To evaluate the role of white-matter tract involvement in executive dysfunction in patients with temporal lobe epilepsy and unilateral hippocampal sclerosis (TLE-HS). 

TLE-HS patients frequently display executive dysfunction (ED). The neuroanatomical substrate of ED in TLE-HS remains poorly understood. In this study, we investigated the role of white-matter tract involvement in ED in TLE-HS.

Patients with unilateral TLE-HS, aged 17-55, education>=8 years, IQ>=70, EEG findings of unilateral or bilateral temporal discharges were studied. Patients and healthy controls fulfilling the same inclusion criteria underwent the Stroop Color and Word Test (SCWT) and a 3T MRI with DTI sequences. DTI Fractional Anisotropy (FA) data was extracted and analyzed using FSL. FA maps were compared with Tract-Based Spatial Statistics (TBSS) voxel-wise analysis. Patients were classified as ED if performance in the SCWT was below minus 1.5 (-1.5) Standard Deviations of the mean performance of healthy controls.

49 patients (30 left and 19 right HS) underwent the SCWT. Performance did not differ between right and left HS. Patients with normal and impaired executive function did not differ in disease duration, antiseizure medication load, and seizure frequency. Both patient groups showed diffuse FA decrease when compared to healthy controls. Compared to TLE-HS patients with normal SCWT performance, patients with ED had more pronounced FA alterations, showing statistically significant decreased FA in the superior longitudinal fasciculi, body of the corpus callosum, forceps major, corona radiata, inferior frontal-occipital fasciculus, uncinate fasciculus and corticospinal tract, and right thalamic radiations.

In this TLE-HS patient population, executive dysfunction was associated with more pronounced widespread WM tract damage, in comparison with TLE-HS patients with preserved executive function.  This finding underscores the role of microstructural WM damage in executive dysfunction in TLE-HS.