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Project Title:  VNSCOR: Probing the Synergistic Effects of Radiation, Altered Gravity and Stress on Behavioral Cognitive and Sensorimotor Functions to Predict Performance Decrement in Astronauts Reduce
Images: icon  Fiscal Year: FY 2022 
Division: Human Research 
Research Discipline/Element:
HRP HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Start Date: 10/01/2019  
End Date: 09/30/2025  
Task Last Updated: 09/23/2021 
Download report in PDF pdf
Principal Investigator/Affiliation:   Rosi, Susanna  Ph.D. / University of California San Francisco 
Address:  Physical Therapy and Neurological Surgery 
1001 Potrero Ave. Bldg #1 Room 101 
San Francisco , CA 94110-3518 
Email: rosis@ptrehab.ucsf.edu 
Phone: 415-206-3708  
Congressional District: 12 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of California San Francisco 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Ferguson , Adam  Ph.D. University of California, San Francisco 
Key Personnel Changes / Previous PI: July 2020 report: Adam Ferguson, Ph.D., Associate Professor, Department of Neurological Surgery, Director of Data Science, Brain and Spinal Injury Center (BASIC), and the Weill Institute for Neurosciences at the University of California, San Francisco is now CoInvestigator. Drs. Mora and Wyrobek and Dr. Mao are no longer CoInvestigators on the project.
Project Information: Grant/Contract No. 80NSSC19K1581 
Responsible Center: NASA JSC 
Grant Monitor: Whitmire, Alexandra  
Center Contact:  
alexandra.m.whitmire@nasa.gov 
Solicitation / Funding Source: 2018 HERO 80JSC018N0001-Crew Health and Performance (FLAGSHIP, OMNIBUS). Appendix A-Flagship, Appendix B-Omnibus 
Grant/Contract No.: 80NSSC19K1581 
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)
(2) Sensorimotor:Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks (Revised as of IRP Rev M)
Human Research Program Gaps: (1) BMed-102:Given exposures to spaceflight hazards (space radiation, isolation), how do we identify individual susceptibility, monitor molecular/biomarkers and acceptable thresholds, and validate behavioral health and CNS/neurological/neuropsychological performance measures and domains of relevance to exploration class 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)
(6) SM-104:Evaluate how weightlessness-induced changes in sensorimotor/vestibular function relate to and/or interact with changes in other brain functions (sleep, cognition, attention) (IRP Rev M)
Flight Assignment/Project Notes: NOTE: End date changed to 09/30/2025 per L. Juliette/JSC (Ed., 5/7/22)

Task Description: The purpose of this application is to: 1) determine the possible synergistic and individual effects of radiation exposure (GCRsim), isolation confinement stress, and altered gravity on behavioral, cognitive, and sensorimotor performance; 2) establish if there are sex-dimorphic responses; 3) develop predictive biomarkers for individual sensitivity; 4) incorporate these results into a predictive statistical model for the extrapolation of performance decrement; and 5) estimate Central Nervous System (CNS) risks in astronauts.

The central hypothesis of this proposal is that there is a synergistic effect of multiple factors (defined by GCRsim, isolation confinement stress, and altered gravity) encountered in deep space exposure that leads to enhanced inflammatory response, promotes synapse loss, and decreases synaptic integrity that leads to long-term loss of sensorimotor, behavioral, and cognitive functions.

The rationale of the proposed research is to understand the mechanisms that underlie the cumulative and synergistic effects of radiation exposure, isolation confinement stress, and altered gravity on behavioral, cognitive, and sensorimotor deficits. Further, we will explore sex-dimorphic responses along with potential peripheral biomarkers associated with simulated deep space travel. Our studies will provide novel information regarding the cellular mechanisms of altered neuronal function involved in simulated deep space conditions (GCRsim, isolation confinement, and altered gravity). Finally, we will incorporate all the results to build risk assessment and performance decrement for astronauts.

We will characterize molecular, cellular, tissue, and behavioral endpoints underlying CNS function in an individual manner with animals prescreening. We will use multiple behavioral and cognitive tests known to be comparable to human performance. We will use state of the art techniques to dissect cellular and molecular changes in the brain. The endpoints will be selected to probe key physiological processes that support tissue homeostasis plasticity in the brain. We will determine if and how cellular and molecular impairments are linked to compromised behavior in motor, social, and cognitive domains. By combining assessments of multiple processes that may have distinct time constants and magnitudes of responses to simulated deep space conditions we will begin to identify operationally-relevant brain functions impacted by the three stressors and relate these to human performance. Furthermore, by comparing outcome measures in both males and females we will begin to understand the distinct aspects of the responses controlled by sex and are therefore more likely to translate to humans.

The proposed aims directly address Human Exploration Research Opportunities (HERO) announcement needs detailed in Appendix A that specify research needs (gaps) related to NASA Research and Technology Development to Support Crew Health and Performance in Space Exploration Missions. The specific gaps this proposal addresses are Topic 1, gap CNS 1 (Are there significant adverse changes in CNS performance in the context and time scale of spaceflight operations? If so, how is significance defined, and which neuropsychological domains are affected? Is there a significant probability that space radiation exposure would result in adverse changes? What are the pathways and mechanisms of change?), CNS 2 (Does space radiation exposure elicit key events in adverse outcome pathways associated with neurological diseases? What are the key events or hallmarks, their time sequence and their associated biomarkers (in-flight or post-flight)?), CNS 5 (How can new knowledge and data from molecular, cellular, tissue and animal models of acute CNS adverse changes or clinical human data, including altered motor and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE-solar particle event?), SM6.1 (Determine if sensorimotor dysfunction during and after long-duration spaceflight affects ability to control spacecraft and associated systems), SM 26 (Determine if exposure to long-duration spaceflight leads to neural structural alterations and if this remodeling impacts cognitive and functional performance), and IM 8 (IM8: We do not know the influence, direct, or synergistic, on the immune system of other physiological changes associated with spaceflight). [Ed. note November 2021: Gaps have been revised since the original proposal Task Description; please refer to the Human Research Roadmap for current gap information: https://humanresearchroadmap.nasa.gov/ ]

Research Impact/Earth Benefits: Our research goals, hypothesis, and proposed aims directly address Human Exploration Research Opportunities (HERO) announcement needs detailed in Appendix A that specify research needs (gaps) related to NASA Research and Technology Development to Support Crew Health and Performance in Space Exploration Missions. The specific gaps this proposal addresses are in Topic 1, CNS 1 “Are there significant adverse changes in CNS performance in the context and time scale of space flight operations? Is there a significant probability that space radiation exposure would result in adverse changes? What are the pathways and mechanisms of change?”; Gap CNS2: “Does space radiation exposure elicit key events in adverse outcome pathways associated with neurological diseases? What are the key events or hallmarks, their time sequence and their associated biomarkers (in-flight or post- flight)?”; SM 26: “Determine if exposure to long-duration spaceflight leads to neuronal structural alterations and if this remodeling impacts cognitive and functional performance.”; IM 8: “We do not know the influence, direct or synergistic, on the immune system of other physiological changes associated with spaceflight.” [Ed. note November 2021: Gaps have since been revised ; please refer to the Human Research Roadmap for current gap information: https://humanresearchroadmap.nasa.gov/ ]

Task Progress & Bibliography Information FY2022 
Task Progress: For the first time we identify GCRsim-induced deficits in spatial learning using composite principal components (PC) scores (optimally weighted z-scores) derived by manifold machine learning as primary endpoints. Spatial learning refers to an organism’s ability to encode information about their environment and to use this information to navigate through it. As astronauts will traverse unknown terrain on a Mars mission, deficits in this cognitive modality would greatly impair mission success. Importantly, we found that brief microglia depletion shortly after exposure mitigates long-term GCRsim-induced deficits in spatial learning, suggesting that while deep space radiation exposure could impair spatial learning there are tools that can alleviate such deficits. We did not observe deficits in other behavioral (anxiety-like, sociability) or cognitive (social memory, and recognition memory) paradigms. Previous findings have shown that charged particle exposure causes deficits in one or more of these measured domains; however, the current data demonstrate that when combined the 5 ions might have different combinatory effects that are not cumulative. While space radiation is the prominent stressor for deep space journeys, there are additional aggravating factors that might impact astronauts, including social isolation, zero gravity, distance from Earth, hostile environment, and altered sleep patterns. Determining if the combination of these stressors with GCRsim exposure impacts behavioral and cognitive function is a crucial next step for mission preparation.

Bibliography Type: Description: (Last Updated: 11/18/2021) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Paladini MS, Feng X, Krukowski K, Rosi S. "Microglia depletion and cognitive functions after brain injury: From trauma to galactic cosmic ray." Neurosci Lett. 2021 Jan 10;741:135462. Epub 2020 Nov 28. https://doi.org/10.1016/j.neulet.2020.135462 ; PMID: 33259927 , Jan-2021
Articles in Peer-reviewed Journals Rienecker KDA, Paladini MS, Grue K, Krukowski K, Rosi S. "Microglia: Ally and enemy in deep space." Neurosci Biobehav Rev. 2021 Jul;126:509-14. Epub 2021 Apr 16. https://doi.org/10.1016/j.neubiorev.2021.03.036 ; PMID: 33862064 , Jul-2021
Articles in Peer-reviewed Journals Krukowski K, Grue K, Becker M, Elizarraras E, Frias ES, Halvorsen A, Koenig-Zanoff M, Frattini V, Nimmagadda H, Feng X, Jones T, Nelson G, Ferguson AR, Rosi S. "The impact of deep space radiation on cognitive performance: From biological sex to biomarkers to countermeasures." Sci Adv. 2021 Oct 15;7(42):eabg6702. https://doi.org/10.1126/sciadv.abg6702 ; PMID: 34652936; PMCID: PMC8519563 , Oct-2021
Project Title:  VNSCOR: Probing the Synergistic Effects of Radiation, Altered Gravity and Stress on Behavioral Cognitive and Sensorimotor Functions to Predict Performance Decrement in Astronauts Reduce
Images: icon  Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
HRP HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Start Date: 10/01/2019  
End Date: 09/30/2023  
Task Last Updated: 07/22/2020 
Download report in PDF pdf
Principal Investigator/Affiliation:   Rosi, Susanna  Ph.D. / University of California San Francisco 
Address:  Physical Therapy and Neurological Surgery 
1001 Potrero Ave. Bldg #1 Room 101 
San Francisco , CA 94110-3518 
Email: rosis@ptrehab.ucsf.edu 
Phone: 415-206-3708  
Congressional District: 12 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of California San Francisco 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Ferguson , Adam  Ph.D. University of California, San Francisco 
Key Personnel Changes / Previous PI: July 2020 report: Adam Ferguson, Ph.D., Associate Professor, Department of Neurological Surgery, Director of Data Science, Brain and Spinal Injury Center (BASIC), and the Weill Institute for Neurosciences at the University of California, San Francisco is now CoInvestigator. Drs. Mora and Wyrobek and Dr. Mao are no longer CoInvestigators on the project.
Project Information: Grant/Contract No. 80NSSC19K1581 
Responsible Center: NASA JSC 
Grant Monitor: Whitmire, Alexandra  
Center Contact:  
alexandra.m.whitmire@nasa.gov 
Solicitation / Funding Source: 2018 HERO 80JSC018N0001-Crew Health and Performance (FLAGSHIP, OMNIBUS). Appendix A-Flagship, Appendix B-Omnibus 
Grant/Contract No.: 80NSSC19K1581 
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)
(2) Sensorimotor:Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks (Revised as of IRP Rev M)
Human Research Program Gaps: (1) BMed-102:Given exposures to spaceflight hazards (space radiation, isolation), how do we identify individual susceptibility, monitor molecular/biomarkers and acceptable thresholds, and validate behavioral health and CNS/neurological/neuropsychological performance measures and domains of relevance to exploration class 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)
(6) SM-104:Evaluate how weightlessness-induced changes in sensorimotor/vestibular function relate to and/or interact with changes in other brain functions (sleep, cognition, attention) (IRP Rev M)
Task Description: The purpose of this application is to: 1) determine the possible synergistic and individual effects of radiation exposure (GCRsim), isolation confinement stress, and altered gravity on behavioral, cognitive, and sensorimotor performance; 2) establish if there are sex-dimorphic responses; 3) develop predictive biomarkers for individual sensitivity; 4) incorporate these results into a predictive statistical model for the extrapolation of performance decrement; and 5) estimate Central Nervous System (CNS) risks in astronauts.

The central hypothesis of this proposal is that there is a synergistic effect of multiple factors (defined by GCRsim, isolation confinement stress, and altered gravity) encountered in deep space exposure that leads to enhanced inflammatory response, promotes synapse loss, and decreases synaptic integrity that leads to long-term loss of sensorimotor, behavioral, and cognitive functions.

The rationale of the proposed research is to understand the mechanisms that underlie the cumulative and synergistic effects of radiation exposure, isolation confinement stress, and altered gravity on behavioral, cognitive, and sensorimotor deficits. Further, we will explore sex-dimorphic responses along with potential peripheral biomarkers associated with simulated deep space travel. Our studies will provide novel information regarding the cellular mechanisms of altered neuronal function involved in simulated deep space conditions (GCRsim, isolation confinement, and altered gravity). Finally, we will incorporate all the results to build risk assessment and performance decrement for astronauts.

We will characterize molecular, cellular, tissue, and behavioral endpoints underlying CNS function in an individual manner with animals prescreening. We will use multiple behavioral and cognitive tests known to be comparable to human performance. We will use state of the art techniques to dissect cellular and molecular changes in the brain. The endpoints will be selected to probe key physiological processes that support tissue homeostasis plasticity in the brain. We will determine if and how cellular and molecular impairments are linked to compromised behavior in motor, social, and cognitive domains. By combining assessments of multiple processes that may have distinct time constants and magnitudes of responses to simulated deep space conditions we will begin to identify operationally-relevant brain functions impacted by the three stressors and relate these to human performance. Furthermore, by comparing outcome measures in both males and females we will begin to understand the distinct aspects of the responses controlled by sex and are therefore more likely to translate to humans.

The proposed aims directly address Human Exploration Research Opportunities (HERO) announcement needs detailed in Appendix A that specify research needs (gaps) related to NASA Research and Technology Development to Support Crew Health and Performance in Space Exploration Missions. The specific gaps this proposal addresses are Topic 1, gap CNS 1 (Are there significant adverse changes in CNS performance in the context and time scale of spaceflight operations? If so, how is significance defined, and which neuropsychological domains are affected? Is there a significant probability that space radiation exposure would result in adverse changes? What are the pathways and mechanisms of change?), CNS 2 (Does space radiation exposure elicit key events in adverse outcome pathways associated with neurological diseases? What are the key events or hallmarks, their time sequence and their associated biomarkers (in-flight or post-flight)?), CNS 5 (How can new knowledge and data from molecular, cellular, tissue and animal models of acute CNS adverse changes or clinical human data, including altered motor and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE-solar particle event?), SM6.1 (Determine if sensorimotor dysfunction during and after long-duration spaceflight affects ability to control spacecraft and associated systems), SM 26 (Determine if exposure to long-duration spaceflight leads to neural structural alterations and if this remodeling impacts cognitive and functional performance), and IM 8 (IM8: We do not know the influence, direct, or synergistic, on the immune system of other physiological changes associated with spaceflight).

Research Impact/Earth Benefits: Our research goals, hypothesis, and proposed aims directly address Human Exploration Research Opportunities (HERO) announcement needs detailed in Appendix A that specify research needs (gaps) related to NASA Research and Technology Development to Support Crew Health and Performance in Space Exploration Missions. The specific gaps this proposal addresses are in Topic 1, CNS 1 “Are there significant adverse changes in CNS performance in the context and time scale of space flight operations? Is there a significant probability that space radiation exposure would result in adverse changes? What are the pathways and mechanisms of change?”; Gap CNS2: “Does space radiation exposure elicit key events in adverse outcome pathways associated with neurological diseases? What are the key events or hallmarks, their time sequence and their associated biomarkers (in-flight or post- flight)?”; SM 26: “Determine if exposure to long-duration spaceflight leads to neuronal structural alterations and if this remodeling impacts cognitive and functional performance.”; IM 8: “We do not know the influence, direct or synergistic, on the immune system of other physiological changes associated with spaceflight.”

Task Progress & Bibliography Information FY2021 
Task Progress: During the first year of the grant we established the work collaboration with the other Virtual NASA Specialized Center of Research (VNSCOR) Principal Investigators (PIs) and we concluded the Definition Phase. Dr. Rosi was asked by the Central Nervous System, Behavioral Health, and Sensorimotor (CBS) team to serve as the leader for the 3 VNSCORs projects. Lead PI for three grant VNSCOR to provide:

Assurance of high quality, integrated-risk research

Standardization of approaches/rationale

Mechanisms to maintain communications (and reduce site burdens)

Consistent information

Efficiently/effectively integrate research efforts

Data management

Integration of research data

Research data submission formats

Computational modeling lead

Throughout the definition phase the Ronca, Rosi, and Sanford groups have agreed upon the A) standardizations (where possible without changing the study objectives) of experimental design for exposure regimen, husbandry, animal sex and ages and data collection schedules. In addition to the animal care specifics, we have developed a unified model for combined space stress that will be used at Brookhaven National Laboratory (BNL) by all investigators, stages of which will be followed by each grant’s specific aims. In brief, all animals will have an identical length of time at BNL under the same husbandry conditions including same diet, undergo the same acclimation, social isolation, microgravity model, GCR dose, similar euthanasia methods, and a minimum of one unified downstream marker in both the blood and brain. To maintain standardization across the three VNSCOR investigators have agreed on: time at BNL, dose, diet, parasite protection, cognitive measures, and blood biomarkers.

Due to COVID-19 we were not able to proceed with Aim 1 as planned. These experiments have been postponed to Spring 2021.

Bibliography Type: Description: (Last Updated: 11/18/2021) 

Show Cumulative Bibliography Listing
 
Articles in Other Journals or Periodicals Paladini MS, Krukowski K, Feng X, Rosi S. "Microglia depletion and cognitive functions after brain injury: from trauma to galactic cosmic ray." Neuroscience Letters. In press as of July 2020. , Jul-2020
Project Title:  VNSCOR: Probing the Synergistic Effects of Radiation, Altered Gravity and Stress on Behavioral Cognitive and Sensorimotor Functions to Predict Performance Decrement in Astronauts Reduce
Images: icon  Fiscal Year: FY 2020 
Division: Human Research 
Research Discipline/Element:
HRP HFBP:Human Factors & Behavioral Performance (IRP Rev H)
Start Date: 10/01/2019  
End Date: 09/30/2023  
Task Last Updated: 10/16/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Rosi, Susanna  Ph.D. / University of California San Francisco 
Address:  Physical Therapy and Neurological Surgery 
1001 Potrero Ave. Bldg #1 Room 101 
San Francisco , CA 94110-3518 
Email: rosis@ptrehab.ucsf.edu 
Phone: 415-206-3708  
Congressional District: 12 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of California San Francisco 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Mao, Xiao Wen  M.D. Loma Linda University 
Mora, Ana  Ph.D. University of California, Berkeley 
Wyrobek, Andrew  Ph.D. Lawrence Berkeley National Laboratory 
Project Information: Grant/Contract No. 80NSSC19K1581 
Responsible Center: NASA JSC 
Grant Monitor: Williams, Thomas  
Center Contact: 281-483-8773 
thomas.j.will1@nasa.gov 
Solicitation / Funding Source: 2018 HERO 80JSC018N0001-Crew Health and Performance (FLAGSHIP, OMNIBUS). Appendix A-Flagship, Appendix B-Omnibus 
Grant/Contract No.: 80NSSC19K1581 
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)
(2) Sensorimotor:Risk of Altered Sensorimotor/Vestibular Function Impacting Critical Mission Tasks (Revised as of IRP Rev M)
Human Research Program Gaps: (1) BMed-102:Given exposures to spaceflight hazards (space radiation, isolation), how do we identify individual susceptibility, monitor molecular/biomarkers and acceptable thresholds, and validate behavioral health and CNS/neurological/neuropsychological performance measures and domains of relevance to exploration class 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)
(6) SM-104:Evaluate how weightlessness-induced changes in sensorimotor/vestibular function relate to and/or interact with changes in other brain functions (sleep, cognition, attention) (IRP Rev M)
Task Description: The purpose of this application is to: 1) determine the possible synergistic and individual effects of radiation exposure (GCRsim), isolation confinement stress, and altered gravity on behavioral, cognitive, and sensorimotor performance; 2) establish if there are sex-dimorphic responses; 3) develop predictive biomarkers for individual sensitivity; 4) incorporate these results into a predictive statistical model for the extrapolation of performance decrement; and 5) estimate Central Nervous System (CNS) risks in astronauts.

The central hypothesis of this proposal is that there is a synergistic effect of multiple factors (defined by GCRsim, isolation confinement stress, and altered gravity) encountered in deep space exposure that leads to enhanced inflammatory response, promotes synapse loss, and decreases synaptic integrity that leads to long-term loss of sensorimotor, behavioral, and cognitive functions.

The rationale of the proposed research is to understand the mechanisms that underlie the cumulative and synergistic effects of radiation exposure, isolation confinement stress, and altered gravity on behavioral, cognitive, and sensorimotor deficits. Further, we will explore sex-dimorphic responses along with potential peripheral biomarkers associated with simulated deep space travel. Our studies will provide novel information regarding the cellular mechanisms of altered neuronal function involved in simulated deep space conditions (GCRsim, isolation confinement, and altered gravity). Finally, we will incorporate all the results to build risk assessment and performance decrement for astronauts.

We will characterize molecular, cellular, tissue, and behavioral endpoints underlying CNS function in an individual manner with animals prescreening. We will use multiple behavioral and cognitive tests known to be comparable to human performance. We will use state of the art techniques to dissect cellular and molecular changes in the brain. The endpoints will be selected to probe key physiological processes that support tissue homeostasis plasticity in the brain. We will determine if and how cellular and molecular impairments are linked to compromised behavior in motor, social, and cognitive domains. By combining assessments of multiple processes that may have distinct time constants and magnitudes of responses to simulated deep space conditions we will begin to identify operationally-relevant brain functions impacted by the three stressors and relate these to human performance. Furthermore, by comparing outcome measures in both males and females we will begin to understand the distinct aspects of the responses controlled by sex and are therefore more likely to translate to humans.

The proposed aims directly address Human Exploration Research Opportunities (HERO) announcement needs detailed in Appendix A that specify research needs (gaps) related to NASA Research and Technology Development to Support Crew Health and Performance in Space Exploration Missions. The specific gaps this proposal addresses are Topic 1, gap CNS 1 (Are there significant adverse changes in CNS performance in the context and time scale of spaceflight operations? If so, how is significance defined, and which neuropsychological domains are affected? Is there a significant probability that space radiation exposure would result in adverse changes? What are the pathways and mechanisms of change?), CNS 2 (Does space radiation exposure elicit key events in adverse outcome pathways associated with neurological diseases? What are the key events or hallmarks, their time sequence and their associated biomarkers (in-flight or post-flight)?), CNS 5 (How can new knowledge and data from molecular, cellular, tissue and animal models of acute CNS adverse changes or clinical human data, including altered motor and cognitive function and behavioral changes be used to estimate acute CNS risks to astronauts from GCR and SPE?), SM6.1 (Determine if sensorimotor dysfunction during and after long-duration spaceflight affects ability to control spacecraft and associated systems), SM 26 (Determine if exposure to long-duration spaceflight leads to neural structural alterations and if this remodeling impacts cognitive and functional performance), and IM 8 (IM8: We do not know the influence, direct, or synergistic, on the immune system of other physiological changes associated with spaceflight).

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2020 
Task Progress: New project for FY2020.

Bibliography Type: Description: (Last Updated: 11/18/2021) 

Show Cumulative Bibliography Listing
 
 None in FY 2020