was observed between the left hypothalamus and bilateral middle frontal gyrus (AlphaSim corrected, P &lt; 0.01). However, significant correlation between altered hypothalamic functional connectivity and PVT performance was not observed after Bonferroni correction (P &gt; 0.05).Conclusion: Our results suggest that TSD can lead to disrupted hypothalamic circuits, which may provide new insight into neural mechanisms of attention impairments following sleep deprivation.

Distinct and Dissociable EEG Networks Are Associated With Recovery of Cognitive Function Following Anesthesia-Induced Unconsciousness

The temporal trajectories and neural mechanisms of recovery of cognitive function after a major perturbation of consciousness is of both clinical and neuroscientific interest. The purpose of the present study was to investigate network-level changes in functional brain connectivity associated with the recovery and return of six cognitive functions after general anesthesia. High-density electroencephalograms (EEG) were recorded from healthy volunteers undergoing a clinically relevant anesthesia protocol (propofol induction and isoflurane maintenance), and age-matched healthy controls. A battery of cognitive tests (motor praxis, visual object learning test, fractal-2-back, abstract matching, psychomotor vigilance test, digital symbol substitution test) was administered at baseline, upon recovery of consciousness (ROC), and at half-hour intervals up to 3 h following ROC. EEG networks were derived using the strength of functional connectivity measured through the weighted phase lag index (wPLI). A partial least squares (PLS) analysis was conducted to assess changes in these networks: (1) between anesthesia and control groups; (2) during the 3-h recovery from anesthesia; and (3) for each cognitive test during recovery from anesthesia. Networks were maximally perturbed upon ROC but returned to baseline 30–60 min following ROC, despite deficits in cognitive performance that persisted up to 3 h following ROC. Additionally, during recovery from anesthesia, cognitive tests conducted at the same time-point activated distinct and dissociable functional connectivity networks across all frequency bands. The results highlight that the return of cognitive function after anesthetic-induced unconsciousness is task-specific, with unique behavioral and brain network trajectories of recovery.