Tract-based benchmarking of limbic abnormalities in temporal lobe epilepsy

PROJECT SUMMARY Epilepsy patient care faces significant challenges, with nearly one-third of patients experiencing drug-resistant seizures and half of those undergoing surgery continuing to have seizures post-intervention. Current diagnostic and treatment paradigms primarily rely on qualitative assessments of brain structure and function, often focusing on grey matter abnormalities. Often overlooked is the critical role of white matter tracts, long-range bundles of axons which support neural synchrony and excitability. Disruptions in white matter organization have been implicated in various neurological conditions, including epilepsy. This growing body of evidence emphasizes the value of studying white matter tracts to elucidate principles of brain organization and offer new insights into disease mechanisms and intervention targets. The goal of this proposal is to provide me with training on state-of-the-art white matter tractometry techniques that will be used to interrogate structural and functional disruptions in temporal lobe epilepsy (TLE). This training will allow me to test the hypothesis that structural abnormalities in the mesial limbic tracts of TLE patients relate to functional disruptions and can be jointly leveraged to delineate epileptogenic networks with enhanced neuroanatomical specificity and generalizability. The project is divided into two main aims. Aim 1 focuses on characterizing atypical tract-based macro- and microstructure in TLE patients using advanced diffusion-weighted MRI techniques. This will involve quantifying deviations from typical structural variability in unilateral TLE patients, with a particular focus on the mesial limbic system. Aim 2 will investigate atypical limbic tract functional connectivity in TLE using functional MRI, assessing how structural abnormalities relate to disruptions in functional connectivity. By integrating multiscale structural and functional measures of both grey and white matter, this research aims to provide a more comprehensive understanding of epileptogenic networks than conventional methods. The insights gained from these aims have the potential to advance our understanding of structure-function relationships in epilepsy and support the development of more precise, personalized diagnostic and treatment strategies for focal epilepsies. Furthermore, this work could lay the foundation for future studies on tract abnormalities in other neurological disorders, carrying potential to inform novel interventions such as targeted tract resections or neuromodulatory therapies.