Maladaptive plasticity in tinnitus — triggers, mechanisms and treatment

Tinnitus, prevalent in up to 15% of the world population, is typically linked to noise-associated hearing loss, but the relationship between noise exposure and tinnitus is not straightforward: not all humans or model animals develop tinnitus after noise-associated cochlear damage, and the mechanisms involved in tinnitus involve central auditory system and nonauditory brain areas. This Review provides an overview of current understanding of neural mechanisms of tinnitus, which is essential for developing effective treatments for this disorder. Tinnitus is a phantom auditory sensation that reduces quality of life for millions of people worldwide, and for which there is no medical cure. Most cases of tinnitus are associated with hearing loss caused by ageing or noise exposure. Exposure to loud recreational sound is common among the young, and this group are at increasing risk of developing tinnitus. Head or neck injuries can also trigger the development of tinnitus, as altered somatosensory input can affect auditory pathways and lead to tinnitus or modulate its intensity. Emotional and attentional state could be involved in the development and maintenance of tinnitus via top-down mechanisms. Thus, military personnel in combat are particularly at risk owing to combined risk factors (hearing loss, somatosensory system disturbances and emotional stress). Animal model studies have identified tinnitus-associated neural changes that commence at the cochlear nucleus and extend to the auditory cortex and other brain regions. Maladaptive neural plasticity seems to underlie these changes: it results in increased spontaneous firing rates and synchrony among neurons in central auditory structures, possibly generating the phantom percept. This Review highlights the links between animal and human studies, and discusses several therapeutic approaches that have been developed to target the neuroplastic changes underlying tinnitus.