Patients with childhood absence epilepsy (CAE) have repeated 5-10 s episodes of unresponsiveness, associated with a """"""""spike-wave"""""""" discharge (SWD) on electroencephalography (EEC). In addition to the deficit during seizures, many children also suffer from milder attention impairment between absence attacks. CAE affects 10-15% of children with epilepsy. The fundamental mechanisms of altered brain function and impaired attention in CAE are not known. Although considered a form of generalized epilepsy, both human and animal data suggest that SWD involve selective cortical and subcortical networks, while sparing other regions. Our central hypothesis is that SWD cause dysfunction in specific networks important for attention, including the medial frontal cortex and thalamus. Impairment of these attention networks may cause deficits both during and between seizures. If confirmed, this may lead to regional therapies targeted at improving impaired attention in patients with CAE. Functional magnetic resonance imaging (fMRI) provides a window to brain function, but is indirectly related to neuronal activity. We will, therefore, map abnormal function in CAE, both at baseline and during seizures, using simultaneous EEG-fMRI and arterial spin labeled cerebral blood flow (CBF) measurements, to more closely estimate neuronal activity changes. This will enable us to determine if attention networks are impaired in CAE, both during seizures and at baseline. We will then test attentional vigilance between and during seizures in CAE using a continuous performance task (CRT). At the same time, we will use functional neuroimaging to determine whether impaired attention between and during seizures is related to abnormal function in specific brain regions.

Public Health Relevance

Impaired attention during and between absence seizures has a major negative impact on patient quality of life due to deficits in school performance, potential for injuries, and social stigma. By understanding the fundamental mechanisms, and brain regions crucial for impaired attention in this patient population, new treatments including designer drugs and other targeted therapies may be developed with the goal of blocking seizures and preserving attention. Understanding mechanisms of impaired attention in this form of epilepsy may have implications for treating other types of epilepsy as well.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Fureman, Brandy E
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Yale University
Schools of Medicine
New Haven
United States
Zip Code
Antwi, Prince; Atac, Ece; Ryu, Jun Hwan et al. (2018) Driving status of patients with generalized spike-wave on EEG but no clinical seizures. Epilepsy Behav 92:5-13
Guo, Jennifer N; Kim, Robert; Chen, Yu et al. (2016) Impaired consciousness in patients with absence seizures investigated by functional MRI, EEG, and behavioural measures: a cross-sectional study. Lancet Neurol 15:1336-1345
Touloumes, George; Morse, Elliot; Chen, William C et al. (2016) Human bedside evaluation versus automatic responsiveness testing in epilepsy (ARTiE). Epilepsia 57:e28-32
Sedigh-Sarvestani, Madineh; Blumenfeld, Hal; Loddenkemper, Tobias et al. (2015) Seizures and brain regulatory systems: consciousness, sleep, and autonomic systems. J Clin Neurophysiol 32:188-93
Punia, Vineet; Farooque, Pue; Chen, William et al. (2015) Epileptic auras and their role in driving safety in people with epilepsy. Epilepsia 56:e182-5
Blumenfeld, Hal; Meador, Kimford; Jackson, Graeme D (2015) Commentary: The return of consciousness to epilepsy seizure classification. Epilepsia 56:345-7
Youngblood, Mark W; Chen, William C; Mishra, Asht M et al. (2015) Rhythmic 3-4Hz discharge is insufficient to produce cortical BOLD fMRI decreases in generalized seizures. Neuroimage 109:368-77
Yoo, Ji Yeoun; Farooque, Pue; Chen, William C et al. (2014) Ictal spread of medial temporal lobe seizures with and without secondary generalization: an intracranial electroencephalography analysis. Epilepsia 55:289-95
Cunningham, Courtney; Chen, William C; Shorten, Andrew et al. (2014) Impaired consciousness in partial seizures is bimodally distributed. Neurology 82:1736-44
Lee, Hyang Woon; Arora, Jagriti; Papademetris, Xenophon et al. (2014) Altered functional connectivity in seizure onset zones revealed by fMRI intrinsic connectivity. Neurology 83:2269-77

Showing the most recent 10 out of 38 publications