The role of GABA in human motor learning

Abstract

GABA modification plays an important role in motor cortical plasticity. We therefore hypothesized that interindividual variation in the responsiveness of the GABA system to modification influences learning capacity in healthy adults. We assessed GABA responsiveness by transcranial direct current stimulation (tDCS), an intervention known to decrease GABA. The magnitude of M1 GABA decrease induced by anodal tDCS correlated positively with both the degree of motor learning and the degree of fMRI signal change within the left M1 during learning. This study therefore suggests that the responsiveness of the GABAergic system to modification may be relevant to short-term motor learning behavior and learning-related brain activity.

Figure 1

Group Mean Reaction Times in Response to an Explicit Sequence Learning Task and a Typical GABA-Optimized Spectrum (A) Group mean reaction time data showing a decrease in reaction times over blocks as the subjects learned the sequence. Blocks 1 and 15 are blocks containing 30 visual cues in a random order, whereas other blocks contained three repetitions of the same sequence. Points are mean ± standard error of the mean. (B) Typical GABA-optimized spectrum showing characteristic peaks for GABA, Glx, and NAA. See also Figure S1.

Figure 2

Baseline Measures (A) Significant positive correlation between baseline GABA:NAA ratio within the M1 voxel and reaction times during random (nonlearning) blocks (r = 0.64, p = 0.03). (B) Group mean activation map in response to the motor boxcar regressor demonstrating activity in a bilateral frontoparietal network. Color bar shows Z statistic values. (C) The left primary sensorimotor cortex showed a significant negative correlation between BOLD signal change in response to the motor boxcar and baseline GABA:NAA ratio. (D) Negative correlation between baseline GABA:NAA ratios and mean BOLD signal change in response to the motor boxcar regressor within a left M1 ROI (r = −0.688, p = 0.01, uncorrected). For full details on how the ROI was derived, see Supplemental Experimental Procedures. See also Figure S2.

Figure 3

Change Measures (A) Significant positive correlation between change in GABA:NAA ratio due to anodal tDCS and change in reaction times due to learning (r = 0.645, p = 0.03). (B) Group mean activation map in response to the learning regressor demonstrating activity in a more limited bilateral frontoparietal network than that evident in response to the motor boxcar regressor (cf. Figure 2B). Color bar shows Z statistic values. (C) One cluster in left primary motor cortex showed a negative correlation between learning-related change in fMRI activity and change in GABA:NAA ratios due to anodal tDCS. (D) Negative correlation between change in GABA:NAA ratios due to anodal tDCS and the learning-related change in fMRI activity in the left M1 ROI (arbitrary units; r = −0.59, p = 0.05, uncorrected). For full details on how the ROI was derived, see Supplemental Experimental Procedures. See also Figure S2.