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All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Linear Mixed-Effects Models for Human-in-the-Loop Tracking Experiment Data

Linear mixed-effects models provide several benefits over more traditional statistical inference tests that are particularly useful for most human-in-the-loop tracking experiment data. However, surprisingly, mixed models are virtually not used for the analysis of tracking experiment data. This paper uses of linear mixed-effects models to analyze combined tracking data from two previous human-in-the-loop roll tracking experiments that compared control behavior metrics collected in both a research aircraft and a motion-base simulator. In the experiments, pilots' behavior under 10 different motion configurations with varying motion filter gains and break frequencies was evaluated and compared to that in the real aircraft. The linear mixed-effects model analysis on the combined dataset confirmed the main statistical outcomes of the individual experiments. The main benefits of mixed models for this type of data were demonstrated by successfully combining data from two experiments that used different experimental conditions and of which one had an additional apparatus and the other a missing participant. Finally, the mixed-model analysis was able to explicitly test for scientifically relevant statistical differences in the dependent measures between the aircraft and simulator, as well as both experiments.

manual control↗
DOE OSTI2025

The temporal onset of associations of cortical proteins with cognitive resilience vary during late life

Background: Cortical proteins associated with cognitive resilience have been identified but their temporal onset in older adults is unknown. We present a multistage approach to first identify cortical proteins associated with cognitive resilience and then examine their associated temporal onset. Methods: We used data from a subset of 1088 decedents from two cohort-studies who had selected reaction monitoring proteomics from the dorsolateral prefrontal cortex, and at least 3 cognitive assessments. Cognition was assessed using a composite derived from 19 tests. We first used linear mixed-effects models to identify cortical proteins associated with cognitive resilience. We then used functional mixed-effects models to examine non-linear associations between proteins and cognitive resilience to identify their temporal onset. Results: Mean age at death was 90 years (SD = 6.4); 69 % were female. On average, cognition started to decline at around 15 years before death, with accelerated decline in the last 7 years. We identified 40 proteins associated with cognitive resilience, of which 17 proteins also showed non-linear associations. Non-linear associations indicated that higher levels of 10 proteins were associated with slower cognitive decline between 23 and 4 years before death. In contrast, higher levels of 7 proteins were associated with faster decline only within the last 7 years before death. Conclusions: Cognitive resilience proteins are differentially related to late-life cognitive aging; the onset of proteins that maintain cognition may begin many years before the onset of proteins that hasten cognitive decline. The temporal onset of cognitive resilience proteins may be crucial for timing efficacious interventions.

Zammit, Andrea↗
NASA NTRS2024

Oculometric Biomarkers of Visuomotor Deficits in Clinically Asymptomatic Patients With Systemic Lupus Erythematosus Undergoing Long-Term Hydroxychloroquine Treatment

Introduction: This study examines a set of oculomotor measurements, or “oculometric” biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. Methods: We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Results: Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Discussion: Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

eye movements↗
NASA NTRS2011

Reliability of Upright and Supine Power Measurements Using an Inertial Load Cycle Ergometer

Practical, reliable, and time efficient methods of measuring muscular power are desirable for both research and applied testing situations. The inertial-load cycling method (ILC; Power/Cycle, Austin, TX) requires subjects to pedal as fast as possible against the inertial load of a flywheel for only 3-5 seconds, which could help reduce the time and effort required for maximal power testing. PURPOSE: 1) To test the intramachine reliability of ILC over 3 separate sessions, 2) to compare postural stance (upright vs. supine) during testing, and 3) to compare the maximal power (Pmax) output measured using ILC to that obtained from traditional isokinetic and leg press testing. METHODS: Subjects (n = 12) were tested on 4 non-consecutive days. The following tests were done on the first day of testing: isometric knee extension, isokinetic knee extension at several speeds, isokinetic power/endurance at 180/sec (Biodex System 4), leg press maximal isometric force, and leg press power/endurance. The other 3 days consisted exclusively of ILC testing. Subjects performed 6 ILC tests in an upright position and 6 ILC tests in a supine position on each day. The starting position was counterbalanced. Mixed-effects linear modeling was used to determine if any differences existed between testing days and between upright and supine for Pmax and revolutions per minute at Pmax (RPMpk). Mixed-modeling was also used to calculate intraclass correlation coefficients (ICC) to determine the reliability of the ILC on each testing day for Pmax and RPMpk (ICCs were calculated separately for upright and supine). gKendall fs Tau a h was used to determine the association between ILC Pmax and isokinetic and leg press data. RESULTS: For Pmax, significant differences were found between days 1 and 2 (upright: p = 0.018; supine: p = 0.014) and between days 1 and 3 (upright: p = 0.001; supine: p = 0.002), but not between days 2 and 3 (upright: p = 0.422; supine: p = 0.501). Pmax ICC values were greater than or equal to 0.97 for all days in both positions. Also, no significant differences between upright and supine postures were found for Pmax. No significant differences between days were found for RPMpk; however, there was a significant posture effect (upright greater than supine). Moderate correlations were observed between ILC Pmax and isokinetic and leg press tests (upright: 0.64-0.79, supine: 0.52-0.82). CONCLUSIONS: Overall, ILC is a very reliable test. Since a significant difference was found between day 1 and the other ILC testing days, it is suggested that day 1 of ILC testing should be used as a familiarization session to allow for subject learning. No significant difference in Pmax was seen from test 3 to test 6. However, an increase of 1.3% was observed from test 4 to test 6. Therefore, although 4 tests may be sufficient for most subjects to produce Pmax, in some cases 6 tests may be required. PRACTICAL APPLICATIONS: No differences were seen in Pmax between upright and supine positions despite differing RPMpk. This suggests that ILC testing can be used to provide reliable testing both in an upright position (appropriate for athletes) and in research (e.g., bed rest) or rehabilitation settings where supine testing is necessary. Future research should evaluate whether peak power measurements obtained with the ILC are sensitive to changes such as that observed with training and de-training.

Wickwire, P. J.↗
NASA NTRS2016

Comparison of Structural and Functional Ocular Outcomes Between 14- and 70 Day Bed Rest

Purpose: To compare structural and functional ocular outcomes in healthy human subjects undergoing 14- and/or 70-day head-down-tilt bed rest (HDTBR). We hypothesized the amount of HDTBR-induced ocular changes be affected by the HDTBR duration. Methods: The studies were conducted at the NASA Flight Analogs Research Unit, The University of Texas Medical Branch at Galveston, Galveston, TX. Participants were selected using NASA standard screening procedures. Standardized NASA screening procedures and bed rest conditions (e.g., strict sleep-wake cycle, standardized diet, continuous video monitoring) were implemented in both studies. Participants maintained a 6deg HDTBR position for 14 and/or 70 consecutive days and did not engage in exercise. Weekly ophthalmological examinations were conducted in the sitting (pre/post-bed rest only) and HDT positions. Ocular outcomes of interest included: near best-corrected visual acuity (BCVA); spherical equivalent, as determined by cycloplegic autorefraction; Goldmann applanation tonometry and iCare (Icare Finland Oy, Espoo, Finland) intraocular pressure (IOP) measurement; color vision; red dot test; modified Amsler grid test; confrontational visual field; stereoscopic color fundus photography; Spectralis OCT (Heidelberg Engineering, GmbH, Heidelberg, Germany) retinal nerve fiber layer thickness (RNFLT), peripapillary and macular retinal thicknesses. Mixed-effects linear models were used to compare pre- and post-HDTBR observations between 14- and 70-day HDTBR for our continuously scaled outcomes.

Cromwell, R. L.↗
NASA NTRSDate not supplied

Light Improves Alertness and Mood during the Sleep Inertial Period following Slow Wave Sleep

Introduction: Waking from sleep, especially slow wave sleep (SWS), is associated with reduced alertness known as sleep inertia. Light improves alertness during sleep deprivation and circadian misalignment. In this study, we assessed the efficacy of light to improve alertness and mood immediately after waking from SWS. Methods: Twelve participants kept a sleep schedule of 8.5 h for 5 nights and 5 h for one night prior to the overnight laboratory visit (confirmed by actigraphy). Participants went to bed at their scheduled habitual bedtime in the laboratory and were monitored by standard polysomnography. After at least 5 min of SWS, participants were awoken and exposed to either red ambient light (control) or blue-enriched bright light (light) for 1 h. During this time, participants completed a subjective scale of alertness (Karolinska Sleepiness Scale, KSS) and visual analogue scales (VAS) of mood at 2 min, 17 min, 32 min, and 47 min after waking. Following this sleep inertia measurement period, all lights were turned off and participants were allowed to return to sleep. They were then awoken again from their subsequent SWS period and exposed to the opposite condition (control or light). A linear mixed-effects model with fixed effects of condition, time, and condition*time and a random effect of participant was used to determine the impact of light across the testing period. An average of baseline responses (pre-sleep) was included as a covariate. Results: Compared to the control condition, participants exposed to bright blue-enriched light reported feeling more alert (KSS: F1,77=4.955, p=.029; VASalert: F1,77=8.226, p=.005), more cheerful (VAScheerful: F1,77=8.615, p=.004), less depressed (VASdepressed: F1,77=4.649, p=.034), and less lethargic (VASlethargic: F1,77=5.652, p=.020). Discussion: Exposure to blue-enriched bright light immediately after waking from SWS may help to improve subjective alertness and mood. Future analyses will explore whether these findings extend to effects on cognitive performance.

alertness↗
NASA NTRSDate not supplied

Blue-enriched Light Improves Alertness and Mood Following Abrupt Awakening from Slow Wave Sleep

INTRODUCTION: All crew on the International Space Station (ISS) have a sleep opportunity at the same time. Emergencies arising during this time require all crew members to be abruptly awoken from sleep and to be alert, ready to work as a team, and to perform safety-critical tasks soon after waking. However, crew may experience sleep inertia after waking, which is associated with reduced alertness, poor mood, and impaired performance, especially if woken from deep sleep (slow wave sleep, SWS). Light has been shown to improve alertness during sleep deprivation and circadian misalignment. In this study, we assessed the efficacy of blue-enriched light to improve alertness and mood immediately after waking from SWS, i.e., during the sleep inertia period. METHODS: Twelve participants kept a sleep schedule of 8.5 h for 5 nights and 5 h for one night prior to the overnight laboratory visit (confirmed by actigraphy). Participants went to bed at their scheduled habitual bedtime in the laboratory and were monitored by standard polysomnography. After at least 5 min of SWS, participants were awoken and exposed to either red ambient light (control) or blue-enriched light (light) for 1 h. During this time, participants completed a subjective scale of alertness (Karolinska Sleepiness Scale, KSS) and visual analogue scales (VAS) of mood at 2 min, 17 min, 32 min, and 47 min after waking. Following this sleep inertia measurement period, all lights were turned off and participants were allowed to return to sleep. They were then awoken again from their subsequent SWS period and exposed to the opposite condition (control or light). A linear mixed-effects model with fixed effects of condition, time, and condition*time and a random effect of participant was used to determine the impact of light across the testing period. An average of baseline responses (pre-sleep) was included as a covariate. RESULTS: Compared to the control condition, participants exposed to blue-enriched light reported feeling more alert (KSS: F1,77=4.955, p=.029; VASalert: F1,77=8.226, p=.005), more cheerful (VAScheerful: F1,77=8.615, p=.004), less depressed (VASdepressed: F1,77=4.649, p=.034), and less lethargic (VASlethargic: F1,77=5.652, p=.020). DISCUSSION: Exposure to blue-enriched light immediately after waking from SWS may help to improve subjective alertness and mood. Future analyses will explore whether these findings extend to effects on cognitive performance. This countermeasure to sleep inertia may be suitable for implementation to alert crew members during mid-sleep emergencies but requires further testing in field settings.

alertness↗
NASA NTRSDate not supplied

Rise and Shine: Using Light as a Countermeasure to Sleep Inertia

INTRODUCTION: Sleep inertia describes the phenomenon of sleepiness and poor performance experienced after waking from sleep. This period of impaired alertness and performance is of significant concern to workers who nap on shift, or work on-call and are required to perform safety-critical tasks soon after waking (e.g., emergency services, healthcare, military). Light has been shown to acutely improve alertness during sleep deprivation and circadian misalignment. In this study, we assessed the efficacy of blue-enriched light to improve alertness and mood immediately after waking from SWS, i.e., during the sleep inertia period. METHODS: Twelve participants kept a sleep schedule of 8.5 h for 5 nights and 5 h for one night prior to the overnight laboratory visit (confirmed by actigraphy). Participants went to bed at their scheduled habitual bedtime in the laboratory and were monitored by standard polysomnography. After at least 5 min of SWS, participants were awoken and exposed to either red ambient light (control) or blue-enriched light (light) for 1 h. During this time, participants completed a subjective scale of alertness (Karolinska Sleepiness Scale, KSS) and visual analogue scales (VAS) of mood at 2 min, 17 min, 32 min, and 47 min after waking. Following this sleep inertia measurement period, all lights were turned off and participants were allowed to return to sleep. They were then awoken again from their subsequent SWS period and exposed to the opposite condition (control or light). A linear mixed-effects model with fixed effects of condition, time, and condition*time and a random effect of participant was used to determine the impact of light across the testing period. An average of baseline responses (pre-sleep) was included as a covariate. RESULTS: Compared to the control condition, participants exposed to blue-enriched light reported feeling more alert (KSS: F1,77=4.955, p=.029; VASalert: F1,77=8.226, p=.005), more cheerful (VAScheerful: F1,77=8.615, p=.004), less depressed (VASdepressed: F1,77=4.649, p=.034), and less lethargic (VASlethargic: F1,77=5.652, p=.020). DISCUSSION: Exposure to blue-enriched light immediately after waking from SWS may help to improve subjective alertness and mood. Future analyses will explore whether these findings extend to effects on cognitive performance. This countermeasure to sleep inertia may be suitable for implementation to alert crew members during mid-sleep emergencies but requires further testing in field settings.

alertness↗
NASA NTRSDate not supplied

Sleep, Sleepiness, and Performance Across Three In-Flight Bunk Rest Opportunities

Introduction: Airline pilots are required to take a rest break in a bunk during long-haul flights in an effort to reduce sleepiness during critical phases of flight. It is unclear, however, whether each rest break affords equal opportunity for sleep. We aimed to characterize sleep, sleepiness, and performance outcomes across three in-flight rest breaks during long-haul flights. Methods: Thirty-seven pilots wore actiwatches and completed sleep diaries for approximately two weeks while flying a variety of long-haul routes (n=126 flights). Self-reported in-flight bunk rest (BR) periods were used to set rest intervals and sleep was estimated within these intervals using actigraphy software (wake threshold set to medium). Pilots provided Karolinska Sleepiness Scale ratings (KSS) and performed a 5-minute psychomotor vigilance task (PVT) before landing. A linear mixed-effects model with participant included as a random effect and allowed to vary by intercept was used to assess differences between BR opportunities. Results : The majority (97%, n=122) of bunk rest periods contained sleep (as estimated by actigraphy). The mean (+/- standard deviation) sleep duration for the first, middle, and third BR opportunity was 152.8 (69.7), 149.2 (44.1), 125.2 (44.9) minutes, respectively. There was a significant effect of BR opportunity for sleep duration (F2,54 = 3.747, p=.03) and KSS (F2,44 = 7.869, p=.001). Bonferroni adjusted planned pairwise contrasts revealed that pilots using the third BR obtained significantly less sleep than in the first BR (p=.029). KSS ratings prior to landing were higher for the third BR compared to both the first (p=.001) and middle BR (p=.017). There were no significant differences for PVT speed or lapses (all p>05). Conclusion: These results suggest that the last rest break is associated with shorter sleep, lower alertness, and no differences in performance relative to the other rest breaks. Further analysis is required to determine whether the higher KSS ratings following the third rest break are associated with sleep inertia, or whether other factors may be involved.

sleepiness↗
NASA NTRS2015

NASA's Functional Task Test: High Intensity Exercise Improves the Heart Rate Response to a Stand Test Following 70 Days of Bedrest

Cardiovascular adaptations due to spaceflight are modeled with 6deg head-down tilt bed rest (BR) and result in decreased orthostatic tolerance. We investigated if high-intensity resistive and aerobic exercise with and without testosterone supplementation would improve the heart rate (HR) response to a 3.5-min stand test and how quickly these changes recovered following BR. During 70 days of BR male subjects performed no exercise (Control, n=10), high intensity supine resistive and aerobic exercise (Exercise, n=9), or supine exercise plus supplemental testosterone (Exercise+T, n=8; 100 mg i.m., weekly in 2-week on/off cycles). We measured HR for 2 min while subjects were prone and for 3 min after standing twice before and 0, 1, 6, and 11 days after BR. Mixed-effects linear regression models were used to evaluate group, time, and interaction effects. Compared to pre-bed rest, prone HR was elevated on BR+0 and BR+1 in Control, but not Exercise or Exercise+T groups, and standing HR was greater in all 3 groups. The increase in prone and standing HR in Control subjects was greater than either Exercise or Exercise+T groups and all groups recovered by BR+6. The change in HR from prone to standing more than doubled on BR+0 in all groups, but was significantly less in the Exericse+T group compared to the Control, but not Exercise group. Exercise reduces, but does not prevent the increase in HR observed in response to standing. The significantly lower HR response in the Exercise+T group requires further investigation to determine physiologic significance.

Laurie, Steven S.↗
NASA NTRSDate not supplied

Changes in Alertness and Performance Over Time During Long-Haul Flying Across Multiple Time Zones

BACKGROUND: Long-haul pilots experience high levels of fatigue and circadian disruptions due to long work hours and flying over multiple time zones. The aim of this study was to describe changes in alertness and performance among flight crews during long-haul flights crossing multiple time zones. METHODS: All pilots flying long-haul operations from a single airline were eligible to participate. All participants collected data for ~2 weeks of their normal work schedule within airline operations, with at least two long-haul rotations, including rest days and layovers. Participants wore an Actiwach throughout the entire study period and completed a sleep diary (at bedtime, upon waking up and after each nap). Each participant completed a 5-min Psychomotor Vigilance Task (PVT) and a Karolinska Sleepiness Scale (KSS) pre-flight, on top-of-descent (TOD; inflight) and at the end of each flight (post-flight). Response speed (1/RT x 1000), lapses (RT > 500 ms), and alertness were assessed over time pre-flight, TOD, post-flight, using mixed-effects models with participant as a random factor. Linear models were assumed for response speed and alertness, while a negative binomial distribution was specified for lapses due to overdispersion. RESULTS: Forty-four long-haul pilots participated in the study (5 female; mean age 44.25 ± 10.06 yrs; mean flight hours 9834.3; ± 5334.1 hrs). Lapses increased post-flight relative to pre-flight (F(2, 665) = 3.67, p < 0.05). There was a main effect of response speed (F(2, 665) = 21.45, p < 0.001) with slower speed inflight and postflight compared to preflight (p < 0.001). The KSS increased over time from M = 4.02 (± 1.35) preflight to M = 5.15 (± 1.58) inflight, to M = 6.7 (± 1.51) postflight (F(2, 701) = 182.63, p < 0.001). DISCUSSION: Our preliminary analyses showed that both performance and subjective alertness worsened from the beginning to the end of a flight. Additional analyses will be conducted to investigate the changes in alertness and performance by direction of travel, sleep history, and flight timing and duration.

long-haul↗
NASA NTRS2010

60 Days of Head-down Bedrest Differentially Alters Venous Function in Lower and Upper Body Between Healthy Men and Women

The incidence of orthostatic intolerance after space flight is disproportionally higher in female compared to male crewmembers (83% vs. 20%). Experimental and human data suggest that the loss of orthostatic tolerance is due, at least in part, to microgravity-induced changes in venous compliance and that these changes are specific to the lower body. It is unknown however, whether the changes in venous compliance are different between males and females after space flight, and whether this is related to the disparity in orthostatic intolerance between the sexes. Using 6deg head-down bed rest (BR) as a model of space flight, we tested the following hypotheses; 1) females, compared to males, would experience a greater increase in venous compliance in dorsal foot veins as an effect of BR and 2) no differences in venous compliance would be found in dorsal hand veins between sexes and across BR days. Using 2-D ultrasound, dorsal hand (DHV) and foot vein (DFV) responses (diameter; expressed as sq mm) to 40 mmHg of congestion pressure (compliance) and to intravenous infusion of phenylephrine (PE; 3160ng/min) were determined in 10 females and 16 males before and after 60 days of BR. The relation between changes in vein diameter (in response to pressure and PE), sex, limb, and BR days were determined using a mixed-effect linear regression. It was found that after 60 days of BR, DFV dilator response to pressure was significantly greater in females and significantly less in males compared to pre-BR. As expected, there were no differences in DHV dilator response between sexes nor was there a significant difference between pre and post measures within groups. Notably, the venoconstrictor response to infusions of PE in the DHV and DFV where similar between sexes and across BR days. In conclusion, this study demonstrates that after 60 days of BR, dorsal foot veins are more compliant in women and less compliant in men. Moreover, the changes in lower body vein compliance in females do not appear to be due to changes in vasoconstrictor tone as their response to PE was preserved and similar to that in males. Taken together these data suggest that the higher incidence of orthostatic intolerance in females after space flight is due to increased venous compliance in the lower body which could translate to lower venous filling pressures and a reduced stroke volume.

Westby, Christian M.↗