Head Down Tilt Bed Rest Plus Elevated CO2 as a Spaceflight Analog: Effects on Cognitive and Sensorimotor Performance.
ABSTRACT: Long duration head down tilt bed rest (HDBR) has been widely used as a spaceflight analog environment to understand the effects of microgravity on human physiology and performance. Reports have indicated that crewmembers onboard the International Space Station (ISS) experience symptoms of elevated CO2 such as headaches at lower levels of CO2 than levels at which symptoms begin to appear on Earth. This suggests there may be combinatorial effects of elevated CO2 and the other physiological effects of microgravity including headward fluid shifts and body unloading. The purpose of the current study was to investigate these effects by evaluating the impact of 30 days of 6° HDBR and 0.5% CO2 (HDBR + CO2) on mission relevant cognitive and sensorimotor performance. We found a facilitation of processing speed and a decrement in functional mobility for subjects undergoing HDBR + CO2 relative to our previous study of HDBR in ambient air. In addition, nearly half of the participants in this study developed signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), a constellation of ocular structural and functional changes seen in approximately one third of long duration astronauts. This allowed us the unique opportunity to compare the two subgroups. We found that participants who exhibited signs of SANS became more visually dependent and shifted their speed-accuracy tradeoff, such that they were slower but more accurate than those that did not incur ocular changes. These small subgroup findings suggest that SANS may have an impact on mission relevant performance inflight via sensory reweighting. New And Noteworthy:We examined the effects of long duration head down tilt bed rest coupled with elevated CO2 as a spaceflight analog environment on human cognitive and sensorimotor performance. We found enhancements in processing speed and declines in functional mobility. A subset of participants exhibited signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), which affects approximately one in three astronauts. These individuals increased their visual reliance throughout the intervention in comparison to participants who did not show signs of SANS.
Project description:Spaceflight-associated neuro-ocular syndrome (SANS) describes a series of morphologic and functional ocular changes in astronauts first reported by Mader and colleagues in 2011. SANS is currently clinically defined by the development of optic disc edema during prolonged exposure to the weightless (microgravity) environment, which currently occurs on International Space Station (ISS). However, as improvements in our understanding of the ocular changes emerge, the definition of SANS is expected to evolve. Other ocular SANS signs that arise during and after ISS missions include hyperopic shifts, globe flattening, choroidal/retinal folds, and cotton wool spots. Over the last 10 years, ~1 in 3 astronauts flying long-duration ISS missions have presented with ?1 of these ocular findings. Commensurate with research that combines disparate specialties (vision biology and spaceflight medicine), lessons from SANS investigations may also yield insight into ground-based ocular disorders, such as glaucomatous optic neuropathy that may have the potential to lessen the burden of this irreversible cause of vision loss on Earth.
Project description:Adverse effects of spaceflight on sensorimotor function have been linked to altered somatosensory and vestibular inputs in the microgravity environment. Whether these spaceflight sequelae have a central nervous system component is unknown. However, experimental studies have shown spaceflight-induced brain structural changes in rodents' sensorimotor brain regions. Understanding the neural correlates of spaceflight-related motor performance changes is important to ultimately develop tailored countermeasures that ensure mission success and astronauts' health.Head down-tilt bed rest (HDBR) can serve as a microgravity analog because it mimics body unloading and headward fluid shifts of microgravity. We conducted a 70-day 6° HDBR study with 18 right-handed males to investigate how microgravity affects focal gray matter (GM) brain volume. MRI data were collected at 7 time points before, during and post-HDBR. Standing balance and functional mobility were measured pre and post-HDBR. The same metrics were obtained at 4 time points over ~90 days from 12 control subjects, serving as reference data.HDBR resulted in widespread increases GM in posterior parietal regions and decreases in frontal areas; recovery was not yet complete by 12 days post-HDBR. Additionally, HDBR led to balance and locomotor performance declines. Increases in a cluster comprising the precuneus, precentral and postcentral gyrus GM correlated with less deterioration or even improvement in standing balance. This association did not survive Bonferroni correction and should therefore be interpreted with caution. No brain or behavior changes were observed in control subjects.Our results parallel the sensorimotor deficits that astronauts experience post-flight. The widespread GM changes could reflect fluid redistribution. Additionally, the association between focal GM increase and balance changes suggests that HDBR also may result in neuroplastic adaptation. Future studies are warranted to determine causality and underlying mechanisms.
Project description:Prolonged microgravity exposure during long-duration spaceflight (LDSF) produces unusual physiologic and pathologic neuro-ophthalmic findings in astronauts. These microgravity associated findings collectively define the "Spaceflight Associated Neuro-ocular Syndrome" (SANS). We compare and contrast prior published work on SANS by the National Aeronautics and Space Administration's (NASA) Space Medicine Operations Division with retrospective and prospective studies from other research groups. In this manuscript, we update and review the clinical manifestations of SANS including: unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and focal areas of ischemic retina (i.e., cotton wool spots). We also discuss the knowledge gaps for in-flight and terrestrial human research including potential countermeasures for future study. We recommend that NASA and its research partners continue to study SANS in preparation for future longer duration manned space missions.
Project description:A subset of long-duration spaceflight astronauts have experienced ophthalmic abnormalities, collectively termed spaceflight-associated neuro-ocular syndrome (SANS). Little is understood about the pathophysiology of SANS; however, microgravity-induced alterations in intracranial pressure (ICP) due to headward fluid shifts is the primary hypothesized contributor. In particular, potential changes in optic nerve (ON) tortuosity and ON sheath (ONS) distension may indicate altered cerebrospinal fluid dynamics during weightlessness. The present longitudinal study aims to provide a quantitative analysis of ON and ONS cross-sectional areas, and ON deviation, an indication of tortuosity, before and after spaceflight. Ten astronauts undergoing ~6-month missions on the International Space Station (ISS) underwent high-resolution magnetic resonance imaging (MRI) preflight and at five recovery time points extending to 1 year after return from the ISS. The mean changes in ON deviation, ON cross-sectional area, and ONS cross-sectional area immediately post flight were -0.14?mm (95% CI: -0.36 to 0.08, Bonferroni-adjusted P?=?1.00), 0.13?mm2 (95% CI -0.66 to 0.91, Bonferroni-adjusted P?=?1.00), and -0.22?mm2 (95% CI: -1.78 to 1.34, Bonferroni-adjusted P?=?1.00), respectively, and remained consistent during the recovery period. Terrestrially, ONS distension is associated with increased ICP; therefore, these results suggest that, on average, ICP was not pathologically elevated immediately after spaceflight. However, a subject diagnosed with optic disc edema (Frisen Grade 1, right eye) displayed increased ONS area post flight, although this increase is relatively small compared to clinical populations with increased ICP. Advanced quantitative MRI-based assessment of the ON and ONS could help our understanding of SANS and the role of ICP.
Project description:Biofilm formation is closely related to the pathogenetic processes of Klebsiella pneumoniae, which frequently causes infections in immunocompromised individuals. The immune system of astronauts is compromised in spaceflight. Accordingly, K. pneumoniae, which used to be isolated from orbiting spacecraft and astronauts, poses potential threats to the health of astronauts and mission security. Microgravity is a key environmental cue during spaceflight. Therefore, determining its effects on bacterial biofilm formation is necessary. In this study, K. pneumoniae ATCC BAA-1705 was exposed to a simulated microgravity (SMG) environment. K. pneumoniae grown under SMG formed thicker biofilms compared with those under normal gravity (NG) control after 2 weeks of subculture. Two indicative dyes (i.e., Congo red and calcofluor) specifically binding to cellulose fibers and/or fimbriae were utilized to reconfirm the enhanced biofilm formation ability of K. pneumoniae grown under SMG. Further analysis showed that the biofilms formed by SMG-treated K. pneumoniae were susceptible to cellulase digestion. Yeast cells mannose-resistant agglutination by K. pneumoniae type 3 fimbriae was more obvious in the SMG group, which suggests that cellulose production and type 3 fimbriae expression in K. pneumoniae were both enhanced under the SMG condition. Transcriptomic analysis showed that 171 genes belonging to 15 functional categories were dysregulated in this organism exposed to the SMG conditions compared with those in the NG group, where the genes responsible for the type 3 fimbriae (mrkABCDF) and its regulator (mrkH) were upregulated.
Project description:A round-trip human mission to Mars is anticipated to last roughly three years. Spaceflight conditions are known to cause loss of bone mineral density (BMD) in astronauts, increasing bone fracture risk. There is an urgent need to understand BMD progression as a function of spaceflight time to minimize associated health implications and ensure mission success. Here we introduce a nonlinear mathematical model of BMD loss for candidate human missions to Mars: (i) Opposition class trajectory (400-600 days), and (ii) Conjunction class trajectory (1000-1200 days). Using femoral neck BMD data (N = 69) from astronauts after 132-day and 228-day spaceflight and the World Health Organization's fracture risk recommendation, we predicted post-mission risk and associated osteopathology. Our model predicts 62% opposition class astronauts and 100% conjunction class astronauts will develop osteopenia, with 33% being at risk for osteoporosis. This model can help in implementing countermeasure strategies and inform space agencies' choice of crew candidates.
Project description:Exposure to microgravity causes alterations in multiple physiological systems, potentially impacting the ability of astronauts to perform critical mission tasks. The goal of this study was to determine the effects of spaceflight on functional task performance and to identify the key physiological factors contributing to their deficits.A test battery comprised of seven functional tests and 15 physiological measures was used to investigate the sensorimotor, cardiovascular, and neuromuscular adaptations to spaceflight. Astronauts were tested before and after 6-month spaceflights. Subjects were also tested before and after 70 d of 6° head-down bed rest, a spaceflight analog, to examine the role of axial body unloading on the spaceflight results. These subjects included control and exercise groups to examine the effects of exercise during bed rest.Spaceflight subjects showed the greatest decrement in performance during functional tasks that required the greatest demand for dynamic control of postural equilibrium which was paralleled by similar decrements in sensorimotor tests that assessed postural and dynamic gait control. Other changes included reduced lower limb muscle performance and increased HR to maintain blood pressure. Exercise performed during bed rest prevented detrimental change in neuromuscular and cardiovascular function; however, both bed rest groups experienced functional and balance deficits similar to spaceflight subjects.Bed rest data indicate that body support unloading experienced during spaceflight contributes to postflight postural control dysfunction. Further, the bed rest results in the exercise group of subjects confirm that resistance and aerobic exercises performed during spaceflight can play an integral role in maintaining neuromuscular and cardiovascular functions, which can help in reducing decrements in functional performance. These results indicate that a countermeasure to mitigate postflight postural control dysfunction is required to maintain functional performance.
Project description:The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and axial body unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6° HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n?=?12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging was used to quantify distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreases in the post-central gyrus and precuneus correlated negatively with balance changes. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.
Project description:Spaceflight is associated with deregulation in the immune system. Head-down bed rest (HDBR) at -6° is believed to be the most practical model for examining multi-system responses to microgravity in humans during spaceflight. In the present study, a 45-day HDBR was performed to investigate the alterations in human immune cell distributions and their functions in response to various stimuli. The effect of countermeasure, Rhodiola rosea (RR) treatment, was also examined. A significant decrease of interferon-? (IFN-?) and interleukin-17 (IL-17) productions by activated T cells, increase of IL-1? and IL-18 by activated B and myeloid cells were observed during HDBR. The upregulation of serum cortisol was correlated with the changes of IL-1 family cytokines. In addition, a significant increase of memory T and B cell and regulatory T cells (Treg) were also detected. The uptake of RR further decreased IFN-? level and slowed down the upregulation of IL-1 family cytokines. These data suggest that for prolonged HDBR and spaceflight, the decreased protective T cell immunity and enhanced proinflammatory cytokines should be closely monitored. The treatment with RR may play an important role in suppressing proinflammatory cytokines but not in boosting protective T cell immunity.
Project description:Spaceflight is a unique environment that includes at least two factors which can negatively impact skeletal health: microgravity and ionizing radiation. We have previously shown that a diet supplemented with dried plum powder (DP) prevented radiation-induced bone loss in mice. In this study, we investigated the capacity of the DP diet to prevent bone loss in mice following exposure to simulated spaceflight, combining microgravity (by hindlimb unloading) and radiation exposure. The DP diet was effective at preventing most decrements in bone micro-architectural and mechanical properties due to hindlimb unloading alone and simulated spaceflight. Furthermore, we show that the DP diet can protect osteoprogenitors from impairments resulting from simulated microgravity. Based on our findings, a dietary supplementation with DP could be an effective countermeasure against the skeletal deficits observed in astronauts during spaceflight.