Tinnitus: animal models and findings in humans.

Chronic tinnitus (ringing of the ears) is a medically untreatable condition that reduces quality of life for millions of individuals worldwide. Most cases are associated with hearing loss that may be detected by the audiogram or by more sensitive measures. Converging evidence from animal models and studies of human tinnitus sufferers indicates that, while cochlear damage is a trigger, most cases of tinnitus are not generated by irritative processes persisting in the cochlea but by changes that take place in central auditory pathways when auditory neurons lose their input from the ear. Forms of neural plasticity underlie these neural changes, which include increased spontaneous activity and neural gain in deafferented central auditory structures, increased synchronous activity in these structures, alterations in the tonotopic organization of auditory cortex, and changes in network behavior in nonauditory brain regions detected by functional imaging of individuals with tinnitus and corroborated by animal investigations. Research on the molecular mechanisms that underlie neural changes in tinnitus is in its infancy and represents a frontier for investigation.