Multimodal functional neuroimaging of epilepsy and Pain

Abstract

The overall goal of this thesis work is to use advanced noninvasive neuroimaging modalities and techniques to study the underlying neurological mechanism of both diseased and healthy brains. The two main applications of this work are for the diagnosis of epilepsy and management of pain. Epilepsy is one of the most prevalent neurological disorders. It affects an estimated 2.7 million Americans. There are two broad types of epilepsies: partial and generalized epilepsy. For patients with drug resistant focal epilepsy, which account for one third of the patient population, surgical resection may provide the opportunity of seizure control. Existing presurgical planning methods are not only invasive in nature; they may also fail to provide additional information needed for surgery due to the relatively limited spatial coverage. On the other hand, idiopathic generalized epilepsy (IGE), unlike focal or partial epilepsy, often affects the whole or a larger portion of the brain without obvious, known cause. Treatment options are more restricted as resection is not a choice. Therefore, it is important to understand the underlying network which generates epileptic activity and through which epileptic activity propagates. The aim of the present study in the epilepsy portion was to use noninvasive imaging techniques including fMRI and EEG to localize epileptic areas for the purpose of assisting surgical planning in the focal epilepsy cases; and to improve our understanding the underlying mechanism of generalized epilepsy, thalamocortical relationship in the IGE cases. Chronic Pain is one of the biggest medical burdens in developed countries, affecting 20% of adult population with estimated economic cost in the United States alone over $150 billion. Functional imaging of brain networks associated with pain processing is of vital importance to aid developing new pain-relief therapies and to better understand the mechanisms of pain perception. The long-term goal of this project is to study the neurological mechanism of subjective perception of pain using non-invasive neuroimaging methods. In the present work of the pain portion, changes brain activities in healthy subjects experiencing sustained external painful stimuli were first studied. Neural activities in patient with sickle cell disease, who often surfer spontaneous acute or chronic pain as one of the comorbidities of the disease, were contrasted with healthy controls to study changes in neural network as a result of prolonged exposure to internal In summary, the present dissertation research developed and evaluated the spatiotemporal imaging approaches for the non-invasive mapping of network activities in the diseased and normal brain. Evaluations were conducted in patient and healthy control groups in order to test the clinical applicability of such a pre-surgical noninvasive imaging tool. An investigation has been conducted to study the widespread GSWDs of generalized epilepsy patients. The spatial resolution has been further improved by adding the component of fMRI through an EEG-fMRI integrated imaging framework. For the application in pain study, two investigations were conducted to study changes in network level activity due to external pain in healthy subjects and spontaneous pain in patients with SCD. All of the results that were obtained suggest the importance of noninvasive spatiotemporal neuroimaging approaches for solving clinical problems and for investigating neuroscience questions. Furthermore, an improved understanding of neurological diseases and their mechanisms would help us to develop and deliver curative treatments of neurological diseases.