Cortical thickness in childhood left focal epilepsy: Thinning beyond the seizure focus

Abstract

Objective: Structural brain differences are found in adults and children with epilepsy, yet pediatric samples have been heterogeneous regarding seizure type, magnetic resonance imaging (MRI) findings, and hemisphere of seizure focus. This study examines whether cortical thickness and surface area differ between children with left-hemisphere focal epilepsy (LHE) and age-matched typically developing (TD) peers. We examined whether age differentially moderated cortical thickness between groups and if cortical thickness was associated with duration of epilepsy, seizure frequency, or neuropsychological functioning.

Methods: Thirty-five children with LHE and 35 TD children completed neuropsychological testing and 3T MR imaging. Neuropsychological measures included general intelligence and executive functioning. All MRIs were normal. Surface-based morphometric processing and analyses were conducted using FreeSurfer 6.0. Regression analyses compared age by cortical thickness differences between groups. Correlational analyses examined associations between cortical thickness in these areas with neuropsychological functioning or epilepsy characteristics.

Results: Left-hemisphere focal epilepsy displayed decreased cortical thickness bilaterally compared to TD controls across 6 brain regions but no differences in surface area. Moderation analyses revealed quadratic relationships between age and cortical thickness for left frontoparietal-cingulate and right superior frontal regions. Higher performance intelligence quotient (IQ) (PIQ) and verbal IQ (VIQ) and fewer parent reported executive function problems were associated with greater cortical thickness in TD children.

Significance: Children with LHE displayed thinner cortex extending beyond the hemisphere of seizure focus. The nonlinear pattern of cortical thickness across age occurring in TD children is not evident in the same manner in children with LHE. These differences in cortical thickness patterns were greatest in children 8-12 years old. Greater cortical thickness was associated with higher IQ and fewer executive control problems in daily activities in TD children. Thus, differences in cortical thickness in the absence of differences in surface area, suggest cortical thickness may be a sensitive proxy of subtle neuroanatomical changes that are related to neuropsychological functioning.

Keywords: Brain development; Executive functioning; FreeSurfer; Neuropsychology; Pediatric.

Figure 1.. Left and Right Hemisphere Cortical Thickness Differences –

Visualization of the cortical thickness differences between LHE and TD using FreeSurfer’s Qdec. Clusters indicate areas where LHE was thinner than TD after Monte-Carlo correction.

Figure 2.. Cortical Thickness by Age Between Groups –

Scatterplots showing the significantly different cortical thickness by age relationships between LHE and TD groups in the A. left frontoparietal-cingulate region and B. right superior frontal region.

Figure 3.. Cortical Thickness and Neuropsychological Performance –

Scatterplots showing significant and non-significant linear relationships between cortical thickness and neuropsychological measures for Combined Sample and Individual Group analyses. Greater PIQ was associated with greater cortical thickness in the a. left frontoparietal-cingulate region (Combined Sample: p<0.01), b. left parieto-occipital junction (Combined Sample: p=0.02; TD: p=0.01), c. right supramarginal gyrus (Combined Sample: p=0.02; TD: p=0.03). Greater VIQ was associated with greater cortical thickness in the d. right parieto-occipital junction (Combined Sample: p=0.01; TD: p=0.03). More parent reported problems of executive function were associated with decreased cortical thickness in the e. left frontoparietal-cingulate region (Combined Sample: BRIEF MI p=0.02), f. right supramarginal region (Combined Sample: BRIEF MI p=0.02). For the TD group only, fewer parent reported problems of executive function were associated with increased cortical thickness in the g. left parieto-occipital junction (TD: BRIEF BRI p=0.04).