Functional Neuroanatomy of Salicylate- and Noise-Induced Tinnitus and Hyperacusis.

Tinnitus and hyperacusis are debilitating conditions often associated with aging or exposure to intense noise or ototoxic drugs. One of the most reliable methods of inducing tinnitus is with high doses of sodium salicylate, the active ingredient in aspirin. High doses of salicylate have been widely used to investigate the functional neuroanatomy of tinnitus and hyperacusis. High doses of salicylate have been used to develop novel behavioral methods to detect the presence of tinnitus and hyperacusis in animal models. Salicylate typically induces a hearing loss of approximately 20 dB which greatly reduces the neural output of the cochlea. As this weak neural signal emerging from the cochlea is sequentially relayed to the cochlear nucleus, inferior colliculus, medial geniculate, and auditory cortex, the neural response to suprathreshold sounds is progressively amplified by a factor of 2-3 by the time the signal reaches the auditory cortex, a phenomenon referred to as enhanced central gain. Sound-evoked hyperactivity also occurred in the amygdala, a region that assigns emotional significance to sensory stimuli. Resting state functional magnetic imaging of the BOLD signal revealed salicylate-induced increases in spontaneous neural activity in the inferior colliculus, medial geniculate body, and auditory cortex as well as in non-auditory areas such as the amygdala, reticular formation, cerebellum, and other sensory areas. Functional connectivity of the BOLD signal revealed increased neural coupling between several auditory areas and non-auditory areas such as the amygdala, cerebellum, reticular formation, hippocampus, and caudate/putamen; these strengthened connections likely contribute to the multifaceted dimensions of tinnitus. Taken together, these results suggest that salicylate-induced tinnitus disrupts a complex neural network involving many auditory centers as well as brain regions involved with emotion, arousal, memory, and motor planning. These extra-auditory centers embellish the basic auditory percepts that results in tinnitus and which may also contribute to hyperacusis.