Review: Neural mechanisms of tinnitus and hyperacusis in acute drug-induced ototoxicity

Richard Salvi, Kelly Radziwon, Senthilvelan Manohar, Ben Auerbach, Dalian Ding, Xiaopeng Liu, Condon Lau, Yu Chen Chen, Guang Di Chen

Research output: Contribution to journalArticlepeer-review


Purpose: Tinnitus and hyperacusis are debilitating conditions often associated with age-, noise-, and drug-induced hearing loss. Because of their subjective nature, the neural mechanisms that give rise to tinnitus and hyperacusis are poorly understood. Over the past few decades, considerable progress has been made in deciphering the biological bases for these disorders using animal models. Method: Important advances in understanding the biological bases of tinnitus and hyperacusis have come from studies in which tinnitus and hyperacusis are consistently induced with a high dose of salicylate, the active ingredient in aspirin. Results: Salicylate induced a transient hearing loss characterized by a reduction in otoacoustic emissions, a moderate cochlear threshold shift, and a large reduction in the neural output of the cochlea. As the weak cochlear neural signals were relayed up the auditory pathway, they were progressively amplified so that the suprathreshold neural responses in the auditory cortex were much larger than normal. Excessive central gain (neural amplification), presumably resulting from diminished inhibition, is believed to contribute to hyperacusis and tinnitus. Salicylate also increased corticosterone stress hormone levels. Functional imaging studies indicated that salicylate increased spontaneous activity and enhanced functional connectivity between structures in the central auditory pathway and regions of the brain associated with arousal (reticular formation), emotion (amygdala), memory/spatial navigation (hippocampus), motor planning (cerebellum), and motor control (caudate/ putamen). Conclusion: These results suggest that tinnitus and hyperacusis arise from aberrant neural signaling in a complex neural network that includes both auditory and nonauditory structures.

Original languageEnglish (US)
Pages (from-to)901-915
Number of pages15
JournalAmerican journal of audiology
Issue number3S
StatePublished - Oct 2021
Externally publishedYes

ASJC Scopus subject areas

  • Speech and Hearing


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