1002 Locations of Focal Cortical Dysplasia in Humans Reflect the Evolution of Primate Cortical Morphology

INTRODUCTION: Focal cortical dysplasias (FCD) are cortical development malformations and one of the leading causes of medically refractory epilepsy in children. The non-uniform distribution of FCDs lacks a clear explanation. Recent evidence indicates variations in gene expression and morphology during prenatal brain development may predispose certain areas to FCD. METHODS: We mapped cortex-wide distribution of FCD (type II imaging appearance) frequency in 294 human children and adults with focal epilepsy recruited across 4 centers. FCD locations were manually segmented from T1-weighted MRI scans, then projected to a cortical template surface (fsaverage). All FCD drawings were flipped to the same hemisphere. Maps of FCD frequency were correlated to surface-based maps of cortical expansion across four non-human primate species (marmoset, capuchin, macaque, and human), as described in Chaplin et al. (2013; DOI=10.1523/JNEUROSCI.2909-13.2013), using Spearman’s rho and spin permutation significance testing. RESULTS: Across patients with epilepsy, the median age at MRI was 8 years (interquartile range=8.35), 47% were female, and 52% of FCD were located on the left. FCD frequency showed a significant positive correlation with primate cortical expansion (Spearman’s rho=0.4, spin-p=0.03). The correlation mainly stemmed from frontal lobe FCD localization and corresponding frontal expansion in humans. Despite high evolutionary expansion, the posterior temporal and temporoparietal cortex did not show increased FCD frequency. CONCLUSIONS: We show a potential relationship between FCD locations and areas of increased cortical expansion in humans, suggesting that regional vulnerability to malformations may follow a developmental trajectory shaped by primate evolution, particularly in the frontal lobe. These findings may guide more focused strategies for epilepsy treatment related to FCD.