Fig 1.
(A) Building large-scale brain network model. Each parcellated cortical region was modeled using the dynamic mean-field models (MFMs) that express the neural activity of coupled excitatory (E) and inhibitory (I) populations. Interactions between 68 brain regions were coupled by structural connectivity (SC) obtained by diffusion magnetic resonance imaging (dMRI) and tractography. (B) tDCS E-fields. The E-fields were generated using tDCS-FEM and rendered with the SimNIBS software package [30]. The normal component of the E-field is mapped to the gray matter mesh surface. (C) Simulation of tDCS effects. The cortical normal electric field derived from finite element modeling (FEM) calculations was converted into equivalent membrane potential changes via the electric field-membrane potential polarization linear relationship. Subsequently, based on the linear proportionality between membrane potential polarization and synaptic gating variables, the tDCS regulatory factor θ was coupled into the synaptic gating variables Si within the large-scale brain network model. (D) DLPFC-tDCS effects on brain network. The effects of DLPFC-tDCS on brain functional networks were investigated from the perspective of static functional connectivity (FC) metrics (global topological, intra-/inter-resting-state network FC,whole-brain FC) and brain complexity (brain network complexity and flexibility, BOLD-structural connectivity relationship). In addition, the propagation mechanism of tDCS was further investigated using dynamic functional connectivity (dFC).
Fig 2.
The tDCS-HBM simulation results for the left dorsolateral prefrontal cortex (DLPFC) tDCS protocol (F3a-Fp2c).
(A) Electric field (E-field) distribution simulated by tDCS finite element model (FEM) and rendered with the SimNIBS software package [30]. (B) The changes in the blood oxygenation level-dependent (BOLD) signal in the anodically stimulated region (L.rMFG) and the cathodically stimulated region (R.LOF). (C) The average firing rates of Without-tDCS and F3a-Fp2c; brain regions with significant differences are visualized on the right. These results were visualized with the BrainNet Viewer toolbox [31]. *: , **:
, ***:
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Fig 3.
The stimulation effects of two DLPFC-tDCS protocols on brain functional network.
(A) Changes in functional connectivity (FC) following DLPFC-tDCS compared to Without-tDCS. These results were visualized using the GRETNA toolbox [32]. (B) Global topology properties changes for Without-tDCS, left DLPFC-tDCS, and right DLPFC-tDCS. Statistical comparisons were conducted between the two DLPFC-tDCS protocols and Without-tDCS using a paired sample t-test. Data are expressed as Mean ± SD. *: , **:
, ***:
. (C) Changes in FC within and between resting-state networks (RSNs) of two DLPFC-tDCS protocols. Whole-brain FC and FC within and between RSNs were statistically compared between two DLPFC-tDCS protocols and a Without-tDCS condition using a paired sample t-test (
). Only nodes with significant differences (paired sample t-test) are colored, while the remaining are white. The color bar indicates the statistical t-value. (D) Between whole-brain and anodically stimulated region FC. Brain regions were categorized into “High-SC” (top 10 regions with the stronger SC to anodically stimulated region) and “Low-SC” (remaining 57 regions). Data represent the t-value for significant changes in FC between whole brain and anodically stimulated regions under two DLPFC-tDCS protocols compared to the Without-tDCS condition. These results were visualized with the BrainNet Viewer toolbox [31].
Fig 4.
Difference in BOLD signal, flexibility, and complexity among three periods in left DLPFC-tDCS protocol (F3a-Fp2c).
(A) The correlation between changes in BOLD signal in whole-brain (excluding the anodically and cathodically stimulated regions) across three periods and the strength of their SC to the anodically stimulated region. Vertical axis: t-values from paired t-tests comparing BOLD signal differences between the stimulation period (During) versus baseline (Without) and recovery (Post) periods (During > Without and During > Post contrasts). Horizontal axis: the strength of SC between whole-brain and the anodically stimulated region. (B) The complexity and flexibility of the brain across three periods. Statistical comparisons of the Without-tDCS, During-stimulation, and Post-stimulation conditions were performed using paired sample t-test. Data are expressed as Mean ± SD. *: , **:
, ***:
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Fig 5.
Dynamic functional connectivity changes in left DLPFC-tDCS protocol (F3a-Fp2c).
The sliding windows are divided into three phases. Phase 1: The window slides throughout the During-stimulation period. Phase 2: The window covers the transition from the During-stimulation to the Post-stimulation period. Phase 3: The window slides throughout the Post-stimulation period. In each phase, five time-varying FC matrices (depicted as small rectangles in the figure) are shown, where each FC matrix represents the statistical comparison using paired sample t-tests between the left DLPFC-tDCS protocol and the Without-tDCS condition. Only the FC in the left DLPFC-tDCS protocol that is significantly different from Without-tDCS (paired sample t-test) is colored, while the remaining are white. Warmer colors indicate an increase in FC, while cooler colors indicate a decrease in FC. Color bars indicate statistical t-values ().
Fig 6.
Impact of structural connectivity on dynamic functional connectivity associated with the stimulated regions in left DLPFC-tDCS protocol (F3a-Fp2c).
(A) Impact of SC on dFC of anodically stimulated region (L.rMFG). (B) Impact of SC on dFC of cathodically stimulated region (L.LOF). The horizontal coordinates represent the changes in FC between whole-brain and stimulated brain regions within each sliding window of left DLPFC-tDCS compared to Without-stimulation. The vertical coordinates represent brain regions after sorting from weak to strong (bottom to top) SC strength between whole-brain and anodically or cathodically stimulated regions. Only the FC in the left DLPFC-tDCS that is significantly different from Without-tDCS (paired sample t-test) is colored, while the remaining nodes are white. Warmer colors correspond to an increase in FC, while cooler colors correspond to a decrease in FC. The color bars indicate statistical t-values ().