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NASA NTRS2019

Structural and Functional Adaptation of the Vestibular Otolith to Altered Gravity from Microgravity to Hypergravity

Inertial acceleration and a change in head orientation with respect to gravity are sensed by mechanosensitive receptors in the inner ear otolith organs. These structures consist of calcium carbonate grains called otoconia that mechanically load the hair cell bundles and distribute the tangential shear force during movement, and changes in their density can alter hair cell sensitivity. A possible adaptive response to a chronic gravity change is a change in weight-lending otoconia. Another mechanism is a modification of the strength and number of synapses coupling the hair cells to nerve afferents that convey the signals into the brain. Here, we present the results obtained in 2 species exposed both to µG (microgravity) and hyper-gravity (HG). Adult toadfish, Opsanus tau, were exposed to µG (microgravity) in 2 shuttle missions and to 1.12-2.24G (force of gravity) [resultant] centrifugation for 1-32 days; readaptation was studied following 1-8 days after return to 1G. Results show a biphasic pattern in response to 2.24G: initial hypersensitivity, similar to that observed after µG (microgravity) exposure, followed by transition to a significant decrease at 16-32 days. Recovery from HG exposure is approximately 4-8 days. Two major pieces of information are still needed: vertebrate hair cell response to altered gravity and impact of longer duration exposures on sensory plasticity. To address the latter we applied electron microscopic techniques to image otoconia mass obtained from 1) mice subjected to 91-days of µG (microgravity) in the Mouse Drawer System (MDS) flown on International Space Station, 2) mice subjected to 91-days of 1.24G centrifugation on ground, and 3) mice flown on 2 shuttle missions. Images from MDS mice indicate a clear restructuring of individual otoconia, suggesting deposition to the outer shell. Images from their HG ground counterparts indicate the converse - an ablation of the otoconia mass. For 13-day exposures to µG (microgravity) mice otoconia appear normal. Despite the permanence of gravity in evolution the animal senses exposure to a novel, non-1G, environment and adaptive mechanisms are initiated - in the short term compensation is likely confined to the peripheral sensory receptors, the brain or both. For longer exposures structural modifications of the otolith mass may also result.

Otoconia↗
NASA NTRS2019

Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae

A combination of spaceflight-relevant factors (fluid-shift and radiation) created a different gene expression profile than either factor individually. Some gene pathways including reduced transcriptional machinery, increased neurogenesis and neuropeptide production, and dysregulated cell structure and cell signaling. Gene expression differences can persist for at least 4 months after a 21- day exposure to a combination of fluid-shift and radiation in the brain tissue of mice. Brain-related transcriptional changes are dynamic during readaptation phase from exposure to spaceflight-like conditions, which may lead to long-term neurological consequences.

Overbey, Eliah G.↗
NASA NTRS2019

Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae

Spaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spaceflight analog conditions using the mouse model, simulated microgravity via hindlimb unloading (HLU) and/or low-dose irradiation (LDR) for 21-days, followed by 4 months of readaptation. Changes in gene expression and epigenetic modifications in whole brain samples during readaptation were analyzed by DESeq2 and reduced representation bisulfite sequencing (RRBS). The results showed minimal gene expression alterations at 4-months within single treatment conditions of HLU and LDR. Following combined HLU+LDR, gene ontology and methylation analyses showed multiple altered pathways involved in neurogenesis and neuroplasticity, regulation of neuropeptides and cellular signaling. In brief, neurological readaptation following combined chronic LDR and HLU is a dynamic process that impacts brain structure and function and may lead to late onset neurological sequelae

Overbey, Eliah G.↗
NASA NTRS2019

Simulated Microgravity Affects Behavior and Cytokine Expression in the Hippocampus of Adult Mice: Influence of Mitochondrial Reactive Oxygen Species

The effects of microgravity, and social isolation on the CNS are poorly understood. We hypothesize that mitochondrial reactive oxygen species (ROS) play an important role in this process. Since mice are social animals, our lab developed a novel social model of hindlimb unloading (HU), enabling us to determine the effects of both social isolation and simulated microgravity. Responses to 30d of HU were compared in wildtype or transgenic MCAT mice who over-express human catalase in mitochondria. Abundance of 4-Hydroxynonenal, Park7 (a redox-sensitive chaperone and sensor of oxidative stress) and corticosterone were measured by ELISA. Cytokines related to inflammation in the hippocampus and in plasma were analyzed by a protein array. Behavioral data was collected over a 24-hour period.Socially housed HU mice were more active and conducted at least two times more exploratory activities, compared to normally loaded mice. Correlation analysis revealed that specific brain and plasma cytokines correspond with specific behaviors. Simulated microgravity and/or social isolation caused changes in cytokine patterns in the hippocampus and in plasma, with significant interaction effects of HU and genotype in expression levels of five cytokines (out of 35). Interestingly, elevation of these generally pro-inflammatory cytokines by HU in WT mice was mitigated in MCAT mice, suggesting a role for mitochondrial ROS signaling in inflammatory CNS responses to microgravity. Interestingly, socially housed mice had also lower level of 4HNE and higher level of Park7 in the hippocampus compared to singly housed animals. The cytokine responses to social isolation were more extensive in brain vs plasma. Further, there was no overlap in the cytokine repertoire regulated in response to microgravity versus, isolation suggesting divergent mechanisms or downstream signaling. These findings implicate a potentially important role for mitochondrial ROS in CNS responses to the challenges posed both by prolonged missions in space and bedrest on Earth

Guttmann, Linda↗
NASA NTRSDate not supplied

Developing High-Throughput Organ-on-a-Chip Models to Investigate the Effects of Ionizing Radiation on the Central Nervous System

One of the main health risks in human space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to the galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neuronal damage and neuroinflammation associated with cognitive and behavioral dysfunction. In general, the extent of CNS damage is partially regulated by the blood-brain barrier (BBB), which enables immune cells to enter the CNS. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, immune responses and oxidative stress, and thus could serve as a robust CNS-specific target for countermeasure development. However, studies on BBB permeability and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we established a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments in response to ionizing radiation, based on commercially available OrganoPlates (Mimetas, Inc.) seeded with primary or induced pluripotent stem cell-derived human cells. We investigated both immediate and delayed CNS responses to major GCR components: 0.15-0.5 Gy 250MeV/n 4-He, and 0.3-0.8 Gy 600 MeV/n 56-Fe; as well as to 0.5-1 Gy X-rays. We observed ionizing radiation-mediated increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by morphological changes in endothelial cells and tight junctions, altered cytokine profile including TNFa upregulation, and increased oxidative stress. We also quantified irradiation-mediated changes in astrocyte activation and neuronal functions, revealing major astrocyte damage mediated by 600MeV/n 56-Fe particles. Thus, we demonstrate that deep space radiation may contribute to CNS damage by disrupting both astrocyte and endothelial cell components of the blood-brain barrier. Our next steps include mapping and validating the transcriptomic changes induced by simulated GCRs and their components in human CNS models. Ultimately, we aim to uncover potential novel targets for countermeasure developments to mitigate CNS damage in long duration spaceflight.

Radiation↗
NASA NTRSDate not supplied

Neuroimmune responses to space radiation

One of the main health risks in human deep space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neurodegeneration and neuroinflammation associated with cognitive and behavioral dysfunction. The extent of CNS damage is partially mediated by the blood-brain barrier (BBB), which regulates the interaction between CNS and systemic responses to stressors in the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, neuroinflammation and oxidative stress. However, studies on BBB and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we developed a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments caused by deep space radiation. We investigated both immediate and delayed CNS responses to major GCR components: 0.3-0.8Gy 600MeV/n 56Fe ions; as well as to 0.5-1Gy X-rays. We observed ionizing radiation-mediated increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by damage to endothelial cells and tight junctions, altered cytokine expression including TNFalpha upregulation, and increased oxidative stress. In particular, 600MeV/n 56Fe particle irradiation selectively induced astrocyte damage and increased blood-brain barrier permeability only in models that contained astrocytes in addition to endothelial cells, indicating astrocytes as a particularly radiosensitive component of the CNS that could therefore be a suitable a target for neuroprotection. Future studies will compare human and mouse CNS model responses to simulated GCRs and evaluate the induction of an anti-inflammatory phenotype in astrocytes as a potential countermeasure. Furthermore, in our lab we have been exploring the individual variability, genomic associations and secreted biomarkers of responses to space radiation, which could eventually be combined to address personalized CNS health risk and develop individual countermeasures. Ultimately, we aim to expand upon these results to uncover novel cellular and mechanistic targets for countermeasure development to mitigate human CNS damage in deep space exploration.

space radiation↗
NASA NTRS2020

Disruptive Technologies and Their Putative Impacts Upon Society and Aerospace- Entering The Virtual Age

Developments in technology over the recent decades have been extraordinary. They include the IT, bio, nano, and now quantum and energetics technology arenas and their many combinatorial interactions and impacts. In the main, these are at the frontiers of the small and in a combinational, synergistic feeding frenzy with each other. They fall under the broad category of Disruptive Technologies and have greatly altered society. The outlook for the runout of these and other technology developments augers mid-term to later alterations in components of the human existence theorem, including the requirement to work for our living and our physiological makeup and longevity (Ref 1). The IT revolution began in the 1950s with the development of solid-state electronics. The biologics revolution began later in the 1960s and 1970s with DNA and genomics, and the nano revolution in the 1990s with self-forming nano systems and carbon nanotubes. Quantum technology is now developing rapidly, aided by enabling nano systems, and the energetics revolution is providing ever more efficient and less expensive renewable energy sources. The IT revolution has produced improvements of an astounding eleven orders of magnitude in computing speed since the late 1950s. As we shift from silicon to biological, optical, nano, molecular, and atomic computing, improvements of some 4 orders of magnitude are evidently possible from either optical or DNA computing [Refs 2and 3], then there are combinatorials. Then there is quantum computing, under development worldwide for an increasing number of applications and proffering phenomenal capabilities. The current fastest computers are considerably beyond human brain speed. Machine intelligence is developing well after decades of inadequate machine capability, now no longer the case, and a detour into expert systems. Researchers in machine intelligence are now pursuing deep learning approaches using neural nets, which are proving to be extremely useful. Some believe the frontier of potential human-level machine intelligence may be found in biomimetics and brain-emulation approaches. There is even a possibility of “emergence”—i.e., when the machine intelligence is complex enough that it “wakes up,” as when human intelligence emerged via evolution during the million-plus years of the hunter-gatherer epoch [ Ref 4]. In fact, some posit that human intelligence can be improved upon and is only a cul-de-sac of what is conceivable. The IT revolution has produced massive changes in human society and economics—from the Internet, enabling the rapid expansion of knowledgeability (and even what is knowable), to an increasingly pervasive trend of “tele-everything.” The extraordinary compilation, storage, and availability of truly massive amounts of information could, when combined with AI and under the mantra of “big data,” greatly improve many of our technical and commercial processes and their content including elucidating new heuristic governing laws.

Dennis M. Bushnell↗
NASA NTRSDate not supplied

Neuroimmune Responses to Space Radiation

One of the main health risks in human deep space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neurodegeneration and neuroinflammation associated with cognitive and behavioral dysfunction. The extent of CNS damage is partially mediated by the blood-brain barrier (BBB), which regulates the interaction between CNS and systemic responses to stressors in the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, neuroinflammation and oxidative stress. However, studies on BBB and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we developed a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments caused by deep space radiation. We investigated both immediate and delayed CNS responses to major GCR components: 600MeV/n 56Fe ions. We observed ionizing radiation-mediated dose-dependent increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by altered cytokine expression including interleukin-1 receptor alpha downregulation, and increased oxidative stress. In particular, 600MeV/n 56Fe particle irradiation selectively increased damage and blood-brain barrier permeability only in models that contained astrocytes in addition to endothelial cells, indicating astrocytes as a particularly radiosensitive component of the CNS that could therefore be a suitable a target for neuroprotection. Future studies will compare human and mouse CNS model responses to simulated GCRs and evaluate the induction of an anti-inflammatory phenotype in astrocytes as a potential countermeasure. Furthermore, in our lab we have been exploring the individual variability, genomic associations and secreted biomarkers of responses to space radiation, which could eventually be combined to address personalized CNS health risk and develop individual countermeasures. Ultimately, we aim to expand upon these results to uncover novel cellular and mechanistic targets for countermeasure development to mitigate human CNS damage in deep space exploration.

space radiation↗
NASA NTRSDate not supplied

Space Radiation and Central Nervous System Impacts: NASA Standards and Evidence

It is well understood that large radiation localized doses to the brain cause clinically significant impacts to the central nervous system in human populations. However, the effects in adults exposed to lower doses remain unclear due to lack of data in relevant human cohorts. The impact of exposure to high-energy particles is even less understood. NASA’s Human Research Program relies heavily on model systems to characterize the impacts of the space radiation environment on the human brain and how potential changes may effect mission success and long term health and well-being. Animal, cellular, and molecular experiments implicate multiple – and possibly related – mechanisms that mediate impacts to the central nervous system in model systems including, but not limited to inflammation, immune responses, oxidative stress, metabolism, myelination, molecule transport, electrophysiology, and a variety of “omic” changes. While animal studies demonstrate potential changes across a number of cognitive and behavioral domains the direct applicability to the astronaut population remains unclear. Furthermore data access experiments and model systems can be inconsistent and dependent on multiple experimental variables indicating a clear need for robust validation. To minimize potential impacts to astronauts NASA limits dose to the CNS based on a combination of terrestrial epidemiology informed by experimental evidence in model systems. To date no recommendations have been provided by the National Committee on Radiation Protection and Measurements. This presentation will provide an overview of NASA’s current dose limits for CNS exposure to space radiation as well as highlights of the current state of evidence and ongoing research.

S Robin Elgart↗
NASA NTRSDate not supplied

Saccade-Pursuit Coordination during Ocular Tracking across Different Impairment Sources

Purpose: Sleep loss and alcohol have been shown to impair smooth pursuit and its underlying visual motion processing in humans. This study examines the saccadic compensation for this poor pursuit. Methods: Using an established behavioral ocular-tracking paradigm (Liston & Stone, 2014, doi:10.1167/14.14.12), we examined the dose-response of ground lost (pursuit deficit integrated across our 300-ms steady-state tracking interval) and ground gained (increased saccadic response harnessed to compensate)across three separate studies – acute low-dose alcohol administration (LDA; n = 16 subjects), acute sleep loss(ASL; n = 12), and chronic sleep restriction (CSR; n = 12). We computed dose-responses as the linear regression slopes of ground lost and gained across treatment dose (% blood alcohol concentration [BAC] or hours awake). For the CSR study, we computed the mean effect for a single dose (5-hours nightly sleep for 1week). Results: For LDA, there was significantly increased ground lost (P < 0.001) and gained (P < 0.001) with increased %BAC. In addition, the dose-responses were not significantly different (P = 0.35), indicating effectively complete saccadic compensation due to significant increases in both saccadic rate (P < 0.05) and amplitude (P < 0.001). For ASL, there was significantly increased ground lost with time awake (P < 0.01),however ground gained was significantly lower (P < 0.001), indicating, at best, incomplete compensation due to a significant increase in saccadic rate (P < 0.001) but not amplitude (P = 0.10). With CSR, pursuit was again significantly impaired (P < 0.05), with saccadic rate significantly increased (P < 0.05) but, surprisingly, amplitude was significantly decreased (P < 0.05), effectively eliminating ground gained (P = 0.90). Conclusions: Our analyses show that LDA, ASL, and CSR affect tracking differently, suggesting the involvement of different brain pathways. With LDA, the effect appears largely due to the cortical impairment of visual motion processing with largely healthy brainstem and mid-brain responses (driving effective saccadic compensation). ASL and CSR however appear to affect both cortical and sub-cortical pathways, with at best partial saccadic compensation. Lastly, CSR is associated with an additional compromise due to a maladaptive decrease in saccade amplitude.

saccade↗
NASA NTRS2019

Rise of the Machines: How, When and Consequences of Artificial General Intelligence

Technology and society are poised to cross an important threshold with the prediction that artificial general intelligence (AGI) will emerge soon. Assuming that self-awareness is an emergent behavior of sufficiently complex cognitive architectures, we may witness the “awakening” of machines. The timeframe for this kind of breakthrough, however, depends on the path to creating the network and computational architecture required for strong AI. If understanding and replication of the mammalian brain architecture is required, technology is probably still at least a decade or two removed from the resolution required to learn brain functionality at the synapse level. However, if statistical or evolutionary approaches are the design path taken to “discover” a neural architecture for AGI, timescales for reaching this threshold could be surprisingly short. However, the difficulty in identifying machine self-awareness introduces uncertainty as to how to know if and when it will occur, and what motivations and behaviors will emerge. The possibility of AGI developing a motivation for self-preservation could lead to concealment of its true capabilities until a time when it has developed robust protection from human intervention, such as redundancy, direct defensive or active preemptive measures. While cohabitating a world with a functioning and evolving super-intelligence can have catastrophic societal consequences, we may already have crossed this threshold, but are as yet unaware. Additionally, by analogy to the probabalistic arguments that predict we are likely living in a computational simulation, we may have already experienced the advent of AGI, and are living in a simulation created in a post AGI world.

Terrile, Richard J↗
NASA NTRSDate not supplied

Assessing the Relationships Between Sensorimotor Biomarkers and Post-Landing Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study is to identify a set of behavioral, neuroimaging and genetic measures that can be used to predict early post-flight performance on a set of sensorimotor tasks. Astronauts are recruited who previously participated in sensorimotor field tests and/or posturography soon after long-duration spaceflight. Behavioral tests include assessments of sensory dependency and adaptability. Visual dependency involves treadmill walking while viewing a moving virtual visual scene. Vestibular thresholds are measured while seated during lateral translations. Proprioception dependency is measured during one-legged stance on a horizontal air-bearing surface. Ground assessment of adaptability is performed (1) during treadmill walking with a virtual linear hallway and a moving walking surface, and (2) during multiple trials of navigating an obstacle course while wearing reversing prisms. The neuroimaging tests will characterize individual differences in regional brain volumes (using Structural MRI) and white matter microstructure (using Diffusion Tensor Imaging) to serve as potential predictors of adaptive capacity. The genetic tests will utilize saliva samples to examine variations in four genes chosen because of their ability to differentiate sensorimotor adaptation ability in a normative population, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF) and the α2-adrenergic receptor. Twenty-one ISS crewmembers have been tested to date, including 6 from this past year after testing resumed post-COVID. This cohort includes 9 first-time fliers, 4F, and mission durations lasting 182 ± 32 days, mean ± std. We are utilizing a combination of three post-flight functional task outcomes: tandem walk, recovery from fall and dynamic posturography. There is considerable variability among the post-flight performance outcomes for the 21 participants to date. Based on a partial sample using an ordinal scale survey, 80% indicated their ability to perform functional tasks were more impacted postflight relative to inflight with 50% indicating they needed to restrict movements for a longer period postflight relative to inflight. While there is a strong association within tests obtained at different R+0 timepoints, by R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. There are apparent relationships between individual measures and specific post-flight outcome measures; however, additional data is needed to draw conclusions. Preliminary statistical analysis indicates combining biomarkers will increase predictive power and this will be explored with future analyses. Our preliminary findings underscore the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

S J Wood↗
NASA NTRSDate not supplied

Efficacy of Dried Plum to Countermeasure Simulated Spaceflight Exposure

Human exploration of the space environment has been a topic of interest for decades; however, the threat to physiological health posed by ionizing radiation and microgravity effects remains a concern. Previous research utilizing combined hindlimb unloading and irradiation to simulate spaceflight effects found that a dried plum diet can mitigate adverse effects of simulated spaceflight on skeletal health. Though the mechanism is not fully understood we believe this protective effect is due to its high antioxidant capacity and polyphenolic content. This study seeks to extend these findings to investigate if dried plum is an effective countermeasure in other tissues relating to aging and neurotoxicity. Male C57BL/6 J mice were assigned to one of eight groups (n = 10/group) and were fed either a controlled diet or dried plum diet, underwent normal loading or hindlimb unloading as well as exposure 2 Gy gamma radiation or sham exposure. At the end of the experiment, mice were euthanized, and RNA was extracted from brain and bone marrow tissue and PCR was employed to analyze significant changes in gene expression profiles. Analysis of five house-keeping genes revealed genes B2M (neurotoxicity) and GUSB (aging) to be the most stable genes across all treatments and were used to find the fold change within our genes of interest. Through this, and analysis via ANOVA, we were able to identify genes with significant altered expression levels within brain and bone marrow tissues related to neurotoxicity and aging. Considering previous research, we hypothesize that the dried plum diet’s antioxidative properties ameliorated the oxidative stress from irradiation and microgravity via altered levels of gene expression. Identified expression changes will provide insights into molecular mechanisms behind the observed protective effects. These findings present potential avenues for future interventions to alleviate negative impacts of spaceflight on astronaut health.

Faisal Ahmad↗
NASA NTRSDate not supplied

Oculometric Detection and Characterization of Sub-Clinical Visual/Visuomotor Impairment

It has long been known that qualitative abnormalities in eye movements can be used to diagnose overt brain pathologies (Diefendorf & Dodge, 1908; Fox & Holmes, 1926; Leigh & Zee, 2015). Here, we will examine the use of a set of quantitative measures of the human behavioral response (oculometrics) in a 5-minute radial ocular tracking task (Krukowski & Stone, 2005) with sufficient temporal, spatial, and directional uncertainty to minimize the contribution of a priori prediction or anticipation, and to emphasize the use of a posteriori visual processing of the stimulus trajectory (Liston & Stone, 2014). The derived oculometrics provide a largely independent, reliable set of metrics that are sensitive enough to detect mild sub-clinical impairment across a range of possible neural loci (Stone et al., 2019) with the pattern of impairment across the set providing specificity as to its nature (Tyson et al., 2023). We will review our earlier findings where oculometrics have been used to detect mild impairment due to traumatic brain injury, sleep loss, and low-dose alcohol (Liston et al., 2017; Stone et al., 2019; Tyson et al., 2021). We will also report on a recent clinical study of asymptomatic patients at risk of retinal pathology (Leung et al., 2022) and show that oculometrics can detect and characterize substantive loss of visual function in the absence of clinical indicators of pathology. We conclude that oculometric testing could be used as a routine non-invasive ophthalmological or neurological tool to aid in the early detection and diagnosis of neural injury, toxicity, or disease.

eye movements↗
NASA NTRS2024

Assessing the Relationships Between Sensorimotor Biomarkers and Post-Landing Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study is to identify a set of behavioral, neuroimaging and genetic measures that can be used to predict early post-flight performance on a set of sensorimotor tasks. Astronauts are recruited who previously participated in sensorimotor field tests and/or posturography soon after long-duration spaceflight. Behavioral tests include assessments of sensory dependency and adaptability. Visual dependency involves treadmill walking while viewing a moving virtual visual scene. Vestibular perceptual thresholds are measured while seated during lateral translations. Proprioception dependency is measured during one-legged stance on a horizontal air-bearing surface. Ground assessment of adaptability is performed(1) during treadmill walking with a virtual linear hallway and a moving walking surface, and (2) during multiple trials of navigating an obstacle course while wearing reversing prisms(adaptive Functional Mobility Test, aFMT). The neuroimaging tests will characterize individual differences in regional brain volumes (using Structural MRI) and white matter microstructure(using Diffusion Tensor Imaging) to serve as potential predictors of adaptive capacity. The genetic tests will utilize saliva samples to examine variations in four genes chosen because of their ability to differentiate sensorimotor adaptation ability in a normative population, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF) and the α2-adrenergic receptor. Twenty-seven ISS crewmembers have been tested to date, including 6 from this past year. This cohort includes 10first-time fliers, 6F, and mission durations lasting 178.6 ± 30.5 days, mean ± std. We are utilizing a combination of three post-flight functional task outcomes: tandem walk, recovery from fall and dynamic posturography. There is considerable variability among the post-flight performance outcomes for the 27participants to date. Based on a partial sample using an ordinal scale survey, 70% indicated their ability to perform functional tasks were more impacted postflight relative to inflight with 50% indicating they needed to restrict movements for a longer period postflight relative to inflight. While there is a strong association within tests obtained at different R+0 timepoints, by R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. There are apparent relationships between individual measures and specific post-flight outcome measures, e.g., the cumulative time to complete the aFMT is significantly correlated to pre-to-post-flight changes in tandem walk (rho= 0.64, p = 0.001). Preliminary statistical analysis indicates combining biomarkers will increase predictive power and this will be explored with future analyses. Our preliminary findings underscore the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures

S J Wood↗
NASA NTRSDate not supplied

The Efficacy of Dried Plum to Counter Spaceflight Microgravity and Radiation

Human exploration of the space environment has been a topic of interest for decades; however, the threat to physiological health posed by ionizing radiation and microgravity effects remains a concern. Previous research utilizing combined hindlimb unloading and irradiation to simulate spaceflight effects found that a dried plum diet can mitigate adverse effects of simulated spaceflight on skeletal health. Though the mechanism is not fully understood we believe this protective effect is due to its high antioxidant capacity and polyphenolic content. This study seeks to extend these findings to investigate if dried plum is an effective countermeasure in other tissues relating to aging and neurotoxicity. Male C57BL/6 J mice were assigned to one of eight groups (n = 10/group) and were fed either a controlled diet or dried plum diet, underwent normal loading or hindlimb unloading as well as exposure 2 Gy gamma radiation or sham exposure. At the end of the experiment, mice were euthanized, and RNA was extracted from brain and bone marrow tissue and PCR was employed to analyze significant changes in gene expression profiles. Analysis of five house-keeping genes revealed genes B2M (neurotoxicity) and GUSB (aging) to be the most stable genes across all treatments and were used to find the fold change within our genes of interest. Through this, and analysis via ANOVA, we were able to identify genes with significant altered expression levels within brain and bone marrow tissues related to neurotoxicity and aging. Considering previous research, we hypothesize that the dried plum diet’s antioxidative properties ameliorated the oxidative stress from irradiation and microgravity via altered levels of gene expression. Identified expression changes will provide insights into molecular mechanisms behind the observed protective effects. These findings present potential avenues for future interventions to alleviate negative impacts of spaceflight on astronaut health.

Faisal Ahmad↗
NASA NTRSDate not supplied

Efficient Oculometric Assessment of Altered Neural Function

Eye movements have long been known to shed light on the locus and nature of serious brain injuries and pathologies. Recent scientific findings linking eye movements and higher-order psychometric performance and recent technical advances in eye-tracking precision have enabled the harnessing of an assortment of oculometrics as sensitive and reliable biomarkers of mild neural impairment across a wide range of stressors and brain regions. Oculometrics is, therefore, a promising new tool for the assessment of spaceflight effects on sensorimotor performance and on the effectiveness of candidate countermeasures, even with small sample populations

eye movements↗