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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

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
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Description
An accurate sense of upper limb position is crucial to reaching movements where sensory information about upper limb position and target location is combined to specify critical features of the movement plan. This dissertation was dedicated to studying the mechanisms of how the brain estimates the limb position in space

An accurate sense of upper limb position is crucial to reaching movements where sensory information about upper limb position and target location is combined to specify critical features of the movement plan. This dissertation was dedicated to studying the mechanisms of how the brain estimates the limb position in space and the consequences of misestimation of limb position on movements. Two independent but related studies were performed. The first involved characterizing the neural mechanisms of limb position estimation in the non-human primate brain. Single unit recordings were obtained in area 5 of the posterior parietal cortex in order to examine the role of this area in estimating limb position based on visual and somatic signals (proprioceptive, efference copy). When examined individually, many area 5 neurons were tuned to the position of the limb in the workspace but very few neurons were modulated by visual feedback. At the population level however decoding of limb position was somewhat more accurate when visual feedback was provided. These findings support a role for area 5 in limb position estimation but also suggest that visual signals regarding limb position are only weakly represented in this area, and only at the population level. The second part of this dissertation focused on the consequences of misestimation of limb position for movement production. It is well known that limb movements are inherently variable. This variability could be the result of noise arising at one or more stages of movement production. Here we used biomechanical modeling and simulation techniques to characterize movement variability resulting from noise in estimating limb position ('sensing noise') and in planning required movement vectors ('planning noise'), and compared that to the variability expected due to noise in movement execution. We found that the effects of sensing and planning related noise on movement variability were dependent upon both the planned movement direction and the initial configuration of the arm and were different in many respects from the effects of execution noise.
ContributorsShi, Ying (Author) / Buneo, Christopher A (Thesis advisor) / Helms Tillery, Stephen (Committee member) / Santello, Marco (Committee member) / He, Jiping (Committee member) / Santos, Veronica (Committee member) / Arizona State University (Publisher)
Created2011
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Description
In the past decade, research on the motor control side of neuroprosthetics has steadily gained momentum. However, modern research in prosthetic development supplements a focus on motor control with a concentration on sensory feedback. Simulating sensation is a central issue because without sensory capabilities, the sophistication of the most advanced

In the past decade, research on the motor control side of neuroprosthetics has steadily gained momentum. However, modern research in prosthetic development supplements a focus on motor control with a concentration on sensory feedback. Simulating sensation is a central issue because without sensory capabilities, the sophistication of the most advanced motor control system fails to reach its full potential. This research is an effort toward the development of sensory feedback specifically for neuroprosthetic hands. The present aim of this work is to understand the processing and representation of cutaneous sensation by evaluating performance and neural activity in somatosensory cortex (SI) during a grasp task. A non-human primate (Macaca mulatta) was trained to reach out and grasp textured instrumented objects with a precision grip. Two different textures for the objects were used, 100% cotton cloth and 60-grade sandpaper, and the target object was presented at two different orientations. Of the 167 cells that were isolated for this experiment, only 42 were recorded while the subject executed a few blocks of successful trials for both textures. These latter cells were used in this study's statistical analysis. Of these, 37 units (88%) exhibited statistically significant task related activity. Twenty-two units (52%) exhibited statistically significant tuning to texture, and 16 units (38%) exhibited statistically significant tuning to posture. Ten of the cells (24%) exhibited statistically significant tuning to both texture and posture. These data suggest that single units in somatosensory cortex can encode multiple phenomena such as texture and posture. However, if this information is to be used to provide sensory feedback for a prosthesis, scientists must learn to further parse cortical activity to discover how to induce specific modalities of sensation. Future experiments should therefore be developed that probe more variables and that more systematically and comprehensively scan somatosensory cortex. This will allow researchers to seek out the existence or non-existence of cortical pockets reserved for certain modalities of sensation, which will be valuable in learning how to later provide appropriate sensory feedback for a prosthesis through cortical stimulation.
ContributorsNaufel, Stephanie (Author) / Helms Tillery, Stephen I (Thesis advisor) / Santos, Veronica J (Thesis advisor) / Buneo, Christopher A (Committee member) / Robert, Jason S (Committee member) / Arizona State University (Publisher)
Created2011
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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

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
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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

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
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Description
In order to successfully implement a neural prosthetic system, it is necessary to understand the control of limb movements and the representation of body position in the nervous system. As this development process continues, it is becoming increasingly important to understand the way multiple sensory modalities are used in limb

In order to successfully implement a neural prosthetic system, it is necessary to understand the control of limb movements and the representation of body position in the nervous system. As this development process continues, it is becoming increasingly important to understand the way multiple sensory modalities are used in limb representation. In a previous study, Shi et al. (2013) examined the multimodal basis of limb position in the superior parietal lobule (SPL) as monkeys reached to and held their arm at various target locations in a frontal plane. Visual feedback was withheld in half the trials, though non-visual (i.e. somatic) feedback was available in all trials. Previous analysis showed that some of the neurons were tuned to limb position and that some neurons had their response modulated by the presence or absence of visual feedback. This modulation manifested in decreases in firing rate variability in the vision condition as compared to nonvision. The decreases in firing rate variability, as shown through decreases in both the Fano factor of spike counts and the coefficient of variation of the inter-spike intervals, suggested that changes were taking place in both trial-by-trial and intra-trial variability. I sought to further probe the source of the change in intra-trial variability through spectral analysis. It was hypothesized that the presence of temporal structure in the vision condition would account for a regularity in firing that would have decreased intra-trial variability. While no peaks were apparent in the spectra, differences in spectral power between visual conditions were found. These differences are suggestive of unique temporal spiking patterns at the individual neuron level that may be influential at the population level.
ContributorsDyson, Keith (Author) / Buneo, Christopher A (Thesis advisor) / Helms-Tillery, Stephen I (Committee member) / Santello, Marco (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Our ability to estimate the position of our body parts in space, a fundamentally proprioceptive process, is crucial for interacting with the environment and movement control. For proprioception to support these actions, the Central Nervous System has to rely on a stored internal representation of the body parts in space.

Our ability to estimate the position of our body parts in space, a fundamentally proprioceptive process, is crucial for interacting with the environment and movement control. For proprioception to support these actions, the Central Nervous System has to rely on a stored internal representation of the body parts in space. However, relatively little is known about this internal representation of arm position. To this end, I developed a method to map proprioceptive estimates of hand location across a 2-d workspace. In this task, I moved each subject's hand to a target location while the subject's eyes were closed. After returning the hand, subjects opened their eyes to verbally report the location of where their fingertip had been. Then, I reconstructed and analyzed the spatial structure of the pattern of estimation errors. In the first couple of experiments I probed the structure and stability of the pattern of errors by manipulating the hand used and tactile feedback provided when the hand was at each target location. I found that the resulting pattern of errors was systematically stable across conditions for each subject, subject-specific, and not uniform across the workspace. These findings suggest that the observed structure of pattern of errors has been constructed through experience, which has resulted in a systematically stable internal representation of arm location. Moreover, this representation is continuously being calibrated across the workspace. In the next two experiments, I aimed to probe the calibration of this structure. To this end, I used two different perturbation paradigms: 1) a virtual reality visuomotor adaptation to induce a local perturbation, 2) and a standard prism adaptation paradigm to induce a global perturbation. I found that the magnitude of the errors significantly increased to a similar extent after each perturbation. This small effect indicates that proprioception is recalibrated to a similar extent regardless of how the perturbation is introduced, suggesting that sensory and motor changes may be two independent processes arising from the perturbation. Moreover, I propose that the internal representation of arm location might be constructed with a global solution and not capable of local changes.
ContributorsRincon Gonzalez, Liliana (Author) / Helms Tillery, Stephen I (Thesis advisor) / Buneo, Christopher A (Thesis advisor) / Santello, Marco (Committee member) / Santos, Veronica (Committee member) / Kleim, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2012
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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

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
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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

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
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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

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