Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation

Abstract

Despite its widespread use in cognitive studies, there is still limited understanding of whether and how transcranial direct current stimulation (tDCS) modulates brain network function. To clarify its physiological effects, we assessed brain network function using functional magnetic resonance imaging (fMRI) simultaneously acquired during tDCS stimulation. Cognitive state was manipulated by having subjects perform a Choice Reaction Task or being at “rest.” A novel factorial design was used to assess the effects of brain state and polarity. Anodal and cathodal tDCS were applied to the right inferior frontal gyrus (rIFG), a region involved in controlling activity large-scale intrinsic connectivity networks during switches of cognitive state. tDCS produced widespread modulation of brain activity in a polarity and brain state dependent manner. In the absence of task, the main effect of tDCS was to accentuate default mode network (DMN) activation and salience network (SN) deactivation. In contrast, during task performance, tDCS increased SN activation. In the absence of task, the main effect of anodal tDCS was more pronounced, whereas cathodal tDCS had a greater effect during task performance. Cathodal tDCS also accentuated the within-DMN connectivity associated with task performance. There were minimal main effects of stimulation on network connectivity. These results demonstrate that rIFG tDCS can modulate the activity and functional connectivity of large-scale brain networks involved in cognitive function, in a brain state and polarity dependent manner. This study provides an important insight into mechanisms by which tDCS may modulate cognitive function, and also has implications for the design of future stimulation studies.

Methodology for tDCS integration with fMRI

“…The study protocol is selected based on several assumptions and hypotheses such as time course of tDCS effect (Nitsche & Paulus, ), cellular mechanism of stimulation (Bikson et al, ; Rahman et al, ), state dependency of tDCS as a subthreshold stimulation method (Hsu, Juan, & Tseng, ; Li et al, ), and dose–response relationship. Ultimately, these considerations get to the heart of how tDCS research benefits from functional MR imaging and how to address inherent challenges in experimental design.…”

“…In contrast, resting‐state fMRI is a technique performed in wakefulness without a superimposed task to execute. If the nature of tDCS is (profoundly) influenced by brain state (Li et al, ; Shahbabaie et al, ), stimulation of different individuals with same current flow profile could lead to different results based on their brain state. In studies where both resting‐state and task‐fMRI is acquired the order of imaging is important meaning if rs‐fMRI is performed after task‐fMRI, the former may affect network activity during the latter (i.e., “brain state” change).…”

“…Moreover, traditional controls (sham, active sham at different location) would not account for dose specific artifacts. In another study, independent component analysis (ICA) was used to automatically classify signal and noise in a concurrent tDCS‐fMRI study (Li et al, ). Manual inspection suggested that using this method noise was removed from each voxel's time series.…”

The Reason Why rTMS and tDCS Are Efficient in Treatments of Depression

“…because effect could be driven by other incidentally affected brain regions." Both tDCS and TMS are shown to initiate these "unintended" effects: Bestmann showed using MRI that TMS of motor cortex below the threshold power can activate some other deeper structures, contrary to previous belief and Li showed similar phenomena in the case of tDCS (Bestmann et al, 2003(Bestmann et al, , 2004Li et al, 2018).…”

“…Bestmann et al (2004) demonstrated that with TMS application below the motor threshold power, MRI can detect a response from areas that were not intended to be stimulated (Bestmann et al, 2004). Li et al (2018) were the first research group to demonstrate that tDCS can activate some structures within DMN. Opitz et al (2015) conclude in their work that even the conductivity constants (dielectric constants for tissue types) used for calculating the effect of stimulation, or simulation, are not adequate for describing the much more demanding reality.…”