Human Auditory Cortex Neurochemistry Reflects the Presence and Severity of Tinnitus

It is not known why tinnitus occurs in some cases of hearing damage but not others. Abnormalities of excitation–inhibition balance could influence whether tinnitus develops and its severity if it does. Animal models of hearing damage, which also produce tinnitus based on behavioral evidence, have identified abnormalities of GABAergic inhibition, both cortically and subcortically. However, the precise relationships of GABA inhibitory changes to tinnitus itself, as opposed to other consequences of hearing damage, remain uncertain. Here, we used magnetic resonance spectroscopy to non-invasively quantify GABA in the left (LAC) and right (RAC) auditory cortices of a group of 14 patients with lateralized tinnitus (eight left ear) and 14 controls matched for age, sex, and hearing. We also explored the potential relationships with other brain metabolites (i.e., choline, N-acetylaspartate, and creatine). The presence of tinnitus was associated with a reduction in auditory cortex GABA concentration. Regardless of tinnitus laterality, post hoc testing indicated reductions that were significant in RAC and nonsignificant in LAC. Tinnitus severity and hearing loss were correlated positively with RAC choline but not GABA. We discuss the results in the context of current models of tinnitus and methodological constraints. SIGNIFICANCE STATEMENT Permanently affecting one in seven adults, tinnitus lacks both widely effective treatments and adequate understanding of its brain mechanisms. Existing animal models represent tinnitus that may not be distinguishable from homeostatic responses to the auditory insults used to induce it. Human studies can be well controlled in this regard but are usually not (with few even matching control subjects for hearing loss) and are limited in scope as a result of relying solely on non-invasive recording techniques. Here, we exploit recent advances in non-invasive spectroscopic techniques to establish, in a human study tightly controlled for hearing loss and hyperacusis, that tinnitus is associated with a significant reduction in auditory cortex GABA concentration, which has implications for understanding and treatment of the condition.