Epilepsy is a devastating disorder affecting one percent of the population. Seizures cannot be controlled by medications in thirty percent of patients with epilepsy, causing significant morbidity and even mortality. In focal neocortical epilepsy (FNE), seizures typically originate from the lateral cortex of the brain. While epilepsy surgery can lead to complete seizure-freedom in patients with medically-intractable focal neocortical epilepsy with current approaches, nearly half of these cases fail to adequately control seizures. Failures in the surgical treatment of FNE stem in part from limited techniques for accurately mapping where seizures originate in the brain (termed the epileptogenic zone), and a limited understanding of epileptic brain networks. The goal of this study is to reach a better understanding of brain network dysfunction in FNE patients. Before undergoing surgical resection of a presumed epileptogenic zone, all epilepsy patients in this study will receive noninvasive magnetoencephalography (MEG) recordings. Invasive procedures will be performed strictly for clinical diagnosis and treatment, and data analysis for research purposes will not subject patients to any additional risk. Non-epileptic control subject volunteers will als undergo noninvasive MEG recordings for comparison. MEG data will be analyzed using customized software to measure resting-state functional connectivity (RSFC) throughout the brain. RSFC is statistical technique used to study coherence between signals from separate brain regions, and it allows examination of abnormal functional connections in the brain. We will also compare pre-operative RSFC maps in epilepsy patients with the resection area defined by post- operative magnetic resonance imaging (MRI), and relate these connectivity patterns to post-operative clinical outcomes. While RSFC studies have been performed in epilepsy patients in the past, most of these have utilized functional MRI techniques, and the results have been inconsistent. Compared to functional MRI, however, MEG allows more direct recordings of brain activity at a higher resolution, representing a novel and promising approach to the study of functional connectivity in epilepsy. Based on preliminary analyses, it is expected that this study will reveal widespread decreased connectivity in focal epilepsy patients compared to controls, but that within individual patients, the epileptogenic zone will represent the region of highest connectivity. Resection of tissue with highest connectivity will predict post- operative seizure freedom. This study will allow a better understanding of brain network dysfunction in epilepsy, and may ultimately lead to new targeted treatments for seizure disorders.

Public Health Relevance

Focal epilepsy is a common and devastating disorder often refractory to medications. This study will use a promising brain imaging technique called magnetoencephalography to study abnormal functional connections in the brains of focal epilepsy patients. The goal is an improved understanding of brain networks in focal epilepsy, which will lead to novel treatments for this disorder.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Fureman, Brandy E
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University of California San Francisco
Schools of Medicine
San Francisco
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Englot, Dario J (2018) A modern epilepsy surgery treatment algorithm: Incorporating traditional and emerging technologies. Epilepsy Behav 80:68-74
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