Foreign Language Learning in Older Adults Modifies Resting-State Functional Connectivity Between the Subcortical Structures and the Cortex

Objectives: Neuroimaging studies suggest that Foreign Language Learning (FLL) influences resting-state functional connectivity (rs-FC) within the neocortex, but its effects on subcortical–cortical connectivity remain unclear. We hypothesize that FLL may specifically affect the rs-FC of subcortical regions involved in integrating cortical networks, leading to adaptive changes in overall brain connectivity. Methods: Twenty-seven healthy older adults were randomly assigned to either a 16-week FLL intervention or a control condition. Resting-state fMRI data were analyzed using seed-based connectivity methods targeting seven subcortical structures. Group differences in rs-FC were examined alongside correlations with maps of the expression of receptors/genes related to plasticity and behavioral performance. Results: FLL induced specific and distributed changes in rs-FC between subcortical and cortical areas. Notably, thalamocortical circuits showed both increases and decreases in connectivity with regions of the default mode network. Increases of striato-cortical connectivity targeted frontal regions. Changes of connectivity spatially overlapped with cortical areas enriched in CB1 receptor density and NTRK2 gene expression. Importantly, FLL also modulated pallidal connectivity, a change that was significantly associated with improvements in semantic memory. Conclusions: The FLL program selectively reorganizes subcortico–cortical networks, particularly those involving the thalamus and the caudate, in a way that supports the biological plausibility of FLL-induced functional plasticity. The alignment with plasticity-related molecular markers and the observed cognitive improvements further support the potential of FLL as an ecologically valid strategy for preserving brain function in later life.