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      The association between subcortical and cortical fMRI and lifetime noise exposure in listeners with normal hearing thresholds

      research-article
      a , b , c , , a , ∗∗ , d , d , d , e , d , e , f , b , c , g
      Neuroimage
      Academic Press
      Noise induced hearing loss, Functional magnetic resonance imaging, Auditory pathways, Auditory brainstem response, ABR, auditory brainstem response, CN, cochlear nucleus, CSF, cerebrospinal fluid, EEG, electroencephalography, EPI, echo planar imaging, fMRI, functional magnetic resonance imaging, GE, gradient echo, HL, hearing level, IC, inferior colliculus, MGB, medial geniculate body, MNI, Montreal Neurological Institute, MPRAGE, magnetization prepared rapid acquisition gradient echo, MRI, magnetic resonance imaging, SENSE, sensitivity encoding, SPL, sound pressure level, TE, echo time, TR, repetition time, TSE, turbo spin echo

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          Abstract

          In animal models, exposure to high noise levels can cause permanent damage to hair-cell synapses (cochlear synaptopathy) for high-threshold auditory nerve fibers without affecting sensitivity to quiet sounds. This has been confirmed in several mammalian species, but the hypothesis that lifetime noise exposure affects auditory function in humans with normal audiometric thresholds remains unconfirmed and current evidence from human electrophysiology is contradictory. Here we report the auditory brainstem response (ABR), and both transient (stimulus onset and offset) and sustained functional magnetic resonance imaging (fMRI) responses throughout the human central auditory pathway across lifetime noise exposure. Healthy young individuals aged 25–40 years were recruited into high (n = 32) and low (n = 30) lifetime noise exposure groups, stratified for age, and balanced for audiometric threshold up to 16 kHz fMRI demonstrated robust broadband noise-related activity throughout the auditory pathway (cochlear nucleus, superior olivary complex, nucleus of the lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). fMRI responses in the auditory pathway to broadband noise onset were significantly enhanced in the high noise exposure group relative to the low exposure group, differences in sustained fMRI responses did not reach significance, and no significant group differences were found in the click-evoked ABR. Exploratory analyses found no significant relationships between the neural responses and self-reported tinnitus or reduced sound-level tolerance (symptoms associated with synaptopathy). In summary, although a small effect, these fMRI results suggest that lifetime noise exposure may be associated with central hyperactivity in young adults with normal hearing thresholds.

          Highlights

          • Neural correlates of lifetime noise exposure using fMRI.

          • Auditory brainstem response (ABR) measured in the same listeners.

          • Tinnitus and reduced sound-level tolerance measured in the same listeners.

          • Enhanced fMRI response to sound onset is associated with high noise exposure.

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          Most cited references53

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          Tinnitus with a normal audiogram: physiological evidence for hidden hearing loss and computational model.

          Ever since Pliny the Elder coined the term tinnitus, the perception of sound in the absence of an external sound source has remained enigmatic. Traditional theories assume that tinnitus is triggered by cochlear damage, but many tinnitus patients present with a normal audiogram, i.e., with no direct signs of cochlear damage. Here, we report that in human subjects with tinnitus and a normal audiogram, auditory brainstem responses show a significantly reduced amplitude of the wave I potential (generated by primary auditory nerve fibers) but normal amplitudes of the more centrally generated wave V. This provides direct physiological evidence of "hidden hearing loss" that manifests as reduced neural output from the cochlea, and consequent renormalization of neuronal response magnitude within the brainstem. Employing an established computational model, we demonstrate how tinnitus could arise from a homeostatic response of neurons in the central auditory system to reduced auditory nerve input in the absence of elevated hearing thresholds.
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            Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates.

            Acoustic overexposure can cause a permanent loss of auditory nerve fibers without destroying cochlear sensory cells, despite complete recovery of cochlear thresholds (Kujawa and Liberman 2009), as measured by gross neural potentials such as the auditory brainstem response (ABR). To address this nominal paradox, we recorded responses from single auditory nerve fibers in guinea pigs exposed to this type of neuropathic noise (4- to 8-kHz octave band at 106 dB SPL for 2 h). Two weeks postexposure, ABR thresholds had recovered to normal, while suprathreshold ABR amplitudes were reduced. Both thresholds and amplitudes of distortion-product otoacoustic emissions fully recovered, suggesting recovery of hair cell function. Loss of up to 30% of auditory-nerve synapses on inner hair cells was confirmed by confocal analysis of the cochlear sensory epithelium immunostained for pre- and postsynaptic markers. In single fiber recordings, at 2 wk postexposure, frequency tuning, dynamic range, postonset adaptation, first-spike latency and its variance, and other basic properties of auditory nerve response were all completely normal in the remaining fibers. The only physiological abnormality was a change in population statistics suggesting a selective loss of fibers with low- and medium-spontaneous rates. Selective loss of these high-threshold fibers would explain how ABR thresholds can recover despite such significant noise-induced neuropathy. A selective loss of high-threshold fibers may contribute to the problems of hearing in noisy environments that characterize the aging auditory system.
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              Toward a Differential Diagnosis of Hidden Hearing Loss in Humans

              Recent work suggests that hair cells are not the most vulnerable elements in the inner ear; rather, it is the synapses between hair cells and cochlear nerve terminals that degenerate first in the aging or noise-exposed ear. This primary neural degeneration does not affect hearing thresholds, but likely contributes to problems understanding speech in difficult listening environments, and may be important in the generation of tinnitus and/or hyperacusis. To look for signs of cochlear synaptopathy in humans, we recruited college students and divided them into low-risk and high-risk groups based on self-report of noise exposure and use of hearing protection. Cochlear function was assessed by otoacoustic emissions and click-evoked electrocochleography; hearing was assessed by behavioral audiometry and word recognition with or without noise or time compression and reverberation. Both groups had normal thresholds at standard audiometric frequencies, however, the high-risk group showed significant threshold elevation at high frequencies (10–16 kHz), consistent with early stages of noise damage. Electrocochleography showed a significant difference in the ratio between the waveform peaks generated by hair cells (Summating Potential; SP) vs. cochlear neurons (Action Potential; AP), i.e. the SP/AP ratio, consistent with selective neural loss. The high-risk group also showed significantly poorer performance on word recognition in noise or with time compression and reverberation, and reported heightened reactions to sound consistent with hyperacusis. These results suggest that the SP/AP ratio may be useful in the diagnosis of “hidden hearing loss” and that, as suggested by animal models, the noise-induced loss of cochlear nerve synapses leads to deficits in hearing abilities in difficult listening situations, despite the presence of normal thresholds at standard audiometric frequencies.
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                Author and article information

                Contributors
                Journal
                Neuroimage
                Neuroimage
                Neuroimage
                Academic Press
                1053-8119
                1095-9572
                01 January 2020
                01 January 2020
                : 204
                : 116239
                Affiliations
                [a ]Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, NG7 2RD, UK
                [b ]National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham, NG1 5DU, UK
                [c ]Hearing Sciences, Division of Clinical Neuroscience, School of Medicine, University of Nottingham, NG7 2UH, UK
                [d ]Manchester Centre for Audiology and Deafness (ManCAD), University of Manchester, Manchester Academic Health Science Centre, M13 9PL, UK
                [e ]National Institute for Health Research (NIHR) Manchester Biomedical Research Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK
                [f ]Department of Psychology, Lancaster University, LA1 4YF, UK
                [g ]University of Nottingham Malaysia, Jalan Broga, 43500, Semeniyh, Selangor Darul Ehsan, Malaysia
                Author notes
                []Corresponding author. National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham, NG1 5DU, UK. Rebecca.dewey@ 123456nottingham.ac.uk
                [∗∗ ]Corresponding author. Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, NG7 2RD, UK. susan.francis@ 123456nottingham.ac.uk
                Article
                S1053-8119(19)30830-4 116239
                10.1016/j.neuroimage.2019.116239
                6905154
                31586673
                dfb36d47-6356-45df-bc82-d519249b6ad4
                © 2019 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 21 May 2019
                : 7 September 2019
                : 30 September 2019
                Categories
                Article

                Neurosciences
                noise induced hearing loss,functional magnetic resonance imaging,auditory pathways,auditory brainstem response,abr, auditory brainstem response,cn, cochlear nucleus,csf, cerebrospinal fluid,eeg, electroencephalography,epi, echo planar imaging,fmri, functional magnetic resonance imaging,ge, gradient echo,hl, hearing level,ic, inferior colliculus,mgb, medial geniculate body,mni, montreal neurological institute,mprage, magnetization prepared rapid acquisition gradient echo,mri, magnetic resonance imaging,sense, sensitivity encoding,spl, sound pressure level,te, echo time,tr, repetition time,tse, turbo spin echo

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