Influence of noninvasive brain stimulation on connectivity and local activation: a combined tDCS and fMRI study

The effect of transcranial direct current stimulation (tDCS) on neurobiological mechanisms underlying executive function in the human brain remains elusive. This study aims at examining the effect of anodal and cathodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) in comparison with sham stimulation on resting-state connectivity as well as functional activation and working memory performance. We hypothesized perturbed fronto-parietal resting-state connectivity during stimulation and altered working memory performance combined with modified functional working memory-related activation. We applied tDCS with 1 mA for 21 min over the DLPFC inside an fMRI scanner. During stimulation, resting-state fMRI was acquired and task-dependent fMRI during working memory task performance was acquired directly after stimulation. N = 36 healthy subjects were studied in a within-subject design with three different experimental conditions (anodal, cathodal and sham) in a double-blind design. Seed-based functional connectivity analyses and dynamic causal modeling were conducted for the resting-state fMRI data. We found a significant stimulation by region interaction in the seed-based ROI-to-ROI resting-state connectivity, but no effect on effective connectivity. We also did not find an effect of stimulation on task-dependent signal alterations in working memory activation in our regions of interest and no effect on working memory performance parameters. We found effects on measures of seed-based resting-state connectivity, while measures of effective connectivity and task-based connectivity did not show any stimulation effect. We could not replicate previous findings of tDCS stimulation effects on behavioral outcomes. We critically discuss possible methodological limitations and implications for future studies.