Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus

Tinnitus, the phantom perception of sound, often occurs as a clinical sequela of auditory traumas. In an effort to develop an objective test and therapeutic approach for tinnitus, the present study was performed in blast-exposed rats and focused on measurements of auditory brainstem responses (ABRs), prepulse inhibition of the acoustic startle response, and presynaptic ribbon densities on cochlear inner hair cells (IHCs). Although the exact mechanism is unknown, the “central gain theory” posits that tinnitus is a perceptual indicator of abnormal increases in the gain (or neural amplification) of the central auditory system to compensate for peripheral loss of sensory input from the cochlea. Our data from vehicle-treated rats supports this rationale; namely, blast-induced cochlear synaptopathy correlated with imbalanced elevations in the ratio of centrally-derived ABR wave V amplitudes to peripherally-derived wave I amplitudes, resulting in behavioral evidence of tinnitus. Logistic regression modeling demonstrated that the ABR wave V/I amplitude ratio served as a reliable metric for objectively identifying tinnitus. Furthermore, histopathological examinations in blast-exposed rats revealed tinnitus-related changes in the expression patterns of key plasticity factors in the central auditory pathway, including chronic loss of Arc/Arg3.1 mobilization. Using a formulation of N-acetylcysteine (NAC) and disodium 2,4-disulfophenyl-N-tert-butylnitrone (HPN-07) as a therapeutic for addressing blast-induced neurodegeneration, we measured a significant treatment effect on preservation or restoration of IHC ribbon synapses, normalization of ABR wave V/I amplitude ratios, and reduced behavioral evidence of tinnitus in blast-exposed rats, all of which accorded with mitigated histopathological evidence of tinnitus-related neuropathy and maladaptive neuroplasticity.

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Cochlear Synaptopathy: A Primary Factor Affecting Speech Recognition Performance in Presbycusis

BioMed Research International ◽

10.1155/2021/6667531 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Zhe Chen ◽

Yanmei Zhang ◽

Junbo Zhang ◽

Rui Zhou ◽

Zhen Zhong ◽

...

Keyword(s):

Speech Recognition ◽

Action Potential ◽

Animal Studies ◽

Signal To Noise Ratio ◽

Recognition Performance ◽

Auditory Pathway ◽

Auditory Brainstem ◽

Auditory Brainstem Responses ◽

Hearing Ability ◽

Summating Potential

The results of recent animal studies have suggested that cochlear synaptopathy may be an important factor involved in presbycusis. Therefore, here, we aimed to examine whether cochlear synaptopathy frequently exists in patients with presbycusis and to describe the effect of cochlear synaptopathy on speech recognition in noise. Based on the medical history and an audiological examination, 94 elderly patients with bilateral, symmetrical, sensorineural hearing loss were diagnosed as presbycusis. An electrocochleogram, auditory brainstem responses, auditory cortical evoked potentials, and speech audiometry were recorded to access the function of the auditory pathway. First, 65 ears with hearing levels of 41-50 dB HL were grouped based on the summating potential/action potential (SP/AP) ratio, and the amplitudes of AP and SP were compared between the two resulting groups. Second, 188 ears were divided into two groups: the normal SP/AP and abnormal SP/AP groups. The speech recognition abilities in the two groups were compared. Finally, the relationship between abnormal electrocochleogram and poor speech recognition (signal-to-noise ratio loss ≥7 dB) was analyzed in 188 ears. The results of the present study showed: (1) a remarkable reduction in the action potential amplitude was observed in patients with abnormal SP/AP ratios; this suggests that cochlear synaptopathy was involved in presbycusis. (2) There was a large proportion of patients with poor speech recognition in the abnormal SP/AP group. Furthermore, a larger number of cases with abnormal SP/AP ratios were confirmed among patients with presbycusis and poor speech recognition. We concluded that cochlear synaptopathy is not uncommon among elderly individuals who have hearing ability deficits, and it may have a more pronounced effect on ears with declining auditory performance in noisy environments.

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Neural Transformation of Dissonant Intervals in the Auditory Brainstem

Music Perception An Interdisciplinary Journal ◽

10.1525/mp.2015.32.5.445 ◽

2015 ◽

Vol 32 (5) ◽

pp. 445-459 ◽

Cited By ~ 4

Author(s):

Kyung Myun Lee ◽

Erika Skoe ◽

Nina Kraus ◽

Richard Ashley

Keyword(s):

Auditory System ◽

Auditory Processing ◽

Response Spectrum ◽

Phase Locking ◽

Auditory Pathway ◽

Auditory Brainstem ◽

Neural Representation ◽

Auditory Brainstem Responses ◽

Distortion Products ◽

Stimulus Waveform

Acoustic periodicity is an important factor for discriminating consonant and dissonant intervals. While previous studies have found that the periodicity of musical intervals is temporally encoded by neural phase locking throughout the auditory system, how the nonlinearities of the auditory pathway influence the encoding of periodicity and how this effect is related to sensory consonance has been underexplored. By measuring human auditory brainstem responses (ABRs) to four diotically presented musical intervals with increasing degrees of dissonance, this study seeks to explicate how the subcortical auditory system transforms the neural representation of acoustic periodicity for consonant versus dissonant intervals. ABRs faithfully reflect neural activity in the brainstem synchronized to the stimulus while also capturing nonlinear aspects of auditory processing. Results show that for the most dissonant interval, which has a less periodic stimulus waveform than the most consonant interval, the aperiodicity of the stimulus is intensified in the subcortical response. The decreased periodicity of dissonant intervals is related to a larger number of nonlinearities (i.e., distortion products) in the response spectrum. Our findings suggest that the auditory system transforms the periodicity of dissonant intervals resulting in consonant and dissonant intervals becoming more distinct in the neural code than if they were to be processed by a linear auditory system.

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Auditory neuropathy in a patient exposed to xylene: case report

The Journal of Laryngology & Otology ◽

10.1017/s0022215108002399 ◽

2008 ◽

Vol 123 (4) ◽

pp. 462-465 ◽

Cited By ~ 4

Author(s):

T H J Draper ◽

D-E Bamiou

Keyword(s):

Case Report ◽

Otoacoustic Emissions ◽

Auditory Pathway ◽

Auditory Brainstem ◽

Auditory Neuropathy ◽

Auditory Brainstem Responses ◽

Test Results ◽

Solvent Exposure ◽

Complex Sounds ◽

Acoustic Reflexes

AbstractObjective:To report the case of an adult patient who developed auditory complaints following xylene exposure, and to review the literature on the effects of solvent exposure on hearing.Case report:The patient presented with a gradual deterioration in his ability to hear in difficult acoustic environments and also to hear complex sounds such as music, over a 40-year period. His symptoms began following exposure to the solvent xylene, and in the absence of any other risk factor. Our audiological investigations revealed normal otoacoustic emissions with absent auditory brainstem responses and absent acoustic reflexes in both ears, consistent with a diagnosis of bilateral auditory neuropathy. Central test results were also abnormal, indicating possible involvement of the central auditory pathway.Conclusions:To our knowledge, this is the first report of retrocochlear hearing loss following xylene exposure. The test results may provide some insight into the effect of xylene as an isolated agent on the human auditory pathway.

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Loss of Cochlear Ribbon Synapse Is a Critical Contributor to Chronic Salicylate Sodium Treatment-Induced Tinnitus without Change Hearing Threshold

Neural Plasticity ◽

10.1155/2020/3949161 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Wei Zhang ◽

Zhe Peng ◽

ShuKui Yu ◽

Qing-Ling Song ◽

Teng-Fei Qu ◽

...

Keyword(s):

Hearing Loss ◽

Acoustic Startle ◽

Acoustic Startle Response ◽

Hearing Threshold ◽

Significant Loss ◽

Acoustic Startle Reflex ◽

Ribbon Synapse ◽

Inner Hair Cell ◽

Adult Rats ◽

Ribbon Synapses

Tinnitus is a common auditory disease worldwide; it is estimated that more than 10% of all individuals experience this hearing disorder during their lifetime. Tinnitus is sometimes accompanied by hearing loss. However, hearing loss is not acquired in some other tinnitus generations. In this study, we injected adult rats with salicylate sodium (SS) (200 mg/kg/day for 10 days) and found no significant hearing threshold changes at 2, 4, 8, 12, 14, 16, 20, or 24 kHz (all p>0.05). Tinnitus was confirmed in the treated rats via Behaviour Testing of Acoustic Startle Response (ASR) and Gap Prepulse Inhibition Test of Acoustic Startle Reflex (GPIAS). A immunostaining study showed that there is significant loss of anti-CtBP2 puncta (a marker of cochlear inner hair cell (HC) ribbon synapses) in treated animals in apical, middle, and basal turns (all p<0.05). The ABR wave I amplitudes were significantly reduced at 4, 8, 12, 14, 16, and 20 kHz (all p<0.05). No significant losses of outer HCs, inner HCs, or HC cilia were observed (all p>0.05). Thus, our study suggests that loss of cochlear inner HC ribbon synapse after SS exposure is a contributor to the development of tinnitus without changing hearing threshold.

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Encoding of a binaural speech stimulus at the brainstem level in middle-aged adults

The Journal of Laryngology & Otology ◽

10.1017/s0022215120002285 ◽

2020 ◽

pp. 1-8

Author(s):

A K Neupane ◽

S K Sinha ◽

K Gururaj

Keyword(s):

Binaural Hearing ◽

Auditory Pathway ◽

Auditory Brainstem ◽

Speech Stimulus ◽

Auditory Brainstem Responses ◽

Middle Aged ◽

Fast Fourier Transform Analysis ◽

Significant Difference ◽

Brainstem Response ◽

Middle Aged Adults

Abstract Objective Binaural hearing is facilitated by neural interactions in the auditory pathway. Ageing results in impairment of localisation and listening in noisy situations without any significant hearing loss. The present study focused on comparing the binaural encoding of a speech stimulus at the subcortical level in middle-aged versus younger adults, based on speech-evoked auditory brainstem responses. Methods Thirty participants (15 young adults and 15 middle-aged adults) with normal hearing sensitivity (less than 15 dB HL) participated in the study. The speech-evoked auditory brainstem response was recorded monaurally and binaurally with a 40-ms /da/ stimulus. Fast Fourier transform analysis was utilised. Results An independent sample t-test revealed a significant difference between the two groups in fundamental frequency (F0) amplitude recorded with binaural stimulation. Conclusion The present study suggested that ageing results in degradation of F0 encoding, which is essential for the perception of speech in noise.

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Effects of auditory pathway anatomy and deafness characteristics? (1): On electrically evoked auditory brainstem responses

Hearing Research ◽

10.1016/j.heares.2006.09.014 ◽

2007 ◽

Vol 223 (1-2) ◽

pp. 48-60 ◽

Cited By ~ 5

Author(s):

Jeanne Guiraud ◽

Stéphane Gallego ◽

Laure Arnold ◽

Patrick Boyle ◽

Eric Truy ◽

...

Keyword(s):

Auditory Pathway ◽

Auditory Brainstem ◽

Auditory Brainstem Responses

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Synaptic Release Potentiation at Aging Auditory Ribbon Synapses

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.756449 ◽

2021 ◽

Vol 13 ◽

Author(s):

Thibault Peineau ◽

Séverin Belleudy ◽

Susanna Pietropaolo ◽

Yohan Bouleau ◽

Didier Dulon

Keyword(s):

Hearing Loss ◽

Acoustic Startle ◽

Auditory Brainstem ◽

Bk Channels ◽

Acoustic Startle Reflex ◽

Inner Hair Cell ◽

Functional Changes ◽

Ribbon Synapses ◽

Age Related ◽

Cadherin 23

Age-related hidden hearing loss is often described as a cochlear synaptopathy that results from a progressive degeneration of the inner hair cell (IHC) ribbon synapses. The functional changes occurring at these synapses during aging are not fully understood. Here, we characterized this aging process in IHCs of C57BL/6J mice, a strain which is known to carry a cadherin-23 mutation and experiences early hearing loss with age. These mice, while displaying a large increase in auditory brainstem thresholds due to 50% loss of IHC synaptic ribbons at middle age (postnatal day 365), paradoxically showed enhanced acoustic startle reflex suggesting a hyperacusis-like response. The auditory defect was associated with a large shrinkage of the IHCs' cell body and a drastic enlargement of their remaining presynaptic ribbons which were facing enlarged postsynaptic AMPAR clusters. Presynaptic Ca2+ microdomains and the capacity of IHCs to sustain high rates of exocytosis were largely increased, while on the contrary the expression of the fast-repolarizing BK channels, known to negatively control transmitter release, was decreased. This age-related synaptic plasticity in IHCs suggested a functional potentiation of synaptic transmission at the surviving synapses, a process that could partially compensate the decrease in synapse number and underlie hyperacusis.

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Variation in interpeak latencies of auditory brainstem responses with age in male adults:An observation

Biomedicine ◽

10.51248/.v41i2.1064 ◽

2021 ◽

Vol 41 (2) ◽

pp. 489-492

Author(s):

Shilpa Khullar ◽

S. Aijaz Abbas Rizvi ◽

Ankur Sachdeva ◽

Archana Sood ◽

Syed Sibte Akbar Abidi

Keyword(s):

Auditory Processing ◽

Hearing Threshold ◽

Auditory Pathway ◽

Auditory Brainstem ◽

Auditory Threshold ◽

Auditory Brainstem Responses ◽

P Value ◽

Conduction Time ◽

Significant Difference ◽

Group 2

Introduction and Aim: Aging of the auditory pathway is a complex phenomenon consisting of changes in the auditory processing along with a significant elevation of the hearing threshold. The aim of our study was to see the variation in interpeak latencies (IPLs) of Auditory Brainstem Responses (ABRs) with advancing age in males. Materials and Methods: It was an observational study conducted on 60 Indian male subjects aged between 20 and 80 years divided into three groups on the basis of age: Group 1: 20-40 years, Group 2: 41-60 years and Group 3: 61-80 years. Auditory threshold and ABRs were recorded and analysed for interpeak latencies (IPLs) – I-III,I-V and III-V in msec.The comparison of data between the groups was done using one – way ANOVA and Tukey Kramer multiple comparison test. The results were considered significantly different between the groups when ‘P value’ was ? 0.05. Results: It was found that there was no significant difference in the auditory threshold and interpeak latencies (IPLs) when comparison was made between the three groups. Conclusion: Hence we conclude thatage does not have any significant influence on neural conduction time of the auditory pathway which is represented by the IPLs in ABRs.

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Neuropatia Auditiva: Avaliação Clínica e Abordagem Diagnóstica

Acta Médica Portuguesa ◽

10.20344/amp.6942 ◽

2016 ◽

Vol 29 (6) ◽

pp. 353 ◽

Cited By ~ 2

Author(s):

Guilherme Machado Carvalho ◽

Beatriz Prista Leão ◽

Priscila Zonzini Ramos ◽

Alexandre Caixeta Guimarães ◽

Arthur Menino Castilho ◽

...

Keyword(s):

Hearing Loss ◽

Case Series ◽

Epidemiological Data ◽

Auditory Pathway ◽

Auditory Brainstem ◽

Auditory Neuropathy ◽

Auditory Brainstem Responses ◽

Profound Deafness ◽

Neuronal Transmission ◽

Patients Experience

Introduction: Auditory neuropathy is a condition in which there is a change in the neuronal transmission of the auditory stimuli. Our objective was to describe the patients’ series within the clinical spectrum of auditory neuropathy. Material and Methods: We designed a transversal, retrospective study, with a description of a consecutive case series. Auditory neuropathy was defined by the presence of acoustic otoemissions plus absent/abnormal auditory brainstem responses with cochlear microphonism. Results: 34 patients with bilateral hearing loss, 23 males and 11 females, were included in the study. Eighty percent of the cases had congenital onset of hearing loss. Acoustic otoemissions were absent in 67% of them. Cochlear microfonism was present in 79% of all cases. Prenatal, perinatal or ambiental factors were present in 35.2% of the cases. Discussion: Medical literature shows great variability in findings related to auditory neuropathy, both in its etiology and epidemiological data. Conclusion: Auditory neuropathy presents a broad spectrum of changes that may result from mild to severe changes in the functioning of the auditory pathway, and in our sample we observed that 80% of Auditory neuropathy have congenital onset of hearing loss and/or with cochlear microphonism identified. 91% of patients experience significant hearing impairment and 53% suffer from severe or profound deafness.

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Development of Tinnitus and Hyperacusis in a Mouse Model of Tobramycin Cochleotoxicity

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.715952 ◽

2021 ◽

Vol 14 ◽

Author(s):

Ryan J. Longenecker ◽

Rende Gu ◽

Jennifer Homan ◽

Jonathan Kil

Keyword(s):

Mouse Model ◽

Recovery Period ◽

Acoustic Startle ◽

Spiral Ganglion ◽

Auditory Brainstem ◽

Acoustic Startle Reflex ◽

Spiral Ganglion Neuron ◽

Brainstem Response ◽

Group 2 ◽

Behavioral Evidence

Aminoglycosides (AG) antibiotics are a common treatment for recurrent infections in cystic fibrosis (CF) patients. AGs are highly ototoxic, resulting in a range of auditory dysfunctions. It was recently shown that the acoustic startle reflex (ASR) can assess behavioral evidence of hyperacusis and tinnitus in an amikacin cochleotoxicity mouse model. The goal of this study was to establish if tobramycin treatment led to similar changes in ASR behavior and to establish whether ebselen can prevent the development of these maladaptive neuroplastic symptoms. CBA/Ca mice were divided into three groups: Group 1 served as a control and did not receive tobramycin or ebselen, Group 2 received tobramycin (200 mg/kg/s.c.) and the vehicle (DMSO/saline/i.p.) daily for 14 continuous days, and Group 3 received the same dose/schedule of tobramycin as Group 2 and ebselen at (20 mg/kg/i.p.). Auditory brainstem response (ABR) and ASR hearing assessments were collected at baseline and 2, 6, 10, 14, and 18 weeks from the start of treatment. ASR tests included input/output (I/O) functions which assess general hearing and hyperacusis, and Gap-induced prepulse inhibition of the acoustic startle (GPIAS) to assess tinnitus. At 18 weeks, histologic analysis showed predominantly normal appearing hair cells and spiral ganglion neuron (SGN) synapses. Following 14 days of tobramycin injections, 16 kHz thresholds increased from baseline and fluctuated over the 18-week recovery period. I/O functions revealed exaggerated startle response magnitudes in 50% of mice over the same period. Gap detection deficits, representing behavioral evidence of tinnitus, were observed in a smaller subset (36%) of animals. Interestingly, increases in ABR wave III/wave I amplitude ratios were observed. These tobramycin data corroborate previous findings that AGs can result in hearing dysfunctions. We show that a 14-day course of tobramycin treatment can cause similar levels of hearing loss and tinnitus, when compared to a 14-day course of amikacin, but less hyperacusis. Evidence suggests that tinnitus and hyperacusis might be common side effects of AG antibiotics.

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