Modulation of brain metabolites by prefrontal transcranial direct current stimulation (tDCS) in healthy subjects - the double-blinded hypothesis

Introduction The physiological effects of transcranial direct current stimulation (tDCS) in non-motor cortex areas are not well understood. The dorsolateral prefrontal cortex (DLPFC) is a key tDCS target in several psychiatric disorders, and mechanisms of tDCS action are of particular interest. We therefore investigated the effects of tDCS over the DLPFC evaluating GABA, glutamate/glutamine (Glx) and glutamate (Glu) concentrations in healthy subjects. Methods Nineteen healthy subjects (11 women, mean age 23) were randomly assigned to active (20 min, 2 mA, 5 × 7 cm electrodes) and sham tDCS using a double-blind, cross-over design. The anode was positioned over F3 (left DLPFC), the cathode over F4 (right DLPFC). A MRS MEGA-PRESS sequence (TE = 68 ms, TR = 2000 ms) was acquired before, during, and after stimulation. Gannet 3.0 and LcModel were used to quantify GABA, Glx and Glu concentrations. Repeated-measures mixed effects models were conducted comparing pre, during and post measurements of active and sham tDCS. Mistakenly, the right and not the left DLPFC was targeted using MRS, therefore evaluating changes induced by cathodal tDCS in the right DLPFC. Results We found a significant reduction of right DLPFC glutamate concentrations during active stimulation (df = 133; P  = .023; effect size d = 0.398) as well as a significant reduction of Glx concentration during active stimulation (df = 133; P  = .007; effect size d = 0.477). No changes of GABA concentration in cortical regions in proximity to the cathode was observed during or after anodal tDCS stimulation. Conclusions Despite the methodological mistake on prefrontal data collection, the results are biologically plausible and contribute to unveil cathodal tDCS mechanisms of action over the right DLPFC. Confirming results of other trials by Stagg et al. (2009) [1] and Kim et al. (2014) [2] , cathodal stimulation exerts inhibitory effects on the brain. However, several methodological factors (e.g electrical field strengths and distribution, tDCS parameters and individual differences) may limit conclusive interpretation.