Mapping cerebellar anatomical heterogeneity in mental and neurological illnesses

Abstract

The cerebellum is linked to motor coordination, cognitive and affective processing, in addition to a wide range of clinical illnesses. To enable robust quantification of individual cerebellar anatomy relative to population norms, we mapped the normative development and aging of the cerebellum across the lifespan using brain scans of >54,000 participants. We estimated normative models at voxel-wise spatial precision, enabling integration with cerebellar atlases. Applying the normative models in independent samples revealed substantial heterogeneity within five clinical illnesses: autism spectrum disorder, mild cognitive impairment, Alzheimer disease, bipolar disorder, and schizophrenia. Notably, individuals with autism spectrum disorder and mild cognitive impairment exhibited increased positive and negative extreme deviations in cerebellar anatomy, while those with schizophrenia and Alzheimer disease showed predominantly negative deviations. Finally, extreme deviations were associated with cognitive scores. Our results provide a voxel-wise mapping of cerebellar anatomy across the human lifespan demonstrating the cerebellum’s nuanced role in different clinical illnesses. This study maps cerebellar anatomy across the lifespan using over 54,000 brain scans from 132 scanning sites and identifies that patients with autism spectrum disorder, mild cognitive impairment, Alzheimer disease, and schizophrenia are likely to have deviations in cerebellar anatomy.