Transcranial Direct Current Stimulation Alters Functional Network Structure in Humans: A Graph Theoretical Analysis

Transcranial direct current stimulation (tDCS) is routinely used in basic and clinical research, but its efficacy has been challenged on a methodological, statistical and technical basis recently. The arguments against tDCS derive from an insufficient understanding of how this technique interacts with brain processes physiologically. Because of its potential as a central tool in neuroscience, it is important to clarify whether tDCS affects neuronal activity. Here, we investigate influences of offline tDCS on network architecture measured by functional magnetic resonance imaging. Applied to one network node only, offline tDCS affects the architecture of the entire functional network. Furthermore, offline tDCS exerts polarity-specific effects on the topology of the functional network attached. Our results confirm in a functioning brain and in a bias free and independent fashion that offline tDCS influences neuronal activity. Moreover, our results suggest that network-specific connectivity has an important role in improving our understanding of the effects of tDCS.

I. Introduction

Transcranial direct current stimulation [1]–[5] (tDCS) has been widely used in the neurosciences [6]–[9] for decades. This is so because interfering techniques like tDCS that are assumed to directly modulate neuronal activity are extremely promising for both basic and applied research as they allow for addressing research questions on the causal relationships between brain states and behaviour [10]–[12]. However, the efficacy of tDCS has been put into question recently [13]–[17] on a methodological, statistical and technical basis. It is thus central to have a closer look at the effects of tDCS on brain activity. In our previous publication [5], we provided evidence that offline tDCS locally affects neuronal responses in accordance with stimulation polarity (i.e. cathodal or anodal) as shown by whole-brain functional magnetic resonance imaging (fMRI) analyses. Nevertheless, the global effect of tDCS on functional brain networks in humans is still not well understood [18], [19], but is central for a better and more informative understanding of the mechanisms of tDCS. Based on our previous findings (whole-brain fMRI results) [5] and on the detailed work on living macaques by Krause et al. (2017) [20], here we decided to investigate, in humans, the outcome of tDCS on the underlying functional architecture of the brain as measured by fMRI using the same experimental settings as reported in Almeida et al. (2017) [5]. There are certain key methodological issues related to the effect of tDCS in the brain that are currently unsolved [12], [13], [21]. These include understanding the technique’s (i) functional focality, i.e. is tDCS limited to local effects on the stimulated area, or do the effects also transfer more globally to the network level as pointed out by Krause et al. (2017) [20]; (ii) specificity of stimulation, i.e. is tDCS-induced interference dependent on general processes such as the spatially wide expansion of the electrical field [22], or is it dependent on more neuronally-specified processes such as functional connectivity between regions; or (iii) modulatory effects, i.e. how does tDCS modulate functional connectivity between brain regions.