Date of Award

January 2012

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Hal Blumenfeld

Subject Area(s)

Medicine

Abstract

Childhood Absence Epilepsy (CAE) is a common cause of pediatric epilepsy characterized by brief episodes of impaired consciousness accompanied by 3-4 Hz generalized spike-wave discharges on EEG. CAE is also known to cause interictal impairment of attention even when seizures are controlled. No studies have yet investigated the neural network dysfunction responsible for these cognitive deficits. In this study we used functional MRI data to define an attention network and measure any alterations in this network in children with absence epilepsy. We used the Continuous Performance Task (CPT), a test of attentional vigilance, and the Repetitive Tapping Task, a motor control test, on 26 patients and 22 matched healthy controls with simultaneous fMRI and EEG recording. This fMRI data was correlated with behavioral performance and used to identify attention regions of interest. According to all performance variables of inattention, the CAE patients performed more poorly than controls on CPT. Areas of activation on fMRI during CPT included the medial frontal cortex (MFC) and bilateral insula/frontal opercula (In/FO). Worse performance on CPT according to all measures of inattention was correlated with decreased fMRI activation in the MFC. The MFC and bilateral In/FO were then used to define an "attention network" which was explored using resting functional connectivity analysis. CAE patients were found to have significantly decreased functional connectivity between the MFC and right anterior In/FO relative to controls. These findings suggest that the function of this attention network is impaired in patients with CAE. Our results provide a functional and anatomic basis for the interictal impairments observed in CAE patients and may allow for the development of improved targeted therapies aimed at these networks.

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