Introduction The understanding of Childhood Absence Epilepsy (CAE) has been revolutionized over the past decade but the biological mechanisms responsible for variable treatment outcomes are unknown. Our purpose was to determine how pre-treatment ictal network pathways, defined using a combined EEG-functional magnetic resonance imaging (EEG-fMRI) and magnetoencephalography (MEG) effective connectivity analysis, were related to treatment response. Methods Sixteen children with newly diagnosed and drug naive CAE had 31 typical absence seizures during EEG-fMRI and 74 during MEG. The spatial extent of the pre-treatment ictal network was defined using fMRI hemodynamic response with an event related independent component analysis (eICA). This spatially defined pre-treatment ictal network supplied prior information for MEG effective connectivity analysis calculated using phase slope index (PSI). Treatment outcome was assessed 2 years following diagnosis and dichotomized to ethosuximide (ETX) treatment responders (N = 11) or non-responders (N = 5). Effective connectivity of the pre-treatment ictal network was compared to the treatment response. Results Patterns of pre-treatment connectivity demonstrated strongest connections in the thalamus and posterior brain regions (parietal, posterior cingulate, angular gyrus, precuneus, and occipital) at delta frequencies and the frontal cortices at gamma frequencies (p Conclusion Pre-treatment ictal connectivity differences in children with CAE were associated with response to anti-epileptic treatment. This is a possible mechanism for the variable treatment response seen in patients sharing the same epilepsy syndrome.
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