Executive functioning and thalamofrontal circuitry in pediatric recent onset idiopathic generalized epilepsy: A prospective longitudinal study

There are several reports indicating that thalamofrontal circuitry is pathophysiological in idiopathic generalized epilepsy (IGE). There are also data indicating that executive dysfunction is a common and prominent neuropsychological morbidity. Because thalamofrontal circuitry underlies executive functioning, abnormalities of this circuit may underlie executive dysfunction. There are few studies in pediatric epilepsy examining either executive functioning or thalamofrontal circuitry in IGE, as most studies examine adults and are retrospective. Examination of early onset cases of IGE is important to determine the timing of the onset of these effects. To date, there are no longitudinal data examining either cognition or neuroimaging in IGE. The purpose of this study was to examine the developmental trajectories of executive functioning, the thalamus, and frontal lobes, as well as their relationship to one another, in a sample of children with recent onset IGE across a two-year period.;Twenty-two healthy children with recent onset IGE and 36 healthy controls completed paper and pencil measures of executive functioning and were also rated by their parents on a range of executive functioning tasks. All children also underwent whole-brain MRI. Voxel-based morphometry (VBM), quantitative MRI (qMRI), and diffusion tensor imaging (DTI) were used to examine the structural integrity of the thalamus and frontal lobes. All testing and MRI scans were repeated two years after baseline assessment.;Although IGE subjects had impaired executive functioning at baseline compared to controls, improvement or stable performance was seen on nearly all measures. In contrast, thalamofrontal structure was moderately impaired at baseline and had a delayed pattern of development in IGE compared to controls. No volumes were related to executive functioning in the IGE group at either time point, but thalamic and frontal volumes were related to executive functioning in the control group at follow-up. VBM analyses showed that the caudate nuclei and cerebellum were related to executive functioning in the IGE group at follow-up, but not the thalamus and frontal lobes were correlated with executive functioning in the control group.;Although the IGE group's executive functioning did not decline over time, their thalamofrontal circuitry did not develop at the same rate as healthy controls. This discrepancy may be due to other neural regions compensating for compromised thalamofrontal integrity. The caudate nuclei and cerebellum may compensate for thalamofrontal abnormalities in IGE.