Gap BMed-108: Given each crewmember will experience multiple spaceflight hazards simultaneously, we need to identify and characterize the potential additive, antagonistic, or synergistic impacts of multiple stressors (e.g., space radiation, altered gravity, isolation, altered immune, altered sleep) on crew health and/or CNS/ cognitive functioning to develop threshold limits and validate countermeasures for any identified adverse crew health and/or operationally-relevant performance outcomes.
Last Published:  07/30/20 02:45:13 PM (Central)
Responsible Element: Human Factors and Behavioral Performance (HFBP)
Status: Open
Description
This Gap addresses the reality of long-duration spaceflight—that each crewmember will experience multiple spaceflight hazards simultaneously.  This fact necessitates that we identify and characterize the potential additive, antagonistic, or synergistic impacts of multiple stressors (e.g., Space Radiation, Altered Gravity, Isolation, altered immune, altered sleep) on crew health and/or CNS/ cognitive functioning to develop threshold limits and validate countermeasures for any identified adverse crew health and/or operationally-relevant performance outcomes.  This approach builds on past, multi-Element research, to determine/develop standardization and recommendations related to animal handling, research facility (e.g., volume, lighting, sound, etc.) and animal/rodent type (species/strains) to increase reliability and 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 brain and operational performance pathways. This risk leverages 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 functions. Current research suggests 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.  Also, the effort to identify biomarkers (blood, behavioral, etc) is linked to past CBS research that correlate with the human behavior and performance.  This past research is being leveraged to determine which positive biomarker statuses are associated with adverse outcome pathways and/or indicate greater possibility of developing neurocognitive disorders.  These neurobehavioral biomarkers (blood, behavioral, etc) identified and linked to past CBS research that correlate with the human behavior and performance. The identification of positive biomarker statuses associated with adverse outcome pathways and/or indicate greater possibility of developing neurocognitive disorders.  They will also provide a conceptual model and heuristic for use in translational and computational models for dose-effect research.
Approach: Research requirements tasks will be used to summarize the literature on how “in-mission” CNS/cognitive/behavioral health relates to, predicts, and may impact on crew health and performance in a synergistic manner. Additionally, ground-based, peer-reviewed research using cell and animal models will be conducted to acquire necessary knowledge for accurate risk calculation and uncertainty reduction for acute adverse CNS/cognitive/behavioral health outcome measures due to space radiation exposure. We will examine the gap between the available information in the extant literature and what is needed for future exploration missions and solicit studies to address those areas. We will solicit studies to develop and validate the potential combinatorial impacts of combined, mission-relevant hazards (e.g., space radiation, isolation, altered gravity). This research will use high fidelity analogs and ultimately ISS. Periodic tech watches will ensure that the most advanced state of the art technology is in use.  Where feasible, we will identify biomarkers of disease pathophysiology and/or progression for use in monitoring adverse acute, “in-mission” CNS/cognitive/behavioral health outcomes and for use in continuity of care perspective relative to spaceflight. A systems biology approach for individual CNS/cognitive/behavioral health and performance adverse changes resulting from multiple exposures  may be needed to form a basis for animal to human extrapolation, and will rely on understanding of molecular and physiological changes in the CNS/cognitive/behavioral performance caused by mission- relevant exposures (e.g., space radiation, isolation, altered gravity) and how these changes relate to acute, “in-mission” and post-flight CNS/cognitive adverse outcomes.  Countermeasures developed will address the pre-, during-, and post-mission phases of exploration missions. Pre-mission vulnerabilities and resiliency, in-mission exposures, and post-mission impacts will be identified and baselined for Earth-levels. 
Target for Closure
Define integrated, multi-risk domains and appropriate metrics that encompass operationally-relevant performance decrements of concern (e.g. attention and executive functions, reaction time, motor skills, neuropsychological and neurobehavioral functions, circadian rhythms, etc.) attention deficits, neuropsychological, neurobehavioral, circadian rhythms, reaction time, motor skills, etc.).

Develop integrated models to assess multiple exposures on CNS/cognitive/behavioral health models of importance to brain performance pathways and processes that contribute to operationally-relevant CNS/cognitive/behavioral health and performance risks, including synaptic dysfunction, impaired neurogenesis, neurodegeneration, neuro-inflammation, etc.

Validated Monitoring tools for post-mission behavioral health.
(1) Identify and incorporate standard, but integrated, exposure conditions and reference measures (e.g., performance outcomes levels and Permissible Exposures Limits) of operationally-relevant performance measures in collaboration with BHP ops.
(2) Quantify the spectrum and dose responses for integrated, multi-hazard exposures on “acute”, in-mission, and post-mission (mission timescale) on functional CNS/cognitive/behavioral performance changes from integrated, mission-relevant exposures (e.g., space radiation, isolation, altered gravity).
(3) Organize CNS/cognitive/behavioral performance reactions to mission-relevant integrated exposures into adverse outcome pathway(s) and brain performance pathways related to known diseases and biomarkers.
(4) Combine CNS/cognitive/behavioral health integrated process models to create model for acute, mission-relevant CNS/cognitive/behavioral risk assessment via model validation and documentation for in-mission risk related to post-mission risk results.
(5) Identified set of psychosocial support, habitability, and bionutritional countermeasures targeting key indicators of an integrated risk to maintain CNS/cognitive/behavioral health and performance.
(6) Verified and validated countermeasures in ground-based analogs with astronaut-like subjects.

Validated set of countermeasures targeted to integrated risk reduction during pre-mission preparation, in-flight adaptation and functional readiness, and post-mission transition/rehabilitation.

Report integrating and synthesizing multiple research studies of immune, nutrition, sleep, circadian dysregulation, etc., contributions to both cognitive performance and demands, stress reduction, cognitive functioning & brain performance pathways and reductions of risks associated with adverse behavioral conditions. 
Mappings
Risk Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
You are here! Gap BMed-108: Given each crewmember will experience multiple spaceflight hazards simultaneously, we need to identify and characterize the potential additive, antagonistic, or synergistic impacts of multiple stressors (e.g., space radiation, altered gravity, isolation, altered immune, altered sleep) on crew health and/or CNS/ cognitive functioning to develop threshold limits and validate countermeasures for any identified adverse crew health and/or operationally-relevant performance outcomes.
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