Patients with childhood absence epilepsy (CAE) often demonstrate impaired interictal attention, even with control of their seizures. No previous study has investigated the brain networks involved in this impairment. We used the continuous performance task (CPT) of attentional vigilance and the repetitive tapping task (RTT), a control motor task, to examine interictal attention in 26 children with CAE and 22 matched healthy controls. Each subject underwent simultaneous 3. T functional magnetic resonance imaging-electroencephalography (fMRI-EEG) and CPT/RTT testing. Areas of activation on fMRI during the CPT task were correlated with behavioral performance and used as seed regions for resting functional connectivity analysis. All behavioral measures reflecting inattention were significantly higher in patients. Correlation analysis revealed that impairment on all measures of inattention on the CPT task was associated with decreased medial frontal cortex (MFC) activation during CPT. In addition, analysis of resting functional connectivity revealed an overall decrease within an 'attention network' in patients relative to controls. Patients demonstrated significantly impaired connectivity between the right anterior insula/frontal operculum (In/FO) and MFC relative to controls. Our results suggest that there is impaired function in an attention network comprising anterior In/FO and MFC in patients with CAE. These findings provide an anatomical and functional basis for impaired interictal attention in CAE, which may allow the development of improved treatments targeted at these networks.
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We are especially grateful to the patients and families who participated, and to the following clinicians who referred patients for the study: A Bhargava, H Blumenfeld, B Bourgeois, W Brown, G Castaneda, RL Cerciello, R Cheng, F DiMario, RB Duckrow, M Engel, J Gaitanis, J Gibbons, L Kan, SR Levy, D Mandelbaum, G Miller, S Moshe S Nallainathan, EJ Novotny, P Overby, S Rothman, R Smith, Y Sogawa, F Testa, S Wolf, and R Young. We also thank Michelle Hampson and Jennifer Roth for helpful discussion about the methods. This work was supported by NIH R01 NS055829 and by the Betsy and Jonathan Blattmachr family .