Baseline effects of transcranial direct current stimulation on glutamatergic neurotransmission and large-scale network connectivity

Abstract

Transcranial direct current stimulation (tDCS) modulates glutamatergic neurotransmission and can be utilized as a novel treatment intervention for a multitude of populations. However, the exact mechanism by which tDCS modulates the brain׳s neural architecture, from the micro to macro scales, have yet to be investigated. Using a within-subjects design, resting-state functional magnetic resonance imaging (rs-fMRI) and proton magnetic resonance spectroscopy ((1)H MRS) were performed immediately before and after the administration of anodal tDCS over right parietal cortex. Group independent component analysis (ICA) was used to decompose fMRI scans into 75 brain networks, from which 12 resting-state networks were identified that had significant voxel-wise functional connectivity to anatomical regions of interest. (1)H MRS was used to obtain estimates of combined glutamate and glutamine (Glx) concentrations from bilateral intraparietal sulcus. Paired sample t-tests showed significantly increased Glx under the anodal electrode, but not in homologous regions of the contralateral hemisphere. Increases of within-network connectivity were observed within the superior parietal, inferior parietal, left frontal-parietal, salience and cerebellar intrinsic networks, and decreases in connectivity were observed in the anterior cingulate and the basal ganglia (p<0.05, FDR-corrected). Individual differences in Glx concentrations predicted network connectivity in most of these networks. The observed relationships between glutamatergic neurotransmission and network connectivity may be used to guide future tDCS protocols that aim to target and alter neuroplastic mechanisms in healthy individuals as well as those with psychiatric and neurologic disorders.

Keywords: Functional network connectivity (FNC); Glutamine–glutamate (Glx); Independent component analysis (ICA); Magnetic resonance spectroscopy (MRS); Parietal lobe; Resting-state functional magnetic resonance imaging (rs-fMRI); Transcranial direct current stimulation (tDCS).

Figure 1. ICA-generated spatial maps of the 13 networks of interest

Spatial maps are plotted as Z-scores, Z > 3.0 and are displayed at the slice showing highest network connectivity. The (x,y,z) MNI coordinates are labeled underneath each component as well as the low-frequency to high-frequency power ratio (LF/HF) for each network. Higher values indicate more power in lower frequency. Color bars correspond to the range of connectivity values derived from a one-sample t-test. Abbreviations: RH, right hemisphere; LH, left hemisphere; PCC, posterior cingulate cortex; ACC, anterior cingulate cortex; SPL, superior parietal lobule; SM, sensorimotor; SPS, superior parietal sulcus.

Figure 2. Statistical parametric maps for the superior parietal lobule network

Differences after tDCS are displayed in red. Voxels exhibiting significant relationships with post-tDCS RH Glx measures are displayed in yellow and LH Glx measures in green (note the Glx relations in precuneus).

Figure 3. Statistical parametric maps for the anterior cingulate network

Statistically significant differences after tDCS are displayed in red. Voxels exhibiting significant relationships with post-tDCS RH Glx measures are displayed in yellow (note the Glx relations in precuneus).

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