INTRODUCTION To date, 559 humans have been flown into space, but long-duration (>300 days) missions are rare (n = 8 total). Long-duration missions that will take humans to Mars and beyond are planned by public and private entities for the 2020s and 2030s; therefore, comprehensive studies are needed now to assess the impact of long-duration spaceflight on the human body, brain, and overall physiology. The space environment is made harsh and challenging by multiple factors, including confinement, isolation, and exposure to environmental stressors such as microgravity, radiation, and noise. The selection of one of a pair of monozygotic (identical) twin astronauts for NASA’s first 1-year mission enabled us to compare the impact of the spaceflight environment on one twin to the simultaneous impact of the Earth environment on a genetically matched subject. RATIONALE The known impacts of the spaceflight environment on human health and performance, physiology, and cellular and molecular processes are numerous and include bone density loss, effects on cognitive performance, microbial shifts, and alterations in gene regulation. However, previous studies collected very limited data, did not integrate simultaneous effects on multiple systems and data types in the same subject, or were restricted to 6-month missions. Measurement of the same variables in an astronaut on a year-long mission and in his Earth-bound twin indicated the biological measures that might be used to determine the effects of spaceflight. Presented here is an integrated longitudinal, multidimensional description of the effects of a 340-day mission onboard the International Space Station. RESULTS Physiological, telomeric, transcriptomic, epigenetic, proteomic, metabolomic, immune, microbiomic, cardiovascular, vision-related, and cognitive data were collected over 25 months. Some biological functions were not significantly affected by spaceflight, including the immune response (T cell receptor repertoire) to the first test of a vaccination in flight. However, significant changes in multiple data types were observed in association with the spaceflight period; the majority of these eventually returned to a preflight state within the time period of the study. These included changes in telomere length, gene regulation measured in both epigenetic and transcriptional data, gut microbiome composition, body weight, carotid artery dimensions, subfoveal choroidal thickness and peripapillary total retinal thickness, and serum metabolites. In addition, some factors were significantly affected by the stress of returning to Earth, including inflammation cytokines and immune response gene networks, as well as cognitive performance. For a few measures, persistent changes were observed even after 6 months on Earth, including some genes’ expression levels, increased DNA damage from chromosomal inversions, increased numbers of short telomeres, and attenuated cognitive function. CONCLUSION Given that the majority of the biological and human health variables remained stable, or returned to baseline, after a 340-day space mission, these data suggest that human health can be mostly sustained over this duration of spaceflight. The persistence of the molecular changes (e.g., gene expression) and the extrapolation of the identified risk factors for longer missions (>1 year) remain estimates and should be demonstrated with these measures in future astronauts. Finally, changes described in this study highlight pathways and mechanisms that may be vulnerable to spaceflight and may require safeguards for longer space missions; thus, they serve as a guide for targeted countermeasures or monitoring during future missions.

The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight.

Background: Particulate air pollution’s physical health effects are well known, but associations between particulate matter (PM) exposure and mental illness have not yet been established. However, ...

Air Pollution (Particulate Matter) Exposure and Associations with Depression, Anxiety, Bipolar, Psychosis and Suicide Risk: A Systematic Review and Meta-Analysis.

A novel component of the European Research Area will require national funders' cooperation.

A New Era

The human gut microbiome can influence health through the brain-gut-microbiome axis. Growing evidence suggests that the gut microbiome can influence sleep quality. Previous studies that have examined sleep deprivation and the human gut microbiome have yielded conflicting results. A recent study found that sleep deprivation leads to changes in gut microbiome composition while a different study found that sleep deprivation does not lead to changes in gut microbiome. Accordingly, the relationship between sleep physiology and the gut microbiome remains unclear. To address this uncertainty, we used actigraphy to quantify sleep measures coupled with gut microbiome sampling to determine how the gut microbiome correlates with various measures of sleep physiology. We measured immune system biomarkers and carried out a neurobehavioral assessment as these variables might modify the relationship between sleep and gut microbiome composition. We found that total microbiome diversity was positively correlated with increased sleep efficiency and total sleep time, and was negatively correlated with wake after sleep onset. We found positive correlations between total microbiome diversity and interleukin-6, a cytokine previously noted for its effects on sleep. Analysis of microbiome composition revealed that within phyla richness of Bacteroidetes and Firmicutes were positively correlated with sleep efficiency, interleukin-6 concentrations and abstract thinking. Finally, we found that several taxa (Lachnospiraceae, Corynebacterium, and Blautia) were negatively correlated with sleep measures. Our findings initiate linkages between gut microbiome composition, sleep physiology, the immune system and cognition. They may lead to mechanisms to improve sleep through the manipulation of the gut microbiome.

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Gut Microbiome Diversity Is Associated with Sleep Physiology in Humans

Sleep deprivation, vigilant attention, and brain function: a review.

To evaluate the quality of available evidence on the effects of environmental noise exposure on sleep a systematic review was conducted. The databases PSYCINFO, PubMed, Science Direct, Scopus, Web of Science and the TNO Repository were searched for non-laboratory studies on the effects of environmental noise on sleep with measured or predicted noise levels and published in or after the year 2000. The quality of the evidence was assessed using GRADE criteria. Seventy four studies predominately conducted between 2000 and 2015 were included in the review. A meta-analysis of surveys linking road, rail, and aircraft noise exposure to self-reports of sleep disturbance was conducted. The odds ratio for the percent highly sleep disturbed for a 10 dB increase in Lnight was significant for aircraft (1.94; 95% CI 1.61–2.3), road (2.13; 95% CI 1.82–2.48), and rail (3.06; 95% CI 2.38–3.93) noise when the question referred to noise, but non-significant for aircraft (1.17; 95% CI 0.54–2.53), road (1.09; 95% CI 0.94–1.27), and rail (1.27; 95% CI 0.89–1.81) noise when the question did not refer to noise. A pooled analysis of polysomnographic studies on the acute effects of transportation noise on sleep was also conducted and the unadjusted odds ratio for the probability of awakening for a 10 dBA increase in the indoor Lmax was significant for aircraft (1.35; 95% CI 1.22–1.50), road (1.36; 95% CI 1.19–1.55), and rail (1.35; 95% CI 1.21–1.52) noise. Due to a limited number of studies and the use of different outcome measures, a narrative review only was conducted for motility, cardiac and blood pressure outcomes, and for children’s sleep. The effect of wind turbine and hospital noise on sleep was also assessed. Based on the available evidence, transportation noise affects objectively measured sleep physiology and subjectively assessed sleep disturbance in adults. For other outcome measures and noise sources the examined evidence was conflicting or only emerging. According to GRADE criteria, the quality of the evidence was moderate for cortical awakenings and self-reported sleep disturbance (for questions that referred to noise) induced by traffic noise, low for motility measures of traffic noise induced sleep disturbance, and very low for all other noise sources and investigated sleep outcomes.

WHO Environmental Noise Guidelines for the European Region: A Systematic Review on Environmental Noise and Effects on Sleep.

BACKGROUND: Sustained high-level cognitive performance is of paramount importance for the success of space missions, which involve environmental, physiological, and psychological stressors that may aff ect brain functions. Despite subjective symptom reports of cognitive fl uctuations in spacefl ight, the nature of neurobehavioral functioning in space has not been clarifi ed. METHODS: We developed a computerized cognitive test battery ( Cognition ) that has sensitivity to multiple cognitive domains and was specifi cally designed for the high-performing astronaut population. Cognition consists of 15 unique forms of 10 neuropsychological tests that cover a range of cognitive domains, including emotion processing, spatial orientation, and risk decision making. Cognition is based on tests known to engage specifi c brain regions as evidenced by functional neuroimaging. Here we describe the fi rst normative and acute total sleep deprivation data on the Cognition test battery as well as several eff orts underway to establish the validity, sensitivity, feasibility, and acceptability of Cognition . RESULTS: Practice eff ects and test-retest variability diff ered substantially between the 10 Cognition tests, illustrating the importance of normative data that both refl ect practice eff ects and diff erences in stimulus set diffi culty in the population of interest. After one night without sleep, medium to large eff ect sizes were observed for 3 of the 10 tests addressing vigilant attention (Cohen ’ s d 5 1.00), cognitive throughput (d 5 0.68), and abstract reasoning (d 5 0.65). CONCLUSIONS: In addition to providing neuroimaging-based novel information on the eff ects of spacefl ight on a range of cognitive functions, Cognition will facilitate comparing the eff ects of ground-based analogues to spacefl ight, increase consistency across projects, and thus enable meta-analyses.

Development and Validation of the Cognition Test Battery for Spaceflight

Study objectives The Psychomotor Vigilance Test (PVT) is reported to be free of practice effects that can otherwise confound the effects of sleep loss and circadian misalignment on performance. This differentiates the PVT from more complex cognitive tests. To the best of our knowledge, no study has systematically investigated practice effects on the PVT across multiple outcome domains, depending on administration interval, and in ecologically more valid settings. Methods We administered a validated 3-minute PVT (PVT-B) 16 times in 45 participants (23 male, mean ± SD age 32.6 ± 7.3 years, range 25-54 years) with administration intervals of ≥10 days, ≤5 days, or 4 times per day. We investigated linear and logarithmic trends across repeated administrations in 10 PVT-B outcome variables. Results The fastest 10% of response times (RT; plin = .0002), minimum RT (plog = .0010), and the slowest 10% of reciprocal RT (plog = .0124) increased while false starts (plog = 0.0050) decreased with repeated administration, collectively decreasing RT variability (plog = .0010) across administrations. However, the observed absolute changes were small (e.g., -0.03 false starts per administration, linear fit) and are probably irrelevant in practice. Test administration interval did not modify the effects of repeated administration on PVT-B performance (all p > .13 for interaction). Importantly, mean and median RT, response speed, and lapses, which are among the most frequently used PVT outcomes, did not change systematically with repeated administration. Conclusions PVT-B showed stable performance across repeated administrations. Combined with its high sensitivity, this corroborates the status of the PVT as the de facto gold standard measure of the neurobehavioral effects of sleep loss and circadian misalignment.

Repeated Administration Effects on Psychomotor Vigilance Test Performance.

Background Neuropsychological changes that may occur due to the environmental and psychological stressors of prolonged spaceflight motivated the development of the Cognition Test Battery. The battery was designed to assess multiple domains of neurocognitive functions linked to specific brain systems. Tests included in Cognition have been validated, but not in high-performing samples comparable to astronauts, which is an essential step toward ensuring their usefulness in long-duration space missions. Methods We administered Cognition (on laptop and iPad) and the WinSCAT, counterbalanced for order and version, in a sample of 96 subjects (50% women; ages 25-56 yr) with at least a Master's degree in science, technology, engineering, or mathematics (STEM). We assessed the associations of age, sex, and administration device with neurocognitive performance, and compared the scores on the Cognition battery with those of WinSCAT. Confirmatory factor analysis compared the structure of the iPad and laptop administration methods using Wald tests. Results Age was associated with longer response times (mean β = 0.12) and less accurate (mean β = -0.12) performance, women had longer response times on psychomotor (β = 0.62), emotion recognition (β = 0.30), and visuo-spatial (β = 0.48) tasks, men outperformed women on matrix reasoning (β = -0.34), and performance on an iPad was generally faster (mean β = -0.55). The WinSCAT appeared heavily loaded with tasks requiring executive control, whereas Cognition assessed a larger variety of neurocognitive domains. Discussion Overall results supported the interpretation of Cognition scores as measuring their intended constructs in high performing astronaut analog samples.Moore TM, Basner M, Nasrini J, Hermosillo E, Kabadi S, Roalf DR, McGuire S, Ecker AJ, Ruparel K, Port AM, Jackson CT, Dinges DF, Gur RC. Validation of the Cognition Test Battery for spaceflight in a sample of highly educated adults. Aerosp Med Hum Perform. 2017; 88(10):937-946.

Validation of the Cognition Test Battery for Spaceflight in a Sample of Highly Educated Adults.

Study Objectives: Environmental noise exposure disturbs sleep and impairs recuperation, and may contribute to the increased risk for (cardiovascular)
disease. Noise policy and regulation are usually based on average responses despite potentially large inter-individual differences in the effects of traffic noise
on sleep. In this analysis, we investigated what percentage of the total variance in noise-induced awakening reactions can be explained by stable interindividual
differences.
Methods: We investigated 69 healthy subjects polysomnographically (mean ± standard deviation 40 ± 13 years, range 18–68 years, 32 male) in this
randomized, balanced, double-blind, repeated measures laboratory study. This study included one adaptation night, 9 nights with exposure to 40, 80, or 120
road, rail, and/or air traffic noise events (including one noise-free control night), and one recovery night.
Results: Mixed-effects models of variance controlling for reaction probability in noise-free control nights, age, sex, number of noise events, and study night
showed that 40.5% of the total variance in awakening probability and 52.0% of the total variance in EEG arousal probability were explained by inter-individual
differences. If the data set was restricted to nights (4 exposure nights with 80 noise events per night), 46.7% of the total variance in awakening probability and
57.9% of the total variance in EEG arousal probability were explained by inter-individual differences. The results thus demonstrate that, even in this relatively
homogeneous, healthy, adult study population, a considerable amount of the variance observed in noise-induced sleep disturbance can be explained by interindividual
differences that cannot be explained by age, gender, or specific study design aspects.
Conclusions: It will be important to identify those at higher risk for noise induced sleep disturbance. Furthermore, the custom to base noise policy and
legislation on average responses should be re-assessed based on these findings.

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Sarah McGuire

Papers

WHO Environmental Noise Guidelines for the European Region: A Systematic Review on Environmental Noise and Effects on Sleep.

Development and Validation of the Cognition Test Battery for Spaceflight

Repeated Administration Effects on Psychomotor Vigilance Test Performance.

Validation of the Cognition Test Battery for Spaceflight in a Sample of Highly Educated Adults.

Inter-individual Differences in the Effects of Aircraft Noise on Sleep Fragmentation