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.

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.

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.

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.

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.

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.

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.

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.

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.

From the bench to exploration medicine: NASA life sciences translational research for human exploration and habitation missions.

NASA's Space Biology and Human Research Program entities have recently spearheaded communications both internally and externally to coordinate the agency's translational research efforts. In this paper, we strongly advocate for translational research at NASA, provide recent examples of NASA sponsored early-stage translational research, and discuss options for a path forward. Our overall objective is to help in stimulating a collaborative research across multiple disciplines and entities that, working together, will more effectively and more rapidly achieve NASA's goals for human spaceflight.

Strength of baseline inter-trial correlations forecasts adaptive capacity in the vestibulo-ocular reflex.

Individual differences in sensorimotor adaptability may permit customized training protocols for optimum learning. Here, we sought to forecast individual adaptive capabilities in the vestibulo-ocular reflex (VOR). Subjects performed 400 head-rotation steps (400 trials) during a baseline test, followed by 20 min of VOR gain adaptation. All subjects exhibited mean baseline VOR gain of approximately 1.0, variable from trial to trial, and showed desired reductions in gain following adaptation with variation in extent across individuals. The extent to which a given subject adapted was inversely proportional to a measure of the strength and duration of baseline inter-trial correlations (ß). ß is derived from the decay of the autocorrelation of the sequence of VOR gains, and describes how strongly correlated are past gain values; it thus indicates how much the VOR gain on any given trial is informed by performance on previous trials. To maximize the time that images are stabilized on the retina, the VOR should maintain a gain close to 1.0 that is adjusted predominantly according to the most recent error; hence, it is not surprising that individuals who exhibit smaller ß (weaker inter-trial correlations) also exhibited the best adaptation. Our finding suggests that the temporal structure of baseline behavioral data contains important information that may aid in forecasting adaptive capacities. This has significant implications for the development of personalized physical therapy protocols for patients, and for other cases when it is necessary to adjust motor programs to maintain movement accuracy in response to pathological and environmental changes.

Repair of Physiologic Time Series: Replacement of Anomalous Data Points to Preserve Fractal Exponents.

Extraction of fractal exponents via the slope of the power spectrum is common in the analysis of many physiological time series. The fractal structure thus characterized is a manifestation of long-term correlations, for which the temporal order of the sample values is crucial. However, missing data points due to artifacts and dropouts are common in such data sets, which can seriously disrupt the computation of fractal parameters. We evaluated a number of methods for replacing missing data in time series to enable reliable extraction of the fractal exponent and make recommendations as to the preferred replacement method depending on the proportion of missing values and any a priori estimate of the fractal exponent.

Inter-Trial Correlations in Predictive-Saccade Endpoints: Fractal Scaling Reflects Differential Control along Task-Relevant and Orthogonal Directions.

Saccades exhibit variation in performance from one trial to the next, even when paced at a constant rate by targets at two fixed locations. We previously showed that amplitude fluctuations in consecutive predictive saccades have fractal structure: the spectrum of the sequence of consecutive amplitudes has a power-law (f-α) form, indicative of inter-trial correlations that reflect the storage of prior performance information to guide the planning of subsequent movements. More gradual decay of these inter-trial correlations coincides with a larger magnitude of spectral slope α, and indicates stronger information storage over longer times. We have previously demonstrated that larger decay exponents (α) are associated with faster adaptation in a saccadic double-step task. Here, we extend this line of investigation to predictive saccade endpoints (i.e., movement errors). Subjects made predictive, paced saccades between two fixed targets along a horizontal or vertical axis. Endpoint fluctuations both along (on-axis) and orthogonal to (off-axis) the direction of target motion were examined for correlations and fractal structure. Endpoints in the direction of target motion had little or no correlation or power-law scaling, suggesting that successive movements were uncorrelated (white noise). In the orthogonal direction, however, the sequence of endpoints did exhibit inter-trial correlations and scaling. In contrast, in our previous work the scaling of saccade amplitudes is strong along the target direction. This may reflect the fact that while saccade amplitudes are neurally programmed, endpoints are not directly controlled but instead serve as a source of error feedback. Hence, the lack of correlations in on-axis endpoint errors suggests that maximum information has been extracted from previous movement errors to plan subsequent movement amplitudes. In contrast, correlations in the off-axis component indicate that useful information still remains in this error (residual) sequence, suggesting that saccades are less tightly controlled along the orthogonal direction.

Assessment of vestibulo-ocular function without measuring eye movements.

BACKGROUND: The vestibulo-ocular reflex (VOR) maintains stable gaze during head motion. Deficiencies lead to apparent world motion due to incomplete stabilization of eyes in space. VOR measurement requires specialized apparatus, trained operators, and significant setup time. NEW METHOD: We present a system (VON: vestibulo-ocular nulling) for rapid vestibulo-ocular assessment without measuring eye movements per se. VON uses a head-mounted motion sensor, laptop computer with user input control, and laser target whose position is controlled by the computer. As the head moves, the target is made to move in the same manner with a gain set by the subject. When the subject sets the gain so the target appears stationary in space, it is stationary on the retinas. One can determine from this gain the extent to which the eyes move in space when the head moves, which is the amount by which the VOR is deficient. From this the gain of the compensatory eye movements is derived. RESULTS: VON was compared with conventional video-based VOR measures. Both methods track expected changes in gain over 20min of adaptation to minifying spectacles. VON measures are more consistent across subjects, and pre-adaptation values are closer to compensatory. COMPARISON WITH EXISTING METHOD: VON is a rapid means to assess vestibulo-ocular performance. As a functional perceptual measure, it accounts for gaze-stabilizing contributions that are not apparent in the standard VOR, such as pursuit and perceptual tolerance. CONCLUSIONS: VON assesses functional VOR performance. Future implementations will make VOR assessment widely available to investigators and clinicians.

A rapid quantification of binocular misalignment without recording eye movements: Vertical and torsional alignment nulling.

BACKGROUND: Small, innate asymmetries between the left and right otolith organs can cause ocular misalignment with symptoms that include double vision and motion sickness. Additionally, ocular misalignment affects nearly 5% of the US population. We have developed a portable, non-invasive technology that uses subjective perception of binocular visual signals to estimate relative binocular alignment. NEW METHOD AND RESULTS: The Vertical Alignment Nulling (VAN) and Torsional Alignment Nulling (TAN) tests ask subjects to view one red and one blue line on a tablet computer while looking through color-matched red and blue filters so that each eye sees only one of the lines. Subjects align the red and blue lines, which are initially vertically offset from one another during VAN or rotated relative to one another during TAN, until they perceive a single continuous line. Ocular misalignments are inferred from actual offsets in the final line positions. During testing, all binocular visual cues are eliminated by employing active-matrix organic light-emitting diode (AMOLED) technology and testing in darkness. VAN and TAN can accurately account for visual offsets induced by prisms, and test-retest reliability is excellent, with resolution better than many current standard clinical tests. COMPARISON WITH EXISTING METHOD(S): VAN and TAN tests are similar to the clinical Lancaster red-green test. However, VAN and TAN employ inexpensive, hand-held hardware that can be self-administered with results that are quickly quantifiable. CONCLUSIONS: VAN and TAN provide simple, sensitive, and quantitative measures of binocular positioning alignment that may be useful for detecting subtle abnormalities in ocular positioning.

Parabolic flight as a spaceflight analog.

Ground-based analog facilities have had wide use in mimicking some of the features of spaceflight in a more-controlled and less-expensive manner. One such analog is parabolic flight, in which an aircraft flies repeated parabolic trajectories that provide short-duration periods of free fall (0 g) alternating with high-g pullout or recovery phases. Parabolic flight is unique in being able to provide true 0 g in a ground-based facility. Accordingly, it lends itself well to the investigation of specific areas of human spaceflight that can benefit from this capability, which predominantly includes neurovestibular effects, but also others such as human factors, locomotion, and medical procedures. Applications to research in artificial gravity and to effects likely to occur in upcoming commercial suborbital flights are also possible.