Abstracts

Rationale: Pediatric epilepsy is associated with compromised quality of life due to behavioral limitations including executive function and motivation. We probed the integrity of the neural systems underlying executive function and reward processing in pediatric epilepsy. Methods: Seventeen non-lesional, medically treated pediatric epilepsy patients 8-17 years of age (mean age 13 years, mean duration of epilepsy 3 years) and individually age and gender-matched healthy community controls completed whole brain functional MRI (fMRI). During fMRI subjects performed a monetary incentive-mediated antisaccade task of response inhibition using an event related design. A cue preceding antisaccade trials indicated if subjects could win points towards a monetary reward or if the trial did not involve a monetary incentive (neutral). Participants completed 4 fMRI runs and activation from correct trials was analyzed for group differences using multivariate analyses. Diffusion tensor imaging (DTI, 6 diffusion gradient orientations with 14 sequential averages, b0=800 s/mm2) scanning was completed by a similar group of 27 epilepsy patients (mean age 13 years, mean duration of epilepsy 3 years) and 88 age approximated controls at 3T. DTI analysis used tract based spatial statistics to localize regions of compromised white matter (lower fractional anisotropy) in patients compared to controls. Results: In the fMRI task, both groups demonstrated improved inhibitory control during reward vs. neutral conditions. However, patients made more inhibitory errors compared to controls. A widely distributed region known to support inhibitory oculomotor control and reward processing was similarly evident in both groups including visual cortex, superior parietal cortex, and orbital frontal cortex. However, patients demonstrated significantly less activation in the middle frontal gyrus, a putative cognitive control region. Higher activation in the middle frontal gyrus was associated with better antisaccade performance in the control group. DTI results showed broadly distributed regions of lower fractional anisotropy in association tracts (uncinate, superior longitudinal fasciculus), projection tracts (anterior thalamic radiations, internal capsule, and cortical spinal tract), and interhemispheric tracts (anterior and posterior corpus callosum) in the patients compared to controls. Patients had lower fractional anisotropy in the internal capsule, an important prefrontal-striatal connection in association with lower fMRI activation in the middle frontal gyrus compared to the controls. Conclusions: Pediatric epilepsy is associated with poorer inhibitory control. While motivational effects may improve cognitive performance, patients demonstrate persistent cognitive limitations which may be associated with poorer prefrontal cortex recruitment and compromised white matter integrity in prefrontal-striatal tracts. Structural and functional brain correlates of cognitive comorbidity may have long term implications for developmental outcome in pediatric epilepsy.