The human biology of spaceflight.

To expand the human exploration footprint and reach Mars in the 2030s, we must explore how humans survive and thrive in demanding, unusual, and novel ecologies (i.e., extreme environments). In the extreme conditions encountered during human spaceflight, there is a need to understand human functioning and response in a more rigorous theoretically informed way. Current models of human performance in space-relevant environments and human space science are often operationally focused, with emphasis on acute physiological or behavioral outcomes. However, integrating current perspectives in human biology allows for a more holistic and complete understanding of how humans function over a range of time in an extreme environment. Here, we show how the use of evolution-informed frameworks (i.e., models of life history theory to organize the adaptive pressures of spaceflight and biocultural perspectives) coupled with the use of mixed-methodological toolkits can shape models that better encompass the scope of biobehavioral human adjustment to long-duration space travel and extra-terrestrial habitation. Further, we discuss how we can marry human biology perspectives with the rigorous programmatic structures developed for spaceflight to model other unknown and nascent extremes.

Team Physiological Dynamics: A Critical Review.

OBJECTIVE: Review the use of physiological measurement in team settings and propose recommendations to improve the state of the science. BACKGROUND: New sensor and analytical capabilities enable exploration of relationships between team members' physiological dynamics. We conducted a review of physiological measures used in research on teams to understand (1) how these measures are theoretically and operationally related to team constructs and (2) what types of validity evidence exist for physiological measurement in team settings. METHOD: We identified 32 articles that investigated task-performing teams using physiological data. Articles were coded on several dimensions, including team characteristics. Study findings were categorized by relationships tested between team physiological dynamics (TPD) and team inputs, mediators/processes, outputs, or psychometric properties. RESULTS: TPD researchers overwhelmingly measure single physiological systems. Although there is research linking TPD to inputs and outputs, the research on processes is underdeveloped. CONCLUSION: We recommend several theoretical, methodological, and statistical themes to expand the growth of the TPD field. APPLICATION: Physiological measures, once established as reliable indicators of team functioning, might be used to diagnose suboptimal team states and cue interventions to ameliorate these states.

Similarities in error processing establish a link between saccade prediction at baseline and adaptation performance.

Adaptive processes are crucial in maintaining the accuracy of body movements and rely on error storage and processing mechanisms. Although classically studied with adaptation paradigms, evidence of these ongoing error-correction mechanisms should also be detectable in other movements. Despite this connection, current adaptation models are challenged when forecasting adaptation ability with measures of baseline behavior. On the other hand, we have previously identified an error-correction process present in a particular form of baseline behavior, the generation of predictive saccades. This process exhibits long-term intertrial correlations that decay gradually (as a power law) and are best characterized with the tools of fractal time series analysis. Since this baseline task and adaptation both involve error storage and processing, we sought to find a link between the intertrial correlations of the error-correction process in predictive saccades and the ability of subjects to alter their saccade amplitudes during an adaptation task. Here we find just such a relationship: the stronger the intertrial correlations during prediction, the more rapid the acquisition of adaptation. This reinforces the links found previously between prediction and adaptation in motor control and suggests that current adaptation models are inadequate to capture the complete dynamics of these error-correction processes. A better understanding of the similarities in error processing between prediction and adaptation might provide the means to forecast adaptation ability with a baseline task. This would have many potential uses in physical therapy and the general design of paradigms of motor adaptation.

Characterizing dehydration in short-term spaceflight using evidence from Project Mercury.

Short-term spaceflight is commonly perceived as posing minimal risk to human health and performance. However, despite their duration, short-term flights potentially induce acute physiological changes that create risk to crews. One such change is dehydration (primarily body water loss) due to a heat-stressed environment. Such loss, if severe and prolonged, can lead to decrements in performance as well as increase the risk of more serious medical conditions. Though the general mechanisms of dehydration are broadly understood, the rate and extent of dehydration in short-term spaceflight has not been characterized. Combining data from the six spaceflights of the US Mercury program with a causal diagram illustrating the mechanisms of dehydration, we fit a path model to estimate the causal effects for all pathways in the causal model. Results demonstrate that Mercury astronauts experienced some degree of dehydration across the range of suited time and that the relationship between suited time and dehydration appears to be logarithmic. We discuss causal interpretations of the results and how the results from this and similar analyses can inform countermeasure development for short-term spaceflight.

Comparison of Asymmetry between Perceptual, Ocular, and Postural Vestibular Screening Tests.

BACKGROUND: A better understanding of how vestibular asymmetry manifests across tests is important due to its potential implications for balance dysfunction, motion sickness susceptibility, and adaptation to new environments. OBJECTIVE: We report the results of multiple tests for vestibular asymmetry in 32 healthy participants. METHODS: Asymmetry was measured using perceptual reports during unilateral centrifugation, oculomotor responses during visual alignment tasks, vestibulo-ocular reflex gain during head impulse tests, and body rotation during stepping tests. RESULTS: A significant correlation was observed between asymmetries of subjective visual vertical and verbal report during unilateral centrifugation. Another significant correlation was observed between the asymmetries of ocular alignment, vestibulo-ocular reflex gain, and body rotation. CONCLUSIONS: These data suggest that there are underlying vestibular asymmetries in healthy individuals that are consistent across various vestibular challenges. In addition, these findings have value in guiding test selection during experimental design for assessing vestibular asymmetry in healthy adults.

Circuits and Biomarkers of the Central Nervous System Relating to Astronaut Performance: Summary Report for a NASA-Sponsored Technical Interchange Meeting.

Biomarkers, ranging from molecules to behavior, can be used to identify thresholds beyond which performance of mission tasks may be compromised and could potentially trigger the activation of countermeasures. Identification of homologous brain regions and/or neural circuits related to operational performance may allow for translational studies between species. Three discussion groups were directed to use operationally relevant performance tasks as a driver when identifying biomarkers and brain regions or circuits for selected constructs. Here we summarize small-group discussions in tables of circuits and biomarkers categorized by (a) sensorimotor, (b) behavioral medicine and (c) integrated approaches (e.g., physiological responses). In total, hundreds of biomarkers have been identified and are summarized herein by the respective group leads. We hope the meeting proceedings become a rich resource for NASA's Human Research Program (HRP) and the community of researchers.

Using prediction errors to drive saccade adaptation: the implicit double-step task.

A prediction-based error signal, neurally computed as the difference between predicted and observed movement outcomes, has been proposed as the driving force for motor learning. This suggests that the generation of predictive saccades to periodically paced targets-whose performance accuracy is actively maintained using this same error signal-invokes the motor-learning network. We examined whether a simple predictive-saccade task (implicit double-step adaptation, in which targets are gradually displaced outward to exaggerate normal hypometric movement errors) can stand in place of a traditional double-step saccade-adaptation task to induce an increase in saccade gain. We find that the implicit double-step adaptation task can induce significant gain-increase adaptation (of comparable magnitude to that of the standard double-step task) in normal control subjects. Unlike control subjects, patients with impaired cerebella are unable to adapt their saccades in response to this paradigm; this implies that the cerebellum is crucial for processing prediction-based error signals for motor learning.

Sensorimotor adaptation error signals are derived from realistic predictions of movement outcomes.

Neural systems that control movement maintain accuracy by adaptively altering motor commands in response to errors. It is often assumed that the error signal that drives adaptation is equivalent to the sensory error observed at the conclusion of a movement; for saccades, this is typically the visual (retinal) error. However, we instead propose that the adaptation error signal is derived as the difference between the observed visual error and a realistic prediction of movement outcome. Using a modified saccade-adaptation task in human subjects, we precisely controlled the amount of error experienced at the conclusion of a movement by back-stepping the target so that the saccade is hypometric (positive retinal error), but less hypometric than if the target had not moved (smaller retinal error than expected). This separates prediction error from both visual errors and motor corrections. Despite positive visual errors and forward-directed motor corrections, we found an adaptive decrease in saccade amplitudes, a finding that is well-explained by the employment of a prediction-based error signal. Furthermore, adaptive changes in movement size were linearly correlated to the disparity between the predicted and observed movement outcomes, in agreement with the forward-model hypothesis of motor learning, which states that adaptation error signals incorporate predictions of motor outcomes computed using a copy of the motor command (efference copy).

Characterizing high-velocity angular vestibulo-ocular reflex function in service members post-blast exposure.

Blasts (explosions) are the most common mechanism of injury in modern warfare. Traumatic brain injury (TBI) and dizziness are common sequelae associated with blasts, and many service members (SMs) report symptoms worsen with activity. The purpose of this study was to measure angular vestibulo-ocular reflex gain (aVOR) of blast-exposed SMs with TBI during head impulse testing. We also assessed their symptoms during exertion. Twenty-four SMs recovering from TBI were prospectively assigned to one of two groups based on the presence or absence of dizziness. Wireless monocular scleral search coil and rate sensor were used to characterize active and passive yaw and pitch head and eye rotations. Visual analog scale (VAS) was used to monitor symptoms during fast walking/running. For active yaw head impulses, aVOR gains were significantly lower in the symptomatic group (0.79 ± 0.15) versus asymptomatic (0.87 ± 0.18), but not for passive head rotation. For pitch head rotation, the symptomatic group had both active (0.915 ± 0.24) and passive (0.878 ± 0.22) aVOR gains lower than the asymptomatic group (active 1.03 ± 0.27, passive 0.97 ± 0.23). Some SMs had elevated aVOR gain. VAS scores for all symptoms were highest during exertion. Our data suggest symptomatic SMs with TBI as a result of blast have varied aVOR gain during high-velocity head impulses and provide compelling evidence of pathology affecting the vestibular system. Potential loci of injury in this population include the following: disruption of pathways relaying vestibular efference signals, differential destruction of type I vestibular hair cells, or selective damage to irregular afferent pathways-any of which may explain the common discrepancy between reports of vestibular-like symptoms and laboratory testing results. Significantly reduced pitch aVOR in symptomatic SMs and peak symptom severity during exertional testing support earlier findings in the chronic blast-exposed active duty SMs.

Space Between the Ears.

What can spaceflight teach us about the brain? Our author, Mark Shelhamer, former chief scientist for the NASA Human Research Program and a professor at the Johns Hopkins School of Medicine, lays out how spaceflight relates to brain function, cognitive performance, and mental abilities.

Incremental Velocity Error as a New Treatment in Vestibular Rehabilitation (INVENT VPT) Trial: study protocol for a randomized controlled crossover trial.

BACKGROUND: A clinical pattern of damage to the auditory, visual, and vestibular sensorimotor systems, known as multi-sensory impairment, affects roughly 2% of the US population each year. Within the population of US military service members exposed to mild traumatic brain injury (mTBI), 15-44% will develop multi-sensory impairment following a mild traumatic brain injury. In the US civilian population, multi-sensory impairment-related symptoms are also a common sequela of damage to the vestibular system and affect ~ 300-500/100,000 population. Vestibular rehabilitation is recognized as a critical component of the management of multi-sensory impairment. Unfortunately, the current clinical practice guidelines for the delivery of vestibular rehabilitation are not evidence-based and primarily rely on expert opinion. The focus of this trial is gaze stability training, which represents the unique component of vestibular rehabilitation. The aim of the Incremental Velocity Error as a New Treatment in Vestibular Rehabilitation (INVENT VPT) trial is to assess the efficacy of a non-invasive, incremental vestibular adaptation training device for normalizing the response of the vestibulo-ocular reflex. METHODS: The INVENT VPT Trial is a multi-center randomized controlled crossover trial in which military service members with mTBI and civilian patients with vestibular hypofunction are randomized to begin traditional vestibular rehabilitation or incremental vestibular adaptation and then cross over to the alternate intervention after a prescribed washout period. Vestibulo-ocular reflex function and other functional outcomes are measured to identify the best means to improve the delivery of vestibular rehabilitation. We incorporate ecologically valid outcome measures that address the common symptoms experienced in those with vestibular pathology and multi-sensory impairment. DISCUSSION: The INVENT VPT Trial will directly impact the health care delivery of vestibular rehabilitation in patients suffering from multi-sensory impairment in three critical ways: (1) compare optimized traditional methods of vestibular rehabilitation to a novel device that is hypothesized to improve vestibulo-ocular reflex performance, (2) isolate the ideal dosing of vestibular rehabilitation considering patient burden and compliance rates, and (3) examine whether recovery of the vestibulo-ocular reflex can be predicted in participants with vestibular symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT03846830 . Registered on 20 February 2019.

Selected discoveries from human research in space that are relevant to human health on Earth.

A substantial amount of life-sciences research has been performed in space since the beginning of human spaceflight. Investigations into bone loss, for example, are well known; other areas, such as neurovestibular function, were expected to be problematic even before humans ventured into space. Much of this research has been applied research, with a primary goal of maintaining the health and performance of astronauts in space, as opposed to research to obtain fundamental understanding or to translate to medical care on Earth. Some people-scientists and concerned citizens-have questioned the broader scientific value of this research, with the claim that the only reason to perform human research in space is to keep humans healthy in space. Here, we present examples that demonstrate that, although this research was focused on applied goals for spaceflight participants, the results of these studies are of fundamental scientific and biomedical importance. We will focus on results from bone physiology, cardiovascular and pulmonary systems, and neurovestibular studies. In these cases, findings from spaceflight research have provided a foundation for enhancing healthcare terrestrially and have increased our knowledge of basic physiological processes.

A model of time estimation and error feedback in predictive timing behavior.

Two key features of sensorimotor prediction are preprogramming and adjusting of performance based on previous experience. Oculomotor tracking of alternating visual targets provides a simple paradigm to study this behavior in the motor system; subjects make predictive eye movements (saccades) at fast target pacing rates (>0.5 Hz). In addition, the initiation errors (latencies) during predictive tracking are correlated over a small temporal window (correlation window) suggesting that tracking performance within this time range is used in the feedback process of the timing behavior. In this paper, we propose a closed-loop model of this predictive timing. In this model, the timing between movements is based on an internal estimation of stimulus timing (an internal clock), which is represented by a (noisy) signal integrated to a threshold. The threshold of the integrate-to-fire mechanism is determined by the timing between movements made within the correlation window of previous performance and adjusted by feedback of recent and projected initiation error. The correlation window size increases with repeated tracking and was estimated by two independent experiments. We apply the model to several experimental paradigms and show that it produces data specific to predictive tracking: a gradual shift from reaction to prediction on initial tracking, phase transition and hysteresis as pacing frequency changes, scalar property, continuation of predictive tracking despite perturbations, and intertrial correlations of a specific form. These results suggest that the process underlying repetitive predictive motor timing is adjusted by the performance and the corresponding errors accrued over a limited time range and that this range increases with continued confidence in previous performance.

Compensating for camera translation in video eye-movement recordings by tracking a representative landmark selected automatically by a genetic algorithm.

It is common in oculomotor and vestibular research to use video or still cameras to acquire data on eye movements. Unfortunately, such data are often contaminated by unwanted motion of the face relative to the camera, especially during experiments in dynamic motion environments. We develop a method for estimating the motion of a camera relative to a highly deformable surface, specifically the movement of a camera relative to the face and eyes. A small rectangular region of interest (ROI) on the face is automatically selected and tracked throughout a set of video frames as a measure of vertical camera translation. The specific goal is to present a process based on a genetic algorithm that selects a suitable ROI for tracking: one whose translation within the camera image accurately matches the actual relative motion of the camera. We find that co-correlation, a statistic describing the time series of a large group of ROIs, predicts the accuracy of the ROIs, and can be used to select the best ROI from a group. After the genetic algorithm finds the best ROIs from a group, it uses recombination to form a new generation of ROIs that inherit properties of the ROIs from the previous generation. We show that the algorithm can select an ROI that will estimate camera translation and determine the direction that the eye is looking with an average accuracy of 0.75 degrees , even with camera translations of 2.5mm at a viewing distance of 120 mm, which would cause an error of 11 degrees without correction.

Incremental angular vestibulo-ocular reflex adaptation to active head rotation.

Studies on motor learning typically present a constant adaptation stimulus, corresponding to the desired final adaptive state. Studies of the auditory and optokinetic systems provide compelling evidence that neural plasticity is enhanced when the error signal driving adaptation is instead adjusted gradually throughout training. We sought to determine whether the angular vestibulo-ocular reflex (aVOR) may be adaptively increased using an incremental velocity error signal (IVE) compared with a conventional constant and large velocity-gain demand (x2). We compared the magnitude of aVOR gain change for these two paradigms across different motion contexts (active and passive). Seven individuals with normal vestibular function and six individuals with unilateral vestibular hypofunction (UVH) were exposed to the IVE and x2 ("control") aVOR demand tasks. Each subject participated in 10 epochs of 30 active head impulses over a 15 min aVOR gain increase training session separately for the IVE and x2 paradigms, separated by either seven days (normal subjects) or 14 days (UVH subjects). For both normal and UVH subjects, both paradigms led to aVOR gain increase during the training session. For the normal subjects, the IVE paradigm led to larger aVOR gain change after training compared to the x2 paradigm, for both active (mean 17.3 +/- 4% vs. mean 7.1 +/- 9%, P = 0.029) and passive (mean 14.2 +/- 5% vs. 4.5 +/- 8%, P = 0.018) head impulses. For subjects with UVH, IVE produced a greater change in aVOR gain for active head impulses (mean 18.2 +/- 9.2% vs. mean -6 +/- 3.8%, P = 0.003). However, aVOR gains for passive head impulses were less consistent after IVE, with only two subjects displaying greater aVOR gain with this incremental paradigm. Some individuals generated compensatory saccades that occurred in the same direction of the deficient aVOR during either training paradigm. Our data suggest that the aVOR is modifiable when the velocity error signal is presented incrementally, and that this adaptation stimulus is particularly effective in the case of unilateral vestibular hypofunction. This has implications for programs of vestibular rehabilitation, where active head rotation is prescribed as a means to improve gaze stability.

The dynamics of parabolic flight: flight characteristics and passenger percepts.

Flying a parabolic trajectory in an aircraft is one of the few ways to create freefall on Earth, which is important for astronaut training and scientific research. Here we review the physics underlying parabolic flight, explain the resulting flight dynamics, and describe several counterintuitive findings, which we corroborate using experimental data. Typically, the aircraft flies parabolic arcs that produce approximately 25 seconds of freefall (0 g) followed by 40 seconds of enhanced force (1.8 g), repeated 30-60 times. Although passengers perceive gravity to be zero, in actuality acceleration, and not gravity, has changed, and thus we caution against the terms "microgravity" and "zero gravity. " Despite the aircraft trajectory including large (45°) pitch-up and pitch-down attitudes, the occupants experience a net force perpendicular to the floor of the aircraft. This is because the aircraft generates appropriate lift and thrust to produce the desired vertical and longitudinal accelerations, respectively, although we measured moderate (0.2 g) aft-ward accelerations during certain parts of these trajectories. Aircraft pitch rotation (average 3°/s) is barely detectable by the vestibular system, but could influence some physics experiments. Investigators should consider such details in the planning, analysis, and interpretation of parabolic-flight experiments.

Veterans have greater variability in their perception of binocular alignment.

INTRODUCTION: A significant population of our wounded veterans suffer long-term functional consequences of visual deficit, disorientation, dizziness, and an impaired ability to read. These symptoms may be related to damage within the otolith pathways that contribute to ocular alignment. The purpose of this study was to compare perception of vertical and torsional ocular alignment between veterans and healthy controls in an upright and supine test position. MATERIALS AND METHODS: Veterans (n = 26) with reports of dizziness were recruited from the East Orange Veterans Administration Hospital. Healthy controls (n = 26) were recruited from both Johns Hopkins University and the East Orange VA. Each subject performed 20 trials each of a novel vertical and torsional binocular alignment perception test. Veterans underwent semicircular canal and otolith pathway function testing. RESULTS: 88% of the Veterans had an absent otolith response. Only the veterans had an abnormally large variability in perception of both vertical and torsional ocular alignment, and in both upright and supine position. Neither post-traumatic stress disorder, nor depression contributed to the misperception in binocular alignment. CONCLUSIONS: Our novel method of measuring vertical and torsional misalignment distinguishes veterans with dizziness from healthy controls. The high prevalence of absent otolith function seems to explain this result. Further studies are needed to better understand the fundamental mechanism responsible for the increased variability of perception of binocular alignment.

Biomedical findings from NASA's Project Mercury: a case series.

The United States first sent humans into space during six flights of Project Mercury from May 1961 to May 1963. These flights were brief, with durations ranging from about 15 min to just over 34 h. A primary purpose of the project was to determine if humans could perform meaningful tasks while in space. This was supported by a series of biomedical measurements on each astronaut before, during (when feasible), and after flight to document the effects of exposure to the spaceflight environment. While almost all of the data presented here have been published in technical reports, this is the first integrated summary of the main results. One unexpected finding emerges: the major physiological changes associated with these short-term spaceflights are correlated more strongly with time spent by the astronaut in a spacesuit than with time spent in space per se. Thus, exposure to the direct stressors of short-duration (up to 34 h) spaceflight was not the dominant factor influencing human health and performance. This is relevant to current spaceflight programs and especially to upcoming commercial flights in which time spent in space (as on a suborbital flight) will be minor compared to the time spent in associated preparation, ascent, and return.

An internal clock for predictive saccades is established identically by auditory or visual information.

Previously we have shown that repetitive predictive saccades to alternating visual targets are mediated by an internal clock. That is, when subjects track a periodic visual stimulus alternating at a high rate (a small inter-stimulus interval, ISI, of 500 or 833 ms), they use an internal estimate of stimulus timing to pre-program the eye movement timing. Auditory pacing tones at the same rate also generate predictive saccades. It is natural to ask if an identical internal clock is used to generate the predictive saccades in each case. We hypothesized that if subjects can use auditory information to establish an internal estimate of stimulus timing--as we demonstrated can be done with visual targets--then the distributions of predictive inter-saccade intervals should demonstrate the well-known "Scalar Property" for either Auditory Cued or Visual Cued stimuli: inter-saccade interval histograms should be almost identical when each is divided by its mean. However, when making reactive saccades to a pacing stimulus (at a low rate), there should be a difference in the timing statistics between Auditory and Visual pacing, due to differences in sensory processing. We report here that the variances of inter-saccade intervals at three predictive pacing rates (ISIs of 500, 833, and 1000 ms) are equivalent, whereas the variance for Auditory Cued Pacing was greater than that for Visual Cued Pacing during reactive saccades at two reactive pacing rates (ISIs of 1667 and 2500 ms). When the inter-saccade interval histograms at the predictive pacing rates were normalized, the distributions were nearly identical for both Visual and Auditory Cued Pacing, which means that the Scalar Property holds for predictive saccades from either pacing stimulus. These results suggest that (1) an internal timing reference (clock) can be established by either auditory or visual information and (2) during predictive tracking the variability in saccade timing is due to the variability in the internal timing representation, while during reactive tracking the variability in saccade timing depends on the sensory modality used to trigger the saccades.