Neuroimaging, energetics, and neuronal activity in spike-wave seizures

Yale University, New Haven CT

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Abstract

DESCRIPTION (provided by applicant): Absence epilepsy is a common seizure disorder in children, associated with 5-10 second episodes of unresponsiveness that can adversely affect a child's academic performance and psychosocial interactions. On EEG, absence seizures are characterized by rhythmic "spike-wave" discharges (SWD), likely generated by corticothalamic neuronal networks. Although absence seizures are classically considered generalized epileptic events, recent studies suggest that focal brain regions are involved while other areas are spared. Our central hypothesis is that specific cortical and subcortical networks are involved in SWD, with some regions displaying increased neuronal activity and others showing decreased activity compared to baseline. Functional neuroimaging has the potential to map regional activity changes during SWD noninvasively throughout the brain. Previous neuroimaging studies have established a strong relationship between fMRI signals and neuronal activity. However, neuroimaging has limited spatiotemporal resolution and is only indirectly related to neuronal activity. These limitations can be overcome by associating fMRI signals with localized energetics and then directly connecting energetics to neuronal activity. Therefore, to accurately characterize the brain regions involved in spike-wave seizures, we propose a multimodal study of SWD in a rat model, using techniques spanning a wide range of spatiotemporal domains. Our specific aims are: 1) To map the cortical and subcortical networks involved in SWD using fMRI, 2) To measure vascular responses and calculate neuroenergetics during SWD, relating imaging signals to neuronal activity, and 3) To directly measure electrophysiological changes during SWD within involved brain regions. This combination of neuroimaging and electrophysiological techniques will allow unambiguous description of changes in neuronal activity throughout the brain during SWD, allowing a comprehensive characterization of the networks involved in these seizures. We expect to find regional heterogeneity, with certain regions showing increases in neuronal activity during SWD, some showing decreases, and sparing of other areas. Knowledge of which cortical and subcortical networks are involved in SWD will guide future studies into the local pathophysiology of absence epilepsy and may lead to the development of targeted treatments. Public Health Relevance: Absence seizures affect 17% of children with epilepsy, and are associated with staring spells that negatively impact a child's school performance and social interactions. A better understanding of the mechanisms of absence seizures and knowledge of which brain regions are involved may lead to better treatments for absence epilepsy and other related seizure disorders.