Identification of Cortical Biomarkers for Seizure Risk in Childhood Epilepsy

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 DESCRIPTION (provided by applicant): Dr. Catherine Chu is a practicing pediatric epileptologist and clinical neurophysiologist at Massachusetts General Hospital (MGH), whose goal is to develop an independent research program utilizing non-invasive human imaging and neurophysiological recordings to improve our understanding of the mechanisms, disease process, and indicators of seizure risk in the developing brain. Dr. Chu proposes to study the most common pediatric epilepsy syndrome, benign epilepsy with Centro temporal spikes (BECTS) using novel methods to integrate advanced neuroimaging, electrophysiology, and signal processing techniques to identify key cortical biomarkers of seizure risk. Despite extensive clinical experience with this disease, it remains a challenge to determine who will benefit from antiepileptic drug (AED) treatment and when it is safe to discontinue. One- third of these children will have only a single seizure, while two-thirds may have recurrent seizures over several years. Although non-treatment or premature taper may result in seizures, chronic AED exposure introduces cognitive side effects in 30-70% of exposed children. A biomarker to isolate which children are at risk for ongoing seizures is needed to prevent the unnecessary consequences of over- or under-medication during critical years of cognitive, psychosocial and behavioral maturation in this large cohort of children. As seizures are thought to result from abnormal cortical excitability and connectivity, Dr. Chu hypothesizes those principled measures of these properties using available non-invasive techniques will identify clinically relevant biomarkers of seizure risk. Dr. Chu has developed preliminary results supporting the feasibility of her proposed approach. Under the joint mentorship of leading translational researchers Drs. Kevin Staley, Sydney Cash and Steven Stufflebeam at MGH, Dr. Chu proposes to first evaluate children with BECTS with active epilepsy and in remission in a cross-sectional study to identify candidate cortical biomarkers for seizure risk using advanced EEG and MRI techniques. She will then assess the utility of adding longitudinal data to the predictive models by re-studying th subjects in the cross sectional dataset one year after initial evaluation. The knowledge gained by these studies will lead to: 1) quantification of the physiological and anatomical processes associated with increased seizure risk in childhood epilepsy; 2) identification of candidate biomarkers of seizure risk which may have broader relevance to other epilepsies; 3) the development of novel tools and advanced expertise to identify and quantify these processes; and 4) preliminary data for an R01-funded clinical trial to test non- invasive biomarkers of seizure risk in childhood epilepsy. The career development program outlined in this proposal provides the candidate with advanced training in multimodal imaging techniques, prospective clinical research, and biostatistics in an outstanding training environment. The expertise that she will develop will position her for a productive independent career in patient-oriented research in which she can focus advanced imaging technologies to address pressing and clinically relevant questions in pediatric epilepsy.