Gamma-aminobutyric acid and glutamate/glutamine associations with tinnitus and hearing loss

The present study aimed to evaluate the association between concentrations of the metabolites gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx), which have predominantly inhibitory and excitatory effects on neural function, respectively, in adults with tinnitus and hearing loss, those with only hearing loss, and controls with neither condition. Metabolite concentrations in all three participant groups were assessed via magnetic resonance spectroscopic imaging in auditory and fronto-parietal regions. The concentration of a third metabolite, creatine (Cre) was also acquired. Ratios of GABA/Cre, Glx/Cre, and Glx/GABA were compared across six manually delineated regions of interest (ROIs). Neither GABA/Cre nor Glx/Cre showed significant group differences in any of the six ROIs. For the Glx/GABA ratio, group-level differences were seen only in the right auditory cortex, where the control group had a significantly larger ratio than the group with tinnitus and hearing loss. While results largely did not replicate previous human work in this area, we cannot exclude the possibility of a neurochemical mechanism underlying any causal relationship between hearing loss and tinnitus, particularly given the finding of altered balance in excitatory/inhibitory metabolites in the right auditory cortex. In the context of previous work, the right auditory cortex is highlighted as a particular region of interest for further investigation. Methodological differences in human studies and inconsistent findings in animal studies have thus far impeded the field’s ability to gain direct insight into the relationship between tinnitus and hearing loss, and so we make some suggestions to help design future studies.