Modulation of network centrality and gray matter microstructure using multi‐session brain stimulation and memory training

Thams, Friederike; Külzow, Nadine; Flöel, Agnes; Antonenko, Daria · 2022 · Crossref

DOI: 10.1002/hbm.25857

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Summary

This study investigates the neural mechanisms underlying behavioral improvements induced by a combined intervention of transcranial direct current stimulation (tDCS) and cognitive training in older adults. While previous research demonstrated that a 3-day visuospatial memory training paired with anodal tDCS over the right temporoparietal cortex improved performance, the specific neurophysiological changes driving these benefits remained unclear. The authors aimed to determine whether this multi-session intervention modulates whole-brain functional network architecture and gray matter microstructure, addressing the gap in understanding how tDCS enhances plasticity in aging brains. The researchers analyzed multimodal magnetic resonance imaging (MRI) data from 35 older adults (including 8 with mild cognitive impairment) who participated in a counter-balanced, placebo-controlled crossover study. Participants underwent three days of object-location memory training while receiving either anodal tDCS or sham stimulation. MRI scans, including resting-state functional MRI (fMRI) and diffusion tensor imaging (DTI), were acquired one day before and after the intervention. To assess functional network changes, the authors employed eigenvector centrality mapping (ECM), a graph-theoretical approach that identifies the relevance of brain regions within the whole-brain network without requiring a priori hypotheses. To evaluate microstructural changes, they analyzed DTI-derived mean diffusivity (MD) in regions identified by the ECM analysis, using training success as a covariate. The results revealed a significant interaction between stimulation condition and time point in bilateral posterior temporooccipital clusters. Specifically, eigenvector centrality decreased in the anodal group compared to the sham group, indicating a functional decoupling of these regions from other highly connected brain areas. This reduction in centrality suggests increased network segregation, potentially counteracting age-related declines in network specificity. Furthermore, an interaction between stimulation condition and training success was observed for gray matter MD in the right lateral occipital complex. In the anodal group, higher training success was significantly associated with decreased MD, reflecting increased tissue density and microstructural plasticity. This association was absent in the sham group. No significant MD changes were found in the left hemisphere clusters. These findings provide the first evidence that gray matter microstructural alterations, measured by MD, are involved in tDCS-enhanced cognitive training. The study demonstrates that combining tDCS with cognitive training induces targeted neuromodulatory effects, specifically reducing functional connectivity centrality in task-relevant regions and promoting microstructural changes linked to learning success. This suggests that the intervention may help restore age-related deficits in network segregation. The results highlight the importance of multi-modal imaging in elucidating the mechanisms of non-invasive brain stimulation and support the development of specific therapeutic interventions for age-associated cognitive decline.

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• cognitive impairment