Frequency-specific Auditory Brainstem Response Research Articles

Auditory Electrophysiological Thresholds With Different Chirps and Their Correlation With Behavioral Thresholds in Hearing-Impaired Children.

Research focusing on changes in the clinical practice of audiological diagnosis has become increasingly necessary, particularly in pediatric audiology. The pursuit of accurate and reliable examinations has intensified given the importance of early detection and intervention in cases of childhood hearing loss. Thus, this study aims to investigate the correlation between electrophysiological auditory thresholds, as obtained through frequency-specific auditory brainstem responses with two distinct chirp stimuli (narrow-band CE-Chirp Level Specific and narrow-band iChirp), in children with hearing impairments. In addition, this research set out to correlate these thresholds with behavioral responses while simultaneously comparing the examination durations relative to the type of stimuli and the degree of hearing loss. A cohort of 20 children (aged 6 months to 12 years) with varying degrees of hearing impairment (ranging from mild to profound) were recruited. The participants underwent bilateral measurement of their electrophysiological thresholds via auditory brainstem responses across different frequencies (500, 1000, 2000, and 4000 Hz), and the timeframe for determining these thresholds was carefully recorded. Subsequently, behavioral thresholds were ascertained using pure-tone audiometry or visual reinforcement audiometry based on the child's age. The data collected was subsequently analyzed using Pearson and Spearman correlation coefficients. To compare examination times, the Student t test and the Kruskal-Wallis test were used. There was a pronounced correlation between the thresholds obtained through both narrow-band chirp stimuli. Moreover, a substantial correlation was found between electrophysiological and behavioral thresholds at 1000, 2000, and 4000 Hz, especially when compared with pure-tone audiometry. The mean differences between the electrophysiological and behavioral thresholds were below 6 dB nHL, and the exam duration was relatively consistent across both devices, averaging 47.63 (±19.41) min for the narrow-band CE-Chirp Level Specific and 52.42 (±26) min for the narrow-band iChirp. Notably, variations in exam duration did not relate to varying degrees of hearing loss when using the narrow-band CE-Chirp Level Specific. Nevertheless, the narrow-band iChirp indicated significantly shorter durations in instances of profound degree measurements, demonstrating a statistically significant difference. The narrow-band CE-Chirp Level Specific and narrow-band iChirp stimuli provided similar estimates of electrophysiological auditory thresholds in children with hearing impairments, giving accurate estimations of behavioral thresholds. The time it took to complete the assessment is comparable between both stimuli. For the narrow-band iChirp, the degree of hearing loss was shown to impact the testing time, and children with profound hearing loss underwent faster exams. Ultimately, this study exhibits significant clinical implications as it reveals that the narrow-band CE-Chirp Level Specific and narrow-band iChirp stimuli could be remarkably promising for clinically exploring electrophysiological thresholds in children with hearing impairments.

Application Progress of Objective Audiological Detection Techniques in Forensic Clinical Medicine.

The qualitative, quantitative, and localization analysis of hearing loss is one of the important contents of forensic clinical research and identification. Pure-tone audiometry is the "gold standard" for hearing loss assessment, but it is affected by the subjective cooperation of the assessed person. Due to the complexity of the auditory pathway and the diversity of hearing loss, the assessment of hearing loss requires the combination of various subjective and objective audiometric techniques, along with comprehensive evaluation based on the case situation, clinical symptoms, and other examinations to ensure the scientificity, accuracy and reliability of forensic hearing impairment assessment. Objective audiometry includes acoustic impedance, otoacoustic emission, and various auditory evoked potentials. The frequency-specific auditory brainstem response (ABR), 40 Hz auditory event related potential, and auditory steady-state response are commonly used for objective hearing threshold assessment. The combined application of acoustic impedance, otoacoustic emission and ABR can be used to locate hearing loss and determine whether it is located in the middle ear, cochlea, or posterior cochlea. This article reviews the application value of objective audiometry techniques in hearing threshold assessment and hearing loss localization, aiming to provide reference for forensic identification of hearing loss.

Optimal f0–phase parameters for auditory brainstem responses to multiband peaky speech

Multiband peaky speech is a new method that uses narrated stories to evoke frequency-specific auditory brainstem responses (ABRs). However, testing times are not clinically feasible; thus, new efforts focus on maximizing response amplitude to facilitate faster testing. Recent work suggests that narrator f0, as well as chirp rather than zero phases, evoke larger ABRs. This study aimed to identify the optimal f0–phase combination for evoking large ABRs with multiband peaky speech. Using 11 stories with original f0s ranging from 114–230 Hz, the mean f0 over 15 minutes was shifted to f0s from 70–220 Hz in 10 Hz steps and then dichotic multiband peaky speech created using zero- and chirp-phases. A validated computational model of the auditory periphery was used to simulate ABRs using a flat 0 dB HL hearing configuration. Based on the simulated wave V amplitudes across all conditions, the optimal parameters for simulated ABRs to multiband peaky speech include stories with original f0s <170 Hz that have been shifted to a 100–110 Hz mean f0 and modified with a chirp-phase profile. Next we plan to confirm these parameters with measured ABR responses from adults with normal hearing. [Work funded by Hearing Health Foundation ERG.]

Auditory Brainstem response electrophysiological thresholds with narrow band chirps stimuli in hearing infants.

to describe reference values for the electrophysiological thresholds obtained in the frequency-specific Auditory Brainstem Response (fsABR) with the NB CE-Chirp® LS and NB iChirp stimuli in hearing infants and to compare the variables: Minimum Levels of Response (MLR), latency, amplitude and examination time. the sample consisted of 74 full-term infants, with a mean age of 23.11 days, 29 females and 45 males. The participants underwent fsABR at the frequencies of 500Hz, 1000Hz, 2000Hz and 4000Hz, to measure the MLR with the NB CE-Chirp® LS stimulus in the Eclipse equipment, and with the NB iChirp stimulus in the SmartEP, all in natural sleep and performed in the same session. The waveforms were evaluated by judges and later, for the comparison of thresholds and examination time, analyzed with the Wilcoxon test. To compare latency and amplitude, the Student's T Test and ANOVA were used for the same variables, but with the same stimulus. The Kruskal-Wallis test was used to compare the examination time at the different frequencies. The MLR and latency at 500Hz and 1000Hz showed a statistically significant difference between the stimuli, with lower thresholds and higher latencies for the NB iChirp. Higher amplitudes were obtained with the NB iChirp stimulus. The average examination time for the threshold investigation in the four frequencies was 40min for each ear. it was possible to present reference values for the MLR and latencies for the NB CE-Chirp® LS and NB iChirp stimuli for hearing infants. In addition, with the NB iChirp, the latency of the responses was influenced by the frequency, but it was the stimulus that provided greater amplitudes. With the NB CE-Chirp® LS, the frequency did not influence latency, except at 500Hz, and the stimulus provided recordings that facilitated the visualization of wave V. There was no difference in the examination time between the stimuli, nor between the test frequencies.

Pegylated Insulin-Like Growth Factor 1 attenuates Hair Cell Loss and promotes Presynaptic Maintenance of Medial Olivocochlear Cholinergic Fibers in the Cochlea of the Progressive Motor Neuropathy Mouse.

The progressive motor neuropathy (PMN) mouse is a model of an inherited motor neuropathy disease with progressive neurodegeneration. Axon degeneration associates with homozygous mutations of the TBCE gene encoding the tubulin chaperone E protein. TBCE is responsible for the correct dimerization of alpha and beta-tubulin. Strikingly, the PMN mouse also develops a progressive hearing loss after normal hearing onset, characterized by degeneration of the auditory nerve and outer hair cell (OHC) loss. However, the development of this neuronal and cochlear pathology is not fully understood yet. Previous studies with pegylated insulin-like growth factor 1 (peg-IGF-1) treatment in this mouse model have been shown to expand lifespan, weight, muscle strength, and motor coordination. Accordingly, peg-IGF-1 was evaluated for an otoprotective effect. We investigated the effect of peg-IGF-1 on the auditory system by treatment starting at postnatal day 15 (p15). Histological analysis revealed positive effects on OHC synapses of medial olivocochlear (MOC) neuronal fibers and a short-term attenuation of OHC loss. Peg-IGF-1 was able to conditionally restore the disorganization of OHC synapses and maintain the provision of cholinergic acetyltransferase in presynapses. To assess auditory function, frequency-specific auditory brainstem responses and distortion product otoacoustic emissions were recorded in animals on p21 and p28. However, despite the positive effect on MOC fibers and OHC, no restoration of hearing could be achieved. The present work demonstrates that the synaptic pathology of efferent MOC fibers in PMN mice represents a particular form of “efferent auditory neuropathy.” Peg-IGF-1 showed an otoprotective effect by preventing the degeneration of OHCs and efferent synapses. However, enhanced efforts are needed to optimize the treatment to obtain detectable improvements in hearing performances.

Cytomegalovirus Seropositivity as a Potential Risk Factor for Increased Noise Trauma Susceptibility.

Context:Cytomegalovirus (CMV) represents the leading congenital viral infection in humans. Although congenital CMV due to vertically transmitted infections is the main cause of CMV-related diseases, adult CMV infections might still be of clinical significance. It is still discussed how far CMV seropositivity, due to horizontal infection in immunocompetent adults, is able to induce significant dysfunction. The present study investigates in how far CMV seropositivity is an additional risk factor for an increasing susceptibility to sensorineural hearing loss induced by acoustic injury during adulthood in a guinea pig CMV (GPCMV) model of noise-induced hearing loss (NIHL).Methods:Two groups (GPCMV seropositive vs. seronegative) of normal hearing adult guinea pigs were exposed to a broadband noise (5–20 kHz) for 2 hours at 115 dB sound pressure level. Frequency-specific auditory brainstem response recordings for determination of auditory threshold shift were carried out and the number of missing outer hair cells was counted 2 weeks after the noise exposure.Results:The data show a slightly increased shift in auditory thresholds in seropositive animals compared to the seronegative control group in response to noise trauma. However, the observed difference was significant at least at high frequencies. The differences in threshold shift are not correlated with outer hair cell loss between the experimental groups.Conclusion:The results point to potential additional pathologies in a guinea pig NIHL model in correlation to GPCMV seropositivity, which should be taken into account when assessing risks of latent/reactivated CMV infection. Due to the relatively slight effect in the present data, the aim of future studies should be a more detailed consideration (e.g., larger sample size) and to localize possible target structures as well as the significance of the infection route.

Inhalation of Molecular Hydrogen, a Rescue Treatment for Noise-Induced Hearing Loss.

Noise exposure is the most important external factor causing acquired hearing loss in humans, and it is strongly associated with the production of reactive oxygen species (ROS) in the cochlea. Several studies reported that the administration of various compounds with antioxidant effects can treat oxidative stress-induced hearing loss. However, traditional systemic drug administration to the human inner ear is problematic and has not been successful in a clinical setting. Thus, there is an urgent need to develop rescue treatment for patients with acute acoustic injuries. Hydrogen gas has antioxidant effects, rapid distribution, and distributes systemically after inhalation.The purpose of this study was to determine the protective efficacy of a single dose of molecular hydrogen (H2) on cochlear structures. Guinea pigs were divided into six groups and sacrificed immediately after or at 1 or 2 weeks. The animals were exposed to broadband noise for 2 h directly followed by 1-h inhalation of 2% H2 or room air. Electrophysiological hearing thresholds using frequency-specific auditory brainstem response (ABR) were measured prior to noise exposure and before sacrifice. ABR thresholds were significantly lower in H2-treated animals at 2 weeks after exposure, with significant preservation of outer hair cells in the entire cochlea. Quantification of synaptophysin immunoreactivity revealed that H2 inhalation protected the cochlear inner hair cell synaptic structures containing synaptophysin. The inflammatory response was greater in the stria vascularis, showing increased Iba1 due to H2 inhalation.Repeated administration of H2 inhalation may further improve the therapeutic effect. This animal model does not reproduce conditions in humans, highlighting the need for additional real-life studies in humans.

Middle Ear Administration of a Particulate Chitosan Gel in an in vivo Model of Cisplatin Ototoxicity.

BackgroundMiddle ear (intratympanic, IT) administration is a promising therapeutic method as it offers the possibility of achieving high inner ear drug concentrations with low systemic levels, thus minimizing the risk of systemic side effects and drug-drug interactions. Premature elimination through the Eustachian tube may be reduced by stabilizing drug solutions with a hydrogel, but this raises the secondary issue of conductive hearing loss.AimThis study aimed to investigate the properties of a chitosan-based particulate hydrogel formulation when used as a drug carrier for IT administration in an in vivo model of ototoxicity.Materials and MethodsTwo particulate chitosan-based IT delivery systems, Thio-25 and Thio-40, were investigated in albino guinea pigs (n = 94). Both contained the hearing protecting drug candidate sodium thiosulfate with different concentrations of chitosan gel particles (25% vs. 40%). The safety of the two systems was explored in vivo. The most promising system was then tested in guinea pigs subjected to a single intravenous injection with the anticancer drug cisplatin (8 mg/kg b.w.), which has ototoxic side effects. Hearing status was evaluated with acoustically evoked frequency-specific auditory brainstem response (ABR) and hair cell counting. Finally, in vivo magnetic resonance imaging was used to study the distribution and elimination of the chitosan-based system from the middle ear cavity in comparison to a hyaluronan-based system.ResultsBoth chitosan-based IT delivery systems caused ABR threshold elevations (p < 0.05) that remained after 10 days (p < 0.05) without evidence of hair cell loss, although the elevation induced by Thio-25 was significantly lower than for Thio-40 (p < 0.05). Thio-25 significantly reduced cisplatin-induced ABR threshold elevations (p < 0.05) and outer hair cell loss (p < 0.05). IT injection of the chitosan- and hyaluronan-based systems filled up most of the middle ear space. There were no significant differences between the systems in terms of distribution and elimination.ConclusionParticulate chitosan is a promising drug carrier for IT administration. Future studies should assess whether the physical properties of this technique allow for a smaller injection volume that would reduce conductive hearing loss.

Improving acquisition time of the frequency-specific auditory brainstem response through simultaneous independently random toneburst sequences

The frequency-specific auditory brainstem response (ABR) is an objective electroencephalographic (EEG) method for estimating auditory thresholds when behavioral thresholds are not attainable, primarily in infants and toddlers. It is recorded by repeatedly presenting brief, band-limited tonebursts and averaging the scalp potential response. In a typical ABR evaluation, measurements are made at multiple intensities, at multiple frequencies, and in both ears, leading to a large combinatorial space and long test times. Here, we present a method of recording the responses at five frequencies in both ears simultaneously, along with preliminary data demonstrating its effectiveness. We created ten toneburst trains—five octave frequencies (500–8000 Hz) by two ears—for simultaneous presentation. Importantly, the toneburst timing for each train was dictated by an independent random process, rather than being periodic. Independent sequences allow separate computation of the ABR to each of the toneburst trains as the cross-correlation of its timing sequence and the EEG recording. Early results suggest substantial improvements in recording time, particularly at lower stimulus intensities. It also appears that cochlear spread of excitation—a problem at high intensities—is mitigated by our method. This improvement in place specificity is predicted by modeling of auditory nerve activity.

Frequency-specific auditory brainstem response testing with age-appropriate sedation

ObjectiveAuditory brainstem response (ABR) testing is the gold-standard procedure for hearing evaluation in pediatric patients who cannot complete a behavioral hearing test. The amount of audiological information obtained depends on the quality of the patient's sleep during the test. In this retrospective database review, we aimed to assess the amount and the characteristics of the audiological information obtained in ABR testing in pediatric patients with age-appropriate sedation. MethodsA retrospective chart review was conducted on 501 consecutive ABR sedation sessions performed between January 2014 and June 2016 at the Tel Aviv Medical Center. Oral triclofos was used for the sedation of younger patients (3–24 months) and intravenous propofol for older patients (>24 months). The dataset included 370 triclofos sessions (in 337 patients) and 131 propofol sessions (in 126 patients). ResultsNone of the children developed complications, and all were discharged on the same day of the evaluation. Among the hearing-impaired children, a mean of 10 (1.8 SD) ABR threshold measurements was obtained from propofol-sedated patients and 9.4 (2.8 SD) measurements from those sedated with triclofos (P = 0.039). The major characteristics of the hearing loss, including its degree, type, and configuration, were obtained from all propofol-sedated patients and from 95% of those sedated with triclofos. ConclusionsA comprehensive evaluation of hearing status can be obtained in ABR testing with age-appropriate sedation. An average number of ∼10 threshold measurements were obtained during ABR testing with age-appropriate sedation, thus allowing for the evaluation of the degree, type and configuration of the hearing loss.

Air and Bone Conduction Frequency-specific Auditory Brainstem Response in Children with Agenesis of the External Auditory Canal.

Introduction The tone-evoked auditory brainstem responses (tone-ABR) enable the differential diagnosis in the evaluation of children until 12 months of age, including those with external and/or middle ear malformations. The use of auditory stimuli with frequency specificity by air and bone conduction allows characterization of hearing profile. Objective The objective of our study was to compare the results obtained in tone-ABR by air and bone conduction in children until 12 months, with agenesis of the external auditory canal. Method The study was cross-sectional, observational, individual, and contemporary. We conducted the research with tone-ABR by air and bone conduction in the frequencies of 500 Hz and 2000 Hz in 32 children, 23 boys, from one to 12 months old, with agenesis of the external auditory canal. Results The tone-ABR thresholds were significantly elevated for air conduction in the frequencies of 500 Hz and 2000 Hz, while the thresholds of bone conduction had normal values in both ears. We found no statistically significant difference between genders and ears for most of the comparisons. Conclusion The thresholds obtained by bone conduction did not alter the thresholds in children with conductive hearing loss. However, the conductive hearing loss alter all thresholds by air conduction. The tone-ABR by bone conduction is an important tool for assessing cochlear integrity in children with agenesis of the external auditory canal under 12 months.

Potencial evocado auditivo de tronco encefálico por frequência específica por via aérea e via óssea em neonatos ouvintes normais

Objetivo determinar os níveis mínimos de resposta (NMR) e a latência da onda V do Potencial Evocado Auditivo de Tronco encefálico por Frequência específica (PEATE-FE) em neonatos ouvintes normais nas frequências de 0.5, 1, 2 e 4 kHz por via aérea e via óssea e determinar valores normativos. Métodos foram avaliados neonatos com audição normal, sendo realizado o PEATE-FE nas frequências de 0.5, 1, 2 e 4 kHz, tanto por via aérea (VA) quanto por via óssea (VO). Para cada frequência, foram avaliadas 12 orelhas em um total de 18 neonatos. A análise dos resultados avaliou o tempo de latência e a presença da onda V até a intensidade de 20 dBnNA para quatro intensidades e para os dois tipos de condução (aérea e óssea). Resultados observou-se aumento da latência da onda V com a diminuição da intensidade e maiores latências nas frequências mais baixas, tanto na VA quanto na VO. Porém, em fortes intensidades, em ambas condições, não houve diferença entre as latências de 0.5 e 1 kHz, contrariando os achados da literatura. Para VA, na frequência de 500 Hz, houve presença da onda V até 30 dBnNA em todas as orelhas, e em 1000 Hz, 11 orelhas (91,66 %) apresentaram resposta em 20 dBnNA; nas demais frequências, 100% das orelhas avaliadas apresentaram resposta em 20 dBnNA. Na VO, a presença da onda V em 20 dBnNA foi observada em todas as frequências estudadas. Conclusão os valores descritos podem ser considerados normativos e utilizados na clinica como padrão de normalidade, auxiliando no diagnóstico diferencial da perda auditiva ao nascimento.

Correlação dos achados do PEATE-FE e da avaliação comportamental em crianças com deficiência auditiva

OBJETIVO: analisar e correlacionar os achados dos Potenciais Evocados Auditivos de Tronco Encefáico por Frequência Específica e da avaliação comportamental, por Via aérea e Via óssea, em crianças com perda auditiva sensorioneural ou mista. MÉTODO: a casuística foi composta por dez crianças com até três anos de idade, diagnosticadas com perda auditiva sensorioneural. Foram realizados os PEATE-FE nas frequências de 0.5, 1, 2 e 4 kHz e a audiometria comportamental nas mesmas frequências, tanto por via aérea como por via óssea. Os resultados dos dois procedimentos foram correlacionados afim de verificar se o PEATE-FE é capaz de predizer o status auditivo de crianças com deficiência auditiva. RESULTADOS: os resultados mostraram forte correlação entre os dois procedimento nas quatro frequências estudadas por via aérea; já na via óssea, foi encontrada forte correlação nas frequências de 0.5, 1 e 2 kHz e moderada em 4 kHz. CONCLUSÃO: os PEATE-FE estimaram a audição com forte precisão quando comparados à audiometria comportamental. Desta forma, a aplicação dos PEATE-FE possibilita a estimativa da audição até que possam ser determinados, com segurança, os limiares comportamentais na população estudada.

Auditory Brainstem Responses to Level-Specific Chirps in Normal-Hearing Adults

Upward chirps are often designed to compensate for the cochlear traveling wave delay which is regarded as independent of stimulation level. A chirp based on a traveling wave model is therefore referred to as a level-independent chirp. Another compensation strategy, for instance based on frequency-specific auditory brainstem response (ABR) latencies, results in a chirp that changes with stimulation level and is therefore referred to as a level-dependent chirp. One such strategy, the direct approach, results in a chirp family that is called the level-specific chirp. The level dependence is in agreement with the findings that the chirp, which generates the largest ABR in normal-hearing adults, has a duration (sweeping rate) that changes with stimulus level. A direct comparison of ABRs to a fixed chirp and to a level-specific chirp has not been performed at higher levels of stimulation where the differences are thought to have the greatest effect on the ABR characteristics from normal-hearing adults. To make a direct comparison of the ABRs to two different chirp stimuli-a level-specific chirp (LS-Chirp) and a level-independent chirp (CE-Chirp)-and to evaluate the hypothesis that at higher levels of stimulation the LS-Chirp generates significantly higher response amplitudes, and produces higher resolution of the different peaks in the ABR than the CE-Chirp. ABRs are recorded in 10 normal-hearing adults (20 ears) in response to three stimuli at four presentation levels using ER-3A insert earphones. The three stimuli are (1) a level-specific chirp (LS-Chirp), (2) a level-independent chirp (CE-Chirp), and (3) a standard 100-μs click as a reference. The recorded ABRs are evaluated by the peak to trough amplitude (wave V), the peak latency (wave V), the frequency of appearance of wave I, III, and V, and the Grand Average waveforms. Amplitude and latency differences are evaluated statistically by the Wilcoxon matched-pair signed rank test. At higher levels (80 dB nHL), the amplitude and waveform resolution of the ABR to the LS-Chirp are significantly higher than to the CE-Chirp. At lower levels (20, 40, and 60 dB nHL), no significant differences are found between the amplitudes of the ABR to the two stimuli, but at 60 dB nHL the waveform resolution is better for the LS-Chirp than for the CE-Chirp. For all levels, the amplitude of the ABRs to the two chirps are significantly larger than to the Click, except at 80 dB nHL where the ABR to the CE-Chirp gets distorted and low in amplitude. The differences between the ABR latencies to the three stimuli are large at higher levels, but small at lower levels. At higher levels, the LS-Chirp and the Click generate similar resolutions of the main ABR peaks, but the ABRs to the LS-Chirp are significantly larger than to the Click. The study confirms the experimental hypothesis that at higher levels of stimulation the LS-Chirp generates significantly higher response amplitudes than both the CE-Chirp and the Click. It also generates a much better response resolution than the CE-Chirp, but the same response resolution as the Click.

Notched-Noise Embedded Frequency Specific Chirps for Objective Audiometry Using Auditory Brainstem Responses

It has been shown recently that chirp-evoked auditory brainstem responses (ABRs) show better performance than click stimulations, especially at low intensity levels. In this paper we present the development, test, and evaluation of a series of notched-noise embedded frequency specific chirps. ABRs were collected in healthy young control subjects using the developed stimuli. Results of the analysis of the corresponding ABRs using a time-scale phase synchronization stability (PSS) measure are also reported. The resultant wave V amplitude and latency measures showed a similar behavior as for values reported in literature. The PSS of frequency specific chirp-evoked ABRs reflected the presence of the wave V for all stimulation intensities. The scales that resulted in higher PSS are in line with previous findings, where ABRs evoked by broadband chirps were analyzed, and which stated that low frequency channels are better for the recognition and analysis of chirp-evoked ABRs. We conclude that the development and test of the series of notched-noise embedded frequency specific chirps allowed the assessment of frequency specific ABRs, showing an identifiable wave V for different intensity levels. Future work may include the development of a faster automatic recognition scheme for these frequency specific ABRs.

Clinical Status of the Auditory Steady-State Response in Infants

Pediatric audiology has seen the inclusion of the auditory steady-state response (ASSR) in clinical test batteries as a valuable diagnostic tool. Its unique stimuli, recording and analysis characteristics allow for applications not previously possible with other auditory evoked responses in infants and young children. Although the long-standing research and clinical validation history of the frequency-specific auditory brain stem response (ABR) make it the current gold standard for estimating hearing thresholds, accumulating evidence is establishing the ASSR as a reliable and accurate tool for the diagnosis of hearing loss in infants. Current test-protocol efficiency and accuracy may be improved by including the ASSR to supplement ABR data and to cross-check test results. This article reviews the ASSR and its current clinical applications and limitations for determining hearing thresholds in infants and young children.

Differential Impact of Temporary and Permanent Noise-Induced Hearing Loss on Neuronal Cell Density in the Mouse Central Auditory Pathway

Although acoustic overstimulation has a major pathophysiological influence on the inner ear, central components of the auditory pathway can also be affected by noise-induced hearing loss (NIHL). The present study investigates the influence of a noise-induced temporary threshold shift (TTS) and/or permanent threshold shift (PTS) on neuronal cell densities in key structures of the central auditory pathway. Mice were noise-exposed (3 h, 5-20 kHz) at 115 dB sound pressure level (SPL) under anesthesia, and were investigated immediately (TTS group, n = 5) after the exposure, or 1 week later (PTS group, n = 6). Unexposed animals were used as controls (n = 7). Frequency-specific auditory brainstem responses (ABR) were recorded to examine auditory thresholds. Cell density was determined within the dorsal (DCN) and ventral (VCN) cochlear nucleus; the central nucleus of the inferior colliculus (ICC); the dorsal, ventral, and medial subdivisions of the medial geniculate body (MGBd, MGBv, and MGBm); and layer I to VI of the primary auditory cortex (AI I-VI). ABR thresholds were significantly elevated in the TTS group (52-69 dB SPL) and in the PTS group (33-42 dB SPL) compared to controls. There was a significant decrease in cell density only in the VCN of the TTS group (-10%), most likely induced by the acute overstimulation of neurons. Cell density was significantly reduced in all investigated auditory structures at 1 week post-exposure (PTS group), except in layer II of the AI (VCN: -30% and DCN: -30% (high-frequency); -39% (low-frequency); ICC: -31%; MGBd: -31%; MGBm: -28%; MGBv: -31%; AI: -10 to 14%). Thus there were dramatic changes within the neuronal cytoarchitecture of the central auditory pathway following a single noise exposure. The present findings should help clinicians to better understand the complex psychoacoustic phenomena of NIHL.

Effectiveness of different approaches for establishing cisplatin-induced cochlear lesions in mice

Conclusions: Mouse cochleae are highly resistant to systemicallyadministered cisplatin. However, cochlear lesions can be produced effectively in mice when cisplatin is applied locally through the round window niche or tympanum. Objective: To explore the optimal approach for creating cisplatin-induced cochlear lesions in mice. Materials and methods: Cisplatin was administered to adult C57BL/6J mice via four approaches: (1) transtympanic injection, (2) round window niche injection, (3) intraperitoneal injection (i.p.) at 4 mg/kg/day for 4 consecutive days, and (4) one 15 mg/kg dose i.p. The hearing was monitored using frequency-specific auditory brainstem responses (ABRs) and distortion-product otoacoustic emissions (DPOAEs). Cochlear pathology was observed in cochleograms with Harris’ hematoxylin staining.Results: Cisplatin applied systemically did not cause any significant ABR threshold elevation across the frequencies tested (2–32 kHz), whereas local application of cisplatin through the round window niche or tympanum resulted in significant ABR threshold elevations from high to medium frequencies. The functional changes were consistent with the cochlear pathology across groups.

Osteoprotegrin Knockout Mice Demonstrate Abnormal Remodeling of the Otic Capsule and Progressive Hearing Loss

The otic capsule, when compared with other bones in the body, is unique in that it undergoes no significant remodeling of bone after development. We previously demonstrated that osteoprotegerin (OPG), which inhibits formation and function of osteoclasts, is produced at high levels in the inner ear of normal mice and secreted into the perilymph from where it diffuses into the surrounding otic capsule bone through a lacunocanalicular system. To test our hypothesis that the high level of OPG may be important in the inhibition of otic capsule remodeling, we studied the light microscopic histology of the otic capsule in OPG knockout mice for evidence of abnormal remodeling of bone. We also tested the hearing in OPG knockout mice to determine whether OPG and its influence on surrounding bone is important for auditory function. Temporal bone histopathology and pathophysiology were compared in homozygous OPG knockout mice and C57BL/6 (B6) mice, the background strain for the knockouts. Auditory function in age-matched animals from each group was evaluated at approximately 4-week intervals from 8 to 21 weeks using frequency-specific auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE). After each of the last three evaluations, the cochleae from one mouse of each group were harvested, processed, and examined by light microscopy. Osteoprotegerin knockout mice demonstrated abnormal remodeling of bone within the otic capsule with multiple foci showing osteoclastic bone resorption and formation of new bone. Such changes were not seen in the age-matched B6 controls. The active bone remodeling process in the knockout animals showed many similarities to otosclerosis seen in human temporal bones. Over the time period that we monitored, auditory function was significantly and progressively compromised in the knockout animals relative to B6 controls. At the earliest age of test (8 wk), the loss was apparent as a mild, high-frequency reduction in sensitivity by ABR. In contrast, DPOAE losses in the knockouts were substantial even at 8 weeks, and by 21 weeks, these losses exceeded our equipment limits. Results of ABR testing showed hearing sensitivity changes in the animals of the background strain were confined largely to the high frequencies, whereas OPG knockouts demonstrated substantial low-frequency shifts in addition to those at high frequencies. The histopathological and pathophysiological findings in OPG knockout mice support the hypothesis that OPG is important in the inhibition of bone remodeling within the otic capsule and the maintenance of normal auditory function. This mouse may provide a valuable animal model of human otosclerosis.

Protective effect of edaravone against the ototoxicity of Pseudomonas aeruginosa exotoxin A

Conclusion. Our findings suggest that edaravone can protect against cochlear damage caused by Pseudomonas aeruginosa exotoxin A (PaExoA). Objective. To analyze the protective effect of a free radical scavenger, edaravone, against the ototoxicity resulting from exposure of the middle ear to PaExoA. Material and methods. In nine groups of albino rats the following solutions were instilled either via the tympanic membrane into the round window niche [intratympanically (i.t.)] or intravenously (i.v.): edaravone (i.v.); edaravone (i.t.); PaExoA (i.t.) + edaravone (i.t.; simultaneously); PaExoA (i.t.) + edaravone (i.t.; 1 h after); PaExoA (i.t.) + edaravone (i.t.; 24 h after); PaExoA (i.t.) + edaravone (i.v.; simultaneously); PaExoA (i.t.) + edaravone (i.v.; 1 h after); PaExoA (i.t.) + edaravone (i.v.; 24 h after); PaExoA (i.t.) + saline (i.v.). Frequency-specific (2–20 kHz) auditory brainstem responses were measured to determine hearing thresholds before and 2, 5 and 10 days after instillation. Results. PaExoA had penetrated from the middle ear into the cochlea and caused hearing loss. This impairment was blocked by intratympanic injection of edaravone when given simultaneously or 1 h after the first instillation of PaExoA, or by intravenous injection of edaravone when given simultaneously. There were significant differences in protective effect between the intratympanic and intravenous routes.