Bubbico Giovanna, Tomaiuolo Federica, Sestieri Carlo, Akhlaghipour Golnoush, Granzotto Alberto, Ferretti Antonio, Perrucci Mauro Gianni, Sensi Stefano L, Delli Pizzi Stefano
Department of Neuroscience, Imaging and Clinical Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
Institute for Advanced Biomedical Technologies (ITAB), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
Brain Behav. 2025 May;15(5):e70565. doi: 10.1002/brb3.70565.
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.
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.
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.
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.
老年人学习外语(FLL)是一种综合认知增强工具,它整合了语言、认知和社会成分,以刺激神经可塑性并促进大脑重组,从而抵消与年龄相关的衰退。虽然先前的研究调查了FLL对皮质连接组的影响,但其对皮质下-皮质静息态功能连接(rs-FC)的影响仍未得到探索。本研究基于小脑在学习和衰老中的作用,聚焦于小脑的连接性。我们假设FLL主要调节小脑最“认知”的亚区域(如小脑脚和后叶)的rs-FC。
对27名参与者的rs-FC模式进行了分析,这些参与者接受了为期4周的FLL方案(n = 14)或对照方案(n = 13)。在体素水平分析中,以不同的小脑区域为种子,我们评估了FLL诱导的小脑-新皮质连接变化。此外,我们使用来自公开数据库的数据,定量评估了连接调制与与神经可塑性相关的神经递质受体表达之间的空间重叠。
FLL组在小脑-新皮质rs-FC方面表现出明显变化,包括I/蚓部IV-V与视觉皮质之间的连接减少,以及小叶VI/VIIb与额叶区域之间的连接增加。涉及I小叶和VI小叶的连接变化在空间上与CB1受体的分布重叠,并且在较小程度上,I小叶/VI小叶与蚓部IV-V的连接变化与mGluR5/GABAa受体的分布重叠。
我们为小脑参与FLL对衰老的有益作用提供了新的见解,进一步突出了CB1受体的作用,其次是mGluR5/GABAa受体的作用。