Gap BMed-103: What are the validated, efficacious treatments (individual or Team-based) and/or countermeasures to prevent adverse behavioral conditions, CNS/neurological, and/or psychiatric disorders caused by either single and/or integrated exposures to spaceflight hazards during exploration class missions?
Last Published:  07/30/20 02:45:13 PM (Central)
Responsible Element: Human Factors and Behavioral Performance (HFBP)
Status: Open
Description
Future human spaceflight exploration missions will exceed the current ISS duration of six-months, with exploration missions projected to take as long as three years, exposing astronauts to stressors over a much longer timeframe. Additionally, the increased autonomy and isolation from Earth may impose a significant psychological strain upon crews.  Possible acute (within mission) risks to the central nervous system (CNS) from galactic cosmic rays (GCR), solar particle events (SPE), and from isolation are a documented concern for human exploration of space. Acute, in mission, CNS/cognitive/behavioral performance risks includes: altered cognitive function, reduced motor function, behavioral and neuropsychological changes, all of which may affect operationally-relevant performance and crew health. To ensure crewmembers are prepared for the demands of these long-duration missions, we need to identify and validate effective countermeasures to promote individual behavioral health and performance and effective treatments to prevent or mitigate adverse behavioral conditions and psychiatric disorders from occurring.  The countermeasures identified will need to consider anticipated mission constraints.  Biomedical countermeasure and biomarkers for cognitive/CNS/behavioral performance risks on which to index countermeasure efficacy are unknown. The identification of operationally-relevant performance linked biomarker thresholds are needed to guide both biological and medical interventions, and their underlying mechanisms, inclusive of exercise and conditioning, as well as dietary countermeasures (e.g., nutritional supplements), to mitigate risks to CNS/cognitive/behavioral performance. It is important to note these countermeasure determinations are distinguished from, but complementary to the physical or mission countermeasures such as shielding, time in solar cycle, or mission duration (e.g. transit times, surface stays). Current ISS operations are based on a six-person international crew living and working for six months in low Earth orbit. While astronauts generally thrive on these missions, there have been anecdotal evidence and research reports of psychosocial issues occurring in spaceflight, both on the ISS and in other environments. Currently, ISS missions are supported by significant infrastructure from social and operational support, including health, psychological, and technical support. Furthermore, ISS operations are based on real-time treatment of medical events related to adverse behavioral conditions (e.g., insomnia) from ground medical personnel. Future missions, however, will be characterized by communication delays and will vastly exceed the current ISS mission duration of six months, increasing the probability of behavioral health issues. Medical treatment will depend on new approaches via asynchronous telemedicine, self-treatment methods, and/or the presence of a medically trained crewmember with skills in psychiatric medicine. There is a need to determine the optimal methods to treat individual behavioral health problems should they occur during exploration class missions, including the use of behavioral health medications, because the types of support provided for ISS operations will not be possible for future exploration missions owing to the prevalence of communication delays and distance from Earth. With exploration missions at greater distance from earth, there are also concerns regarding the increased risks for significant adverse changes in CNS performance in the context and time scale of spaceflight operations. Given the significant probability that space radiation exposure will result in adverse changes, uncertainty exists as to how to define the operationally-relevant significance of those changes and to identify which neuropsychological domains, pathways and mechanisms of change are most likely.  Therefore, an understanding of autonomous, non-pharmacological treatment methods is needed to help remedy behavioral health problems in individual crewmembers due to the circumstances expected during remote long-duration and/or long-distance exploration missions. To gain this knowledge, it is necessary to understand the role that asynchronous telemedicine would play between a mission crewmember and a mission control mental health professional in providing support and therapy, and how such a method would compare with the efficacy of real-time, face-to-face methods. It is also important to define when cognitive behavioral therapy should be employed versus problem solving therapy, social skills training, or other evidence-based therapies and for which problem set(s). Furthermore, it is essential to define the frequency and mission stage at which coping skills and interpersonal problem solving should be implemented. The impact of these support systems and the psychosocial countermeasures needed for long duration exploration missions (<6; 6-12; >12 months) beyond low Earth orbit are not known.  
Approach: A multifaceted, transdisciplinary, integrated risk approach, which involves a combination of examining research findings from related gaps and soliciting new research studies to provide missing information, is needed for gap closure. First, determining and understanding the key threats and indicators depends on early prediction, detection and assessment of CNS/cognitive/behavioral health decrements. Next, there is a need for data on selection of individuals who are more resistant to developing CNS/cognitive/behavioral health problems in isolation and confinement and after exposures to space radiation and altered gravity. These factors will aid in the prevention of CNS/cognitive/behavioral health problems by detailing the best methods for mitigating the risks, developing countermeasures, and for maintaining social support from Earth to crewmembers. Gap closure will depend on  the conduct of additional research to identify potential CNS/cognitive/behavioral challenges and treatments within the context of the exploration mission environment.  Research specific to the spaceflight environment using animal and cell models must be compiled to calculate the magnitude of this risk and to help establish the validity of the operationally-relevant performance thresholds and to help establish a permissible exposure limit (PEL) for the integrated risk.  Previous near-term experimental research has focused on assessing effects from 2 to 4 particle types; this has recently been broadened to include up to 33 different ion-energy combinations and low dose-rate GCR mixed-fields, considered more relevant for astronaut risk projections.  Data mining of past, ground-based, peer-reviewed research using cell and animal models is needed to determine the current state of knowledge and to establish more targeted future research that will to acquire knowledge necessary to accurately calculate risk and reduce uncertainty of acute adverse CNS/cognitive/behavioral performance outcome measures due to space radiation and other mission-relevant spaceflight hazard exposures. Where feasible, there is a need to identify biomarkers of disease pathophysiology that can be used to monitor adverse acute CNS/cognitive/behavioral outcomes and select standardized measures to monitor during missions.  Given the lack of human epidemiology data on which to estimate this potentially synergistic, combined risk, there is a need for models that can project CNS/cognitive/behavioral performance risks.  It is expected that the mechanistic understanding acquired from near-term research will set the course for the identification of effective countermeasure approaches through establishment of appropriate indexed biomarkers and model systems for use in selection and validation of candidate standardized measures.  Solicited research is needed that focuses on 1) identifying potential clinical CNS/cognitive/behavioral challenges that may affect crewmembers during autonomous, long duration and/or distance exploration missions; 2) identifying treatment options for the set of identified CNS/cognitive/behavioral challenges; and 3) validation of the set of identified treatment/countermeasure options. Countermeasures developed will address the pre-, during-, and post-mission phases of exploration missions. From the threats and promoters identified and baselined for Earth-levels, current countermeasures and readiness levels of research deliverables (tools and technologies) will be reviewed. 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 countermeasures to fill this gap. These countermeasures will be validated in high fidelity exploration analogs and ultimately the ISS. Periodic tech watches will ensure that the most advanced state-of-the-art technology is in use.  Lastly, based on the research findings, there is a need to develop an integrated suite of treatment protocols for treating challenges to CNS/cognitive/behavioral operationally-relevant performance experienced during exploration missions.
Metrics for Interim Progress:
-Identify appropriate experimental models, paradigms, and endpoints for the assessment of acute, in-mission radiation effects on the CNS, as well as the effects of isolation and other mission relevant hazards exposures.
-Determine the dose responses and existence of threshold doses of space radiation for functional CNS/cognitive/behavioral performance changes using appropriate animal model systems (e.g. rodent, NHP).
-Identify the pathophysiological mechanisms underlying functional CNS/cognitive/behavioral performance changes due to mission-relevant exposures to spaceflight hazards (e.g., space radiation, isolation, altered gravity).
-Broaden initial experiments to investigate a larger number of mission-relevant GCR particle types and energies, including mixed fields representative of GCR and different shielding configurations including the Martian surface, as they relate to mission-relevant operational performance. -Broaden initial experiments to investigate effects of dose protraction or fractionation on operationally-relevant performance and in-mission health.
-Develop methods for relating animal endpoints to human endpoints of CNS/cognitive/behavioral performance using multiple experimental models (e.g. rodents, NHPs, humans).
-Determine the feasibility of identifying key biomarkers/indexed metrics with functional or pathophysiological process correlations (disease-linked biomarkers) of mission-relevant exposures to spaceflight hazards (e.g., space radiation, isolation, altered gravity).
-Determine how to relate functional endpoints and key biomarker measurements to potential mission decrements in CNS/cognitive/behavioral performance.
-Identify relevant mechanisms and  biomarker (indexed metrics) panels to monitor therapeutic and countermeasure efficacy for acute, in-mission, CNS/cognitive/behavioral effects (SPE; SPE+GCR, +isolation, +altered gravity).
-Identify and validate candidate countermeasure for adverse acute CNS outcomes.
-Identify relevant mechanisms and biomarkers (indexed metrics) panel to monitor therapeutic efficacy for post-mission CNS/cognitive/behavioral performance relevant effects (SPE; SPE+GCR, +isolation, +altered gravity); particularly as relates to mitigating risks of future exploration missions.
-Identify and validate candidate countermeasure for adverse post-mission CNS/cognitive/behavioral outcomes.   
Target for Closure
Develop a validated set of psychosocial support countermeasures targeting key mechanisms that maintain individual behavioral health and performance. These countermeasures should be targeted to pre-mission preparation, in-flight adaptation and functional readiness, and post-mission transition/rehabilitation.

Identify and incorporate standard exposure conditions and reference measures in collaboration with BHP Operations.

Quantify the particle spectrum and dose responses for acute (mission timescale) functional CNS changes from space radiation exposure.

Organize CNS reactions to radiation exposure into adverse outcome pathway(s) related to known diseases and biomarkers.

Leverage multiple risks’ data and solicit for transdisciplinary identification and validation of biomarkers (e.g., immune, etc) that have been collected and associated with some change in operationally-relevant performance and/or indicative of potential adverse cognitive outcome (e.g., change in blood-brain-barrier) to assess long-term effects/vulnerabilities that only appear post-mission.

Determine the operational significance of adverse changes elicited by mission-relevant exposures to spaceflight hazards (e.g., space radiation, isolation, altered gravity).    
(1) Identified set of operationally-relevant CNS/cognitive/behavioral performance challenges that may affect crewmembers in exploration environments.  
(2) Identified set of psychosocial support countermeasures targeting key indicators to maintain behavioral health and performance.    
(3) Verified and validated countermeasures in ground-based analogs with astronaut-like subjects.
(4) Identified set of validated non-pharmacological treatment methods for the identified behavioral challenges.    
(5) Identified operationally-relevant performance/crew health thresholds for implementation of pharmacological treatment of the identified CNS/cognitive/behavioral challenges.

Identification of indexed metrics to monitor therapeutic efficacy for acute, in-mission, and post-mission, CNS/cognitive/behavioral performance and crew health effects due to mission-relevant space exploration exposures (e.g., space radiation exposure, isolation, altered gravity).

Identification and validation of candidate countermeasures that modulate adverse outcome pathways and  mitigate in-mission health and performance impacts and reduce mission-relevant post-mission effects on CNS/cognitive/behavioral performance. 
Mappings
Risk Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
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