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NASA NTRS2003

Computational Hemodynamic Simulation of Human Circulatory System under Altered Gravity

A computational hemodynamics approach is presented to simulate the blood flow through the human circulatory system under altered gravity conditions. Numerical techniques relevant to hemodynamics issues are introduced to non-Newtonian modeling for flow characteristics governed by red blood cells, distensible wall motion due to the heart pulse, and capillary bed modeling for outflow boundary conditions. Gravitational body force terms are added to the Navier-Stokes equations to study the effects of gravity on internal flows. Six-type gravity benchmark problems are originally presented to provide the fundamental understanding of gravitational effects on the human circulatory system. For code validation, computed results are compared with steady and unsteady experimental data for non-Newtonian flows in a carotid bifurcation model and a curved circular tube, respectively. This computational approach is then applied to the blood circulation in the human brain as a target problem. A three-dimensional, idealized Circle of Willis configuration is developed with minor arteries truncated based on anatomical data. Demonstrated is not only the mechanism of the collateral circulation but also the effects of gravity on the distensible wall motion and resultant flow patterns.

Kim. Chang Sung↗

NASA NTRS2003

The Hyperwall

This paper presents the hyperwall, a visualization cluster that uses coordinated visualizations for interactive exploration of multidimensional data and simulations. The system strongly leverages the human eye-brain system with a generous 7x7 array offlat panel LCD screens powered by a beowulf clustel: With each screen backed by a workstation class PC, graphic and compute intensive applications can be applied to a broad range of data. Navigational tools are presented that allow for investigation of high dimensional spaces.

Biegel, Bryan A.↗

NASA NTRS2003

Summary of Research Adaptions of Visceral and Cerebral Resistance Arteries to Simulated Microgravity

The proposed studies were designed address the effects of simulated microgravity on vascular smooth muscle and endothelial cell function in resistance arteries isolated from visceral tissues (spleen, mesentery and kidneys) and cerebrum. Alterations in vascular function induced by microgravity are particularly relevant to the problems of orthostatic intolerance and reduced exercise capacity experienced by astronauts upon re-entry into the earth's gravitational field. Decrements in contractile function or enhanced vasodilatory responsiveness of peripheral resistance arteries could lead to decreased peripheral resistance and orthostatic hypotension. Alternatively, augmentation of contractile function in cerebral resistance arteries could lead to increased cerebral vascular resistance and diminished perfusion of the brain. The Specific Aims and hypotheses were proposed in this grant. Following each of the Specific Aims, progress toward addressing that specific aim is presented. With the exception of Specific Aim VI (see aim for details), all aims have been experimentally addressed as proposed. The final six months of the granting period will be used for manuscript preparation; manuscripts in preparation will contain results from Specific Aims I-IV. Results from Specific Aims V and VI have been published.

Delp, Michael↗

NASA NTRS2003

The Neurolab Spacelab Mission: Neuroscience Research in Space: Results from the STS-90, Neurolab Spacelab Mission

Neurolab (STS-90) represents a major scientific achievement that built upon the knowledge and capabilities developed during the preceding 15 successful Spacelab module missions. NASA proposed a dedicated neuroscience research flight in response to a Presidential declaration that the 1990's be the Decade of the Brain. Criteria were established for selecting research proposals in partnership with the National Institutes of Health (NM), the National Science Foundation, the Department of Defense, and a number of the International Space Agencies. The resulting Announcement of Opportunity for Neurolab in 1993 resulted in 172 proposals from scientists worldwide. After an NIH-managed peer review, NASA ultimately selected 26 proposals for flight on the Neurolab mission.

Buckey, Jay C., Jr.↗

NASA NTRS2003

The Effects of Spaceflight on the Rat Circadian Timing System

Two fundamental environmental influences that have shaped the evolution of life on Earth are gravity and the cyclic changes occurring over the 24-hour day. Light levels, temperature, and humidity fluctuate over the course of a day, and organisms have adapted to cope with these variations. The primary adaptation has been the evolution of a biological timing system. Previous studies have suggested that this system, named the circadian (circa - about; dies - a day) timing system (CTS), may be sensitive to changes in gravity. The NASA Neurolab spaceflight provided a unique opportunity to evaluate the effects of microgravity on the mammalian CTS. Our experiment tested the hypotheses that microgravity would affect the period, phasing, and light sensitivity of the CTS. Twenty-four Fisher 344 rats were exposed to 16 days of microgravity on the Neurolab STS-90 mission, and 24 Fisher 344 rats were also studied on Earth as one-G controls. Rats were equipped with biotelemetry transmitters to record body temperature (T(sub b)) and heart rate (HR) continuously while the rats moved freely. In each group, 18 rats were exposed to a 24-hour light-dark (LD 12:12) cycle, and six rats were exposed to constant dim red-light (LL). The ability of light to induce a neuronal activity marker (c-fos) in the circadian pacemaker of the brain, the suprachiasmatic nucleus (SCN), was examined in rats studied on flight days two (FD2) and 14 (FD14), and postflight days two (R+1) and 14 (R+13). The flight rats in LD remained synchronized with the LD cycle. However, their T(sub b), rhythm was markedly phase-delayed relative to the LD cycle. The LD flight rats also had a decreased T(sub b) and a change in the waveform of the T(sub b) rhythm compared to controls. Rats in LL exhibited free-running rhythms of T(sub b), and HR; however, the periods were longer in microgravity. Circadian period returned to preflight values after landing. The internal phase angle between rhythms was different in flight than in one-G. Compared with control rats, the flight rats exhibited no change in HR. Finally, the LD FD2 flight rats demonstrated a reduced sensitivity to light as shown by significantly reduced c-fos expression in the SCN in comparison with controls. These findings constitute the first demonstration that microgravity affects the fundamental properties of the mammalian circadian timing system, specifically by influencing the clock's period, and its ability to maintain temporal organization and phase angle of synchronization to an external LD cycle.

Fuller, Charles A.↗

NASA NTRS2003

System Identification of X-33 Neural Network

Modern flight control research has improved spacecraft survivability as its goal. To this end we need to have a failure detection system on board. In case the spacecraft is performing imperfectly, reconfiguration of control is needed. For that purpose we need to have parameter identification of spacecraft dynamics. Parameter identification of a system is called system identification. We treat the system as a black box which receives some inputs that lead to some outputs. The question is: what kind of parameters for a particular black box can correlate the observed inputs and outputs? Can these parameters help us to predict the outputs for a new given set of inputs? This is the basic problem of system identification. The X33 was supposed to have the onboard capability of evaluating the current performance and if needed to take the corrective measures to adapt to desired performance. The X33 is comprised of both rocket and aircraft vehicle design characteristics and requires, in general, analytical methods for evaluating its flight performance. Its flight consists of four phases: ascent, transition, entry and TAEM (Terminal Area Energy Management). It spends about 200 seconds in ascent phase, reaching an altitude of about 180,000 feet and a speed of about 10 to 15 Mach. During the transition phase which lasts only about 30 seconds, its altitude may increase to about 190,000 feet but its speed is reduced to about 9 Mach. At the beginning of this phase, the Main Engine is Cut Off (MECO) and the control is reconfigured with the help of aerosurfaces (four elevons, two flaps and two rudders) and reaction control system (RCS). The entry phase brings down the altitude of X33 to about 90,000 feet and its speed to about Mach 3. It spends about 250 seconds in this phase. Main engine is still cut off and the vehicle is controlled by complex maneuvers of aerosurfaces. The last phase TAEM lasts for about 450 seconds and the altitude and speed, both are reduced to zero. The present attempt, as a start, focuses only on the entry phase. Since the main engine remains cut off in this phase, there is no thrust acting on the system. This considerably simplifies the equations of motion. We introduce another simplification by assuming the system to be linear after some non-linearities are removed analytically from our consideration. Under these assumptions, the problem could be solved by Classical Statistics by employing the least sum of squares approach. Instead we chose to use the Neural Network method. This method has many advantages. It is modern, more efficient, can be adapted to work even when the assumptions are diluted. In fact, Neural Networks try to model the human brain and are capable of pattern recognition.

Aggarwal, Shiv↗

NASA NTRS2003

A Real Attention-Getter

While most parents would agree that playing videos games is the antithesis of time well spent for their children, recent advances involving NASA biofeedback technology are proving otherwise. The same techniques used to measure brain activity in NASA pilots during flight simulation exercises are now a part of a revolutionary video game system that is helping to improve overall mental awareness for Americans of all ages, including those who suffer from Attention Deficit Hyperactivity Disorder (ADHD).

Source record↗

NASA NTRS2003

Differentially Variable Component Analysis (dVCA): Identifying Multiple Evoked Components using Trial-to-Trial Variability

Electric potentials and magnetic fields generated by ensembles of synchronously active neurons in response to external stimuli provide information essential to understanding the processes underlying cognitive and sensorimotor activity. Interpreting recordings of these potentials and fields is difficult as each detector records signals simultaneously generated by various regions throughout the brain. We introduce the differentially Variable Component Analysis (dVCA) algorithm, which relies on trial-to-trial variability in response amplitude and latency to identify multiple components. Using simulations we evaluate the importance of response variability to component identification, the robustness of dVCA to noise, and its ability to characterize single-trial data. Finally, we evaluate the technique using visually evoked field potentials recorded at incremental depths across the layers of cortical area VI, in an awake, behaving macaque monkey.

Knuth, Kevin H.↗

NASA NTRS1999

A Quantitative Study of Oxygen as a Metabolic Regulator

An acute reduction in oxygen (O2) delivery to a tissue is generally associated with a decrease in phosphocreatine, increases in ADP, NADH/NAD, and inorganic phosphate, increased rates of glycolysis and lactate production, and reduced rates of pyruvate and fatty acid oxidation. However, given the complexity of the human bioenergetic system and its components, it is difficult to determine quantitatively how cellular metabolic processes interact to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). Of special interest is the determination of mechanisms relating tissue oxygenation to observed metabolic responses at the tissue, organ, and whole body levels and the quantification of how changes in tissue O2 availability affect the pathways of ATP synthesis and the metabolites that control these pathways. In this study, we extend a previously developed mathematical model of human bioenergetics to provide a physicochemical framework that permits quantitative understanding of O2 as a metabolic regulator. Specifically, the enhancement permits studying the effects of variations in tissue oxygenation and in parameters controlling the rate of cellular respiration on glycolysis, lactate production, and pyruvate oxidation. The whole body is described as a bioenergetic system consisting of metabolically distinct tissue/organ subsystems that exchange materials with the blood. In order to study the dynamic response of each subsystem to stimuli, we solve the ordinary differential equations describing the temporal evolution of metabolite levels, given the initial concentrations. The solver used in the present study is the packaged code LSODE, as implemented in the NASA Lewis kinetics and sensitivity analysis code, LSENS. A major advantage of LSENS is the efficient procedures supporting systematic sensitivity analysis, which provides the basic methods for studying parameter sensitivities (i.e., changes in model behavior due to parameter variation). Sensitivity analysis establishes relationships between model predictions and problem parameters (i.e., initial concentrations, rate coefficients, etc). It helps determine the effects of uncertainties or changes in these input parameters on the predictions, which ultimately are compared with experimental observations in order to validate the model. Sensitivity analysis can identify parameters that must be determined accurately because of their large effect on the model predictions and parameters that need not be known with great precision because they have little or no effect on the solution. This capability may prove to be important in optimizing the design of experiments, thereby reducing the use of animals. This approach can be applied to study the metabolic effects of reduced oxygen delivery to cardiac muscle due to local myocardial ischemia and the effects of acute hypoxia on brain metabolism. Other important applications of sensitivity analysis include identification of quantitatively relevant pathways and biochemical species within an overall mechanism, when examining the effects of a genetic anomaly or pathological state on energetic system components and whole system behavior.

Radhakrishnan, Krishnan↗

NASA NTRS2003

A Comparison of Model Calculation and Measurement of Absorbed Dose for Proton Irradiation

With the increase in the amount of time spent EVA that is necessary to complete the construction and subsequent maintenance of ISS, it will become increasingly important for ground support personnel to accurately characterize the radiation exposures incurred by EVA crewmembers. Since exposure measurements cannot be taken within the organs of interest, it is necessary to estimate these exposures by calculation. To validate the methods and tools used to develop these estimates, it is necessary to model experiments performed in a controlled environment. This work is such an effort. A human phantom was outfitted with detector equipment and then placed in American EMU and Orlan-M EVA space suits. The suited phantom was irradiated at the LLUPTF with proton beams of known energies. Absorbed dose measurements were made by the spaceflight operational dosimetrist from JSC at multiple sites in the skin, eye, brain, stomach, and small intestine locations in the phantom. These exposures are then modeled using the BRYNTRN radiation transport code developed at the NASA Langley Research Center, and the CAM (computerized anatomical male) human geometry model of Billings and Yucker. Comparisons of absorbed dose calculations with measurements show excellent agreement. This suggests that there is reason to be confident in the ability of both the transport code and the human body model to estimate proton exposure in ground-based laboratory experiments.

Zapp, N.↗

NASA NTRS2003

Dynamic modulation of ocular orientation during visually guided saccades and smooth-pursuit eye movements

Rotational disturbances of the head about an off-vertical yaw axis induce a complex vestibuloocular reflex pattern that reflects the brain's estimate of head angular velocity as well as its estimate of instantaneous head orientation (at a reduced scale) in space coordinates. We show that semicircular canal and otolith inputs modulate torsional and, to a certain extent, also vertical ocular orientation of visually guided saccades and smooth-pursuit eye movements in a similar manner as during off-vertical axis rotations in complete darkness. It is suggested that this graviceptive control of eye orientation facilitates rapid visual spatial orientation during motion.

Non-NASA Center↗

NASA NTRS2003

Persistent neural activity in head direction cells

Many neurons throughout the rat limbic system discharge in relation to the animal's directional heading with respect to its environment. These so-called head direction (HD) cells exhibit characteristics of persistent neural activity. This article summarizes where HD cells are found, their major properties, and some of the important experiments that have been conducted to elucidate how this signal is generated. The number of HD and angular head velocity cells was estimated for several brain areas involved in the generation of the HD signal, including the postsubiculum, anterior dorsal thalamus, lateral mammillary nuclei and dorsal tegmental nucleus. The HD cell signal has many features in common with what is known about how neural integration is accomplished in the oculomotor system. The nature of the HD cell signal makes it an attractive candidate for using neural network models to elucidate the signal's underlying mechanisms. The conditions that any network model must satisfy in order to accurately represent how the nervous system generates this signal are highlighted and areas where key information is missing are discussed.

Non-NASA Center↗

NASA NTRS2003

Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: bifurcation and melanopsin immunoreactivity

The circadian clock in the suprachiasmatic nucleus (SCN) receives direct retinal input via the retinohypothalamic tract (RHT), and the retinal ganglion cells contributing to this projection may be specialized with respect to direct regulation of the circadian clock. However, some ganglion cells forming the RHT bifurcate, sending axon collaterals to the intergeniculate leaflet (IGL) through which light has secondary access to the circadian clock. The present studies provide a more extensive examination of ganglion cell bifurcation and evaluate whether ganglion cells projecting to several subcortical visual nuclei contain melanopsin, a putative ganglion cell photopigment. The results showed that retinal ganglion cells projecting to the SCN send collaterals to the IGL, olivary pretectal nucleus, and superior colliculus, among other places. Melanopsin-immunoreactive (IR) ganglion cells are present in the hamster retina, and some of these cells project to the SCN, IGL, olivary pretectal nucleus, or superior colliculus. Triple-label analysis showed that melanopsin-IR cells bifurcate and project bilaterally to each SCN, but not to the other visual nuclei evaluated. The melanopsin-IR cells have photoreceptive characteristics optimal for circadian rhythm regulation. However, the presence of moderately widespread bifurcation among ganglion cells projecting to the SCN, and projection by melanopsin-IR cells to locations distinct from the SCN and without known rhythm function, suggest that this ganglion cell type is generalized, rather than specialized, with respect to the conveyance of photic information to the brain. Copyright 2003 Wiley-Liss, Inc.

NASA Discipline Neuroscience↗

NASA NTRS2003

Organization of projections from the raphe nuclei to the vestibular nuclei in rats

Previous anatomic and electrophysiological evidence suggests that serotonin modulates processing in the vestibular nuclei. This study examined the organization of projections from serotonergic raphe nuclei to the vestibular nuclei in rats. The distribution of serotonergic axons in the vestibular nuclei was visualized immunohistochemically in rat brain slices using antisera directed against the serotonin transporter. The density of serotonin transporter-immunopositive fibers is greatest in the superior vestibular nucleus and the medial vestibular nucleus, especially along the border of the fourth ventricle; it declines in more lateral and caudal regions of the vestibular nuclear complex. After unilateral iontophoretic injections of Fluoro-Gold into the vestibular nuclei, retrogradely labeled neurons were found in the dorsal raphe nucleus (including the dorsomedial, ventromedial and lateral subdivisions) and nucleus raphe obscurus, and to a minor extent in nucleus raphe pallidus and nucleus raphe magnus. The combination of retrograde tracing with serotonin immunohistofluorescence in additional experiments revealed that the vestibular nuclei receive both serotonergic and non-serotonergic projections from raphe nuclei. Tracer injections in densely innervated regions (especially the medial and superior vestibular nuclei) were associated with the largest numbers of Fluoro-Gold-labeled cells. Differences were observed in the termination patterns of projections from the individual raphe nuclei. Thus, the dorsal raphe nucleus sends projections that terminate predominantly in the rostral and medial aspects of the vestibular nuclear complex, while nucleus raphe obscurus projects relatively uniformly throughout the vestibular nuclei. Based on the topographical organization of raphe input to the vestibular nuclei, it appears that dense projections from raphe nuclei are colocalized with terminal fields of flocculo-nodular lobe and uvula Purkinje cells. It is hypothesized that raphe-vestibular connections are organized to selectively modulate processing in regions of the vestibular nuclear complex that receive input from specific cerebellar zones. This represents a potential mechanism whereby motor activity and behavioral arousal could influence the activity of cerebellovestibular circuits.

NASA Discipline Neuroscience↗

NASA NTRS2003

Nitric oxide in microgravity-induced orthostatic intolerance: relevance to spinal cord injury

Prolonged exposure to microgravity results in cardiovascular deconditioning which is marked by orthostatic intolerance in the returning astronauts and recovering bed-ridden patients. Recent studies conducted in our laboratories at University of California, Irvine have revealed marked elevation of nitric oxide (NO) production in the kidney, heart, brain, and systemic arteries coupled with significant reduction of NO production in the cerebral arteries of microgravity-adapted animals. We have further demonstrated that the observed alteration of NO metabolism is primarily responsible for the associated cardiovascular deconditioning. Recovery from acute spinal cord injury (SCI) is frequently complicated by orthostatic intolerance that is due to the combined effects of the disruption of efferent sympathetic pathway and cardiovascular deconditioning occasioned by prolonged confinement to bed. In this presentation, I will review the nature of altered NO metabolism and its role in the pathogenesis of microgravity-induced cardiovascular deconditioning. The possible relevance of the new findings to orthostatic intolerance in patients with acute SCI and its potential therapeutic implications will be discussed.

Review↗

NASA NTRS2003

[The role of the serotonin system in the stress response of various cells]

The recombinant mouse brain serotonin receptor (5HT1c) was used to study the response of plant cells and oocytes to a stress signal activated by the serotonin-serotonin receptor interaction and associated Ca2+ flow. Based on plant expression vectors, recombinant constructs were obtained to direct production of 5HT1c fused with the green fluorescent protein in plant cells. The mRNAs for hybrid proteins were synthesized in an in vitro transcription system. The expression and function of the hybrid protein and the function of the associated ion channels were electrophysiologically studied in Xenopus laevis oocytes injected with the hybrid mRNA. The hybrid protein was functional and changed the operation of the Ca2+ channel in oocytes. To study the expression of the hybrid constructs in plant cells, the in vitro transcription product was inoculated in tobacco leaves, which then fluoresced.

Non-NASA Center↗

NASA NTRS2000

Effects of microgravity on vestibular development and function in rats: genetics and environment

Our anatomical and behavioral studies of embryonic rats that developed in microgravity suggest that the vestibular sensory system, like the visual system, has genetically mediated processes of development that establish crude connections between the periphery and the brain. Environmental stimuli also regulate connection formation including terminal branch formation and fine-tuning of synaptic contacts. Axons of vestibular sensory neurons from gravistatic as well as linear acceleration receptors reach their targets in both microgravity and normal gravity, suggesting that this is a genetically regulated component of development. However, microgravity exposure delays the development of terminal branches and synapses in gravistatic but not linear acceleration-sensitive neurons and also produces behavioral changes. These latter changes reflect environmentally controlled processes of development.

manned↗

NASA NTRS2003

Common endocrine control of body weight, reproduction, and bone mass

Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.

NASA Discipline Regulatory Physiology↗