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Project Title:  Hyper.Campus - Effects of Artificial Gravity on Structural and Functional Plasticity During Head-Down Tilt Bed Rest Reduce
Images: icon  Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
HRP HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Start Date: 04/10/2018  
End Date: 08/31/2021  
Task Last Updated: 02/14/2022 
Download report in PDF pdf
Principal Investigator/Affiliation:   Stahn, Alexander  Ph.D. / University of Pennsylvania 
Address:  Division of Sleep and Chronobiology, Department of Psychiatry 
423 Guardian Dr, 1016 Blockley Hall 
Philadelphia , PA 19104-4865 
Email: astahn@pennmedicine.upenn.edu 
Phone: 215-898-9667  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Pennsylvania 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Dinges, David  Ph.D. University of Pennsylvania 
Gunga, Hanns-Christian  M.D. Charite - Universitatsmedizin Berlin, Germany 
Gur, Ruben  Ph.D. University of Pennsylvania 
Kuehn, Simone  Ph.D. Max Planck Institute for Human Development Berlin, Germany 
Roalf, David  Ph.D. University of Pennsylvania 
Basner, Mathias  M.D., Ph.D. University of Pennsylvania 
Garcia, Caroline  Ph.D. University Medical Center Hamburg-Eppendorf 
Hartley, Tom  Ph.D. University of York 
Riecke, Bernhard  Ph.D. Simon Fraser University  
Miller, Noah  Ph.D. Simon Fraser University 
Moore, Tyler  Ph.D. University of Pennsylvania 
Friedl-Werner, Anika  Ph.D. Charité-Universitätsmedizin Berlin 
Brauns, Katharina  Ph.D. Charité-Universitätsmedizin Berlin 
Key Personnel Changes / Previous PI: February 2022 final report: CoInvestigators changed in the past two years; see CoInvestigator field for FY2021 vs. FY2020 report. February 2019 report: Two PhD students, who are critical to the study, are included as key to study implementation: • Anika Werner, Charite - Universitatsmedizin Berlin, Institute of Physiology, Center for Space Medicine and Extreme Environments Berlin, CharitéCrossOver (CCO), Charitéplatz 1, Virchowweg 6, 10117 Berlin, Email: anika.werner@charite.de, and Katharina Brauns, Charite - Universitatsmedizin Berlin, Institute of Physiology, Center for Space Medicine and Extreme Environments Berlin, CharitéCrossOver (CCO), Charitéplatz 1, Virchowweg 6, 10117 Berlin, Email: Katharina.brauns@charite.de
Project Information: Grant/Contract No. 80NSSC18K0765 
Responsible Center: NASA JSC 
Grant Monitor: Whitmire, Alexandra  
Center Contact:  
alexandra.m.whitmire@nasa.gov 
Solicitation / Funding Source: 2015-16 HERO NNJ15ZSA001N-AGBR. Appendix G: Physiological & Behavioral Responses in Humans to Intermittent Artificial Gravity during Bed Rest 
Grant/Contract No.: 80NSSC18K0765 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Human Research Program Risks: (1) HFBP Bmed:Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders (IRP Rev J)
Human Research Program Gaps: (1) BMed-101:We need to identify, quantify, and validate the key selection factors for astronaut cognitive and behavioral strengths (e.g., resiliency) and operationally-relevant performance threats for increasingly Earth independent, long-duration, autonomous, and/or long-distance exploration missions (IRP Rev L)
(2) BMed-103:What are the validated, efficacious treatments (individual or Team-based) and/or countermeasures to prevent adverse behavioral conditions, CNS/neurological, and/or psychiatric disorders caused by either single and/or integrated exposures to spaceflight hazards during exploration class missions? (IRP Rev L)
(3) BMed-105:Given the potentially negative spaceflight associated CNS/cognitive changes and behavioral experiences of stressors during long-duration missions (e.g., isolation, confinement, reduced sensory stimulation, altered gravity, space radiation), what are validated medical or dietary countermeasures to mitigate stressors impacting on CNS / cognition / behavioral health? (IRP Rev L)
(4) BMed-107:What are the long-term changes and risks to astronaut health post-mission that, when using a continuity of care model, helps retrospectively identify and understand individual susceptibility (e.g., hereditary, dose, thresholds) to mitigate adverse CNS, cognitive, and behavioral health changes resulting from long-duration exploration missions, promoting the behavioral health of current and future crews? (IRP Rev L)
(5) BMed-108:Given each crewmember will experience multiple spaceflight hazards simultaneously, we need to identify and characterize the potential additive, antagonistic, or synergistic impacts of multiple stressors (e.g., space radiation, altered gravity, isolation, altered immune, altered sleep) on crew health and/or CNS/ cognitive functioning to develop threshold limits and validate countermeasures for any identified adverse crew health and/or operationally-relevant performance outcomes (IRP Rev L)
Flight Assignment/Project Notes: NOTE: End date changed to 8/31/2021 per NSSC information (Ed., 1/11/21)

Task Description: This project addressed the risk of Adverse Behavioral Conditions and Psychiatric Disorders, and the need to validate countermeasures that promote individual behavioral health and performance during exploration class missions. As part of the NASA/ESA AGBRESA (NASA/European Space Agency/Artificial Gravity Bed Rest – European Space Agency) study we investigated the effects of artificial gravity (AG) as a countermeasure during 60 days of head down tilt bed rest (HDBR) on brain changes and its behavioral significance. N=24 subjects were randomly allocated to one of three groups: (1) HDBR only (N=8); (2) HDBR plus daily intermittent AG comprising of 6 bouts of 5 min AG (N=8); and (3) HDBR plus daily continuous AG comprising of 30 min AG (N=8). We identified structural and functional brain changes using magnetic resonance imaging (MRI), and specifically targeted neural correlates of spatial cognition, i.e., the hippocampal formation, parahippocampus, insula, striatum, caudate nucleus, and precuneus. Spatial abilities were investigated using a variety of tasks assessing spatial updating, path integration, perspective taking, wayfinding, and spatial learning and memory formation. Given that spatial abilities are also tightly coupled to executive functions, we additionally administered two paradigms to quantify flexible coordination of multiple task-sets using a switching task, and a dual task based on a psychological refractory period paradigm. Furthermore, we used the Cognition test battery to screen changes in general cognitive performance. Finally, we also collected blood and saliva samples to identify the time course of key neurotrophins (i.e., BDNF, IGF-1, VEGF, NF-L) and pro-inflammatory markers (i.e., Il-1b, Il-6, and TNFa) associated with the effects of bed rest and AG. To assess the acute effects of the AG countermeasure, blood samples were collected in the morning as well as after selected AG sessions. Together, these data provide important information about the neurophysiological mechanisms and pathways related to the effects of HDBR and the AG countermeasure. The study had the following specific aims (SA):

SA 1: Investigate the effects of HDBR with and without artificial gravity on gray and white matter volume, subcortical volume, myelination, functional connectivity, and task-related brain activation: We assessed subjects with quantitative structural and functional MRI before, during, and after HDBR.

SA 2: Investigate the effects of HDBR with and without artificial gravity on cognitive performance: To assess the relation between brain structural and functional changes and changes in cognitive performance, we performed a unique set of sensitive but unobtrusive cognitive measurement tools with and without MRI before, during, and after HDBR. The tasks are designed and scheduled to avoid any masking effects due to repetitive testing and/or changing body posture, and specifically probe the anatomical correlates that were expected to be most vulnerable to the detrimental effects of HDBR, i.e., the hippocampus, the cingulate cortex, and the prefrontal cortex.

SA 3: Investigate the effects of HDBR with and without artificial gravity on biochemical markers of stress and neuroplasticity: We took sample blood and saliva samples after an overnight fast in the morning two times bed rest, five times during bed rest, and two times after bed rest. In addition, five blood samples were taken during bed rest immediately after the AG intervention. These samples will be analyzed for BDNF, IGF- 1, VEGF, NF-L, Il-1b, Il-6, and TNFa. At identical time points we also collected a saliva sample in the morning and evening to assess changes in cortisol levels. These data were expected to provide valuable information for the potential underlying neurophysiological mechanisms and pathways related to the effects of HDBR and the AG countermeasure.

Research Impact/Earth Benefits: With the proposed work we relevantly contributed to the goal of the Human Research Program (HRP) to provide human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration. Combing neuroimaging, biochemical and behavioral data our results support the development of countermeasures and provide mission planners and system developers with strategies for monitoring and mitigating crew health and performance risks during long-duration space missions. Moreover, exploring the neurobehavioral effects of bed rest and their mechanisms promotes research on the role of inactivity in health and disease on Earth. This could have implications for situations or conditions in which physical activity levels become severely restricted, including medical conditions like myotonic dystrophy and fibromyalgia, prolonged physical inactivity due to confinement to bed rest in clinical settings, and a lack of inactivity associated with sedentary lifestyles.

Task Progress & Bibliography Information FY2021 
Task Progress: The study was performed at German Space Agency (DLR) DLR :envihab ( https://www.dlr.de/envihab/en/desktopdefault.aspx/tabid-6890/ ), and involved two campaigns of 12 participants each. Data for the first campaign were collected between February and June 2019. Eight men and four women participated in this campaign and had the following group assignments: bed rest only (CTRL) (3 men, 1 woman), bed rest with continuous artificial gravity exposure (cAG) (3 men, 1 woman), and bed rest with intermittent artificial gravity exposure iAG (2 men, 2 women). In August 2019 twelve participants (6 men, 6 women) were recruited for the second campaign. Due to an unprecedented number of personal withdrawals and medical drop-outs, five subjects had to be replaced. 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 women, mean age: 34 yrs). Data collection was completed in December 2019. Overall, data acquisition rates and data quality were excellent. We collected 7438 data points out of a total of 7592 (97.9%). The main findings for specific aim are summarized below.

Aim 1: Investigate the effects of HDBR with and without artificial gravity on Brain Structure and Function. We hypothesized that long-duration bed rest would impair brain structure and function, and that these effects would most affect brain areas associated with spatial cognition. Our findings confirmed this hypothesis as indicated by significant decreases in bilateral gray matter volume of the insula and reductions of the right dentate gyrus volume in response to bed rest. We also expected that any adverse neurobehavioral effects would be reduced by the AG countermeasure. This was confirmed by stability of insula and dentate gyrus volumes in both intervention groups receiving the AG countermeasure. Mean reductions in dentate gyrus volume during bed rest were significantly associated with increased mean concentrations of NF-L, a marker of axonal injury and degeneration. We also identified several significant correlations between changes in insula gray matter volumes and changes in NF-L, IGF-1, TNFa, and Il-1b. The changes in dentate gyrus volume were significantly associated with changes in cognitive performance. We observed a significant relationship between changes in accuracy of the Four Mountains Task, a task included in the Spatial Cognition battery and assessing allocentric spatial memory formation. In addition, we found a nearly significant correlation between changes in dentate gyrus volume and performance of the Emotion Recognition Task of the Cognition battery. In line with that, task functional imaging using the emotion recognition task showed a reduced BOLD response after 59 days of bed rest.

Aim 2: Investigate the effects of HDBR with and without artificial gravity on cognitive performance. The emotion recognition task of the Cognition battery revealed a gradual decrease in speed during HDBR. With increasing time spent in HDBR, participants required longer time to decide which facial emotion was expressed. The Cognition survey also showed that participants were also more likely to select categories with negative valence over categories with neutral or positive valence. Except for workload, which was rated lower in the CTRL group, continuous or intermittent AG did not modify the effect of HDBR on cognitive performance or subjective responses. These findings are very much in line with data that we collected using two standard tasks to assess executive control, i.e., a switching and dual task paradigm performed before and after HDBR, which did not reveal any clear interactions of performance between experimental groups in response to HDBR. Spatial Cognition batteries suggested a tendency for improved performance in the AG countermeasure groups relative to CTRL. Precision numerically decreased for the most difficult condition in the Spatial Updating Task in CTRL during HDBR relative baseline, whereas performance in iAG and cAG remained stable. We also found higher improvements in precision in medium (2-Turn) and difficult (3-Turn) conditions of the Point to Origin Task in iAG compared to cAG and CTRL. Likewise, response speed in the Four Mountains Task, which is a task assessing topographical mapping, was significantly increased during HDBR relative to baseline in iAG and cAG, but not CTRL. Accuracy in the Four Mountains Task also significantly increased during HDBR in iAG, but not in cAG and CTRL. The Cognitive Mapping Task revealed a considerable (though not statistically significant) effect for cAg and iAG, suggesting the AG supported the ability to accurately integrate new spatial memories into a cognitive map, a process which is hypothesized to significantly rely on hippocampal activation. Along these lines we observed numerically higher accuracy scores in cAG and iAG relative to CTRL in the Plus Maze for conditions that required subjects to switch from an egocentric response to an allocentric navigational strategy. Finally, we observed similar effects (again, not statistically significant though) for efficiency of a classical paradigm to assess spatial orientation, the Spatial Orientation Task. In summary, these data suggest potential benefits of the AG countermeasure, and particularly iAG on spatial cognition. This was also reflected when accuracy, speed, and efficiency were summarized across tasks, which showed the changes in accuracy from baseline to HDBR are significantly larger in iAG compared to the changes from baseline in cAG and CTRL. However, given the small sample sizes and variation between groups, these effects need to be interpreted cautiously, and require confirmation in further studies.

Aim 3: Investigate the effects of HDBR with and without artificial gravity on biochemical markers of stress and neuroplasticity. Analyses of the acute molecular responses to AG showed a significant increase in IGF-1, and a significant decrease in NF-L and TNFa after the AG intervention compared to before AG. This was effect was observed in both iAG and cAG. Furthermore, cAG was characterized by an increase in Il-1b following the AG exposure. Given that the daily timing of the AG intervention varied between and within subjects, it remains unclear whether the results can be attributed to the intervention, or, are at least somewhat caused by biological rhythms. The sample before AG was always collected in the morning after an overnight fast, whereas the sample after AG was collected immediately after completion of the AG exposure. Because no data were collected at identical time points in the CTRL group, we cannot verify whether the observed acute molecular changes were affected by circadian variation. IGF-1 also showed the most pronounced effect in response to HDBR. IGF-1 was upregulated in response during HDBR, and then decreased again during the recovery irrespective of the experimental group. Il-6 and TNFa considerably peaked on the first day of recovery, whereas the effect for Il-6 was slightly, but significantly, more pronounced in CTRL compared to iAG and cAG. Given the potent role of IGF-1 in modulating neuronal transmission, metabolism and morphology, and neuroprotective capacities, on the one hand, and the role of NF-L and TNFa as predictors for cognitive decline, and neuropathological conditions on the other, future studies are needed to clarify the potential of AG to positively affect the molecular dynamics associated with neurobehavioral adaptations.

Bibliography Type: Description: (Last Updated: 02/16/2022) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Stahn A, Ruparel K, Roalf D, Gur RC, Friedl-Werner A, Brauns K, Gunga HC, Mulder E, Mühl C, Gerlach D, Dinges DF, Basner M, Kühn S. "Hyper.Campus - Effects of Artificial Gravity on Structural and Functional Brain Plasticity During Head-Down Tilt Bed Rest." NASA 2022 Human Research Program Investigators’ Workshop "Enabling the Future: the Pathway to the Moon and Mars", Virtual, February 7-10, 2022.

Abstracts. NASA 2022 Human Research Program Investigators’ Workshop "Enabling the Future: the Pathway to the Moon and Mars", Virtual, February 7-10, 2022. , Feb-2022

Articles in Peer-reviewed Journals Basner M, Dinges DF, Howard K, Moore TM, Gur RC, Mühl C, Stahn, AC. "Continuous and intermittent artificial gravity as a countermeasure to the cognitive effects of 60 days of head-down tilt bed rest." Front Physiol. 2021 Mar 17;12:643854. https://doi.org/10.3389/fphys.2021.643854 ; PMID: 33815148; PMCID: PMC8009974 , Mar-2021
Articles in Peer-reviewed Journals Basner M, Stahn AC, Nasrini J, Dinges DF, Moore TM, Gur RC, Mühl C, Macias BR, Laurie SS. "Effects of head-down tilt bed rest plus elevated CO2 on cognitive performance." J Appl Physiol (1985). 2021 Apr 1;130(4):1235-46. https://doi.org/10.1152/japplphysiol.00865.2020 ; PMID: 33630672; PMCID: PMC8262780 , Apr-2021
Articles in Peer-reviewed Journals Casario K, Howard K, Cordoza M, Hermosillo E, Ibrahim L, Larson O, Nasrini J, Basner M. "Acceptability of the Cognition Test Battery in astronaut and astronaut-surrogate populations." Acta Astronautica. 2022 Jan;190:14-23. Available online 24 September 2021. https://doi.org/10.1016/j.actaastro.2021.09.035 , Jan-2022
Project Title:  Hyper.Campus - Effects of Artificial Gravity on Structural and Functional Plasticity During Head-Down Tilt Bed Rest Reduce
Images: icon  Fiscal Year: FY 2020 
Division: Human Research 
Research Discipline/Element:
HRP HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Start Date: 04/10/2018  
End Date: 08/31/2021  
Task Last Updated: 01/30/2020 
Download report in PDF pdf
Principal Investigator/Affiliation:   Stahn, Alexander  Ph.D. / University of Pennsylvania 
Address:  Division of Sleep and Chronobiology, Department of Psychiatry 
423 Guardian Dr, 1016 Blockley Hall 
Philadelphia , PA 19104-4865 
Email: astahn@pennmedicine.upenn.edu 
Phone: 215-898-9667  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Pennsylvania 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Buchert, Ralph  Ph.D. University Medical Center Hambrug-Eppendorf, Germany 
Dinges, David  Ph.D. University of Pennsylvania 
Gunga, Hanns-Christian  M.D. Charite - Universitatsmedizin Berlin, Germany 
Gur, Ruben  Ph.D. University of Pennsylvania 
Kuehn, Simone  Ph.D. Max Planck Institute for Human Development Berlin, Germany 
Maggioni, Martina  Ph.D. Charite - Universitatsmedizin Berlin, Germany 
Roalf, David  Ph.D. University of Pennsylvania 
Shoemaker, Kevin  Ph.D. University of Western Ontario, Canada 
Basner, Mathias  M.D., Ph.D. University of Pennsylvania 
Key Personnel Changes / Previous PI: February 2019 report: Two PhD students, who are critical to the study, are included as key to study implementation: • Anika Werner, Charite - Universitatsmedizin Berlin, Institute of Physiology, Center for Space Medicine and Extreme Environments Berlin, CharitéCrossOver (CCO), Charitéplatz 1, Virchowweg 6, 10117 Berlin, Email: anika.werner@charite.de, and Katharina Brauns, Charite - Universitatsmedizin Berlin, Institute of Physiology, Center for Space Medicine and Extreme Environments Berlin, CharitéCrossOver (CCO), Charitéplatz 1, Virchowweg 6, 10117 Berlin, Email: Katharina.brauns@charite.de
Project Information: Grant/Contract No. 80NSSC18K0765 
Responsible Center: NASA JSC 
Grant Monitor: Williams, Thomas  
Center Contact: 281-483-8773 
thomas.j.will1@nasa.gov 
Solicitation / Funding Source: 2015-16 HERO NNJ15ZSA001N-AGBR. Appendix G: Physiological & Behavioral Responses in Humans to Intermittent Artificial Gravity during Bed Rest 
Grant/Contract No.: 80NSSC18K0765 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Human Research Program Risks: (1) HFBP Bmed:Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders (IRP Rev J)
Human Research Program Gaps: (1) BMed-101:We need to identify, quantify, and validate the key selection factors for astronaut cognitive and behavioral strengths (e.g., resiliency) and operationally-relevant performance threats for increasingly Earth independent, long-duration, autonomous, and/or long-distance exploration missions (IRP Rev L)
(2) BMed-103:What are the validated, efficacious treatments (individual or Team-based) and/or countermeasures to prevent adverse behavioral conditions, CNS/neurological, and/or psychiatric disorders caused by either single and/or integrated exposures to spaceflight hazards during exploration class missions? (IRP Rev L)
(3) BMed-105:Given the potentially negative spaceflight associated CNS/cognitive changes and behavioral experiences of stressors during long-duration missions (e.g., isolation, confinement, reduced sensory stimulation, altered gravity, space radiation), what are validated medical or dietary countermeasures to mitigate stressors impacting on CNS / cognition / behavioral health? (IRP Rev L)
(4) BMed-107:What are the long-term changes and risks to astronaut health post-mission that, when using a continuity of care model, helps retrospectively identify and understand individual susceptibility (e.g., hereditary, dose, thresholds) to mitigate adverse CNS, cognitive, and behavioral health changes resulting from long-duration exploration missions, promoting the behavioral health of current and future crews? (IRP Rev L)
(5) BMed-108:Given each crewmember will experience multiple spaceflight hazards simultaneously, we need to identify and characterize the potential additive, antagonistic, or synergistic impacts of multiple stressors (e.g., space radiation, altered gravity, isolation, altered immune, altered sleep) on crew health and/or CNS/ cognitive functioning to develop threshold limits and validate countermeasures for any identified adverse crew health and/or operationally-relevant performance outcomes (IRP Rev L)
Flight Assignment/Project Notes: NOTE: End date changed to 8/31/2021 per NSSC information (Ed., 1/11/21)

Task Description: The Human Factors and Behavioral Performance (HFBP) Element of the NASA Human Research Program (HRP) defines the prevention of adverse health consequences including neurocognitive impairment as one of the key milestones of Artificial Gravity (AG) countermeasure developments. Remarkably, the neurophysiological correlate of cognitive performance changes (especially spatial cognition) associated with AG has received little attention. In fact, research on the effects of intermittent AG on structural and functional changes of the brain is presently lacking completely. While the entire brain may be prone to structural and functional changes as a result of body unloading and AG, the hippocampal formation -- a key area for the brain for memory formation and spatial navigation and one of the only two human brain areas exhibiting neurogenesis -- is expected to be highly vulnerable to stress and a key target for mitigating neurocognitive impairments. The overarching goal of the present proposal is therefore to quantify the effects of different protocols of intermittent AG during 60 days of HDBR (head down bed rest) on cortical neuroplasticity related to behavioral outcomes associated with neural control of the cardiovascular system and spatial cognition, and biochemical correlates. Using state-of-the art neuroimaging, ultrasound imaging, and cognitive tools, measures made in HDBR participants will be contrasted with a control group matched for gender, age, and educational background. The data will also be compared to data from two additional European Space Agency (ESA) HDBR studies of the same length, as well as data obtained from long-duration International Space Station (ISS) missions, Antarctic expeditions, and Human Exploration Research Analog (HERA) isolation studies. These studies employ very similar procedures that allow comparing the effectiveness of AG to exercise as well as to nutritional countermeasures. At the end of the project, we will have a clear understanding whether, and to what extent, any effects on neuroplasticity and behavioral health associated with HDBR can be augmented by a centrifugation countermeasure.

Research Impact/Earth Benefits: With the proposed work we will relevantly contribute to the goal of the Human Research Program (HRP) to provide human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration. This work will also help to identify and validate measures (1) that can be used for the selection of individuals that are highly resilient to the key behavioral health and performance threats and (2) to monitor behavioral health and performance during exploration class missions that can be used for the selection of individuals. Combing neuroimaging, biochemical, and behavioral data our results will relevantly contribute to the development of countermeasures and provide mission planners and system developers with strategies for monitoring and mitigating crew health and performance risks during long-duration space missions. Moreover, exploring the neurobehavioral effects of bed rest and their mechanisms will promote research on the role of inactivity in health and disease on Earth. This could have implications for situations or conditions in which physical activity levels become severely restricted, including medical conditions like myotonic dystrophy and fibromyalgia, prolonged physical inactivity due to confinement to bed rest in clinical settings, and a lack of inactivity due to sedentary lifestyles.

Task Progress & Bibliography Information FY2020 
Task Progress: In the past 12 months we implemented and performed the study at the DLR :envihab. Specifically, we (1) shipped and implemented the hardware at DLR (German Aerospace Center), (2) trained DLR staff to successfully collect all data, and (3) acquired the data in N=24 participants (16 men, 8 women). Overall, data acquisition rates and data quality were excellent, exceeding 98% for all measures. Preliminary data analyses of the structural imaging data were presented at the Investigators' Workshop (HRP IWS 2020) meeting.

Bibliography Type: Description: (Last Updated: 02/16/2022) 

Show Cumulative Bibliography Listing
 
Abstracts for Journals and Proceedings Stahn A, Dinges DF, Roalf D, Gur R, Brauns K, Werner A, Gunga HC, Riecke B, Wolbers T, Hartley T, Buchert R, Basner M, Kühn S. "Hyper.Campus - Effects of Artificial Gravity on Structural and Functional Brain Plasticity During Head-Down Tilt Bed Rest." Presented at the "Human Exploration Small Steps Lead to Giant Leaps: Translating Research into Space Exploration." 2020 NASA Human Research Program Investigators' Workshop, Galveston, TX, January 27-30, 2020.

Detailed Program. 2020 NASA Human Research Program Investigators' Workshop, Galveston, TX, January 27-30, 2020. , Jan-2020

Abstracts for Journals and Proceedings Stahn A, Dinges DF, Roalf D, Gur R, Brauns K, Werner A, Gunga HC, Riecke B, Wolbers T, Hartley T, Buchert R, Kühn S, Basner M "Hyper.Campus - Effects of Artificial Gravity on Structural and Functional Brain Plasticity During Head-Down Tilt Bed Rest" Presented at the "Human Exploration and Discovery: the Moon, Mars, and Beyond." 2019 NASA Human Research Program Investigators' Workshop, Galveston, TX, January 22-25, 2019.

Detailed Program of the 2019 NASA Human Research Program Investigators' Workshop, Galveston, TX, January 22-25, 2019. , Jan-2019

Project Title:  Hyper.Campus - Effects of Artificial Gravity on Structural and Functional Plasticity During Head-Down Tilt Bed Rest Reduce
Images: icon  Fiscal Year: FY 2019 
Division: Human Research 
Research Discipline/Element:
HRP HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Start Date: 04/10/2018  
End Date: 12/31/2020  
Task Last Updated: 02/10/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Stahn, Alexander  Ph.D. / University of Pennsylvania 
Address:  Division of Sleep and Chronobiology, Department of Psychiatry 
423 Guardian Dr, 1016 Blockley Hall 
Philadelphia , PA 19104-4865 
Email: astahn@pennmedicine.upenn.edu 
Phone: 215-898-9667  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Pennsylvania 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Buchert, Ralph  Ph.D. University Medical Center Hambrug-Eppendorf, Germany 
Dinges, David  Ph.D. University of Pennsylvania 
Gunga, Hanns-Christian  M.D. Charite - Universitatsmedizin Berlin, Germany 
Gur, Ruben  Ph.D. University of Pennsylvania 
Kuehn, Simone  Ph.D. Max Planck Institute for Human Development Berlin, Germany 
Maggioni, Martina  Ph.D. Charite - Universitatsmedizin Berlin, Germany 
Roalf, David  Ph.D. University of Pennsylvania 
Shoemaker, Kevin  Ph.D. University of Western Ontario, Canada 
Basner, Mathias  M.D., Ph.D. University of Pennsylvania 
Key Personnel Changes / Previous PI: February 2019 report: Two PhD students, who are critical to the study, are included as key to study implementation: • Anika Werner, Charite - Universitatsmedizin Berlin, Institute of Physiology, Center for Space Medicine and Extreme Environments Berlin, CharitéCrossOver (CCO), Charitéplatz 1, Virchowweg 6, 10117 Berlin, Email: anika.werner@charite.de, and • Katharina Brauns, Charite - Universitatsmedizin Berlin, Institute of Physiology, Center for Space Medicine and Extreme Environments Berlin, CharitéCrossOver (CCO), Charitéplatz 1, Virchowweg 6, 10117 Berlin, Email: Katharina.brauns@charite.de
Project Information: Grant/Contract No. 80NSSC18K0765 
Responsible Center: NASA JSC 
Grant Monitor: Williams, Thomas  
Center Contact: 281-483-8773 
thomas.j.will1@nasa.gov 
Solicitation / Funding Source: 2015-16 HERO NNJ15ZSA001N-AGBR. Appendix G: Physiological & Behavioral Responses in Humans to Intermittent Artificial Gravity during Bed Rest 
Grant/Contract No.: 80NSSC18K0765 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Human Research Program Risks: (1) HFBP Bmed:Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders (IRP Rev J)
Human Research Program Gaps: (1) BMed-101:We need to identify, quantify, and validate the key selection factors for astronaut cognitive and behavioral strengths (e.g., resiliency) and operationally-relevant performance threats for increasingly Earth independent, long-duration, autonomous, and/or long-distance exploration missions (IRP Rev L)
(2) BMed-103:What are the validated, efficacious treatments (individual or Team-based) and/or countermeasures to prevent adverse behavioral conditions, CNS/neurological, and/or psychiatric disorders caused by either single and/or integrated exposures to spaceflight hazards during exploration class missions? (IRP Rev L)
(3) BMed-105:Given the potentially negative spaceflight associated CNS/cognitive changes and behavioral experiences of stressors during long-duration missions (e.g., isolation, confinement, reduced sensory stimulation, altered gravity, space radiation), what are validated medical or dietary countermeasures to mitigate stressors impacting on CNS / cognition / behavioral health? (IRP Rev L)
(4) BMed-107:What are the long-term changes and risks to astronaut health post-mission that, when using a continuity of care model, helps retrospectively identify and understand individual susceptibility (e.g., hereditary, dose, thresholds) to mitigate adverse CNS, cognitive, and behavioral health changes resulting from long-duration exploration missions, promoting the behavioral health of current and future crews? (IRP Rev L)
(5) BMed-108:Given each crewmember will experience multiple spaceflight hazards simultaneously, we need to identify and characterize the potential additive, antagonistic, or synergistic impacts of multiple stressors (e.g., space radiation, altered gravity, isolation, altered immune, altered sleep) on crew health and/or CNS/ cognitive functioning to develop threshold limits and validate countermeasures for any identified adverse crew health and/or operationally-relevant performance outcomes (IRP Rev L)
Task Description: The Human Factors and Behavioral Performance (HFBP) Element of the NASA Human Research Program (HRP) defines the prevention of adverse health consequences including neurocognitive impairment as one of the key milestones of Artificial Gravity (AG) countermeasure developments. Remarkably, the neurophysiological correlate of cognitive performance changes (especially spatial cognition) associated with AG has received little attention. In fact, research on the effects of intermittent AG on structural and functional changes of the brain is presently lacking completely. While the entire brain may be prone to structural and functional changes as a result of body unloading and AG, the hippocampal formation -- a key area for the brain for memory formation and spatial navigation and one of the only two human brain areas exhibiting neurogenesis -- is expected to be highly vulnerable to stress and a key target for mitigating neurocognitive impairments. The overarching goal of the present proposal is therefore to quantify the effects of different protocols of intermittent AG during 60 days of HDBR (head down bed rest) on cortical neuroplasticity related to behavioral outcomes associated with neural control of the cardiovascular system and spatial cognition, and biochemical correlates. Using state-of-the art neuroimaging, ultrasound imaging, and cognitive tools, measures made in HDBR participants will be contrasted with a control group matched for gender, age, and educational background. The data will also be compared to data from two additional European Space Agency (ESA) HDBR studies of the same length, as well as data obtained from long-duration International Space Station (ISS) missions, Antarctic expeditions, and Human Exploration Research Analog (HERA) isolation studies. These studies employ very similar procedures that allow comparing the effectiveness of AG to exercise as well as to nutritional countermeasures. At the end of the project, we will have a clear understanding whether, and to what extent, any effects on neuroplasticity and behavioral health associated with HDBR can be augmented by a centrifugation countermeasure.

Research Impact/Earth Benefits: With the proposed work we will relevantly contribute to the goal of the Human Research Program (HRP) to provide human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration. This work will also help to identify and validate measures (1) that can be used for the selection of individuals that are highly resilient to the key behavioral health and performance threats and (2) to monitor behavioral health and performance during exploration class missions that can be used for the selection of individuals. Combing neuroimaging, biochemical, and behavioral data our results will relevantly contribute to the development of countermeasures and provide mission planners and system developers with strategies for monitoring and mitigating crew health and performance risks during long-duration space missions. Moreover, exploring the neurobehavioral effects of bed rest and their mechanisms will promote research on the role of inactivity in health and disease on Earth. This could have implications for situations or conditions in which physical activity levels become severely restricted, including medical conditions like myotonic dystrophy and fibromyalgia, prolonged physical inactivity due to confinement to bed rest in clinical settings, and a lack of inactivity due to sedentary lifestyles.

Task Progress & Bibliography Information FY2019 
Task Progress: In the past 12 months we assessed the feasibility of the originally proposed aims with respect to the available facilities and other constraints, maximized their scientific return, and developed strategies to successfully implement the experiments as part of the AGBRESA (Artificial Gravity Bed Rest – European Space Agency) study. Specifically, we accomplished the following project milestones: 1) optimized, defined, and tested the brain imaging protocol, 2) optimized and defined cognitive paradigms and biochemical sampling, 3) finalized the study schedule of the experiment with respect to the integration of all experiments of the AGBRESA study, 4) prepared procedures for training and administration of neuroimaging protocol, cognitive tasks, and biochemical assessments, 5) obtained NASA Institutional Review Board (IRB) approval to perform the experiment.

Bibliography Type: Description: (Last Updated: 02/16/2022) 

Show Cumulative Bibliography Listing
 
 None in FY 2019
Project Title:  Hyper.Campus - Effects of Artificial Gravity on Structural and Functional Plasticity During Head-Down Tilt Bed Rest Reduce
Images: icon  Fiscal Year: FY 2018 
Division: Human Research 
Research Discipline/Element:
HRP HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Start Date: 04/10/2018  
End Date: 12/31/2020  
Task Last Updated: 01/09/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Stahn, Alexander  Ph.D. / University of Pennsylvania 
Address:  Division of Sleep and Chronobiology, Department of Psychiatry 
423 Guardian Dr, 1016 Blockley Hall 
Philadelphia , PA 19104-4865 
Email: astahn@pennmedicine.upenn.edu 
Phone: 215-898-9667  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of Pennsylvania 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Buchert, Ralph  Ph.D. Charite - Universitatsmedizin Berlin, Germany 
Dinges, David  Ph.D. University of Pennsylvania 
Gunga, Hanns-Christian  M.D. Charite - Universitatsmedizin Berlin, Germany 
Gur, Ruben  Ph.D. University of Pennsylvania 
Kuehn, Simone  Ph.D. Max Planck Institute for Human Development Berlin, Germany 
Maggioni, Martina  Ph.D. Charite - Universitatsmedizin Berlin, Germany 
Roalf, David  Ph.D. University of Pennsylvania 
Shoemaker, Kevin  Ph.D. University of Western Ontario, Canada 
Key Personnel Changes / Previous PI: Two PhD students, who are critical to the study, are included as key to study implementation: • Anika Werner, Charite - Universitatsmedizin Berlin, Institute of Physiology, Center for Space Medicine and Extreme Environments Berlin, CharitéCrossOver (CCO), Charitéplatz 1, Virchowweg 6, 10117 Berlin, Email: anika.werner@charite.de, and • Katharina Brauns, Charite - Universitatsmedizin Berlin, Institute of Physiology, Center for Space Medicine and Extreme Environments Berlin, CharitéCrossOver (CCO), Charitéplatz 1, Virchowweg 6, 10117 Berlin, Email: Katharina.brauns@charite.de
Project Information: Grant/Contract No. 80NSSC18K0765 
Responsible Center: NASA JSC 
Grant Monitor: Williams, Thomas  
Center Contact: 281-483-8773 
thomas.j.will1@nasa.gov 
Solicitation / Funding Source: 2015-16 HERO NNJ15ZSA001N-AGBR. Appendix G: Physiological & Behavioral Responses in Humans to Intermittent Artificial Gravity during Bed Rest 
Grant/Contract No.: 80NSSC18K0765 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Human Research Program Risks: (1) HFBP Bmed:Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders (IRP Rev J)
Human Research Program Gaps: (1) BMed-101:We need to identify, quantify, and validate the key selection factors for astronaut cognitive and behavioral strengths (e.g., resiliency) and operationally-relevant performance threats for increasingly Earth independent, long-duration, autonomous, and/or long-distance exploration missions (IRP Rev L)
(2) BMed-103:What are the validated, efficacious treatments (individual or Team-based) and/or countermeasures to prevent adverse behavioral conditions, CNS/neurological, and/or psychiatric disorders caused by either single and/or integrated exposures to spaceflight hazards during exploration class missions? (IRP Rev L)
(3) BMed-105:Given the potentially negative spaceflight associated CNS/cognitive changes and behavioral experiences of stressors during long-duration missions (e.g., isolation, confinement, reduced sensory stimulation, altered gravity, space radiation), what are validated medical or dietary countermeasures to mitigate stressors impacting on CNS / cognition / behavioral health? (IRP Rev L)
(4) BMed-107:What are the long-term changes and risks to astronaut health post-mission that, when using a continuity of care model, helps retrospectively identify and understand individual susceptibility (e.g., hereditary, dose, thresholds) to mitigate adverse CNS, cognitive, and behavioral health changes resulting from long-duration exploration missions, promoting the behavioral health of current and future crews? (IRP Rev L)
(5) BMed-108:Given each crewmember will experience multiple spaceflight hazards simultaneously, we need to identify and characterize the potential additive, antagonistic, or synergistic impacts of multiple stressors (e.g., space radiation, altered gravity, isolation, altered immune, altered sleep) on crew health and/or CNS/ cognitive functioning to develop threshold limits and validate countermeasures for any identified adverse crew health and/or operationally-relevant performance outcomes (IRP Rev L)
Task Description: The Human Factors and Behavioral Performance (HFBP) Element of the NASA Human Research Program (HRP) defines the prevention of adverse health consequences including neurocognitive impairment as one of the key milestones of Artificial Gravity (AG) countermeasure developments. Remarkably, the neurophysiological correlate of cognitive performance changes (especially spatial cognition) associated with AG has received little attention. In fact, research on the effects of intermittent AG on structural and functional changes of the brain is presently lacking completely. While the entire brain may be prone to structural and functional changes as a result of body unloading and AG, the hippocampal formation -- a key area for the brain for memory formation and spatial navigation and one of the only two human brain areas exhibiting neurogenesis -- is expected to be highly vulnerable to stress and a key target for mitigating neurocognitive impairments. The overarching goal of the present proposal is therefore to quantify the effects of different protocols of intermittent AG during 60 days of HDBR (head down bed rest) on cortical neuroplasticity related to behavioral outcomes associated with neural control of the cardiovascular system and spatial cognition, and biochemical correlates. Using state-of-the art neuroimaging, ultrasound imaging, and cognitive tools, measures made in HDBR participants will be contrasted with a control group matched for gender, age, and educational background. The data will also be compared to data from two additional European Space Agency (ESA) HDBR studies of the same length, as well as data obtained from long-duration International Space Station (ISS) missions, Antarctic expeditions, and Human Exploration Research Analog (HERA) isolation studies. These studies employ very similar procedures that allow comparing the effectiveness of AG to exercise as well as to nutritional countermeasures. At the end of the project, we will have a clear understanding whether, and to what extent, any effects on neuroplasticity and behavioral health associated with HDBR can be augmented by a centrifugation countermeasure.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2018 
Task Progress: New project for FY2018.

Bibliography Type: Description: (Last Updated: 02/16/2022) 

Show Cumulative Bibliography Listing
 
 None in FY 2018