UC San Diego

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy in adults. Anterior temporal lobectomy (ATL), i.e., the surgical removal of the anterior portion of the affected temporal lobe, is a common treatment for patients with focal, refractory TLE. ATLs require the severing of several key white matter tracts and may theoretically initiate a cascade of degenerative changes in frontotemporal networks. Nonetheless, structural factors that give rise to post-surgical changes in frontotemporal networks are rarely studied longitudinally. Indeed, ATL presents a prime experimental design opportunity where one can assess for post-surgical change and answer mechanistic questions of executive dysfunction in TLE.

In this dissertation, we built on our past observations that a particular frontotemporal white matter tract, the uncinate fasciculus (UF), is critical to executive functioning in TLE. We tested the hypothesis that the severing of the temporal segment of the UF during ATL creates a cascade of degenerative events in interconnected brain regions that may mediate executive function. We used a multi-modal imaging approach (i.e., diffusion tensor imaging, or DTI combined with magnetic resonance imaging, or MRI) to test whether patients with TLE who undergo ATL show diffusional changes in the frontal section of the UF consistent with Wallerian degeneration. We determined whether these changes correlate with performance changes in executive function tasks. Specifically, we quantified white matter microstructure in sections of the UF before and after surgery, and measured the association between the DTI changes with changes in patients’ executive abilities (i.e., task-switching, verbal fluency, inhibition).

Our results showed that UF is a tract with distinct microstructural damage in both the frontal and temporal sections even before ATL. We also found that UF sections both exhibit statistically significant diffusivity changes following ATL on the side ipsilateral to surgery, and that the changes observed for frontal UF are concordant with Wallerian degeneration. Surprisingly, we found that patients undergoing ATL showed significant improvement on one aspect of executive functioning (i.e., task-switching), with no post-ATL changes in verbal fluency or inhibition at the group level. However, we found no correlations between changes in frontal UF diffusivity and task-switching performance.