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 i s 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 i s 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.

Public Health Relevance

Childhood absence epilepsy causes transitory impairments of consciousness and lead to accidents, social stigma, and poor school performance in children. Mapping the relationship between variable task performance, electrophysiology, and fMRI changes may lead to improved, targeted therapies and improve quality of life for patients.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Predoctoral Individual National Research Service Award (F31)
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NST-2 Subcommittee (NST)
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Fureman, Brandy E
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Yale University
Internal Medicine/Medicine
Schools of Medicine
New Haven
United States
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Guo, Jennifer N; Kothari, Jay S; Leckman, James F et al. (2016) Successful Treatment of Tourette Syndrome With Electroconvulsive Therapy: A Case Report. Biol Psychiatry 79:e13-4
Danielson, Nathan B; Guo, Jennifer N; Blumenfeld, Hal (2011) The default mode network and altered consciousness in epilepsy. Behav Neurol 24:55-65