Modulation of resting-state networks following repetitive transcranial alternating current stimulation of the dorsolateral prefrontal cortex

Transcranial alternating current stimulation (tACS) offers a unique method to temporarily manipulate the activity of the stimulated brain region in a frequency-dependent manner. However, it is not clear if repetitive modulation of ongoing oscillatory activity with tACS over multiple days can induce changes in grey matter resting-state functional connectivity and white matter structural integrity. The current study addresses this question by applying multiple-session theta band stimulation on the left dorsolateral prefrontal cortex (L-DLPFC) during arithmetic training. Fifty healthy participants (25 males and 25 females) were randomly assigned to the experimental and sham groups, half of the participants received individually adjusted theta band tACS, and half received sham stimulation. Resting-state functional magnetic resonance (rs-fMRI) and diffusion-weighted imaging (DWI) data were collected before and after 3 days of tACS-supported procedural learning training. Resting-state network analysis showed a significant increase in connectivity for the frontoparietal network (FPN) with the precuneus cortex. Seed-based analysis with a seed defined at the primary stimulation site showed an increase in connectivity with the precuneus cortex, posterior cingulate cortex (PCC), and lateral occipital cortex. There were no effects on the structural integrity of white matter tracts as measured by fractional anisotropy, and on behavioral measures. In conclusion, the study suggests that multi-session task-associated tACS can produce significant changes in resting-state functional connectivity; however, changes in functional connectivity do not necessarily translate to changes in white matter structure or behavioral performance.