Abstracts

Rationale: Childhood and adolescent onset of focal epilepsy (FE) occurs during ongoing decreased cortical thickness (CT) and increased sulcal depth (SD) [1]. This study predicted that the normal significant association between CT and SD in the frontal and occipital cortex of healthy children (HC) is not found in age and gender matched FE patients. It determined if the significant CT-SD associations in the FE subjects are related to illness effects (age of onset and seizure control/frequency), a perinatal marker (birth weight) [2, 3], and/or a clinical marker (family history of epilepsy) [4]. Methods: High-resolution 3D MR images were obtained on 43 FE (6.1-15.3 years) and 46 TD subjects (6.1-16.2 years) in a 1.5 Tesla scanner. After removal of non-brain tissue from MR images, image voxels were classified into different tissue types. Cortical surface representations at the geometric center of the 3D gray matter (GM) tissue were extracted. Cortical thickness at each point in the cortical GM mantle was defined as the sum of the distances from this point to the GM/white matter and GM/CSF tissue boundaries. A surface-based spatial normalization technique was used to match anatomically homologous cortical features across subjects before performing cross-subject comparison. Parents provided seizure variable, birth weight, and family history of seizures information. Associations between CT and SD were examined using correlational analyses. Due to the multiple number of regions examined, a significance level of p<.005 was adopted. For those associations that were significant at the p<.005 level, partial correlations, controlling for age, birth weight, age of onset, seizure frequency, and family history of seizures, were determined to examine the effect of these variables on the CT-SD associations. Results: Figure 1 presents the significant CT-SD negative relationship in the medialfronto-orbital (r=-.42, p =.005) region in the HC and positive association in the precentral (r=.50, p =.0008) and postcentral regions (r=.43, p =.004) of the FE group. Within the FE group, the postcentral CT-SD association remained significant (r=0.43, p=.009) controlling for seizure variables. Seizure variables were unrelated to the precentral CT-SD association in FE. There was an age effect in the HC group, but the CT-SD correlation remained significant (r=-.36, p=.02). Age, birth weight, and family history of seizures played no role in the FE pre- and postcentral CT-SD correlations. Conclusions: Given the reciprocal CT-SD relationship in the HC of the later maturing medial fronto-orbital region, the significant positive association in the earlier maturing pre- and post-central FE cortex implies a developmental abnormality/delay in brain maturation. These findings highlight the need to examine if motivation, reward, and cognitive modulation of affect, subserved by the medialfronto-orbital [5], are impaired in children with FE and their possible relationship with cognitive and psychiatric comorbidities.