Short Title: NeuroMapping

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Behavioral Health & Performance (BHP) Element Research Operations and Integration (ROI)

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:
Changes in brain structure and function may play a direct role in spaceflight-associated sensorimotor and cognitive dual task deficits, and may further impact the long-term health of astronauts. The objective of this study is to perform structural (volumetric MRI and diffusion tensor imaging (DTI)) and functional (sensorimotor and cognitive task) MRI (fMRI) and functional connectivity MRI (fcMRI)) brain imaging to identify changes in crewmember neurocognitive function due to long-duration space flight. The central hypothesis of this study is that measures of brain structure, function, and network integrity will change from pre to post flight in crewmembers.  Moreover, the prediction is that these changes will correlate with changes in the indices of cognitive, sensory, and motor function from pre flight, to in flight, and post flight, in a neuroanatomically selective fashion.

This study implements an interdisciplinary approach using cutting edge neuroimaging techniques and a broad range test battery of sensory, motor, and cognitive assessments to investigate neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight.

This task also informs VIIP1 gap and the HCI and BMed Risks.

Short Title: CBS NHP CNS Radiation/Performance Data Mining (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):

Solicited

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.

Short Title: CBS BioNutritional CMs Data Mining (Smith)

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):

Directed

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

Short Title: Vestibular Health

Responsible HRP Element: Human Health Countermeasures

Collaborating Org(s):

Funding Status: Active - Currently funded and in progress

Procurement Mechanism(s):

Solicited

Aims:

• Examine the head position relative to the body and, if tilted look for the presence of an ocular tilt reaction.
   
• Determine the subjective nonvisual vertical using the test of the finger. A deviation of the subjective vertical occurs in more than 90 % of all acute unilateral peripheral and central vestibular disorders.
   
• Examine the subject for nystagmus when the gaze is straight-ahead or directed right, left, up, and down. Frenzel lenses help to differentiate between a peripheral vestibular spontaneous nystagmus that can be suppressed by visual fixation and a central fixation nystagmus that is present during fixation.
   
• Perform positioning maneuver to determine if there is a positioning nystagmus or positioning vertigo, and also to differentiate between a BPPV and a central positional or positioning nystagmus.
   
• Examine three different types of eye movements (smooth pursuit, saccades, gaze-holding function) for central eye movement disorders such as saccadic smooth pursuit, gaze-evoked nystagmus, disorder of saccades as well as impaired visual fixation suppression of the VOR. If patients with acute vertigo have central ocular motor disorders, this suggests a central origin.
   
• Perform the head-impulse test as well as slow active head rotation addressing the question of a unilateral or bilateral functional deficit of the VOR.
   
• Perform whole body rotation and whole-body translation to evaluate whether the subjective perception of motion by the semicircular canals and otoliths is accurate

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):

Solicited

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.

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):

Solicited

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.

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):

Solicited

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.

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):

Directed

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.

Short Title: CBS Facility/Animal Translation Standards

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Health Countermeasures (HHC) Element Space Radiation (SR) Element

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

Directed

Aims:
Directed study to determine/develop standardization and recommendations related to animal handling, research facility (e.g., volume, lighting, sound, etc.) & animal/rodent type (species/strains) to increase reliability & validity of animal to human translational research yields by increasing standardization between radiobiological and neurobehavioral methodology, identification and application of genotype to phenotype, biomarkers, and to regional pathophysiology related to operationally-relevant brain performance pathways. From biomarkers to performance measures, it is vital to standardize measurements and tests across PIs for this integrated approach to ensure the reproducibility, reliability, and robustness of tests.

Short Title: CBS GCRSim Exposure Response Study

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Health Countermeasures (HHC) Element Space Radiation (SR) Element

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

Solicited

Aims:
This project “integrates” transdisciplinary approach with multiple research arms that use simulated galactic cosmic ray fields as the core feature with experimental design and conceptualization to assess interaction and time order-effects of radiation exposure (RE), isolation & confinement stress (ICS), and SM (sensorimotor responses to simulated microgravity). This project will use standardized handling and behavioral tests, assess brain physiology (including Blood-Brain-Barrier patency and function), molecular signaling, biomarker changes, and lead to computational modeling to characterize and predict changes in operationally-relevant “Brain Performance Pathways”. For purposes of this solicitation, NASA defines “Brain Performance Pathways” as the neural circuitry and associated molecular, cellular and physiological processes that underlie specific behaviors or sets of behaviors expressed in animal models that are translatable to humans.

Short Title: CBS RR: NHP Model Brain Performance Pathways

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Health Countermeasures (HHC) Element Space Radiation (SR) Element

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

Solicited

Aims:
The conceptualization of Brain Performance Pathways (BPP) is based on how the architecture of brain networks at rest guide the connectivity patterns that emerge during the performance of various tasks (i.e., modularity measured during "resting states" predicts working memory performance and stimulus detection in a perceptual task).  Past CNS research focuses on single ions and dosages, identifying differential sensitivity of brain tissue that is more likely to disrupt modular brain organization (i.e., Brain Performance Pathways).

Short Title: CBS Stress Response, Cross-species Homology Study NHPs

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Health Countermeasures (HHC) Element Space Radiation (SR) Element

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

Solicited

Aims:
Research project focused on developing scientifically plausable, heuristic, computational models using Non-Human Primates (NHP) and radiation exposures (both clinical and space relevant,  in combination with other CBS realted spaceflight stressors) in order to assess, characterize and derive and valdiate operationally-relevant  models of performance outcome levels relative to radiation exposures (in combination with other CBS realted spaceflight stressors), dose effects and countermeasures for CBS integrated risk exposures in humans. An important aspect of this effect involves the conceptualization of research that is "reverse translation" in which consideration is given to the specific biological markers with significant operationally-relevant performance consequences are first determined in human models and then applied to an animal model to see if they exist and that they reflect the same performance decrements as evidenced in humans. This approach will facilitate the identification of novel biomarkers linked to different levels of performance (impact by CBS synergistic risks) with the introduction of CBS integrated risk at different stages of mission-relevant performance demands in the animal models. This also offers the potential to identify biomarkers related to the brain performance pathways.

Short Title: CBS Cortical Reorganization (RFP)

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Health Countermeasures (HHC) Element Space Radiation (SR) Element

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

Solicited

Aims:
Specific focal impacts on brain regions are important for us to understand since cortical organization reveals a “between-module connectivity” that when disrupted, is associated with widespread cognitive dysfunction. This underscores the  importance of conceptualizing Brain Performance Pathways (BPP) and the role of a modular structure in enabling brain processes that support a wide range of operationally-relevant behaviors. This also potentially relates to the putative role of "Cognitive Reserve" and potential for a measures of cortical organization to serve as a "biomarker." This is evidenced by research that demonstrates an “intelligence” relationship that is revealed with cortical organization, with those scoring higher on IQ tests showing smaller functional connectivity changes between “resting state” and “task performance states” (suggesting more efficient adaptation to task demands). Given the different sensitivities of brain tissue to both types and dosages of radiation, stress, and altered gravity, we need to assess the potential role of the connectivity patterns as representative of BPPs to assess differential vulnerabilities to modular networks and just as importantly, determine how a more modular brain network may potentiate CMs (e.g., the potential for up-regulation in neurotrophic factors that have been associated with greater exercise-related changes in brain connectivity). 

Short Title: CBS NSCOR #1: Single Beam GCRsim Mixed Field

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Health Countermeasures (HHC) Element Space Radiation (SR) Element

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

Solicited

Aims:
Large-scale research study to assess integrated CBS risk by incorporating needed topics such as radiation biological effects (RBEs), Glial cell responding, stress response, cross-species homology, animal mood/social/cognition, sleep/stress/cognition, neural plasticity, dose rate effect for multiple measures related to CBS risk.

Short Title: CBS RR: HCAAM Intelligent System: Monitoring & CMs Performance Pathways

Responsible HRP Element: Human Factors and Behavioral Performance

Collaborating Org(s):

Human Health Countermeasures (HHC) Element Space Radiation (SR) Element

Funding Status: Planned-Funded - Task expected to be within budget

Procurement Mechanism(s):

Solicited

Aims:
-Conduct Research Review focused on potential human system adaptations with autonomous systems and habitat in order to maintain operationally-relevant performance by leveraging both countermeasures  (CM) and Human Capabilities Assessment for Autonomous Missions (HCAAM) Intelligent System that monitors Brain Performance Pathways and then responds with appropriate countermeasures to mitigate risk and/or compensate for decrements in performance throughout mission.