Date of Award

9-21-2010

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Hal Blumenfeld

Second Advisor

Dennis Spencer

Third Advisor

Laura Ment

Abstract

Absence seizures in Childhood Absence Epilepsy (CAE) are 5 10 second episodes of impaired consciousness that are characterized on electroencephalography (EEG) by frontally-predominant, 3 4 Hz spike and wave discharges (SWD). The aims of this study were to use simultaneous EEG, functional magnetic resonance imaging (fMRI), and behavioral testing to identify the neural networks involved in absence seizures as well as to examine the timecourse of those ictal fMRI changes. It was hypothesized that absence seizures involve wide-reaching neural networks including the areas traditionally associated with normal attention processing and that absence seizures produce fMRI signal changes not only during the seizure, but before and after it as well. In this study, we recorded 88 absence seizures from a cohort of 42 children with pure CAE. These seizures were recorded as subjects participated in simultaneous EEG-fMRI scanning while engaged in a continuous performance task (CPT) of attentional vigilance or a repetitive tapping task (RTT) requiring repetitive motor activity. Using a novel, voxel-based percent fMRI change analysis combined with a volume of interest analysis, the second-by-second fMRI signal timecourse of the absence seizures were examined across numerous brain regions of interest, from 20 seconds before seizure onset through 40 seconds after seizure onset. EEG frequency analysis revealed seizures with a mean duration of 6.6 seconds and an abrupt onset and ending that were comprised of frontally-predominant, 3 4 Hz SWD. Ictal behavioral testing demonstrated abrupt onset of impairments during periods of SWD. These behavioral impairments were typical of CAE absence seizures in that impairments were greater in the CPT of attentional vigilance (omission error rate, OER = 81%) than in RTT testing (OER = 39 %) (p < 0.003). The ictal fMRI changes we observed varied depending upon the method of fMRI signal analysis used. Using the traditional general liner model, and assuming the standard hemodynamic response (HRF) function, this study replicated results consistent with previous ictal absence fMRI studies showing ictal activations primarily in the thalamus and ictal deactivations in traditional default mode areas. Using a more data-driven, novel voxel-based fMRI percentage change analysis to examine the ictal fMRI timecourse on a second-by-second basis, both ictally as well as pre- and post- ictally, this study, however, demonstrated ictal involvement of diverse brain regions before, during, and after the seizure. Activation was demonstrated up to 16 seconds before seizure onset, starting first in the parietal and orbital-medial frontal cortices and progressing to lateral frontal and lateral temporal cortices followed by the occipital and Rolandic cortices and finally the thalamus. Deactivation followed a similar anatomic progression and lasted up to 17 seconds after the end of SWD. These findings reveal a complex and long-lasting sequence of fMRI changes in CAE absence seizures that are not detectable by conventional HRF modeling and are important in the understanding and eventual treatment of absence seizures associated with CAE.

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