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

Impacts of spaceflight experience on human brain structure

Abstract Spaceflight induces widespread changes in human brain morphology. It is unclear if these brain changes differ with varying mission duration or spaceflight experience history (i.e., novice or experienced, number of prior missions, time between missions). Here we addressed this issue by quantifying regional voxelwise changes in brain gray matter volume, white matter microstructure, extracellular free water (FW) distribution, and ventricular volume from pre- to post-flight in a sample of 30 astronauts. We found that longer missions were associated with greater expansion of the right lateral and third ventricles, with the majority of expansion occurring during the first 6 months in space then appearing to taper off for longer missions. Longer inter-mission intervals were associated with greater expansion of the ventricles following flight; crew with less than 3 years of time to recover between successive flights showed little to no enlargement of the lateral and third ventricles. These findings demonstrate that ventricle expansion continues with spaceflight with increasing mission duration, and inter-mission intervals less than 3 years may not allow sufficient time for the ventricles to fully recover their compensatory capacity. These findings illustrate some potential plateaus in and boundaries of human brain changes with spaceflight