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NASA NTRSDate not supplied

Behavioral Medicine Risks and Mitigations in Isolated, Confined, and Extreme Environments

Human spaceflight beyond low Earth orbit will present unique environmental challenges to astronauts’ operational performance and well-being. Crews will need to work and live in confined and hazardous environments for prolonged missions that involve variable workloads and limitations to privacy, food options, exercise capabilities, leisure outlets, and communication with ground support personnel and loved ones. Currently, behavioral and cognitive risks of spaceflight are mitigated by selecting exceptionally resilient crews and providing extensive individual and team skills training pre-mission, as well as in-mission crew support via a suite of countermeasures targeting sleep and performance optimization, stress management, family support, and team cohesion. However, current countermeasures are difficult or impossible to implement in long-distance exploration as they require real-time communication with Earth and routine resupply. New countermeasure approaches are needed to adapt and enhance the current complement for the new challenges ahead. NASA therefore conducts research at ground-based spaceflight analogs to aid in characterizing the behavioral and cognitive risks of living and working in isolated, confined, and extreme (ICE) operational environments. Antarctic research stations are among the few long-duration ICE analogs in existence and are therefore uniquely positioned to support behavioral medicine research to enable human exploration beyond Earth. In this review, we will discuss previous and ongoing efforts to better understand spaceflight behavioral medicine risks, as well as validate new countermeasure approaches for future missions to the moon and Mars.

Behavioral Health↗

NASA NTRSDate not supplied

Sex differences and deep space stressors: effects of 5-ion gcrsim, simulated microgravityand social isolation on immune function, brain, and behavior in mice

This project is testing the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance. Specific Aims for this project are to: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. Here we report findings from our studies of mature (24-week-old) male and female mice exposed to simulated 5-Ion GCRsim (0, 5, 15, or 50cGy) at the NASA Space Radiation Laboratory (NSRL) followed by combinatorial exposures to 15cGy, simulated microgravity via head-down tilt (hindlimb unloading) and social isolation. Immune, brain and behavioral (sensorimotor, risk-taking & cognitive) measures were acquired at ‘Acute’ (IR+24hrs, IR+72hrs), ‘Intermediate’ (IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) to inform biological responses anticipated during a transit to Mars. This project addresses NASA’s efforts to characterize risks and identify appropriate countermeasures in both women and men in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Supported by the NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18 18FLAG 2 0028.

behavioral sciences↗

NASA NTRS2022

FY22 X-Hab: Rochester Institute of Technology: Gamification and Performance-Based Monitoring of Sensorimotor Training Activities

Proprioception is the body’s ability to sense movement, action, and location. Proprioceptive training is crucial for astronauts because humans balance system, cognitive functions, and muscle tone heavily rely on Earth’s gravity. The goal of this project is to create a training system that strengthens those characteristics to ensure astronauts not only maintain their coordination and cognitive skills, but improve upon them as well. Furthermore, the system’s live biofeedback provides astronauts with sensorimotor feedback to correct any balance dysfunction. The completed system prototype and data collected from it will support NASA’s knowledge base about the use of gamification for sensorimotor training activities.

Griffin Brown↗

NASA NTRSDate not supplied

An Oculometric Standard to Assess the Performance of the Ocular System for Long Duration Spaceflight

Changes in the human brain, due to spaceflight, have been a challenge to the space program since its inception; a challenge that is becoming more acute as extended International Space Station (ISS) missions become routine, a return to crewed lunar exploration is about to begin, and a multi-year crewed trip to Mars is being planned. Determining the extent to which neurophysiological adaptations may adversely impact performance in operational tasks, assessing the full-time course of these changes, and identifying/mitigating any potential long-term health consequences are crucial steps required to enable safe crew-autonomous, long-duration, deep-space missions. Vision is the predominant perceptual sense used to guide cognition and motor control in humans. Thus, it is critical for the success of any future, long-duration mission to understand how long-term exposure to microgravity and to other stressors of spaceflight and their interactions, impact visual function. This is an especially challenging task given the small and disparate samples from which we have been and will be able to collect human performance data. NASA has recently been carefully tracking spaceflight-induced ophthalmic changes, driven in large part by the fluid shifts related to microgravity. In particular, a recent study of Optical Coherence Tomography (OCT) postflight measures revealed that more than two-thirds of US crew members experience significant increases in retinal thickness after 6month or longer ISS missions. Space Associated Neuro-ocular Syndrome (SANS) also includes visual acuity decrements and other ocular structural changes that could adversely impact in-flight performance as missions become longer. However, the impact of spaceflight on the visual system is not limited to the retina. Recent comparisons of pre-and post-flight brain images have revealed structural changes throughout the brain that implicate visual, visuomotor, and visual-cognitive pathways, consistent with observed functional impacts (e.g., decreased speed/accuracy/timing of fine goal-oriented movements). Current limitations on inflight testing make it very difficult to determine when and under what conditions SANS and other disruptions of human neurological subsystems arise. Currently, one cannot anticipate the time course and extent of impairment and recovery. This study addresses this knowledge gap by creating an integrated framework of the relevant existing literature on visual and oculomotor function during spaceflight with an eye towards complementing current structural measures of visuomotor impairment with new oculometric standard measures. Using eye-movement based visual function assessment and diagnostics would provide a valuable enhancement of crew health and performance monitoring in support of deepspace exploration.

Vision↗

NASA NTRS2023

Galvanic Vestibular Reduction Modifies Perception of Coriolis Cross-Coupling and Delays Motion Sickness Onset

INTRODUCTION: Alterations in vestibular sensory processing following G-transitions lead to head movement sensitivity and motion sickness upon return to Earth’s gravity. The purpose of this study was to evaluate whether a non-pharmaceutical tool using galvanic vestibular reduction (GVR) could suppress disorienting illusions and mitigate motion sickness. A similar approach using anodal (inhibitory) currents delivered to both ears has been shown to result in a selective reversible ablation of irregular vestibular afferents [1]. METHODS: Using a repeated measures counter-balanced design, motion sickness and perception were obtained in 26 subjects during Coriolis cross-coupling stimuli on a rotating chair across three GVR treatment interventions: throughout stimulus testing (prevention), following symptom onset (rescue), and placebo control. The GVR peak current was maintained at 2.5 mA across subjects and across prevention / rescue sessions. Subjects performed up to 10 sets of pitch head movements during constant rotation. For each set, head movement was cued every 10 seconds, alternating between pitch forward (chin resting to chest) and pitch backward (head upright) for a total of 7 forward and backward movements. During each head movement, subjects were asked to use a joystick to record the magnitude of their perceived rotation along three axes. During the 2-minute pause between sets, motion sickness symptom scoring was obtained using the Pensacola Diagnostic Index and subject discomfort (0-20) ratings. Performance on a sensorimotor and cognitive test battery was measured during a fourth session to map changes in GVR level with functional performance. RESULTS: Fourteen of the 26 subjects were not susceptible to the motion stressor (i.e., did not reach an endpoint in the control condition). While the time to endpoint, or number of head movements, did not significantly vary across the three GVR conditions in the remaining subjects, the symptom levels were significantly lower through the third set of head movements when GVR was on throughout the testing. Initiating GVR following symptom onset did not appear to alter the symptom progression nor time to motion sickness endpoint. Based on the joystick measures, GVR significantly modified the perceived roll and pitch sensation during head movements, reducing the amplitude of tilt in most subjects. It is important to note that comparable levels of GVR did not impair performance on a functional test battery including mobility, balance and cognitive tasks. DISCUSSION: Our findings suggest GVR may be useful in reducing disorienting roll and pitch illusions and delaying the onset of motion sickness. Further enhancements will be required to individualize the stimulation amplitude and optimize the waveform delivery. Adapting this non-pharmaceutical countermeasure approach to allow self-administered titration of current amplitude during recovery would enable transfer to post-flight treatment of motion sickness. [1] Minor L. B. and Goldberg J. M. (1991) J Neurosci 11, 1636-48. 109, 889-894.

G N Pradhan↗

NASA NTRS2022

Sex Differences in Perceptions of Sleep Inertia Following Nighttime Awakenings

Study Objectives: The influence of biological sex on sleep inertia symptoms is currently unknown. We investigated the role of sex differences in the subjective experience and objective cognitive manifestation of sleep inertia following nighttime awakenings. Methods: Thirty-two healthy adults (16 female, 25.91 ± 5.63 years) completed a one-week at-home study with one experimental night during which sleep was measured by polysomnography and participants were awakened during their habitual sleep time. Participants completed a psychomotor vigilance task (PVT), Karolinska Sleepiness Scale (KSS), visual analog mood scales, and a descending subtraction task (DST) prior to sleep (baseline) and at 2, 12, 22, and 32 minutes after awakening. A series of mixed-effects models with Bonferroni-corrected post-hoc tests were used to examine the main effects of test bout and sex, and their interaction, with a random effect of participant, and order of wake-up and sleep history as covariates. Results: All outcomes except for percent correct on the DST showed a significant main effect of test bout, with worse performance after waking compared to baseline (all p s < .003). Significant effects of sex ( p = .002) and sex × test bout ( p = .01; R 2 M = .49, R 2 C = .69) were observed for KSS, with females reporting a greater increase in sleepiness from baseline to after waking compared to males. Conclusions : These results suggest that while females reported feeling sleepier than males following nighttime awakenings, their cognitive performance was comparable. Future research is needed to determine whether perceptions of sleepiness influence decision-making during the transition from sleep to wakefulness.

Sleep inertia↗

NASA NTRSDate not supplied

Sex Differences in Perceptions of Sleep Inertia Following Nighttime Awakenings

Study Objectives: The influence of biological sex on sleep inertia symptoms is currently unknown. We investigated the role of sex differences in the subjective experience and objective cognitive manifestation of sleep inertia following nighttime awakenings. Methods: Thirty-two healthy adults (16 female, 25.91 ± 5.63 years) completed a one-week at-home study with one experimental night during which sleep was measured by polysomnography and participants were awakened during their habitual sleep time. Participants completed a psychomotor vigilance task (PVT), Karolinska Sleepiness Scale (KSS), visual analog mood scales, and a descending subtraction task (DST) prior to sleep (baseline) and at 2, 12, 22, and 32 minutes after awakening. A series of mixed-effects models with Bonferroni-corrected post-hoc tests were used to examine the main effects of test bout and sex, and their interaction, with a random effect of participant, and order of wake-up and sleep history as covariates. Results: All outcomes except for percent correct on the DST showed a significant main effect of test bout, with worse performance after waking compared to baseline (all ps < .003). Significant effects of sex (p = .002) and sex × test bout (p = .01; R2M = .49, R2C = .69) were observed for KSS, with females reporting a greater increase in sleepiness from baseline to after waking compared to males. Conclusions: These results suggest that while females reported feeling sleepier than males following nighttime awakenings, their cognitive performance was comparable. Future research is needed to determine whether perceptions of sleepiness influence decision-making during the transition from sleep to wakefulness.

sleep inertia↗

NASA NTRSDate not supplied

Limitations on the Use of Eye-Tracking Data to Understand Operator Awareness

In the last 20 years, a number of accidents and incidents in commercial aviation have pointed to poor flight crew awareness of basic flight path parameters (e.g., airspeed, bank, pitch). As a result, there is a desire to improve pilot situation awareness and how attention is allocated. Eye-tracking has been a commonly used measure of awareness; it can aid in understanding whether specific indications were fixated, and perhaps how a pilot gathered information (that is, which indications in which sequence). In this paper, we discuss limitations on what eye-tracking data can reveal about pilot awareness and understanding. First, previous studies (e.g., Sarter et al., 2007) have shown that fixation on an indication may not ensure awareness or understanding. Further, an operator may have awareness of information not fixated. Additional measures—such as self-report or control inputs—can help to better establish the extent of pilot awareness and understanding. Second, sequences of fixations (scan patterns) have also become a performance measure. While a small number of recognized scan patterns have been validated for a small set of parameters on the Primary Flight Display (PFD), scan patterns have not been identified to support the broader context of flight path management or flight operations. More important is to understand the full set of drivers underlying the larger pattern of eye fixations; this approach moves away from the idea of well-established scan patterns as a marker of skilled performance and gives a larger role to pilot cognition. Pilots have various reasons to direct attention to specific elements on the interface, such as: - feedback tied to control inputs - a check on compliance with flight path targets - a reaction to an alert or a call out - attempt to understand an unexpected indication - assess progress toward a flight path target The importance of cognition is further implicated in the finding that pilot interviews show that fixating typically is accompanied by expectation; generally, pilots have a strong expectation of what value or indication they will see, which allows more efficient integration of information and an ability to identify indications that suggest an alternative account of the current system state. We will describe a range of eye-tracking measures and how they should and should not be used.

aviation↗

NASA NTRSDate not supplied

Effects Of Five-Ion Galactic Cosmic Radiation Simulation On Immune Function, Brain, And Behavior In Male And Female Mice

Exposure to galactic cosmic radiation is a principal consideration of spaceflight missions, and with upcoming missions to the Moon and Mars, it is increasingly imperative to elucidate the effects of space travel beyond the lower Earth orbit. Additionally, with the first female astronaut to soon travel to the Moon there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. To simulate the type of radiation exposure occurring during spaceflight, model organisms can be exposed to relevant doses via Five-Ion Galactic Cosmic Radiation Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. We have investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy. Following exposure, immune, brain and behavioral (sensorimotor, risk-taking and cognitive) measures were acquired at ‘Acute’ (IR+24hrs, IR+72hrs), ‘Intermediate’ (IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) to inform biological responses anticipated during a transit to Moon and Mars. There were pronounced sex differences observed in all outcome measurements, while very few radiation induced effects were observed. Those dose effects that were observed were primarily in cytokine expression and less so in behavioral measurements. Further studies will investigate if radiation, microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance, ultimately to characterize risks and identify appropriate countermeasures in both women and men in anticipation of future deep space missions.

Stephanie Puukila↗

NASA NTRS2023

Progressively Enabling Earth Independent Medical Operations (EIMO)

This panel presents the findings from a series of Technical Interchange Meetings (TIMs) hosted by the Exploration Medical Capability Element (ExMC) in NASA’s Human Research Program. The topics for the TIMs were derived from a 2-day conference of senior leaders and subject matters experts that collectively outlined a multi-faceted strategy designed to optimize crew health and performance through an increasingly autonomous medical approach. The first abstract in this panel outlines the scope of issues related to data collection, usage, transmission and computing capacity to facilitate EIMO. The second presentation provides an overview of the challenges in developing curricula and advanced training tools to baseline knowledge, skills and abilities (KSA), verify clinical competency and assure retention during prolonged durations inherent in exploration-class missions. An overview of the complicated medical supply and resource chain necessary to facilitate EIMO is provided in the third presentation of this panel. The final presentation in this EIMO panel surveys the breadth and depth of demands on cognitive load expected to be experienced by crew on an exploration mission and proposes strategies to mitigate the prospect of cognitive overload through methods to shift task load from the crew to multi-modal artificial intelligence based medical support systems. Taken together, these presentations summarize the challenges to be expected and potential solution spaces to be explored and developed to progressively enable increasing autonomous medical operations to support crewed missions beyond low earth orbit. Through EIMO focused pre-mission planning, integrated data architecture design, innovative training development and AI-assisted task load management, the gradual transition of medical care and decision making from terrestrial to space-based assets enabling support of astronaut health and performance and reducing overall mission risk is achievable.

Jay Lemery↗

NASA NTRSDate not supplied

Progressively Enabling Earth Independent Medical Operations (EIMO)

John Lemery↗

NASA NTRSDate not supplied

Jet Lag, Sleep Timing, and Sleep Inertia

This chapter explores the causes, consequences, and countermeasures of jet lag, mistimed sleep, and sleep inertia. Jet lag can occur when rapidly crossing multiple time zones (e.g., trans-meridian travel for long-haul pilots). The desynchrony between the body’s biological clock, or circadian rhythm, and the new day-night cycle can lead to indigestion, sleep disturbances, fatigue, and cognitive impairments. Mistimed sleep can also occur within a time zone. In the case of night shiftwork, sleep is displaced to the daytime which leads to poor sleep and increased fatigue at night due to the combination of pressures from the two-process model of sleep regulation: sleep loss (homeostatic pressure); and being awake when the body is promoting sleep (circadian pressure). There is also a third process of sleep regulation called sleep inertia, which refers to the brief period of fatigue and impaired cognitive performance experienced after waking. Sleep inertia can be a fatigue risk for transportation workers who work on-call (e.g., emergency services) or who nap on shift (e.g., long-haul truck drivers) and are required to perform a safety-critical task soon after waking. For each of these fatigue risks, strategic exposure to bright light can be used to help realign sleep timing and to promote alertness.

sleep inertia↗

NASA NTRS2026

Effects of Multisensory Virtual Reality Nature on Affect, Presence, and Restorativeness

Virtual reality (VR) can provide access to restorative environments and sensory stimulation for individuals in isolated, confined, and extreme environments. We developed a nature-based VR intervention featuring three scenes (Garden, Forest, Beach) and examined the effects of multisensory augmentation with location-based olfactory, wind, and thermal stimuli (VR+OWT). Over a two-week period, fifty-one participants were assigned to a no-intervention control, standard audiovisual VR, or augmented VR (VR+OWT) condition. Data collection included weekly assessments of affect, stress, and cognitive performance; post-VR measures of affect, presence, and perceived restorativeness; and open-ended feedback. Both VR and VR+OWT groups produced immediate and sustained reductions in negative affect with no sustained systematic benefits on cognitive performance. The addition of olfactory, wind, and thermal stimuli enhanced presence for some scenes; however, feedback indicated that sensory mismatches and stimulus intensity occasionally detracted from the experience and may have contributed to lower coherence ratings in the VR+OWT group. In contrast, the perceived restorativeness of the VR environment was driven primarily by scene content (Garden vs Forest vs Beach) rather than the level of sensory stimulation. These findings support the potential of virtual nature to promote well-being and underscore the importance of coherence across sensory modalities for multisensory augmentation.

Virtual Reality Intervention↗

DOE OSTI2021

Machine Intelligence to Detect, Characterise, and Defend against Influence Operations in the Information Environment

Social media has enabled a new era of manipulation in the information and cognitive domains. Deceptive content—misleading, falsified, and fabricated—is routinely created and spread in the modern social media environment with the intent to create confusion and widen political and social divides, and exploit the societal conflict exacerbated by these divides in the real-world (aka physical domain). Such disinformation campaigns demonstrate a threat to the integrity of economic, political, cultural, public health, and national security institutions around the world. In this work we overview our artificial intelligence (AI) capabilities to detect, describe, and defend against information operations on Twitter as an example social platform to understand the influence of misleading and falsified content diffusion and better enable those charged with defending against such manipulation to enable responsive parties to counter it. We first present novel linguistically-informed deep learning (DL) models for misinformation and disinformation detection, and present an in-depth linguistic analysis of psycho-linguistic markers across broad deception categories. We then demonstrate how our models perform in the multilingual and multimodal setting and categorize falsified and misleading content based on the intent to deceive. We also provide a large-scale analysis to describe user behavior and spread patterns while engaging with deceptive content and report novel findings about the immediate diffusion of deceptive content by characterizing the vulnerable sub-populations and their demographics, and explicitly measuring speed and scale of deception spread to uncover who shares deceptive content, how quickly, how much, and how evenly. In addition, we measure audience reactions to misinformation and disinformation at scale, distinguishing the reactions of users identified as bots versus humans. Finally, we take advantage of deep translation and generation models to create unique solutions for real-time defense against digital deception and discuss how to apply causal inference to prescribe and intervene into strategic communications jointly across information, cognitive, and physical domains.

artificial intelligence, deep learning, neural lan↗

DOE OSTI2021

Tonal Emergence: An agent-based model of tonal coordination

Humans have a remarkable capacity for coordination. Our ability to interact and act jointly in groups is crucial to our success as a species. Joint Action (JA) research has often concerned itself with simplistic behaviors in highly constrained laboratory tasks. But there has been a growing interest in understanding complex coordination in more open-ended contexts. In this regard, collective music improvisation has emerged as a fascinating model domain for studying basic JA mechanisms in an unconstrained and highly sophisticated setting. A number of empirical studies have begun to elucidate coordination mechanisms underlying joint musical improvisation, but these empirical findings have yet to be cached out in a working computational model. The present work fills this gap by presenting TonalEmergence, an idealized agent-based model of improvised musical coordination. TonalEmergence models the coordination of notes played by improvisers to generate harmony (i.e., tonality), by simulating agents that stochastically generate notes biased towards maximizing harmonic consonance given their partner’s previous notes. Here, the model replicates an interesting empirical result from a previous study of professional jazz pianists: feedback loops of mutual adaptation between interacting agents support the production of consonant harmony. The model is further explored to show how complex tonal dynamics, such as the production and dissolution of stable tonal centers, are supported by agents that are characterized by (i) a tendency to strive toward consonance, (ii) stochasticity, and (iii) a limited memory for previously played notes. TonalEmergence thus provides a grounded computational model to simulate and probe the coordination mechanisms underpinning one of the more remarkable feats of human cognition: collective music improvisation.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2024

Non-DNA radiosensitive targets that initiate persistent behavioral deficits in rats exposed to space radiation

Predicting future CNS risks for astronauts during deep-space missions will rely substantially on ground-based rodent data with space-relevant ions and behaviors. For rats, the accumulated evidence indicates that less densely ionizing radiation, such as 4 He and 12 C ions, induce behavior deficits at lower doses than densely ionizing ions, such as 48 Ti and 56 Fe. However, this observation conflicts with standard somatic radiobiology, in which densely ionizing ions are generally more effective than less densely ionizing ions, and where the DNA/nucleus is the accepted target for radiation-induced tumorigenesis, cytogenetic aberrations, genetic mutations, and reproductive cell death. To gain deeper insight into the subcellular nature of the radiation targets for behavior risks, we compared the effects of dose, fluence, and linear energy transfer (LET) of 4 He and 56 Fe particles using existing datasets for four distinct behavioral outcomes in rats: elevated plus maze (EPM-anxiety), novel object recognition (NOR-memory), operant responding (OR-response to environmental stimuli), and attentional set-shifting (ATSET-cognitive flexibility). We confirmed that less densely ionizing particles (except protons) showed ~100-fold lower threshold doses than densely ionizing particles for behavioral deficits (0.1–1 cGy for 4 He vs. 15–100 cGy for 56 Fe). However, when analyzed by fluence the behavioral responses converged, indicating that 4 He and 56 Fe were equally effective on a per-track basis. When analyzed by LET, there were ~100-fold differences in the LET for maximum effectiveness for behavioral deficits and DNA endpoints (~1 vs ~100 keV/μm, respectively). These unique features of radiation-induced behavioral deficits (high sensitivity to particles in the 1-keV/μm range, insensitivity to protons in the 0.2 keV/μm range, and isofluence dependence for particles with LET>1 keV/μm) provide evidence in support of a new hypothesis of sub-micron sized radiosensitive targets for behavioral effects consistent with the thickness of plasma membranes and/or small subcellular structures, smaller than a whole synapse. Like our behavior findings, mouse immature oocyte killing which is known to have a plasma membrane target was also better explained by fluence, rather than dose. In contrast, fluence analyses for DNA/nuclear endpoints in somatic cells (e.g., tumor induction, chromosome aberrations) showed opposite results, suggesting that behavior targets are not DNA. Our findings raise questions regarding the identity of subcellular targets and the multi-cellular functional unit for behavior risks, low-dose susceptibility, and generalizability from rat to other species and astronauts.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

DOE OSTI2025

Subventricular Accumulation of Cu in the Aging Mouse Brain Does Not Associate with Anticipated Increases in Markers of Oxidative Stress

Natural aging is associated with mild memory loss and cognitive decline, and age is the greatest risk factor for neurodegenerative diseases, such as Alzheimer’s disease. There is substantial evidence that oxidative stress is a major contributor to both natural aging and neurodegenerative disease, and coincidently, levels of redox active metals such as Fe and Cu are known to be elevated later in life. Recently, a pronounced age-related increase in Cu content has been reported to occur in mice and rats around a vital regulatory brain region, the subventricular zone of lateral ventricles. In our study herein, we have characterized lateral ventricle Cu content in a unique murine model of accelerated aging, senescence accelerated mouse-prone 8 (SAMP8) mice. Our results confirm an age-related increase in ventricle Cu content, consistent with the studies by others in wild-type mice and rats. Specifically, we observed Cu content to increase over the time frame 1 to 5 months and 5 to 9 months, but interestingly, no significant increase occurred between 9 and 12 months (although brain Cu content at 12 months was significantly elevated relative to 1 and 5 month-old animals). Despite the magnitude of Cu increase observed within the cells that comprise the subventricular zone of lateral ventricles (average 3 mM Cu, with isolated subcellular concentrations of 17 mM), we did not detect spectroscopic markers of thiol oxidation, protein aggregation, or lipid oxidation. The lack of evidence for oxidative stress in ex vivo animal tissue is in contrast to in vitro studies demonstrating that thiol, protein, and lipid oxidation is pronounced at these Cu concentrations. We suggest that our findings most likely indicate that the Cu ions in this brain region are sequestered in an unreactive form, possibly extended chains of Cu-thiolate complexes, which do not readily redox cycle in the aqueous cytosol. In conclusion, these results also appear to partially challenge the long-held view that age-related increases in brain metal content drive oxidative stress as we did not observe a concomitant association between age-related Cu increase and markers of oxidative stress, nor did we observe a net increase in Cu content between mice aged 9 and 12 months.

X-ray fluorescence↗

DOE OSTI2021

Usability Evaluation of the Innovation Portal and Integrated Capability Analysis Platform

The usability evaluation of the ICAP and IP tools was conducted as part of the United States (U.S.) Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) ION effort with two evaluators for the Idaho National Laboratory. Many nuclear operations in the United States are facing challenges of increased business, operations, and maintenance costs due to subsidized renewables and natural gas. The commercial NPP industry has looked to other industries to develop methods such as Integrated Operations (IO) to use available technologies to reduce operating costs. One concept for reducing costs that has been developed is the Integrated Operations for Nuclear (ION). A capability Stack model was developed as part of the ION effort to break down information related to People, Technology, Processes, and Governance (PTPG). The Innovation Portal (IP) and Integrated Capability Analysis Platform (ICAP) were created from the Capability Stack model as part of the ION effort to help utilities reduce O&M costs by identifying work reduction opportunities. Two heuristic evaluations and a cognitive walkthrough of the ICAP and IP tools were completed to identify usability issues to further develop the tools for use in the ION effort. Usability issues identified were rated by priority levels and across both tools. The priority levels identified were high (5), medium (11), and low (10). Recommendation were made to help reduce usability issues of the systems and help increase the user response rate of using the systems once they are implemented for utilities. Future work on designs for the IP tool and additional heuristic evaluations and external testing are being developed to continue refinement of the ICAP and IP tools for the ION effort.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗