The Genetics of Cerebellar Structure and Associations With Cognitive Performance: A Twin Magnetic Resonance Imaging...

The cerebellum, traditionally associated with motor control, is increasingly recognized for its involvement in higher-order cognitive functions. However, the role of cerebellar subregions in cognition remains underexplored, as are the roles of genetic factors on cerebellar structure and brain-behavioral associations. The primary goal of this study was to investigate the relationship between cerebellar subregion volumes and cognitive performance. A secondary aim was to quantify the genetic contributions to cerebellar structure and determine the degree to which any brain-behavior associations were genetically mediated. 3T anatomic MRI data from N = 932 typically developing individuals from the Human Connectome Project were used for this study. Twenty-seven cerebellar regions of interest (ROIs) were automatically parcellated using CerebNet. Three additional lobar-level ROIs were derived from smaller measures. Nine functional domains (six cognitive and three motor) related to known or suspected cerebellar function were selected. Linear regression analyses were conducted to identify correlations between cerebellar volumes and cognitive outcomes, adjusting for age, sex, and overall brain volume. Univariate and bivariate quantitative genetic modeling was then performed in OpenMx. There were numerous statistically significant phenotypic associations between cognitive measures and cerebellar lobar and lobular volumes, particularly in the IPL, AL, bilateral cortices, left lobule V, right lobule VI, vermis, and vermis lobule VIII, each meeting the threshold of p < 0.02 across at least four out of nine cognitive domains. The vermis and vermis lobule VIII were of particular note, showing even stronger associations (p < 0.0009 across three domains). Cognitive measures were modestly heritable, and cerebellar ROIs were highly heritable. Quantitative genetic models suggested that brain-behavior associations are largely driven by shared environmental factors. Our findings identify novel associations between specific cerebellar subregions and cognitive performance, highlighting the vermis as a critical structure. We also provide a detailed map of the quantitative genetics of human cerebellar structure. Future studies are warranted.