Alterations of gray matter volumes and connectivity in patients with tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is an inherited genetic disorder caused by mutations in the TSC1 or TSC2 genes, encoding hamartin and tuberin. We aimed to evaluate structural volumes and connectivity of patients with TSC compared to those of healthy subjects. We consecutively enrolled 13 patients with a diagnosis of TSC and 15 age- and sex-matched healthy control subjects. Subjects underwent three-dimensional volumetric T1-weighted imaging, suitable for a quantitative analysis. Structural volumes were investigated using FreeSurfer image analysis software, and structural connectivity was calculated from a connectivity matrix, which was estimated from the correlation analysis of structural volumes using the Brain Analysis using Graph Theory software package. Differences in structural volumes and connectivity were analyzed between patients with TSC and healthy subjects. There were no differences of cortical volumes between the patients with TSC and healthy controls. However, we found decreased gray matter volumes in several subcortical regions in the patients with TSC compared to those in healthy controls, specifically in the putamen (0.3212 vs. 0.3841%, p = 0.001), even after multiple corrections. Regarding global structural connectivity, the small-worldness index was significantly decreased in patients with TSC compared to that in healthy controls (0.907 vs. 0.977, p = 0.049). This study revealed structural volumes and connectivity in patients with TSC that are significantly different from those in healthy controls. These alterations have implications for the pathogenesis of TSC.