Dual-montage high-definition transcranial direct current stimulation (HD-tDCS) modulates the neural dynamics serving working memory

Abstract

Verbal working memory (WM) is a critical cognitive construct supporting a broad range of daily functions. Neuroimaging studies have highlighted the involvement of prefrontal-occipital circuitry in WM, but specific regional contributions and possible laterality effects remain unclear. Transcranial direct current stimulation (tDCS) is an emerging technique that noninvasively modulates the excitability of neural populations, with studies showing stimulation effects on both local and distant but connected cortices. Herein, we utilized a novel dual-montage, high-definition tDCS (HD-tDCS) approach to evaluate the impact on functional brain dynamics and WM performance. Forty-five healthy adults underwent dual-montage HD-tDCS with 2.0 mA anodal stimulation applied over the midline occipital cortices and either the left or right dorsolateral prefrontal cortices (DLPFC) concurrently, or sham to both sites during three sessions. Following stimulation, participants completed a verbal WM task during magnetoencephalography (MEG). Whole-brain, voxel-wise maps were subjected to 1 × 3 repeated measure ANOVAs to probe stimulation effects. We found that left DLPFC-occipital stimulation induced stronger theta responses in the left superior temporal cortices, left supramarginal gyrus, left angular gyrus, and the right parietal cortices, while attenuated alpha responses were observed in the bilateral parietal cortices following right compared to left DLPFC-occipital stimulation and sham. Additionally, both active stimulation montages modulated oscillatory responses in the bilateral inferior frontal, the right lateral occipital cortices and other critical WM network regions during the encoding and maintenance phases. In conclusion, our results show that dual-montage anodal HD-tDCS differentially modulates spectrally and temporally distinct oscillatory responses, suggesting clear functional dissociations between left and right prefrontal regions during WM processing. These findings highlight the potential of tDCS in advancing our understanding of the unique contribution of each region in the network, which long-term could inform clinical interventions.

Keywords: Dorsal lateral prefrontal cortex (DLPFC); Dual-montage; Magnetoencephalography (MEG); Transcranial direct current stimulation (tDCS); Working memory (WM).

Fig. 1.. HD-tDCS current flow modeling, task paradigm, and study timeline.

Current flow modeling revealed relatively focal stimulation over the prefrontal and occipital cortices. Participants received 20 min of anodal HD-tDCS using a dual-montage design (i.e., left DLPFC – occipital, right DLPFC – occipital, sham) that was administered across three visits separated by about a week (M = 10.6 days) using a pseudorandomized cross-over design. After stimulation, participants completed a verbal WM task during MEG. Briefly, a fixation cross embedded within an empty 2 × 3 gird was presented on the screen, followed by six consonants for 2 s (encoding). The six consonants then disappeared for 3 s (maintenance) and a single probe letter appeared in the upper middle box of the grid for 0.9 s (retrieval). Participants were asked to respond as to whether the probe was among the six consonants presented during the encoding grid.

Fig. 2.. Time-frequency spectrograms during the verbal working memory task.

Grand-averaged time-frequency spectrograms of MEG sensors exhibiting one or more significant oscillatory responses, with gamma activity at the top and theta and alpha activity at the bottom. All signal power data are expressed as percent differences from baseline, with the scale bars shown on the far right for each spectrogram. The boxes indicate the time-frequency windows that were significantly different from baseline and thus used for beamforming. The dotted vertical lines indicate the onset of the encoding grid (0.0 s), as well as the beginning (2.0 s) and end (5.0 s) of the maintenance period. Note that significant responses can also be seen during the retrieval period, but these responses were not examined due to the planned task differences between in-set and out-of-set trials.

Fig. 3.. HD-tDCS effects on theta oscillations during encoding.

Whole-brain 1 × 3 RM-ANOVAs were performed to examine significant stimulation effects on theta activity during encoding. Significant effects were found in the (a) left supramarginal gyrus, (b) left angular gyrus, (c) left superior temporal gyrus, and (d) right parietal cortices. Post hoc testing revealed stronger theta responses in the left supramarginal gyrus, left angular gyrus, and the right parietal cortices following both left and right DLPFC-occipital stimulation compared to sham. Left DLPFC-occipital stimulation also induced stronger theta responses in the left superior temporal gyrus compared to both right DLPFC-occipital stimulation and sham. Note that the red-yellow color scheme in the brain maps reflect increases in theta power (i.e. increased neural activity). SG: supramarginal gyrus (SG); AG: angular gyrus; STG: superior temporal gyrus. *p < .05, **p < .005, ***p < .001.

Fig. 4.. HD-tDCS effects on alpha oscillations during late encoding.

Whole brain 1 × 3 RM-ANOVAs were performed to examine stimulation effects on alpha activity during the encoding period. Significant effects were found in the (a, b) bilateral superior parietal, (c) right cerebellum, and (d) right inferior frontal gyrus. Post hoc testing revealed weaker alpha responses (i.e., less negative relative to baseline) in the right cerebellum and the right inferior frontal cortices following both left and right active stimulation compared to sham, while right DLPFC-occipital stimulation induced weaker alpha oscillations in the bilateral superior parietal cortices relative to sham, as well as weaker alpha responses relative to left DLPFC-occipital stimulation in the right parietal cortices. Note that the blue-green color scheme used in the brain maps reflects weaker alpha power (i.e., more negative relative to baseline). SPC: Superior parietal cortices; IFG: Inferior frontal gyrus. **p < .005, ***p < .001.

Fig. 5.. HD-tDCS effects on maintenance related neural oscillatory activity.

Whole brain 1 × 3 RM-ANOVAs were used to examine stimulation effects on alpha and gamma activity during the memory maintenance period. Significant effects were found in the (a) left IFG for alpha oscillations and the (b) right lateral occipital cortices for gamma activity. Post hoc testing revealed weaker alpha responses in the left IFG following left DLPFC-occipital stimulation relative to both right DLPFC-occipital stimulation and sham. For gamma responses, left DLPFC-occipital stimulation induced stronger oscillations in the right lateral occipital cortices relative to both right DLPFC-occipital stimulation and sham. The blue-green color scheme in the top brain map represents weaker alpha power (i.e., more negative relative to baseline), while the red-yellow color schemes in the bottom brain reflects increased gamma power (i.e., stronger neural activity). IFG: Inferior frontal gyrus; LOC: Lateral occipital cortices. **p < .005, ***p < .001.