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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 37 records · Page 2

Soleus H-reflex gain in humans walking and running under simulated reduced gravity

The Hoffmann (H-) reflex is an electrical analogue of the monosynaptic stretch reflex, elicited by bypassing the muscle spindle and directly stimulating the afferent nerve. Studying H-reflex modulation provides insight into how the nervous system centrally modulates stretch reflex responses.A common measure of H-reflex gain is the slope of the relationship between H-reflex amplitude and EMG amplitude. To examine soleus H-reflex gain across a range of EMG levels during human locomotion, we used simulated reduced gravity to reduce muscle activity. We hypothesised that H-reflex gain would be independent of gravity level.We recorded EMG from eight subjects walking (1.25 m s-1) and running (3.0 m s-1) at four gravity levels (1.0, 0.75, 0.5 and 0.25 G (Earth gravity)). We normalised the stimulus M-wave and resulting H-reflex to the maximal M-wave amplitude (Mmax) elicited throughout the stride to correct for movement of stimulus and recording electrodes relative to nerve and muscle fibres. Peak soleus EMG amplitude decreased by ~30% for walking and for running over the fourfold change in gravity. As hypothesised, slopes of linear regressions fitted to H-reflex versus EMG data were independent of gravity for walking and running (ANOVA, P > 0.8). The slopes were also independent of gait (P > 0.6), contrary to previous studies. Walking had a greater y-intercept (19.9% Mmax) than running (-2.5% Mmax; P < 0.001). At all levels of EMG, walking H-reflex amplitudes were higher than running H-reflex amplitudes by a constant amount. We conclude that the nervous system adjusts H-reflex threshold but not H-reflex gain between walking and running. These findings provide insight into potential neural mechanisms responsible for spinal modulation of the stretch reflex during human locomotion.

Non-NASA Center↗

Effects of normal aging on visuo-motor plasticity

Normal aging is associated with declines in neurologic function. Uncompensated visual and vestibular problems may have dire consequences including dangerous falls. Visuo-motor plasticity is a form of behavioral neural plasticity, which is important in the process of adapting to visual or vestibular alteration, including those changes due to pathology, pharmacotherapy, surgery or even entry into microgravity or an underwater environment. To determine the effects of aging on visuo-motor plasticity, we chose the simple and easily measured paradigm of visual-motor rearrangement created by using visual displacement prisms while throwing small balls at a target. Subjects threw balls before, during and after wearing a set of prisms which displace the visual scene by twenty degrees to the right. Data obtained during adaptation were modeled using multilevel modeling techniques for 73 subjects, aged 20 to 80 years. We found no statistically significant difference in measures of visuo-motor plasticity with advancing age. Further studies are underway examining variable practice training as a potential mechanism for enhancing this form of behavioral neural plasticity.

Clinical Trial↗

Molecular selection in a unified evolutionary sequence

With guidance from experiments and observations that indicate internally limited phenomena, an outline of unified evolutionary sequence is inferred. Such unification is not visible for a context of random matrix and random mutation. The sequence proceeds from Big Bang through prebiotic matter, protocells, through the evolving cell via molecular and natural selection, to mind, behavior, and society.

Review, Tutorial↗

Deep Space Radiation Affects Neurovascular Functions in Human Organ-on-a-Chip Models

A major health risk for human deep space exploration is central nervous system (CNS) damage by galactic cosmic ray radiation. Simulated galactic cosmic rays or their components, especially the high- linear energy transfer (LET) particles such as 56 Fe ions, cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates the interactions between CNS and the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal health and neuroinflammation. However, there have been few studies on BBB and astrocyte functions in regulating CNS responses, especially in human tissue/organ analogs. Therefore, we utilized a high-throughput human 3D organ-on-a-chip system, seeded with induced pluripotent stem cell-derived endothelial cells, astrocytes and neurons, to study human neurovascular responses to simulated deep space radiation. We investigated BBB permeability, oxidative stress, cellular and tissue damage, and secreted factors over the time period of 24 hours-1 week after irradiation with 0.25-0.5 Gy 5-ion simplified simulated galactic cosmic rays and 0.3-0.8 Gy high-LET 600MeV/n 56 Fe particles, and compared the outcomes to low-LET irradiation with 0.1-1 Gy doses of X-rays and gamma rays. Both high and low-LET radiation increased neurovascular permeability, caused oxidative stress, damaged endothelial cells and tight junctions, and altered expression of inflammatory cytokines. Ionizing radiation- induced neurovascular permeability and oxidative stress peaked at 3 days after irradiation and were further exacerbated by the presence of astrocytes. Furthermore, in response to particle irradiation, astrocytes stimulated interleukin-1 signaling by inhibiting the expression of interleukin-1 receptor antagonist. Thus, we also evaluated interleukin-1 receptor antagonist as a potential countermeasure against particle radiation. Ultimately, our results may help develop countermeasures to mitigate human CNS damage in deep space exploration.

Sonali D Verma↗

Nitric oxide production by cultured human aortic smooth muscle cells: stimulation by fluid flow

This study demonstrated that exposure of cultured human aortic smooth muscle cells (SMC) to fluid flow resulted in nitric oxide (NO) production, monitored by nitrite and guanosine 3',5'-cyclic monophosphate production. A rapid burst in nitrite production rate was followed by a more gradual increase throughout the period of flow exposure. Neither the initial burst nor the prolonged nitrite production was dependent on the level of shear stress in the range of 1.1-25 dyn/cm2. Repeated exposure to shear stress after a 30-min static period restimulated nitrite production similar to the initial burst. Ca(2+)-calmodulin antagonists blocked the initial burst in nitrite release. An inhibitor of nitric oxide synthase (NOS) blocked nitrite production, indicating that changes in nitrite reflect NO production. Treatment with dexamethasone or cycloheximide had no effect on nitrite production. Monoclonal antibodies directed against the inducible and endothelial NOS isoforms showed no immunoreactivity on Western blots, whereas monoclonal antibodies directed against the neuronal NOS gave specific products. These findings suggest that human aortic SMC express a constitutive neuronal NOS isoform, the enzymatic activity of which is modulated by flow.

Non-NASA Center↗

On the nature and evolution of the neural bases of human language

The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on the brains of human beings and other species provides insight into the evolution of the brain bases of human language. The neural substrate that regulated motor control in the common ancestor of apes and humans most likely was modified to enhance cognitive and linguistic ability. Speech communication played a central role in this process. However, the process that ultimately resulted in the human brain may have started when our earliest hominid ancestors began to walk.

Review, Tutorial↗

Investigation of Neural Strategies of Visual Search

The goal of this project was to measure how neurons in the superior colliculus (SC) change their activity during a visual search task. Specifically, we proposed to measure how the activity of these neurons was altered by the discriminability of visual targets and to test how these changes might predict the changes in the subjects performance. The primary rationale for this study was that understanding how the information encoded by these neurons constrains overall search performance would foster the development of better models of human performance. Work performed during the period supported by this grant has achieved these aims. First, we have recorded from neurons in the superior colliculus (SC) during a visual search task in which the difficulty of the task and the performance of the subject was systematically varied. The results from these single-neuron physiology experiments shows that prior to eye movement onset, the difference in activity across the ensemble of neurons reaches a fixed threshold value, reflecting the operation of a winner-take-all mechanism. Second, we have developed a model of eye movement decisions based on the principle of winner-take-all . The model incorporates the idea that the overt saccade choice reflects only one of the multiple saccades prepared during visual discrimination, consistent with our physiological data. The value of the model is that, unlike previous models, it is able to account for both the latency and the percent correct of saccade choices.

Krauzlis, Richard J.↗

Neural Network Development Tool (NETS)

Artificial neural networks formed from hundreds or thousands of simulated neurons, connected in manner similar to that in human brain. Such network models learning behavior. Using NETS involves translating problem to be solved into input/output pairs, designing network configuration, and training network. Written in C.

Baffes, Paul T.↗

Effect of contrast on the perception of direction of a moving pattern

A series of experiments examining the effect of contrast on the perception of moving plaids was performed to test the hypothesis that the human visual system determines the direction of a moving plaid in a two-staged process: decomposition into component motion followed by application of the intersection-of-contraints rule. Although there is recent evidence that the first tenet of the hypothesis is correct, i.e., that plaid motion is initially decomposed into the motion of the individual grating components, the nature of the second-stage combination rule has not yet been established. It was found that when the gratings within the plaid are of different contrast the preceived direction is not predicted by the intersection-of-constraints rule. There is a strong (up to 20 deg) bias in the direction of the higher-constrast grating. A revised model, which incorporates a contrast-dependent weighting of perceived grating speed as observed for one-dimensional patterns, can quantitatively predict most of the results. The results are then discussed in the context of various models of human visual motion processing and of physiological responses of neurons in the primate visual system.

Stone, L. S.↗

Effect of contrast on the perceived direction of a moving plaid

A series of experiments examining the effect of contrast on the perception of moving plaids is performed. This was done to test the hypothesis put forth by Adelson and Movshon (1982) that the human visual system determines the direction of a moving plaid in a two-staged process: decomposition into component motion followed by application of the intersection of constraints rule. When the gratings within the plaid are of different contrast, the perceived direction is not predicted by the intersection of constraints rule. There is a strong (up to 20 deg) bias in the direction of the higher-contrast grating. A revised model, which incorporates a contrast-dependent weighting of perceived grating speed as observed for one-dimensional patterns (Thompson, 1982), can quantitatively predict most of the results. Results are discussed in the context of various models of human visual motion processing and of physiological responses of neurons in the primate visual system.

Stone, L. S.↗

Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

Goodwin, T. J.↗

Plasma membrane ordering agent pluronic F-68 (PF-68) reduces neurotransmitter uptake and release and produces learning and memory deficits in rats

A substantial body of evidence indicates that aged-related changes in the fluidity and lipid composition of the plasma membrane contribute to cellular dysfunction in humans and other mammalian species. In the CNS, reductions in neuronal plasma membrane order (PMO) (i.e., increased plasma membrane fluidity) have been attributed to age as well as the presence of the beta-amyloid peptide-25-35, known to play an important role in the neuropathology of Alzheimer's disease (AD). These PMO increases may influence neurotransmitter synthesis, receptor binding, and second messenger systems as well as signal transduction pathways. The effects of neuronal PMO on learning and memory processes have not been adequately investigated, however. Based on the hypothesis that an increase in PMO may alter a number of aspects of synaptic transmission, we investigated several neurochemical and behavioral effects of the membrane ordering agent, PF-68. In cell culture, PF-68 (nmoles/mg SDS extractable protein) reduced [3H]norepinephrine (NE) uptake into differentiated PC-12 cells as well as reduced nicotine stimulated [3H]NE release. The compound (800-2400 microg/kg, i.p., resulting in nmoles/mg SDS extractable protein in the brain) decreased step-through latencies and increased the frequencies of crossing into the unsafe side of the chamber in inhibitory avoidance training. In the Morris water maze, PF-68 increased the latencies and swim distances required to locate a hidden platform and reduced the time spent and distance swam in the previous target quadrant during transfer (probe) trials. PF-68 did not impair performance of a well-learned working memory task, the rat delayed stimulus discrimination task (DSDT), however. Studies with 14C-labeled PF-68 indicated that significant (pmoles/mg wet tissue) levels of the compound entered the brain from peripheral (i.p.) injection. No PF-68 related changes were observed in swim speeds or in visual acuity tests in water maze experiments, rotorod performance, or in tests of general locomotor activity. Furthermore, latencies to select a lever in the DSDT were not affected. These results suggest that PF-68 induced deficits in learning and memory without confounding peripheral motor, sensory, or motivational effects at the tested doses. Furthermore, none of the doses induced a conditioned taste aversion to a novel 0.1% saccharin solution indicating a lack of nausea or gastrointestinal malaise induced by the compound. The data indicate that increases in neuronal plasma membrane order may have significant effects on neurotransmitter function as well as learning and memory processes. Furthermore, compounds such as PF-68 may also offer novel tools for studying the role of neuronal PMO in mnemonic processes and changes in PMO resulting from age-related disorders such as AD.

Poloxamer/pharmacology↗

Three-Dimensional Normal Human Neutral Progenitor Tissue-Like Assemblies: A Model for Persistent Varicella-Zoster Virus Infection and Platform to Study Oxidate Stress and Damage in Multiple Hit Scenarios

The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpes virus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex three-dimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6]. By combining the RFs of microgravity, radiation, and viral infection we will demonstrate that living in the space environment leads to significant physiological consequences for the peripheral and subsequently the central nervous system (PNS, CNS) associated with OSaD generation and consequentially endangers long-duration and exploration-class missions.

Goodwin, Thomas J.↗

Developing High-Throughput Organ-On-A-Chip Models to Investigate the Effects of Ionizing Radiation on the Central Nervous System

One of the main health risks in human space exploration is central nervous system (CNS) damage by ionizing radiation. Irradiation with simulated GCRs or their components, or high doses of low-LET radiation such as gamma rays, in animal models has been shown to cause neuronal damage together with glial cell activation and neuroinflammation and has been associated with prolonged cognitive and behavioral dysfunction. The extent of CNS damage in response to any insult, including ionizing radiation, is partially regulated by the blood-brain barrier (BBB), which enables immune cells to enter the CNS. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, immune responses and oxidative stress, and thus could serve as a robust CNS-specific target for countermeasure development. However, studies on BBB permeability and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we have established a high throughput 3D organ-on-a-chip system to study human CNS functions in response to ionizing radiation, with the eventual goal of adapting it to spaceflight missions. We utilized commercially available OrganoPlate system (Mimetas, Inc.) seeded with primary or induced pluripotent stem cell-derived human cells for developing 3D neuronal-astrocytic and BBB models. We investigated both immediate and delayed CNS dose responses to 0.5-1 Gy X-rays by measuring BBB permeability and morphology, and astrocyte activation. We have also quantified secreted markers of oxidative stress and cell viability. In the future, we are planning to monitor dendritic, axonal and synaptic changes in neurons, evaluate the combined exposures to simulated microgravity and ionizing radiation, and compare the responses to low and high-LET ionizing radiation. We anticipate these studies could indicate novel cellular and mechanistic targets for countermeasure developments to improve CNS functions in astronauts.

Malkani, Sherina↗

GABAA receptor subunit gene expression in human prefrontal cortex: comparison of schizophrenics and controls

The prefrontal cortex of schizophrenics is hypoactive and displays changes related to inhibitory, GABAergic neurons, and GABAergic synapses. These changes include decreased levels of glutamic acid decarboxylase (GAD), the enzyme for GABA synthesis, upregulation of muscimol binding, and downregulation of benzodiazepine binding to GABAA receptors. Studies in the visual cortex of nonhuman primates have demonstrated that gene expression for GAD and for several GABAA receptor subunit polypeptides is under control of neuronal activity, raising the possibility that similar mechanisms in the hypoactive prefrontal cortex of schizophrenics may explain the abnormalities in GAD and in GABAA receptor regulation. In the present study, which is the first of its type on human cerebral cortex, levels of mRNAs for six GABAA receptor subunits (alpha 1, alpha 2, alpha 5, beta 1, beta 2, gamma 2) and their laminar expression patterns were analyzed in the prefrontal cortex of schizophrenics and matched controls, using in situ hybridization histochemistry and densitometry. Three types of laminar expression pattern were observed: mRNAs for the alpha 1, beta 2, and gamma 2 subunits, which are the predominant receptor subunits expressed in the mature cortex, were expressed at comparatively high levels by cells of all six cortical layers, but most intensely by cells in lower layer III and layer IV. mRNAs for the alpha 2, alpha 5, and beta 1 subunits were expressed at lower levels; alpha 2 and beta 1 were expressed predominantly by cells in layers II, III, and IV; alpha 5 was expressed predominantly in layers IV, V, and VI. There were no significant changes in overall mRNA levels for any of the receptor subunits in the prefrontal cortex of schizophrenics, and the laminar expression pattern of all six receptor subunit mRNAs did not differ between schizophrenics and controls. Because gene expression for GABAA receptor subunits is not consistently altered in the prefrontal cortex of schizophrenics, the previously reported upregulation of muscimol binding sites and downregulation of benzodiazepine binding sites in the prefrontal and adjacent cingulate cortex of schizophrenics are possibly due to posttranscriptional modifications of mRNAs and their translated polypeptides.

NASA Discipline Neuroscience↗

Investigating Neuro-Consequences of Spaceflight Using Drosophila Melanogaster

Research on human acclimation to spaceflight, including the recent NASA's Twin Study, reports complex effects of the spaceflight environment on health, with both acute and prolonged changes in multiple tissues. Spaceflight includes multiple factors such as microgravity, ionizing radiation, physiological stress, and disrupted circadian rhythms, that have been shown to contribute to pathophysiological responses that target immunity, bone and muscle integrity, cardiovascular and nervous systems. In this study, we used a well-established spaceflight model organism, Drosophila melanogaster, to assess spaceflight-associated changes on the nervous system. With 75% disease gene orthology to humans, short generation time, large sample size and ease of genetic, neuronal and behavioral studies, Drosophila is an excellent model to study nervous system dysfunction. Here, we present results from MVP-Fly-01 spaceflight mission that was launched on SpaceX CRS-14. The MVP hardware (developed by Techshot) used in this mission enabled us to have an in-flight 1g centrifuge, to distinguish the changes resulting from gravity versus those induced by other environmental factors associated with spaceflight. 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 microgravity 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) compared to in-flight 1g controls, 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.

Iyer, Janani↗

Shared motion signals for human perceptual decisions and oculomotor actions

A fundamental question in primate neurobiology is to understand to what extent motor behaviors are driven by shared neural signals that also support conscious perception or by independent subconscious neural signals dedicated to motor control. Although it has clearly been established that cortical areas involved in processing visual motion support both perception and smooth pursuit eye movements, it remains unknown whether the same or different sets of neurons within these structures perform these two functions. Examination of the trial-by-trial variation in human perceptual and pursuit responses during a simultaneous psychophysical and oculomotor task reveals that the direction signals for pursuit and perception are not only similar on average but also co-vary on a trial-by-trial basis, even when performance is at or near chance and the decisions are determined largely by neural noise. We conclude that the neural signal encoding the direction of target motion that drives steady-state pursuit and supports concurrent perceptual judgments emanates from a shared ensemble of cortical neurons.

Visual Cortex/physiology↗

Effect of 670-nm Light-Emitting Diode Light On Neuronal Cultures

Light close to and within the near infrared range has documented benefits for promoting wound healing in human and animal studies. Our preliminary results using light-emitting diodes (LEDs) in this range have also demonstrated two-to five-fold increases in growth-phase-specific DNA synthesis in normal fibroblasts, muscle cells, osteoblasts, and mucosal epithelial cells in tissue cultures. However, the mechanisms of action of such light on cells are poorly understood. We hypothesized that the therapeutic effects of such light result from the stimulation of cellular events associated with increases in cytochrome oxidase activity. As a first step in testing our hypothesis, we subjected primary neuronal cultures to impulse blockade by tetrodotoxin (TTX), a voltage-dependent sodium channel blocker, and applied LED light at 670 nm to determine if it could partially or fully reverse the reduction of cytochrome oxidase activity by TTX. The wavelength and parameters were previously tested to be beneficial for wound healing.

Wong-Riley, Margaret T. T.↗