Effects of Kainic Acid-Induced Auditory Nerve Damage on Envelope-Following Responses in the Budgerigar (Melopsittacus undulatus)

Wilson, John L.; Abrams, Kristina S.; Henry, Kenneth S.

doi:10.1007/s10162-020-00776-x

Cited by 12 publications

(9 citation statements)

References 60 publications

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“…EFR amplitude reductions occurred consistently across the three longitudinally-monitored budgerigars (Fig.4A), and was attributed to a histology-verified reduction in auditory-nerve peripheral axons and cell bodies (Fig.4B). The histology confirms that KA introduces cochlear synaptopathy in budgeri-gars, and the additionally performed DPOAE analysis in Wang et al (2023); Wilson et al (2021) furthermore demonstrates the selectivity of KA to AN synapses and cells without damaging the OHCs. As Fig.4A depicts, EFR amplitude reductions occur instantly after KA administration, and recover slightly to an overall reduced amplitude over the following weeks.…”

Section: Resultssupporting

confidence: 60%

“…B Representative cross sections of the budgerigar cochlea from a control ear (left) and from an ear exposed to 1-mM kainic-acid solution (12 weeks post exposure; right). Sections are stained for DAPI and Myosin 7A, and are from the location 50-60% of the distance from the apex to the base (2-kHz cochlear frequency; see Wang et al, 2023). Kainic-acid exposure causes marked reduction of auditory-nerve (AN) peripheral axons and cell bodies in the AN ganglion, without impacting the hair-cell epithelium.…”

Section: Resultsmentioning

confidence: 99%

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Deciphering compromised speech-in-noise intelligibility in older listeners: the role of cochlear synaptopathy

Garrett¹,

Vasilkov

Mauermann³

et al. 2020

Preprint

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Damage to auditory-nerve-ber synapses (i.e. cochlear synaptopathy) degrades the neural coding of sound and is predicted to impair sound perception in noisy listening environments. However, establishing a causal relationship between synaptopathy and speech 15 intelligibility is di cult because we have no direct access to synapse counts in humans. Hence, we rely on the quality of noninvasive auditory-evoked potential (AEP) markers developed in rodent studies of histologically-veri ed synaptopathy. However, there are a number of reasons which render the interpretation of these markers in humans di cult. To bridge this translational gap, we apply a multi-method approach to enable a meaningful interpretation of the relationship 20 between the histopathology of sensorineural hearing loss (SNHL) and speech perception. We rst selected a synaptopathy-sensitive AEP marker and veri ed its sensitivity (i) in an animal model using a Kainic-acid induced synaptopathy, and (ii), via auditory model simulations which connect the histopathology of SNHL to the source generators of AEPs. Secondly, we restricted the frequency content of the speech-material to ensure that both AEP and speech metrics targeted 25 similar cochlear frequency regions and associated auditory coding mechanisms. Following this approach, we studied the relative contribution of AEP markers of synaptopathy and hearing sensitivity to speech recognition thresholds in 44 listeners (24 women) of di erent ages and SNHL pro les. Our analysis shows that synaptopathy plays an important role for speech intelligibility in noise, but that outer-hair-cell integrity predicts performance in the absence of 30 noise. Our results corroborate conclusions from animal studies regarding the prevalence of age-related synaptopathy, and its occurrence before outer-hair-cell loss damage. Signi cance StatementTemporal-bone histology demonstrates that cochlear synaptopathy, i.e. damage to inner-hair-cell 35 auditory-nerve ber synapses, sets in before sensory cell damage and associated hearing threshold elevation. Clinical practice assesses hearing status on the basis of audiometric thresholds, and is hence overlooking a -likely prevalent-aspect of sensorineural hearing damage given that ageing, noise exposure or ototoxic drugs can cause synaptopathy. We present a multi-method approach to study the relationship between synaptopathy and speech intelligibility and address an important 40 1 of 40 unresolved issue in hearing science, namely why speech-intelligibility-in-noise degrades as we age, even when hearing sensitivity remains normal. Our study outcomes have important implications for hearing diagnostics and treatment. AbbreviationsAN(F) -auditory nerve ( ber); 45 BB -broadband; CF -characteristic frequency; CN -cochlear nucleus; DPOAE -distortion product otoacoustic emission; EEG -electroencephalography; 50 EFR -envelope following response; H/M/LSR bers -high/medium/low spontaneous rate bers; HI -hearing-impaired; HP -highpass ltered; IC -inferior colliculus; 55 IHC -inner hair cell; IQR...

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Section: Resultssupporting

confidence: 60%

Section: Resultsmentioning

confidence: 99%

Deciphering compromised speech-in-noise intelligibility in older listeners: the role of cochlear synaptopathy

Garrett¹,

Vasilkov

Mauermann³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…and brainstem processing (Dolphin and Mountain, 1992;Purcell et al, 2004;Zhong et al, 2014;Wilson et al, 2021). Furthermore, kainic-acid-induced EFR reductions match auditory brainstem response (ABR) wave-I amplitude reductions well for modulation frequencies above 80 Hz (Wilson et al, 2021).…”

Section: Introductionmentioning

confidence: 75%

Envelope following responses for hearing diagnosis: Robustness and methodological considerations

Biest¹,

Keshishzadeh²,

Keppler

et al. 2023

The Journal of the Acoustical Society of America

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Recent studies have found that envelope following responses (EFRs) are a marker of age-related and noise- or ototoxic-induced cochlear synaptopathy (CS) in research animals. Whereas the cochlear injury can be well controlled in animal research studies, humans may have an unknown mixture of sensorineural hearing loss [SNHL; e.g., inner- or outer-hair-cell (OHC) damage or CS] that cannot be teased apart in a standard hearing evaluation. Hence, a direct translation of EFR markers of CS to a differential CS diagnosis in humans might be compromised by the influence of SNHL subtypes and differences in recording modalities between research animals and humans. To quantify the robustness of EFR markers for use in human studies, this study investigates the impact of methodological considerations related to electrode montage, stimulus characteristics, and presentation, as well as analysis method on human-recorded EFR markers. The main focus is on rectangularly modulated pure-tone stimuli to evoke the EFR based on a recent auditory modelling study that showed that the EFR was least affected by OHC damage and most sensitive to CS in this stimulus configuration. The outcomes of this study can help guide future clinical implementations of electroencephalography-based SNHL diagnostic tests.

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“…Kainic acid is a kainate receptor agonist and a potent neuroexcitatory amino acid (Ferkany et al 1982). Kainic acid is commonly used to study effects of experimental ablation (Gil-Loyzaga & Pujol 1990; Zheng et al 1996; Wilson et al 2021) and injected in the cochlear apex (Lichtenhan et al 2016a; Lee et al 2019). Kainic acid of 2.16 mM (in artificial perilymph consisting of NaCl of 127.5 mM, KCl of 3.5 mM, NaHCO 3 of 25 mM, CaCl 2 of 1.3 mM, MgCl 2 of 1.2 mM, NaH 2 PO 4 of 0.75 mM, and glucose of 11 mM) was prepared in a 50 µL gas-tight syringe (1710TLL, Hamilton Syringe).…”

Section: Methodsmentioning

confidence: 99%

A Guinea Pig Model Suggests That Objective Assessment of Acoustic Hearing Preservation in Human Ears With Cochlear Implants Is Confounded by Shifts in the Spatial Origin of Acoustically Evoked Potential Measurements Along the Cochlear Length

Lee,

Hartsock,

Salt

et al. 2024

Ear &Amp; Hearing

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Objectives: Our recent empirical findings have shown that the auditory nerve compound action potential (CAP) evoked by a low-level tone burst originates from a narrow cochlear region tuned to the tone burst frequency. At moderate to high sound levels, the origins shift to the most sensitive audiometric regions rather than the extended high-frequency regions of the cochlear base. This means that measurements evoked from extended high-frequency sound stimuli can shift toward the apex with increasing level. Here we translate this study to understand the spatial origin of acoustically evoked responses from ears that receive cochlear implants, an emerging area of research and clinical practice that is not completely understood. An essential step is to first understand the influence of the cochlear implant in otherwise naive ears. Our objective was to understand how function of the high-frequency cochlear base, which can be excited by the intense low-frequency sounds that are frequently used for objective intra- and postoperative monitoring, can be influenced by the presence of the cochlear implant. Design: We acoustically evoked responses and made measurements with an electrode placed near the guinea pig round window. The cochlear implant was not utilized for either electrical stimulation or recording purposes. With the cochlear implant in situ, CAPs were acoustically evoked from 2 to 16 kHz tone bursts of various levels while utilizing the slow perfusion of a kainic acid solution from the cochlear apex to the cochlear aqueduct in the base, which sequentially reduced neural responses from finely spaced cochlear frequency regions. This cochlear perfusion technique reveals the spatial origin of evoked potential measurements and provides insight on what influence the presence of an implant has on acoustical hearing. Results: Threshold measurements at 3 to 11 kHz were elevated by implantation. In an individual ear, thresholds were elevated and lowered as cochlear implant was respectively inserted and removed, indicative of “conductive hearing loss” induced by the implant. The maximum threshold elevation occurred at most sensitive region of the naive guinea pig ear (33.66 dB at 8 kHz), making 11 kHz the most sensitive region to acoustic sounds for guinea pig ears with cochlear implants. Conversely, the acute implantation did not affect the low-frequency, 500 Hz thresholds and suprathreshold function, as shown by the auditory nerve overlapped waveform. As the sound pressure level of the tone bursts increased, mean data show that the spatial origin of CAPs along the cochlear length shifted toward the most sensitive cochlear region of implanted ears, not the extended high-frequency cochlear regions. However, data from individual ears showed that after implantation, measurements from moderate to high sound pressure levels originate in places that are unique to each ear. Conclusions: Alterations to function of the cochlear base from the in situ cochlear implant may influence objective measurements of implanted ears that are frequently made with intense low-frequency sound stimuli. Our results from guinea pigs advance the interpretation of measurements used to understand how and when residual acoustic hearing is lost in human ears receiving a cochlear implant.

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Effects of Kainic Acid-Induced Auditory Nerve Damage on Envelope-Following Responses in the Budgerigar (Melopsittacus undulatus)

Cited by 12 publications

References 60 publications

Deciphering compromised speech-in-noise intelligibility in older listeners: the role of cochlear synaptopathy

Deciphering compromised speech-in-noise intelligibility in older listeners: the role of cochlear synaptopathy

Envelope following responses for hearing diagnosis: Robustness and methodological considerations

A Guinea Pig Model Suggests That Objective Assessment of Acoustic Hearing Preservation in Human Ears With Cochlear Implants Is Confounded by Shifts in the Spatial Origin of Acoustically Evoked Potential Measurements Along the Cochlear Length

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