Head Down Tilt Bed Rest Plus Elevated CO2 as a Spaceflight Analog: Effects on Cognitive and Sensorimotor Performance

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 C 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 C 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 Frontiers in Human Neuroscience | www.frontiersin.org 1 October 2019 | Volume 13 | Article 355Lee et al. Spaceflight Analog Effects on Behavior mobility. A subset of participants exhibited signs of Spaceflight Associated Neuroocular 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 SAN

Visual Bias Predicts Gait Adaptability in Novel Sensory Discordant Conditions

We designed a gait training study that presented combinations of visual flow and support-surface manipulations to investigate the response of healthy adults to novel discordant sensorimotor conditions. We aimed to determine whether a relationship existed between subjects visual dependence and their postural stability and cognitive performance in a new discordant environment presented at the conclusion of training (Transfer Test). Our training system comprised a treadmill placed on a motion base facing a virtual visual scene that provided a variety of sensory challenges. Ten healthy adults completed 3 training sessions during which they walked on a treadmill at 1.1 m/s while receiving discordant support-surface and visual manipulations. At the first visit, in an analysis of normalized torso translation measured in a scene-movement-only condition, 3 of 10 subjects were classified as visually dependent. During the Transfer Test, all participants received a 2-minute novel exposure. In a combined measure of stride frequency and reaction time, the non-visually dependent subjects showed improved adaptation on the Transfer Test compared to their visually dependent counterparts. This finding suggests that individual differences in the ability to adapt to new sensorimotor conditions may be explained by individuals innate sensory biases. An accurate preflight assessment of crewmembers biases for visual dependence could be used to predict their propensities to adapt to novel sensory conditions. It may also facilitate the development of customized training regimens that could expedite adaptation to alternate gravitational environments

Serum malondialdehyde and serum glutathione peroxidase levels in pregnant women with and without preeclampsia

Background: Preeclampsia is a pregnancy-specific disorder that affects 10% of all pregnancies which contributes heavily to maternal mortality and perinatal morbidity. Several studies have shown that oxidative stress plays an important role in the pathogenesis of preeclampsia. However, the association has not been proven indisputably. So, the study was done with the view to determine serum malondialdehyde and glutathione peroxidase levels in pregnant women with and without preeclampsia and to compare the levels between the two groups of participants. Methods: This is a cross-sectional study conducted in the Department of Biochemistry and Department of Obstetrics and Gynaecology, RIMS. 55 preeclamptic patients and 55 pregnant women without preeclampsia were recruited as cases and controls respectively. Results: Serum malondialdehyde was found to be significantly higher in cases (1280.02±619.55ng/ml) than the controls (826.51±599.84ng/ml) and glutathione peroxidase levels were found to be significantly decreased in the preeclamptic women (224.49±201.29pg/ml) when compared to the normal healthy pregnant women (448±350.54 pg/ml. Serum malondialdehyde levels were found to be positively correlated with blood pressure. Conclusions: Serum malondialdehyde was increased in preeclampsia and serum glutathione levels was decreased in preeclamptic pregnant women when compared to the pregnant women without preeclampsia. Serum malondialdehyde levels were significantly correlated with high blood pressure. The oxidant-antioxidant system may be involved in the etiology of preeclampsia, however the cause and effect relation needs further evaluation

Mycobacterial cultures contain cell size and density specific sub-populations of cells with significant differential susceptibility to antibiotics, oxidative and nitrite stress

The present study shows the existence of two specific sub-populations of Mycobacterium smegmatis and Mycobacterium tuberculosis cells differing in size and density, in the mid-log phase (MLP) cultures, with significant differential susceptibility to antibiotic, oxidative, and nitrite stress. One of these sub-populations (similar to 10% of the total population), contained short-sized cells (SCs) generated through highly-deviated asymmetric cell division (ACD) of normal/long-sized mother cells and symmetric cell divisions (SCD) of short-sized mother cells. The other sub-population (similar to 90% of the total population) contained normal/long-sized cells (NCs). The SCs were acid-fast stainable and heat-susceptible, and contained high density of membrane vesicles (MVs, known to be lipid-rich) on their surface, while the NCs possessed negligible density of MVs on the surface, as revealed by scanning and transmission electron microscopy. Percoll density gradient fractionation of MLP cultures showed the SCs-enriched fraction (SCF) at lower density (probably indicating lipid-richness) and the NCs-enriched fraction (NCF) at higher density of percoll fractions. While live cell imaging showed that the SCs and the NCs could grow and divide to form colony on agarose pads, the SCF, and NCF cells could independently regenerate MLP populations in liquid and solid media, indicating their full genomic content and population regeneration potential. CFU based assays showed the SCF cells to be significantly more susceptible than NCF cells to a range of concentrations of rifampicin and isoniazid (antibiotic stress), H2O2 (oxidative stress),and acidified NaNO2 (nitrite stress). Live cell imaging showed significantly higher susceptibility of the SCs of SC-NC sister daughter cell pairs, formed from highly-deviated ACD of normal/long-sized mother cells, to rifampicin and H2O2, as compared to the sister daughter NCs, irrespective of their comparable growth rates. The SC-SC sister daughter cell pairs, formed from the SCDs of short-sized mother cells and having comparable growth rates, always showed comparable stress-susceptibility. These observations and the presence of M. tuberculosis SCs and NCs in pulmonary tuberculosis patients' sputum earlier reported by us imply a physiological role for the SCs and the NCs under the stress conditions. The plausible reasons for the higher stress susceptibility of SCs and lower stress susceptibility of NCs are discussed

Study protocol to examine the effects of spaceflight and a spaceflight analog on neurocognitive performance: extent, longevity, and neural bases

Abstract Background Long duration spaceflight (i.e., 22 days or longer) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes. Whether spaceflight also affects other central nervous system functions such as cognition is yet largely unknown, but of importance in consideration of the health and performance of crewmembers both in- and post-flight. We are therefore conducting a controlled prospective longitudinal study to investigate the effects of spaceflight on the extent, longevity and neural bases of sensorimotor and cognitive performance changes. Here we present the protocol of our study. Methods/design This study includes three groups (astronauts, bed rest subjects, ground-based control subjects) for which each the design is single group with repeated measures. The effects of spaceflight on the brain will be investigated in astronauts who will be assessed at two time points pre-, at three time points during-, and at four time points following a spaceflight mission of six months. To parse out the effect of microgravity from the overall effects of spaceflight, we investigate the effects of seventy days head-down tilted bed rest. Bed rest subjects will be assessed at two time points before-, two time points during-, and three time points post-bed rest. A third group of ground based controls will be measured at four time points to assess reliability of our measures over time. For all participants and at all time points, except in flight, measures of neurocognitive performance, fine motor control, gait, balance, structural MRI (T1, DTI), task fMRI, and functional connectivity MRI will be obtained. In flight, astronauts will complete some of the tasks that they complete pre- and post flight, including tasks measuring spatial working memory, sensorimotor adaptation, and fine motor performance. Potential changes over time and associations between cognition, motor-behavior, and brain structure and function will be analyzed. Discussion This study explores how spaceflight induced brain changes impact functional performance. This understanding could aid in the design of targeted countermeasures to mitigate the negative effects of long-duration spaceflight.http://deepblue.lib.umich.edu/bitstream/2027.42/112560/1/12883_2013_Article_922.pd

Neural Working Memory Changes During a Spaceflight Analog With Elevated Carbon Dioxide: A Pilot Study

Spaceflight missions to the International Space Station (ISS) expose astronauts to microgravity, radiation, isolation, and elevated carbon dioxide (CO₂), among other factors. Head down tilt bed rest (HDBR) is an Earth-based analog for spaceflight used to study body unloading, fluid shifts, and other factors unrelated to gravitational changes. While in space, astronauts need to use mental rotation strategies to facilitate their adaptation to the ISS environment. Therefore, spatial working memory is essential for crewmember performance. Although the effects of HDBR on spatial working memory have recently been studied, the results are still inconclusive. Here, we expand upon past work and examine the effects of HDBR with elevated CO₂ (HDBR + CO₂) on brain activation patterns during spatial working memory performance. In addition, we compare brain activation between 30 days of HDBR + CO₂ and 70 days of HDBR to test the isolated effect of CO₂. Eleven subjects (6 males, 5 females; mean age = 34 ± 8 years) underwent six functional magnetic resonance imaging (fMRI) sessions pre-, during, and post-HDBR + CO₂. During the HDBR + CO₂ intervention, we observed decreasing activation in the right middle frontal gyrus and left regions of the cerebellum, followed by post-intervention recovery. We detected several correlations between brain and behavioral slopes of change with the HDBR + CO₂ intervention. For example, greater increases in activation in frontal, temporal and parietal regions were associated with larger spatial working memory improvements. Comparing the HDBR + CO₂ group to data from our previous 70-day HDBR study, we found greater decreases in activation in the right hippocampus and left inferior temporal gyrus for the HDBR + CO₂ group over the course of the intervention. Together, these findings increase our understanding of the neural mechanisms of HDBR, elevated levels of CO₂ and spaceflight-related changes in spatial working memory performance

The Impact of 6 and 12 Months in Space on Human Brain Structure and Intracranial Fluid Shifts

As plans develop for Mars missions, it is important to understand how long-duration spaceflight impacts brain health. Here we report how 12-month (n = 2 astronauts) versus 6-month (n = 10 astronauts) missions impact brain structure and fluid shifts. We collected MRI scans once before flight and four times after flight. Astronauts served as their own controls; we evaluated pre- to postflight changes and return toward preflight levels across the 4 postflight points. We also provide data to illustrate typical brain changes over 7 years in a reference dataset. Twelve months in space generally resulted in larger changes across multiple brain areas compared with 6-month missions and aging, particularly for fluid shifts. The majority of changes returned to preflight levels by 6 months after flight. Ventricular volume substantially increased for 1 of the 12-month astronauts (left: +25%, right: +23%) and the 6-month astronauts (left: 17 ± 12%, right: 24 ± 6%) and exhibited little recovery at 6 months. Several changes correlated with past flight experience; those with less time between subsequent missions had larger preflight ventricles and smaller ventricular volume increases with flight. This suggests that spaceflight-induced ventricular changes may endure for long periods after flight. These results provide insight into brain changes that occur with longduration spaceflight and demonstrate the need for closer study of fluid shift

Neural Correlates of Vestibular Processing During a Spaceflight Analog With Elevated Carbon Dioxide (CO₂): A Pilot Study

Astronauts return to Earth from spaceflight missions with impaired mobility and balance; recovery can last weeks postflight. This is due in large part to the altered vestibular signaling and sensory reweighting that occurs in microgravity. The neural mechanisms of spaceflight-induced vestibular changes are not well understood. Head-down-tilt bed rest (HDBR) is a common spaceflight analog environment that allows for study of body unloading, fluid shifts, and other consequences of spaceflight. Subjects in this context still show vestibular changes despite being in Earth’s gravitational environment, potentially due to sensory reweighting. Previously, we found evidence of sensory reweighting and reduced neural efficiency for vestibular processing in subjects who underwent a 70-day HDBR intervention. Here we extend this work by evaluating the impact of HDBR paired with elevated carbon dioxide (CO₂) to mimic International Space Station conditions on vestibular neural processing. Eleven participants (6 males, 34 ± 8 years) completed 30 days of HDBR combined with 0.5% atmospheric CO₂ (HDBR + CO₂). Participants underwent six functional magnetic resonance imaging (fMRI) sessions pre-, during, and post- HDBR + CO₂ while we measured brain activity in response to pneumatic skull taps (a validated method of vestibular stimulation). We also measured mobility and balance performance several times before and after the intervention. We found support for adaptive neural changes within the vestibular system during bed rest that subsequently recovered in several cortical and cerebellar regions. Further, there were multiple brain regions where greater pre- to post- deactivation was associated with reduced pre- to post- balance declines. That is, increased deactivation of certain brain regions associated with better balance post-HDBR + CO₂. We also found that, compared to HDBR alone (n = 13 males; 29 ± 3 years) HDBR + CO₂ is associated with greater increases in activation of multiple frontal, parietal, and temporal regions during vestibular stimulation. This suggests interactive or additive effects of bed rest and elevated CO₂. Finally, we found stronger correlations between pre- to postHDBR + CO₂ brain changes and dependence on the visual system during balance for subjects who developed signs of Spaceflight-Associated Neuro-ocular Syndrome Frontiers in Systems Neuroscience | www.frontiersin.org 1 January 2020 | Volume 13 | Article 80Hupfeld et al. Neural Vestibular Processing With HDBR + CO₂ (SANS). Together, these findings have clear implications for understanding the neural mechanisms of bed rest and spaceflight-related changes in vestibular processing, as well as adaptation to altered sensory inputs

Understanding the Effects of Long-duration Space Flight on Astronant Functional Task Performance

Space flight is known to cause alterations in multiple physiological systems including changes in sensorimotor, cardiovascular, and neuromuscular systems. These physiological changes cause balance, gait and visual disturbances, cardiovascular deconditioning, and loss of muscle mass and strength. These changes may affect a crewmember's ability to perform critical mission tasks immediately after landing on a planetary surface. To understand how changes in physiological function affect functional performance, an interdisciplinary pre- and postflight testing regimen, Functional Task Test (FTT), was developed to systematically evaluate both astronaut functional performance and related physiological changes. Ultimately this information will be used to assess performance risks and inform the design of countermeasures for exploration class missions. We are currently conducting the FTT study on International Space Station (ISS) crewmembers before and after 6-month expeditions. Additionally, in a corresponding study we are using the FTT protocol on subjects before and after 70 days of 6deg head-down bed-rest as an analog for space flight. Bed-rest provides the opportunity for us to investigate the role of prolonged axial body unloading in isolation from the other physiological effects produced by exposure to the microgravity environment of space flight. Therefore, the bed rest analog allows us to investigate the impact of body unloading on both functional tasks and on the underlying physiological factors that lead to decrement in performance and then compare them with the results obtained in our space flight study. Functional tests included ladder climbing, hatch opening, jump down, manual manipulation of objects and tool use, seat egress and obstacle avoidance, recovery from a fall and object translation tasks. Physiological measures included assessments of postural and gait control, dynamic visual acuity, fine motor control, plasma volume, heart rate, blood pressure, orthostatic intolerance, upper- and lower-body muscle strength, power, endurance, control, and neuromuscular drive. ISS crewmembers were tested three times before flight, and on 1, 6, and 30 days after landing. Bed-rest subjects were tested three times before bed-rest and immediately after getting up from bed-rest as well as 1, 6, and 12 days after reambulation