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

Abstract

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.

Keywords: Dorsolateral prefrontal cortex (DLPFC); Frontoparietal network; Functional connectivity; Functional magnetic resonance imaging (fMRI); Transcranial alternating current stimulation (tACS).

Fig. 1

The design of the study. Participants engaged in a 5-day experiment. On day 1, baseline assessments, including demographic, handedness, and mood (MDBF) questionnaires, were filled in. The participant performed computerized working memory (WM; N-Back task) and proactive interference (recent probes task, RPT) tasks. MRI scans were collected after questionnaires and behavioral measures. Alpha peak was assessed from Day 2 to Day 4, and individualized stimulation was administered, during which participants engaged in arithmetic training tasks. On day 5, MRI scanning, arithmetic tasks, N-back task, and proactive interference tasks similar to baseline measures were carried out

Fig. 2

Changes in functional connectivity for FPN. (A) shows connectivity changes between the FPN network and a cluster in the precuneus cortex after stimulation training. (B) shows the follow-up analysis. An increase in resting state functional connectivity in the stimulation group, while a decrease in the sham group was observed. The error bars indicate the standard deviation

Fig. 3

Seed-based connectivity analysis was performed by defining a seed at the stimulated brain region as shown in (A). (B) shows the significant clusters, including Precuneus Cortex, Cingulate Gyrus, posterior division, and Occipital Cortex. (C) shows the change in connectivity for the identified clusters in the experimental and sham groups. An increase in connectivity was observed in the experimental group, while a decrease was observed in the sham group for all three clusters. The error bars indicate the standard deviation

Fig. 4

The study observed an increase in FA values for the white matter tracts L-SLF (A), L-IFOF (B), and L-ATR (C) in both the experimental and sham groups. However, there were no significant differences found in the FA values between the two groups for the selected tracts when analyzing their interaction. The error bars represent standard deviation