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Stroke remains the leading cause of adult disability in developed countries. Most survivors live with residual motor impairments that severely diminish independence and quality of life. After stroke, the only accepted treatment for these patients is motor rehabilitation. However, the amount and kind of rehabilitation required to induce clinically significant improvements in motor function is rarely given due to the constraints of our current health care system. Research reported in this dissertation contributes towards developing adjuvant therapies that may augment the impact of motor rehabilitation and improve functional outcome. These studies have demonstrated reorganization of maps within motor cortex as a function of experience in both healthy and brain-injured animals by using intracortical microstimulation technique. Furthermore, synaptic plasticity has been identified as a key neural mechanism in directing motor map plasticity, evidenced by restoration of movement representations within the spared cortical tissue accompanied by increase in synapse number translating into motor improvement after stroke. There is increasing evidence that brain-derived neurotrophic factor (BDNF) modulates synaptic and morphological plasticity in the developing and mature nervous system. Unfortunately, BDNF itself is a poor candidate because of its short half-life, low penetration through the blood brain barrier, and activating multiple receptor units, p75 and TrkB on the neuronal membrane. In order to circumvent this problem efficacy of two recently developed novel TrkB agonists, LM22A-4 and 7,8-dihydroxyflavone, that actively penetrate the blood brain barrier and enhance functional recovery. Findings from these dissertation studies indicate that administration of these pharmacological compounds, accompanied by motor rehabilitation provide a powerful therapeutic tool for stroke recovery.
ContributorsWarraich, Zuha (Author) / Kleim, Jeffrey A (Thesis advisor) / Stabenfeldt, Sarah (Committee member) / Tillery, Stephen-Helms (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2013
Description
The development of advanced, anthropomorphic artificial hands aims to provide upper extremity amputees with improved functionality for activities of daily living. However, many state-of-the-art hands have a large number of degrees of freedom that can be challenging to control in an intuitive manner. Automated grip responses could be built into artificial hands in order to enhance grasp stability and reduce the cognitive burden on the user. To this end, three studies were conducted to understand how human hands respond, passively and actively, to unexpected perturbations of a grasped object along and about different axes relative to the hand. The first study investigated the effect of magnitude, direction, and axis of rotation on precision grip responses to unexpected rotational perturbations of a grasped object. A robust "catch-up response" (a rapid, pulse-like increase in grip force rate previously reported only for translational perturbations) was observed whose strength scaled with the axis of rotation. Using two haptic robots, we then investigated the effects of grip surface friction, axis, and direction of perturbation on precision grip responses for unexpected translational and rotational perturbations for three different hand-centric axes. A robust catch-up response was observed for all axes and directions for both translational and rotational perturbations. Grip surface friction had no effect on the stereotypical catch-up response. Finally, we characterized the passive properties of the precision grip-object system via robot-imposed impulse perturbations. The hand-centric axis associated with the greatest translational stiffness was different than that for rotational stiffness. This work expands our understanding of the passive and active features of precision grip, a hallmark of human dexterous manipulation. Biological insights such as these could be used to enhance the functionality of artificial hands and the quality of life for upper extremity amputees.
ContributorsDe Gregorio, Michael (Author) / Santos, Veronica J. (Thesis advisor) / Artemiadis, Panagiotis K. (Committee member) / Santello, Marco (Committee member) / Sugar, Thomas (Committee member) / Helms Tillery, Stephen I. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Situations of sensory overload are steadily becoming more frequent as the ubiquity of technology approaches reality--particularly with the advent of socio-communicative smartphone applications, and pervasive, high speed wireless networks. Although the ease of accessing information has improved our communication effectiveness and efficiency, our visual and auditory modalities--those modalities that today's computerized devices and displays largely engage--have become overloaded, creating possibilities for distractions, delays and high cognitive load; which in turn can lead to a loss of situational awareness, increasing chances for life threatening situations such as texting while driving. Surprisingly, alternative modalities for information delivery have seen little exploration. Touch, in particular, is a promising candidate given that it is our largest sensory organ with impressive spatial and temporal acuity. Although some approaches have been proposed for touch-based information delivery, they are not without limitations including high learning curves, limited applicability and/or limited expression. This is largely due to the lack of a versatile, comprehensive design theory--specifically, a theory that addresses the design of touch-based building blocks for expandable, efficient, rich and robust touch languages that are easy to learn and use. Moreover, beyond design, there is a lack of implementation and evaluation theories for such languages. To overcome these limitations, a unified, theoretical framework, inspired by natural, spoken language, is proposed called Somatic ABC's for Articulating (designing), Building (developing) and Confirming (evaluating) touch-based languages. To evaluate the usefulness of Somatic ABC's, its design, implementation and evaluation theories were applied to create communication languages for two very unique application areas: audio described movies and motor learning. These applications were chosen as they presented opportunities for complementing communication by offloading information, typically conveyed visually and/or aurally, to the skin. For both studies, it was found that Somatic ABC's aided the design, development and evaluation of rich somatic languages with distinct and natural communication units.
ContributorsMcDaniel, Troy Lee (Author) / Panchanathan, Sethuraman (Thesis advisor) / Davulcu, Hasan (Committee member) / Li, Baoxin (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2012
Description
Bacteriophage (phage) are viruses that infect bacteria. Typical laboratory experiments show that in a chemostat containing phage and susceptible bacteria species, a mutant bacteria species will evolve. This mutant species is usually resistant to the phage infection and less competitive compared to the susceptible bacteria species. In some experiments, both susceptible and resistant bacteria species, as well as phage, can coexist at an equilibrium for hundreds of hours. The current research is inspired by these observations, and the goal is to establish a mathematical model and explore sufficient and necessary conditions for the coexistence. In this dissertation a model with infinite distributed delay terms based on some existing work is established. A rigorous analysis of the well-posedness of this model is provided, and it is proved that the susceptible bacteria persist. To study the persistence of phage species, a "Phage Reproduction Number" (PRN) is defined. The mathematical analysis shows phage persist if PRN > 1 and vanish if PRN < 1. A sufficient condition and a necessary condition for persistence of resistant bacteria are given. The persistence of the phage is essential for the persistence of resistant bacteria. Also, the resistant bacteria persist if its fitness is the same as the susceptible bacteria and if PRN > 1. A special case of the general model leads to a system of ordinary differential equations, for which numerical simulation results are presented.
ContributorsHan, Zhun (Author) / Smith, Hal (Thesis advisor) / Armbruster, Dieter (Committee member) / Kawski, Matthias (Committee member) / Kuang, Yang (Committee member) / Thieme, Horst (Committee member) / Arizona State University (Publisher)
Created2012
Description
The ability to plan, execute, and control goal oriented reaching and grasping movements is among the most essential functions of the brain. Yet, these movements are inherently variable; a result of the noise pervading the neural signals underlying sensorimotor processing. The specific influences and interactions of these noise processes remain unclear. Thus several studies have been performed to elucidate the role and influence of sensorimotor noise on movement variability. The first study focuses on sensory integration and movement planning across the reaching workspace. An experiment was designed to examine the relative contributions of vision and proprioception to movement planning by measuring the rotation of the initial movement direction induced by a perturbation of the visual feedback prior to movement onset. The results suggest that contribution of vision was relatively consistent across the evaluated workspace depths; however, the influence of vision differed between the vertical and later axes indicate that additional factors beyond vision and proprioception influence movement planning of 3-dimensional movements. If the first study investigated the role of noise in sensorimotor integration, the second and third studies investigate relative influence of sensorimotor noise on reaching performance. Specifically, they evaluate how the characteristics of neural processing that underlie movement planning and execution manifest in movement variability during natural reaching. Subjects performed reaching movements with and without visual feedback throughout the movement and the patterns of endpoint variability were compared across movement directions. The results of these studies suggest a primary role of visual feedback noise in shaping patterns of variability and in determining the relative influence of planning and execution related noise sources. The final work considers a computational approach to characterizing how sensorimotor processes interact to shape movement variability. A model of multi-modal feedback control was developed to simulate the interaction of planning and execution noise on reaching variability. The model predictions suggest that anisotropic properties of feedback noise significantly affect the relative influence of planning and execution noise on patterns of reaching variability.
ContributorsApker, Gregory Allen (Author) / Buneo, Christopher A (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / Santos, Veronica (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2012
Description
Effective tactile sensing in prosthetic and robotic hands is crucial for improving the functionality of such hands and enhancing the user's experience. Thus, improving the range of tactile sensing capabilities is essential for developing versatile artificial hands. Multimodal tactile sensors called BioTacs, which include a hydrophone and a force electrode array, were used to understand how grip force, contact angle, object texture, and slip direction may be encoded in the sensor data. Findings show that slip induced under conditions of high contact angles and grip forces resulted in significant changes in both AC and DC pressure magnitude and rate of change in pressure. Slip induced under conditions of low contact angles and grip forces resulted in significant changes in the rate of change in electrode impedance. Slip in the distal direction of a precision grip caused significant changes in pressure magnitude and rate of change in pressure, while slip in the radial direction of the wrist caused significant changes in the rate of change in electrode impedance. A strong relationship was established between slip direction and the rate of change in ratios of electrode impedance for radial and ulnar slip relative to the wrist. Consequently, establishing multiple thresholds or establishing a multivariate model may be a useful method for detecting and characterizing slip. Detecting slip for low contact angles could be done by monitoring electrode data, while detecting slip for high contact angles could be done by monitoring pressure data. Predicting slip in the distal direction could be done by monitoring pressure data, while predicting slip in the radial and ulnar directions could be done by monitoring electrode data.
ContributorsHsia, Albert (Author) / Santos, Veronica J (Thesis advisor) / Santello, Marco (Committee member) / Helms Tillery, Stephen I (Committee member) / Arizona State University (Publisher)
Created2012
Description
In vertebrate outer retina, changes in the membrane potential of horizontal cells affect the calcium influx and glutamate release of cone photoreceptors via a negative feedback. This feedback has a number of important physiological consequences. One is called background-induced flicker enhancement (BIFE) in which the onset of dim background enhances the center flicker response of horizontal cells. The underlying mechanism for the feedback is still unclear but competing hypotheses have been proposed. One is the GABA hypothesis, which states that the feedback is mediated by gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter released from horizontal cells. Another is the ephaptic hypothesis, which contends that the feedback is non-GABAergic and is achieved through the modulation of electrical potential in the intersynaptic cleft between cones and horizontal cells. In this study, a continuum spine model of the cone-horizontal cell synaptic circuitry is formulated. This model, a partial differential equation system, incorporates both the GABA and ephaptic feedback mechanisms. Simulation results, in comparison with experiments, indicate that the ephaptic mechanism is necessary in order for the model to capture the major spatial and temporal dynamics of the BIFE effect. In addition, simulations indicate that the GABA mechanism may play some minor modulation role.
ContributorsChang, Shaojie (Author) / Baer, Steven M. (Thesis advisor) / Gardner, Carl L (Thesis advisor) / Crook, Sharon M (Committee member) / Kuang, Yang (Committee member) / Ringhofer, Christian (Committee member) / Arizona State University (Publisher)
Created2012
Description
Salmonella enterica is a gastrointestinal (GI) pathogen that can cause systemic diseases. It invades the host through the GI tract and can induce powerful immune responses in addition to disease. Thus, it is considered as a promising candidate to use as oral live vaccine vectors. Scientists have been making great efforts to get a properly attenuated Salmonella vaccine strain for a long time, but could not achieve a balance between attenuation and immunogenicity. So the regulated delayed attenuation/lysis Salmonella vaccine vectors were proposed as a design to seek this balance. The research work is progressing steadily, but more improvements need to be made. As one of the possible improvements, the cyclic adenosine monophosphate (cAMP) -independent cAMP receptor protein (Crp*) is expected to protect the Crp-dependent crucial regulator, araC PBAD, in these vaccine designs from interference by glucose, which decreases synthesis of cAMP, and enhance the colonizing ability by and immunogenicity of the vaccine strains. In this study, the cAMP-independent crp gene mutation, crp-70, with or without araC PBAD promoter cassette, was introduced into existing Salmonella vaccine strains. Then the plasmid stability, growth rate, resistance to catabolite repression, colonizing ability, immunogenicity and protection to challenge of these new strains were compared with wild-type crp or araC PBAD crp strains using western blots, enzyme-linked immunosorbent assays (ELISA) and animal studies, so as to evaluate the effects of the crp-70 mutation on the vaccine strains. The performances of the crp-70 strains in some aspects were closed to or even exceeded the crp+ strains, but generally they did not exhibit the expected advantages compared to their wild-type parents. Crp-70 rescued the expression of araC PBAD fur from catabolite repression. The strain harboring araC PBAD crp-70 was severely affected by its slow growth, and its colonizing ability and immunogenicity was much weaker than the other strains. The Pcrp crp-70 strain showed relatively good ability in colonization and immune stimulation. Both the araC PBAD crp-70 and the Pcrp crp-70 strains could provide certain levels of protection against the challenge with virulent pneumococci, which were a little lower than for the crp+ strains.
ContributorsShao, Shihuan (Author) / Curtiss, Roy (Thesis advisor) / Arizona State University (Publisher)
Created2012
Description
Humans moving in the environment must frequently change walking speed and direction to negotiate obstacles and maintain balance. Maneuverability and stability requirements account for a significant part of daily life. While constant-average-velocity (CAV) human locomotion in walking and running has been studied extensively unsteady locomotion has received far less attention. Although some studies have described the biomechanics and neurophysiology of maneuvers, the underlying mechanisms that humans employ to control unsteady running are still not clear. My dissertation research investigated some of the biomechanical and behavioral strategies used for stable unsteady locomotion. First, I studied the behavioral level control of human sagittal plane running. I tested whether humans could control running using strategies consistent with simple and independent control laws that have been successfully used to control monopod robots. I found that humans use strategies that are consistent with the distributed feedback control strategies used by bouncing robots. Humans changed leg force rather than stance duration to control center of mass (COM) height. Humans adjusted foot placement relative to a "neutral point" to change running speed increment between consecutive flight phases, i.e. a "pogo-stick" rather than a "unicycle" strategy was adopted to change running speed. Body pitch angle was correlated by hip moments if a proportional-derivative relationship with time lags corresponding to pre-programmed reaction (87 ± 19 ms) was assumed. To better understand the mechanisms of performing successful maneuvers, I studied the functions of joints in the lower extremities to control COM speed and height. I found that during stance, the hip functioned as a power generator to change speed. The ankle switched between roles as a damper and torsional spring to contributing both to speed and elevation changes. The knee facilitated both speed and elevation control by absorbing mechanical energy, although its contribution was less than hip or ankle. Finally, I studied human turning in the horizontal plane. I used a morphological perturbation (increased body rotational inertia) to elicit compensational strategies used to control sidestep cutting turns. Humans use changes to initial body angular speed and body pre-rotation to prevent changes in braking forces.
ContributorsQiao, Mu, 1981- (Author) / Jindrich, Devin L (Thesis advisor) / Dounskaia, Natalia (Committee member) / Abbas, James (Committee member) / Hinrichs, Richard (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2012
Description
Approximately 1.7 million people in the United States are living with limb loss and are in need of more sophisticated devices that better mimic human function. In the Human Machine Integration Laboratory, a powered, transtibial prosthetic ankle was designed and build that allows a person to regain ankle function with improved ankle kinematics and kinetics. The ankle allows a person to walk normally and up and down stairs, but volitional control is still an issue. This research tackled the problem of giving the user more control over the prosthetic ankle using a force/torque circuit. When the user presses against a force/torque sensor located inside the socket the prosthetic foot plantar flexes or moves downward. This will help the user add additional push-off force when walking up slopes or stairs. It also gives the user a sense of control over the device.
ContributorsFronczyk, Adam (Author) / Sugar, Thomas G. (Thesis advisor) / Helms-Tillery, Stephen (Thesis advisor) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2012