Tinnitus: animal models and findings in humans

Abstract

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.

Fig 1

Psychoacoustic properties of tinnitus. a Sound frequencies judged to resemble tinnitus (Likeness Rating) and the center frequency of band pass maskers giving optimal forward suppression of tinnitus (residual Inhibition, RI Depth) track the region of audiometric threshold shift (from Roberts et al. 2008). A likeness rating of 40 denotes a sound beginning to resemble tinnitus. Sound thresholds (broken lines) are considered normal when ≤ 20 dB HL. WN RI depth after a white noise masker. b, c When audiometric notches are present, Likeness Ratings (b) and RI Depth (c) follow this principle. Two individual subjects are shown in (b) from Noreña et al. (2002) and one subject in (c) from Roberts (2007). During RI in (a) and (c, lower panel), tinnitus elimination corresponds to an RI depth of −5.0

Fig 2

A comparison of the responses to a /ba/–/pa/ continuum (a–c) and early gap (d–f) conditions from the same recording site. Dot displays (left column) and PSTH (middle column) are organized vertically according to VOT or gap duration and horizontally for time since the onset of the leading noise burst. Time windows for evaluation of the PSTHs to the trailing stimulus are selected (between dot lines) according to VOT or gap duration and the latency of peak response for the leading noise burst. Compare in the right panels the average normalized maximum firing rate for the vowel (top) and trailing noise burst after the early gap (bottom) obtained before (filled circles) and after (open circles) the acoustic trauma (±SE). The sigmoid curves provide the best statistical fit to the data. Note that fitted curves for both the /ba/–/pa/ continuum and the early gap condition are shifted toward longer VOT or gap duration. FRmax maximum firing rate. From Tomita et al. (2004)

Fig 3

Summary of main results of resting-state functional connectivity studies in tinnitus. The major networks highlighted are default-mode network (DMN, blue), limbic network involved in stress (green), auditory network (red), the visual network (orange), several attention networks (specifically the dorsal attention network and the executive control of attention, purple). Positive correlations between regions that are stronger in tinnitus patients than controls are shown in solid lines; negative correlations are shown as dashed lines. Connections are labeled with letters representing the studies in which they were reported: a Schmidt et al. (2013). b Burton et al. (2012). c Maudoux et al. (2012). d Kim et al. (2012). PCC posterior cingulate cortex; mpfc medial prefrontal cortex; lifg left inferior frontal gyrus; parahipp parahippocampus; aud cortex auditory cortex; fef frontal eye fields. Modified from Husain and Schmidt (2014)