Prefrontal transcranial direct current stimulation changes connectivity of resting-state networks during fMRI

Abstract

Transcranial direct current stimulation (tDCS) has been proposed for experimental and therapeutic modulation of regional brain function. Specifically, anodal tDCS of the dorsolateral prefrontal cortex (DLPFC) together with cathodal tDCS of the supraorbital region have been associated with improvement of cognition and mood, and have been suggested for the treatment of several neurological and psychiatric disorders. Although modeled mathematically, the distribution, direction, and extent of tDCS-mediated effects on brain physiology are not well understood. The current study investigates whether tDCS of the human prefrontal cortex modulates resting-state network (RSN) connectivity measured by functional magnetic resonance imaging (fMRI). Thirteen healthy subjects underwent real and sham tDCS in random order on separate days. tDCS was applied for 20 min at 2 mA with the anode positioned over the left DLPFC and the cathode over the right supraorbital region. Patterns of resting-state brain connectivity were assessed before and after tDCS with 3 T fMRI, and changes were analyzed for relevant networks related to the stimulation-electrode localizations. At baseline, four RSNs were detected, corresponding to the default mode network (DMN), the left and right frontal-parietal networks (FPNs) and the self-referential network. After real tDCS and compared with sham tDCS, significant changes of regional brain connectivity were found for the DMN and the FPNs both close to the primary stimulation site and in connected brain regions. These findings show that prefrontal tDCS modulates resting-state functional connectivity in distinct functional networks of the human brain.

Figures

Figure 1.

Experimental protocol. Real and sham tDCS conditions were applied in random order after baseline fMRI scans within a double-blind, crossover design.

Figure 2.

Study-specific masks. A, RSN masks were created using the group average ICA of all subjects including all conditions. B, Electrode position masks were defined according to EEG positions F3 (anode) and Fp2 (cathode) of the international 10–20 electrode system. A representative T1 image projected on the MNI-T1 Colin 1 mm template (Holmes et al., 1998) from one of the subjects illustrates the localization of the stimulation electrodes.

Figure 3.

Group analysis of RSN time series. Group analysis of resting-state time series of the 13 subjects revealed four resting-state networks. A, The DMN, left FPN (L FPN), right FPN (R FPN), and SRN are shown before real tDCS, after real tDCS, and after sham tDCS, respectively. B, Group ICA RSNs derived from resting-state scans of all individuals during all conditions. Group analyses of RSN time series are shown for the conditions baseline1, baseline2, after real tDCS, and after sham tDCS.

Figure 4.

Effects of tDCS on connectivity. Connectivity differences within the RSNs (RSNc 1–3) for the contrasts (after real tDCS > baseline1) > (after sham tDCS > baseline2). Results are cluster corrected for familywise errors (p < 0.05). Resting-state network contrast (RSNc) 1 corresponds to the contrast in the DMN, RSNc 2 corresponds to the contrast in the left FPN, and RSNc 3 corresponds to the contrast in the right FPN (radiological convention). Numbers correspond to the clusters presented in Table 1.

Figure 5.

Exploratory analysis of whole-brain tDCS effects. RSN contrasts resulting from the contrast baseline1 > baseline2, real tDCS > baseline12, sham tDCS > baseline12, (after real > before real) > (after sham > before sham), and inverse contrasts for each of the four networks detected after stimulation [resting-state network contrast (RSNc) 1 corresponds to the contrast on the DMN, RSNc 2 to the contrast on the left FPN, RSNc 3 to the contrast on the right FPN, and RSNc4 to the contrast of the SRN]. Numbers correspond to the clusters presented in Table 2. Red color scales represent functional correlation for the contrast (after real tDCS > baseline1) > (after sham tDCS > baseline2), and blue color represents functional correlation for the contrast after real tDCS > baseline1 baseline2). Radiological convention: p < 0.001 (uncorrected); cluster size, >20 voxels.