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Description
There is increasing interest in the medical and behavioral health communities towards developing effective strategies for the treatment of chronic diseases. Among these lie adaptive interventions, which consider adjusting treatment dosages over time based on participant response. Control engineering offers a broad-based solution framework for optimizing the effectiveness of such interventions. In this thesis, an approach is proposed to develop dynamical models and subsequently, hybrid model predictive control schemes for assigning optimal dosages of naltrexone, an opioid antagonist, as treatment for a chronic pain condition known as fibromyalgia. System identification techniques are employed to model the dynamics from the daily diary reports completed by participants of a blind naltrexone intervention trial. These self-reports include assessments of outcomes of interest (e.g., general pain symptoms, sleep quality) and additional external variables (disturbances) that affect these outcomes (e.g., stress, anxiety, and mood). Using prediction-error methods, a multi-input model describing the effect of drug, placebo and other disturbances on outcomes of interest is developed. This discrete time model is approximated by a continuous second order model with zero, which was found to be adequate to capture the dynamics of this intervention. Data from 40 participants in two clinical trials were analyzed and participants were classified as responders and non-responders based on the models obtained from system identification. The dynamical models can be used by a model predictive controller for automated dosage selection of naltrexone using feedback/feedforward control actions in the presence of external disturbances. The clinical requirement for categorical (i.e., discrete-valued) drug dosage levels creates a need for hybrid model predictive control (HMPC). The controller features a multiple degree-of-freedom formulation that enables the user to adjust the speed of setpoint tracking, measured disturbance rejection and unmeasured disturbance rejection independently in the closed loop system. The nominal and robust performance of the proposed control scheme is examined via simulation using system identification models from a representative participant in the naltrexone intervention trial. The controller evaluation described in this thesis gives credibility to the promise and applicability of control engineering principles for optimizing adaptive interventions.
ContributorsDeśapāṇḍe, Sunīla (Author) / Rivera, Daniel E. (Thesis advisor) / Si, Jennie (Committee member) / Tsakalis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2011
Description
This study focuses on state estimation of nonlinear discrete time systems with constraints. Physical processes have inherent in them, constraints on inputs, outputs, states and disturbances. These constraints can provide additional information to the estimator in estimating states from the measured output. Recursive filters such as Kalman Filters or Extended Kalman Filters are commonly used in state estimation; however, they do not allow inclusion of constraints in their formulation. On the other hand, computational complexity of full information estimation (using all measurements) grows with iteration and becomes intractable. One way of formulating the recursive state estimation problem with constraints is the Moving Horizon Estimation (MHE) approximation. Estimates of states are calculated from the solution of a constrained optimization problem of fixed size. Detailed formulation of this strategy is studied and properties of this estimation algorithm are discussed in this work. The problem with the MHE formulation is solving an optimization problem in each iteration which is computationally intensive. State estimation with constraints can be formulated as Extended Kalman Filter (EKF) with a projection applied to estimates. The states are estimated from the measurements using standard Extended Kalman Filter (EKF) algorithm and the estimated states are projected on to a constrained set. Detailed formulation of this estimation strategy is studied and the properties associated with this algorithm are discussed. Both these state estimation strategies (MHE and EKF with projection) are tested with examples from the literature. The average estimation time and the sum of square estimation error are used to compare performance of these estimators. Results of the case studies are analyzed and trade-offs are discussed.
ContributorsJoshi, Rakesh (Author) / Tsakalis, Konstantinos (Thesis advisor) / Rodriguez, Armando (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2013
Description
The problem of systematically designing a control system continues to remain a subject of intense research. In this thesis, a very powerful control system design environment for Linear Time-Invariant (LTI) Multiple-Input Multiple-Output (MIMO) plants is presented. The environment has been designed to address a broad set of closed loop metrics and constraints; e.g. weighted H-infinity closed loop performance subject to closed loop frequency and/or time domain constraints (e.g. peak frequency response, peak overshoot, peak controls, etc.). The general problem considered - a generalized weighted mixed-sensitivity problem subject to constraints - permits designers to directly address and tradeoff multivariable properties at distinct loop breaking points; e.g. at plant outputs and at plant inputs. As such, the environment is particularly powerful for (poorly conditioned) multivariable plants. The Youla parameterization is used to parameterize the set of all stabilizing LTI proper controllers. This is used to convexify the general problem being addressed. Several bases are used to turn the resulting infinite-dimensional problem into a finite-dimensional problem for which there exist many efficient convex optimization algorithms. A simple cutting plane algorithm is used within the environment. Academic and physical examples are presented to illustrate the utility of the environment.
ContributorsPuttannaiah, Karan (Author) / Rodriguez, Armando A (Thesis advisor) / Tsakalis, Konstantinos S (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2013
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
This thesis presents a multi-modal motion tracking system for stroke patient rehabilitation. This system deploys two sensor modules: marker-based motion capture system and inertial measurement unit (IMU). The integrated system provides real-time measurement of the right arm and trunk movement, even in the presence of marker occlusion. The information from the two sensors is fused through quaternion-based recursive filters to promise robust detection of torso compensation (undesired body motion). Since this algorithm allows flexible sensor configurations, it presents a framework for fusing the IMU data and vision data that can adapt to various sensor selection scenarios. The proposed system consequently has the potential to improve both the robustness and flexibility of the sensing process. Through comparison between the complementary filter, the extended Kalman filter (EKF), the unscented Kalman filter (UKF) and the particle filter (PF), the experimental part evaluated the performance of the quaternion-based complementary filter for 10 sensor combination scenarios. Experimental results demonstrate the favorable performance of the proposed system in case of occlusion. Such investigation also provides valuable information for filtering algorithm and strategy selection in specific sensor applications.
ContributorsLiu, Yangzi (Author) / Qian, Gang (Thesis advisor) / Olson, Loren (Committee member) / Si, Jennie (Committee member) / Arizona State University (Publisher)
Created2010
Description
This dissertation examines modeling, design and control challenges associatedwith two classes of power converters: a direct current-direct current (DC-DC) step-down (buck)
regulator and a 3-phase (3-ϕ) 4-wire direct current-alternating current
(DC-AC) inverter. These are widely used for power transfer in a variety of industrial
and personal applications. This motivates the precise quantification of conditions
under which existing modeling and design methods yield satisfactory designs, and
the study of alternatives when they don’t. This dissertation describes a method
utilizing Fourier components of the input square wave and the inductor-capacitor (LC)
filter transfer function, which doesn’t require the small ripple approximation. Then,
trade-offs associated with the choice of the filter order are analyzed for integrated buck
converters with a constraint on their chip area. Design specifications which would
justify using a fourth or sixth order filter instead of the widely used second order
one are examined. Next, sampled-data (SD) control of a buck converter is analyzed.
Three methods for the digital controller design are studied: analog design followed
by discretization, direct digital design of a discretized plant, and a “lifting” based
method wherein the sampling time is incorporated in the design process by lifting
the continuous-time design plant before doing the controller design. Specifically,
controller performance is quantified by studying the induced-L2 norm of the closed
loop system for a range of switching/sampling frequencies. In the final segment of
this dissertation, the inner-outer control loop, employed in inverters with an
inductor-capacitor-inductor (LCL) output filter, is studied. Closed loop sensitivities for the
loop broken at the error and the control are examined, demonstrating that traditional
methods only address these properties for one loop-breaking point. New controllers
are then provided for improving both sets of properties.
ContributorsSarkar, Aratrik (Author) / Rodriguez, Armando A (Thesis advisor) / Si, Jennie (Committee member) / Mittelmann, Hans D (Committee member) / Tsakalis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2021
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
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