Date of Award

8-3-2009

Document Type

Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Hal Blumenfeld

Abstract

Animal models allow for detailed investigation of neuronal function, particularly invasive localization and developmental studies not possible in humans. This thesis will review the technical challenges of simultaneous EEG-fMRI, and epileptogenesis studies in animal models, including issues related to anesthesia, movement, signal artifact, physiology, electrode compatibility, data acquisition, and data analysis, and review recent findings from simultaneous EEG-fMRI studies in epilepsy and other fields. Original research will be presented on the localization of neuronal networks involved during spike-and-wave seizures in the WAG/Rij rat, a model of human absence epilepsy. Simultaneous EEG-fMRI at 9 Tesla, complimented by parallel electrophysiology, including Multiple Unit Activity (MUA), Local Field Potential (LFP), and Cerebral Blood Flow (CBF) measurements were employed to investigate the functioning of neuronal networks. This work indicates that while BOLD signal increases in the Somaotsensory Cortex and Thalamus during SWD are associated with MUA, LFP, and CBF increases, BOLD signal decreases in the Caudate are associated with CBF decreases and relatively larger increase in LFP and smaller increase in MUA. Complimenting the localization studies, original research will also be presented on the development of spike-and-wave epilepsy in the C3H/Hej mouse, a model which will allow for more advanced genetic and molecular investigation. This work shows seizure development progressing though immature, transitional, and mature stages.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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