Functional Neuroimaging in Childhood Absence Epilepsy

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Seizures have both transient and enduring effects on nervous system function. In childhood absence epilepsy (CAE) seizures consist of brief 5-10 s episodes of unresponsiveness, associated with a 3-4 Hz spike-wave discharge (SWD) on electroencephalography (EEG). CAE affects 10-15% of children with epilepsy. In addition to transient attention deficits during seizures, many children also suffer from milder chronic deficits in attention between absence episodes. An important feature of attention deficits in CAE is that they vary in severity from one seizure to the next, and from one patient to the next. The fundamental mechanisms of variable impaired attention during and between absence seizures are not known. Functional magnetic resonance imaging (fMRI) has elucidated brain areas that normally participate in attention, including the anterior cingulate/medial frontal cortex, thalamus and other regions. Recent investigations suggest that absence seizures, long considered a "generalized" form of epilepsy, in fact preferentially involve specific brain networks while sparing others. Therefore, our central hypothesis is that absence seizures disrupt function in localized attention networks, leading to deficits both during and between seizures. Repeated severe impairment during seizures may be related to chronic impairment between seizures. We plan to investigate the underlying neural basis of fluctuations in attention in CAE through simultaneous behavioral, EEG, and fMRI recordings. Our first aim will be to characterize behavior during seizures using two tasks of sustained performance over time, which require different levels of attentional vigilance. Task performance will be used to categorize seizures as being associated with good or impaired performance, and we will correlate the severity of deficits during seizures with chronic deficits between seizures. Our second aim is to relate EEG changes with the variable task performance found in Aim 1. EEG power at the 3-4 Hz seizure frequency, and gamma frequency signals previously associated with attention, will be analyzed in frontal attention networks and correlated with task performance. Our third aim is to use fMRI during absence seizures to identify changes in specific attention areas such as the anterior cingulate/medial frontal cortex, thalamus, or other regions related to impaired performance. We will also relate the severity of fMRI changes during seizures to fMRI measures of chronic network dysfunction between seizures, using methods such as resting functional connectivity analysis. Understanding the fundamental mechanisms of variable impaired attention in CAE may lead to improved, targeted therapies to prevent both the transient impairments during seizures, and chronic persistent deficits.