Functional Specialization is Independent of Microstructural Variation in Cerebellum but Not in Cerebral Cortex

ABSTRACT The human brain is understood to follow fundamental principles linking form (such as microstructure and anatomical connectivity) to function (perceptual, motor, cognitive, emotional, and other processes). Most of this understanding is based on knowledge of the cerebral cortex, where functional specialization is thought to be closely linked to microstructural variation as well as anatomical connectivity. The Universal Cerebellar Transform (UCT) theory has posited that the cerebellum has a different form-function organization in which microstructure is uniform, and in which functional specialization is determined solely by anatomical connectivity with extracerebellar structures. All cerebellar functions may thus be subserved by a common microstructural - and hence computational - substrate. Here we tested this hypothesis by measuring microstructural variation and functional specialization as indexed by magnetic resonance imaging in 1003 healthy humans. Cerebral cortex exhibited the expected pattern of microstructure-function correlation, but functional specialization was independent of microstructural variation in the cerebellum. These findings support the idea that cerebellar functional specialization is not determined by microstructure, and hence that cerebellar functions may be computationally constant across domains. SIGNIFICANCE STATEMENT The cerebellum is estimated to contain more than half the neurons in the human brain, is known to be involved in motoric, cognitive, and emotional functions, and is implicated in many neurological and neuropsychological disorders, but remains far less studied than the cerebral cortex. The Universal Cerebellar Transform (UCT) theory posits that one uniform computation underlies all cerebellar functions across multiple domains, but testing that idea has been difficult. Here we find that unlike the cerebral cortex, in which microstructural variation is associated with functional variation, the cerebellum exhibits relatively uniform microstructure across functionally distinct regions. These findings support UCT theory, and draw a sharp distinction between form-function relations in the cerebellum versus the cerebral cortex.