Modulation of GABA and resting state functional connectivity by transcranial direct current stimulation

Abstract

We previously demonstrated that network level functional connectivity in the human brain could be related to levels of inhibition in a major network node at baseline (Stagg et al., 2014). In this study, we build upon this finding to directly investigate the effects of perturbing M1 GABA and resting state functional connectivity using transcranial direct current stimulation (tDCS), a neuromodulatory approach that has previously been demonstrated to modulate both metrics. FMRI data and GABA levels, as assessed by Magnetic Resonance Spectroscopy, were measured before and after 20 min of 1 mA anodal or sham tDCS. In line with previous studies, baseline GABA levels were negatively correlated with the strength of functional connectivity within the resting motor network. However, although we confirm the previously reported findings that anodal tDCS reduces GABA concentration and increases functional connectivity in the stimulated motor cortex; these changes are not correlated, suggesting they may be driven by distinct underlying mechanisms.

Keywords: GABA; brain stimulation; functional connectivity; human; neuroscience; plasticity; resting state networks; tDCS.

Figure 1.. Experimental design.

All subjects participated in two testing sessions with either anodal or sham tDCS, the order of which was counterbalanced across the group. GABA was measured at three time points (baseline, during, post) and resting state connectivity was measured at two time points (baseline, post). Timeline shown is an estimate of the length of the scans in minutes. DOI: http://dx.doi.org/10.7554/eLife.08789.002

Figure 2.. Representative (A) MR spectrum and (B) Group mean motor resting state network.

DOI: http://dx.doi.org/10.7554/eLife.08789.003

Figure 3.. A significant relationship between M1-GABA and the strength of the motor network measured from the same region was identified at baseline (r = −0.62, p < 0.01).

DOI: http://dx.doi.org/10.7554/eLife.08789.004

Figure 4.. Change in GABA before, during, and after anodal tDCS relative to the sham condition.

(A) Gradual decrease in GABA levels was observed during anodal stimulation with the most prominent decrease approximately 10–15 min after stimulation has finished (Post1). Break in the lines indicate a time gap when approximately 7 min of resting state acquisition was performed immediately after tDCS stimulation. Timescale shows the approximate time from the beginning of the scan session. (Post 1: t(11) = −4.14, p < 0.01; Post 2: t(11) = −2.86, p = 0.02). DOI: http://dx.doi.org/10.7554/eLife.08789.005

Figure 5.. Change in functional connectivity before and after Anodal tDCS and the Sham condition.

(A) Anodal tDCS applied to M1, significantly increased functional connectivity within M1 of the motor network (t (11) = −2.45, p = 0.03). (B) There were no differences in the sham condition (t(11) = 0.07, p = 0.95). DOI: http://dx.doi.org/10.7554/eLife.08789.006

Figure 6.. No significant relationship was demonstrated between GABA levels after tDCS and the strength of the motor network.

DOI: http://dx.doi.org/10.7554/eLife.08789.007