Maladaptive central plasticity and suprathreshold hearing disorders in humans with sensorineural hearing loss and their relation to biomarkers of cochlear synaptopathy

项目4 -项目总结

Project 4 – Project Summary Hearing disorders are typically studied and treated from the perspective of wanting to make inaudible sounds audible. Yet three of the most common and debilitating adult hearing complaints reflect just the opposite problem: not what persons cannot hear, but what they cannot stop hearing. Older adults or persons with a history of noise exposure are often assaulted by the irrepressible perception of phantom sounds (tinnitus), they experience moderate intensity sounds as loud, distressing, or even painful (hyperacusis), and they struggle to suppress the awareness of background noise sources when listening to a target speaker. Although age, noise exposure, and hearing status are risk factors for these perceptual disorders, the connection is indirect at best, prompting much speculation about the intervening neural processes that may be more closely related. Animal research suggests that the underlying cause of these disorders may be rooted in a dialog gone wrong between cochlear primary afferent neurons and neurons in sound processing centers of the brain. Cochlear neural degeneration (CND) has been shown to trigger a compensatory plasticity process in the central auditory pathway that often over- shoots the mark, rendering central auditory neurons hyperactive, hypersensitive, hyper-synchronized, and internally ‘noisy’. A broad consensus from work published in many animal species and hearing loss paradigms suggests that maladaptive central plasticity that arises as a consequence of CND is proximally linked to the behavioral manifestation of tinnitus, hyperacusis, and selective difficulties hearing in noise. This hypothesis has been difficult to test in human subjects owing to the challenge of measuring risk factors, auditory peripheral status, central plasticity signatures, and detailed behavioral phenotyping of these hearing disorders in the same subjects. Here, by performing central neural, autonomic, and psychophysical measurements in the same subjects that have also undergone extensive auditory peripheral testing in Project 3, we have developed an innovative and exhaustive approach to put this hypothesis to the test in human subjects. Aim 1 of Project 4 will use novel EEG measures to test the hypothesis that more pronounced levels of estimated CND (CNDe) is associated with increased neural gain, poor neural encoding of rapid stimulus temporal features, and poor neural suppression of task-irrelevant noise sources. Aim 2 will utilize novel autonomic measures of sound-evoked changes in pupil dilation, skin conductance, heart rate, and micro facial expressions to test the hypothesis that more pronounced CNDe is associated with abnormally strong autonomic recruitment during effortful listening and in response to emotionally evocative sounds. Aim 3 will combine the neural and autonomic measures above with detailed behavioral phenotyping. Using causal mediation analysis, Aim 3 will determine how CNDe, central gain, temporal encoding, distractor noise source suppression, and affective sound processing specifically relate to a spectrum of suprathreshold hearing disorders, as identified by measurements of multi-talker speech intelligibility, tinnitus psychoacoustics, tinnitus burden, loudness psychoacoustics, and hyperacusis burden.