Microstructural and functional plasticity following repeated brain stimulation during cognitive training in non-demented older adults

Abstract The combination of repeated behavioral training with transcranial direct current stimulation (tDCS) holds promise to exert benefial effects on brain function beyond the trained task. However, little is known about the underlying mechanisms. This was adressed by multimodal magnetic resonance imaging (MRI) before and after a three-week executive function training with prefrontal excitatory tDCS in 48 older adults. Results demonstrate that training combined with active tDCS enhanced prefrontal white matter microstructure which predicted individual performance gain. Training-plus-tDCS also resulted in microstructural grey matter reductions at the stimulation site, and increased prefrontal functional connectivity. We provide insight into the mechanisms underlying neuromodulatory interventions, suggesting tDCS-induced changes in fiber organization and myelin formation, glia-related and synaptic processes in the target region, and synchronization within targeted functional networks. These findings advance the mechanistic understanding of neural tDCS effects, thereby contributing to more targeted neural network modulation in future experimental and translation tDCS applications.