Hyper.Campus-Effects of Artificial Gravity on Structural and Functional Brain Plasticity During Head-Down Tilt Bed Rest

Abstract

Artificial gravity (AG) is emerging as a candidate countermeasure against cardiovascular and musculoskeletal deconditioning associated with long duration spaceflight. Remarkably, the neural basis of cognitive performance changes (especially spatial cognition) associated with AG have received little attention. In fact, research on the effects of intermittent AG on structural and functional changes of the brain is lacking. Whereas the entire brain may be prone to structural and functional changes as a result of body unloading and AG, the hippocampal formation is a key area due to its role in spatial learning, memory, and navigation. Furthermore, the hippocampus is one of only two areas of the human brain capable of adult neurogenesis, suggesting it may be a key target for mitigating neurocognitive impairments associated with bed rest. To address this gap, we aimed to investigate effects of longduration bed rest and the efficacy of AG as a countermeasure on brain plasticity and their behavioral significance. As part of the joint NASA and ESA bed rest experiment using AG as a countermeasure (AGBRESA), we investigated the impact of 60 days of -6° head down-tilt bed rest with and without AG using two different centrifugation protocols (intermittent vs. continuous exposure) on brain structure and function, cognitive performance and key neurotrophic growth factors. A total of N=24 subjects were randomly assigned to one of the three following groups of N=8: bed rest only (CTRL), bed rest plus intermittent AG (iAG), bed rest plus continuous AG (cAG). Our primary outcomes were structural and functional changes of the brain using high-resolution imaging sequences. In addition to structural and resting state functional imaging, we also employed various fMRI tasks, specifically targeting pattern separation and affective processing. Neurobehavioral testing comprised a range of tasks, assessing visuospatial navigation, working memory and executive control. Saliva and venous blood samples were collected to better understand the mechanisms underlying any changes in brain structure and function. The study was conducted at DLR :envihab, and involved two campaigns of 12 participants each. The final sample included the target N=24 subjects with N=8 CTRL (6 men, 2 women, mean age: 35 yrs), N=8 cAG (5 men, 3 women, mean age: 32 yrs), and N=8 iAG (5 men, 3 woman, mean age: 34 yrs). The following data were collected, and analyzed: (1) 96 multimodal brain imaging sessions performed on BDC-3, HDT30, HDT59, and R+11 (100% of nominal); (2) 120 sessions of Spatial Cognition Battery 1 comprising four tasks, and administered on BDC-3, HDT2, HDT30, HDT59, and R+12 (99.4% of nominal); (3) 24 sessions of Spatial Cognition Battery 2 comprising four tasks administered on HDT59 or HDT60 (93.3% of nominal); (4) 312 sessions of NASA’s Cognition Battery comprising 10 tasks performed on BDC-9, BDC-7, BDC-6, HDT1, HDT3, HDT5, HDT14, HDT28, HDT42, HDT57, R+1, R+5, and R+12 (98.84% of nominal); (5) 432 collections of saliva cortisol collected in the morning and evening on BDC-6, BDC-3, HDT2, HDT14, HDT30, HDT42, HDT56, R+1, and R+10 (99.6% of nominal); and (6) 296 venous blood collections collected in the morning and after AG (only during HDBR) on BDC-6, BDC-3, HDT02, HDT14, HDT30, HDT42, HDT56, R+1, and R+10, providing a total of 2072 samples to determine BDNF, IGF-1, VEGF, NF-L, IL-1b, IL-6, and TNa (99% of nominal). In this presentation we summarize the main findings of neuroimaging, cognitive, and biochemical measures. Our primary outcome focused on high resolution hippocampal imaging. The findings confirm our previous data showing impairments of hippocampal plasticity in response to bed rest, and adverse effects on spatial cognition. Furthermore, our findings suggest that AG seems to mitigate some of these effects, and deserves further consideration as a countermeasure to reduce neurobehavioral risks during exploration class space missions