Polarity-sensitive modulation of cortical neurotransmitters by transcranial stimulation

Abstract

Transcranial direct current stimulation (tDCS) modulates cortical excitability and is being used for human studies more frequently. Here we probe the underlying neuronal mechanisms by measuring polarity-specific changes in neurotransmitter concentrations using magnetic resonance spectroscopy (MRS). MRS provides evidence that excitatory (anodal) tDCS causes locally reduced GABA while inhibitory (cathodal) stimulation causes reduced glutamatergic neuronal activity with a highly correlated reduction in GABA, presumably due to the close biochemical relationship between the two neurotransmitters.

Figure 1.

A, Typical placement of the 2 × 2 × 2 cm voxel within the left sensorimotor cortex. B, GABA optimized 3 T spectrum, showing resonances from NAA, GABA, and Glx. C, Changes in neurotransmitter-to-NAA ratios, given as percentage change from baseline values (mean ± SD). *p < 0.05, **p < 0.01. D, No change in absolute NAA quantification is seen in any stimulus condition. E, F, The decreases seen in both GABA (E) and Glx (F) following stimulation were sustained over the 20 min scanning period.

Figure 2.

A, Typical 7 T spectrum, showing creatine (Cr), NAA, glutamate (Glu), and glutamine (Gln) resonances. B, Glutamate-to-creatine ratios within the sensorimotor cortex in individual subjects. *p < 0.05.