Consistent cerebellar pathway-cognition associations across pre-adolescents & young adults: a diffusion MRI study of 9000+ participants
Authors: Zekelman Leo R. , Cetin-Karayumak Suheyla , Chen Yuqian , Almeida Melyssa , Legarreta Jon Haitz , Rushmore Jarrett , Pieper Steve , Lan Zhou , Desmond John E. , Baird Lissa C. , Makris Nikos , Rathi Yogesh , Zhang Fan , Golby Alexandra J. , O’Donnell Lauren J. 
Published: February 2025

AbstractThe cerebellum, long implicated in movement, is now recognized as a contributor to higher-order cognition. The cerebellar pathways provide key structural links between the cerebellum and cerebral regions integral to language, memory, and executive function. Here, we present a large-scale, cross-sectional diffusion MRI (dMRI) analysis investigating the relationships between cerebellar pathway microstructure and cognitive performance in over 9,000 participants spanning pre-adolescence (n>8,000 from the ABCD dataset) and young adulthood (n>900 from the HCP-YA dataset). We assessed the microstructure of five cerebellar pathways—the inferior, middle, and superior cerebellar peduncles; the parallel fibers; and input/Purkinje fibers—using three dMRI measures of fractional anisotropy, mean diffusivity, and number of streamlines. Cognitive performance was evaluated using seven NIH Toolbox assessments of language, executive function, and memory. In both datasets, we found numerous significant associations between cerebellar pathway microstructure and cognitive performance. These associations showed a strong correlation across the two datasets (r = 0.47, p < 0.0001), underscoring the reliability of cerebellar dMRI-cognition relationships in pre-adolescents and young adults. In both datasets, the strongest associations were found between the superior cerebellar peduncle and performance on language assessments, suggesting this pathway plays an important role in language function across age groups. In young adults, but not pre-adolescents, parallel fiber microstructure was linked to inhibitory control, suggesting that contributions to attentional processes may emerge or strengthen with maturation. Overall, our findings highlight the important role of cerebellar pathways in cognition and the utility of large-scale datasets for advancing our understanding of brain-cognition relationships.SignificanceThis study provides strong evidence linking cerebellar pathway tissue microstructure to cognition across large populations of preadolescent children and young adults. By leveraging diffusion MRI tractography and cognitive performance data from two major datasets, we identify significant relationships between cerebellar pathway microstructure and cognitive performance. Importantly, findings are significantly correlated across datasets, pointing to the consistency of these relationships, bridging age groups and acquisitions. These results highlight the cerebellar pathways’ integral role in cognitive functioning and underscore the value of large-scale, population-based studies in advancing our understanding of brain-cognition relationships.Classification1) Biological Sciences, Neuroscience; 2) Social Sciences, Psychological and Cognitive Sciences