Learning a Foreign Language in Older Adults Shapes the Functional Connectivity of Distinct Cerebellar Sub‐Regions With Cortical Areas Rich in CB1 Receptor Expression

Background: Foreign language learning (FLL) in older adults is a comprehensive cognitive enhancement tool that integrates linguistic, cognitive, and social components to stimulate neuroplasticity and promote brain reorganization to counteract age-related decline. While previous studies have investigated the impact of FLL on the cortical connectome, its effects on subcortical-cortical resting-state functional connectivity (rs-FC) remain unexplored. The present study focuses on the connectivity of the cerebellum, based on its involvement in learning and aging. We hypothesize that FLL primarily modulates the rs-FC of the most "cognitive" cerebellar sub-regions, such as the crus and the posterior lobules. Methods: The rs-FC pattern was analyzed in 27 participants who underwent a 4-week FLL (n = 14) or a control (n = 13) protocol. Using distinct cerebellar regions as seeds in voxel-wise analyses, we evaluated FLL-induced changes in cerebellar-neocortical connectivity. Furthermore, we quantitatively assessed the spatial overlap between the connectivity modulations and the expression of neurotransmitter receptors associated with neuroplasticity, using data from publicly available repositories. Results: The FLL group showed distinct changes in cerebellar-neocortical rs-FC, including reduced connectivity between Crus I/Vermis IV-V and the visual cortex and increased connectivity between Lobule VI/VIIb and frontal regions. The connectivity changes involving Crus I and Lobule VI spatially overlapped with the distribution of CB1 receptors and, to a lesser extent, between the connectivity changes of Crus I/Lobule VI and Vermis IV-V and mGluR5/GABAa receptors. Conclusions: We provide new insights into the involvement of the cerebellum in the beneficial effects of FLL in aging, further highlighting the role of CB1 receptors and, secondarily, mGluR5/GABAa receptors.