Surface-based morphometry reveals caudate subnuclear structural damage in patients with premotor Huntington disease

In patients with premotor Huntington's disease (pmHD), literature has reported decreases in caudate volume. However, the regional vulnerability of the caudate nucleus to pmHD remains to be clarified. We aimed to determine whether regional structural damage of the caudate nucleus was present in pmHD and was correlated with clinical profile using a surface-based morphometric technique applied to T1-weighted MRI. The study cohort consisted of 14 volunteers with genetically confirmed pmHD (6 males; 41.8 ± 13.2 years) and 11 age- and sex-matched controls (5 males; 46.2 ± 11.9 years, p > 0.3). On 3-T T1-weighted images, bilateral caudate volumes were manually delineated. The resulting labels were converted to a surface, triangulated with 1002 points equally distributed across subjects using SPHARM-PDM. Displacement vectors were then computed between each individual and a template surface representing the whole cohort. Computing point-wise Jacobian determinants (JD) from these vectors quantified local volumes. We found decreases in bilateral global caudate volumes in the pmHD group compared to controls (t = 3.4; p = 0.002). Point-wise analysis of local volumes mapped caudate atrophy in pmHD primarily onto medial surface (t > 2.7; FDR < 0.05), with most pronounced changes in anteromedial subdivision. In a combined group of patients and controls, volume within the area presenting significant group difference was positively correlated with scores of executive function (r = 0.7; p < 0.001) and working memory (r = 0.6; p = 0.002). In patients, the caudate atrophy was associated with increase in disease burden (r = 0.7; p = 0.005). Caudate subnuclear atrophy measured using our surface-based morphometric technique is evident in pmHD, correlates with clinical variables, and may provide a more sensitive biomarker than global volumes.