Visual cortical GABA and depth of amblyopia are negatively correlated

Amblyopia is a neurodevelopmental disorder that is characterized by reduced visual acuity, atypical binocular integration, and heightened perceptual suppression. Physiology studies in animal models suggest that intracortical GABAergic inhibition might play an important role in mediating amblyopic visual deficits. Magnetic resonance spectroscopy (MRS) and fMRI findings in normally sighted persons (NSP) have demonstrated a negative correlation between occipital GABA concentration and visually evoked fMRI response amplitude. To better understand the relationships among occipital GABA, fMRI responses to visual stimulation, and perceptual suppression in human amblyopia and normal vision, we collected MRS, fMRI, and psychophysical data from both persons with amblyopia (PWA) and NSP. MR spectra that were optimized for GABA measurements were obtained from a voxel positioned bilaterally along the calcarine sulcus, and fMRI responses to checkerboard stimuli were recorded in retinotopically-defined early visual cortical areas. In PWA, we found a robust negative correlation between the depth of amblyopia (interocular difference in visual acuity) and occipital GABA concentration. This relationship was specific to visual cortex and was not observed in a sensorimotor cortical control region. Finally, our data in NSP were consistent with the negative relationship between occipital GABA and fMRI visual cortical response amplitude that has been reported in other studies. However, in PWA, the same relationship between occipital GABA and fMRI response amplitude was absent, or possibly reversed. Taken together, our findings provide evidence that intracortical GABAergic inhibition is a component of the pathology of human amblyopia. We speculate that lower levels of visual cortical GABA in individuals with deep amblyopia represent a compensatory decrease in inhibition that limits the ability of the amblyopic eye to perceptually suppress the fellow eye.