Abstracts

Rationale: EEG-fMRI studies of generalized epileptiform activity have identified a consistent pattern of blood oxygen level dependent (BOLD) signal change in group studies (1-3). However individual variability is noted in BOLD change and the reasons for this are not clear. Genetic generalized epilepsy (GGE) displays complex inheritance patterns and is likely to involve multiple genetic elements (4). In this study we explored the role of genetic factors on event related BOLD signal change during EEG-fMRI by studying twins and siblings with concordant and discordant GGE syndromes. We hypothesized greater genetic and clinical heterogeneity between siblings would be reflected in greater heterogeneity in activation maps. Methods: Three sibling pairs (including one monozygotic twin pair) with GGE were recruited through the EEG departments of the Austin Hospital and the Royal Children's Hospital in Melbourne. EEG-fMRI, data pre-processing and event related analysis was performed as described in our previous study on absence epilepsy (2). All studies were performed on a 3-T GE Signa LX whole-body scanner (General Electric, Milwaukee, Wisconsin). fMRI data were pre-processed and analyzed using SPM8 (Statistical Parametric Mapping, Welcome Department of Imaging Neuroscience, London, United Kingdom). A Pearson's correlation coefficient was calculated comparing all voxels between each sibling pair to quantify the degree of similarity. As a comparator, three subjects with GGE, who each had two EEG-fMRI studies of similar duration, were studied. Results: The Pearson's correlation coefficient for the three subjects studied twice was 0.43-0.77. Monozyotic twins with juvenile absence epilepsy had a similarly high correlation of 0.58. A non-twin sibling pair with same syndrome (eyelid myoclonia with absence) had a correlation of 0.4, whereas the sibling pair with different syndromes had the lowest correlation of 0.23. Conclusions: Our findings demonstrate that greater phenotypic and genotypic similarity leads to a stronger correlation in BOLD change across the brain. This suggests that genetic factors may contribute to the pattern of BOLD change seen with event related analysis of epileptiform events. References: 1. Bai X, Vestal M, Berman R, et al. Dynamic time course of typical childhood absence seizures: EEG, behavior, and functional magnetic resonance imaging. J Neurosci 2010;30:5884-5893. 2. Carney PW, Masterton RA, Harvey AS, Scheffer IE, Berkovic SF, Jackson GD. The core network in absence epilepsy. Differences in cortical and thalamic BOLD response. Neurology 2010;75:904-911. 3. Moeller F, Siebner HR, Wolff S, et al. Simultaneous EEG-fMRI in drug-naive children with newly diagnosed absence epilepsy. Epilepsia 2008;49:1510-1519. 4. Mulley JC, Scheffer IE, Harkin LA, Berkovic SF, Dibbens LM. Susceptibility genes for complex epilepsy. Human Molecular Genetics. 2005;14 Spec No. 2:R243-249.