Hearing loss often triggers an inescapable buzz (tinnitus) and causes everyday sounds to become intolerably loud (hyperacusis), but exactly where and how this occurs in the brain is unknown. To identify the neural substrate for these debilitating disorders, we induced both tinnitus and hyperacusis with an ototoxic drug (salicylate) and used behavioral, electrophysiological, and functional magnetic resonance imaging (fMRI) techniques to identify the tinnitus–hyperacusis network. Salicylate depressed the neural output of the cochlea, but vigorously amplified sound-evoked neural responses in the amygdala, medial geniculate, and auditory cortex. Resting-state fMRI revealed hyperactivity in an auditory network composed of inferior colliculus, medial geniculate, and auditory cortex with side branches to cerebellum, amygdala, and reticular formation. Functional connectivity revealed enhanced coupling within the auditory network and segments of the auditory network and cerebellum, reticular formation, amygdala, and hippocampus. A testable model accounting for distress, arousal, and gating of tinnitus and hyperacusis is proposed.
One in three adults over the age of 65 will experience a significant loss of hearing. This is often worsened by related conditions, such as: tinnitus, an unexplained constant buzzing or ringing sound; and hyperacusis, whereby everyday sounds are perceived as too loud or painful.
Most hearing loss is caused by damage to the sound-sensitive cells within a structure in the inner ear called the cochlea. Some studies have also identified regions of the brain that show abnormal activity in people with tinnitus and hyperacusis. However, the results from different patients have often been inconsistent and sometimes contradictory, and so it remains unclear what exactly causes these conditions.
To overcome this problem, Chen et al. made use of the fact that tinnitus and hyperacusis are common short-term side effects of certain drugs and measured the brain activity in rats before and after they were given one such drug. Before receiving the drug, the rats had first been trained to expect to receive a food pellet from the left side of their cage when they heard a steady buzzing sound. The rats were also trained to expect a food pellet from their right if they heard nothing at all. Shortly after receiving the drug, the rats often failed to respond correctly in the ‘quiet tests’ and behaved like they were already experiencing a constant buzzing sound, as would be expected if they had tinnitus. Further tests confirmed that the drug also triggered behavior in the rats that is typical of people with hyperacusis.
Chen et al. then discovered that the drug treatment reduced the nerve signals that are sent from a rat's cochlea. Moreover, the drug treatment greatly increased the activity in response to sound within parts of the rat's brain; these and other parts of the brain also became overactive in drug-treated rats in the absence of sound. Finally, further experiments revealed that drug-treated rats had stronger connections between these brain regions than in normal rats.
Chen et al. used these results to propose a model to explain the underlying causes of tinnitus and hyperacusis. However, because the drug treatment only induces short-term hearing impairment, further studies are needed to see if this model also applies when these conditions are long-term.