Last Published:
03/26/21 03:33:57 PM (Central)
Responsible Element: Human Factors and Behavioral Performance (HFBP)
Status: Open
Given the extended duration and/or distance from Earth of future spaceflight missions, crewmembers will be exposed to multiple individual and simultaneous spaceflight hazards (e.g., space radiation, isolation, altered gravity) for extended periods of time. However, there is a lack of human epidemiology data on which to estimate these risks, making projection based on scaling to human data not currently possible for central nervous system (CNS) risks. Possible acute (within mission) risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are a documented concern for human exploration of space, as are risks due to isolation and confinement, circadian dysregulation, and cerebral fluid shifts in altered gravity. Acute CNS risks include: altered cognitive function, reduced motor function, behavioral and neuropsychological changes, all of which may affect performance and human health. Research specific to the spaceflight environment using animal and cell models using near-term experimental research focused on low dose-rate relevant types and exposures of GCR must be compiled to calculate the magnitude of this risk by scaling these results to human data while assessing potential synergistic risks of multiple stressors. Since it is anticipated that exploration class missions will become increasingly autonomous, a largely different model of psychological care provided to crewmembers is needed. This increased autonomy will increase the need to identify and validate measures to monitor behavioral health and performance during exploration class missions to determine acceptable thresholds for these measures. There is a need for objective, reliable, and sensitive methods or tools for monitoring and measuring changes in individual behavioral and cognitive health and performance so that flight surgeons and operational psychologists can provide support. Objective assessments of the crewmember's psychological well-being in conjunction with the crewmember's subjective reports can provide the context needed to more accurately assess the astronaut’s cognitive and behavioral health and performance. In addition, evidence indicates that gathering objective information would be highly valuable in astronaut selection and training and can provide mission planners and operators with critical information on individual adaptation and functioning so that if decrements are detected these can be evaluated on a case-by-case basis and a more personalized countermeasure approach can be provided. The contributions of individual sensitivity (genetic, epigenetic, previous injury, age, sex/gender, etc.) to possible acute and late risks to the CNS from space radiation exposure, isolation, circadian dysregulation, and brain morphology shifts in altered gravity on overall crew health and performance are undetermined. While it is necessary to determine the impact of environmental factors on sleep and performance, as well as the mission requirements that disrupt circadian rhythms and sleep, there are varied ways through which individuals respond to stressors. Recent studies have documented that there are large stable (trait-like) differences among individuals in the degree of cognitive deficits experienced during sleep loss. Such evidence is needed to identify, establish, and validate performance outcome limits (POLs) and Permissible Exposure Limits (PELs) for these hazards individually and in combination.
Approach:
Ground-based, peer-reviewed research using cell and animal models to acquire necessary knowledge for accurate risk quantification and uncertainty reduction for central nervous system (CNS) adverse changes due to space radiation exposure. Where feasible, identify biomarkers of cognitive/CNS/behavioral performance changes and/or disease prognosis/progression and outcome pathways for use in monitoring early, in-mission, or adverse late operationally-relevant outcomes. Research approaches are establishing the molecular basis of operationally-relevant, cognitive performance/CNS reactions to HZE nuclei exposure. An integrated research approach is needed that focuses on the potential synergistic impacts to the central nervous system (CNS), impacts of isolation on Behavioral Medicine (B), and the sensorimotor (S) and broader cognitive impacts of altered gravity (i.e., CBS Integrated Research Plan). The CBS Integrated Research Plan is a systems biology approach focused on the potential CNS adverse outcome pathways that form a basis for animal to human extrapolation, and relies on an understanding of molecular and physiological changes in the CNS caused by individual or potentially synergistic actions of space radiation, isolation, and altered gravity, and how these changes relate to adverse operationally-relevant performance outcomes. This approach will rely on understanding of molecular and physiological changes in the cognitive/CNS domains caused by space radiation. Intermediate CNS models of important pathways and processes that contribute to cognitive/CNS risks including synapse dysfunction, impaired neurogenesis, proteinopathies, neurodegeneration, chronic oxidative stress, neuro-inflammation, etc., will be generated and developed into a model for operationally-relevant cognitive/CNS risk assessment.
In conjunction with this effort, it is necessary to set exploration-class mission acceptable levels (thresholds) for the key behavioral health and performance indicators. The astronaut corps is comprised of highly selected, motivated and skilled individuals who out-perform other healthy adults while working operationally. Therefore thresholds will need to be normed to the astronaut population. A threshold represents a level above or below which would indicate a meaningful or reliable change and thus can trigger mitigation action. The change could be a percentage change in a set of behaviors from baseline levels or at specific times during the mission (e.g., third quarter). We will then develop and validate the measures and tools that are sensitive, reliable, and feasible to monitor behavioral health and performance. We will utilize high fidelity analogs to validate the set of effective measures for monitoring. These measures will be vetted with SMEs and evidence will be updated accordingly. During the development and validation of those tools, a critical step is to establish a baseline for thresholds regarding individual behavioral health and performance for exploration class missions. This will enable experts (e.g., flight surgeons, BHP Operations) and astronauts themselves, to more accurately monitor and manage crewmember behavioral health status. Setting crewmember thresholds is important to the understanding and mitigating of off-nominal individual behaviors during exploration missions of varying duration (e.g., <6; 6-12; >12 months). Currently, such metrics do not exist for ISS missions, and neither do astronaut norms for many of the parameters of import. The goal is to develop astronaut norms where needed and to standardize metrics to provide the ability to objectively detect, assess, and manage off-nominal events, and predict future off-nominal events that may compromise a mission and increase the risk of behavioral health and performance decrements. Individualized, real-time tools that provide rapid feedback and assessment will be needed for exploration class missions. From the key threats and promoters of behavioral health identified and baselined for Earth-levels, current measures and readiness levels of research deliverables (tools and technologies) will be reviewed. The baseline will allow for future monitoring of long duration crews. Astronaut norms will need to be developed for this set of behaviors where possible, or extrapolated from healthy, astronaut-like population. The tools for detecting and assessing cognitive and behavioral health status will need to be tested in high fidelity analogs for sensitivity, reliability as well as feasibility and acceptability for astronauts. Finally an integrated testing of countermeasures will test the full suite of integrated countermeasures.
Metrics for Interim Progress:
Determine impact of individual susceptibility on space radiation dose responses, possible dose thresholds, latency to onset and severity of acute and late operationally-relevant cognitive/CNS and behavioral performance outcomes.
Identifying individual factors that mediate the degree to which an external stressor affects the individual will inform individual countermeasure recommendations.
Can we identify/validate advancing technological innovations in areas of Brain-Computer Interface (BCI), Artificial Intelligence (AI), neurophysiological processes, workload and cognitive performance thresholds for autonomous, long-duration expeditionary/exploration missions?
Use multiple research approaches involving neuroergonomics that uses non-invasive neurophysiological tools to measure known correlates of mental effort to assess workload during a task as well as machine learning to classify mental workload states via brain activity to identify cognitive performance thresholds.
Use ground-based, peer-reviewed research using cell and animal models conducted to acquire necessary knowledge for accurate risk calculation and uncertainty reduction for acute adverse cognitive/CNS behavioral performance outcome measures due to mission-relevant individual or combined exposures (e.g., space radiation, isolation, altered gravity).
-Identify appropriate experimental models, paradigms and endpoints for assessment of acute radiation effects on the CNS.
-Identify the pathophysiological mechanisms underlying functional CNS change.
-Determine the space radiation dose responses and existence of threshold doses for functional CNS changes using appropriate animal model systems (e.g. rodent, NHP)
-Broaden initial experiments to investigate higher fidelity radiation fields (e.g., a larger number of GCR particle types and energies including mixed fields) representative of GCR and different shielding configurations including the Martian surface.
Determine impact of previous CNS injury on space radiation dose responses, possible dose thresholds, latency to onset and severity of acute and late CNS effects.
Determine feasibility of indexed biomarker approaches for monitoring individual susceptibility for monitoring acute (in-mission) and late (post-mission) operationally-relevant cognitive/CNS and behavioral performance outcomes.
Identified behavioral and/or physiological marker(s) for individual vulnerabilities and resiliencies to sleep loss and circadian rhythm disruption based on the amount of variance seen in performance, across individuals in controlled experimental studies.
Acquire data from astronauts to relate space radiation exposure and individual sensitivity to acute and late operationally-relevant cognitive/CNS and behavioral performance outcomes.
Define risk domains and appropriate metrics that encompass operationally-relevant performance decrements of concern (e.g. memory, attention and executive functions, motor skills, reasoning/decision making, reaction time, other neuropsychological or neurobehavioral domains, etc).
Develop intermediate cognitive/CNS/behavioral performance models of important outcome pathways and processes that contribute to CNS risks, including synaptic dysfunction, proteinopathies, chronic oxidative stress, impaired neurogenesis, neurodegeneration, neuro-inflammation, etc.
Combine cognitive/CNS process impacts and operationally-relevant change due to exposure to spaceflight hazards exposures to create a model for cognitive/CNS and behavioral risk assessment.
Operationally-relevant cognitive and behavioral performance model validation and documentation.
Determine the operational significance of adverse changes elicited by mission-relevant space radiation, isolation, circadian disruption, etc. exposures.
Quantify the spectrum and dose responses for acute (mission timescale) functional cognitive/CNS/Behavioral operationally-relevant performance changes from space radiation and isolation exposures.
-Organize cognitive/CNS reactions to radiation exposure into adverse outcome pathway(s) related to known diseases and biomarkers.
-Identify behavioral and/or physiological biomarkers linking individual vulnerabilities and resiliency to sleep loss and circadian rhythm and sensitivity to other mission relevant exposures (e.g., space radiation, isolation, altered gravity) and outcome measures.
-Identification of factors that would affect individual risk (both acute, inflight, and post-mission) to the cognitive/CNS/behavioral status from mission-relevant exposures (e.g., space radiation, isolation, altered gravity) and assessment of these factors in a study in astronauts.
-Model cognitive/CNS/operationally-relevant performance reactions to radiation and isolation exposures to identify adverse outcome pathway(s) related to known cognitive or behavioral risks, or conditions of impaired performance, and link to biomarkers at molecular, cellular, tissue levels of organization.
Identification and validation of an integrated suite of minimally obtrusive tools that have been verified (meets functional requirements) and validated (content, construct, and where applicable, criterion-related validity), as well as evaluated for feasibility and acceptability in high fidelity ground analogs and/or spaceflight, to monitor and measure operationally-relevant performance changes due to mission-relevant exposures, to include measures of sleep and associated changes to performance and cognitive function unobtrusively, while providing operationally relevant feedback related to sleep and operationally-relevant performance.
Monitoring measures validated for feasibility and acceptability in high fidelity ground analogs of different durations (<6 months; 6-12 months; >12 months).
Quantified and validated set of mission acceptable thresholds for individual behavioral health and performance during exploration class missions.
Identified and incorporated standard exposure conditions and reference measures.
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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?
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Active
Task Book:
Entry Unavailable
Principal Investigator:
Costes, Sylvain
Short Title:
Mapping peripheral immune signatures
Responsible HRP Element:
Space Radiation
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Aim 1. Blood-based biomarker signature to improve biodosimetry in response to simulated GCRs and their components.
Aim 2. Define blood-based biomarkers of individual susceptibility to simulated GCRs and their components.
Aim 3. Evaluate relative biological effectiveness (RBE) between biomarkers and dose rate effects.
Category:
Risk Characterization, Quantification
Subcategory:
Description:
Multi-variate modeling of biomarkers for dosimetry, personalized responses and RBE.
Internal Customers:
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Dinges, David
Short Title:
Adaptation and Resilience NSCOR
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
The overarching goal of this proposal is to characterize the three less well-understood NIMH RDoC domains related to positive valence, negative valence, and social processes as they relate to the performance, adaptation, and resilience of individuals living and working in ICC/ICE environments. The investigator team will identify predictive indicators and biomarkers for resilience and adaptation in individuals and teams, to aid in astronaut selection and individualized countermeasure development with the goal to maintain and optimize performance capability and behavioral health during long-duration exploration missions (LDEM).
The specific aims of this study are:
Aim 1: Identify and quantify individual differences in adaptation and resilience, key threats to and promoters of mission relevant behavioral health and performance. The investigator team will use components of the RDoC framework to look across individual risk factors in order to identify and validate molecular, circuitry and physiological measures that can be used for monitoring and selection of individuals who are highly resilient to the key behavioral health and performance threats during autonomous, long duration and/or long distance exploration missions.
Aim 1a. Perform a comprehensive literature review of the RDoC framework to identify the units of analysis (e.g., cells, etc.) of the individual risk factors most related to LDEMs and positive valence, negative valence and social processes domains.
Aim 1b. Identify how the risk factors within those three RDoC domains relate to performance outcomes, resiliency, and adaptation in LDEMs.
Aim 2: Identify neural circuits and molecular/cellular mechanisms underlying adaptation and resilience in a rodent model using cross-species equivalency.
Aim 3: Encompasses the biological basis of social support to assess individual sociability and the neurobehavioral contributions to resiliency and/or adaptability of engaging positively in social interactions, tolerance, and awareness (e.g., affiliation, attachment).
Aim 4: Identify how meaningful work mediates the relationship between risk factors, the valence and social process domains, and operational outcomes, as well as direct effects of meaningful work on performance. The intent is to identify a sensitive, reliable, valid, and feasible set of measures for measuring and monitoring meaningfulness of work in spaceflight.
Aim 4a. An additional aim and
primary objective was added to assess the effects of plant growth and fresh
food on behavioral health in an isolated, confinement and extreme (ICE)
environment using the Neumayer III Station of Antarctica. The specific aim is
to identify the research participant’s experiences growing plants and
vegetables and the availability of fresh food using a series of self-reported
measures related to meaningful work and to relate terrestrial research results
to those of the ISS-Veggie project.
Aim 5: Encompasses the need to identify how positive and negative valence systems impact on psychological well-being and performance when confronted with the adverse conditions found in prolonged space flight. We will identify biomarkers and psychological report measures associated with the effects of well-being on performance and determine their contribution to the positive/negative valence systems involved in individual adaptation and resilience.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO], ICE Field Analog, Long Duration (4 months or more) – isolated, confined and extreme; may not have spaceflight mission scenario [e.g., Antarctica]
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Number of Subjects
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50
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Category:
Countermeasure
Subcategory:
Protocol
Description:
Final report summarizing research efforts including: individual risk factors most associated with positive valence, negative valence, and social process domains, and how they relate to performance, adaptation, and resilience. In addition, results aims to include: evidence on how fluctuations in work meaningfulness, changes in the physical environment, the degree of sociability, and other external factors such as food, mediate the relationship between risk factors and outcomes.
a. Supplemental work will include a report on Aim 4a., above, related to the
Veggie on ICE research at Neumayer III Station: A report
analysis comparing
the veggie survey and other behavioral health and performance data collected as
part of the “NSCOR for Evaluating Risk Factors and Biomarkers for Adaptation
and Resilience to Spaceflight: Emotional Valence and Social Processes in
ICC/ICE Environments.”
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
A better understanding of the key threats, indicators, and evolution of the team throughout its life cycle for autonomous, long duration and/or distance exploration missions; psychological measures that can be used to select individuals most likely to maintain team function for autonomous, long duration and/or distance exploration missions;.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Category:
Study Results
Subcategory:
Customer Requested Study or Analysis
Description:
Sensitive, reliable, and valid measures that are feasible in the context of spaceflight for assessing relevant constructs including adaptability, emotional regulation, sociability, meaningfulness of work, and personal well-being.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Lemere, Cynthia
Short Title:
ApoE Late CNS/CVD
Responsible HRP Element:
Space Radiation
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
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Aim 1: investigate late CNS/CVD Effects of Simplified 5-ion Mixed Field Beam (normalized to 500 mGy) GCR IRR in Male & Female AD Tg and WT Mice.
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Aim 2: investigate Late CNS/CVD Effects of Simplified 5-ion Mixed Field Beam IRR in Male and Female APP/E3 and APP/E4 Tg and WT Mice.
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Aim 3: investigate Acute and Late CNS and CVD Effects of Simplified 5-ion Mixed Field Beam Space Radiation on Human Cells In Vitro
Category:
Subcategory:
Description:
Annual and final reports and peer reviewed publications.
Internal Customers:
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Dinges, David
Short Title:
Behavioral Core Measures
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
The overarching goal of this project is to build on a successful record of unobtrusive, software-based measurement of behavioral health indicators (e.g., mood, cognitive function, physical and mental fatigue, sleep quality) to develop an integrated standardized suite of behavioral health measurement tools (SBMT) that would be quite feasible to implement within the constraints of spaceflight research, ground-based analogs (both short- and long-duration), and prolonged missions in isolated, confined, extreme environments lasting up to 12 months or longer.
The suite of behavioral medicine measures in development for standardized use in ground analogs relevant to the spaceflight context. The Standardized Behavioral Measures Tool or SBMT will include (a) the Cognition battery, (b) Visual Analog Scales (VAS) of perceived mental and physical exhaustion, fatigue, stress, workload, conflict and sleep quality, (c) actigraphy for monitoring sleep/wake activity, (d) an audio journal, (e) the Space Dock task as an operational performance measure, and (f) additional non-invasive measures relevant to behavioral medicine informed by a comprehensive literature review. The SBMT will be evaluated for its including the task of taking the information on measurement feasibility, flexibility and acceptability during post-mission assessments in the participants studied in HERA, and ISS.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO], ICE Field Analog, Long Duration (4 months or more) – isolated, confined and extreme; may not have spaceflight mission scenario [e.g., Antarctica]
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Number of Subjects
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22
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Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
NRA final report providing evidence on the measures to detect, monitor and assess behavioral health of individuals in isolation and confinement. This task will contribute to gap closure by providing a standard with which countermeasure effectiveness can be evaluated.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Category:
Technology or Tool
Subcategory:
Computational Models or Simulations
Description:
Suite of standardized measures, predictive of behavioral & operational outcomes as an integrative and intuitive research platform to administer a suite of standardized measures predictive of behavioral and operational outcomes called the Standardized Behavioral Measures Tool (SBMT).
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
Med Ops - Medical Operations
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Lockley, Steven
Short Title:
Biomarkers for Behavioral Health
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Ground study to determine optimal methods for detecting individual vulnerabilities and resiliences to sleep loss and circadian desynchronization. Findings will help inform individualized countermeasure regimens for spaceflight. Touchpoint with Sleep
Aim 1: Perform individualized analyses and modeling of our extensive laboratory data set from inpatient studies ranging from 4-74 days including biomarkers such as sleep (EEG, actigraphy, logs); repeated measures of neurocognitive performance including attention, vigilance, motor control, and short-term memory; repeated measures of alertness (waking EEG, subjective scales); circadian phase (melatonin, cortisol, temperature); stress and activation (heart rate variability, blood pressure, catecholamines, cortisol), metabolism (lipid metabolism, glucose metabolism), immune function (cytokine and chemokine rhythms) and mood (clinical questionnaires, subjective scales) and multiple other physiological and metabolic measures.
Aim 2: Conduct a series of short 7-day inpatient studies on astronaut-aged healthy male and female volunteers to test the sensitivity and specificity of multiple biomarkers to predict inter-individual responses to sleep and circadian challenges.
Aim 3: Evaluate the feasibility and utility of implementing a standardized set of objective and subjective predictive biomarkers for neurocognitive impairment and behavioral health outcomes in Antarctica.
Ground Analog Resources
Ground-Based Flight Analogs
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ICE Field Analog, Long Duration (4 months or more) – isolated, confined and extreme; may not have spaceflight mission scenario [e.g., Antarctica]
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Number of Subjects
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20
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Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Report that describes optimal methods for detecting vulnerabilities and resiliencies. Will also serve to inform individualized countermeasures.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Goel, Namni
Short Title:
Biomarkers of Stress and Resilience
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
This proposal has four specific aims:
Aim 1: Determine whether candidate biomarkers, including cardiovascular measures, change in response to high performance demands and acute sleep loss stressors.
Aim 2: Evaluate the predictive validity of a set of candidate biomarkers, including cardiovascular measures, for neurobehavioral susceptibility to the stressors in Aim 1.
Aim 3: Identify candidate biomarkers that differentiate susceptible and resilient individuals in responses to the stressors in Aim 1.
Aim 4: Determine the stability of candidate biomarkers from pre-mission to in-mission baseline and from in-mission recovery to post-mission.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Long Duration (4 months or more) – isolated and confined with spaceflight mission scenario [e.g., NEK/Russian Chamber], Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO]
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Number of Subjects
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38
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Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Biomarkers evidence
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Weil, Michael
Short Title:
Cancer Biomarkers
Responsible HRP Element:
Space Radiation
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Project 1 - identify biomarkers for susceptibility to HZE ion carcinogenesis and for early disease detection using genetic and systems biology approaches. Uses integrative “omics” approaches over multiple levels of biological organization and involves multiple species.
Project 2 - focuses on the mechanisms underlying the increased malignancy of HZE ion-induced tumors compared with their spontaneous or γ- ray-induced counterparts.
Project 3 - examines the critical question of risk from protracted exposures to high LET radiation at low doses and dose rates. Uses chronic exposures to high LET associated neutron radiation as a surrogate for conditions of space-relevant fluence rates and total doses to estimate the carcinogenic effects.
Project 4 - utilizes the resources (irradiated mice and “omics” results) generated in the first three projects to study the neurobehavioral consequences of HZE ion and neutron exposures and whether they are related to cancer outcome measures and predicted by the same or distinct biomarkers
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Annual and final reports and peer reviewed publications providing research results supporting the further development of accurate risk quantification methods in assessing radiation carcinogenesis. Studies will provide low dose rate information for high LET irradiations as well as identifying potential mechanisms for increased metastatic potential of heavy ions for risk modeling. Studies will also provide evidence on the effects of chronic low dose-rate exposures to high LET radiation on cognition as well as the identification of biomarkers predictive of radiation-induced cognitive decrements.
Internal Customers:
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Cekanaviciute, Egle
Short Title:
CBS Astrocyte Mediator (Cekanaviciute)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
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Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Specific Aim 1. Define human astrocyte responses to ionizing radiation. We will map
the dose response and time course of astrocyte responses to X-rays, and 0.5Gy 5-ion simulated
GCRs to identify their relative biological effectiveness (RBE). We will quantify astrocyte gene
expression and correlate it with physiological outcomes: cytokine secretion, cell death and
oxidative stress, to define whether irradiated astrocytes adopt A1 or A2 phenotypes.
Specific Aim 2. Investigate how astrocytes regulate neuronal damage in response to
simulated GCRs. We will utilize 3D CNS TOC models (Mimetas OrganoPlates, Figures 2, 3.)
to define 0.5Gy 5-ion simulated GCR-induced neuronal damage and evaluate the contribution of
astrocytes to regulating it.
Specific Aim 3. Examine whether inducing A1/A2 astrocyte phenotypes could serve
as a countermeasure to simulated GCRs. We will induce TOC astrocyte differentiation into
either A1 or A2 phenotype, and examine whether they exacerbate or inhibit neuronal damage
caused by 0.5Gy simulated GCRs.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
We propose to utilize for the first time a novel high-throughput human tissue-on-a-chip model for 3D neuronal/astrocyte cultures. We will investigate the morphological and physiological outcomes as well as gene expression changes at after simulated space radiation exposure (5-ion simulation of galactic cosmic rays, 500mGy) and compare them to the responses to gamma radiation in order to establish the relative biological effectiveness. We will also evaluate the necessity and sufficiency of astrocytes in regulating radiation responses by establishing experimental models where astrocytes are either the only cell type that is irradiated, or the only cell type that escapes irradiation.Finally, we will test
astrocytes as targets for countermeasures, which has not been done before in the context of spaceflight, and thus could lead to novel breakthroughs.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Smith, Scott
Short Title:
CBS BioNutritional CMs Data Mining (Smith)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
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Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
1. Complete a systematic review of the literature to describe the interrelationship of nutrition (and specific nutrients) with CBS systems and risks. Identify potential nutritional countermeasures of relevance to the CBS systems and risks, focusing on how these countermeasures may influence performance outcomes.
a. Development of a comprehensive database of relevant research that allows for an assessment of the methodological quality of included studies.
b. Summarize the extent, range, and nature of nutritional countermeasures that potentially mitigate the individual and synergistic impacts of the three CBS risks.
2. Summarize relevant research findings in order to provide a scientifically plausible rationale for an integrated risk mitigation approach using nutritional countermeasures while addressing the implications for these countermeasures in the context of missionrelated factors (e.g., immune system alterations, food systems) related to crew health and operational performance.
a. Identify research conducted with animals to identify plausible approaches for use of animal models in the identification and validation of nutritional countermeasures for use in the CBS Integrated Research Plan.
3. Identify biomarkers associated with nutrition and nutritional countermeasures and their relevance to a) structural and functional changes to brain, b) associated dose-response
effects related to physiological changes, and/or c) real-time performance outcomes.
4. Use results of this literature-based research to identify gaps in knowledge related to a) potential synergistic effects of deep space travel (e.g., impacts of isolation and confinement and altered gravity, and radiation effects), b) potential use of CMs to prevent or intervene, and c) potential biomarkers for both human spaceflight and translational models. In particular, identify research gaps in the existing literature related to nutritional CMs as they relate to:
- Mechanisms
- Pathways
- Order effects validation
- Biomarkers
- Potential interactions with other countermeasures
- development/refinement of standards
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
This project is focused on nutrition, and seeks to compile a review of existing literature relating nutrition and the CBS risks. Specifically, this review will:
1. identify nutrition research related to an integrated risk posed by radiation, isolation, confinement, and the sensorimotor adaptations of altered gravity
2. identify the utility of nutrient (and/or related metabolite) biomarkers in assessing this risk.
3. identify potential benefits of nutrient countermeasures for prevention and/or
intervention to ensure sustained crew health and performance
4. identify plausible biochemical pathways that account for the effectiveness of the countermeasures
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Wyrobek, Andrew
Short Title:
CBS CNS Damage Signaling Neuropathology (Wyrobek)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
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Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Original Study Aims
Aim 1. Characterize the persistence of radiation-induced molecular abnormalities in cortex and hippocampus after low-dose exposures to 56Fe particles, and compare the predictions for CNS tissue damage and late-onset neuropathologies in similarly irradiated mice and rats.
Aim 1a: Use archived CNS tissue from SD rats collected at 4 and 9 months after low-dose exposures, and generate new transcriptomics (3’TAGseq) and new metabolomics profiles (untargeted metabolism and targeted complex lipids) from cortex and hippocampus. These data will be integrated with prior proteomics profiles from hippocampus at 9 months after exposure to build a predictive model of CNS tissue damage and risks for neuropathology, with emphasis on vascular and immune abnormalities.
Aim 1b: Compare molecular responses in cortex and hippocampus of mice and rats at 9 months after exposure to evaluate cross- species consistency. The predictive model will be built using integrating bioinformatics and biostatistical approaches.
AIM 2. Identify persistent bio-effect markers in peripheral blood and CSF that correlate with molecular damage in CNS vascular or immune functions.
Aim2A will investigate the metabolomics profiles of archived CSF and archived peripheral blood plasma for the same animals.
AIM 2B will determine whether the blood metabolites associated with CNS tissue damage correlate with individual variation in radiation-susceptibility for anxiety as measured in the elevated plus maze.
CBS Supplement Aims
Aim 1. Characterize and build computational models for the effects of age-at-exposure and dose
fractionation (repeated exposures) on performance in each of three behavioral domains, using
NASA-provided data sets.
Aim 1a. Evaluate the age-at-exposure and dose fractionation data sets for data quality across ions, exposure regimens, study design, and behavioral outcomes, and for suitability for multivariate modeling of risks for specific behavioral domains.
Aim 1b. Build single-ion risk models that incorporate age-at-exposure and dose-fractionation effects for each behavioral domain, using data sets that pass the Aim 1a evaluation criteria.
Aim 1c. Build multi-ion risk models that integrate the age-at-exposure and dose-fractionation effects for each behavioral domain from the single ion models of Aim 1b. The risk predictions of the different behavioral domains will be evaluated using both experimental exposure regimens and GCR-relevant estimates for ion spectra and doses.
Aim 2. Characterize and build computational models for exposure dose and effect modifiers of performance in three behavioral domains, using NASA-provided data sets.
Aim 2a. Evaluate the dose-response and effect-modifier data sets for data quality across ions, exposure regimens, study design, and behavioral outcomes, and for suitability for multivariate modeling of risks for specific behavioral domains. Effect modifiers to be assessed may include strain/genotype, sex, and diet group, depending on the data sets provided.
Aim 2b. Build single-ion risk models that incorporate dose-response and effect-modifier effects for each behavioral domain, using data sets that pass the Aim 2a evaluation criteria.
Aim 2c. Build multi-ion risk models that incorporate dose-response and effect-modifier effects for each behavioral domain, based on the findings of the single ion models of Aim 2b. The risk predictions of the different behavioral domains will be evaluated using both experimental exposure regimens and GCR-relevant estimates for ion spectra and doses.
Aim 3. Apply advanced statistical methods to integrate the risk estimates from Aim 1 and Aim 2 into a unified model to predict individual-level risk for specific behavioral domains.
Aim 4. Evaluate NASA-provided data sets for building computational models for associations of
CNS tissue biomarkers with performance in three behavioral domains.
Aim 4a. Evaluate the CNS tissue biomarker and behavioral outcomes data set for data quality across exposure regimens and behavioral outcomes, and for suitability for multivariate modeling of risks for specific behavioral domains. Effect modifiers that maybe available include strain/genotype and age at exposure. The data sets expected to be available for aim 4 are likely to be single ion experiments with molecular biomarker data from a few CNS sub-regions in animals tested for behavioral outcomes.
Aim 4b. Build single-ion risk models for CNS tissue biomarkers for each behavioral domain, using data sets that pass the Aim 4a evaluation criteria
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
1. The proposed research will provide molecular information on the effects of age at radiation exposure, time of tissue collection after exposure, and effects of genomic background on dose response and thresholds for Central Nervous System (CNS) pathways associated with radiation-damage response and neuropathology. This information will provide time information on early and late neuro-pathological changes associated with vascular damage and inflammation that will support establishment of acute and late (CNS) Permissible Exposure Limits (PELs). Our research plan will identify low-dose thresholds for the expression of unique molecular changes and changes in pathways associated with neuropathology.
2. The proposed proteomic and metabolomic research results will be used to identify CNS subregion-specific responses as well as common radiation responses, and to identify mouse-rat cross-genome-risk biomarkers and pathways for the development of molecular countermeasures. This research will examine the molecular evidence that common pathways are affected by HZE exposure in three CNS subregions of the same animal in cerebral spinal fluid (CSF), cortex and hippocampus. This research will focus on molecular changes and signaling pathways after low dose exposure, with emphasis on molecular changes associated with vascular damage and inflammation.
The knowledge gained in this research project will (a) provide data to compare low-dose tissue response across brain subregions in two rodent species (rats and mice), (b) provide evidence of dose-dependence and persistence of pathways associated with neurotoxicity (e.g., inflammation, vascular damage) across CNS subregions in two species, and (c) inform identification of CNS biomarkers and mechanism-based radioprotective countermeasures.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
CBS Supplement Deliverables
1.Evaluate and apply individual-level data on exposure to space radiation, effect modifiers, biomarkers, and/or behavioral outcomes from NASA-funded research to build and estimate the performance of multivariate models to predict individual-level risks of space radiation on operation-relevant performance in distinct behavioral domains.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Raber, Jacob
Short Title:
CBS GCRsim, HU Effects on BPP (Raber)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
|
Human Factors and Behavioral Performance (HFBP) Element |
Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
|
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
|
|
Aims:
Aim 1. Determine the effects of mixed beam irradiation in the presence and absence of hindlimb unloading on behavioral and cognitive performance and determine whether these effects are associated with alterations in metabolic pathways in two pertinent brain regions in WAG rats.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Conduct a metabolomics analysis of the two pertinent brain regions (all likelihood, hippocampus and cortex).
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Peter, Roma
Short Title:
CBS Operational Performance Measures (Roma)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
|
Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
|
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
|
|
Aims:
Identification and integration of operationally-relevant performance tasks from available performance measures across disciplines to determine necessary and sufficient performance measures for use in future research (working group). Scope of this effort is to identify the BHP Ops relevant performance measures and link these to Brain Performance Pathways for use by Translational Modeling efforts.
Aim 1. Thorough review of NASA technical and internal documents and the scientific literature and input from NASA Operations experts, identify the core tasks, individual and team performance abilities, and behavioral health and performance competencies for long-duration space exploration missions.
Aim 2. Thorough review of the CNS/SM/BMed scientific literature and NASA technical and internal documents, identify the constituent neurobehavioral processes (e.g., attention, short-term memory, verbal communication), Brain Performance Pathways, and neurobehavioral, neuroanatomical, and neurochemical substrates underlying each of the core tasks, individual and team performance abilities, and behavioral health and performance competencies for long-duration space exploration missions identified in Aim 1.
Aim 3. Thorough review of the CNS/SM/BMed scientific literature and NASA technical and internal documents, identify and assess the sensitivity, reliability, validity, translational potential, and redundancy of existing research measures of the constituent neurobehavioral processes, Brain Performance Pathways, and neurobehavioral, neuroanatomical, and neurochemical substrates underlying the core tasks, individual and team performance abilities, and behavioral health and performance competencies for long-duration space exploration missions identified in Aim 2.
Aim 4. Integrate the results of Aims 1-3 into a spreadsheet summarizing the findings and allowing for identification of relative strengths and weaknesses of each potential operational performance measure and potential redundancy of measures via overlapping Brain Performance Pathways.
Aim 5. If available, incorporate into the summary spreadsheet created in Aim 4 the results of other CBS Operational Performance Measures and CBS integrated datamining Directed Tasks. This may include, but is not limited to, CBS Data Mining (PI A. Mulavara), CBS NHP CNS Radiation/Performance Data Mining (PI TBD), and CBS RR: Neurobehavioral Biomarkers Performance/Pathway (PI TBD).
Aim 6. Draft a report summarizing the project, including rationale/background, methodology, results, and discussion. Recommend to NASA an evidence-based set(s) of candidate operationally-relevant Brain Performance Pathways measures applicable across multiple Risk areas for use in an integrated, translational CNS/BMed/SM research plan.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
-Recommendations for concise set of operationally-relevant human performance measures for future CBS research (radiation, stress, altered gravity)
-Given identified operationally-relevant tasks related to crew performance, identification of scientifically plausible Brain Performance Pathways for those operationally-relevant measures for subsequent use and linkage to Translational models linking animal performance and brain function/structure changes to human performance measures (behavior, biomarker, predictive models)
-Identification/recommendations operational performance changes in standards/guidelines changed in NASA STD 3001 (e.g., monitoring frequency based on length/amount of radiation exposure along with cumulative effects of other spaceflight stressors).
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Desai, Rajeev
Short Title:
CBS RR: Neurobehavioral Biomarkers Performance/Pathway (Desai)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
|
Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
|
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
|
|
Aims:
Original Study Aims
Integrated research review for identifying neurobehavioral biomarkers: due to the effects of spaceflight stressors of radiation, altered gravity and isolation/confinement, and cutting-edge neuroscience results from psychopathology related to stress and vulnerabilities to psychiatric disorders; to identify correlative contributions of brain regions identified as relevant to operational performance. Determine specific neurobehavioral biomarkers from tissue dose variation, associated biomarkers for human & rodent cognition and performance. Incorporate Space Biology cross-cutting biomarker project from spaceflight hazards.
CBS Supplement Aims
- Complete neurochemical analysis from the Pre frontal cortex (PFC) and Ventral Tegmental Area (VTA) in a full cohort of mice exposed to acute or chronic GCR vs controls (n = 10-12/group). Neurochemical data will be related to the completed neurobehavioral (economic demand and PVT) data in these mice.
- Impact of mild sleep deprivation on a) neurochemical signatures in the VTA and PFC, b) behavior performance on economic demand, PVT, and an object location memory (OLM)/updating task that vary in difficulty, address different aspects of cognition.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
-Neurobehavioral biomarkers (blood, behavioral, etc) identified and linked to past CBS research that correlate with the human behavior and performance.
-Identification of positive biomarker statuses associated with adverse outcome pathways and/or indicate greater possibility of developing neurocognitive disorders.
-Provide conceptual model and heuristic for use in translational and computational models for dose-effect research. Computational models to identify potential operationally-relevant performance linkages to brain’s modular network organization that is more adaptable to new environments and supporting complex behaviors and sub-networks that support “associative” processes like executive function. Current research suggest that more modular brain networks enable complex cognitive processes and neuroplasticity and, further, may provide insight into the mechanisms underlying the effectiveness of interventions of potential relevance in mitigating integrated risks.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
CBS Supplement Deliverables
1.The data set will permit mapping GCR-induced alterations in neurochemical signatures in a key brain performance pathway (i.e., projections from VTA to PFC) that is involved in neurobehavioral and complex cognitive processes, including cognitive control/flexibility, reward-based learning, and attention/vigilance.
2.Provide the baseline information necessary to critically evaluate if/how a carefully controlled sleep deprivation paradigm alters endpoints that can be functionally linked to neurobehavioral performance
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Nelson, Gregory
Short Title:
CBS VNSCOR #1 - Radiation Dose Rate Effectiveness Factors (Nelson)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
|
Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
|
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
|
|
Aims:
Nelson/Davis Virtual NSCOR: The project is an experimental campaign combined with "Mechanisms of Radiation-Induced Neurobehavioral Defictis" (PI: Davis)(see above) to quantify responses for an interrelated set of central nervous system (CNS) outcome measures in mice to acute and protracted exposures to protons at a dose of 0.5 Gy and sham controls; acute and protracted exposures to 0.25 and 0.5 Gy of charged particles, and acute and protracted exposures to 0.5 and 1.5 Gy of gamma rays. All proposed work will use wild type mice and will be performed under IACUC approved protocols in AAALAC-certified facilities at Loma Linda University (LLU), the University of California, Irvine (UCSF) and Brookhaven National Laboratory (BNL). For all three specific aims the species is Mus musculus, strain C57Bl/6J. Ages are 5 - 6 months at acquisition and the beginning of 42 day irradiation procedures. Sexes are males and females. Scheduled euthanasia's are at 1 week, 30 days, 90 days, 6 months and 12 months post-irradiation. Behavioral testing will occur prior to the use of the same animals for terminal assays. All outcome measures will be quantified in males (N=960) and a subset of measures less prone to sex-dependent variability will be quantified in females (N=220) for a total of N = 1180.
Aim 1: Quantify responses for an interrelated set of CNS outcome measures in mice to acute and protracted exposures to protons at a dose of 0.5 Gy and sham controls. Derive DREFs for the set of outcome measures.
Aim 2: Quantify responses for an interrelated set of CNS outcome measures in mice to acute and protracted exposures to simulated galactic cosmic ray (GCRsim) radiation at doses of 0.25 and 0.5 Gy. Derive DREFs for the set of outcome measures.
Aim 3: Quantify responses for an interrelated set of CNS outcome measures in mice to protracted exposures to 137Cs gamma radiation at doses of 0.75 and 2.0 Gy. Combine results with those of specific aim 2 to determine RBEs for the set of outcome measures for protracted GCRsim exposure.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
-Goal of the proposed project is to determine dose rate effectiveness factors (DREFs) and relative biological effectiveness factors (RBEs) for an interrelated set of central nervous system (CNS) outcome measures in mice following protracted exposures to protons and a simulated galactic cosmic ray spectrum of charged particles (GCRsim). These factors are required to extrapolate dose-response measurements based on acute laboratory exposures to the protracted exposure condition of space flight. The outcome measures include: 1) behavior in four neuropsychological domains – cognition, affect, social interactions, and sensorimotor, 2)neuron activity pattern imaging parameters for synaptic excitability and plasticity, 3) synaptic number and composition, 4) markers of oxidative stress; neuroinflammation, and synapse composition. Because the different outcome measures are dependent on different (but interrelated) processes and tissue components, a family of DREFs and RBEs will be derived.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Davis, Catherine
Short Title:
CBS VNSCOR #1- Mechanisms of Radiation-Induced Neurobehavioral Deficits (Davis)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
|
Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
|
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
|
|
Aims:
Nelson/Davis Virtual NSCOR: Revised Specific Aims: This research builds on previous studies that demonstrated that proton and HZE exposures result in individual differences in deficits in sustained attention, but more general deficits in recognition memory. This current project is combined with "Responses to the Nervous System to Chronic, Low Dosed Charged Particle Irradiation" (PI: Nelson)(See below)
Aim 1a: This aim proposes to investigate the time-course of radiation-induced deficits in sustained attention and social processing following protracted exposure to the five-ion galactic cosmic ray (GCR) simulation (total
dose: 0.5 Gy).
Aim 1b: This aim proposes to investigate the time-course of radiation-induced deficits in sustained attention and social processing following protracted exposure to the heavy ions only in the “five-ion” galactic cosmic ray (GCR) simulation. Thus, these exposures will include protracted exposures to 4He, 28Si, 16O, and 56Fe only (total dose: 0.5 Gy).
Aim 1c: This aim proposes to investigate the time-course of radiation-induced deficits in sustained attention and social processing following protracted exposure to protons (total dose: 0.5 Gy).
Aim 1d: This aim proposes to investigate the time-course of radiation-induced deficits in sustained attention and social processing following acute exposure to 4He ions (250 MeV/ n) at two different exposure doses (5 and 25 cGy).
Aim 2a: This aim proposes to investigate the time course of neuronal and other molecular markers following exposure to the GCR simulation (Aim 1a-c) and 4He exposure (Aim 1d). The time points for testing include: 7 days, 1 month, 3 months, and 6 months post-irradiation.
Aim 2b: This aim proposes to investigate the effects of silencing the regions of the medial prefrontal cortex, including the prelimbic, infralimbic, and anterior cingulate cortices, on sustained attention and social processing in order to determine possible mechanisms of radiation-induced changes in these behaviors.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
- Assess the effects of acute and fractionated HZE exposures on cognitive domains relevant to astronaut performance (e.g., attention, social cognition).
- Examine the effects of other space flight factors in combination with HZE exposure on neurobehavioral performance.
- Assess the effects of HZE exposure on neuronal activation in behavioral task-specific brain regions, including the mPFC, a region important for numerous cognitive domains and executive function.
- Determine the severity of HZE induced deficits by comparing them to pharmacogenetic silencing of the different subregions of the mPFC
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Rosi, Susanna
Short Title:
CBS VNSCOR #2- Effects of GRCsim/HU/ICE on Behavior with Risk Prediction Model (Rosi)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
|
Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
|
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
|
|
Aims:
To ensure human safety during interplanetary space travel, we must understand the health risks of the stressors encountered in space, including ionizing radiation, confinement and altered gravity and develop mechanism-based models and tools to protect astronauts against negative effects of these stressors, especially those that affect behaviors critical for mission success. The central hypothesis of this proposal is that (a) exposure to CSS induces inflammatory responses and loss of synaptic integrity in behavior-controlling brain subregions that differ between males and females, (b) correlates of CNS inflammation are detectable in peripheral blood, and (c) quantitative measures of CNS tissue and plasma responses after CSS exposures can be used to build predictive models of differential susceptibility of males and females for long-term loss of sensorimotor, behavioral and cognitive functions.
Aim 1. Characterize the relative contributions of radiation, social and gravity stressors on sensorimotor, behavioral and cognitive functions and their possible synergistic interactions.
Aim 2. Investigate the quantitative relationships between neuroinflammation and synaptic changes in mice with sensorimotor, behavioral and cognitive deficits following combined spaceflight stress.
Aim 3. Characterize the molecular profiles in peripheral blood of mice exposed to CSS to develop surrogate blood biomarkers of susceptibility and resistance for specific behavioral impairments.
Aim 4. Integrate the relationships between tissue damage markers and behavior phenotypes in male and female mice exposed to space stressors, and develop multivariate models that predict impaired performance for behaviors that are relevant to astronauts on deep space missions.
Category:
Subcategory:
Description:
The purpose of this proposed study 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) to estimate CNS risks in astronauts.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Ronca, April
Short Title:
CBS VNSCOR #2: Effects of GCRsim/HU/ICE on Immune, Performance with Dietary CM Dev (Ronca)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
|
Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
|
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
|
|
Aims:
The overall goal is to minimize risks in both male and female astronauts that are associated with long-term, deep space missions. This will be achieved to generate research results on biomarkers, brain morphology and function, performance pathways, and functional behavioral performance impairments, necessary inputs for computational human health risk models of combined space exposures. The successful completion of this work will provide a clear understanding of synergistic interactions between space environment factors in relation to crew health and performance during extended missions beyond the Van Allen belts.
Aim 1: Determine dose dependence of acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and behavioral performance responses in crew age-matched adult male and female mice.
Aim 2: Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune and nervous system responses in crew age-matched male and female mice mimicking deep space missions.
Aim 3: Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN) in reversing immune, brain and behavioral/cognitive performance effects after acute ‘Five-Ion GCR Simulation’ exposure in socially isolated, IR and simulated microgravity exposed male and female mice, mimicking deep space missions.
Category:
Subcategory:
Description:
Fundamental questions addressed in this project examine mouse sex differences in response to major environmental factors associated with deep space:
(1) Does exposure to IR, either singly and in combination with simulated microgravity and social isolation, result in an elevation of brain reactive oxygen species (ROS), immune dysfunction, altered morphology and function in brain areas related to cognition and behavior?
(2) What is the preferred reference dose,using the Simplified Five-ion GCR Simulation at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratories (BNL), exposures that will allow for studies of both increased and decreased effects confirming combinatorial effects with other deep space factors (i.e., microgravity and social isolation)?
(3) Can immune and inflammatory markers serve as biomarkers for CNS structural and functional changes?
(4) What is the time course relative to IR, HU and social isolation for emergence of immune, brain, and performance measures?
(5) Do the observed CNS alterations lead to behavioral and cognitive impairments?
(6)What Brain Performance Pathways are implicated in HU and IR singly and in combination?
(7) Can administration of the dietary antioxidant, nicotinamide mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis, ameliorate these changes?
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Sanford, Larry
Short Title:
CBS VNSCOR #2: Impact of GCRsim/HU/ICE /Sleep on Brain Function (Sanford)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
|
Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
|
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
|
|
Aims:
This project aims to determine the individual and synergistic effects of simulated microgravity (hindlimb suspension (HLS)), social isolation (SI) and space radiation (SR) on sleep, ability to cope with additional stress, and on temporal perception and sensorimotor function in male and female Wistar rats that show individual differences in stress resilience and vulnerability.
Aim 1: Effects of SI, HLS and SR on sleep architecture, activity, stress system responsivity, extinction learning, and anticipatory activity.
Aim 2. Determine synergistic effects of SR and SI and of SR and HLS on sleep architecture, activity, stress system responsivity, extinction learning, and anticipatory activity.
Aim 3. Determine synergistic effects of SR and SI and of SR and HLS on neural communication.
Aim 4. Determine synergistic effects of SR, SI and HLS on immune system.
Category:
Subcategory:
Description:
1. This project will provide functional assessment of alterations in multiple systems (sleep and arousal, stress, sensorimotor, central and peripheral immune system, brain cognitive and emotional regulatory systems, and ability to perceive time) in response to SR and environmental challenges astronauts may encounter.
2. Experiments will assess whether order of stress experience alters health and performance outcomes.
3. The experiments also will determine whether resilience and vulnerability in the sleep and arousal system effects ability to perform and will determine whether there are gender differences in responses to inflight challenges.
4. Assessment of peripheral brain derived neurotropic factor as a predictor of resilience and vulnerability.
5. Assessment of functional and structural changes in neurocircuitry that regulates important cognitive, memory and emotional behaviors.
6. These data will provide foundational data for multi-factorial models predictive of functional and structural changes in systems important for astronaut health and performance.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Chung, Caroline
Short Title:
CNS Biomarkers of RT Toxicity
Responsible HRP Element:
Space Radiation
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
|
|
Aims:
- Aim 1: Identify clinical characteristics, biofluid biomarkers and imaging features on baseline and follow-up multiparametric MRI that predict for cognitive decline following radiation exposure to the brain.
- Aim 2: Evaluate the relationship between changes in specific aspects of cognitive function with radiation dosimetry in the whole brain and brain subregions in patients receiving radiation to the brain.
- Aim 3: Identify early changes in multiparametric MRI measures that predict for subsequent changes in brain structure following radiation to the brain in preclinical and clinical studies.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
The deliverable will be an evaluation of MRI as noninvasive imaging modality for detection of early indicators of cerebrovascular and CNS decrements following radiotherapy.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
The deliverable will be an evaluation of biofluid markers and functional cognitive parameters for detection of early indicators of CNS decrements following radiotherapy
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Rabin, Bernard
Short Title:
CNS Individual Differences
Responsible HRP Element:
Space Radiation
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
|
|
Aims:
Aim 1: Evaluate the relationship between HZE particle- and proton-induced changes in behavior
and neuronal function in relation to the time and pattern of exposure.
Aim 2: Evaluate the role of individual characteristics on the responsiveness of the organism to
the effects of exposure to NASA relevant doses of HZE particles and protons on neurocognitive
and neuronal function.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Annual and final reports and peer reviewed publications.
Internal Customers:
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Limoli, Charles
Short Title:
CNS Mechanisms
Responsible HRP Element:
Space Radiation
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
|
|
Aims:
Aim 1: Ascertain the extent that charged particle irradiation elicits acute (2 week) and chronic (1 and 3 month) decrements in cognition dependent on hippocampal, medial prefrontal cortical and neocortical regions of the rodent brain. Determine if/how pharmacologic interventions designed to deplete microglia or inhibit CB1 activity alter cognition following charged particle exposure.
Aim 2: Quantify the extent of structural, synaptic, epigenetic and electrophysiologic alterations in neurons from specific regions of the brain following charged particle irradiation with and without specific pharmacologic interventions designed to inhibit CB1 activation.
Aim 3: Elucidate the functional importance of microglia and microglia-derived exosome mediated paracrine interactions in the irradiated brain. Determine how depletion of microglia affects structural and synaptic plasticity following charged particle irradiation. In vitro organotypic and acute slice studies will complement in vivo studies in defining the effect of microglial depletion and how microglia-derived exosome mediated signaling modifies target cell physiology. Additional in vitro studies will define the kinetics of vesicle secretion following irradiation and characterize the functional cargo (mitochondria, protein, mRNA, miRNA).
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Annual and final reports and peer reviewed publications providing evidence for radiation-induced acute CNS adverse outcomes. Studies will provide a mechanistic understanding of the biochemical, structural and electrophysiological changes induced by radiation exposure that alter function to impact cognition.
Internal Customers:
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Beard, Tina
Short Title:
Cognition and Fine Motor Skills Normative Data Collection
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
The contributions of fine-motor skills to responses will be assessed by two sub-tests within the Cognition Test Battery (CTB) (i.e., the Motor Praxis and the Psychomotor Vigilance Test) and within a second test battery under development at NASA, the Fine Motor Skills Test Battery(FMSTB) in the same pilot population.
Aims:
1. Obtain normative data in an astronaut-like population on the FMSTB sub-tests.
2. Evaluate the reliability and precision of the short and long versions of the FMSTB.
3. Determine if the point and drag sub-tests of the FMSTB are measuring a similar motor response.
4. Correlate use of the stylus with use of the index finger when taking the FMSTB.
5. Identify how many sessions are required to establish asymptotic performance on the FMSTB.
6. Collect normative data on the CTB sub-tests in an astronaut-like population.
7. Determine fine motor contributions for each CTB sub-test.
8. Assess if these data replicate well-known covariates of motor and cognitive performance (i.e., age, education, parental education, flight hours).
This task will contribute to gap closure by providing normative data on two monitoring tools (CTB, FMSTB) in a high performing population.
Category:
Study Results
Subcategory:
Customer Requested Study or Analysis
Description:
Report on the contributions of fine-motor skills to responses will be assessed by two sub-tests within the CTB (i.e., the Motor Praxis and the Psychomotor Vigilance Test) and within a second test battery under development at NASA, the Fine Motor Skills Test Battery, or FMSTB in the same pilot population.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
St Hilaire, Melissa
Short Title:
Estimate of Circadian Phase
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
The 24-hour circadian clock controls the timing and pattern of sleep, alertness, performance and mood, disruption of which has a major impact on safety. The circadian clock also controls many other aspects of human physiology, perturbation of which will affect longer-term health and well-being. It is imperative that the timing of the circadian clock is measured routinely, as a standard measure of health and behavior, during long-duration space missions to ensure that these multiple brain and body systems are not disrupted and misaligned from each other. Once measured circadian rhythms can be resynchronized to the desired time using a number of countermeasures, including bright light, melatonin, and potentially exercise and meal timing.
The specific aims are:
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Validate the use of real-time measures of saliva cortisol and blood cholesterol to derive circadian phase.
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To develop a method to derive circadian phase from as few as three salivary cortisol and/or blood cholesterol samples.
Other Resources
Other Resources Needed?
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Yes
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Category:
Technology or Tool
Subcategory:
Systems Solutions, Prototype Hardware or Software
Description:
Algorithm developed as the main deliverable of this proposal will be implemented in a user-friendly software tool that takes as input the cortisol and/or cholesterol concentrations and the time the sample was taken and provides as output the circadian phase calculation.
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Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Roma, Peter
Short Title:
HFBP Exploration Measures for LDMs
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
This task will allow HRP to establish, evaluate, and manage a common set of measures for use in spaceflight and analog research to: develop baselines, systematically characterize risk likelihood and consequences, and assess effectiveness of countermeasures that work for human factors and behavioral performance risk factors. This task will provide “standard measures” as the foundation to achieve consistent research measures for data-sharing in HERA and to meet the highly constrained, operationally-focused data gathering and analysis that allows for greater consistency in the research methods that are very specific to NASA HRP standard measures development. Additionally, the set of BHP standardized measures in the HERA analog reflects the more operational nature of the measures while allowing the multiple and frequent internal and external collaborations required to execute this study.
The study aims to:
1. Provide a set of BHP standard measurements for investigators to use in proposed projects.
2. Enable comparison of multiple missions across spaceflight analog campaigns to quantify risk using reliable metric-based data.
3. Provide database for data-mining and integrative modeling and increase research data quality and transfer to LSDA.
This task will contribute to gap closure by facilitating all tasks using the HERA analog in the BMed, Sleep, and Team risk areas and by testing measures and monitoring tools for the Long Duration Mission Transit.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO]
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Number of Subjects
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32
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Category:
Technology or Tool
Subcategory:
Informatics
Description:
Standardized data across the BMed, Team, and Sleep risks for HERA campaigns to be deposited into the LSDA and shared with other HERA Investigators.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Roma, Peter
Short Title:
HFBP Exploration Measures in HERA for Mars
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
This will allow HRP to establish, evaluate, and manage a common set of measures for use in spaceflight and analog research to: develop baselines, systematically characterize risk likelihood and consequences, and assess effectiveness of countermeasures that work for human factors and behavioral performance risk factors. This task will provide “standard measures” as the foundation to achieve consistent research measures for data-sharing in HERA and to meet the highly constrained, operationally-focused data gathering and analysis that allows for greater consistency in the research methods that are very specific to NASA HRP standard measures development. Additionally, the set of HFBP standardized measures in the HERA analog reflects the more operational nature of the measures while allowing the multiple and frequent internal and external collaborations required to execute this study.
This study aims to:
1. Provide a set of HFBP standard measurements for investigators to use in proposed projects.
2. Enable comparison of multiple missions across spaceflight analog campaigns to quantify risk using reliable metric-based data.
3. Provide database for data-mining and integrative modeling and increase research data quality and transfer to LSDA.
This task will contribute to gap closure by facilitating tasks using the HERA analog in the BMed, Sleep, and Team risk areas and by testing measures and monitoring tools for Surface Operations.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO]
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Number of Subjects
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32
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Category:
Technology or Tool
Subcategory:
Informatics
Description:
Standardized data across the BMed, Team, and Sleep risks for HERA to be deposited into the LSDA and shared with other HERA investigators.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Roma, Pete
Short Title:
HFBP Exploration Measures in NEK
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
This will allow HRP to establish, evaluate, and manage a common set of measures for use in spaceflight and analog research to: develop baselines, systematically characterize risk likelihood and consequences, and assess effectiveness of countermeasures that work for human factors and behavioral performance risk factors. This task will provide “standard measures” as the foundation to achieve consistent research measures for data-sharing in HERA and to meet the highly constrained, operationally-focused data gathering and analysis that allows for greater consistency in the research methods that are very specific to NASA HRP standard measures development. Additionally, the set of BHP standardized measures in the NEK analog reflects the more operational nature of the measures while allowing the multiple and frequent internal and external collaborations required to execute this study.
Aims:
1. Provide a set of BHP standard measurements for investigators to use in proposed projects.
2. Enable comparison of multiple missions across spaceflight analog campaigns to quantify risk using reliable metric-based data.
3. Provide database for data-mining and integrative modeling and increase research data quality and transfer to LSDA.
This task will contribute to gap closure by facilitating all tasks using the IBMP NEK Chamber analog in the BMed, Sleep, and Team risk areas.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Long Duration (4 months or more) – isolated and confined with spaceflight mission scenario [e.g., NEK/Russian Chamber], Controlled Research Analog, Medium Duration (2 to 4 months) – isolated and confined with spaceflight mission scenario, Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO]
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Number of Subjects
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18
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Category:
Technology or Tool
Subcategory:
Informatics
Description:
Standardized data across the BMed, Team, and Sleep risks for IBMP NEK Chamber analog to be deposited into the LSDA and shared with other NEK analog Investigators.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Eisch, Amelia
Short Title:
HZE Behavior and Neural Circuitry
Responsible HRP Element:
Space Radiation
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Aim 1: The impact of HZE particles on other tests in the cognitive domain. Using the “flexible battery” of tests offered by the touchscreen operant platform, we will identify a behavioral framework for the HZE particle-induced improvement in pattern separation.
Aim 2: The impact of HZE particles on behaviors in the affective/social domain.
Aim 3: Indices of neural network perturbation underlying HZE particle exposure induced improved pattern separation
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Evidence related to the long-term health of neural networks needed to complete deep space missions, specifically whether HZE particle irradiation induced improvements in pattern separation is beneficial or detrimental to mission success.
Internal Customers:
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Britten, Richard
Short Title:
HZE Neuroproteome- CBS Supplement (Britten)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
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Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Original HZE Neuroproteome Task was completed by SR in 2019, and a CBS Supplement awarded to explore the Sex Differences as an add-on to the original aims.
Aim 1. Determine the Threshold dose for the induction of HISMI and HIASSI following exposure to 56Fe, 48Ti, and 28Si particles when delivered as a single dose.
Aim 2. Determine the Threshold dose for the induction of HISMI and HIASSI following exposure to 56Fe, 48Ti, and 28Si particles when delivered in three fractions over a 5-day period.
Aim 3. Identify changes in the neuroproteome that are associated with susceptibility or resistance to developing HISMI and HIASSI following exposure to 56Fe particles.
Aim 4. Determine the mechanism of HISMI and HIASSI induced by HZE particles of differing LET.
CBS Supplement Aim 1: Establish the impact that that re-irradiation with 10 cGy of simplified (5-ion) CGRsim beam has on the ATSET performance of male Wistar rats that maintained a functional ATSET performance after exposure to 10 cGy of either He or GCRsim.
CBS Supplement Aim 2: Establish the impact that that re-irradiation with 10 cGy of simplified (5-ion) CGRsim beam has on the ATSET performance of female Wistar rats that maintained a functional ATSET performance after exposure to 10 cGy of either He or GCRsim.
Other Resources
Other Resources Needed?
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Yes
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Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Final Report giving insight into the underlying cause for HZE-induced neurocognitive failure
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
CBS Supplement 1. Information on the robustness of single-exposure experiments to predict the impact of repeated episodic radiation exposures (such as will be encountered on the mission to Mars) on neurocognition.
CBS Supplement 2. Performance in Attentional Set shifting-ATSET will be assessed after a single exposure (He or GCRsim) and after a second exposure (~6 months later) to the 5-ion GCRsim beam.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Roma, Pete
Short Title:
ISS HRP Spaceflight Exploration Measures (HFBP) for Gateway
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
This will allow HRP to establish, evaluate, and manage a common set of measures for use in spaceflight and analog research to: develop baselines, systematically characterize risk likelihood and consequences, and assess effectiveness of countermeasures that work for human factors and behavioral performance risk factors. This task will provide “standard measures” as the foundation to achieve consistent research measures for data-sharing in ISS and to meet the highly constrained, operationally-focused data gathering and analysis that allows for greater consistency in the research methods that are very specific to NASA HRP standard measures development. Additionally, the set of standardized measures on the ISS reflects the more operational nature of the measures while allowing the multiple and frequent internal and external collaborations required to execute this study.
Aims:
1. Provide a set of standard measurements from HFBP towards the HRP standard measures for investigators to use in proposed projects.
2. Enable comparison of multiple missions across spaceflight analog campaigns to quantify risk using reliable metric-based data.
3. Provide database for data-mining and integrative modeling and increase research data quality and transfer to LSDA.
This task will contribute to gap closure by facilitating all tasks using ISS in the BMed, Sleep, and Team risk areas and by testing measures and monitoring tools for the Deep Space Gateway missions.
Category:
Technology or Tool
Subcategory:
Informatics
Description:
Standardized data across the BMed, Team, and Sleep risks for ISS to be deposited into the LSDA and shared with other ISS Investigators, including use for future data-mining.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Norman, Ryan
Short Title:
MERA
Responsible HRP Element:
Space Radiation
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
The Multi-model Ensemble Risk Assessment project will develop an ensemble modeling approach for risk assessment where REID acceptance is determined based on the region of overlap between multiple predictive models allowing a straight forward method to input information derived from multiple sources including international risk prediction models.
Specific Aims:
Aim 1: Determine mathematical formulism to implement multiple probabilistic and deterministic risk models into a single risk framework.
Aim 2: Identify common risk quantification parameters across cancer, cardiovascular disease, and late neurodegeneration consistent with Human System Risk Board quality of life consequences.
Aim 3: Develop visualization of results to support risk communication and decision making.
Aim 4: Develop multi-scale model for the evaluation of countermeasure efficacy based on human epidemiology and radiobiology data from NSRL.
Aim 5: Develop methodology to down select models for inclusion and retirement including appropriate weighting factors.
Models will be configuration managed and fully documented in accordance with appropriate NASA software develop standards
Category:
Technology or Tool
Subcategory:
Computational Models or Simulations
Description:
PEL updates; Risk Model
delivery to operations.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Alfano, Candice
Short Title:
Neurobehavioral Conditions List
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
This task aims to develop and validate a measure (i.e., checklist) through which flight surgeons can systematically evaluate symptoms of adverse neurobehavioral conditions that may occur over long-duration exploration missions.
Aim 1: To summarize available evidence of psychological and behavioral symptoms
experienced in isolated, confined, extreme (ICE) environments and exploration spaceflight based on comprehensive literature reviews and interviews with subject matter experts.
Aim 2:
To define and compare the prevalence, severity, and duration of discrete psychological/behavioral symptoms experienced among HERA and Antarctic winterover cohorts, including concurrent and sequential overlap with physical health symptoms.
Aim 3: To explore relationships among cognitive/perception performance, sleep
patterns and biomarkers of stress with psychological and behavioral symptoms in ICE
environments.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO], ICE Field Analog, Long Duration (4 months or more) – isolated, confined and extreme; may not have spaceflight mission scenario [e.g., Antarctica]
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Number of Subjects
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126
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Category:
Technology or Tool
Subcategory:
Informatics
Description:
A validated measure (i.e., checklist) to assess the symptoms of adverse neurobehavioral conditions that may occur during long-duration exploration missions.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Zhang, Quan
Short Title:
NINScan
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
This study is part of the 1-Year Mission complement of studies led by the NASA Human Research Program. This study is based on the premise that sleep serves as the central physiological regulator of cognitive / behavioral, neurophysiological, and immune functions. Therefore, the study of sleep quality and duration on orbit may yield important insights into etiology and mechanisms of adverse cognitive/behavioral, space flight associated neuro-ocular syndrome (SANS), and immunological responses during long duration deep space exploration missions. We therefore propose to use an integrated approach combining assessments of (1) sleep quality and duration, (2) intracranial fluids distribution, (3) cognitive performance, and (4) immunological response, (5) changes in these physiological measures relative to sleep quality and duration. We propose to collect data on crewmembers participating in integrated one-year mission project (i1YMP) aboard the International Space Station (ISS), and demographically matched control subjects in Human Exploration Research Analog (HERA) for missions of similar durations. The outcomes of the study will contribute to quantification of crew health and performance risks associated with human spaceflight, and aid in development of technologies for monitoring and mitigating crew health and performance. Specific aims include:
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Characterize cognitive and operational task performance changes during the i1YMP on the ISS.
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Characterize brain and systemic physiology changes during i1YMP on the ISS.
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Characterize the effects of sleep duration and quality on cerebral and whole-body hemodynamics on ISS and in HERA.
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Quantify the effects of sleep duration and quality on immune response.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO]
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Number of Subjects
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30
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Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Quantification of the crew health and performance risks associated with human spaceflight for the various exploration missions: using NINScan-SE, Cognition, ROBoT-r, physiologic and detailed immune monitoring technology aboard the ISS and HERA for integrated assessment of sleep duration and quality, as well as their effects on behavioral performance, intracranial fluid distribution, and immune function.
Development of technologies to provide mission planners and system developers with strategies for monitoring and mitigating crew health and performance risks: by combining spaceflight-analog-validated technologies and deploying them in i1YMP.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Flynn-Evans, Erin
Short Title:
Operational Fatigue Modeling Validation
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Software using mathematical
models can help inform assessments related to work-rest schedules and implementation
of fatigue countermeasures. Branches of
the military, for example, use the Sleep, Activity, Fatigue and Task
Effectiveness (SAFTE) model to predict performance effectiveness relative to
sleep-wake history. Other relevant
modeling efforts have included the development of the Circadian Performance
Simulation Software (CPSS) by Brigham and Women’s Hospital, and the
Individualized Fatigue Meter by Pulsar Informatics. NASA, the National Space Biomedical Research
Institute, and other agencies have supported the development of such software
solutions to provide predictions of performance capability relative to
sleep-wake history. Software solutions can inform real-time task
scheduling decisions and aid implementation of countermeasures such as caffeine
and lighting – especially important, given that the proper scheduling of such
countermeasures is essential to their effectiveness.
Mathematical models can
therefore be used operationally in future space exploration missions, to inform
the scheduling of mission-related tasks and the timing of fatigue-related
countermeasures. This topic is soliciting proposals to evaluate the use of such
a tool, as a means through which autonomous crews in a simulated spaceflight
mission can appropriately implement fatigue-related countermeasures, and for
understanding how a crew medical officer (who would be a participant in the study)
and/or an individual crewmember will use the information to make countermeasure
recommendations and real-time scheduling changes.
This task seeks to assess, in an operational environment (the Habitat Exploration Research Analog, or HERA, at Johnson Space Center), the acceptability, usability, and overall feasibility of sleep-wake models and
associated software, to make informed decisions for long-duration space
exploration missions (LDEMs), when ground support will be minimized and crews
will function more autonomously.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO]
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Number of Subjects
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16
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Category:
Technology or Tool
Subcategory:
Computational Models or Simulations
Description:
Modeling software to aid in the scheduling of 'critical' tasks and fatigue-related countermeasures (e.g., lighting, caffeine). Guidelines regarding the operational use of such tools.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
SMOD - Space Medicine Operations Division
Is a Customer-Supplier Agreement (CSA) Required?
Yes
Task Book:
Entry
Principal Investigator:
Strangman, Gary
Short Title:
Operational Performance Measures: ROBoT
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Aim 1: Characterize operational task performance changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.
Aim 2: Characterize brain and systemic physiology changes during 45-day HERA missions, including the roles of time-in-mission, workload, sleep debt, and operational emergencies.
Aim 3: Identify physiological or behavioral variables that predict operational performance.
Aim 4: Quantify the influence of behavioral health countermeasures on both operational performance and (neuro)physiological measures.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO]
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Number of Subjects
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32
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Category:
Study Results
Subcategory:
Description:
The knowledge-deliverables of this project will describe: (i) changes in operationally-relevant (ROBoT) performance during the HERA mission in a well-controlled analog study of substantial size; (ii) changes in cerebral and systemic physiology associated with HERA mission parameters as well as operational performance, (iii) identification of potential predictors of future ROBoT performance, and (iv) the influence of the investigated countermeasure(s) on operational performance and physiology.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Duda, Kevin
Short Title:
Performance, Workload, and Situation Awareness
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Study Aim: Characterize the behavioral health and performance effects of a simulated Long Duration Exploration Mission (LDEM) in HERA on flight performance, workload, and situation awareness during representative spaceflight operational tasks.
A series of experiments will be conducted using the simulated spaceflight scenarios and real-time metrics engine to quantify performance, workload, and situation awareness in each task during the HERA mission. Analysis will be conducted for each scenario and meta-analysis across scenarios will be conducted to determine commonalities and to determine absolute performance thresholds. These metrics will also be correlated to data collected as part of the BHP Standardized Measures, including sleep/wake cycle, actigraphy, and a cognitive battery.
Deliverables include the analysis of data collected during these HERA missions, in the form of publishable research results, that can be directly used to address the HRR Risks and Gaps.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO]
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Number of Subjects
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32
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Category:
Study Results
Subcategory:
Description:
Analysis of data collected during these HERA missions, in the form of publishable research results, that can be directly used to address the HRR Risks and Gaps
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Yule, Steven
Short Title:
Simulation-based CMs
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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Exploration Medical Capability (ExMC) Element |
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Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Aim 1: Analyze the role of crew behavioral skills in successful outcomes of simulated inflight
medical events.
Aim 2: Identify features of spaceflight in-flight medical events that can be managed autonomously by flight crew.
Aim 3: Investigate efficacy of unobtrusive sensors to monitor crew physiological arousal
during in-flight medical event management.
Other Resources
Other Resources Needed?
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Yes
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Category:
Technology or Tool
Subcategory:
Computational Models or Simulations
Description:
Validated simulation platform and measurement tools to mitigate the risk of mission failure due to inadequate medial event management
Internal Customers:
Exploration Medical Capability
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Britten, Richard
Short Title:
Sleep Deprivation SR
Responsible HRP Element:
Space Radiation
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Aim 1: Impact of sleep-fragmentation on Attentional Set Shifting performance.
Aim 2: Impact of sleep fragmentation occurring at pre- or post-HZE exposure on Attentional Set Shifting performance.
Aim 3: The Impact of HZE exposure on sleep related EEG, and sleep homeostasis.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Evidence related to the impact of sleep deprivation on neurocognitive impairment is needed to complete deep space missions, specifically HZE particle exposure impacts on Attentional Set Shifting peformance.
Internal Customers:
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Basner, Mathias
Short Title:
Spatial Cognition
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
This study is part of the 1-Year Mission Complement of studies led by the NASA Human Research Program. This study represents an international collaboration consisting of two projects: Project A: Neurostructural and Cognitive Changes During Long Duration Low-Earth Orbit Missions: Cognition (PI Basner) and Project B: Spatial Cognition and Hippocampal Plasticity During Long-Duration Low-Earth Orbit Missions: HypoCampus in i1YMP (PI Stahn)) with synergistic aims to be carried out in a joint effort by DLR/ESA and NASA. It addresses the HRP Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders, HRP's requirement to demonstrate the presence or absence of unacceptable deleterious neurocognitive effects beyond six-month expeditions. Two in scanner techniques, fMRI while performing the Cognition test battery (Part A) and a special grid cell scan and Pattern Separation Task (Part B), they will determine the biological basis for any changes in cognitive performance, with a focus on hippocampal plasticity (Part B). The specific aims of this study are:
Project A:
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Effects of Long-Duration Low-Earth Orbit Missions on Cognition Performance
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Normative Cognitive Performance Data as a Baseline for Future Long-Duration Missions
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Brain Structural, Functional and Connectivity Substrates of Changes in Cognitive Performance Induced by Long-Duration Low-Earth Orbit Missions
Project B:
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Visuospatial Brain Domain Changes Induced by Low-Earth Orbit Missions
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Effects of Long-Duration Low-Earth Orbit Missions on Visuo-Spatial Cognition
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Biological Basis of Neurocognitive Changes During Low-Earth Orbit Missions
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Determine if cognitive performance assessed during months 7-12 in the year-long crew compares to cognitive performance assessed during months 1-6 in the standard 6 month crew adjusting for any difference in performance between crews pre-flight. Assess the presence or absence of deleterious neurocognitive effects beyond the experience base of six-month expedition.Assess spatial cognition before, during and after spaceflight, determine key neurotrophic and growth factors at identical time points and identify specific changes in hippocampal plasticity and visuospatial performance in order to predict changes in neuroplasticity and neurobehavioral coping during spaceflight.Demonstrate the impacts of isolation and environmental stressors on visuospatial brain domain changes and spatial navigation.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Category:
Technology or Tool
Subcategory:
Informatics
Description:
Generate and deliver to NASA a normative database and a database that can serve as a baseline for future long duration missions and one for standard duration missions (should analyses indicate that inflight performance during months 7-12 differs from performance during months 1-6).This study will deliver a single comprehensive set of integrated neuroimaging and neurocognitive tools for the evaluation and ultimately prevention of adverse effects on brain structure and function.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Rosi, Susanna
Short Title:
SR Synaptic Functions- CBS Supplement (Rosi)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
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Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
The Original SR Synaptic Function Task was completed by SR in 2019, and supplemented by CBS for the supplemental aims listed below.
The purpose of this application is to determine how space-relevant doses of radiation affect dendritic maintenance as it pertains to synaptic functions and memory. We hypothesize that space radiation, even at low doses, impairs synaptic functions with negative consequences for cognition and that these effects are mediated by oxidative stress and inflammation. We will use novel mouse models with neuronal-specific overexpression of an antioxidant enzyme to address the role of oxidative stress. The mice will be exposed to space-relevant doses of proton, 56Fe, or 16O and analyzed for acute and late effects. Experimental endpoints will include cognitive functions, dendritic structures and synaptic functions, molecules that control the dendritic system, inflammatory responses, and indices of oxidative stress. This systematic approach will allow us: 1) to connect the functional output of cognition to the molecular pathway that controls synaptic plasticity and memory; and 2) to determine the role of oxidative stress and inflammation in space radiation-mediated changes.
CBS Supplement Specific Aim 1: Study why female mice appear to be more protected than males from GCR. This will be accomplished by examining male/female differences in synaptic composition and microglia activation, the genetic signature of microglia after GCR exposure, sex differences in the genetic signature for the repopulated microglia population.
CBS Supplement Specific Aim 2: Study the possibility of a differential effect of NMDA receptor changes between males and females.
CBS Supplement Specific Aim 3: Map molecular changes to plausible brain performance areas with demonstrated connection between changes in molecular pathways for brain structure changes – predictive of performance decrements.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Final Report on how space-relevant doses of radiation affect dendritic maintenance as it pertains to synaptic functions and memory
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Category:
Study Results
Subcategory:
Customer Requested Study or Analysis
Description:
CBS Supplement 1) Determine what are the differences in synaptic composition and microglia activation in the various brain regions involved in cognitive deficits after GCR exposure between male and female.
CBS Supplement 2) Determine what is the genetic signature of microglia in male versus female acutely and chronically after exposure to GCR.
CBS Supplement 3) Is microglia depletion and repopulation able to rescue cognitive deficits in male and female mice after GCR exposure and what are the sex differences in the genetic signature of the repopulated microglia population.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
O'Banion, Kerry
Short Title:
Toxic Protein Neurodegenerative
Responsible HRP Element:
Space Radiation
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
Aim 1: Assess the role of LRP1 at the BBB on Aβ clearance at different radiation doses and post-exposure durations in WT mice using established tracer techniques. LRP1 expression levels in brain microvessels and parenchyma will be determined and correlated with Aβ clearance.
Aim 2: Evaluate the role of the glymphatic system in radiation induced accumulation of brain Aβ, and inulin, an ISF flow marker, at different radiation doses and post-exposure durations in wild-type (WT) mice. Alterations in ISF flow will be correlated with measures of astrocyte activation and
neuroinflammation.
Aim 3: Determine the effects of radiation on the proliferative capacity of microglia during normal response to injury in WT mice, and for the ability of microglia to phagocytize Aβ in vivo using APP/PS1 mice. Alterations will be correlated with measures of neuroinflammation and evidence of microglial phenotypic changes, including senescence.
Aim 4: Establish mechanisms linking cellular changes to Aβ accumulation, we will attempt to reduce radiation-associated effects on AD pathology and cognition using a radio-protective and anti-inflammatory drug that also enhances Aβ clearance from the brain.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Annual and final reports and peer reviewed publications.
Internal Customers:
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Stankovic, Aleksandra
Short Title:
VR Stimulation in ICE
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
This study will investigate the feasibility of nature based sensory stimulation using VR to promote stress management and relaxation by (1) adding an interactive component to the VR-based sensory stimulation, to promote engagement and to facilitate therapeutic release; (2) deploying and testing this platform in ICE for feasibility and validation; (3) incorporating non-intrusive physiological monitoring, and (4) examining quantifiable neurophysiological response to stimulation exposure, individual variability in responses, and longitudinal and dose-response characteristics of exposure impacts.
Aim 1: To evaluate the acceptance, perceived effectiveness, and operational feasibility of various VR parameters for relaxation, restoration, and therapeutic release, based on usage in operational ICE.
Aim 2: To manipulate various aspects of VR presentation (e.g. duration, scene content, biofeedback presentation, addition of haptic cues) in the laboratory to optimize the VR experience for relaxation, restoration, and therapeutic release.
Aim 3: To assess experimentally the impact of various core aspects of a VR based sensory stimulation platform for relaxation and therapeutic release (e.g. length, scene content, interactivity, haptic cues) by altering these elements and assessing before and after VR presentation (1) psychophysiological response (to assess relaxation) and (2) performance on an operationally-relevant task (as a measure of cognitive performance and attention restoration), within ICE across the mission duration.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO], ICE Field Analog, Long Duration (4 months or more) – isolated, confined and extreme; may not have spaceflight mission scenario [e.g., Antarctica]
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Number of Subjects
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0
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Category:
Countermeasure
Subcategory:
Protocol
Description:
An operational protocol for understanding the psychophysiological processes related to sensory stimulation, crew health, and human performance. These processes may help identify individual differences related to environmental stressors and the need for sensory stimulation and approaches that can lead to new insights into how sensory stimulation affects physiological and psychological functioning (e.g., neurobiological reactivity, sensorimotor performance).
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Seidler, Rachael
Short Title:
CBS Recovery Timeline of Spaceflight-Induced CNS Changes
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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Human Health Countermeasures (HHC) Element |
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Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
SA1: Determine the recovery timeline of spaceflight-induced ocular changes (e.g., signs of SANS such as optic disc edema) and changes in brain structure, function, and fluid shifts, measuring out to five years post flight. Aim 1a will comprise prospective assessments, while Aim 1b will leverage follow up testing on crewmembers who participated in the PI’s Neuromapping flight study and those crewmembers who have existing retrospective pre and post flight MRI scans.
SA2:
Determine the associations between spaceflight-induced brain and
ocular structural and fluid changes with ocular function, cognitive function, sleep
quality and quality of life
Category:
Subcategory:
Description:
The overarching objective of this project is to elucidate the persistence of spaceflight-induced ocular and brain changes, as well as quantify their association with long-term health because determining this is critically important as we extend the duration and distance of human space travel in the near future.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Basner, Mathias
Short Title:
CBS Long-Term Brain Structural and Functional Consequences of Spaceflight
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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Human Health Countermeasures (HHC) Element |
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Funding Status:
Active - Currently funded and in progress
Procurement Mechanism(s):
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Aims:
SA1: Determine long-term consequences of spaceflight on cognitive performance.
SA2: Determine long-term consequences of spaceflight on brain structural, functional and connectivity substrates of changes in cognitive performance.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
The overarching objective of this international ground study is to advance knowledge about the long-term consequences of spaceflight-induced changes in brain structure and function. Proposer’s will monitor changes in astronaut brain structure and function up to 3-years post-flight to determine 1) whether they persist in some astronauts, 2) if so, for how long, and 3) whether there are any long-term health consequences.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Completed
Task Book:
Entry
Principal Investigator:
Grabham, Peter
Short Title:
3D CNS
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
The primary objective of the research in this proposal is to increase our understanding of the effects of space radiation on the human central nervous system with an emphasis on neurodegeneration. We are using a relatively new approach to this question by using available human stem cells to create 3-dimensional tissue models. These can represent human neural tissue more closely than 2-dimensional monolayers. Human cells of three of the main types in the brain will be cultured and differentiated in 3-D matrix gels and used to determine the effects of space radiation by assaying for specific endpoints related to degeneration in neurons. This is achieved by live and fixed stain 3-D imaging together with assays for secreted proteins. 3-D cultures are grown in gels as monocultures and as a multi-cell ‘neurovascular unit’ built on an existing model of human vessels. Such a model can complement animal and cell studies to produce new and more complete data on the effects of space radiation on the human nervous system.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Research will provide new cellular model of the human neurovascular system for use in assessment of radiation effects on degenerative changes in the CNS, in support of CNS Gap 2 closure.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Raber, Jacob
Short Title:
apoE
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
1A. Determine if E isoform is associated with radiation-induced apoptosis of neural precursor cells in the dentate SGZ
1B. Determine the role of E isoform in the development of radiation-induced cognitive deficits and whether the severity of these deficits are associated with apoptosis of neural precursor cells in the dentate SGZ. Mice will be tested 3 months following radiation
1C. Determine how E isoform affects neurogenesis following 56Fe- irradiation, and determine if this effect is related to the severity of radiation-induced cognitive deficits
2A. Determine if the presence of a specific E isoform is associated with markers of oxidative stress following radiation injury
2B. Determine if the antioxidant a-lipoic acid enhances cognitive function and reduces radiation-induced cognitive impairments and whether this ability is E isoform-dependent.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Research will provide evidence on impact of individual sensitivity and antioxidants on acute cognitive decrements following SR exposure, in support of closure of CNS Gap 3.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Chang, Polly
Short Title:
Brain Protein Homeostasis
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
In this proposal, we plan to conduct in-depth investigations of those cellular pathways that regulate the removal of damaged proteins, repair of DNA damage, and response to conditions of oxidative stress through protein modifications in the brain. Protein modification by ubiquitin is a highly regulated process that is catalyzed by specific enzyme families that are capable of modifying the correct protein in the correct cellular location at the correct time in order to control important processes such as the maintenance of genomic stability, cell cycle progression, removal of damaged or misfolded proteins, impaired autophagy, apoptosis, and gene transcription. Depending on the radiation dose and beam quality, particle radiation may cause significant damage to proteins and oxidative stress in the cells in the central nervous system, leading to dysfunction of the cellular ubiquitin-related pathways, an increase in the levels of extracellular ubiquitin and persistent subsequent downstream effects on regulation of stress-associated signaling pathways in many different cell types within the CNS, precipitating neurodegenerative disease.
We hypothesize that quantitative changes in cellular ubiquitin pools occur when neuronal cells are exposed to particle radiation and aim to study the impact of protein degradation after particle radiation using both in vitro and in vivo model systems.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Final Report on the impacts of radiation on the CNS, particularly dysfunction of the cellular ubiquitin-related pathways, levels of extracellular ubiquitin and subsequent downstream effects on the regulation of stress-associated signaling pathways
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Britten, Richard
Short Title:
Brain Proteome
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
Aim 1. Identify changes in the neuroproteome that are associated with Hze-induced spatial memory impairments (HISMI) and HZE-induced Attentional Set Shifting Impairments (HIASSI).
Aim 2. Identify proteins that are present in the serum and CSF that are biomarkers of an individual rat¿s susceptibility to HISMI/HIASSI.
Aim 3. Determine the LET-dependency for HISMI and HIASSI, and whether the threshold dose is modified by prior exposure to protons, and if the underlying mechanisms of HISMI and HIASSI is constant irrespective of the LET of the Hze particle.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Evidence on radiation dose thresholds and quality effects on late behavioral endpoints that will contribute to CNS gap 2 closure by provding data for risk characterization.
Internal Customers:
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Bracken, Bethany
Short Title:
CAPT PICARD - SBIR2
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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Behavioral Health & Performance (BHP) Element |
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Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
Task design and related hardware and software impose cognitive and physical demands on an operator, and thus drive the workload associated with a task. Astronauts on long-duration missions will potentially have long periods of low workload and short bursts of high workload combined with reduced workload capacity that need to be taken into account for system and mission design. Both high task demand and reduced workload capacity at any phase of a flight may lead to performance errors, which could potentially compromise mission objectives, and consequently the mission. An unobtrusive workload tool is needed during system development to ensure that the use of the system is associated with acceptable workload, as well as during real-time use of systems, to drive schedule modifications or to adapt interfaces based on the current workload the astronaut is experiencing.
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Based on the current state of the art and recommendations from the Phase1 effort develop a workload tool prototype to measure, assess, and predict astronaut workload unobtrusively.
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Test and validate the tool. The technology should also be predictive of astronaut workload during long-duration operations.
The task will contribute to gap closure by providing an unobtrusive workload measurement tool for long-duration missions.
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO]
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Number of Subjects
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16
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Category:
Technology or Tool
Subcategory:
Informatics
Description:
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Report
on development of a workload tool.
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Report
on the test and validation of the tool.
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Unobtrusive
workload tool.
This
work will result in a tool/method for measuring workload unobtrusively, which
will contribute to closure of the MPTASK-01 gap, as well as the BHP SLEEP-02
gap. It will provide a means of predicting workload during development of an
interface (and thus providing an indication of the need to redesign), as well
as a measurement that can be used in real time, to allow for schedule changes
to mitigate the high workload.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Mulavara, Ajit
Short Title:
CBS Data Mining (Mulavara)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
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Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
Literature review and assessment of NASA-funded current and completed research findings relevant to this integrated risk. Identify behavioral and physiological (biomarker) cellular, molecular changes & brain regions linked to specific effects of targeted GCR simulation ions, simulated altered gravity stressor and/or space flight with translational relevance to operational performance measures. Identify Brain Performance Pathway neural circuitry responsible for operationally-relevant behavior characteristics to determine similar neuronal circuits maintaining coherent functions; assess artificial stimulation of the particular network (sensitive to CBS means—radiation, isolation & confinement, altered gravity) that generate predicted responses; and identify biomarkers that influence or act as the carriers of the network activity (neurotransmitters and other biomarkers with messenger activity) that predict the relevant behavioral changes.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
-Summary of existing research results
-Identification of operationally-relevant brain performance pathways (map of anatomical regions to performance outcomes)
-Identification of knowledge gaps
-Recommendations for specific areas needing further research
-Biomarker candidates to GRC modeling cross-cutting project
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Desai, Rajeev
Short Title:
CBS NHP CNS Radiation/Performance Data Mining (Desai)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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Human Health Countermeasures (HHC) Element |
Space Radiation (SR) Element |
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Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
- Conducting a comprehensive and systematic evaluation of existing research in NHP on the acute and long-term impact of exposure to spaceflight stressors on NHP CNS-related function;
- Identifying applied and mechanistic research gaps on the acute and long-term impact of exposure to spaceflight stressors on CNS-related function that need to be conducted in a translationally-relevant manner in NHP
- Providing recommendations for NASA regarding the availability, validity, and limitations of NHP models in future targeted research that will address critical gaps to mitigate these spaceflight hazards that currently have the potential to catastrophically “surprise” NASA by an event or response to circumstances (spaceflight stressors) during deep space missions they did not anticipate.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
1. A comprehensive and systematic evaluation of existing research on the acute and long-term impact of exposure to spaceflight stressors on NHP CNS-related neurobiological, neurochemical, neurobehavioral and cognitive function.
2. Describe critical research gaps and priorities in NHPs related to the CBS Integration Research Plan that ought to be considered by NASA moving forward to bridge the key knowledge gaps that currently exist in deciphering rodent data to humans. Provide a consideration of NHP model as gold standard animal model for assessing the dose-effects of radiation on operationally-relevant Brain Performance Pathways, POL/PEL development, and potential pharmaceutical development as countermeasures.
3. Provide a roadmap of recommendations for NASA regarding the availability, validity, and strengths and limitations of NHP models in future targeted research, including points of contact between existing NASA-relevant rodent assays and functional NHP analogs.
Internal Customers:
Human Factors and Behavioral Performance
Human Health Countermeasures
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Eisch, Amelia
Short Title:
Cellular Hippocampal
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
- In Aim 1, using behavioral tests with which we have recently published (delayed non-match to pattern radial arm maze for fine spatial distribution; Guo et al., Nat Med 2011), we will explore our hypothesis that space radiation decreases pattern separation in a dose- and LET-dependent manner.
- In Aim 2, using transgenic mice we have developed that allow inducible YFP labeling of neural stem cells and their progeny (nestin-CreERT2/R26R mice; Lagace et al., J Neurosci 2007), we will explore our hypothesis that space radiation negatively impacts both adult-generated (Aim 2a) and embryonic-generated (Aim 2b) DG neurons.
- In Aim 3, using transgenic mice developed by our colleagues that allow profiling of translating RNA in genetically-defined DG neural cells [BAC-TRAP mice, aka bacterial artificial chromosome translating ribosome affinity purification; Dougherty et al., Cell 2008], we will explore our hypothesis that space radiation causes discrete changes in DG neural cell types in a dose- and LET-dependent manner. Unlike currently used approaches to assess total RNA profiles from cellularly heterogeneous samples (e.g. laser capture dissection and subsequent microarray analysis), the bac-TRAP approach allows purification of specific cell types via ribosome tag and a quantitative comparison of translating RNA profiles in genetically-distinct DG cells (e.g. neural stem cells, adult-generated immature granule cell neurons, and embryonic-generated mature granule cell neurons using BAC-TRAP PBK, DCX, and Cx3Cl1 mouse lines, respectively).
Tissue from Aims 1-3 will be examined using immunohistochemistry, epifluorescent and confocal microscopy, stereologic cell counting, and morphological analysis, and tissue from Aim 3 will be explored using microarrays on the translating RNA pools and qRT-PCR. Taken together, these aims will allow us to test our overall hypothesis that radiation will have distinct, long-lasting effects on the behavioral, cellular, and molecular integrity of the hippocampus. Thus, these results will expedite the quest to estimate CNS radiation risks due to GCR exposure.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Evidence on how space radiation influences hippocampal Dentate Gyrus structure and functional consequences of these changes which will contribute to CNS Gap 2 closure.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Raber, Jacob
Short Title:
CNS Epigenetics
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
- In Specific Aim 1, we will test the hypothesis that low-dose whole body irradiation with 56Fe or 28Si ions or protons has short- and long-term effects on cognitive performance in object recognition and spatial learning and memory requiring navigation.
- In Specific Aim 2, we will test the hypothesis that low dose whole body irradiation with 56Fe or 28Si ions or protons has short- and long-term effects on hippocampal networks involving Arc, and that cognitive injury following space irradiation is associated with changes in hippocampal network stability.
- In Specific Aim 3, we will test the hypothesis that cognitive changes following space irradiation are associated with alterations in DNA methylation and expression of Arc and other genes involved in learning and memory.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Research provides information on radiation induced changes in hippocampal network stability and epigenetic mechanisms in the development of cognitive dysfunction after space irradiation. Data will support risk characterization and mechanistic understanding in support of CNS Gap 1 closure.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Hienz, Robert
Short Title:
Cogni-behavioral
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
To assess the biological consequences of living in the space radiation environment via the application of a comprehensive animal model to determine the effects of radiation exposure on neurobehavioral tests of vigilance and impulsivity
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Research will provide evidence on utility of animal version of the psychomotor visual test for assessment of impacts of space radiation on cognitive endpoints relevant for exploration class missions, in support of CNS Gap 1.
Internal Customers:
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Basner, Mathias
Short Title:
Cognition
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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National Space Biomedical Research Institute (NSBRI) |
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Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
Specific Aim 1: Development of short-duration adaptive versions of CATS neuropsychological
tests for spaceflight
Specific Aim 2: Establish learning curves for CATS neuropsychological tests and validate
sensitivity to sleep deprivation
Specific Aim 3: CATS Toolkit software development and optimization for spaceflight
Specific Aim 4: Space Analog field testing, astronaut learning curves, and astronaut norms for
performance feedback algorithm development
Specific Aim 5: International Space Station (ISS) feasibility study
Ground Analog Resources
Ground-Based Flight Analogs
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ICE Field Analog, Long Duration (4 months or more) – isolated, confined and extreme; may not have spaceflight mission scenario [e.g., Antarctica]
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Number of Subjects
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24
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Category:
Technology or Tool
Subcategory:
Informatics
Description:
A comprehensive, neuroscience-validated, cognitive test battery for real-time evaluation of astronauts in space. An interim milestone in 2016 will include a report on the development and validation of this countermeasure.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
Med Ops - Medical Operations
Is a Customer-Supplier Agreement (CSA) Required?
Yes
Task Book:
Entry
Principal Investigator:
Basner, Mathias
Short Title:
Cognition (ISS-12)
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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National Space Biomedical Research Institute (NSBRI) |
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Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
This study aims to test and implement the NeuroCATs toolkit on the ISS-12 mission. This will permit rapid assessment of performance in cognitive, social-emotional and sensorimotor domains and help inform whether cognitive changes may exist over an extended duration in space.
Category:
Technology or Tool
Subcategory:
Informatics
Description:
A comprehensive, neuroscience-validated, cognitive test battery for real-time evaluation of astronauts in space. This will include a report on the development and validation of this countermeasure during the ISS12 mission. This will inform gap closure by developing an effective method for monitoring cognitive performance during exploration missions.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Basner, Mathias
Short Title:
Cognition Administration Order
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
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National Space Biomedical Research Institute (NSBRI) |
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Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
Aim 1: Disentangle practice effects and stimulus set difficulty effects to make Cognition administration more flexible.
Aim 2: Investigate the effects of administration rate of the Cognition test battery on practice effects.
The study will provide regression estimates that adjust for the effects of both administration order (i.e., practice effects) and difficulty of stimulus sets (which vary between batteries). These can be used to make all Cognition administration regimens comparable. The study will also show whether practice effects differ depending on the interval between Cognition administrations, which will inform pre- and in-flight testing schedules.
Category:
Study Results
Subcategory:
Customer Requested Study or Analysis
Description:
Final report summarizing study aims, methods, and study results: The study will provide regression estimates that adjust for the effects of both administration order (i.e., practice effects) and difficulty of stimulus sets (which vary between batteries). These can be used to make all Cognition administration regimens comparable. The study will also show whether practice effects differ depending on the interval between Cognition administrations, which will inform pre- and in-flight testing schedules.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Lemere, Cynthia
Short Title:
Cognition and Biomarkers in AD
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
The specific aims of this study are:
Aim 1. Determine the gender-specific early and late effects of space radiation on cognition, synaptic changes, Alzheimer’s Disease (AD) pathogenesis, cerebral blood flow (CBF) and neuroinflammation (GE180 PET) in a well-characterized Alzheimer’s Tg mouse model bearing 2 familial mutations (APPswe and PS1dE9) associated with early-onset AD and strain-, age, and gender-matched C57BL/6 WT mice.
Aim 2. Comparison of the effects of a single dose versus fractionated irradiation with 1000 MeV/μ 56 Fe ions on cognition and locomotion, as well as changes in cerebral blood flow, brain volume, neuroinflammation, synapses, AD pathogenesis and neuron loss.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
The overall goal of this project is to identify early and late effects of space radiation on the connections between nerve cells in the brain (i.e, synapses) inflammation and cognition so that one can assess the CNS risk to future astronauts involved in long-duration lunar missions and/or a mission to Mars. These early changes, along with changes in brain inflammation that may relay signals between cells in the brain and blood flow, may help define those individuals at risk for developing long-term learning and memory problems.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Basner, Mathias
Short Title:
Cognition in HERA
Responsible HRP Element:
Human Factors and Behavioral Performance
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
Aim 1: Test feasibility of regular COG data acquisition in the space analog environment of HERA
Aim 2: Perform descriptive analysis of changes in cognitive performance with time in mission and related to mission stressors
Aim 3: Measure rest activity patterns and light exposure with actigraphs
Aim 4: Test feasibility of proximity data acquisition in HERA
Ground Analog Resources
Ground-Based Flight Analogs
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Controlled Research Analog, Short Duration (2 months or less) – isolated and confined with spaceflight mission scenario [e.g., HERA, NEEMO]
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Number of Subjects
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32
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Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Final report summarizing the findings from a systematic assessment of cognitive performance as well as an unobtrusive measure of crew cohesion in HERA crewmembers that are confined to the HERA facility.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Gur, Ruben
Short Title:
Cognition Penn Validation
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
|
National Space Biomedical Research Institute (NSBRI) |
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Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
Validate Cognition battery in high-performing medically and psychiatrically screened subjects. Compare laptop and iPad versions of Cognition.
Other Resources
Other Resources Needed?
|
Yes
|
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
final report with initial validation of the Cognition battery (reliability, correlations among the tests, item consistency, criterion validity relative to gender) including comparability between laptop and iPad versions.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Gur, Ruben
Short Title:
Cognition Validation Follow-On Study
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
|
National Space Biomedical Research Institute (NSBRI) |
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Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
Evaluate Cognition and WinSCAT performance after a longer time interval without having performed a test. The study will bring back the participants from the previous study. This would result in inter-test intervals ranging from 6 months to 18 months, with an average of 11 months. Half of the subjects will take the practice version of each test before taking the full version again. This will establish whether a practice version of each test is enough to boost performance after a longer time interval without intervening tests.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Evidence determining whether a practice version of each test in the Cognition battery is enough to boost performance after a longer time internal without intervening tests.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
Williams, Thomas
Short Title:
Cognition vs. WinSCAT
Responsible HRP Element:
Human Factors and Behavioral Performance
Collaborating Org(s):
|
National Space Biomedical Research Institute (NSBRI) |
|
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
Independently validate Behavioral Core Measures’ Cognition battery to compare with WinSCAT, establish norms, and quantify the extent of inter- and intraindividual variation in mental effort during testing.
Category:
Study Results
Subcategory:
Customer Requested Study or Analysis
Description:
1. Final report outlining the findings of the independent validation of the Cognition Battery along with the development of psychometrically robust normative tables with the potential link to “mental effort” will provide NSBRI and NASA with a comprehensive understanding of the capabilities and limitations of the Cognition Battery as well as an increased understanding of how the Cognition Battery compares to currently used model, the WinSCAT. The report will be provided to NSBRI and NASA BHP Element and BHP Operations.
2. Secondly, a presentation will summarize findings that can be used to brief operational personnel on interpreting the tests of the Cognition Battery (and WinSCAT) to help provide feedback that is meaningful and relevant to both astronauts and flight surgeons in using these measures.
Internal Customers:
Human Factors and Behavioral Performance
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Wang, Huichen
Short Title:
DNA Repair
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
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Aims:
In the present proposal, we introduce an in vitro model of neural progenitors (neurospheres), which is derive from the brain of mouse embryo from neurodegenerative transgenic mice to study the detrimental effects of space radiation at the mechanistic level. Using this biological model, we will study DNA damage repair and apoptosis of proliferating and differentiated neural progenitor exposed to low dose of high charge and energy nuclei and protons.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Study will provide evidence on impact of space radiation on DNA repair and apoptotic processes in a neural progenitor cell model, and will provide mechanistic insights in support of CNS gap 2 closure.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Haley, Gwendolen
Short Title:
Effects of Alpha Lipotic Acid on Mice
Responsible HRP Element:
Space Radiation
Collaborating Org(s):
|
National Space Biomedical Research Institute (NSBRI) |
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Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
- To determine the short-term effects of 56Fe radiation irradiation on hippocampal function and assess whether these effects are sex-dependent. Mice will be irradiated at 0, 0.1, 0.2, or 0.5 Gy and behaviorally tested 1-2 weeks following radiation.
- To determine whether the severity of the cognitive effects are associated with reduced choline acetyltransferase (ChAT) immunoreactive cell bodies in the medial septum and nucleus basalis and ChAT immunoreactive fibers in the hippocampus and cortex. Following behavioral testing, ChAT cell number and fiber density will be determined using immunohistochemistry and measures of ROS by western blot.
- To determine the ability of the dietary supplement lipoic acid (LA) to antagonize the effects of 56Fe irradiation on hippocampus-dependent cognitive function, measures of ROS, and ChAT immunoreactive cell bodies in the medial septum and nucleus basalis and ChAT immunoreactive fibers in the hippocampus and cortex. Mice will be sham-irradiated or irradiated at a dose causing maximal cognitive injury in Aim 1 and receive regular diet or LA-containing diet starting one week prior to behavioral testing. Brains will be processed as in Aim 2.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Final Report
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Nelson, Gregory
Short Title:
Epigenetic C. elegans
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
This task is focussed directly on identifying the genes and pathways that regulate non-targeted damage formation. The high genetic homology between C. elegans and mammalian gene networks should enable predictions of homologous signaling pathways that are operational in mammals, including humans. This should, in turn, improve the understanding of the role of non-targeted effects in the low radiation dose environment and suggest mitigation strategies.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Research will provide evidence on role of individual sensitivity and intercellular communication in radiation response, in support of CNS Gap 3 closure.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Vlkolinsky, Roman
Short Title:
Functional Decline - Alzheimers
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
Comparison of proton, silicon and iron radiation on selected neurophysiological end points in APP/PS1 tg mice will provide valuable information about the risks of space radiation-induced neurodegenerative processes. The functional endpoints will be directly correlated with expression of immunohistochemical markers of neurodegeneration, including amyloid plaque load, synaptic proteins and the presence of neuroinflammatory cytokines. This information can be directly related to risks of AD onset in human subjects.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Characterization of space radiation impacts on neurophysiological endpoints correlated with markers of neurodegeneration. Research will provide risk characterization in support of CNS Gap 2 closure.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Characterization of space radiation impacts on neurophysiological endpoints correlated with markers of neurodegeneration. Research will provide risk characterization in support of CNS Gap 2 closure.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Rabin, Bernard
Short Title:
Heavy NeuroB
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
- To further characterize HZE particle-induced behavioral and neurochemical deficits
- To determine the neural mechanisms underlying the changes in performance
- To determine how individual characteristics (age and gender) may influence the responsiveness to HZE particle irradiation
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Research will provide evidence on LET dependence of behavioral and neurocognitive endpoints following radiation exposure in support of CNS Gap 1 closure.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry Unavailable
Principal Investigator:
O'Banion, Kerry
Short Title:
Hippocampal
Responsible HRP Element:
Space Radiation
Collaborating Org(s):
|
Department of Energy (DoE) |
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Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
We have profiled gene expression patterns in the dentate gyrus and find significant effects at even the lowest doses tested (3 cGy). Further analysis of our extensive microarray data is underway to better understand the microenvironmental changes elicited by radiation that influence neuronal cell genesis and survival.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Research will provide evidence, through global gene expression profiling, on low-dose radiation effects on the microenvironment in the adult mammalian brain, which may impact neurogenesis in the dentate gyrus. Evidence will support closure of CNS Gap 1.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Goldstein, Lee
Short Title:
Hippocampal-Dependent Learning
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
- Examine the long-term impact of space radiation (SR) on hippocampal-dependent spatial learning and memory
- Evaluate the potential of SR to accelerate Alzheimer's disease pathogenesis and neuropathology
- Evaluate a novel non-invasive laser-based eye scanner to detect and monitor molecular changes in the lens of the eye induced by radiation exposure and Alzheimer's disease pathology
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Evidence on the long-term impact of space radiation on hippocampal-dependent spatial learning and memory will provide risk characterization in support CNS gap 2 closure.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Britten, Richard
Short Title:
HZE Cognitive
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
1) identify the high-LET radiations that have the greatest impact on the ability of animals to recall imprinted memories and to learn new memory skills;
2) use PET imaging to identify the regions of the brain that are functionally inactivated when brain function is inhibited by Hze radiation
3) establish the relative importance of radiation-induced cell death and signal malfunction in the inhibition of brain function after exposure to radiations with low, medium and high-LETs;
4) develop a blood-based assay that can be used to monitor the astronauts for early signs of radiation-induced memory function deficit.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Evidence on radiation dose thresholds and quality effects on early neurocognitive endpoints that will contribute to CNS Gap 1 closure by providing data for risk characterization.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Rabin, Bernard
Short Title:
HZE Individual CNS
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
- Evaluate the effects of repeated subthreshold exposures to HZE particles and protons on cognitive and neuronal deficits and how they relate to the characteristics of the specific particle.
- Determine the relationship between changes in performance and HZE particle- and proton-induced changes in oxidative stress, inflammation, signaling molecules and autophagy in key brain regions.
- Determine how individual characteristics, including age and sex, may influence the responsiveness of the individual to HZE particle irradiation.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Research will characterize the impact of gender and age on modulation of the effects of space radiation exposure on neurocognitive endpoints important in early CNS effects. Research will provide risk characterization in support of CNS Gap 3 closure.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Yu, Yongjia
Short Title:
HZE Neural
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
- Determine the impact of 56Fe and gamma-ray irradiation on proliferation and differentiation of K048 cells in vitro.
- Determine gene expression patterns and apoptotic responses of proliferating and differentiating K048 cells following 56Fe and gamma-ray irradiation.
- Determine whether in vitro primed K048 cells can differentiate into neurons when grafted into neurogenic and non-neurogenic regions of rat brains damaged by 56Fe and gamma-rays.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Research to provide evidence on mechanisms of radiation effects on differentiation and proliferation of neural stem cells, in support of CNS Gap 1 closure.
Internal Customers:
Space Radiation
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Chen, Benjamin
Short Title:
HZE Neurogenesis
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
|
Aims:
The proposed research utilizes two novel transgenic mouse models for a comprehensive analysis of adult neural stem cells and their progeny in vivo for the temporal events of cells survival, proliferation, and differentiation in response various low- or high-LET radiation. The resulting information on the long-term neurogenic and/or degenerative activities will provide accurate assessments of CNS risks after space radiation exposure.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Evidence on radiation dose thresholds and radiation quality impacts on populations dynamics of adult neural stem cells and their progeny. These data will contribute to CNS Gap 2 closure by providing data for risk characterization.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
O'Banion, Kerry
Short Title:
HZE Neuroinflammation
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
|
Aims:
- In our first aim we will endeavor to use a sufficient dose range in order to compare outcomes with the physiologic and pathologic endpoints established in our current data using gamma radiation.
- In our second aim, we will use specific inhibitors of cyclooxygenase-2 to determine if prostaglandins play a key role in the neuroinflammatory response to HZE particles.
Category:
Risk Characterization, Quantification
Subcategory:
Evidence or Risk Characterization
Description:
Research to test efficacy of a biological countermeasure on mitigation of neuroinflammation associated with long term cognitive impairment following radiation exposure, in support of CNS Gap 4 closure.
Internal Customers:
None
External Customers:
None
Is a Customer-Supplier Agreement (CSA) Required?
No
Task Book:
Entry
Principal Investigator:
Limoli, Charles
Short Title:
Induced Genomic
Responsible HRP Element:
Space Radiation
Funding Status:
Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
|
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Aims:
- Elucidate the dose-response relationship for the induction of genomic instability in neural precursor cells cultured in vitro or isolated from mouse brain after exposure to protons and iron ions.
- Determine if chronic changes in cellular redox state alter the dose response relationship determined above and predispose neural precursor cells to proton- and iron ion-induced genomic instability.
- Determine if differentiation of genomically unstable neural precursor cells is altered in vitro, or if neurogenesis is altered in vivo when unstable precursor cells are implanted into the brains of control or irradiated mice.