Abstracts

Rationale: Epilepsy during critical periods of cognitive development may pose a disruption of neurodevelopmental processes underlying maturation of cognition and brain development. Paroxysmal discharges in idiopathic childhood onset epilepsy can undermine the establishment of a functional network supporting executive function. We were interested in characterizing executive function and examining the contribution of the integrity of the supporting white matter including cortical and subcortical circuits. Methods: Participants were 35 well-characterized (mean age 12.8, SD 2.7; 19 males), well-controlled, medically treated epilepsy patients with normal IQ ages 8-17 who were age, gender and IQ matched to healthy controls with no history of neurological or psychiatric disorders. No patients had MRI findings to account for seizures. The mean duration of epilepsy in the patient group was 3.5 years (SD 2.8). The patients were on no more than 2 medications. Participants completed a battery of neurobehavioral tests including a control task of speed of processing and an antisaccade task of response inhibition as measures of executive function as well as psychiatric assessment. A subgroup of 18 patients completed MRI studies including diffusion tensor imaging scans. Voxel-wise analyses were conducted to compare fractional anisotropy in white matter tracts between patients and a panel of 41 age-matched controls. Results: There was no significant difference patients and controls in the speed of processing task, indicating intact basic sensorimotor function in the epilepsy cohort. In contrast,the epilepsy group showed impaired antisaccade performance reflecting limitations in response inhibition. Early age of epilepsy onset, complex partial subtype, and attention deficit disorder exacerbated this effect. Chronologic age at the time of testing also influenced the results with a trend towards reaching normative levels by mid-adolescence. The DTI results demonstrate decreased fractional anisotropy in the patient group in a widely distributed cortical and subcortical circuitry including frontostriatal connections, long association tracts, and the corpus callosum (p < .05). There were positive significant correlations between antisaccade performance and fractional anisotropy in the control patients in these regions of interest that were not significant for the patient group, particularly in frontostriatal tracts. Conclusions: Taken together the results indicate that even idiopathic pediatric epilepsy of short duration may undermine neurodevelopmental brain-behavior relationships. These effects may be driven by subject characteristics such as early age of disease onset, complex partial seizure subtype, and psychiatric comorbidity. Compromised executive function was seen in conjunction with disrupted frontostriatal circuitry. These results suggest that aspects of epilepsy characteristics may underlie vulnerability to neurodevelopmental processes supported by cortical and subcortical white matter circuitry.