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Using light and X-ray scattering to untangle complex neuronal orientations and validate diffusion MRI

Disentangling human brain connectivity requires an accurate description of nerve fiber trajectories, unveiled via detailed mapping of axonal orientations. However, this is challenging because axons can cross one another on a micrometer scale. Diffusion magnetic resonance imaging (dMRI) can be used to infer axonal connectivity because it is sensitive to axonal alignment, but it has limited spatial resolution and specificity. Scattered light imaging (SLI) and small-angle X-ray scattering (SAXS) reveal axonal orientations with microscopic resolution and high specificity, respectively. Here, we apply both scattering techniques on the same samples and cross-validate them, laying the groundwork for ground-truth axonal orientation imaging and validating dMRI. We evaluate brain regions that include unidirectional and crossing fibers in human and vervet monkey brain sections. SLI and SAXS quantitatively agree regarding in-plane fiber orientations including crossings, while dMRI agrees in the majority of voxels with small discrepancies. We further use SAXS and dMRI to confirm theoretical predictions regarding SLI determination of through-plane fiber orientations. Scattered light and X-ray imaging can provide quantitative micrometer 3D fiber orientations with high resolution and specificity, facilitating detailed investigations of complex fiber architecture in the animal and human brain.

59 BASIC BIOLOGICAL SCIENCES↗

Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering

Myelinated axons (nerve fibers) efficiently transmit signals throughout the brain via action potentials. Multiple methods that are sensitive to axon orientations, from microscopy to magnetic resonance imaging, aim to reconstruct the brain's structural connectome. As billions of nerve fibers traverse the brain with various possible geometries at each point, resolving fiber crossings is necessary to generate accurate structural connectivity maps. However, doing so with specificity is a challenging task because signals originating from oriented fibers can be influenced by brain (micro)structures unrelated to myelinated axons. X-ray scattering can specifically probe myelinated axons due to the periodicity of the myelin sheath, which yields distinct peaks in the scattering pattern. Here, in this work, we show that small-angle X-ray scattering (SAXS) can be used to detect myelinated, axon-specific fiber crossings. We first demonstrate the capability using strips of human corpus callosum to create artificial double- and triple-crossing fiber geometries, and we then apply the method in mouse, pig, vervet monkey, and human brains. We compare results to polarized light imaging (3D-PLI), tracer experiments, and to outputs from diffusion MRI that sometimes fails to detect crossings. Given its specificity, capability of 3-dimensional sampling and high resolution, SAXS could serve as a ground truth for validating fiber orientations derived using diffusion MRI as well as microscopy-based methods.

59 BASIC BIOLOGICAL SCIENCES↗

Intracranial Fluid Redistribution During a Spaceflight Analog

The neural correlates of spaceflight-induced sensorimotor impairments are unknown. Head down-tilt bed rest (HDBR) serves as a microgravity analog because it mimics the headward fluid shift and limb unloading of spaceflight. We investigated focal brain white matter (WM) changes and fluid shifts during 70 days of 6 deg HDBR in 16 subjects who were assessed pre (2x), during (3x), and post-HDBR (2x). Changes over time were compared to those in control subjects (n=12) assessed four times over 90 days. Diffusion MRI was used to assess WM microstructure and fluid shifts. Free-Water Imaging, derived from diffusion MRI, was used to quantify the distribution of intracranial extracellular free water (FW). Additionally, we tested whether WM and FW changes correlated with changes in functional mobility and balance measures. HDBR resulted in FW increases in fronto-temporal regions and decreases in posterior-parietal regions that largely recovered by two weeks post-HDBR. WM microstructure was unaffected by HDBR. FW decreased in the post-central gyrus and precuneus. We previously reported that gray matter increases in these regions were associated with less HDBR-induced balance impairment, suggesting adaptive structural neuroplasticity. Future studies are warranted to determine causality and underlying mechanisms.

Koppelmans, Vincent↗

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.↗

Behavioral, Brain Imaging and Genomic Measures to Predict Functional Outcomes Post - Bed Rest and Spaceflight

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. These alterations may disrupt crewmembers' ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from spaceflight 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 spaceflight, 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. Our approach includes: 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; and 3) assessment of genotypic markers of genetic polymorphisms in the catechol-O-methyl transferase, dopamine receptor D2, and brain-derived neurotrophic factor genes and genetic polymorphisms of alpha2-adrenergic receptors that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate that these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration spaceflight and exposure to an analog bed rest environment. We will be conducting a retrospective study, leveraging data already collected from relevant ongoing or completed bed rest and spaceflight studies. These data will be combined with predictor metrics that will be collected prospectively (as described for 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. To date we have completed a study on 15 normal subjects with all of the above measures. In this presentation we will discuss the optimized set of tests for predictive metrics to be used for evaluating post mission adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive capacity, brain structure and functional capacities, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

Mulavara, A. P.↗

Behavioral, Brain Imaging and Genomic Measures to Predict Functional Outcomes Post-Bed Rest and Space Flight

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. These alterations may disrupt crewmembers' ability to perform mission critical functional tasks requiring ambulation, manual control and gaze stability. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts are affected will 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 spaceflight, which crewmembers are likely to experience greater challenges to their adaptive capacities. The goals of this project are to identify and characterize this set of predictive measures. Our approach includes: 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; and 3) assessment of genetic polymorphisms in the catechol-O-methyl transferase, dopamine receptor D2, and brain-derived neurotrophic factor genes and genetic polymorphisms of alpha2-adrenergic receptors that play a role in the neural pathways underlying sensorimotor adaptation. We anticipate that these predictive measures will be significantly correlated with individual differences in sensorimotor adaptability after long-duration spaceflight and exposure to an analog bed rest environment. We will be conducting a retrospective study, leveraging data already collected from relevant ongoing or completed bed rest and spaceflight studies. This data will be combined with predictor metrics that will be collected prospectively (as described for behavioral, brain imaging and genomic measures) from these returning subjects to build models for predicting post spaceflight and bed rest adaptive capability. In this presentation we will discuss the optimized set of tests for predictive metrics to be used for evaluating post mission adaptive capability as manifested in their outcome measures. Comparisons of model performance will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive ability, brain structure, brain function, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to mitigate the deleterious effects of spaceflight.

Mulavara, A. P.↗

Patch2Self2: Self-supervised Denoising on Coresets via Matrix Sketching

Diffusion MRI (dMRI) non-invasively maps brain white matter yet necessitates denoising due to low signal-to-noise ratios. Patch2Self (P2S) employing self-supervised techniques and regression on a Casorati matrix effectively denoises dMRI images and has become the new de-facto standard in this field. P2S however is resource intensive both in terms of running time and memory usage as it uses all voxels (n) from all-but-one held-in volumes (d-1) to learn a linear mapping Phi : \mathbb R ^ n x(d-1) \mapsto \mathbb R ^ n for denoising the held-out volume. The increasing size and dimensionality of higher resolution dMRI acquisitions can make P2S infeasible for large-scale analyses. This work exploits the redundancy imposed by P2S to alleviate its performance issues and inspect regions that influence the noise disproportionately. Specifically this study makes a three-fold contribution: (1) We present Patch2Self2 (P2S2) a method that uses matrix sketching to perform self-supervised denoising. By solving a sub-problem on a smaller sub-space so called coreset we show how P2S2 can yield a significant speedup in training time while using less memory. (2) We present a theoretical analysis of P2S2 focusing on determining the optimal sketch size through rank estimation a key step in achieving a balance between denoising accuracy and computational efficiency. (3) We show how the so-called statistical leverage scores can be used to interpret the denoising of dMRI data a process that was traditionally treated as a black-box. Experimental results on both simulated and real data affirm that P2S2 maintains denoising quality while significantly enhancing speed and memory efficiency achieved by training on a reduced data subset.

Fadnavis, Shreyas↗

Tractometry of the Human Connectome Project: resources and insights

The Human Connectome Project (HCP) has become a keystone dataset in human neuroscience, with a plethora of important applications in advancing brain imaging methods and an understanding of the human brain. We focused on tractometry of HCP diffusion-weighted MRI (dMRI) data. We used an open-source software library (pyAFQ; https://yeatmanlab.github.io/pyAFQ) to perform probabilistic tractography and delineate the major white matter pathways in the HCP subjects that have a complete dMRI acquisition (n = 1,041). We used diffusion kurtosis imaging (DKI) to model white matter microstructure in each voxel of the white matter, and extracted tract profiles of DKI-derived tissue properties along the length of the tracts. We explored the empirical properties of the data: first, we assessed the heritability of DKI tissue properties using the known genetic linkage of the large number of twin pairs sampled in HCP. Second, we tested the ability of tractometry to serve as the basis for predictive models of individual characteristics (e.g., age, crystallized/fluid intelligence, reading ability, etc.), compared to local connectome features. To facilitate the exploration of the dataset we created a new web-based visualization tool and use this tool to visualize the data in the HCP tractometry dataset. Finally, we used the HCP dataset as a test-bed for a new technological innovation: the TRX file-format for representation of dMRI-based streamlines. We released the processing outputs and tract profiles as a publicly available data resource through the AWS Open Data program's Open Neurodata repository. We found heritability as high as 0.9 for DKI-based metrics in some brain pathways. We also found that tractometry extracts as much useful information about individual differences as the local connectome method. We released a new web-based visualization tool for tractometry—“Tractoscope” (https://nrdg.github.io/tractoscope). We found that the TRX files require considerably less disk space-a crucial attribute for large datasets like HCP. In addition, TRX incorporates a specification for grouping streamlines, further simplifying tractometry analysis.

59 BASIC BIOLOGICAL SCIENCES↗

Novel pore size-controlled, susceptibility matched, 3D-printed MRI phantoms

We report the design concept and fabrication of MRI phantoms, containing blocks of aligned microcapillaires that can be stacked into larger arrays to construct diameter distribution phantoms or fractured, to create a “powder-averaged” emulsion of randomly oriented blocks for vetting or calibrating advanced MRI methods, that is, diffusion tensor imaging, AxCaliber MRI, MAP-MRI, and multiple pulsed field gradient or double diffusion-encoded microstructure imaging methods. The goal was to create a susceptibility-matched microscopically anisotropic but macroscopically isotropic phantom with a ground truth diameter that could be used to vet advanced diffusion methods for diameter determination in fibrous tissues. Two-photon polymerization, a novel three-dimensional printing method is used to fabricate blocks of capillaries. Double diffusion encoding methods were employed and analyzed to estimate the expected MRI diameter. Susceptibility-matched microcapillary blocks or modules that can be assembled into large-scale MRI phantoms have been fabricated and measured using advanced diffusion methods, resulting in microscopic anisotropy and random orientation. This phantom can vet and calibrate various advanced MRI methods and multiple pulsed field gradient or diffusion-encoded microstructure imaging methods. We demonstrated that two double diffusion encoding methods underestimated the ground truth diameter.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Spaceflight Effect on White Matter Structural Integrity

Recent reports of elevated brain white matter hyperintensity (WMH) counts and volume in postflight astronaut MRIs suggest that further examination of spaceflight's impact on the microstructure of brain white matter is warranted. To this end, retrospective longitudinal diffusion-weighted MRI scans obtained from 15 astronauts were evaluated. In light of the recent reports of microgravity-induced cephalad fluid shift and gray matter atrophy seen in astronauts, we applied a technique to estimate diffusion tensor imaging (DTI) metrics corrected for free water contamination. This approach enabled the analysis of white matter tissue-specific alterations that are unrelated to fluid shifts, occurring from before spaceflight to after landing. After spaceflight, decreased fractional anisotropy (FA) values were detected in an area encompassing the superior and inferior longitudinal fasciculi and the inferior fronto-occipital fasciculus. Increased radial diffusivity (RD) and decreased axial diffusivity (AD) were also detected within overlapping regions. In addition, FA values in the corticospinal tract decreased and RD measures in the precentral gyrus white matter increased from before to after flight. The results show disrupted structural connectivity of white matter in tracts involved in visuospatial processing, vestibular function, and movement control as a result of spaceflight. The findings may help us understand the structural underpinnings of the extensive spaceflight-induced sensorimotor remodeling. Prospective longitudinal assessment of the white matter integrity in astronauts is needed to characterize the evolution of white matter microstructural changes associated with spaceflight, their behavioral consequences, and the time course of recovery. Supported by a grant from the National Space Biomedical Research Institute, NASA NCC 9-58.

Lee, Jessica K.↗

The Case for Optimized Edge-Centric Tractography at Scale

The anatomic validity of structural connectomes remains a significant uncertainty in neuroimaging. Edge-centric tractography reconstructs streamlines in bundles between each pair of cortical or subcortical regions. Although edge bundles provides a stronger anatomic embedding than traditional connectomes, calculating them for each region-pair requires exponentially greater computation. We observe that major speedup can be achieved by reducing the number of streamlines used by probabilistic tractography algorithms. To ensure this does not degrade connectome quality, we calculate the identifiability of edge-centric connectomes between test and re-test sessions as a proxy for information content. We find that running PROBTRACKX2 with as few as 1 streamline per voxel per region-pair has no significant impact on identifiability. Variation in identifiability caused by streamline count is overshadowed by variation due to subject demographics. This finding even holds true in an entirely different tractography algorithm using MRTrix. Incidentally, we observe that Jaccard similarity is more effective than Pearson correlation in calculating identifiability for our subject population.

59 BASIC BIOLOGICAL SCIENCES↗

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.↗

Nonideal stability analysis of differentially rotating plasmas with global curvature effects

The linear stability of global nonaxisymmetric modes in differentially rotating, magnetized, nonideal plasma is critical to classifying turbulence and transport phenomena. We investigate the competition between the local magneto-rotational instability (MRI) and the magneto-curvature instability (MCI)—a distinct nonaxisymmetric low-frequency curvature-driven global branch that appears alongside MRI. Here, to accomplish this, we developed a nonideal global spectral method, which is validated against NIMROD code simulations. This spectral approach allows for the direct derivation of an extended effective potential formalism and a resistive Alfvénic resonance condition, providing a framework for direct analysis of energy contributions and confinement mechanisms. Our study reveals that the global, low-frequency MCI persists at low magnetic Reynolds numbers (Rm), whereas the localized, high-frequency MRI is stabilized by diffusive broadening of its structure around its Alfvénic resonances. Consequently, we identify the global MCI branch as the primary onset mechanism for nonaxisymmetric magnetohydrodynamic instability in systems with finite curvature, e.g., astrophysical rotators. We establish distinct parameter regimes for mode dominance: MCI prevails in geometrically moderate-thickness disks with intermediate curvature and radial gaps, while MRI dominates in thin, low-curvature disks with large radial gaps. Mode competition is also highly sensitive to the flow profile, particularly vorticity and its gradient, with nonuniform shear profiles exhibiting more robust instability due to flow curvature (i.e., the second derivative of the flow profile) and shear contributions. A key outcome is the development of spectral diagrams derived from the global spectral method. These diagrams comprehensively map dominant instabilities and their characteristics, offering a predictive tool for critical onset parameters (i.e., flow curvature, magnetic field, and Rm) and facilitating the interpretation of experimental and simulation results. Notably, these diagrams demonstrate that the global MCI is generally the sole unstable mode at the initial onset of nonaxisymmetric instability.

Haywood, Alexander [Princeton Univ., NJ (United St↗

Assessing the Relationships Between Sensorimotor Biomarkers and Post-Landing Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study is to identify a set of behavioral, neuroimaging and genetic measures that can be used to predict early post-flight performance on a set of sensorimotor tasks. Astronauts are recruited who previously participated in sensorimotor field tests and/or posturography soon after long-duration spaceflight. Behavioral tests include assessments of sensory dependency and adaptability. Visual dependency involves treadmill walking while viewing a moving virtual visual scene. Vestibular thresholds are measured while seated during lateral translations. Proprioception dependency is measured during one-legged stance on a horizontal air-bearing surface. Ground assessment of adaptability is performed (1) during treadmill walking with a virtual linear hallway and a moving walking surface, and (2) during multiple trials of navigating an obstacle course while wearing reversing prisms. The neuroimaging tests will characterize individual differences in regional brain volumes (using Structural MRI) and white matter microstructure (using Diffusion Tensor Imaging) to serve as potential predictors of adaptive capacity. The genetic tests will utilize saliva samples to examine variations in four genes chosen because of their ability to differentiate sensorimotor adaptation ability in a normative population, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF) and the α2-adrenergic receptor. Twenty-one ISS crewmembers have been tested to date, including 6 from this past year after testing resumed post-COVID. This cohort includes 9 first-time fliers, 4F, and mission durations lasting 182 ± 32 days, mean ± std. We are utilizing a combination of three post-flight functional task outcomes: tandem walk, recovery from fall and dynamic posturography. There is considerable variability among the post-flight performance outcomes for the 21 participants to date. Based on a partial sample using an ordinal scale survey, 80% indicated their ability to perform functional tasks were more impacted postflight relative to inflight with 50% indicating they needed to restrict movements for a longer period postflight relative to inflight. While there is a strong association within tests obtained at different R+0 timepoints, by R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. There are apparent relationships between individual measures and specific post-flight outcome measures; however, additional data is needed to draw conclusions. Preliminary statistical analysis indicates combining biomarkers will increase predictive power and this will be explored with future analyses. Our preliminary findings underscore the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

S J Wood↗

Assessing the Relationships Between Sensorimotor Biomarkers and Post-Landing Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study is to identify a set of behavioral, neuroimaging and genetic measures that can be used to predict early post-flight performance on a set of sensorimotor tasks. Astronauts are recruited who previously participated in sensorimotor field tests and/or posturography soon after long-duration spaceflight. Behavioral tests include assessments of sensory dependency and adaptability. Visual dependency involves treadmill walking while viewing a moving virtual visual scene. Vestibular perceptual thresholds are measured while seated during lateral translations. Proprioception dependency is measured during one-legged stance on a horizontal air-bearing surface. Ground assessment of adaptability is performed(1) during treadmill walking with a virtual linear hallway and a moving walking surface, and (2) during multiple trials of navigating an obstacle course while wearing reversing prisms(adaptive Functional Mobility Test, aFMT). The neuroimaging tests will characterize individual differences in regional brain volumes (using Structural MRI) and white matter microstructure(using Diffusion Tensor Imaging) to serve as potential predictors of adaptive capacity. The genetic tests will utilize saliva samples to examine variations in four genes chosen because of their ability to differentiate sensorimotor adaptation ability in a normative population, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF) and the α2-adrenergic receptor. Twenty-seven ISS crewmembers have been tested to date, including 6 from this past year. This cohort includes 10first-time fliers, 6F, and mission durations lasting 178.6 ± 30.5 days, mean ± std. We are utilizing a combination of three post-flight functional task outcomes: tandem walk, recovery from fall and dynamic posturography. There is considerable variability among the post-flight performance outcomes for the 27participants to date. Based on a partial sample using an ordinal scale survey, 70% indicated their ability to perform functional tasks were more impacted postflight relative to inflight with 50% indicating they needed to restrict movements for a longer period postflight relative to inflight. While there is a strong association within tests obtained at different R+0 timepoints, by R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. There are apparent relationships between individual measures and specific post-flight outcome measures, e.g., the cumulative time to complete the aFMT is significantly correlated to pre-to-post-flight changes in tandem walk (rho= 0.64, p = 0.001). Preliminary statistical analysis indicates combining biomarkers will increase predictive power and this will be explored with future analyses. Our preliminary findings underscore the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. We expect that understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance will improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures

S J Wood↗

Assessing the Relationships Between Sensorimotor Biomarkers and Post-Landing Functional Task Performance

Spaceflight drives adaptive changes in healthy individuals appropriate for sensorimotor function in a microgravity environment. These changes are maladaptive for return to earth's gravity. The inter-individual variability of sensorimotor decrements is striking, although poorly understood. The goal of this study was to identify a set of behavioral, neuroimaging and genetic measures that can be used to predict early post-flight performance on a set of sensorimotor tasks. Astronauts were recruited who previously participated in sensorimotor field tests and/or posturography soon after long-duration spaceflight. Behavioral tests included assessments of sensory dependency and adaptability. Visual dependency involved treadmill walking while viewing a moving virtual visual scene. Vestibular perceptual thresholds were measured while seated during lateral translations. Proprioception dependency was measured during one-legged stance on a horizontal air-bearing surface. Ground assessment of adaptability was performed (1) during treadmill walking with a virtual linear hallway and a moving walking surface, and (2) during multiple trials of navigating an obstacle course while wearing reversing prisms (adaptive Functional Mobility Test, aFMT). The neuroimaging tests characterized individual differences in regional brain volumes (using Structural MRI) and white matter microstructure (using Diffusion Tensor Imaging) to serve as potential predictors of adaptive capacity. The genetic tests utilized saliva samples to examine variations in four genes chosen because of their ability to differentiate sensorimotor adaptation ability in a normative population, including Catechol-O-methyltransferase (COMT), Dopamine Receptor D2 (DRD2), Brain-derived neurotrophic factor (BDNF) and the α2-adrenergic receptor. Thirty ISS crewmembers were recruited, including 12 first-time fliers, 6F, and mission durations lasting 185.5 ± 45.5 days, mean ± std. We utilized a combination of three post-flight functional task outcomes: tandem walk, recovery from fall and dynamic posturography. There was considerable variability among all post-flight performance outcomes. Based on an ordinal scale survey, 72% indicated their ability to perform functional tasks were more impacted postflight relative to inflight with 50% indicating they needed to restrict movements for a longer period postflight relative to inflight. While there is a strong association within tests obtained at different R+0 timepoints, by R+24 hr performance on one post-flight test does not necessarily correlate with performance on other post-flight tests. Preliminary statistical analysis indicates combining biomarkers will increase predictive power and this will be explored with future analyses. Our preliminary findings underscore the importance of a comprehensive post-flight test battery including different types of tasks with varying sensory feedback. Understanding the relationships between these sensorimotor biomarkers and post-flight functional task performance improve both our understanding of the individual variability and our strategy to optimize sensorimotor countermeasures.

biomarkers↗

Magnetorotational instability in a swirling partially ionized gas

ABSTRACT The magnetorotational instability (MRI) has been proposed as the method of angular momentum transport that enables accretion in astrophysical discs. However, for weakly ionized discs, such as protoplanetary discs, it remains unclear whether the combined non-ideal magnetohydrodynamic (MHD) effects of Ohmic resistivity, ambipolar diffusion, and the Hall effect make these discs MRI stable. While much effort has been made to simulate non-ideal MHD MRI, these simulations make simplifying assumptions and are not always in agreement with each other. Furthermore, it is difficult to directly observe the MRI astrophysically because it occurs on small scales. Here, we propose the concept of a swirling gas experiment of weakly ionized argon gas between two concentric cylinders threaded with an axial magnetic field that can be used to study non-ideal MHD MRI. For our proposed experiment, we derive the hydrodynamic equilibrium flow and a dispersion relation for MRI that includes the three non-ideal effects. We solve this dispersion relation numerically for the parameters of our proposed experiment. We find it should be possible to produce a non-ideal MRI in such an experiment because of the Hall effect, which increases the MRI growth rate when the vertical magnetic field is anti-aligned with the rotation axis. As a proof of concept, we also present experimental results for a hydrodynamic flow in an unmagnetized prototype. We find that our prototype has a small, but non-negligible, α-parameter that could serve as a baseline for comparison to our proposed magnetized experiment, which could be subject to additional turbulence from the MRI.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

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.↗