Altered Cortical Morphometry in Pre-manifest Huntington’s Disease: Cross-sectional Data from the IMAGE-HD Study

Huntington’s disease (HD) is an inherited progressive neurodegenerative disease mainly associated with subcortical striatal atrophy. There is also strong evidence showing cerebral atrophy and cortical thinning; however, limited research has investigated altered patterns of cortical folding in this disease. Here, we investigated cortical morphometry via both gyrification index (GI, a measure of cortical folding) and cortical thinning. The localized GI was examined using a novel GI, namely LB-GI. As part of a cross-sectional study, pre-manifest (pre-HD) individuals (n = 29) and matched controls (n = 29) underwent T1-MRI using data from the IMAGE-HD study. Compared to controls, pre-HD individuals demonstrated significantly lower GI in the left superior parietal and the right superior temporal regions and greater cortical thinning in the bilateral pre-central and the superior frontal gyri and left caudal middle frontal gyrus, as well as the superior parietal region. For the first time, we report evidence of abnormal localized cortical folding in pre-HD. We also provide evidence that cortical folding impacts different regions of the cortical surface more so than cortical thickness. As a result, we propose a potential new biological marker that may increase our understanding of the neuropathology of HD. Greater understanding of brain changes could inform new therapeutic approaches and target points for clinical trials.