Translational Machine Learning for Epilepsy Therapy


Book Description

Continuous medical data monitoring is playing an increasingly important role in patient care, both in and out the hospital. Diagnosing and treating patients with epilepsy is especially reliant on continuous EEG monitoring to identify and respond to seizures. However, as use of continuous EEG becomes more common, both for long-term inpatient monitoring and in ambulatory or implanted devices, the burden of study interpretation is rapidly outpacing available physician resources. In particular, the advent of implanted neuroresponsive devices for treating medically-refractory epilepsy is generating large, streaming datasets potentially lasting for several years and containing hundreds of seizures. The current need for manual review of long-term, continuous EEG data introduces tremendous health care costs and can result in significant delays in seizure diagnosis and treatment. Automated data processing is essential to improve data usage, accurately and rapidly detect seizures, and provide scalability in clinical practice. This thesis aims to develop platforms for automated data analysis and event detection using custom machine learning algorithms for application in the intensive care unit and in implanted neural devices. The work presented in this thesis progresses through the development of each component of an automated data analysis platform. The first section describes a system for real-time data analysis and caretaker notification in the ICU, with a focus on the process necessary to harness multi-modal data from clinical recording sources. The next section details the process of developing machine learning algorithms for seizure detection. In this section, I present novel seizure detection strategies as well as a competition designed to crowdsource algorithm development. This work produced several highly-accurate, open-source seizure detection methods, validated in extended human implanted device data, along with pipelines to facilitate algorithm application and benchmarking in new datasets. The last section covers the integration of data management and seizure detection for implementation in next-generation medical devices. I present a novel paradigm to leverage cloud computing resources for seizure detection in an implanted device. This system is then implemented in vivo using a canine epilepsy model, with real-time seizure detection on streaming data from Medtronic's RC+S neurostimulating device. These algorithms and flexible analysis platforms are a step toward automating analysis of EEG data for epilepsy therapy. It is my hope that such systems will improve medical data usage, reshape caretaker workflow, and increase the clinical power of continuous medical monitoring.







Application of Machine Learning to Epileptic Seizure Onset Detection and Treatment


Book Description

(cont.) In this thesis we also discuss how our detector can be embedded within a low power, implantable medical device to enable the delivery of just-in-time therapy that has the potential to either eliminate or attenuate the clinical symptoms associated with seizures. Finally, we report on the in-hospital use of our detector to enable delay-sensitive therapeutic and diagnostic applications. We demonstrate the feasibility of using the algorithm to control the Vagus Nerve Stimulator (an implantable neuro stimulator for the treatment of intractable seizures), and to initiate ictal SPECT (a functional neuroimaging modality useful for localizing the cerebral site of origin of a seizure).










Machine Learning for Prediction of Anticonvulsive Drug Treatment Outcomes in Mecp2-Deficient Mice


Book Description

Anticonvulsive drug (ACD) treatments produce inconsistent outcomes, often necessitating patients to go through several drug trials before a successful treatment can be found. In this thesis we apply a novel approach, using machine learning techniques to predict epilepsy treatment outcomes of commonly used ACDs. Machine learning algorithms were trained and evaluated using features obtained from intracranial electroencephalogram (iEEG) recordings of the epileptiform discharges observed in Mecp2-deficient mouse model of the Rett Syndrome. Our work on Mecp2-deficient mice focuses on low frequency oscillations (LFO), high frequency oscillations (HFO) and their interactions through cross-frequency coupling (CFC) to reveal iEEG based biomarkers that track epileptic seizure pathology. Our findings revealed: variability across discharge events using iEEG recordings, progression of longer duration discharges over five developmental time points, and the increased cross-frequency coupling index ICFC of the delta (2-5 Hz) rhythm with the fast ripple (400-600 Hz) rhythm in discharge events. These results suggest a link between long duration discharges with elevated ICFC to the epileptic seizure pathology. Using the ICFC to label post-treatment outcomes we trained Support Vector Machines (SVM) and Random Forest (RF) machine learning classifiers on time-based, normalized power and CFC comodulogram features to predict the efficacy of ACD treatments. The results indicate that the performance of the comodulogram features yielded better predictions and were further improved when combined with time-based features. Hence, machine learning techniques were able to rank ACDs by estimating likelihood scores for successful treatment outcome. Identifying the most appropriate ACD treatment a priori would reduce the burdens of drug trials and provide patient specific treatment options that could lead to substantial improvements in patient quality of life.




Machine Learning-driven Patient-specific Early Seizure Detection for Neuromodulation Devices


Book Description

Epilepsy is a chronic disorder of the brain that predisposes individuals to experiencing recurrent and unprovoked seizures affecting 50 million people worldwide. Recent advances in fundamental neuroscience and implantable electronics have enabled the development of neuromodulation devices for the treatment of epilepsy. Modern neuromodulation devices detect abnormal electrical activity in the brain associated with seizures and activate electrical stimulation to prevent seizures from occurring. Today, there is a growing trend towards integrating machine learning for seizure detection on such devices to improve their efficacy. This thesis assesses the suitability of current machine learning models for neuromodulation devices by evaluating their seizure detection performance and efficiency in resource-constrained environments. Particular emphasis is placed on comparing traditional machine learning to modern deep learning models. This thesis will show that, in the seizure detection context, deep learning models can be implemented in a compact and resource-efficient way despite their computational complexity.




Conn's Translational Neuroscience


Book Description

Conn’s Translational Neuroscience provides a comprehensive overview reflecting the depth and breadth of the field of translational neuroscience, with input from a distinguished panel of basic and clinical investigators. Progress has continued in understanding the brain at the molecular, anatomic, and physiological levels in the years following the 'Decade of the Brain,' with the results providing insight into the underlying basis of many neurological disease processes. This book alternates scientific and clinical chapters that explain the basic science underlying neurological processes and then relates that science to the understanding of neurological disorders and their treatment. Chapters cover disorders of the spinal cord, neuronal migration, the autonomic nervous system, the limbic system, ocular motility, and the basal ganglia, as well as demyelinating disorders, stroke, dementia and abnormalities of cognition, congenital chromosomal and genetic abnormalities, Parkinson's disease, nerve trauma, peripheral neuropathy, aphasias, sleep disorders, and myasthenia gravis. In addition to concise summaries of the most recent biochemical, physiological, anatomical, and behavioral advances, the chapters summarize current findings on neuronal gene expression and protein synthesis at the molecular level. Authoritative and comprehensive, Conn’s Translational Neuroscience provides a fully up-to-date and readily accessible guide to brain functions at the cellular and molecular level, as well as a clear demonstration of their emerging diagnostic and therapeutic importance. Provides a fully up-to-date and readily accessible guide to brain functions at the cellular and molecular level, while also clearly demonstrating their emerging diagnostic and therapeutic importance Features contributions from leading global basic and clinical investigators in the field Provides a great resource for researchers and practitioners interested in the basic science underlying neurological processes Relates and translates the current science to the understanding of neurological disorders and their treatment




Big Data in Psychiatry and Neurology


Book Description

Big Data in Psychiatry and Neurology provides an up-to-date overview of achievements in the field of big data in Psychiatry and Medicine, including applications of big data methods to aging disorders (e.g., Alzheimer’s disease and Parkinson’s disease), mood disorders (e.g., major depressive disorder), and drug addiction. This book will help researchers, students and clinicians implement new methods for collecting big datasets from various patient populations. Further, it will demonstrate how to use several algorithms and machine learning methods to analyze big datasets, thus providing individualized treatment for psychiatric and neurological patients. As big data analytics is gaining traction in psychiatric research, it is an essential component in providing predictive models for both clinical practice and public health systems. As compared with traditional statistical methods that provide primarily average group-level results, big data analytics allows predictions and stratification of clinical outcomes at an individual subject level. Discusses longitudinal big data and risk factors surrounding the development of psychiatric disorders Analyzes methods in using big data to treat psychiatric and neurological disorders Describes the role machine learning can play in the analysis of big data Demonstrates the various methods of gathering big data in medicine Reviews how to apply big data to genetics




Jasper's Basic Mechanisms of the Epilepsies


Book Description

Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.