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

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.