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At least 19 records

Physiological and Molecular Genetic Effects of Time-Varying Electromagnetic Fields on Human Neuronal Cells

The present investigation details the development of model systems for growing two- and three-dimensional human neural progenitor cells within a culture medium facilitated by a time-varying electromagnetic field (TVEMF). The cells and culture medium are contained within a two- or three-dimensional culture vessel, and the electromagnetic field is emitted from an electrode or coil. These studies further provide methods to promote neural tissue regeneration by means of culturing the neural cells in either configuration. Grown in two dimensions, neuronal cells extended longitudinally, forming tissue strands extending axially along and within electrodes comprising electrically conductive channels or guides through which a time-varying electrical current was conducted. In the three-dimensional aspect, exposure to TVEMF resulted in the development of three-dimensional aggregates, which emulated organized neural tissues. In both experimental configurations, the proliferation rate of the TVEMF cells was 2.5 to 4.0 times the rate of the non-waveform cells. Each of the experimental embodiments resulted in similar molecular genetic changes regarding the growth potential of the tissues as measured by gene chip analyses, which measured more than 10,000 human genes simultaneously.

Goodwin, Thomas J.↗

An Optimization of Pulsed ElectroMagnetic Fields Study

To date, in our research we have focused on the use of normal human neuronal progenitor (NHNP) cells because of their importance in human nervous system regeneration, development and maintenance, but we have developed 2-D and 3-D bioreactors that can accommodate any cell line. In this Project, we will include the use of tissues important for physiological regeneration: Human osteoblasts or chondrocytes, and vascular cells. Our initial results with the NHNP cells were quite startling using extremely low-level electromagnetic fields (5 microtesla at 10Hz; 6mA). The low-amplitude, rapidly time-varying electromagnetic fields exert a very potent effect on the proliferation, morphology, and gene expression of the cells in culture, both in standard 2-dimensional culture plates as well as cells organized into 3-dimensional tissue-like assemblies (TLAs) in a 3D bioreactor. We have replicated our preliminary results many, many times, have analyzed the gene expression using gene arrays (followed by Luminex analysis for protein production), and have monitored cell proliferation, orientation, morphology, and glucose metabolism, and we are confident that we have a stable and reliable model to study the control of high-level cellular processes by application of low-amplitude, time varying electromagnetic fields (TVEMF) (1, 2). In additional studies at the University of Michigan, we have been able to generate functional in vitro engineered mammalian skeletal muscle, and have employed nerve-muscle co-culture techniques to promote axonal sprouting. We believe that nearly all tissues, in particular, neural, are susceptible to the influences of low-level TVEMF.

Goodwin, Thomas J.↗

Spindle neurons of the human anterior cingulate cortex

The human anterior cingulate cortex is distinguished by the presence of an unusual cell type, a large spindle neuron in layer Vb. This cell has been noted numerous times in the historical literature but has not been studied with modern neuroanatomic techniques. For instance, details regarding the neuronal class to which these cells belong and regarding their precise distribution along both ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking. In the present study, morphological features and the anatomic distribution of this cell type were studied using computer-assisted mapping and immunocytochemical techniques. Spindle neurons are restricted to the subfields of the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density in anterior portions of this area than in posterior portions, and tapering off in the transition zone between anterior and posterior cingulate cortex. Furthermore, a majority of the spindle cells at any level is located in subarea 24b on the gyral surface. Immunocytochemical analysis revealed that the neurofilament protein triple was present in a large percentage of these neurons and that they did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI into the cingulum bundle revealed that these cells are projection neurons. Finally, spindle cells were consistently affected in Alzheimer's disease cases, with an overall loss of about 60%. Taken together, these observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.

Non-NASA Center↗

Influence of respiratory motor neurone activity on human autonomic and haemodynamic rhythms

Although humans hold great advantages over other species as subjects for biomedical research, they also bring major disadvantages. One is that among the many rhythmic physiological signals that can be recorded, there is no sure way to know which individual change precedes another, or which change represents cause and which represents effect. In an attempt to deal with the inherent complexity of research conducted in intact human subjects, we developed and used a structural equation model to analyse responses of healthy young men to pharmacological changes of arterial pressure and graded inspiratory resistance, before and after vagomimetic atropine. Our model yielded a good fit of the experimental data, with a system weighted R2 of 0.77, and suggested that our treatments exerted both direct and indirect influences on the variables we measured. Thus, infusions of nitroprusside and phenylephrine exerted all of their direct effects by lowering and raising arterial pressure; the changes of R-R intervals, respiratory sinus arrhythmia and arterial pressure fluctuations that these drugs provoked, were indirect consequences of arterial pressure changes. The only direct effect of increased inspiratory resistance was augmentation of arterial pressure fluctuations. These results may provide a new way to disentangle and understand responses of intact human subjects to experimental forcings. The principal new insight we derived from our modelling is that respiratory gating of vagal-cardiac motor neurone firing is nearly maximal at usual levels of arterial pressure and inspiratory motor neurone activity.

Non-NASA Center↗

3D Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent VZV Infection

Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

Goodwin, Thomas J.↗

The cortex transform - Rapid computation of simulated neural images

With a goal of providing means for accelerating the image processing, machine vision, and testing of human vision models, an image transform was designed, which makes it possible to map an image into a set of images that vary in resolution and orientation. Each pixel in the output may be regarded as the simulated response of a neuron in human visual cortex. The transform is amenable to a number of shortcuts that greatly reduce the amount of computation.

Watson, Andrew B.↗

Overview of the Neurolab Spacelab mission

Neurolab is a NASA Spacelab mission with multinational cooperative participation that is dedicated to research on the nervous system. The nervous systems of all animal species have evolved in a one-g environment and are functionally influenced by the presence of gravity. The absence of gravity presents a unique opportunity to gain new insights into basic neurologic functions as well as an enhanced understanding of physiological and behavioral responses mediated by the nervous system. The primary goal of Neurolab is to expand our understanding of how the nervous system develops, functions in, and adapts to microgravity space flight. Twenty-six peer reviewed investigations using human and nonhuman test subjects were assigned to one of eight science discipline teams. Individual and integrated experiments within these teams have been designed to collect a wide range of physiological and behavior data in flight as well as pre- and postflight. Information from these investigations will be applicable to enhancing the well being and performance of future long duration space travelers, will contribute to our understanding of normal and pathological functioning of the nervous system, and may be applied by the medical community to enhance the health of humans on Earth.

manned↗

Spatial updating in human parietal cortex

Single neurons in monkey parietal cortex update visual information in conjunction with eye movements. This remapping of stimulus representations is thought to contribute to spatial constancy. We hypothesized that a similar process occurs in human parietal cortex and that we could visualize it with functional MRI. We scanned subjects during a task that involved remapping of visual signals across hemifields. We observed an initial response in the hemisphere contralateral to the visual stimulus, followed by a remapped response in the hemisphere ipsilateral to the stimulus. We ruled out the possibility that this remapped response resulted from either eye movements or visual stimuli alone. Our results demonstrate that updating of visual information occurs in human parietal cortex.

NASA Discipline Neuroscience↗

Bioinspired engineering of exploration systems for NASA and DoD

A new approach called bioinspired engineering of exploration systems (BEES) and its value for solving pressing NASA and DoD needs are described. Insects (for example honeybees and dragonflies) cope remarkably well with their world, despite possessing a brain containing less than 0.01% as many neurons as the human brain. Although most insects have immobile eyes with fixed focus optics and lack stereo vision, they use a number of ingenious, computationally simple strategies for perceiving their world in three dimensions and navigating successfully within it. We are distilling selected insect-inspired strategies to obtain novel solutions for navigation, hazard avoidance, altitude hold, stable flight, terrain following, and gentle deployment of payload. Such functionality provides potential solutions for future autonomous robotic space and planetary explorers. A BEES approach to developing lightweight low-power autonomous flight systems should be useful for flight control of such biomorphic flyers for both NASA and DoD needs. Recent biological studies of mammalian retinas confirm that representations of multiple features of the visual world are systematically parsed and processed in parallel. Features are mapped to a stack of cellular strata within the retina. Each of these representations can be efficiently modeled in semiconductor cellular nonlinear network (CNN) chips. We describe recent breakthroughs in exploring the feasibility of the unique blending of insect strategies of navigation with mammalian visual search, pattern recognition, and image understanding into hybrid biomorphic flyers for future planetary and terrestrial applications. We describe a few future mission scenarios for Mars exploration, uniquely enabled by these newly developed biomorphic flyers.

Space Flight↗

The cerebellum: a neuronal learning machine?

Comparison of two seemingly quite different behaviors yields a surprisingly consistent picture of the role of the cerebellum in motor learning. Behavioral and physiological data about classical conditioning of the eyelid response and motor learning in the vestibulo-ocular reflex suggests that (i) plasticity is distributed between the cerebellar cortex and the deep cerebellar nuclei; (ii) the cerebellar cortex plays a special role in learning the timing of movement; and (iii) the cerebellar cortex guides learning in the deep nuclei, which may allow learning to be transferred from the cortex to the deep nuclei. Because many of the similarities in the data from the two systems typify general features of cerebellar organization, the cerebellar mechanisms of learning in these two systems may represent principles that apply to many motor systems.

Non-NASA Center↗

Insect-Inspired Flight Control for Unmanned Aerial Vehicles

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

Thakoor, Sarita↗

Biological neural networks as model systems for designing future parallel processing computers

One of the more interesting debates of the present day centers on whether human intelligence can be simulated by computer. The author works under the premise that neurons individually are not smart at all. Rather, they are physical units which are impinged upon continuously by other matter that influences the direction of voltage shifts across the units membranes. It is only the action of a great many neurons, billions in the case of the human nervous system, that intelligent behavior emerges. What is required to understand even the simplest neural system is painstaking analysis, bit by bit, of the architecture and the physiological functioning of its various parts. The biological neural network studied, the vestibular utricular and saccular maculas of the inner ear, are among the most simple of the mammalian neural networks to understand and model. While there is still a long way to go to understand even this most simple neural network in sufficient detail for extrapolation to computers and robots, a start was made. Moreover, the insights obtained and the technologies developed help advance the understanding of the more complex neural networks that underlie human intelligence.

Ross, Muriel D.↗

A Role for MST Neurons in Heading Estimation

A template model of human visual self-motion perception, which uses neurophysiologically realistic "heading detectors", is consistent with numerous human psychophysical results including the failure of humans to estimate their heading (direction of forward translation) accurately under certain visual conditions. We tested the model detectors with stimuli used by others in single-unit studies. The detectors showed emergent properties similar to those of MST neurons: (1) Sensitivity to non-preferred flow; Each detector is tuned to a specific combination of flow components and its response is systematically reduced by the addition of nonpreferred flow, and (2) Position invariance; The detectors maintain their apparent preference for particular flow components over large regions of their receptive fields. It has been argued that this latter property is incompatible with MST playing a role in heading perception. The model however demonstrates how neurons with the above response properties could still support accurate heading estimation within extrastriate cortical maps.

Stone, L. S.↗

A Role for MST Neurons in Heading Estimation

A template model of human visual self-motion perception (Perrone, JOSA, 1992; Perrone & Stone, Vis. Res., in press), which uses neurophysiologically realistic "heading detectors", is consistent with numerous human psychophysical results (Warren & Hannon, Nature, 1988; Stone & Perrone, Neuro. Abstr., 1991) including the failure of humans to estimate their heading (direction of forward translation) accurately under certain visual conditions (Royden et al., Nature, 1992). We tested the model detectors with stimuli used by others in- single-unit studies. The detectors showed emergent properties similar to those of MST neurons: 1) Sensitivity to non-preferred flow. Each detector is tuned to a specific combination of flow components and its response is systematically reduced by the addition of nonpreferred flow (Orban et al., PNAS, 1992), and 2) Position invariance. The detectors maintain their apparent preference for particular flow components over large regions of their receptive fields (e.g. Duffy & Wurtz, J. Neurophys., 1991; Graziano et al., J. Neurosci., 1994). It has been argued that this latter property is incompatible with MST playing a role in heading perception. The model however demonstrates how neurons with the above response properties could still support accurate heading estimation within extrastriate cortical maps.

Stone, Leland Scott↗

Technical and commerical challenges in high Tc SQUIDs and their industrial applications

A SQUID is the most sensitive device for measuring changes in magnetic flux. Since its discovery in the sixties, scientists have made consistent efforts to apply SQUID's to various applications. Instruments that are the most sensitive in their respective categories have been built, such as SQUID DC susceptometer that is now manufactured by Quantum Design, pico-voltmeter which could measure 10(exp -14) volts, and gravitational wave detectors. One of the most successful applications of SQUID's is in magnetoencephalography, a non-invasive technique for investigating neuronal activity in the living human brain. This technique employs a multi-channel SQUID magnetometer that maps the weak magnetic field generated by small current when information is processed in brain, and its performance is marvelous.

Lu, D. F.↗

Cortical neuronal cytoskeletal changes associated with FIV infection

HIV-1 infection is often complicated by central nervous system (CNS) dysfunction. Degenerative neuronal changes as well as neuronal loss have been documented in individuals with AIDS. Feline immunodeficiency virus (FIV) infection of cats provides a model for both the immune and the central nervous system manifestations of HIV infection of humans. In this study we have examined neurons in the frontal cortex of feline immunodeficiency virus-infected cats and controls for immunoreactivity with SMI 32, an antibody recognizing a non-phosphorylated epitope on neurofilaments. We noted a significant increase in the number of immunoreactive pyramidal cells in infected animals compared to controls. The changes seen in the neuronal cytoskeleton as a consequence of the inoculation with FIV were similar to those seen in humans undergoing the normal aging process as well as those suffering from neurological diseases, including Alzheimer's and dementia pugilistica. The changes we noted in the feline brain were also similar to that reported in animals with traumatic injuries or with spontaneously occurring or induced motor neuron diseases, suggesting that the increase in reactivity represents a deleterious effect of FIV on the central nervous system.

Non-NASA Center↗

Protecting Neural Structures and Cognitive Function During Prolonged Space Flight by Targeting the Brain Derived Neurotrophic Factor Molecular Network

Brain derived neurotrophic factor (BDNF) is the main activity-dependent neurotrophin in the human nervous system. BDNF is implicated in production of new neurons from dentate gyrus stem cells (hippocampal neurogenesis), synapse formation, sprouting of new axons, growth of new axons, sprouting of new dendrites, and neuron survival. Alterations in the amount or activity of BDNF can produce significant detrimental changes to cortical function and synaptic transmission in the human brain. This can result in glial and neuronal dysfunction, which may contribute to a range of clinical conditions, spanning a number of learning, behavioral, and neurological disorders. There is an extensive body of work surrounding the BDNF molecular network, including BDNF gene polymorphisms, methylated BDNF gene promoters, multiple gene transcripts, varied BDNF functional proteins, and different BDNF receptors (whose activation differentially drive the neuron to neurogenesis or apoptosis). BDNF is also closely linked to mitochondrial biogenesis through PGC-1alpha, which can influence brain and muscle metabolic efficiency. BDNF AS A HUMAN SPACE FLIGHT COUNTERMEASURE TARGET Earth-based studies reveal that BDNF is negatively impacted by many of the conditions encountered in the space environment, including oxidative stress, radiation, psychological stressors, sleep deprivation, and many others. A growing body of work suggests that the BDNF network is responsive to a range of diet, nutrition, exercise, drug, and other types of influences. This section explores the BDNF network in the context of 1) protecting the brain and nervous system in the space environment, 2) optimizing neurobehavioral performance in space, and 3) reducing the residual effects of space flight on the nervous system on return to Earth

Schmidt, M. A.↗