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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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In the late 1960s, Granger published a seminal study on causality in time series, using linear interdependencies and information transfer. Recent developments in the field of information theory have introduced new methods to investigate the transfer of information in dynamical systems. Using concepts from Chaos and Markov theory, much of

In the late 1960s, Granger published a seminal study on causality in time series, using linear interdependencies and information transfer. Recent developments in the field of information theory have introduced new methods to investigate the transfer of information in dynamical systems. Using concepts from Chaos and Markov theory, much of these methods have evolved to capture non-linear relations and information flow between coupled dynamical systems with applications to fields like biomedical signal processing. This thesis deals with the application of information theory to non-linear multivariate time series and develops measures of information flow to identify significant drivers and response (driven) components in networks of coupled sub-systems with variable coupling in strength and direction (uni- or bi-directional) for each connection. Transfer Entropy (TE) is used to quantify pairwise directional information. Four TE-based measures of information flow are proposed, namely TE Outflow (TEO), TE Inflow (TEI), TE Net flow (TEN), and Average TE flow (ATE). First, the reliability of the information flow measures on models, with and without noise, is evaluated. The driver and response sub-systems in these models are identified. Second, these measures are applied to electroencephalographic (EEG) data from two patients with focal epilepsy. The analysis showed dominant directions of information flow between brain sites and identified the epileptogenic focus as the system component typically with the highest value for the proposed measures (for example, ATE). Statistical tests between pre-seizure (preictal) and post-seizure (postictal) information flow also showed a breakage of the driving of the brain by the focus after seizure onset. The above findings shed light on the function of the epileptogenic focus and understanding of ictogenesis. It is expected that they will contribute to the diagnosis of epilepsy, for example by accurate identification of the epileptogenic focus from interictal periods, as well as the development of better seizure detection, prediction and control methods, for example by isolating pathologic areas of excessive information flow through electrical stimulation.
ContributorsPrasanna, Shashank (Author) / Jassemidis, Leonidas (Thesis advisor) / Tsakalis, Konstantinos (Thesis advisor) / Tepedelenlioğlu, Cihan (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Development of post-traumatic epilepsy (PTE) after traumatic brain injury (TBI) is a major health concern (5% - 50% of TBI cases). A significant problem in TBI management is the inability to predict which patients will develop PTE. Such prediction, followed by timely treatment, could be highly beneficial to TBI patients.

Development of post-traumatic epilepsy (PTE) after traumatic brain injury (TBI) is a major health concern (5% - 50% of TBI cases). A significant problem in TBI management is the inability to predict which patients will develop PTE. Such prediction, followed by timely treatment, could be highly beneficial to TBI patients. Six male Sprague-Dawley rats were subjected to a controlled cortical impact (CCI). A 6mm piston was pneumatically driven 3mm into the right parietal cortex with velocity of 5.5m/s. The rats were subsequently implanted with 6 intracranial electroencephalographic (EEG) electrodes. Long-term (14-week) continuous EEG recordings were conducted. Using linear (coherence) and non-linear (Lyapunov exponents) measures of EEG dynamics in conjunction with measures of network connectivity, we studied the evolution over time of the functional connectivity between brain sites in order to identify early precursors of development of epilepsy. Four of the six TBI rats developed PTE 6 to 10 weeks after the initial insult to the brain. Analysis of the continuous EEG from these rats showed a gradual increase of the connectivity between critical brain sites in terms of their EEG dynamics, starting at least 2 weeks prior to their first spontaneous seizure. In contrast, for the rats that did not develop epilepsy, connectivity levels did not change, or decreased during the whole course of the experiment across pairs of brain sites. Consistent behavior of functional connectivity changes between brain sites and the "focus" (site of impact) over time was demonstrated for coherence in three out of the four epileptic and in both non-epileptic rats, while for STLmax in all four epileptic and in both non-epileptic rats. This study provided us with the opportunity to quantitatively investigate several aspects of epileptogenesis following traumatic brain injury. Our results strongly support a network pathology that worsens with time. It is conceivable that the observed changes in spatiotemporal dynamics after an initial brain insult, and long before the development of epilepsy, could constitute a basis for predictors of epileptogenesis in TBI patients.
ContributorsTobin, Edward (Author) / Iasemidis, Leonidas (Thesis advisor) / Tsakalis, Konstantinos (Committee member) / Muthuswamy, Jitendran (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Approximately 1% of the world population suffers from epilepsy. Continuous long-term electroencephalographic (EEG) monitoring is the gold-standard for recording epileptic seizures and assisting in the diagnosis and treatment of patients with epilepsy. However, this process still requires that seizures are visually detected and marked by experienced and trained electroencephalographers. The

Approximately 1% of the world population suffers from epilepsy. Continuous long-term electroencephalographic (EEG) monitoring is the gold-standard for recording epileptic seizures and assisting in the diagnosis and treatment of patients with epilepsy. However, this process still requires that seizures are visually detected and marked by experienced and trained electroencephalographers. The motivation for the development of an automated seizure detection algorithm in this research was to assist physicians in such a laborious, time consuming and expensive task. Seizures in the EEG vary in duration (seconds to minutes), morphology and severity (clinical to subclinical, occurrence rate) within the same patient and across patients. The task of seizure detection is also made difficult due to the presence of movement and other recording artifacts. An early approach towards the development of automated seizure detection algorithms utilizing both EEG changes and clinical manifestations resulted to a sensitivity of 70-80% and 1 false detection per hour. Approaches based on artificial neural networks have improved the detection performance at the cost of algorithm's training. Measures of nonlinear dynamics, such as Lyapunov exponents, have been applied successfully to seizure prediction. Within the framework of this MS research, a seizure detection algorithm based on measures of linear and nonlinear dynamics, i.e., the adaptive short-term maximum Lyapunov exponent (ASTLmax) and the adaptive Teager energy (ATE) was developed and tested. The algorithm was tested on long-term (0.5-11.7 days) continuous EEG recordings from five patients (3 with intracranial and 2 with scalp EEG) and a total of 56 seizures, producing a mean sensitivity of 93% and mean specificity of 0.048 false positives per hour. The developed seizure detection algorithm is data-adaptive, training-free and patient-independent. It is expected that this algorithm will assist physicians in reducing the time spent on detecting seizures, lead to faster and more accurate diagnosis, better evaluation of treatment, and possibly to better treatments if it is incorporated on-line and real-time with advanced neuromodulation therapies for epilepsy.
ContributorsVenkataraman, Vinay (Author) / Jassemidis, Leonidas (Thesis advisor) / Spanias, Andreas (Thesis advisor) / Tsakalis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Microbial fuel cells(MFC) use micro-organisms called anode-respiring bacteria(ARB) to convert chemical energy into electrical energy. This process can not only treat wastewater but can also produce useful byproduct hydrogen peroxide(H2O2). Process variables like anode potential and pH play important role in the MFC operation and the focus of this dissertation

Microbial fuel cells(MFC) use micro-organisms called anode-respiring bacteria(ARB) to convert chemical energy into electrical energy. This process can not only treat wastewater but can also produce useful byproduct hydrogen peroxide(H2O2). Process variables like anode potential and pH play important role in the MFC operation and the focus of this dissertation are pH and potential control problems.

Most of the adaptive pH control solutions use signal-based-norms as cost functions, but their strong dependency on excitation signal properties makes them sensitive to noise, disturbances, and modeling errors. System-based-norm( H-infinity) cost functions provide a viable alternative for the adaptation as they are less susceptible to the signal properties. Two variants of adaptive pH control algorithms that use approximate H-infinity frequency loop-shaping (FLS) cost metrics are proposed in this dissertation.

A pH neutralization process with high retention time is studied using lab scale experiments and the experimental setup is used as a basis to develop a first-principles model. The analysis of such a model shows that only the gain of the process varies significantly with operating conditions and with buffering capacity. Consequently, the adaptation of the controller gain (single parameter) is sufficient to compensate for the variation in process gain and the focus of the proposed algorithms is the adaptation of the PI controller gain. Computer simulations and lab-scale experiments are used to study tracking, disturbance rejection and adaptation performance of these algorithms under different excitation conditions. Results show the proposed algorithm produces optimum that is less dependent on the excitation as compared to a commonly used L2 cost function based algorithm and tracks set-points reasonably well under practical conditions. The proposed direct pH control algorithm is integrated with the combined activated sludge anaerobic digestion model (CASADM) of an MFC and it is shown pH control improves its performance.

Analytical grade potentiostats are commonly used in MFC potential control, but, their high cost (>$6000) and large size, make them nonviable for the field usage. This dissertation proposes an alternate low-cost($200) portable potentiostat solution. This potentiostat is tested using a ferricyanide reactor and results show it produces performance close to an analytical grade potentiostat.
ContributorsJoshi, Rakesh (Author) / Tsakalis, Konstantinos (Thesis advisor) / Rodriguez, Armando (Committee member) / Torres, Cesar (Committee member) / Spanias, Andreas (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Buck converters are electronic devices that changes a voltage from one level to a lower one and are present in many everyday applications. However, due to factors like aging, degradation or failures, these devices require a system identification process to track and diagnose their parameters. The system identification process should

Buck converters are electronic devices that changes a voltage from one level to a lower one and are present in many everyday applications. However, due to factors like aging, degradation or failures, these devices require a system identification process to track and diagnose their parameters. The system identification process should be performed on-line to not affect the normal operation of the device. Identifying the parameters of the system is essential to design and tune an adaptive proportional-integral-derivative (PID) controller.

Three techniques were used to design the PID controller. Phase and gain margin still prevails as one of the easiest methods to design controllers. Pole-zero cancellation is another technique which is based on pole-placement. However, although these controllers can be easily designed, they did not provide the best response compared to the Frequency Loop Shaping (FLS) technique. Therefore, since FLS showed to have a better frequency and time responses compared to the other two controllers, it was selected to perform the adaptation of the system.

An on-line system identification process was performed for the buck converter using indirect adaptation and the least square algorithm. The estimation error and the parameter error were computed to determine the rate of convergence of the system. The indirect adaptation required about 2000 points to converge to the true parameters prior designing the controller. These results were compared to the adaptation executed using robust stability condition (RSC) and a switching controller. Two different scenarios were studied consisting of five plants that defined the percentage of deterioration of the capacitor and inductor within the buck converter. The switching logic did not always select the optimal controller for the first scenario because the frequency response of the different plants was not significantly different. However, the second scenario consisted of plants with more noticeable different frequency responses and the switching logic selected the optimal controller all the time in about 500 points. Additionally, a disturbance was introduced at the plant input to observe its effect in the switching controller. However, for reasonable low disturbances no change was detected in the proper selection of controllers.
ContributorsSerrano Rodriguez, Victoria Melissa (Author) / Tsakalis, Konstantinos (Thesis advisor) / Bakkaloglu, Bertan (Thesis advisor) / Rodriguez, Armando (Committee member) / Spanias, Andreas (Committee member) / Arizona State University (Publisher)
Created2016
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Description
From time immemorial, epilepsy has persisted to be one of the greatest impediments to human life for those stricken by it. As the fourth most common neurological disorder, epilepsy causes paroxysmal electrical discharges in the brain that manifest as seizures. Seizures have the effect of debilitating patients on a physical

From time immemorial, epilepsy has persisted to be one of the greatest impediments to human life for those stricken by it. As the fourth most common neurological disorder, epilepsy causes paroxysmal electrical discharges in the brain that manifest as seizures. Seizures have the effect of debilitating patients on a physical and psychological level. Although not lethal by themselves, they can bring about total disruption in consciousness which can, in hazardous conditions, lead to fatality. Roughly 1\% of the world population suffer from epilepsy and another 30 to 50 new cases per 100,000 increase the number of affected annually. Controlling seizures in epileptic patients has therefore become a great medical and, in recent years, engineering challenge.



In this study, the conditions of human seizures are recreated in an animal model of temporal lobe epilepsy. The rodents used in this study are chemically induced to become chronically epileptic. Their Electroencephalogram (EEG) data is then recorded and analyzed to detect and predict seizures; with the ultimate goal being the control and complete suppression of seizures.



Two methods, the maximum Lyapunov exponent and the Generalized Partial Directed Coherence (GPDC), are applied on EEG data to extract meaningful information. Their effectiveness have been reported in the literature for the purpose of prediction of seizures and seizure focus localization. This study integrates these measures, through some modifications, to robustly detect seizures and separately find precursors to them and in consequence provide stimulation to the epileptic brain of rats in order to suppress seizures. Additionally open-loop stimulation with biphasic currents of various pairs of sites in differing lengths of time have helped us create control efficacy maps. While GPDC tells us about the possible location of the focus, control efficacy maps tells us how effective stimulating a certain pair of sites will be.



The results from computations performed on the data are presented and the feasibility of the control problem is discussed. The results show a new reliable means of seizure detection even in the presence of artifacts in the data. The seizure precursors provide a means of prediction, in the order of tens of minutes, prior to seizures. Closed loop stimulation experiments based on these precursors and control efficacy maps on the epileptic animals show a maximum reduction of seizure frequency by 24.26\% in one animal and reduction of length of seizures by 51.77\% in another. Thus, through this study it was shown that the implementation of the methods can ameliorate seizures in an epileptic patient. It is expected that the new knowledge and experimental techniques will provide a guide for future research in an effort to ultimately eliminate seizures in epileptic patients.
ContributorsShafique, Md Ashfaque Bin (Author) / Tsakalis, Konstantinos (Thesis advisor) / Rodriguez, Armando (Committee member) / Muthuswamy, Jitendran (Committee member) / Spanias, Andreas (Committee member) / Arizona State University (Publisher)
Created2016