Differential tDCS and tACS Effects on Working Memory-Related Neural Activity and Resting-State Connectivity

Abstract

Transcranial direct and alternating current stimulation (tDCS and tACS, respectively) entail capability to modulate human brain dynamics and cognition. However, the comparability of these approaches at the level of large-scale functional networks has not been thoroughly investigated. In this study, 44 subjects were randomly assigned to receive sham (N = 15), tDCS (N = 15), or tACS (N = 14). The first electrode (anode in tDCS) was positioned over the left dorsolateral prefrontal cortex, the target area, and the second electrode (cathode in tDCS) was placed over the right supraorbital region. tDCS was delivered with a constant current of 2 mA. tACS was fixed to 2 mA peak-to-peak with 6 Hz frequency. Stimulation was applied concurrently with functional magnetic resonance imaging (fMRI) acquisitions, both at rest and during the performance of a verbal working memory (WM) task. After stimulation, subjects repeated the fMRI WM task. Our results indicated that at rest, tDCS increased functional connectivity particularly within the default-mode network (DMN), while tACS decreased it. When comparing both fMRI WM tasks, it was observed that tDCS displayed decreased brain activity post-stimulation as compared to online. Conversely, tACS effects were driven by neural increases online as compared to post-stimulation. Interestingly, both effects primarily occurred within DMN-related areas. Regarding the differences in each fMRI WM task, during the online fMRI WM task, tACS engaged distributed neural resources which did not overlap with the WM-dependent activity pattern, but with some posterior DMN regions. In contrast, during the post-stimulation fMRI WM task, tDCS strengthened prefrontal DMN deactivations, being these activity reductions associated with faster responses. Furthermore, it was observed that tDCS neural responses presented certain consistency across distinct fMRI modalities, while tACS did not. In sum, tDCS and tACS modulate fMRI-derived network dynamics differently. However, both effects seem to focus on DMN regions and the WM network-DMN shift, which are highly affected in aging and disease. Thus, albeit exploratory and needing further replication with larger samples, our results might provide a refined understanding of how the DMN functioning can be externally modulated through commonly used non-invasive brain stimulation techniques, which may be of eventual clinical relevance.

Keywords: resting-state functional magnetic resonance imaging (rs-fMRI); task-based functional magnetic resonance imaging (tb-fMRI); transcranial alternating current stimulation (tACS); transcranial direct current stimulation (tDCS); working memory (WM).

FIGURE 1

Study protocol. (A) Assignment of participants to one of the experimental groups. (B) Stimulation montage for all groups, with the first electrode (anode for tDCS) centered over the F3 (in red) and the second electrode (cathode for tDCS) placed over the FP2 (in blue) in a 10–10 system map. (C) Timeline of the procedures accomplished before, during and after the tES-MRI protocol. tDCS, transcranial direct current stimulation; tACS, transcranial alternating current stimulation; tES, transcranial electrical stimulation; MRI, magnetic resonance imaging; rs-fMRI, resting-state functional MRI; hr-3D, high-resolution three-dimensional.

FIGURE 2

Selected networks and their respective ROIs location. (A) Cognitive networks with their corresponding ROIs in red for the DMN, in light blue for the lFPN, in dark blue for the rFPN, and in green for the ECN. (B) Control networks with their corresponding ROIs in purple for the SMN and in orange for the VMN. DMN, default-mode network; lFPN, left fronto-parietal network; rFPN, right fronto-parietal network; ECN, executive-control network; SMN, sensorimotor network; VMN, visual-medial network. For ROI abbreviations see Table 1.

FIGURE 3

Seed-to-seed statistically significant results within the DMN (in red) and the ECN (in green) for: (A) interaction between groups, (B) tDCS > sham, (C) tACS < sham, and (D) tDCS > tACS. tDCS, transcranial direct current stimulation; tACS, transcranial alternating current stimulation. For ROI abbreviations see Table 1.

FIGURE 4

Comparison between the online and post-stimulation fMRI n-back tasks in each group. (A) Online vs. post-stimulation results in the tDCS group. (B) Online vs. post-stimulation results in the tACS group. Top: statistically significant fMRI activity maps on the standard MNI for each contrast of interest. Results are shown in red-yellow for higher activations (or lower deactivations) online as compared to post-stimulation. Down: plots of mean BOLD signal values at the fMRI clusters considering sham, tDCS and tACS where significant differences between both fMRI n-back tasks were found. Data are presented as mean with standard error of the mean (SEM). tDCS, transcranial direct current stimulation; tACS, transcranial alternating current stimulation; BOLD, blood oxygen level dependent.

FIGURE 5

Online fMRI n-back task results. (A) tACS vs. sham results are shown in red-yellow. (B) tDCS vs. tACS results are shown in green. Left: statistically significant fMRI activity maps on the standard MNI for each contrast of interest and group comparison. Right: plots of mean BOLD signal values at the fMRI clusters considering sham, tDCS and tACS where significant differences between groups were found. Data are presented as mean with SEM. tACS, transcranial alternating current stimulation; tDCS, transcranial direct current stimulation; BOLD, blood oxygen level dependent.

FIGURE 6

Post-stimulation fMRI n-back task results. (A) tDCS vs. sham results are shown in red-yellow for higher activations and blue-light blue for lower activations. (B) tDCS vs. tACS results are shown in green. Left and up: statistically significant fMRI activity maps on the standard MNI for each contrast of interest and group comparison. Right and below: plots of mean BOLD signal values at the fMRI clusters considering sham, tDCS and tACS where significant differences between groups were found. Data are presented as mean with SEM. tDCS, transcranial direct current stimulation; tACS, transcranial alternating current stimulation; BOLD, blood oxygen level dependent.

FIGURE 7

Scatter plot showing the relationship at the highest WM load between tDCS-induced changes in BOLD signal post-stimulation when compared to online within the fMRI cluster where tDCS showed less activity than sham after stimulation (Figure 6A, blue-light blue fMRI cluster) and RT post-stimulation as compared to online. Data are presented with z scores. tDCS, transcranial direct current stimulation; BOLD, blood oxygen level dependent; Diff, difference; RT, reaction time.

FIGURE 8

Scatter plots showing the relationships in the tDCS group between (A) mPFC-lIPL rs-FC and post-stimulation 3 > 0-back BOLD signal (in the tDCS < sham fMRI cluster) and (B) lIPL-lCer rs-FC and 1 > 0-back difference in BOLD signal (in the post-stimulation – online fMRI cluster). Data are presented with z scores. tDCS, transcranial direct current stimulation; BOLD, blood oxygen level dependent; Diff, difference; mPFC, medial prefrontal cortex; lIPL, left inferior parietal lobule; rs-FC, resting-state functional connectivity; lCer, left cerebellum.