Neural correlates of impaired consciousness in childhood absence epilepsy

Yale University, New Haven CT

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Abstract

DESCRIPTION (provided by applicant): Childhood absence epilepsy (CAE) is a generalized form of epilepsy causing transitory impairments of consciousness. However, this impairment during seizures is not an all-or-nothing phenomenon but variably affects task performance in patients. Absence seizures are seen as 3-4 Hz spike-and-wave discharges on electroencephalography (EEG) and cause a time course of blood oxygenation changes in brain areas seen in functional magnetic resonance imaging (fMRI). It is unknown how absence seizures cause variable impairments of consciousness in patients. Preliminary data suggests that attention network areas including the medial frontal cortex/anterior cingulate (MFC/ACC) and bilateral insula are selectively affected in absence epilepsy between seizures. Our central hypothesis is that absence epilepsy affects attention network areas during seizures to variably impair behavior. We plan to investigate the underlying neural basis of fluctuations in behavior during seizures through simultaneous behavioral, EEG, and fMRI recordings in pediatric CAE patients during absence seizures. Our first aim will be to characterize behavior during seizures using two tasks of continuous 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 behavior and performance in epochs of time over the course of seizures will be compared. Our second aim is to relate EEG changes with the variable task performance found in Aim 1. EEG power at the 3-4 Hz and high frequency gamma bands previously associated with attention, as well as prototypical 100 ms EEG topographies associated with distinct brain states, will be correlated with task performance. Our third aim is to relate behavior to changes in fMRI signals by analyzing the time course and network connectivity of the MCC/ACC and bilateral insula. Impaired neocortical function and cognitive deficits significantly reduce the quality of life in patients with CAE. Understanding the fundamental mechanisms of variable behavior in focal epilepsy may lead to improved, targeted therapies for this disorder.