Postoperative Changes in the Uncinate Fasciculus in Patients with Refractory Temporal Lobe Epilepsy

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

Postoperative Changes in the Uncinate Fasciculus in Patients with Refractory Temporal Lobe Epilepsy

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

Variability in the analysis of a single neuroimaging dataset by many teams

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2–5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.Depto. de Psicobiología y Metodología en Ciencias del ComportamientoFac. de PsicologíaTRUEpu