Tinnitus, Diminished Sound-Level Tolerance, and Elevated Auditory Activity in Humans With Clinically Normal Hearing Sensitivity

Abstract

Gu JW, Halpin CF, Nam E-C, Levine RA, Melcher JR. Tinnitus, diminished sound-level tolerance, and elevated auditory activity in humans with clinically normal hearing sensitivity. J Neurophysiol 104: 3361-3370, 2010. First published September 29, 2010 doi:10.1152/jn.00226.2010. Phantom sensations and sensory hypersensitivity are disordered perceptions that characterize a variety of intractable conditions involving the somatosensory, visual, and auditory modalities. We report physiological correlates of two perceptual abnormalities in the auditory domain: tinnitus, the phantom perception of sound, and hyperacusis, a decreased tolerance of sound based on loudness. Here, subjects with and without tinnitus, all with clinically normal hearing thresholds, underwent 1) behavioral testing to assess sound-level tolerance and 2) functional MRI to measure soundevoked activation of central auditory centers. Despite receiving identical sound stimulation levels, subjects with diminished sound-level tolerance (i.e., hyperacusis) showed elevated activation in the auditory midbrain, thalamus, and primary auditory cortex compared with subjects with normal tolerance. Primary auditory cortex, but not subcortical centers, showed elevated activation specifically related to tinnitus. The results directly link hyperacusis and tinnitus to hyperactivity within the central auditory system. We hypothesize that the tinnitus-related elevations in cortical activation may reflect undue attention drawn to the auditory domain, an interpretation consistent with the lack of tinnitus-related effects subcortically where activation is less potently modulated by attentional state. The data strengthen, at a mechanistic level, analogies drawn previously between tinnitus/ hyperacusis and other, nonauditory disordered perceptions thought to arise from neural hyperactivity such as chronic neuropathic pain and photophobia.

Increased contralateral suppression of otoacoustic emissions indicates a hyperresponsive medial olivocochlear system in humans with tinnitus and hyperacusis

“…If SLT had been ignored, and the two tinnitus groups (high and low SLT) had been compared with the two no-tinnitus groups, little or no difference in contralateral suppression would have been found. An important point is that lowered tolerance of sound was not usually reported spontaneously by the low-SLT subjects of the present study (see also Gu et al 2010Gu et al , 2012. Lower tolerance only became apparent through questionnaire responses and LDL measurement.…”

“…The SLT questionnaire consisted of three items about sound tolerance in everyday life (Gu et al 2010;Tyler et al 2003). Subjects rated their agreement with the following statements on a scale from 0 (completely disagree) to 100 (completely agree): 1) Many everyday sounds are unbearably loud to me; 2) Sounds that others believe are moderately loud are too loud for me; and 3) I hear very soft sounds that others with normal hearing do not hear.…”

“…Extreme intolerance, or very low SLT, corresponds to clinical hyperacusis, where even moderate-level sounds are considered uncomfortable (Baguley 2003;Tyler et al 2003). SLT tends to be reduced in people with tinnitus compared with threshold-matched controls without tinnitus, although the ranges of SLT for those with and without tinnitus are overlapping (Gu et al 2010;Hébert et al 2013). SLT is a potentially important variable here because the MOC system, as a controller of cochlear gain, is positioned to influence loudness and therefore SLT.…”

Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity because of decreased GABAergic inhibition

“…The ability of FA imaging to reveal hyperactive auditory brainstem circuits in vitro is an important advancement in the field of tinnitus. Although hyperactivity may or may not be the cause of tinnitus (29,30), hyperactivity provides a reliable marker of tinnitus that has also been seen in the inferior colliculus and the auditory cortex (13,23,(31)(32)(33). Given that FA imaging allows for measurement of circuit activity levels at different auditory nuclei within the same animal, FA imaging experiments in vitro are expected to provide information about the development of tinnitus.…”

“…Finally, FA imaging has advantages over other imaging techniques that exploit intrinsic signals. PET and MRI studies have shown elevated blood flow and increased sound-evoked blood oxygenation leveldependent (BOLD) responses in central auditory structures of individuals experiencing tinnitus (9,10,23). Although PET and MRI rely on intrinsic changes, they are not suitable for mechanistic studies, unlike FA imaging, which allows us to address mechanistic details of tinnitus induction and expression.…”