Neural Mechanisms of Tinnitus

Abstract Tinnitus is the perception of sound that is independent from an external stimulus. Despite the word tinnitus being derived from the Latin verb for ring, tinnire, it can present as buzzing, hissing, or clicking. Tinnitus is generated centrally in the auditory pathway; however, the neural mechanisms underlying this generation have been disputed for decades. Although it is well accepted that tinnitus is produced by damage to the auditory system by exposure to loud sounds, the level of damage required and how this damage results in tinnitus are unclear. Neural recordings in the auditory brainstem, midbrain, and forebrain of animals with models of tinnitus have revealed increased spontaneous firing rates, capable of being perceived as a sound. There are many proposed mechanisms of how this increase is produced, including spike-timing-dependent plasticity, homeostatic plasticity, central gain, reduced inhibition, thalamocortical dysrhythmia, and increased inflammation. Animal studies are highly useful for testing these potential mechanisms because the noise damage can be carefully titrated and recordings can be made directly from neural populations of interest. These studies have advanced the field greatly; however, the limitations are that the variety of models for tinnitus induction and quantification are not well standardized, which may explain some of the variability seen across studies. Human studies use patients with tinnitus (but an unknown level of cochlear damage) to probe neural mechanisms of tinnitus. They use noninvasive methods, often recoding gross evoked potentials, oscillations, or imaging brain activity to determine if tinnitus sufferers show altered processing of sounds or silence. These studies have also revealed putative neural mechanisms of tinnitus, such as increased delta- or gamma-band cortical activity, altered Bayesian prediction of incoming sound, and changes to limbic system activity. Translation between animal and human studies has allowed some neural correlates of tinnitus to become more widely accepted, which has in turn allowed deeper research into the underlying mechanism of the correlates. As the understanding of neural mechanisms of tinnitus grows, the potential for treatments is also improved, with the ultimate goal being a true treatment for tinnitus perception.