Macromolecule-suppressed GABA measurements correlate more strongly with behavior than macromolecule-contaminated GABA+ measurements

Abstract

The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is known to be fundamental to the neuronal processes underlying visual orientation and vibrotactile frequency and amplitude discrimination. Previous studies have demonstrated that performance on visual and vibrotactile psychophysics tasks is associated with in vivo measurements of “GABA+” levels – a measure of GABA substantially contaminated by a macromolecular (MM) signal. Here, we establish that these prior findings are indeed driven by the GABA fraction of that signal. Edited magnetic resonance spectroscopy (MRS) was used to measure GABA with and without MM suppression in the sensorimotor (SM1) and occipital cortices in 14 healthy male adults. Volunteers also underwent psychophysical experiments to assess their performance on visual orientation discrimination and vibrotactile amplitude and frequency discrimination. We show that MM-suppressed GABA levels correlate more strongly with individual differences in vibrotactile (in the case of SM1 GABA; amplitude: r = −0.63, p = 0.03; frequency: r = −0.62, p = 0.02) and visual orientation (in the case of occipital GABA; r = −0.59, p = 0.05) discrimination thresholds than GABA levels contaminated by MM (vibrotactile amplitude: r = −0.36, p = 0.30; vibrotactile frequency: r = −0.53, p = 0.09; visual orientation: r = 0.21, p = 0.55). These findings further support the view that measurements of endogenous GABA acquired with edited MRS can usefully probe neurochemical–behavioral relationships in humans. Moreover, the more specific measurement of GABA used in this study provides increased statistical power to observe these regionally specific relationships.