Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in auditory-limbic-arousal-cerebellar network

TLDR

Hearing loss can trigger tinnitus and hyperacusis, yet the precise brain loci and mechanisms remain unknown. The study aimed to locate the neural substrates of tinnitus and hyperacusis by inducing them with salicylate and applying behavioral, electrophysiological, and fMRI methods. The authors used salicylate to induce the conditions and employed behavioral tests, electrophysiology, and fMRI to map the resulting network. Salicylate suppressed cochlear output but amplified sound‑evoked activity in the amygdala, medial geniculate, and auditory cortex, and resting‑state fMRI revealed hyperactivity and enhanced connectivity within an auditory network that extends to the cerebellum, amygdala, reticular formation, and hippocampus, supporting a model of distress, arousal, and gating in tinnitus and hyperacusis.

Abstract

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.