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

作者：G. Bubbico, Federica Tomaiuolo, C. Sestieri, Golnoush Akhlaghipour, A. Granzotto, Antonio Ferretti, M. Perrucci, S.L. Sensi, Stefano Delli Pizzi · 发表于：Aging Medicine · 年份：2026 · DOI：10.1002/agm2.70073 · 研究领域：Medicine

ABSTRACT 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 thala...