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NASA NTRS2001

HZE particle radiation induces tissue-specific and p53-dependent mutagenesis in transgenic animals

Transgenic animals, with the integrated target gene, provide a unique approach for measuring and characterizing mutations in any tissue of the animal. We are using the plasmid-based lacZ transgenic mice with different p53 genetic background to examine radiation-induced genetic damage resulting from exposure to heavy particle radiation. We measured lacZ mutation frequencies (MF) in the brain and spleen tissues at various times after exposing animals to an acute dose of 1 Gy of 1GeV/amu iron particles. MF in the spleen of p53+/+ animals increased up to 2.6-fold above spontaneous levels at 8 weeks post irradiation. In contrast, brain MF from the same animals increased 1.7-fold above controls in the same period. In the p53-/- animals, brain MF increased to 2.2-fold above spontaneous levels at 1 week after treatment, but returned to control levels thereafter. Radiation also induced alterations in the spectrum of mutants in both tissues, accompanied by changes in the frequency of mutants with deletions extending past the transgene into mouse genomic DNA. Our results indicate that the accumulation of transgene MF after radiation exposure is dependant on the tissue examined as well as the p53 genetic background of the animals.

Non-NASA Center↗

NASA NTRS1997

Cosmic Ray Hits in the Central Nervous System at Solar Maximum

It has been suggested that a manned mission to Mars be launched at solar maximum rather than at solar minimum to minimize the radiation exposure to galactic cosmic rays. It is true that the number of hits from highly ionizing particles to critical regions in the brain will be less at solar maximum, and it is of some interest to estimate how much less. We present here calculations for several sites within the brain from iron ions (z = 26) and from particles with charge, z, greater than or equal to 15. The same shielding configurations and sites in the brain used in an earlier paper for solar minimum are employed so that direct comparison of results between the two solar activity conditions can be made. A simple pressure-vessel wall and an equipment room onboard a spacecraft are chosen as shielding examples. In the equipment room, typical results for the thalamus (100 mm2 area) are that the probability of any given cell nucleus being hit decreases from 10 percent at solar minimum to 6 percent at solar maximum for particles with z greater than or equal to 15 and from 2.3 percent to 1.3 percent for iron ions. We conclude that this modest decrease in hit frequency (less than a factor of two) is not a compelling reason to avoid solar minimum for a manned mission to Mars.

Curtis, S. B.↗

NASA NTRS1998

Role of heat shock protein Hsp25 in the response of the orofacial nuclei motor system to physiological stress

Although expression of the small heat shock protein family member Hsp25 has been previously observed in the central nervous system (CNS), both constitutively and upon induction, its function in the CNS remains far from clear. In the present study we have characterized the spatial pattern of expression of Hsp25 in the normal adult mouse brain as well as the changes in expression patterns induced by subjecting mice to experimental hyperthermia or hypoxia. Immunohistochemical analysis revealed a surprisingly restricted pattern of constitutive expression of Hsp25 in the brain, limited to the facial, trigeminal, ambiguus, hypoglossal and vagal motor nuclei of the brainstem. After hyperthermia or hypoxia treatment, significant increases in the levels of Hsp25 were observed in these same areas and also in fibers of the facial and trigeminal nerve tracts. Immunoblot analysis of protein lysates from brainstem also showed the same pattern of induction of Hsp25. Surprisingly, no other area in the brain showed expression of Hsp25, in either control or stressed animals. The highly restricted expression of Hsp25 implies that this protein may have a specific physiological role in the orofacial motor nuclei, which govern precise coordination between muscles of mastication and the pharynx, larynx, and face. Its rapid induction after stress further suggests that Hsp25 may serve as a specific molecular chaperone in the lower cholinergic motor neurons and along their fibers under conditions of stress or injury. Copyright 1998 Elsevier Science B.V.

Non-NASA Center↗

NASA NTRS1993

The chronic infusion of nicotine into the developing chick embryo does not alter the density of (-)-[3H]nicotine-binding sites or vestibular function

(-)-Nicotine (1.2 mg/day) or saline was infused into chick embryos (Gallus domesticus) for 10 days beginning 12 h beyond the eight day of incubation (E8 + 12 h). Twelve h beyond the eighteenth day of incubation (E18 + 12 h), the eggs were opened to access the embryos and subcutaneous skull electrodes placed. Short latency vestibular response thresholds and input/output functions were determined to assess neurophysiological consequences of chronic nicotine administration. Samples of serum and extraembryonic (amniotic and albumen) fluid were analyzed by gas chromatography-mass spectrometry to determine the levels of nicotine and its major metabolite, cotinine. The brains were removed and divided into diencephalon and mesencephalon and the density of (-)-[3H]nicotine binding sites in each brain area was measured. Nicotine and cotinine were found in the serum and extraembryonic fluid, but nicotinic receptors were not up-regulated in the brains of animals infused with nicotine in comparison to controls. Vestibular response thresholds also did not differ between nicotine-treated and control animals.

NASA Discipline Neuroscience↗

NASA NTRS2004

Hematopoietic Stem Cell Therapy to Countermeasure Cancer in Astronauts during Exploration of Deep Space

Exposure to cosmic radiation can cause chromosomal mutations, which may lead to cancer in astronauts engaged in space exploration. Therefore, our goals are to develop countermeasures to prevent space-induced cancer using hematopoietic stem cell therapy (HSCT) and gene therapy. This presentation focuses on HSCT for cancer. Our previous experiments on a simulated, space-induced immuno-deficiency model (mouse hind limb unloading ) indicated that transplanted hematopoietic stem cells (HSCs) could enhance the host's immunity by effectively eliminating bacterial infection (Ohi S, et. al. J Grav Physiol 10, P63-64, 2003; Ohi S, et. al. Proceedings of the Space Technology and Applications International Forum (STAIF) . American Institute of Physics, New York, pp. 938-950, 2004). Hence, we hypothesized that the HSCs might be effective in combating cancer as well. Studies of cocultured mouse HSCs with beta-galactosidase marked rat gliosarcoma spheroids (9L/lacZ), a cancer model, indicated antagonistic interactions , resulting in destruction of the spheroids by HSCs. Trypan Blue dye-exclusion assays were consistent with the conclusion. These results show potential usehlness of HSCT for cancer. Currently, the NASA Hydrodynamic Focusing Bioreactor (HFB), a space analog tissue/cell culture system, is being used to study invasion of the gliosarcoma (GS) spheroids into mouse brain with or without co-cultured HSCs. This may simulate the metastasis of gliosarcoma to brain. There is a tendency for the HSCs to inhibit invasion of GS spheroids into brain, as evidenced by the X-gal staining.

Ohi, S.↗

NASA NTRS2005

Coping with Trial-to-Trial Variability of Event Related Signals: A Bayesian Inference Approach

In electro-neurophysiology, single-trial brain responses to a sensory stimulus or a motor act are commonly assumed to result from the linear superposition of a stereotypic event-related signal (e.g. the event-related potential or ERP) that is invariant across trials and some ongoing brain activity often referred to as noise. To extract the signal, one performs an ensemble average of the brain responses over many identical trials to attenuate the noise. To date, h s simple signal-plus-noise (SPN) model has been the dominant approach in cognitive neuroscience. Mounting empirical evidence has shown that the assumptions underlying this model may be overly simplistic. More realistic models have been proposed that account for the trial-to-trial variability of the event-related signal as well as the possibility of multiple differentially varying components within a given ERP waveform. The variable-signal-plus-noise (VSPN) model, which has been demonstrated to provide the foundation for separation and characterization of multiple differentially varying components, has the potential to provide a rich source of information for questions related to neural functions that complement the SPN model. Thus, being able to estimate the amplitude and latency of each ERP component on a trial-by-trial basis provides a critical link between the perceived benefits of the VSPN model and its many concrete applications. In this paper we describe a Bayesian approach to deal with this issue and the resulting strategy is referred to as the differentially Variable Component Analysis (dVCA). We compare the performance of dVCA on simulated data with Independent Component Analysis (ICA) and analyze neurobiological recordings from monkeys performing cognitive tasks.

Ding, Mingzhou↗

NASA NTRS2005

Journal of Gravitational Physiology, Volume 12, Number 1

The following topics were covered: System Specificity in Responsiveness to Intermittent -Gx Gravitation during Simulated Microgravity in Rats; A Brief Overview of Animal Hypergravity Studies; Neurovestibular Adaptation to Short Radius Centrifugation; Effect of Artificial Gravity with Exercise Load by Using Short-Arm Centrifuge with Bicycle Ergometer as a Countermeasure Against Disused Osteoporosis; Perception of Body Vertical in Microgravity during Parabolic Flight; Virtual Environment a Behavioral and Countermeasure Tool for Assisted Gesture in Weightlessness: Experiments during Parabolic Flight; Artificial Gravity: Physiological Perspectives for Long-Term Space Exploration; Comparison of the Effects of DL-threo-Beta-Benzyloxyaspartate on the Glutamate Release from Synaptosomes before and after Exposure of Rats to Artificial Gravity; Do Perception and Postrotatory Vestibulo-Ocular Reflex Share the Same Gravity Reference?; Vestibular Adaptation to Changing Gravity Levels and the Orientation of Listing's Plane; Compound Mechanism Hypothesis on +Gz - Induced Brain Injury and Dysfunction of Learning and Memory; Environmental Challenge Impairs Prefrontal Brain Functions; Effect of 6-Days of Support Withdrawal on Characteristics of Balance Function; Hypergravity-Induced Changes of Neuronal Activities in CA1 Region of Rat Hippocampus; Audiological Findings in Antiorthostatic Position Modelling Microgravitation; Investigating Human Cognitive Performance during Spaceflight; The Relevance of the Minimization of Torque Exchange with the Environment in Weightlessness is Confirmed by Asimulation Study; Characteristics of the Eyes Pursuit Function during Readaptation to Terrestrial Gravity after Prolonged Flights Aboard the International Space Station; Comparison of Cognitive Performance Tests for Promethazine Pharmacodynamics in Human Subjects; Structural Reappraisal of Dendritic Tree of Cerebellar Purkinje Cell for Novel Functional Modeling of Elementary Sensorimotor Adaptive Processes; Orpheus 0 G or Ear in Microgravity to Establish Symptoms Concomittant of Inner and Middle Ear and Osteoporosis in Microgravity; Understanding Visual Perception in the Perspective of Gravity; Cortical Regions Associated with Orthostatic Stress in Conscious Humans; Restoration of Central Blood Volume: Application of a Simple Concept and Simple Device to Counteract Cardiovascular Instability in Syncope and Hemorrhage; WISE-2005: Integrative Cardiovascular Responses with LBNP during 60-Day Bed Rest in Women; Intracranial Pressure Increases during Weightlessness. A Parabolic Flights Study; Lower Limb & Portal Veins Echography for Predicting Risk of Thrombosis during a 90-D Bed Rest; Calf Tissue Liquid Stowage and Muscular and Deep Vein Distension in Orthostatic Tests after a 90-Day Head Down Bed Rest; Morphology of Brain Vessels in the Tail Suspended Rats Exposed to Intermittent 2 G; Alterations in Vasoreactivity of Femoral Artery Induced by Hindlimb Unweighting are Related to the Changes of Contractile Protein in Rats; and Respiratory Sinus Arrhythmia: A Marker of Decreased Parasympathetic Modulation after Short Duration.

Fuller, Charles A.↗

NASA NTRS2005

Insect-Inspired Flight Control for Unmanned Aerial Vehicles

Flight-control and navigation systems inspired by the structure and function of the visual system and brain of insects have been proposed for a class of developmental miniature robotic aircraft called "biomorphic flyers" described earlier in "Development of Biomorphic Flyers" (NPO-30554), NASA Tech Briefs, Vol. 28, No. 11 (November 2004), page 54. These form a subset of biomorphic explorers, which, as reported in several articles in past issues of NASA Tech Briefs ["Biomorphic Explorers" (NPO-20142), Vol. 22, No. 9 (September 1998), page 71; "Bio-Inspired Engineering of Exploration Systems" (NPO-21142), Vol. 27, No. 5 (May 2003), page 54; and "Cooperative Lander-Surface/Aerial Microflyer Missions for Mars Exploration" (NPO-30286), Vol. 28, No. 5 (May 2004), page 36], are proposed small robots, equipped with microsensors and communication systems, that would incorporate crucial functions of mobility, adaptability, and even cooperative behavior. These functions are inherent to biological organisms but are challenging frontiers for technical systems. Biomorphic flyers could be used on Earth or remote planets to explore otherwise difficult or impossible to reach sites. An example of an exploratory task of search/surveillance functions currently being tested is to obtain high-resolution aerial imagery, using a variety of miniaturized electronic cameras. The control functions to be implemented by the systems in development include holding altitude, avoiding hazards, following terrain, navigation by reference to recognizable terrain features, stabilization of flight, and smooth landing. Flying insects perform these and other functions remarkably well, even though insect brains contains fewer than 10(exp -4) as many neurons as does the human brain. Although most insects have immobile, fixed-focus eyes and lack stereoscopy (and hence cannot perceive depth directly), they utilize a number of ingenious strategies for perceiving, and navigating in, three dimensions. Despite their lack of stereoscopy, insects infer distances to potential obstacles and other objects from image motion cues that result from their own motions in the environment. The concept of motion of texture in images as a source of motion cues is denoted generally as the concept of optic or optical flow. Computationally, a strategy based on optical flow is simpler than is stereoscopy for avoiding hazards and following terrain. Hence, this strategy offers the potential to design vision-based control computing subsystems that would be more compact, would weigh less, and would demand less power than would subsystems of equivalent capability based on a conventional stereoscopic approach.

Thakoor, Sarita↗

NASA NTRS2014

Customizing Countermeasure Prescriptions using Predictive Measures of Sensorimotor Adaptability

Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the readapation phase following a return to a gravitational environment. These alterations may lead to disruption in the ability to perform mission critical functional tasks during and after these gravitational transitions. Astronauts show significant inter-subject variation in adaptive capability following gravitational transitions. The ability to predict the manner and degree to which each individual astronaut will be affected would improve the effectiveness of a countermeasure comprised of a training program designed to enhance sensorimotor adaptability. Due to this inherent individual variability we need to develop predictive measures of sensorimotor adaptability that will allow us to predict, before actual space flight, which crewmember will experience challenges in adaptive capacity. Thus, obtaining this information will allow us to design and implement better sensorimotor adaptability training countermeasures that will be customized for each crewmember's unique adaptive capabilities. Therefore the goals of this project are to: 1) develop a set of predictive measures capable of identifying individual differences in sensorimotor adaptability, and 2) use this information to design sensorimotor adaptability training countermeasures that are customized for each crewmember's individual sensorimotor adaptive characteristics. To achieve these goals we are currently pursuing the following specific aims: Aim 1: Determine whether behavioral metrics of individual sensory bias predict sensorimotor adaptability. For this aim, subjects perform tests that delineate individual sensory biases in tests of visual, vestibular, and proprioceptive function. Aim 2: Determine if individual capability for strategic and plastic-adaptive responses predicts sensorimotor adaptability. For this aim, each subject's strategic and plastic-adaptive motor learning abilities are assessed using a test of locomotor function designed specifically to delineate both mechanisms. Aim 3: Develop predictors of sensorimotor adaptability using brain structural and functional metrics. We will measure individual differences in regional brain volumes (structural MRI), white matter integrity (diffusion tensor imaging, or DTI), functional network integrity (resting state functional connectivity MRI), and sensorimotor adaptation task-related functional brain activation (functional MRI). We decided to complete the data collection for Specific Aims 1, 2 and 3 simultaneously on the same subjects to increase data capture. By having the same subjects perform all three specific aims we can enhance our ability to detect how a wider range of factors can predict adaptability in a specific individual. This provides a much richer database and potentially a better understanding of the predictive power of the selected factors. In this presentation I will discuss preliminary data obtained to date.

Bloomberg, J. J.↗

NASA NTRS2014

Focal Gray Matter Plasticity as a Function of Long Duration Head Down Tilted Bed Rest: Preliminary Results

Long duration spaceflight (i.e., 22 days or longer) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. The microgravity environment is an important causal factor for spaceflight induced sensorimotor changes. Whether these sensorimotor changes are solely related to peripheral changes from reduced vestibular stimulation, body unloading, body fluid shifts or that they may be related to structural and functional brain changes is yet unknown. However, a recent study reported associations between microgravity and flattening of the posterior eye globe and protrusion of the optic nerve [1] possibly as the result of increased intracranial pressure due to microgravity induced bodily fluid shifts [3]. Moreover, elevated intracranial pressure has been related to white matter microstructural damage [2]. Thus, it is possible that spaceflight may affect brain structure and thereby cognitive functioning. Long duration head down tilt bed rest has been suggested as an exclusionary analog to study microgravity effects on the sensorimotor system [4]. Bed rest mimics microgravity in body unloading and bodily fluid shifts. In consideration of the health and performance of crewmembers both in- and post-flight, we are conducting a prospective longitudinal 70-day bed rest study as an analog to investigate the effects of microgravity on brain structure [5]. Here we present results of the first six subjects. Six subjects were assessed at 12 and 7 days before-, at 7, 30, and ~70 days in-, and at 8 and 12 days post 70 days of bed rest at the NASA bed rest facility in UTMB, Galveston, TX, USA. At each time point structural MRI scans (i.e., high resolution T1-weighted imaging and Diffusion Tensor Imaging (DTI)) were obtained using a 3T Siemens scanner. Focal changes over time in gray matter density were assessed using the voxel based morphometry 8 (VBM8) toolbox under SPM. Longitudinal processing in VBM8 includes linear registration of each scan to the mean of the subject and subsequently transforming all scans in to MNI space by applying the warp from the mean subject to MNI to the individual gray matter segmentations. Modulation was applied so that all images represented the volume of the original structure in native space. Voxel wise analysis was carried out on the gray matter images after smoothing, using a flexible factorial design with family wise error correction. Focal changes in white matter microstructural integrity were assessed using tract based spatial statistics (TBSS) as part of FMRIB software library (FSL). TBSS registers all DTI scans to standard space. It subsequently creates a study specific white matter skeleton of the major white matter tracts. For each subject, for each DTI metric (i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)), the maximum value in a line perpendicular to the skeleton tract is projected to the skeleton. Non-parametric permutation based t-tests and ANOVA's were used for voxel-wise comparison of the skeletons. For both VBM and TBSS, comparison of pre bed rest measurements did not show significant differences. VBM analysis revealed decreased gray matter density in bilateral areas including the frontal medial cortex, the insular cortex and the caudate (see Figure) from 'pre to in bed rest'. Over the same time period, there was an increase in gray matter density in the cerebellum, occipital-, and parietal cortex, including the precuneus (see Figure). The majority of these changes did not recover from 'during to post bed rest'. TBSS analysis did not reveal significant changes in white matter microstructural integrity after correction for multiple comparisons. Uncorrected analyses (p<.015) revealed an increase in RD in the cerebellum and brainstem from pre bed rest to the first week in bed rest that did not recover post bed rest. Extended bed rest, which is an analog for microgravity, can result in gray matter changes and potentially in microstructural white matter changes in areas that are important for neuro motor behavior and cognition. These changes did not recover at two weeks post bed rest. Whether the effects of bed rest wear off at longer times post bed rest, and if they are associated with behavior are important questions that warrant further research.

Koppelmans, V.↗

NASA NTRS2014

Focal Gray Matter Plasticity as a Function of Long Duration Bedrest: Preliminary Results

Long duration spaceflight (i.e., 22 days or longer) has been associated with changes in sensorimotor systems, resulting in difficulties that astronauts experience with posture control, locomotion, and manual control. It is unknown whether and how spaceflight impacts sensorimotor brain structure and function, and whether such changes may potentially underlie behavioral effects. Long duration head down tilt bed rest has been used repeatedly as an exclusionary analog to study microgravity effects on the sensorimotor system [1]. Bed rest mimics microgravity in body unloading and bodily fluid shifts. We are currently testing sensorimotor function, brain structure, and brain function pre and post a 70‐day bed rest period. We will acquire the same measures on NASA crewmembers starting in 2014. Here we present the results of the first eight bed rest subjects. Subjects were assessed at 12 and 7 days before‐, at 7, 30, and ~70 days in‐, and at 8 and 12 days post 70 days of bed rest at the NASA bed rest facility, UTMB, Galveston, TX, USA. At each time point structural MRI scans (i.e., high resolution T1‐weighted imaging and Diffusion Tensor Imaging (DTI)) were obtained using a 3T Siemens scanner. Focal changes over time in gray matter density were assessed using the voxel based morphometry 8 (VBM8) toolbox under SPM. Focal changes in white matter microstructural integrity were assessed using tract based spatial statistics (TBSS) as part of the FMRIB software library (FSL). TBSS registers all DTI scans to standard space. It subsequently creates a study specific white matter skeleton of the major white matter tracts. Non‐parametric permutation based t‐tests and ANOVA's were used for voxel‐wise comparison of the skeletons. For both VBM and TBSS, comparison of the two pre bed rest measurements did not show significant differences. VBM analysis revealed decreased gray matter density in bilateral areas including the frontal medial cortex, the insular cortex and the caudate nucleus from pre to in bed rest. Over the same time period, there was an increase in gray matter density in the cerebellum, occipital, and parietal cortices. The majority of these changes did not recover from during to post bed rest. TBSS analyses will also be presented. Extended bed rest, which is an analog for microgravity, can result in gray matter changes and potentially in microstructural white matter changes in areas that are important for neuromotor behavior and cognition. These changes did not recover at two weeks post bed rest. These results have significant public health implications, and will also aid in interpretation of our future data obtained pre and post spaceflight. Whether the effects of bed rest wear off at longer times post bed rest, and if they are associated with behavior are important questions that warrant further research.

Koppelmans, V.↗

NASA NTRS2014

Focal Gray Matter Plasticity as a Function of Long Duration Head-down Tilt Bed Rest

Koppelmans, Vincent↗

NASA NTRS2015

Evalution of a DE-Identification Process for Ocular Imaging

Medical privacy of NASA astronauts requires an organized and comprehensive approach when data are being made available outside NASA systems. A combination of factors, including the uniquely small patient population, the extensive medical testing done on these individuals, and the relative cultural popularity of the astronauts puts them at a far greater risk to potential exposure of personal information than the general public. Therefore, care must be taken to ensure that the astronauts' identities are concealed. Magnetic Resonance Imaging (MRI) medical data is a recent source of interest to researchers concerned with the development of Visual Impairment due to Intracranial Pressure (VIIP) in the astronaut population. Each vision MRI scan of an astronaut includes 176 separate sagittal images that are saved as an "image series" for clinical use. In addition to the medical information these image sets provide, they also inherently contain a substantial amount of non-medical personally identifiable information (PII) such as-name, date of birth, and date of exam. We have shown that an image set of this type can be rendered, using free software, to give an accurate representation of the patient's face. This currently restricts NASA from dispensing MRI data to researchers in a deidentified format. Automated software programs, such as the Brain Extraction Tool, are available to researchers who wish to de-identify MRI sagittal brain images by "erasing" identifying characteristics such as the nose and jaw on the image sets. However, this software is not useful to NASA for vision research because it removes the portion of the images around the eye orbits, which is the main area of interest to researchers studying the VIIP syndrome. The Lifetime Surveillance of Astronaut Health program has resolved this issue by developing a protocol to de-identify MRI sagittal brain images using Showcase Premier, a DICOM (Digital Imaging and Communications in Medicine) software package. The software allows manual editing of one image from a patient's image set to be automatically applied to the entire image series. This new approach would allow a new level of access to untapped medical imaging data relating to VIIP that can be utilized by researchers while protecting the privacy of the astronauts. In the next step toward finalizing this technique, NASA clinical radiology consultants will test the images to verify removal of all metadata and PII.

LaPelusa, Michael B.↗

NASA NTRS2016

Process for Upgrading Cognitive Assessment Capabilities Onboard the International Space Station

MOTIVATION: Spaceflight poses varied and unique risks to the brain and cognitive functioning including radiation exposure, sleep disturbance, fatigue, fluid shifts (increased intracranial pressure), toxin exposure, elevated carbon dioxide, and traumatic brain injury, among others. These potential threats to cognitive functioning are capable of degrading performance and compromising mission success. Furthermore, the threats may increase in severity, and new types of threats may emerge for longer duration exploration missions. This presentation will describe the process used to identify gaps in our current approach, evaluate best practices in cognitive assessment, and transition new cognitive assessment tools to operational use. OVERVIEW: Risks to brain health and performance posed by spaceflight missions require sensitive tools to assess cognitive functioning of astronauts in flight. The Spaceflight Cognitive Assessment Tool for Windows (WinSCAT) is the automated cognitive assessment tool currently deployed onboard the International Space Station (ISS). WinSCAT provides astronauts and flight surgeons with objective data to monitor neurocognitive functioning. WinSCAT assesses 5 discrete cognitive domains, is sensitive to changes in cognitive functioning, and was designed to be completed in less than 15 minutes. However, WinSCAT does not probe other areas of cognitive functioning that might be important to mission success. Researchers recently have developed batteries that may expand current capabilities, such as increased sensitivity to subtle fluctuations in cognitive functioning. Therefore, we engaged in a systematic process review in order to improve upon our current capabilities and incorporate new advances in cognitive assessment. This process included a literature review on newer measures of neurocognitive assessment, surveys of operational flight surgeons at NASA regarding needs and gaps in our capabilities, and expert panel review of candidate cognitive measures and assessment issues and procedures. SIGNIFICANCE: Our process and the results that flowed from it may be helpful to aeromedical professionals charged with transitioning research findings to operational use. Our specific findings regarding cognitive assessment tools are of significance to professionals who must assess readiness to perform in mission critical situations in environments involving threats to cognition and performance

Picano, J. J.↗

NASA NTRS2016

Holodeck Testbed Project

The main objective of the Holodeck Testbed is to create a cost effective, realistic, and highly immersive environment that can be used to train astronauts, carry out engineering analysis, develop procedures, and support various operations tasks. Currently, the Holodeck testbed allows to step into a simulated ISS (International Space Station) and interact with objects; as well as, perform Extra Vehicular Activities (EVA) on the surface of the Moon or Mars. The Holodeck Testbed is using the products being developed in the Hybrid Reality Lab (HRL). The HRL is combining technologies related to merging physical models with photo-realistic visuals to create a realistic and highly immersive environment. The lab also investigates technologies and concepts that are needed to allow it to be integrated with other testbeds; such as, the gravity offload capability provided by the Active Response Gravity Offload System (ARGOS). My main two duties were to develop and animate models for use in the HRL environments and work on a new way to interface with computers using Brain Computer Interface (BCI) technology. On my first task, I was able to create precise computer virtual tool models (accurate down to the thousandths or hundredths of an inch). To make these tools even more realistic, I produced animations for these tools so they would have the same mechanical features as the tools in real life. The computer models were also used to create 3D printed replicas that will be outfitted with tracking sensors. The sensor will allow the 3D printed models to align precisely with the computer models in the physical world and provide people with haptic/tactile feedback while wearing a VR (Virtual Reality) headset and interacting with the tools. Getting close to the end of my internship the lab bought a professional grade 3D Scanner. With this, I was able to replicate more intricate tools at a much more time-effective rate. The second task was to investigate the use of BCI to control objects inside the hybrid reality ISS environment. This task looked at using an Electroencephalogram (EEG) headset to collect brain state data that could be mapped to commands that a computer could execute. On this Task, I had a setback with the hardware, which stopped working and was returned to the vendor for repair. However, I was still able to collect some data, was able to process it, and started to create correlation algorithms between the electrical patterns in the brain and the commands we wanted the computer to carry out. I also carried out a test to investigate the comfort of the headset if it is worn for a long time. The knowledge gained will benefit me in my future career. I learned how to use various modeling and programming tools that included Blender, Maya, Substance Painter, Artec Studio, Github, and Unreal Engine 4. I learned how to use a professional grade 3D scanner and 3D printer. On the BCI Project I learned about data mining and how to create correlation algorithms. I also supported various demos including a live demo of the hybrid reality lab capabilities at ComicPalooza. This internship has given me a good look into engineering at NASA. I developed a more thorough understanding of engineering and my overall confidence has grown. I have also realized that any problem can be fixed, if you try hard enough, and as an engineer it is your job to not only fix problems but to embrace coming up with solutions to those problems.

Arias, Adriel↗

NASA NTRS2016

Dynamic Filtering Improves Attentional State Prediction with fNIRS

Brain activity can predict a person's level of engagement in an attentional task. However, estimates of brain activity are often confounded by measurement artifacts and systemic physiological noise. The optimal method for filtering this noise - thereby increasing such state prediction accuracy - remains unclear. To investigate this, we asked study participants to perform an attentional task while we monitored their brain activity with functional near infrared spectroscopy (fNIRS). We observed higher state prediction accuracy when noise in the fNIRS hemoglobin [Hb] signals was filtered with a non-stationary (adaptive) model as compared to static regression (84% +/- 6% versus 72% +/- 15%).

Harrivel, Angela R.↗

NASA NTRS2019

Effects of Altered Gravity on the Central Nervous System of Drosophila melanogaster

A comprehensive understanding of the effects of spaceflight and altered gravity on human physiology is necessary for continued human space exploration and long-term space habitation. Spaceflight includes multiple factors such as microgravity, hypergravity, ionizing radiation, physiological stress, and disrupted circadian rhythms and these have been shown to contribute to pathophysiological responses that target immunity, bone and muscle integrity, cardiovascular and nervous systems. In terrestrial conditions, some of these factors can lead to cancer and neuroimmunological disorders. In this study, we used a well-established spaceflight model organism, Drosophila melanogaster, to assess spaceflight-associated changes in the nervous system. We hypothesize that exposure to altered gravity triggers the oxidative stress response, leading to impairments in the nervous system. To test this hypothesis, we used two experimental paradigms: 1) hypergravity, using the ground-based chronic acceleration model, and 2) spaceflight conditions, which includes exposure to microgravity and in-flight space 1g controls. In our ground studies, acute hypergravity resulted in an induction of oxidative stress-related genes with an increase in reactive oxygen species (ROS) in fly brains. Additionally, we observed a depressed locomotor phenotype in these flies (p<0.05). These flies also show a decreased dopaminergic neuron counts in the fly brain upon exposure to acute hypergravity (p<0.05). Thus, the data suggest that altered gravity has a profound effect on the fly nervous system. Similarly, we observe behavioral impairments (p<0.001) and synaptic deficits, including decreased synaptic connections (p<0.05), in 3rd instar larvae which were developed in space. Furthermore, space-grown adults show a decrease in neuronal (p<0.05) and dendritic field (p<0.01) in adult brains coupled with an increased number of apoptotic cells (p<0.001), suggesting increased neuronal loss under spaceflight conditions. In summary, we observe that altered gravity leads to gross neurological deficits. To better understand the long-term effects of spaceflight on the nervous system, longitudinal and multigenerational changes were also identified. This study will help elucidate the different approaches to prevent nervous system dysfunction in astronauts during spaceflight, while also contributing to a better understanding of the pathways that are related to some CNS disorders on Earth.

nervous system↗

NASA NTRS2019

Evaluating Effects of Altered Gravity on the Nervous System Using D. melanogaster

A comprehensive understanding of the effects of spaceflight and altered gravity on human physiology is necessary for continued human space exploration and long-term space habitation. The oxidative stress response has been identified in astronauts exposed to short- and long-term space missions that are exposed to the multitude of stress factors of spaceflight, including altered gravity and radiation exposure. Reactive oxygen species (ROS) are byproducts of homeostatic cellular metabolism, yet when overproduced the oxidative stress response ensues, rendering molecules destructive causing cell death and inflammation. Controlling aberrant ROS production is necessary to prevent pathological consequences, in particular within the nervous system, since neurons are extremely sensitive overexpressed ROS insults. We hypothesize that exposure to altered gravity triggers the oxidative stress response, leading to impairments in the nervous system. In this study, we used a well-established spaceflight model organism, Drosophila melanogaster, to assess altered gravity associated changes in the nervous system using a ground-based hypergravity model. Acute hypergravity resulted in an induction of oxidative stress-related genes with an increase in reactive oxygen species (ROS) in fly brains (p<0.001). Also, qPCR analysis shows that parkin gene expression is significantly reduced in these fly brains(p<0.05). Additionally, chronic hypergravity resulted in depressed locomotor phenotype in these flies (p<0.05) in conjunction to decreased dopaminergic neuron counts (p<0.0001) and increased apoptosis in these fly brains (p<0.0001). Further, assessment of neurological changes, including the neuronal architecture, synaptic integrity and genetic regulation caused by hypergravity conditions were noted. Overall, our results validate chronic hypergravity simulation as a behavioral model to study spaceflight effects, and oxidative stress pathway as a potential avenue for countermeasure development for astronauts undergoing short- and long-term missions and for neurodegenerative research on Earth.

Mhatre, Siddhita↗