Mapping Cerebellar Anatomical Heterogeneity in Mental and Neurological Illnesses

Abstract

The cerebellum has been 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 > 54k 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′s disease, bipolar disorder, and schizophrenia. Notably, individuals with autism spectrum disorder and mild cognitive impairment exhibited increased numbers of both positive and negative extreme deviations in cerebellar anatomy, while schizophrenia and Alzheimer′s disease predominantly showed negative deviations. Finally, extreme deviations were associated with cognitive scores. Our results provide a voxel-wise mapping of cerebellar anatomy across the human lifespan and clinical illnesses, demonstrating cerebellum9s nuanced role in shaping human neurodiversity across the lifespan and in different clinical illnesses.