White matter tracts supporting memory and language functions: a tractography based study in Temporal Lobe Epilepsy

Temporal Lobe Epilepsy (TLE) is the most common type of focal epilepsy, characterized by focal epileptogenic zone in the temporal lobe, which provokes specific cognitive alterations associated to the damaged area, such as memory and language impairments. The cerebral cortex has long been regarded as the major locus of cognitive function, but recently there has been an increasing interest in investigating the involvement of white matter (WM). The latter allows the communication between different cerebral areas, therefore it is necessary to also study the impact of possible WM alterations on epilepsy manifestation and the neuropsychological profile. This thesis aimed at investigating the involvement of specific bundles in memory and language functions, deepening the impact of WM alterations on these cognitive domains. The selected participants were pharmaco-resistant TLE patients with left and right epileptogenic focus, who underwent surgery in order to be seizure-free. Their memory and language functions were assessed before and a year after surgery, while WM bundles and their impairment were assessed using advanced MRI tractography. The behavioural results showed a worse memory and language outcome for TLE patients with left epileptogenic focus, while MRI detected significant microstructural alterations in all patients. More specifically, advanced indexes (e.g., neurite density, NDI) revealed more microstructural alterations compared to classical diffusion indexes (e.g., fractional anisotropy). Further, NDI of the left Superior Longitudinal Fasciculus explained 13% of the variation in the phonological fluency. These findings suggest a moderate role of WM associative bundles in supporting language function but further investigations are necessary to deeper investigate this relationship. In conclusion, the present work underlines the importance of investigating the integrity of WM bundles when treating specific pathologies because it allows to better understand which structures are involved in cognition and how we can intervene to help patients to recover their normal functioning.