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Description
The basal ganglia are four sub-cortical nuclei associated with motor control and reward learning. They are part of numerous larger mostly segregated loops where the basal ganglia receive inputs from specific regions of cortex. Converging on these inputs are dopaminergic neurons that alter their firing based on received and/or predicted rewarding outcomes of a behavior. The basal ganglia's output feeds through the thalamus back to the areas of the cortex where the loop originated. Understanding the dynamic interactions between the various parts of these loops is critical to understanding the basal ganglia's role in motor control and reward based learning. This work developed several experimental techniques that can be applied to further study basal ganglia function. The first technique used micro-volume injections of low concentration muscimol to decrease the firing rates of recorded neurons in a limited area of cortex in rats. Afterwards, an artificial cerebrospinal fluid flush was injected to rapidly eliminate the muscimol's effects. This technique was able to contain the effects of muscimol to approximately a 1 mm radius volume and limited the duration of the drug effect to less than one hour. This technique could be used to temporarily perturb a small portion of the loops involving the basal ganglia and then observe how these effects propagate in other connected regions. The second part applied self-organizing maps (SOM) to find temporal patterns in neural firing rate that are independent of behavior. The distribution of detected patterns frequency on these maps can then be used to determine if changes in neural activity are occurring over time. The final technique focused on the role of the basal ganglia in reward learning. A new conditioning technique was created to increase the occurrence of selected patterns of neural activity without utilizing any external reward or behavior. A pattern of neural activity in the cortex of rats was selected using an SOM. The pattern was then reinforced by being paired with electrical stimulation of the medial forebrain bundle triggering dopamine release in the basal ganglia. Ultimately, this technique proved unsuccessful possibly due to poor selection of the patterns being reinforced.
ContributorsBaldwin, Nathan Aaron (Author) / Helms Tillery, Stephen I (Thesis advisor) / Castaneda, Edward (Committee member) / Buneo, Christopher A (Committee member) / Muthuswamy, Jitendran (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2014
Description
Interictal spikes, together with seizures, have been recognized as the two hallmarks of epilepsy, a brain disorder that 1% of the world's population suffers from. Even though the presence of spikes in brain's electromagnetic activity has diagnostic value, their dynamics are still elusive. It was an objective of this dissertation to formulate a mathematical framework within which the dynamics of interictal spikes could be thoroughly investigated. A new epileptic spike detection algorithm was developed by employing data adaptive morphological filters. The performance of the spike detection algorithm was favorably compared with others in the literature. A novel spike spatial synchronization measure was developed and tested on coupled spiking neuron models. Application of this measure to individual epileptic spikes in EEG from patients with temporal lobe epilepsy revealed long-term trends of increase in synchronization between pairs of brain sites before seizures and desynchronization after seizures, in the same patient as well as across patients, thus supporting the hypothesis that seizures may occur to break (reset) the abnormal spike synchronization in the brain network. Furthermore, based on these results, a separate spatial analysis of spike rates was conducted that shed light onto conflicting results in the literature about variability of spike rate before and after seizure. The ability to automatically classify seizures into clinical and subclinical was a result of the above findings. A novel method for epileptogenic focus localization from interictal periods based on spike occurrences was also devised, combining concepts from graph theory, like eigenvector centrality, and the developed spike synchronization measure, and tested very favorably against the utilized gold rule in clinical practice for focus localization from seizures onset. Finally, in another application of resetting of brain dynamics at seizures, it was shown that it is possible to differentiate with a high accuracy between patients with epileptic seizures (ES) and patients with psychogenic nonepileptic seizures (PNES). The above studies of spike dynamics have elucidated many unknown aspects of ictogenesis and it is expected to significantly contribute to further understanding of the basic mechanisms that lead to seizures, the diagnosis and treatment of epilepsy.
ContributorsKrishnan, Balu (Author) / Iasemidis, Leonidas (Thesis advisor) / Tsakalis, Kostantinos (Committee member) / Spanias, Andreas (Committee member) / Si, Jennie (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
Mechanical properties of cells are important in maintaining physiological functions of biological systems. Quantitative measurement and analysis of mechanical properties can help understand cellular mechanics and its functional relevance and discover physical biomarkers for diseases monitoring and therapeutics.
This dissertation presents a work to develop optical methods for studying cell mechanics which encompasses four applications. Surface plasmon resonance microscopy based optical method has been applied to image intracellular motions and cell mechanical motion. This label-free technique enables ultrafast imaging with extremely high sensitivity in detecting cell deformation. The technique was first applied to study intracellular transportation. Organelle transportation process and displacement steps of motor protein can be tracked using this method. The second application is to study heterogeneous subcellular membrane displacement induced by membrane potential (de)polarization. The application can map the amplitude and direction of cell deformation. The electromechanical coupling of mammalian cells was also observed. The third application is for imaging electrical activity in single cells with sub-millisecond resolution. This technique can fast record actions potentials and also resolve the fast initiation and propagation of electromechanical signals within single neurons. Bright-field optical imaging approach has been applied to the mechanical wave visualization that associated with action potential in the fourth application. Neuron-to-neuron viability of membrane displacement was revealed and heterogeneous subcellular response was observed.
All these works shed light on the possibility of using optical approaches to study millisecond-scale and sub-nanometer-scale mechanical motions. These studies revealed ultrafast and ultra-small mechanical motions at the cellular level, including motor protein-driven motions and electromechanical coupled motions. The observations will help understand cell mechanics and its biological functions. These optical approaches will also become powerful tools for elucidating the interplay between biological and physical functions.
This dissertation presents a work to develop optical methods for studying cell mechanics which encompasses four applications. Surface plasmon resonance microscopy based optical method has been applied to image intracellular motions and cell mechanical motion. This label-free technique enables ultrafast imaging with extremely high sensitivity in detecting cell deformation. The technique was first applied to study intracellular transportation. Organelle transportation process and displacement steps of motor protein can be tracked using this method. The second application is to study heterogeneous subcellular membrane displacement induced by membrane potential (de)polarization. The application can map the amplitude and direction of cell deformation. The electromechanical coupling of mammalian cells was also observed. The third application is for imaging electrical activity in single cells with sub-millisecond resolution. This technique can fast record actions potentials and also resolve the fast initiation and propagation of electromechanical signals within single neurons. Bright-field optical imaging approach has been applied to the mechanical wave visualization that associated with action potential in the fourth application. Neuron-to-neuron viability of membrane displacement was revealed and heterogeneous subcellular response was observed.
All these works shed light on the possibility of using optical approaches to study millisecond-scale and sub-nanometer-scale mechanical motions. These studies revealed ultrafast and ultra-small mechanical motions at the cellular level, including motor protein-driven motions and electromechanical coupled motions. The observations will help understand cell mechanics and its biological functions. These optical approaches will also become powerful tools for elucidating the interplay between biological and physical functions.
ContributorsYang, Yunze (Author) / Tao, Nongjian (Thesis advisor) / Wang, Shaopeng (Committee member) / Goryll, Michael (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2016
Description
Brain-machine interfaces (BMIs) were first imagined as a technology that would allow subjects to have direct communication with prosthetics and external devices (e.g. control over a computer cursor or robotic arm movement). Operation of these devices was not automatic, and subjects needed calibration and training in order to master this control. In short, learning became a key component in controlling these systems. As a result, BMIs have become ideal tools to probe and explore brain activity, since they allow the isolation of neural inputs and systematic altering of the relationships between the neural signals and output. I have used BMIs to explore the process of brain adaptability in a motor-like task. To this end, I trained non-human primates to control a 3D cursor and adapt to two different perturbations: a visuomotor rotation, uniform across the neural ensemble, and a decorrelation task, which non-uniformly altered the relationship between the activity of particular neurons in an ensemble and movement output. I measured individual and population level changes in the neural ensemble as subjects honed their skills over the span of several days. I found some similarities in the adaptation process elicited by these two tasks. On one hand, individual neurons displayed tuning changes across the entire ensemble after task adaptation: most neurons displayed transient changes in their preferred directions, and most neuron pairs showed changes in their cross-correlations during the learning process. On the other hand, I also measured population level adaptation in the neural ensemble: the underlying neural manifolds that control these neural signals also had dynamic changes during adaptation. I have found that the neural circuits seem to apply an exploratory strategy when adapting to new tasks. Our results suggest that information and trajectories in the neural space increase after initially introducing the perturbations, and before the subject settles into workable solutions. These results provide new insights into both the underlying population level processes in motor learning, and the changes in neural coding which are necessary for subjects to learn to control neuroprosthetics. Understanding of these mechanisms can help us create better control algorithms, and design training paradigms that will take advantage of these processes.
ContributorsArmenta Salas, Michelle (Author) / Helms Tillery, Stephen I (Thesis advisor) / Si, Jennie (Committee member) / Buneo, Christopher (Committee member) / Santello, Marco (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2015
Description
Toward the ambitious long-term goal of a fleet of cooperating Flexible Autonomous Machines operating in an uncertain Environment (FAME), this thesis addresses several
critical modeling, design and control objectives for ground vehicles. One central objective was to show how off-the-shelf (low-cost) remote-control (RC) “toy” vehicles can be converted into intelligent multi-capability robotic-platforms for conducting FAME research. This is shown for two vehicle classes: (1) six differential-drive (DD) RC vehicles called Thunder Tumbler (DDTT) and (2) one rear-wheel drive (RWD) RC car called Ford F-150 (1:14 scale). Each DDTT-vehicle was augmented to provide a substantive suite of capabilities as summarized below (It should be noted, however, that only one DDTT-vehicle was augmented with an inertial measurement unit (IMU) and 2.4 GHz RC capability): (1) magnetic wheel-encoders/IMU for(dead-reckoning-based) inner-loop speed-control and outer-loop position-directional-control, (2) Arduino Uno microcontroller-board for encoder-based inner-loop speed-control and encoder-IMU-ultrasound-based outer-loop cruise-position-directional-separation-control, (3) Arduino motor-shield for inner-loop motor-speed-control, (4)Raspberry Pi II computer-board for demanding outer-loop vision-based cruise- position-directional-control, (5) Raspberry Pi 5MP camera for outer-loop cruise-position-directional-control (exploiting WiFi to send video back to laptop), (6) forward-pointing ultrasonic distance/rangefinder sensor for outer-loop separation-control, and (7) 2.4 GHz spread-spectrum RC capability to replace original 27/49 MHz RC. Each “enhanced”/ augmented DDTT-vehicle costs less than 175 but offers the capability of commercially available vehicles costing over 500. Both the Arduino and Raspberry are low-cost, well-supported (software wise) and easy-to-use. For the vehicle classes considered (i.e. DD, RWD), both kinematic and dynamical (planar xy) models are examined. Suitable nonlinear/linear-models are used to develop inner/outer-loopcontrol laws.
All demonstrations presented involve enhanced DDTT-vehicles; one the F-150; one a quadrotor. The following summarizes key hardware demonstrations: (1) cruise-control along line, (2) position-control along line (3) position-control along curve (4) planar (xy) Cartesian stabilization, (5) cruise-control along jagged line/curve, (6) vehicle-target spacing-control, (7) multi-robot spacing-control along line/curve, (8) tracking slowly-moving remote-controlled quadrotor, (9) avoiding obstacle while moving toward target, (10) RC F-150 followed by DDTT-vehicle. Hardware data/video is compared with, and corroborated by, model-based simulations. In short, many capabilities that are critical for reaching the longer-term FAME goal are demonstrated.
critical modeling, design and control objectives for ground vehicles. One central objective was to show how off-the-shelf (low-cost) remote-control (RC) “toy” vehicles can be converted into intelligent multi-capability robotic-platforms for conducting FAME research. This is shown for two vehicle classes: (1) six differential-drive (DD) RC vehicles called Thunder Tumbler (DDTT) and (2) one rear-wheel drive (RWD) RC car called Ford F-150 (1:14 scale). Each DDTT-vehicle was augmented to provide a substantive suite of capabilities as summarized below (It should be noted, however, that only one DDTT-vehicle was augmented with an inertial measurement unit (IMU) and 2.4 GHz RC capability): (1) magnetic wheel-encoders/IMU for(dead-reckoning-based) inner-loop speed-control and outer-loop position-directional-control, (2) Arduino Uno microcontroller-board for encoder-based inner-loop speed-control and encoder-IMU-ultrasound-based outer-loop cruise-position-directional-separation-control, (3) Arduino motor-shield for inner-loop motor-speed-control, (4)Raspberry Pi II computer-board for demanding outer-loop vision-based cruise- position-directional-control, (5) Raspberry Pi 5MP camera for outer-loop cruise-position-directional-control (exploiting WiFi to send video back to laptop), (6) forward-pointing ultrasonic distance/rangefinder sensor for outer-loop separation-control, and (7) 2.4 GHz spread-spectrum RC capability to replace original 27/49 MHz RC. Each “enhanced”/ augmented DDTT-vehicle costs less than 175 but offers the capability of commercially available vehicles costing over 500. Both the Arduino and Raspberry are low-cost, well-supported (software wise) and easy-to-use. For the vehicle classes considered (i.e. DD, RWD), both kinematic and dynamical (planar xy) models are examined. Suitable nonlinear/linear-models are used to develop inner/outer-loopcontrol laws.
All demonstrations presented involve enhanced DDTT-vehicles; one the F-150; one a quadrotor. The following summarizes key hardware demonstrations: (1) cruise-control along line, (2) position-control along line (3) position-control along curve (4) planar (xy) Cartesian stabilization, (5) cruise-control along jagged line/curve, (6) vehicle-target spacing-control, (7) multi-robot spacing-control along line/curve, (8) tracking slowly-moving remote-controlled quadrotor, (9) avoiding obstacle while moving toward target, (10) RC F-150 followed by DDTT-vehicle. Hardware data/video is compared with, and corroborated by, model-based simulations. In short, many capabilities that are critical for reaching the longer-term FAME goal are demonstrated.
ContributorsLin, Zhenyu (Author) / Rodriguez, Armando Antonio (Committee member) / Si, Jennie (Committee member) / Berman, Spring Melody (Committee member) / Arizona State University (Publisher)
Created2015
Description
Stroke remains a leading cause of adult disability in the United States. In recent studies, chronic vagus nerve stimulation (VNS) has been proven to enhance functional recovery when paired with motor rehabilitation training after stroke. Other studies have also demonstrated that delivering VNS during the onset of a stroke may elicit some neuroprotective effects as observed in remaining neural tissue and motor function. While these studies have demonstrated the benefits of VNS as a treatment or therapy in combatting stroke damage, the mechanisms responsible for these effects are still not well understood or known. The aim of this research was to further investigate the mechanisms underlying the efficacy of acute VNS treatment of stroke by observing the effect of VNS when applied after the onset of stroke. Animals were randomly assigned to three groups: Stroke animals received cortical ischemia (ET-1 injection), VNS+Stroke animals received acute VNS starting within 48 hours after cortical ischemia and continuing once per day for three days, or Control animals which received neither the injury nor stimulation. Results showed that stroke animals receiving acute VNS had smaller lesion volumes and larger motor cortical maps than those in the Stroke group. The results suggest VNS may confer neuroprotective effects when delivered within the first 96 hours of stroke.
ContributorsOkada, Kristen Yuri (Author) / Kleim, Jeffrey A (Thesis advisor) / Si, Jennie (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Arizona State University (Publisher)
Created2019