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Chronic Lunar Dust Exposure on Rat Cornea: Evaluation by Gene Expression Profiling

Lunar dust is capable of entering habitats and vehicle compartments by sticking to spacesuits or other objects that are transferred into the spacecraft from the lunar surface and has been reported to cause irritation upon exposure. During the Apollo missions, crewmembers reported irritation specifically to the skin and eyes after contamination of the lunar and service modules. It has since been hypothesized that ocular irritation and abrasion might occur as a result of such exposure, impairing crew vision. Recent work has shown that both ultrafine and unground lunar dust exhibited minimal irritancy of the ocular surface (i.e., cornea); however, the assessment of the severity of ocular damage resulting from contact of lunar dust particles to the cornea has focused only on macroscopic signs of mechanical irritancy and cytotoxicity. Given the chemical reactive properties of lunar dust, exposure of the cornea may contribute to detrimental effects at the molecular level including but not limited to oxidative damage. Additionally, low level chronic exposures may confound any results obtained in previous acute studies. We report here preliminary results from a tissue sharing effort using 10‐week‐old Fischer 344 male rats chronically exposed to filtered air or jet milled lunar dust collected during Apollo 14 using a Jaeger‐NYU nose‐only chamber for a total of 120 hours (6 hours daily, 5 days a week) over a 4‐week period. RNA was isolated from corneas collected from rats at 1 day and 7 days after being exposed to concentrations of 0, 20, and 60 mg/m3 of lunar dust. Microarray analysis was performed using the Affymetrix GeneChip Rat Genome 230 2.0 Array with Affymetrix Expression Console and Transcriptome Analysis Console used for normalization and secondary analysis. An Ingenuity iReport"TM" was then generated for canonical pathway identification. The number of differentially expressed genes identified increases with dose compared to controls suggesting a more severe response to the lunar dust insult at higher levels. Pathways of interests that have been identified in all exposed samples include oxidative stress response, mitochondrial dysfunction, fibrosis, epithelial healing, TGF-Beta signaling, and extracellular matrix remodeling. Several biological processes related to cell migration, cellular proliferation, and eye development were also identified to be altered by exposure to lunar dust. Our preliminary results suggest that even a chronic insult of lunar dust as low as 20 mg/m(exp 3) elicits a molecular response in cornea tissue. Lunar dust on the surface of the moon would have the added properties of ionization and activation potentially leading to further damage to the cornea and greater sensitivity to any other environmental insult such as exposure to radiation. Additional studies are required to fully assess the risk of vision impairment and the mechanistic responses initiated in cornea exposed to lunar dust as well as the potential for long‐term effects to astronaut health

Theriot, C. A.↗

Improving Early Adaptation Following Long Duration Spaceflight by Enhancing Vestibular Information

Crewmember adapted to the microgravity state may need to egress the vehicle within a few minutes for safety and operational reasons after g-transitions. The transition from one sensorimotor state to another consists of two main mechanisms: strategic and plastic-adaptive and have been demonstrated in astronauts returning after long duration space flight. Strategic modifications represent "early adaptation" -immediate and transitory changes in control that are employed to deal with short-term changes in the environment. If these modifications are prolonged then plastic-adaptive changes are evoked that modify central nervous system function, automating new behavioral responses. More importantly, this longer term adaptive recovery mechanism was significantly associated with their strategic ability to recover on the first day after return to Earth G. We are developing a method based on stochastic resonance (SR) to enhance information transfer by improving the brain's ability to detect vestibular signals especially when combined with balance training exercises for rapid improvement in functional skill, for standing and mobility. The countermeasure to improve post-flight balance and locomotor disturbances is a stimulus delivery system that is wearable/portable providing low imperceptible levels of white noise based binaural bipolar electrical stimulation of the vestibular system (stochastic vestibular stimulation, SVS). The techniques for improving signal detection using SVS may thus provide additional information to improve such strategic abilities and thus help in significantly reducing the number of days required to recover functional performance to preflight levels after long duration space flight. We have conducted a series of studies to document the efficacy of SVS stimulation on balance/locomotion tasks on unstable surfaces and motion tracking tasks during intra-vestibular system conflicts. In an initial study, we showed that SVS improved overall balance performance while standing on an unstable surface indicating that SVS may be sufficient to provide a comprehensive countermeasure approach for improving postural stability. In a second study, we showed that SVS improved locomotor performance on a treadmill mounted on an oscillating platform indicating that SVS may also be used to maximize locomotor performance during walking in unstable environments. In a third study, SVS was evaluated during an otolith-canal conflict scenario in a variable radius centrifuge at low frequency of oscillation (0.1 Hz) on both eye movements and perceptual responses (using a joystick) to track imposed oscillations. The variable radius centrifuge provides a selective tilting sensation that is detectable only by the otolith organs providing conflicting information from the canal organs of the vestibular system (intra-vestibular conflict). Results show that SVS significantly reduced the timing difference between both the eye movement responses as well as the perceptual tracking responses with respect to the imposed tilt sensations. These results indicate that SVS can improve performance in sensory conflict scenarios like that experienced during space flight. Such a SR countermeasure will act synergistically along with the pre-and in-flight adaptability training protocols providing an integrated, multi-disciplinary countermeasure capable of fulfilling multiple requirements making it a comprehensive and cost effective countermeasure approach to enhance sensorimotor capabilities following long-duration space flight.

Mulavara, Ajitkumar↗

Functional Imaging of Human Vestibular Cortex Activity Elicited by Skull Tap and Auditory Tone Burst

The aim of the current study was to characterize the brain activation in response to two modes of vestibular stimulation: skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit saccular Vestibular Evoked Myogenic Potentials (VEMP) (Colebatch & Halmagyi 1992; Colebatch et al. 1994). Some researchers have reported that airconducted skull tap elicits both saccular and utricle VEMPs, while being faster and less irritating for the subjects (Curthoys et al. 2009, Wackym et al., 2012). However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of cortical activity. Both forms of stimulation target the otolith response, which provides a measurement of vestibular function independent from semicircular canals. This is of high importance for studying the vestibular disorders related to otolith deficits. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, pre and post central gyri, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation (Bottini et al., 1994; Dieterich et al., 2003; Emri et al., 2003; Schlindwein et al., 2008; Janzen et al., 2008). Here we hypothesized that the skull tap elicits the similar pattern of cortical activity as the auditory tone burst. Subjects put on a set of MR compatible skull tappers and headphones inside the 3T GE scanner, while lying in supine position, with eyes closed. All subjects received both forms of the stimulation, however, the order of stimulation with auditory tone burst and air-conducted skull tap was counterbalanced across subjects. Pneumatically powered skull tappers were placed bilaterally on the cheekbones. The vibration of the cheekbone was transmitted to the vestibular cortex, resulting in vestibular response (Halmagyi et al., 1995). Auditory tone bursts were also delivered for comparison. To validate our stimulation method, we measured the ocular VEMP outside of the scanner. This measurement showed that both skull tap and auditory tone burst elicited vestibular evoked activation, indicated by eye muscle response. Our preliminary analyses showed that the skull tap elicited activation in medial frontal gyrus, superior temporal gyrus, postcentral gyrus, transverse temporal gyrus, anterior cingulate, and putamen. The auditory tone bursts elicited activation in medial frontal gyrus, superior temporal gyrus, superior frontal gyrus, precentral gyrus, inferior and superior parietal lobules. In line with our hypothesis, skull taps elicited a pattern of cortical activity closely similar to one elicited by auditory tone bursts. Further analysis will determine the extent to which the skull taps can replace the auditory tone stimulation in clinical and basic science vestibular assessments.

Noohi, Fatemeh↗

Public-Private Collaborations with Earth-Space Benefits

The NASA Human Health and Performance Center (NHHPC) was established in October 2010 to promote collaborative problem solving and project development to advance human health and performance innovations benefiting life in space and on Earth. The NHHPC, which now boasts over 150 corporate, government, academic and non-profit members, has convened four successful workshops and engaged in multiple collaborative projects. The virtual center facilitates member engagement through a variety of vehicles, including annual in-person workshops, webcasts, quarterly electronic newsletters, web postings, and the new system for partner engagement. NHHPC workshops serve to bring member organizations together to share best practices, discuss common goals, and facilitate development of the collaborative projects. The most recent NHHPC workshop was conducted in November 2013 on the topic of "Accelerating Innovation: New Organizational Business Models," and focused on various collaborative approaches successfully used by organizations to achieve their goals. Past workshops have addressed smart media and health applications, connecting through collaboration, microbiology innovations, and strategies and best practices in open innovation. A fifth workshop in Houston, Texas, planned for September 18, 2014, will feature "Innovation Through Co-Development: Engaging Partners". One area of great interest to NASA is mobile health applications, including mobile laboratory analytics, health monitoring, and close loop sensing, all of which also offer ground-based health applications for remote and underserved areas. Another project being coordinated by NASA and the Health and Environmental Sciences Institute is the pursuit of one to several novel strategies to increase medication stability that would enable health care in remote terrestrial settings as well as during space flight. NASA has also funded work with corporate NHHPC partner GE, seeking to develop ultrasound methodologies that will enable NASA to further understand the eye changes related to long-duration space flight. The adaptation of ultrasound to this type of eye examination could also expand the use of ultrasound in health care on the Earth in settings where MRIs are not available. To further engage NHHPC members and facilitate partnership development for NASA, the NHHPC created and deployed an engagement system in 2014 that facilitates identification and evaluation of technical needs and opportunities among all NHHPC members.

Davis, Jeffrey R.↗

Effects of Long Duration Spaceflight on Venous and Arterial Compliance in Astronants

1. Project Overview Visual impairment and intracranial pressure (VIIP) is a spaceflight-associated medical condition affecting at least a third of American astronauts who have flown International Space Station (ISS) missions. VIIP is defined primarily by visual acuity deficits and anatomical changes to eye structures. In some astronauts, eye-related changes do not revert back to the preflight state upon return to Earth. Our team will study some of the possible causes for this syndrome. This will be achieved by reviewing previous astronaut data for factors that may predispose astronauts to higher rates of developing this syndrome or greater severity of symptoms. Additionally, we will conduct 3 separate experiments that will characterize vessels in the head and neck and measure the effects of the experimental conditions on ocular structures and function. 2. Technical Summary The primary objective of this study is to determine whether vascular compliance is altered by spaceflight and whether such adaptations are related to the incidence of the VIIP. In particular, we will measure ocular parameters and vascular compliance in vessels of the head and neck in astronauts who have no spaceflight experience (Ground), in astronauts before, during, and after spaceflight (Flight), and in bed rest subjects with conditions similar to spaceflight (Bed Rest). Additionally, we will analyze astronaut data from the Lifetime Surveillance of Astronaut Health (LSAH) archives to determine which factors might be predictive of the development of VIIP (Data Mining). The project will be conducted in four separate, but related parts. Hypothesis The central hypothesis of this proposal is that exposure to the spaceflight environment aboard the ISS may lead to development of the VIIP syndrome (increased intracranial pressure and impaired visual acuity) and that this may be related to alterations in venous and/or arterial compliance in the head and neck. Specific Aims 1. To determine whether noninvasive measures of venous and arterial compliance are altered by long-duration spaceflight exposure in ISS astronauts and whether these changes are related to the development of the VIIP syndrome. (Flight) 2. To determine whether previous spaceflight experience predispose astronauts to lower venous compliance and/or the development of the VIIP syndrome. (Ground + Flight) 3. To use a 14-day, 6deg head-down-tilt bed rest as a model of spaceflight, to evaluate the effect of aging on vascular compliance using a subject population similar to younger (25-35 yr) and older (45-55 yr) astronaut cohorts. (Bed Rest) 4. To determine what factors contribute to lower venous compliance and/or the development of the VIIP syndrome in astronauts. (Data Mining) 3. Earth Applications This research may inform the mechanisms that regulate blood/fluid flow in and out of the brain in the head and neck. This information may help with understanding of the mechanisms behind idiopathic intracranial hypertension. 4. Link to NASA Taskbook Entry Not Yet Available

Platts, Steven↗

Prospective Observational Study of Ocular Health in ISS Crews - The Ocular Health Study

The Visual Impairment Intracranial Pressure (VIIP) syndrome is currently NASA's number one human space flight risk. The syndrome, which is related to microgravity exposure, manifests with changes in visual acuity (hyperopic shifts, scotomas), changes in eye structure (optic disc edema, choroidal folds, cotton wool spots, globe flattening, and dilated optic nerve sheaths), and in some cases with documented increased intracranial pressure (ICP) postflight. While the eye appears to be the main affected end organ of this syndrome, the ocular effects are thought to be related to underlying changes in the vascular system and the central nervous system. The leading hypotheses for the development of VIIP involve microgravity-induced head-ward fluid shifts along with a loss of gravity-assisted drainage of venous blood from the brain, leading to cephalic congestion, decreased CSF resorption and increased ICP. Since 70% of ISS crewmembers have manifested clinical signs or symptoms of the VIIP syndrome, it is assumed that the majority have some degree of ICP elevation in-flight compared to the ground. Prolonged elevations of ICP can cause long-term reduced visual acuity and loss of peripheral visual fields, and have been reported to cause mild cognitive impairment in the analog terrestrial population of Idiopathic Intracranial Hypertension (IIH). These potentially irreversible health consequences underscore the importance of identifying the factors that lead to this syndrome and mitigating them.

Otto, C.↗

Risk of Oxidative Damage to Bone from Increased Iron Stores During Space Flight

Iron stores are increased secondary to neocytolysis of red blood cells and a high dietary intake of iron during space flight. This raises concerns about the risk of excess iron causing oxidative damage in many tissues, including bone. Biomarkers of iron status, oxidative damage, and bone resorption during space flight were analyzed for 23 (16 M/7 F) International Space Station crewmembers as part of the Nutrition SMO project. Up to 5 in-flight blood samples and 24-h urine pools were collected over the course of the 4-6 month missions. Serum iron increased slightly during space flight and was decreased at landing (P < 0.0004). An increase in serum ferritin early in flight (217% in women and 68% in men, P < 0.0004), returning to preflight concentrations at landing, and a decrease in transferrin and transferrin receptors during flight indicated that a transient increase in iron stores occurred. No inflammatory response was observed during flight. The oxidative damage markers 8-hydroxy-2'-deoxyguanosine and prostaglandin F(sub 2(alpha)) were positively correlated (both P < 0.001) with serum ferritin. A greater area under the curve for ferritin during flight was correlated with greater changes in bone mineral density of several bone regions after flight (1). In a separate study (2), a ground-based investigation was conducted that examined the combined effects of radiation exposure and iron overload on sensitivity to radiation injury in several physiological systems in 12-wk male Sprague-Dawley rats. The rats were acclimated to an adequate iron diet (45 mg iron (ferric citrate)/kg diet) for 3 wk and then assigned to one of four groups: adequate iron (Fe) diet/no radiation, adequate Fe diet/ radiation, moderately high Fe diet (650 mg Fe (ferric citrate)/kg diet)/no radiation, and moderately high Fe diet/radiation. Animals remained on the assigned diet for 4 wk. Starting on day 14 of experimental diet treatment, animals were exposed to a fractionated dose (0.375 Gy) of Cs-137 every other day (3 Gy total dose). On day 29 (24 h after last radiation exposure), animals were euthanized. Oxidative stress markers in the liver, bone, eyes, and serum were assessed. There was evidence that the iron diet contributed to DNA damage as well as radiation exposure in the liver, eyes, and bone. Together, the results suggest that increased iron stores do constitute a risk factor for oxidative damage and bone resorption, during space flight and on Earth. Funded by the Human Health and Countermeasures Element of the NASA Human Research Program.

Zwart, S. R.↗

Using Tests Designed to Measure Individual Sensorimotor Subsystem Perfomance to Predict Locomotor Adaptability

Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the readapation phase following a return to a gravitational environment. These alterations may lead to disruption in the ability to perform mission critical functions during and after these gravitational transitions. Astronauts show significant inter-subject variation in adaptive capability following gravitational transitions. The way each individual's brain synthesizes the available visual, vestibular and somatosensory information is likely the basis for much of the variation. Identifying the presence of biases in each person's use of information available from these sensorimotor subsystems and relating it to their ability to adapt to a novel locomotor task will allow us to customize a training program designed to enhance sensorimotor adaptability. Eight tests are being used to measure sensorimotor subsystem performance. Three of these use measures of body sway to characterize balance during varying sensorimotor challenges. The effect of vision is assessed by repeating conditions with eyes open and eyes closed. Standing on foam, or on a support surface that pitches to maintain a constant ankle angle provide somatosensory challenges. Information from the vestibular system is isolated when vision is removed and the support surface is compromised, and it is challenged when the tasks are done while the head is in motion. The integration and dominance of visual information is assessed in three additional tests. The Rod & Frame Test measures the degree to which a subject's perception of the visual vertical is affected by the orientation of a tilted frame in the periphery. Locomotor visual dependence is determined by assessing how much an oscillating virtual visual world affects a treadmill-walking subject. In the third of the visual manipulation tests, subjects walk an obstacle course while wearing up-down reversing prisms. The two remaining tests include direct measures of knee and ankle proprioception and a functional movement assessment that screens for movement restrictions and asymmetries. To assess each subject's locomotor adaptability subjects walk for twenty minutes on a treadmill that oscillates laterally at 0.3 Hz. Throughout the test metabolic cost provides a measure of exertion and step frequency provides a measure of stability. Additionally, at four points during the perturbation period, reaction time tests are used to probe changes in the amount of mental effort being used to perform the task. As with the adaptive capability observed in astronauts during gravitational transitions, our data shows significant variability between subjects. To aid in the analysis of the results, custom software tools have been developed to enhance in the visualization of the large number of output variables. Preliminary analyses of the data collected to date do not show a strong relationship between adaptability and any single predictor variable. Analysis continues to identify a multifactorial predictor outcome "signature" that do inform us of locomotor adaptability.

Peters, B. T.↗

Lumped Parameter Models of the Central Nervous System for VIIP Research

INTRODUCTION: Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit, such as to Mars and asteroids, expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome [1]. It has been hypothesized that the headward shift of cerebral spinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn induces VIIP syndrome through biomechanical pathways [1, 2]. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the realted IWS abstracts submitted by Nelson et al., Feola et al. and Ethier et al. METHODS: We have developed a nine compartment CNS model (Figure 1) capable of both time-dependent and steady state fluid transport simulations, based on the works of Stevens et al. [3]. The breakdown of compartments within the model includes: vascular (3), CSF (2), brain (1) and extracranial (3). The boundary pressure in the Central Arteries [A] node is prescribed using an oscillating pressure function PA(t) simulating the carotid pulsatile pressure wave as developed by Linninger et al. [4]. For each time step, pressures are integrated through time using an adaptive-timestep 4th and 5th order Runga-Kutta solver. Once pressures are found, constitutive equations are used to solve for flowrates (Q) between each compartment. In addition to fluid flow between the different compartments, compliance (C) interactions between neighboring compartments are represented. We are also developing a second CNS model based on the works of Linninger et al. [4] which takes a more granular approach to represent the interactions of the intracranial and spinal compartments with the inclusion of arteries, arterioles, capillaries, venules, veins, venous sinus, and ventricles. The flow through the arteries, veins and CSF compartments are governed by continuity, momentum and distensibility balance equations. Furthermore, unlike the Stevens et al. approach, the Monro-Kellie doctrine of constant cranial volume and the bi-phasic nature of the brain parenchyma are implemented. These features appear to be more consistent with the physiologic and anatomical behavior of the CNS, and follow a modeling philosophy similar to the lumped parameter eye model that is intended to be integrated with the CNS model. However, Linninger’s approach has never been implemented to include hydrostatic gradient and microgravity simulation capabilities. Therefore, we aim at implement this modeling approach for spaceflight simulations and assess its overall applicability to VIIP research. OBJECTIVES: We will present verification and validation test results for both models, as well as head-to-head comparison to explore their strengths and limitations with respect to mathematical implementation and physiological significance for VIIP research. In doing so, we hope to provide some guidance to the HRP research community on how to appropriately leverage lumped parameter models for space biomedical research.

Vera, J.↗

Automating Stowage Operations for the International Space Station

A challenge for any proposed mission is to demonstrate convincingly that the proposed systems will in fact deliver the science promised. Funding agencies and mission design personnel are becoming ever more skeptical of the abstractions that form the basis of the current state of the practice with respect to approximating science return. To address this, we have been using automated planning and scheduling technology to provide actual coverage campaigns that provide better predictive performance with respect to science return for a given mission design and set of mission objectives given implementation uncertainties. Specifically, we have applied an adaptation of ASPEN and SPICE to the Eagle-Eye domain that demonstrates the performance of the mission design with respect to coverage of science imaging targets that address climate change and disaster response. Eagle-Eye is an Earth-imaging telescope that has been proposed to fly aboard the International Space Station (ISS).

box packing↗

Mission Design Evaluation Using Automated Planning for High Resolution Imaging of Dynamic Surface Processes from the ISS

A challenge for any proposed mission is to demonstrate convincingly that the proposed systems will in fact deliver the science promised. Funding agencies and mission design personnel are becoming ever more skeptical of the abstractions that form the basis of the current state of the practice with respect to approximating science return. To address this, we have been using automated planning and scheduling technology to provide actual coverage campaigns that provide better predictive performance with respect to science return for a given mission design and set of mission objectives given implementation uncertainties. Specifically, we have applied an adaptation of ASPEN and SPICE to the Eagle-Eye domain that demonstrates the performance of the mission design with respect to coverage of science imaging targets that address climate change and disaster response. Eagle-Eye is an Earth-imaging telescope that has been proposed to fly aboard the International Space Station (ISS).

International Space Station↗

Vestibulo-Ocular Responses to Vertical Translation using a Hand-Operated Chair as a Field Measure of Otolith Function

The translational Vestibulo-Ocular Reflex (tVOR) is an important otolith-mediated response to stabilize gaze during natural locomotion. One goal of this study was to develop a measure of the tVOR using a simple hand-operated chair that provided passive vertical motion. Binocular eye movements were recorded with a tight-fitting video mask in ten healthy subjects. Vertical motion was provided by a modified spring-powered chair (swopper.com) at approximately 2 Hz (+/- 2 cm displacement) to approximate the head motion during walking. Linear acceleration was measured with wireless inertial sensors (Xsens) mounted on the head and torso. Eye movements were recorded while subjects viewed near (0.5m) and far (approximately 4m) targets, and then imagined these targets in darkness. Subjects also provided perceptual estimates of target distances. Consistent with the kinematic properties shown in previous studies, the tVOR gain was greater with near targets, and greater with vision than in darkness. We conclude that this portable chair system can provide a field measure of otolith-ocular function at frequencies sufficient to elicit a robust tVOR.

Wood, S. J.↗

Gaze Stabilization During Locomotion Requires Full Body Coordination

Maintaining gaze stabilization during locomotion places substantial demands on multiple sensorimotor subsystems for precise coordination. Gaze stabilization during locomotion requires eye-head-trunk coordination (Bloomberg, et al., 1997) as well as the regulation of energy flow or shock-wave transmission through the body at high impact phases with the support surface (McDonald, et al., 1997). Allowing these excessive transmissions of energy to reach the head may compromise gaze stability. Impairments in these mechanisms may lead to the oscillopsia and decreased dynamic visual acuity seen in crewmembers returning from short and long duration spaceflight, as well as in patients with vestibular disorders (Hillman, et al., 1999). Thus, we hypothesize that stabilized gaze during locomotion results from full-body coordination of the eye-head-trunk system combined with the lower limb apparatus. The goal of this study was to determine how multiple, interdependent full- body sensorimotor subsystems aiding gaze stabilization during locomotion are functionally coordinated, and how they adaptively respond to spaceffight.

Mulavara, A. P.↗

The Visual Impairment Intracranial Pressure Syndrome in Long Duration NASA Astronauts: An Integrated Approach

The Visual Impairment Intracranial Pressure (VIIP) syndrome is currently NASA's number one human space flight risk. The syndrome, which is related to microgravity exposure, manifests with changes in visual acuity (hyperopic shifts, scotomas), changes in eye structure (optic disc edema, choroidal folds, cotton wool spots, globe flattening, and distended optic nerve sheaths). In some cases, elevated cerebrospinal fluid pressure has been documented postflight reflecting increased intracranial pressure (ICP). While the eye appears to be the main affected end organ of this syndrome, the ocular affects are thought to be related to the effect of cephalad fluid shift on the vascular system and the central nervous system. The leading hypotheses for the development of VIIP involve microgravity induced head-ward fluid shifts along with a loss of gravity-assisted drainage of venous blood from the brain, both leading to cephalic congestion and increased ICP. Although not all crewmembers have manifested clinical signs or symptoms of the VIIP syndrome, it is assumed that all astronauts exposed to microgravity have some degree of ICP elevation in-flight. Prolonged elevations of ICP can cause long-term reduced visual acuity and loss of peripheral visual fields, and has been reported to cause mild cognitive impairment in the analog terrestrial population of Idiopathic Intracranial Hypertension (IIH). These potentially irreversible health consequences underscore the importance of identifying the factors that lead to this syndrome and mitigating them.

Otto, C. A.↗

Functional Imaging of Human Vestibular Cortex Activity Elicited by Skull Tap and Auditory Tone Burst

The current study characterizes brain activation in response to two modes of vestibular stimulation: skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit either the vestibulo-spinal reflex (saccular-mediated colic Vestibular Evoked Myogenic Potentials (cVEMP)), or the ocular muscle response (utricle-mediated ocular VEMP (oVEMP)). Some researchers have reported that air-conducted skull tap elicits both saccular and utricle-mediated VEMPs, while being faster and less irritating for the subjects. However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of cortical activity. Both forms of stimulation target the otolith response, which provides a measurement of vestibular function independent from semicircular canals. This is of high importance for studying otolith-specific deficits, including gait and balance problems that astronauts experience upon returning to earth. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation. Here we hypothesized that skull taps elicit similar patterns of cortical activity as the auditory tone bursts, and previous vestibular imaging studies. Subjects wore bilateral MR compatible skull tappers and headphones inside the 3T GE scanner, while lying in the supine position, with eyes closed. Subjects received both forms of the stimulation in a counterbalanced fashion. Pneumatically powered skull tappers were placed bilaterally on the cheekbones. The vibration of the cheekbone was transmitted to the vestibular system, resulting in the vestibular cortical response. Auditory tone bursts were also delivered for comparison. To validate our stimulation method, we measured the ocular VEMP outside of the scanner. This measurement showed that both skull tap and auditory tone burst elicited vestibular evoked myogenic potentials, indicated by eye muscle responses. We further assessed subjects' postural control and its correlation with vestibular cortical activity. Our results provide the first evidence of using skull taps to elicit vestibular activity inside the MRI scanner. By conducting conjunction analyses we showed that skull taps elicit the same activation pattern as auditory tone bursts (superior temporal gyrus), and both modes of stimulation activate previously identified vestibular cortical regions. Additionally, we found that skull taps elicit more robust vestibular activity compared to auditory tone bursts, with less reported aversive effects. This further supports that the skull tap could replace auditory tone burst stimulation in clinical interventions and basic science research. Moreover, we observed that greater vestibular activation is associated with better balance control. We showed that not only the quality of balance (indicated by the amount of body sway) but also the ability to maintain balance for a longer time (indicated by the balance time) was associated with individuals' vestibular cortical excitability. Our findings support an association between vestibular cortical activity and individual differences in balance. In sum, we found that the skull tap stimulation results in activation of canonical vestibular cortex, suggesting an equally valid, but more tolerable stimulation method compared to auditory tone bursts. This is of high importance in longitudinal vestibular assessments, in which minimizing aversive effects may contribute to higher protocol adherence.

Noohi, F.↗

A New GaAs Laser Radar for Atmospheric Measurements

A special GaAs lidar using fiber coupled diode lasers was constructed for the purpose of measuring the extinction coefficient distribution within a large atmospheric volume at a rate compatible with atmospheric kinematics. The technique is based on taking backscatter signature ratios over spatial increments after the returns are normalized by pulse integration. Essential aspects of the lidar design are beam pulse power, repetition rate, detection system dynamic range and decay linearity. It was necessary to preclude the possibility of eye hazard under any operating conditions, including directly viewing the emitting aperture at close distance with a night-adapted eye. The electronic signal processing and control circuits were built to allow versatile operations. Extinction coefficient measurements were made in fog and clouds using a low-power laboratory version of the lidar, demonstrating feasibility. Data are presented showing range squared corrected backscatter profiles converted to extinction coefficient profiles, temporal signal fluctuations, and solar induced background noise. These results aided in the design of the lidar which is described. Functional tests of this lidar and the implications relevant to the design of a prototype model are discussed. This work was jointly sponsored by Sperry Rand Corporation under its Independent Research and Development program; the Air Force Avionics Laboratory, Wright Field, Dayton, Ohio; and the Naval Ammunition Depot, Crane, Indiana.

Brown, R. T.↗

Analysis of Retinal Vascular Branching in Human Subjects Undergoing 70-Day Head-Down Tilt by NASAs VESGEN Software

Significant risks for visual impairment were discovered recently in astronauts following spaceflight, especially after long-duration missions. We hypothesize that microgravity-induced fluid shifts result in pathological changes within the retinal vasculature that precede visual and other ocular impairments. We therefore are analyzing retinal vessels in healthy subjects before and after head-down tilt (HDT), a ground-based microgravity analog with NASA's VESsel GENeration Analysis (VESGEN) software. Methods. Spectralis® infrared (IR) fundus images were collected from both eyes of 6 subjects before and after 70 days of bed rest at 6 degree HDT (NASA Campaign 11). For our retrospective study, branching patterns in arterial and venous trees are mapped by VESGEN into vessel branching generations (Gx) that are quantified by parameters such as densities of vessel length (Lv), area (Av), number (Nv) and fractal dimension (Df) as described previously for diabetic retinopathy (IOVS 51(1):498). Results are further assigned by VESGEN into groups of large (G1-3), medium (G4-6) and small (G≥7) vessels. Results. All subjects remained asymptomatic throughout duration of HDT. To date, we have analyzed one IR image from each of the 12 eyes. Interestingly, two groups of the masked study population identified by VESGEN are distinguished by the presence or absence of small veins (G≥7). For example, L≥7 and Av≥7 are 2.7+/-1.3 E-4 px/px2 and 7.2+/-3.6 E-4 px2/px2 in 6 retinas, but 0 in the other 6 retinas. Nonetheless, the space-filling properties of the entire venous trees were remarkably uniform by all parameters, such as Df = 1.56+/-0.02 for 6 retinas with G≥7 and 1.55+/-0.02 for retinas without G≥7. No small arteries (G≥7) were detected. Conclusions. For our preliminary masked analysis, two groups of venous trees with and without small veins (G≥7) were clearly revealed by VESGEN. Upon completing all images and unmasking the subject status of before and after HDT, we will determine whether differences in the presence or absence of small veins are important correlates, and perhaps reliable predictors, of other ocular and physiological adaptations to prolonged head-down tilt and microgravity. Clinical methods for examining adaptive microvascular remodeling in the retina to microgravity space flight are not currently established.

Fractal↗

Stroboscopic Goggles as a Countermeasure for Dynamic Visual Acuity and Landing Sickness in Crewmembers Returning from Long-Duration Spaceflight

Long-term exposure to microgravity causes sensorimotor adaptations that result in functional deficits upon returning to a gravitational environment. At landing, the vestibular system and the central nervous system, responsible for coordinating head and eye movements via the vestibulo-occular reflex (VOR), are adapted to microgravity and must re-adapt to the Earth's gravitational environment. This re-adaptation causes decrements in gaze control and dynamic visual acuity, with astronauts reporting oscillopsia and blurred vision. These effects are caused by retinal slip, or the inability to keep an image focused on their retina, which is thought to drive motion sickness symptoms experienced upon landing. Retinal slip can be estimated by dynamic visual acuity (DVA); visual acuity while in motion. Peters et al. (2011) find that DVA is worsened in astronauts by an average of 0.75 eye-chart lines one day after landing. Previously, the use of stroboscopic goggles has shown to be effective in minimizing motion sickness symptoms due to retinal slip (Reschke et al. 2007). In this study, we simulated the decrement in DVA caused by sensorimotor re-adaptation by using minifying lenses and then testing the efficacy of stroboscopic goggles in preventing retinal slip and improving DVA. Dynamic visual acuity is assessed using an oscillating chair developed in the Neuroscience Laboratory at JSC. This chair is motor-driven and oscillates vertically at 2 Hz with a vertical displacement of +/- 2 cm to simulate the vertical translations that occur while walking. As the subject is being oscillated, they are asked to discern the direction of Landolt-C optotypes of varying sizes and record their direction using a gamepad. The visual acuity thresholds are determined using an algorithm that alters the size of the optotype based on the previous responses of the subject using a forced-choice best parameter estimation that is able to rapidly converge on the threshold value. Visual acuity thresholds were determined both for static (seated) and dynamic (oscillating) conditions. Dynamic visual acuity is defined as the difference between the dynamic and static conditions. We found that healthy subjects (n=20) have a significantly impaired DVA while wearing the minifying lenses, demonstrating that the VOR is in an adaptive state and retinal slip is occurring. When subjects' acuity was tested wearing the stroboscopic goggles with the minifying lenses, there was no significant difference in their DVA compared to their baseline DVA. This suggests that stroboscopic goggles are preventing retinal slip and would function as an efficient countermeasure for VOR adaptations and thus help mitigate landing sickness symptoms experienced by long-duration crewmembers. These goggles might also be used to counter blurred vision (caused by retinal slip) experienced by crewmembers during launch where the vehicle vibrations are greatest. The stroboscopic effect could be built into a section of their head mounted displays on the visor of their helmets to be used in these high vibration situation if a mission critical task is necessary.

Rosenberg, M. J. F.↗