| Background. Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults. TLE is typically associated with mesiotemporal atrophy on MRI, but ample data suggests further structural damage in neocortical regions and the thalamus. However, the underlying pathogenesis and relevance of these changes are poorly understood.;Methods. We carried out the following experiments: 1. Mapping the extent of neocortical thinning and assessing its relationship to mesiotemporal pathology. 2. Mapping progressive cortical thinning in TLE through cross-sectional and longitudinal analyses. 3. Assessing the clinical value of cortical thickness measurements in TLE by investigating their reproducibility and relationship to surgical outcome. 4. Assessing organizational disruptions in cortico-cortical networks in TLE through a graph-theoretical analysis of cortical thickness correlations. 5. Analyzing the relationship between cortical thinning and thalamo-cortical connectivity. Local patterns of thalamic changes were assessed using thalamic surface-shape analysis. 6. Analyzing the relationship between cortical thinning and disruptions of subcortical white matter quantified by diffusion tensor imaging tractography.;Results. We observed marked and progressive cortical thinning in TLE in mainly temporo-limbic and fronto-central cortices. Patterns of thinning were reproducible across datasets and bootstrap simulations, and seen in patients with and without hippocampal atrophy. The degree of fronto-central cortical thinning correlated to atrophy in medial thalamic divisions, as well as to microstructural derangements in underlying white matter tracts. In operated patients, local patterns of cortical thinning as well as patterns of large-scale disruptions in cortico-cortical network organization related to post-surgical seizure recurrence.;Significance. TLE is associated with widespread cortical thinning and large-scale structural network disruptions, indicating a systemic nature of brain pathology in this disorder. Cortical thinning is progressive and correlates with the degree of pathology in thalamic divisions, likely indicating damage due to seizure spread from mesiotemporal to thalamo-cortical networks. Local cortical thickness measurements and data from cortical thickness correlation networks provided useful information for surgical outcome prediction, and may ultimately improve the presurgical assessment in individual TLE patients.;Purpose. Our overall goal was to analyze the topography and progression of neocortical thinning, its clinical relevance, and its relationship to patterns of connectivity in drug-resistant TLE using MRI-based cortical thickness measurements. |
