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At least 55 records · Page 3

SpaceDock: A Performance Task Platform for Spaceflight Operations

Preliminary evidence during both short- and long-duration spaceflight indicates that perceptual-motor coordination changes occur and persist in-flight. However, there is presently no in-flight method for evaluating astronaut performance on mission-critical tasks such as docking. We present a portable platform we have developed for attempting and evaluating docking, and describe the results of a pilot study wherein flight novices learned the docking task. Methods: A dual-joystick, six degrees of freedom platform-called SpaceDock-was developed to enable portable, adaptable performance testing in a spaceflight operations setting. Upon this platform, a simplified docking task was created, involving a constant rate of approach towards a docking target and requiring the user to correct translation in two dimensions and attitude orientation along one dimension (either pitch or roll). Ten flight naive subjects performed the task over a 45 min period and all joystick inputs and timings were collected, from which we could successfully reconstruct travel paths, input profiles and relative target displacements. Results: Subjects exhibited significant improvements in docking over the course of the experiment. Learning to compensate for roll-alterations was robust, whereas compensation for pitch-alterations was not in evidence in this population and relatively short training period. Conclusion: The SpaceDock platform can provide a novel method for training and testing subjects, on a spaceflight-relevant task, and can be used to examine behavioral learning, strategy use, and has been adapted for use in brain imaging experiments.

Marshburn, Thomas H.↗

Physiological and Subjective Responses of Pilots during Advanced Air Mobility Flight Testing with Automated Systems

Aviation is constantly evolving, mostly due to the integration of automated systems into the National Airspace System. This presents a host of challenges and opportunities. NASA’s Advanced Air Mobility (AAM) project has taken a significant leap forward with a research flight test led by the Integration of Automated Systems (IAS) sub-project. This effort focused on assessing automated flight deck algorithms essential for supporting high-density Urban Air Mobility (UAM) operations. Carrying out a two-ship flight test in UAM Maturity Level 4 scenarios, the team evaluated state-of-the-art algorithms, including Hazard Perception and Avoidance (HPA) and flight path management (FPM) systems. This paper investigates into pilots’ physiological and subjective responses during the flight scenarios conducted. In collaboration with Lockheed Martin Advanced Technology Laboratories (ATL), we collected and analyzed live-flight biometric data using eye tracking, mobile brain imaging, and heart rate sensors. The study provides insights into pilots’ workload and cognitive engagement while navigating automated tools, leveraging both biometric data and post-encounter subjective assessments. The research highlights the interaction between human operators and automated systems, contributing valuable lessons learned about gathering human data in live-flight environments. The knowledge acquired from this study enhances our understanding of human factors in automated flight and informs future studies attempting to undertake similar feats.

Kevin J. Monk↗

Physiological and Subjective Responses of Pilots During Advanced Air Mobility Flight Testing With Automated Systems

Aviation is constantly evolving, mostly due to the integration of automated systems into the National Airspace System. This presents a host of challenges and opportunities. NASA's Advanced Air Mobility (AAM) project has taken a significant leap forward with a research flight test led by the Integration of Automated Systems (IAS) sub-project. This effort focused on assessing automated flight deck algorithms essential for supporting high-density Urban Air Mobility (UAM) operations. Carrying out a two-ship flight test in UAM Maturity Level 4 scenarios, the team evaluated state-of-the-art algorithms, including Hazard Perception and Avoidance (HPA) and flight path management (FPM) systems. This presentation focuses on results of pilots' physiological and subjective responses during the flight scenarios conducted. In collaboration with Lockheed Martin Advanced Technology Laboratories (ATL), we collected and analyzed live-flight biometric data using eye tracking, mobile brain imaging, and heart rate sensors. The data provides insights into pilots' workload and cognitive engagement while navigating automated tools, leveraging both biometric data and post-encounter subjective assessments. The research highlights the interaction between human operators and automated systems, contributing valuable lessons learned about gathering human data in live-flight environments. The knowledge acquired from this endeavor enhances our understanding of human factors in automated flight and informs future studies attempting to undertake similar feats.

air mobility↗

Assessment of Demographic, Genetic, and Imaging Variables Associated With Brain Resilience and Cognitive Resilience to Pathological Tau in Patients With Alzheimer Disease

Importance: Better understanding is needed of the degree to which individuals tolerate Alzheimer disease (AD)-like pathological tau with respect to brain structure (brain resilience) and cognition (cognitive resilience). Objective: To examine the demographic (age, sex, and educational level), genetic (APOE-ε4 status), and neuroimaging (white matter hyperintensities and cortical thickness) factors associated with interindividual differences in brain and cognitive resilience to tau positron emission tomography (PET) load and to changes in global cognition over time. Design, setting, an participants: In this cross-sectional, longitudinal study, tau PET was performed from June 1, 2014, to November 30, 2017, and global cognition monitored for a mean [SD] interval of 2.0 [1.8] years at 3 dementia centers in South Korea, Sweden, and the United States. The study included amyloid-β-positive participants with mild cognitive impairment or AD dementia. Data analysis was performed from October 26, 2018, to December 11, 2019. Exposures: Standard dementia screening, cognitive testing, brain magnetic resonance imaging, amyloid-β PET and cerebrospinal fluid analysis, and flortaucipir (tau) labeled with fluor-18 (18F) PET. Main outcomes and measures: Separate linear regression models were performed between whole cortex [18F]flortaucipir uptake and cortical thickness, and standardized residuals were used to obtain a measure of brain resilience. The same procedure was performed for whole cortex [18F]flortaucipir uptake vs Mini-Mental State Examination (MMSE) as a measure of cognitive resilience. Bivariate and multivariable linear regression models were conducted with age, sex, educational level, APOE-ε4 status, white matter hyperintensity volumes, and cortical thickness as independent variables and brain and cognitive resilience measures as dependent variables. Linear mixed models were performed to examine whether changes in MMSE scores over time differed as a function of a combined brain and cognitive resilience variable. Results: A total of 260 participants (145 [55.8%] female; mean [SD] age, 69.2 [9.5] years; mean [SD] MMSE score, 21.9 [5.5]) were included in the study. In multivariable models, women (standardized β = -0.15, P = .02) and young patients (standardized β = -0.20, P = .006) had greater brain resilience to pathological tau. Higher educational level (standardized β = 0.23, P < .001) and global cortical thickness (standardized β = 0.23, P < .001) were associated with greater cognitive resilience to pathological tau. Linear mixed models indicated a significant interaction of brain resilience × cognitive resilience × time on MMSE (β [SE] = -0.235 [0.111], P = .03), with steepest slopes for individuals with both low brain and cognitive resilience. Conclusions and relevance: Results of this study suggest that women and young patients with AD have relative preservation of brain structure when exposed to neocortical pathological tau. Interindividual differences in resilience to pathological tau may be important to disease progression because participants with both low brain and cognitive resilience had the most rapid cognitive decline over time.

60 APPLIED LIFE SCIENCES↗

Electroencephalographic imaging of higher brain function

High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. Electroencephalography (EEG) provides temporal resolution in the millisecond range. However, traditional EEG technology and practice provide insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. Recent advances help to overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical images, and by correcting the distortion caused by volume conduction of EEG signals through the skull and scalp. In addition, statistical measurements of sub-second interdependences between EEG time-series recorded from different locations can help to generate hypotheses about the instantaneous functional networks that form between different cortical regions during perception, thought and action. Example applications are presented from studies of language, attention and working memory. Along with its unique ability to monitor brain function as people perform everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

Non-NASA Center↗

Infrared Imaging System for Studying Brain Function

A proposed special-purpose infrared imaging system would be a compact, portable, less-expensive alternative to functional magnetic resonance imaging (fMRI) systems heretofore used to study brain function. Whereas a typical fMRI system fills a large room, and must be magnetically isolated, this system would fit into a bicycle helmet. The system would include an assembly that would be mounted inside the padding in a modified bicycle helmet or other suitable headgear. The assembly would include newly designed infrared photodetectors and data-acquisition circuits on integrated-circuit chips on low-thermal-conductivity supports in evacuated housings (see figure) arranged in multiple rows and columns that would define image coordinates. Each housing would be spring-loaded against the wearer s head. The chips would be cooled by a small Stirling Engine mounted contiguous to, but thermally isolated from, the portions of the assembly in thermal contact with the wearer s head. Flexible wires or cables for transmitting data from the aforementioned chips would be routed to an integrated, multichannel transmitter and thence through the top of the assembly to a patch antenna on the outside of the helmet. The multiple streams of data from the infrared-detector chips would be sent to a remote site, where they would be processed, by software, into a three-dimensional display of evoked potentials that would represent firing neuronal bundles and thereby indicate locations of neuronal activity associated with mental or physical activity. The 3D images will be analogous to current fMRI images. The data would also be made available, in real-time, for comparison with data in local or internationally accessible relational databases that already exist in universities and research centers. Hence, this system could be used in research on, and for the diagnosis of response from the wearer s brain to physiological, psychological, and environmental changes in real time. The images would also be stored in a relational database for comparison with corresponding responses previously observed in other subjects.

Mintz, Frederick↗

Multi-modal imaging of a single mouse brain over five orders of magnitude of resolution

Mammalian neurons operate at length scales spanning six orders of magnitude; they project millimeters to centimeters across brain regions, are composed of micrometer-scale-diameter myelinated axons, and ultimately form nanometer scale synapses. Capturing these anatomical features across that breadth of scale has required imaging samples with multiple independent imaging modalities. Translating between the different modalities, however, requires imaging the same brain with each. Here, we imaged the same postmortem mouse brain over five orders of spatial resolution using MRI, whole brain micrometer-scale synchrotron x-ray tomography ($\mu$CT), and large volume automated serial electron microscopy. Using this pipeline, we can track individual myelinated axons previously relegated to axon bundles in diffusion tensor MRI or arbitrarily trace neurons and their processes brain-wide and identify individual synapses on them. This pipeline provides both an unprecedented look across a single brain's multi-scaled organization as well as a vehicle for studying the brain's multi-scale pathologies.

59 BASIC BIOLOGICAL SCIENCES↗

EVAP: A two-photon imaging tool to study conformational changes in endogenous Kv2 channels in live tissues

A primary goal of molecular physiology is to understand how conformational changes of proteins affect the function of cells, tissues, and organisms. Here, we describe an imaging method for measuring the conformational changes of the voltage sensors of endogenous ion channel proteins within live tissue, without genetic modification. We synthesized GxTX-594, a variant of the peptidyl tarantula toxin guangxitoxin-1E, conjugated to a fluorophore optimal for two-photon excitation imaging through light-scattering tissue. We term this tool EVAP (Endogenous Voltage-sensor Activity Probe). GxTX-594 targets the voltage sensors of Kv2 proteins, which form potassium channels and plasma membrane–endoplasmic reticulum junctions. GxTX-594 dynamically labels Kv2 proteins on cell surfaces in response to voltage stimulation. To interpret dynamic changes in fluorescence intensity, we developed a statistical thermodynamic model that relates the conformational changes of Kv2 voltage sensors to degree of labeling. We used two-photon excitation imaging of rat brain slices to image Kv2 proteins in neurons. We found puncta of GxTX-594 on hippocampal CA1 neurons that responded to voltage stimulation and retain a voltage response roughly similar to heterologously expressed Kv2.1 protein. Our findings show that EVAP imaging methods enable the identification of conformational changes of endogenous Kv2 voltage sensors in tissue.

59 BASIC BIOLOGICAL SCIENCES↗

Physiological Observations and Omics to Develop Personalized Sensormotor Adaptability Countermeasures Using Bed Rest and Space Flight Data

Astronauts experience sensorimotor disturbances during the initial exposure to microgravity and during the re-adapation phase following a return to an earth-gravitational environment. These alterations may disrupt the ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from space flight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. For such an approach to succeed, we must develop predictive measures of sensorimotor adaptability that will allow us to foresee, before actual space flight, which crewmembers are likely to experience the greatest challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures that include: 1) behavioral tests to assess sensory bias and adaptability quantified using both strategic and plastic-adaptive responses; 2) imaging to determine individual brain morphological and functional features using structural magnetic resonance imaging (MRI), diffusion tensor imaging, resting state functional connectivity MRI, and sensorimotor adaptation task-related functional brain activation; 3) genotype markers for genetic polymorphisms in Catechol-O-Methyl Transferase, Dopamine Receptor D2, Brain-derived neurotrophic factor and genetic polymorphism of alpha2-adrenergic receptor that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration space flight and an analog bed rest environment. We will be conducting a retrospective study leveraging data already collected from relevant ongoing/completed bed rest and space flight studies. These data will be combined with predictor metrics that will be collected prospectively - behavioral, brain imaging and genomic measures; from these returning subjects to build models for predicting post-mission (bed rest - non-astronauts or space flight - astronauts) adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions against decrements in post-mission adaptive capability. This ability will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

Mulavara, A. P.↗

Relationship of estrogen synthesis capacity in the brain with obesity and self-control in men and women

Significance Obesity is a major public health problem in a growing proportion of children and adults in the developed world. Estrogen influences body weight and behavioral responses to appetitive stimuli. Estrogen biosynthesis is catalyzed by the enzyme aromatase in all organs measured, including the brain. Using the aromatase radiotracer [ 11 C]vorozole, we measured aromatase availability in the amygdala in healthy-weight to obese adults. Obesity was associated with lower aromatase availability and less constraint independent of sex and age. Variability in brain estrogen synthesis may contribute to obesity by directly regulating feeding and broadly by affecting self-control. These findings suggest that brain aromatase imaging offers a method for characterizing the role of brain estrogen in obesity and other impairments in self-regulation.

Biegon, Anat↗

Upscaling X-ray nanoimaging to macroscopic specimens

Upscaling X-ray nanoimaging to macroscopic specimens has the potential for providing insights across multiple length scales, but its feasibility has long been an open question. By combining the imaging requirements and existing proof-of-principle examples in large-specimen preparation, data acquisition and reconstruction algorithms, the authors provide imaging time estimates for howX-ray nanoimaging can be scaled to macroscopic specimens. To arrive at this estimate, a phase contrast imaging model that includes plural scattering effects is used to calculate the required exposure and corresponding radiation dose. The coherent X-ray flux anticipated from upcoming diffraction-limited light sources is then considered. This imaging time estimation is in particular applied to the case of the connectomes of whole mouse brains. To image the connectome of the whole mouse brain, electron microscopy connectomics might require years, whereas optimized X-ray microscopy connectomics could reduce this to one week. Furthermore, this analysis points to challenges that need to be overcome (such as increased X-ray detector frame rate) and opportunities that advances in artificial-intelligence-based `smart' scanning might provide. While the technical advances required are daunting, it is shown that X-ray microscopy is indeed potentially applicable to nanoimaging of millimetre- or even centimetre-size specimens.

97 MATHEMATICS AND COMPUTING↗

Characterization of Humanized Mouse Model of Organophosphate Poisoning and Detection of Countermeasures via MALDI-MSI

Organophosphoate (OP) chemicals are known to inhibit the enzyme acetylcholinesterase (AChE). Studying OP poisoning is difficult because common small animal research models have serum carboxylesterase, which contributes to animals’ resistance to OP poisoning. Historically, guinea pigs have been used for this research; however, a novel genetically modified mouse strain (KIKO) was developed with nonfunctional serum carboxylase (Es1 KO) and an altered acetylcholinesterase (AChE) gene, which expresses the amino acid sequence of the human form of the same protein (AChE KI). KIKO mice were injected with 1xLD50 of an OP nerve agent or vehicle control with or without atropine. After one to three minutes, animals were injected with 35 mg/kg of the currently fielded Reactivator countermeasure for OP poisoning. Postmortem brains were imaged on a Bruker RapifleX ToF/ToF instrument. Data confirmed the presence of increased acetylcholine in OP-exposed animals, regardless of treatment or atropine status. More interestingly, we detected a small amount of Reactivator within the brain of both exposed and unexposed animals; it is currently debated if reactivators can cross the blood–brain barrier. Further, we were able to simultaneously image acetylcholine, the primary affected neurotransmitter, as well as determine the location of both Reactivator and acetylcholine in the brain. This study, which utilized sensitive MALDI-MSI methods, characterized KIKO mice as a functional model for OP countermeasure development.

2-PAM↗

PET Imaging of Leg Arteries for Determining the Input Function in PET/MRI Brain Studies Using a Compact, MRI-Compatible PET System

In this work, we used a compact, high-resolution, and magnetic resonance imaging (MRI)-compatible positron emission tomography (PET) camera (VersaPET) to assess the feasibility of measuring the image-derived input function (IDIF) from arteries in the leg with the ultimate goal of enabling fully quantitative PET brain imaging without blood sampling. We used this approach in five 18 F-FDG PET/MRI brain studies in which the input function was also acquired using the gold standard of serial arterial blood sampling. After accounting for partial volume, dispersion, and calibration effects, we compared the metabolic rates of glucose (MRglu) quantified from VersaPET IDIFs in 80 brain regions to those using the gold standard and achieved a bias and variability of <5% which is within the range of reported test-retest values for this type of study. We also achieved a strong linear relationship (R 2 >0.97) against the gold standard across regions. The results of this preliminary study are promising and support further studies to optimize methods, validate in a larger cohort, and extend to the modeling of other radiotracers.

47 OTHER INSTRUMENTATION↗

BrainXcan identifies brain features associated with behavioral and psychiatric traits using large-scale genetic and imaging data

Advances in brain MRI have enabled many discoveries in neuroscience. Case-control comparisons of brain MRI features have highlighted potential causes of psychiatric and behavioral disorders. However, due to the cost and difficulty of collecting MRI data, most studies have small sample sizes, limiting their reliability. Furthermore, reverse causality complicates interpretation because many observed brain differences are the result rather than the cause of the disease. Here we propose a method (BrainXcan) that leverages the power of large-scale genomewide association studies (GWAS) and reference brain MRI data to discover new mechanisms of disease etiology and validate existing ones. BrainXcan tests the association with genetic predictors of brain MRI-derived features and complex traits to pinpoint relevant brain-wide and region-specific features. Requiring only genetic data, BrainXcan allows us to test a host of hypotheses on mental illness, across many MRI modalities, using public data resources. For example, our method shows that reduced axonal density across the brain is associated with schizophrenia risk, consistent with the disconnectivity hypothesis. We also find that the hippocampus volume is associated with schizophrenia risk, highlighting the potential of our approach. Taken together, our results show the promise of BrainXcan to provide insights into the biology of GWAS traits.

Association study↗