Abstracts

Rationale: Executive dysfunction is frequently reported in patients with refractory MTLE, even in the absence of frontal lobe pathology on conventional MRI. Diffusion tensor imaging (DTI) is a relatively new imaging tool that can detect microstructural white matter compromise, and therefore, has been used to reveal microscopic white matter damage in patients with MTLE. The purpose of this study was to investigate the relationship between frontotemporal white matter compromise and executive dysfunction in patients with MTLE. Methods: Diffusion tensor imaging (DTI) was performed in 17 patients with MTLE (9 left; 8 right) and 17 healthy controls. Fiber tracts were generated using an automated probabalistic DTI atlas that was derived from manual tracings in healthy controls and MTLEs. Fractional anisotropy (FA) was calculated for four fiber tracts that innervate the frontal lobes, and therefore, may contribute to executive functioning [uncinate fasciculus (UF), arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), and cingulum bundle (CING)]. Neuropsychological measures of executive functioning from the Delis-Kaplan Executive Functions System (Verbal Fluency; Trail Making Test) were obtained and Spearman rho correlations were performed to evaluate the relationship between fiber FA and cognitive performances. Results: Controls performed significantly better than patients with right and left MTLE on all measures of executive functioning (i.e., verbal fluency, category switching, and letter-number switching). FA values were lower in patients with MTLE relative to controls, and this was largely accounted for by bilaterally reduced FA in patients with left MTLE. No significant correlations were found among fiber FA values and cognitive performances in controls. In patients with MTLE, lower FA of the left AF was associated with poorer verbal fluency scores; whereas, lower FA of the right CING was associated with poorer scores on a measure of category switching. No correlations were found between FA of the IFOF or UF and neuropsychological measures. Conclusions: Our results suggest that microstructural compromise to frontotemporal and cingulum white matter fibers is associated with impaired fluency and cognitive flexibility, respectively. These structure-function relationships help to further elucidate substrates of executive dysfunction in patients with refractory TLE. Supported by K23 NS056091 & GE Healthcare