Reversal of an existing hearing loss by gene activation in Spns2 mutant mice.

Hearing loss is highly heterogeneous, but one common form involves a failure to maintain the local ionic environment of the sensory hair cells reflected in a reduced endocochlear potential. We used a genetic approach to ask whether this type of pathology can be reversed, using the Spns2tm1a mouse mutant known to show this defect. By activating Spns2 gene transcription at different ages after the onset of hearing loss, we found that an existing auditory impairment can be reversed to give close to normal thresholds for an auditory brainstem response (ABR), at least at low to mid stimulus frequencies. Delaying the activation of Spns2 led to less effective recovery of ABR thresholds, suggesting that there is a critical period for intervention. Early activation of Spns2 not only led to improvement in auditory function but also to protection of sensory hair cells from secondary degeneration. The genetic approach we have used to establish that this type of hearing loss is in principle reversible could be extended to many other diseases using available mouse resources.

Relative changes in the cochlear summating potentials to paired-clicks predict speech-in-noise perception and subjective hearing acuity.

Objective assays of human cochlear synaptopathy (CS) have been challenging to develop. It is suspected that relative summating potential (SP) changes are different in listeners with CS. In this proof-of-concept study, young, normal-hearing adults were recruited and assigned to a low/high-risk group for having CS based on their extended audiograms (9-16 kHz). SPs to paired-clicks with varying inter-click intervals isolated non-refractory receptor components of cochlear activity. Abrupt increases in SPs to paired- vs single-clicks were observed in high-risk listeners. Critically, exaggerated SPs predicted speech-in-noise and subjective hearing abilities, suggesting relative SP changes to rapid clicks might help identify putative synaptopathic listeners.

Neural Contributions to the Cochlear Summating Potential: Spiking and Dendritic Components.

Using electrocochleography, the summating potential (SP) is a deflection from baseline to tones and an early rise in the response to clicks. Here, we use normal hearing gerbils and gerbils with outer hair cells removed with a combination of furosemide and kanamycin to investigate cellular origins of the SP. Round window electrocochleography to tones and clicks was performed before and after application of tetrodotoxin to prevent action potentials, and then again after kainic acid to prevent generation of an EPSP. With appropriate subtractions of the response curves from the different conditions, the contributions to the SP from outer hair cells, inner hair cell, and neural "spiking" and "dendritic" responses were isolated. Like hair cells, the spiking and dendritic components had opposite polarities to tones - the dendritic component had negative polarity and the spiking component had positive polarity. The magnitude of the spiking component was larger than the dendritic across frequencies and intensities. The onset to tones and to clicks followed a similar sequence; the outer hair cells responded first, then inner hair cells, then the dendritic component, and then the compound action potential of the spiking response. These results show the sources of the SP include at least the four components studied, and that these have a mixture of polarities and magnitudes that vary across frequency and intensity. Thus, multiple possible interactions must be considered when interpreting the SP for clinical uses.

Electrophysiological and histomorphological changes of cochlea in miniature pigs after abrasion of round window niches.

Background: In operations of cochlea implantation (CI), many surgeons choose to drill a window on the bone wall of cochlea basic rotation, when more and more patients receive CI with residual hearing, what damage this step would result in is unclear.Objective: To study the effect to inner ear hair cells which is caused by drilling during CI.Methods: 6 miniature pigs are equally divided into two groups, Round window niche of each pig in the experimental group was milled, while the pigs in control group wasn't. After implanting depth of 6.5, 11.5 and 20 mm, round window electrocochleography was recorded to analyze the change of cochlea microphonic (CM) potentials respectively, histomorphological changes was observed.Results: Thresholds of CM in experimental group were higher than that of control group at different depth, amplitudes were smaller. In further group, cilia of inner hair cells (IHC) at bottom rotation were significantly damaged. After operation, ABR hearing threshold of experimental group was higher, differences at low frequency region were more obvious.Conclusions: Damage caused by mulling round window niche may seriously affect the function of the hair cells. Damage of the IHC is greater than OHC. CI through round window may protect residual hearing.

How low must you go? Effects of low-level noise on cochlear neural response.

Prolonged exposure to low-level noise has often been used scientifically as well as clinically to induce neuroplastic changes within the central auditory pathway in order to reduce central gain, suppress tinnitus and hyperacusis, and modulate different features of central auditory processing. A fundamental assumption underling these studies is that the noise exposure levels are so low that they have no effect on the neural output of the cochlea. Therefore, functional changes occurring in the central auditory pathway must be the results of central rather than peripheral changes. In an attempt to identify long-term noise exposures that did not cause peripheral changes, we measured the compound action potential (CAP) input/output functions from control rats and rats exposed for 6-weeks to 18-24 kHz noise presented at 25, 45, 55, 65, 75 or 85 dB SPL. Exposures >65 dB SPL significantly increased CAP thresholds; the critical intensity (Ct) below which no threshold shift occurred was estimated to be 55 dB SPL. Exposures >55 dB SPL significantly reduced suprathreshold CAP amplitudes; the critical intensity (Ca) below which no amplitude change was predicted to occur was a remarkably low level of 19 dB SPL. These results demonstrate that even extremely low-intensity long duration exposures can disrupt the neural output of the cochlea; these peripheral modifications are likely to contribute to the extensive compensatory changes observed at multiple levels of the central auditory pathway, neural network changes aimed at re-establishing homeostasis.

Cochlear Microphonics in Hearing Preservation Cochlear Implantees.

OBJECTIVES: The intracochlear electrocochleography (ECoG) could be recorded directly from the cochlear implant (CI) electrode in CI recipients with residual hearing. The primary objective of this study is to identify the most sensitive frequency to record cochlear microphonics (CM) in CI users with a wide degree of hearing abilities and deep electrode insertion. The secondary objective is to identify the optimum location within the cochlea to record intracochlear potentials. MATERIALS AND METHODS: CMs were recorded from the CI electrodes in eight females and eight males implanted with CIs Pulsar, Concerto, or Sonata, Med-El Corp. RESULTS: Among the tone pips of various frequencies, 1k or 500 Hz were the most sensitive for CI users. The most sensitive place in the cochlea to record the CM potentials depended on the tone frequency used. The deeper into the cochlea the mean maximum CM peak-to-peak amplitude was measured, the lower the stimulating tone frequency was. CONCLUSION: The most optimal recording parameters identified for intracochlear CM recording can be useful for intraoperative and postoperative monitoring of cochlear health in CI users with residual hearing.

An analytic approach to identifying the sources of the low-frequency round window cochlear response.

The cochlear microphonic, traditionally thought of as an indication of electrical current flow through hair cells, in conjunction with suppressing high-pass noise or tones, is a promising method of assessing the health of outer hair cells at specific locations along the cochlear partition. We propose that the electrical potential recorded from the round window in gerbils in response to low-frequency tones, which we call cochlear response (CR), contains significant responses from multiple cellular sources, which may expand its diagnostic purview. In this study, CR is measured in the gerbil and modeled to identify its contributing sources. CR was recorded via an electrode placed in the round window niche of sixteen Mongolian gerbils and elicited with a 45 Hz tone burst embedded in 18 high-pass filtered noise conditions to target responses from increasing regions along the cochlear partition. Possible sources were modeled using previously-published hair cell and auditory nerve response data, and then weighted and combined using linear regression to produce a model response that fits closely to the mean CR waveform. The significant contributing sources identified by the model are outer hair cells, inner hair cells, and the auditory nerve. We conclude that the low-frequency CR contains contributions from several cellular sources.

The Tectorial Membrane: Mechanical Properties and Functions.

The tectorial membrane (TM) is widely believed to play a critical role in determining the remarkable sensitivity and frequency selectivity that are hallmarks of mammalian hearing. Recently developed mouse models of human hearing disorders have provided new insights into the molecular, nanomechanical mechanisms that underlie resonance and traveling wave properties of the TM. Herein we review recent experimental and theoretical results detailing TM morphology, local poroelastic and electromechanical interactions, and global spread of excitation via TM traveling waves, with direct implications for cochlear mechanisms.

The Effect of Test, Electrode, and Rate on Electrocochleography Measures.

BACKGROUND: Electrocochleography (ECochG) is the measurement of stimulus-related cochlear potentials and the compound action potential (AP). Its primary clinical application is with the assessment of inner ear disorders. There are few studies examining the variability of ECochG measures. PURPOSE: The objective of the study was to examine the effect of test (i.e., initial versus retest), electrode (i.e., extratympanic versus tympanic), and stimulus rate (i.e., 7.7 versus 77.7/sec) on ECochG indices (i.e., summating potential [SP] amplitude, AP latency, AP amplitude, SP/AP amplitude ratio, and SP/AP area ratio). RESEARCH DESIGN: Correlational and three-factor repeated measures designs were employed. STUDY SAMPLE: Eighteen normal-hearing young adults participated. DATA COLLECTION AND ANALYSIS: ECochG responses were obtained with 90 dB nHL click stimuli for an initial test and retest at two stimulus rates with a commercially available extratympanic (TIPtrode™) and tympanic (Lilly TM-Wick) electrode. Separate repeated measures linear mixed-model analysis of variance examined the effect of test, electrode, and rate for all ECochG indices. Test-retest variability was also examined with correlation analyses; an examination of mean test-retest differences and their 95% confidence intervals (CI); and construction of Bland-Altman plots. RESULTS: The presence of SP and AP responses varied across experimental conditions. Electrode and rate were statistically significant predictors (p < 0.05) of SP and AP responses: SP and AP responses were more likely to be present with the tympanic electrode and at the slow rate. Statistically significant correlations (p < 0.05) were found between initial tests and retests with all ECochG indices with both electrodes with the exception of SP amplitude with the TIPtrode™ electrode. There were no significant main effects of test (initial versus retest) or interactions of test and electrode or rate for any of the ECochG indices (p > 0.05). The 95% CI of the mean test-retest differences contained 0 confirming that the effect of test was not statistically significant. There was a statistically significant main effect of electrode (p < 0.05) on three ECochG measures. The Lilly TM-Wick electrode produced larger SP amplitudes, AP amplitudes, and SP/AP area ratios than TIPtrode™ electrodes. A statistically significant main effect of rate (p < 0.05) was identified for all ECochG measures. The effect of rate on AP latency and amplitude was expected. Increasing the stimulus rate prolonged the AP latency and decreased AP amplitude. SP amplitude was larger for the faster rate. CONCLUSIONS: There was no difference between electrodes with regard to test-retest measures. However, considering the higher likelihood of ECochG SP and AP responses and larger SP amplitude, SP/AP amplitude ratio, and SP/AP area ratio indices, the tympanic electrode placement is recommended for clinical practice. The addition of a fast stimulus rate may be considered for enhanced SP amplitude, SP/AP amplitude ratio, and SP/AP area ratio albeit with the consideration of the loss of SP and AP responses in some individuals.

Development of intra-operative assessment system for ossicular mobility and middle ear transfer function.

Objective measurements of the ossicular mobility have not been commonly performed during the surgery, and the assessment of ossicular mobility is made by palpation in most cases. Palpation is inherently subjective and may not always be reliable, especially in milder degrees of ossicular fixation and in the case of multiple fixation. Although several devices have been developed to quantitatively measure the ossicular mobility during surgery, they have not been widely used. In this study, a new system with a hand-held probe which enables intraoperative quantitative measurements of ossicular mobility has been developed. This system not only measures the ossicular mobility, but also investigates "local" transmission characteristics of the middle ear by directly applying vibration to the ossicles and measuring cochlear microphonic. The basic performance of this system was confirmed by measuring the mobility of artificial ossicles and cochlear microphonics in an animal experiment. Our system may contribute to selection of a better surgical method and reducing the risks of revision surgery.

Postoperative Electrocochleography from Hybrid Cochlear Implant users: An Alternative Analysis Procedure.

OBJECTIVE: Shorter electrode arrays and soft surgical techniques allow for preservation of acoustic hearing in many cochlear implant (CI) users. Recently, we developed a method of using the Neural Response Telemetry (NRT) system built in Custom Sound EP clinical software to record acoustically evoked electrocochleography (ECoG) responses from an intracochlear electrode in Nucleus Hybrid CI users (Abbas et al., 2017). We recorded responses dominated by the hair cells (cochlear microphonic, CM/DIF) and the auditory nerve (auditory nerve neurophonic, ANN/SUM). Unfortunately, the recording procedure was time consuming, limiting potential clinical applications. This report describes a modified method to record the ECoG response more efficiently. We refer to this modified technique as the "short window" method, while our previous technique (Abbas et al., 2017) is referred as the "long window" method. In this report, our goal was to 1) evaluate the feasibility of the short window method to record the CM/DIF and ANN/SUM responses, 2) characterize the reliability and sensitivity of the measures recorded using the short window method, and 3) evaluate the relationship between the CM/DIF and ANN/SUM measures recorded using the modified method and audiometric thresholds. METHOD: Thirty-four postlingually deafened adult Hybrid CI users participated in this study. Acoustic tone bursts were presented at four frequencies (250, 500, 750, and 1000 Hz) at various stimulation levels via an insert earphone in both condensation and rarefaction polarities. Acoustically evoked ECoG responses were recorded from the most apical electrode in the intracochlear array. These two responses were subtracted to emphasize the CM/DIF responses and added to emphasize the ANN/SUM responses. Response thresholds were determined based on visual inspection of time waveforms, and trough-to-peak analysis technique was used to quantify response amplitudes. Within-subject comparison of responses measured using both short and long window methods were obtained from seven subjects. We also assessed the reliability and sensitivity of the short window method by comparing repeated measures from 19 subjects at different times. Correlations between CM/DIF and ANN/SUM measures using the short window recording method and audiometric thresholds were also assessed. RESULTS: Regardless of the recording method, CM/DIF responses were larger than ANN/SUM responses. Responses obtained using the short window method were positively correlated to those obtained using the conventional long window method. Subjects who had stable acoustic hearing at two different time points had similar ECoG responses at those points, confirming high test-retest reliability of the short window method. Subjects who lost hearing between two different time points showed increases in ECoG thresholds, suggesting that physiologic ECoG responses are sensitive to audiometric changes. Correlations between CM/DIF and ANN/SUM thresholds and audiometric thresholds at all tested frequencies were significant. CONCLUSION: This study compares two different recording methods. Intracochlear ECoG measures recorded using the short window technique were efficient, reliable, and repeatable. We were able to collect more frequency specific data with the short window method, and observed similar results between the long window and short window methods. Correlations between physiological thresholds and audiometric thresholds were similar to those reported previously using the long window method (Abbas et al., 2017). This is an important finding because it demonstrates that clinically-available software can be used to measure frequency-specific ECoG responses with enhanced efficiency, increasing the odds that this technique might move from the laboratory into clinical practice.

[Auditory evoked potentials in children with auditory neuropathy spectrum disorder]. / Slukhovye vyzvannye potentsialy u detei s zabolevaniem spektra auditornykh neiropatii.

The objective of the present study was to estimate peculiarities of the auditory brainstem evoked potentials (ABR), auditory steady-state responses (ASSR) and cortical auditory evoked potentials (CAEP) in the children presenting with bilateral auditory neuropathy spectrum disorder (ANSD). The study included 100 patients with bilateral ANSD diagnosed based on the positive response of otoacoustic emissions (OAEs) and/or cochlear microphonic (CM) detection, while no synchronous neural activity was detected in the ABR test. Cochlear microphonic was the main clue for the ANSD diagnosing, because OAE was absent in both ears of 49 children. ABR testing revealed no response bilaterally in 72 cases (out of 100). In contrast to ABR, the ASSR thresholds were detectable at all the four main frequencies in both ears in 73 % of the cases (47 out of the 64 tested ones). Both ABR and ASSR in most cases were incomparable with the behavioral audiometric thresholds. 28 children underwent CAEP testing. In 7 cases out of 8 with mild hearing loss detectable CAEP were recorded. CAEP registration in l7 children making use of the hearing aids and in 3 children after cochlear implantation revealed, in the majority of the cases, the concordance between CAEP detectability with behavioral thresholds and rehabilitation outcomes with fairly good speech intelligibility. It is concluded that the ABR registration with CM evaluation is the most informative test for ANSD diagnosis. However, ABR as well as ASSR is useless for the estimation of the behavioral thresholds. The results of this study suggest that the presence or absence of CAEPs can provide some indication of the audibility of a speech sound in the children with ANSD; however this method requires further investigation.

Spectral Ripples in Round-Window Cochlear Microphonics: Evidence for Multiple Generation Mechanisms.

The cochlear microphonic (CM) results from the vector sum of outer hair cell transduction currents excited by a stimulus. The classical theory of CM generation-that the response measured at the round window is dominated by cellular sources located within the tail region of the basilar membrane (BM) excitation pattern-predicts that CM amplitude and phase vary little with stimulus frequency. Contrary to expectations, CM amplitude and phase-gradient delay measured in response to low-level tones in chinchillas demonstrate a striking, quasiperiodic pattern of spectral ripples, even at frequencies > 5 kHz, where interference with neurophonic potentials is unlikely. The spectral ripples were reduced in the presence of a moderate-level saturating tone at a nearby frequency. When converted to the time domain, only the delayed CM energy was diminished in the presence of the saturator. We hypothesize that the ripples represent an interference pattern produced by CM components with different phase gradients: an early-latency component originating within the tail region of the BM excitation and two delayed components that depend on active cochlear processing near the peak region of the traveling wave. Using time windowing, we show that the early, middle, and late components have delays corresponding to estimated middle-ear transmission, cochlear forward delays, and cochlear round-trip delays, respectively. By extending the classical model of CM generation to include mechanical and electrical irregularities, we propose that middle components are generated through a mechanism of "coherent summation" analogous to the production of reflection-source otoacoustic emissions (OAEs), while the late components arise through a process of internal cochlear reflection related to the generation of stimulus-frequency OAEs. Although early-latency components from the passive tail region typically dominate the round-window CM, at low stimulus levels, substantial contributions from components shaped by active cochlear processing provide a new avenue for improving CM measurements as assays of cochlear health.

The Summating Potential Is a Reliable Marker of Electrode Position in Electrocochleography: Cochlear Implant as a Theragnostic Probe.

OBJECTIVE: For the increasing number of cochlear implantations in subjects with residual hearing, hearing preservation, and thus the prevention of implantation trauma, is crucial. A method for monitoring the intracochlear position of a cochlear implant (CI) and early indication of imminent cochlear trauma would help to assist the surgeon to achieve this goal. The aim of this study was to evaluate the reliability of the different electric components recorded by an intracochlear electrocochleography (ECochG) as markers for the cochleotopic position of a CI. The measurements were made directly from the CI, combining intrasurgical diagnostics with the therapeutical use of the CI, thus, turning the CI into a "theragnostic probe." DESIGN: Intracochlear ECochGs were measured in 10 Dunkin Hartley guinea pigs of either sex, with normal auditory brainstem response thresholds. All subjects were fully implanted (4 to 5 mm) with a custom six contact CI. The ECochG was recorded simultaneously from all six contacts with monopolar configuration (retroauricular reference electrode). The gross ECochG signal was filtered off-line to separate three of its main components: compound action potential, cochlear microphonic, and summating potential (SP). Additionally, five cochleae were harvested and histologically processed to access the spatial position of the CI contacts. Both ECochG data and histological reconstructions of the electrode position were fitted with the Greenwood function to verify the reliability of the deduced cochleotopic position of the CI. RESULTS: SPs could be used as suitable markers for the frequency position of the recording electrode with an accuracy of ±1/4 octave in the functioning cochlea, verified by histology. Cochlear microphonics showed a dependency on electrode position but were less reliable as positional markers. Compound action potentials were not suitable for CI position information but were sensitive to "cochlear health" (e.g., insertion trauma). CONCLUSIONS: SPs directly recorded from the contacts of a CI during surgery can be used to access the intracochlear frequency position of the CI. Using SP monitoring, implantation may be stopped before penetrating functioning cochlear regions. If the technique was similarly effective in humans, it could prevent implantation trauma and increase hearing preservation during CI surgery. Diagnostic hardware and software for recording biological signals with a CI without filter limitations might be a valuable add-on to the portfolios of CI manufacturers.

Validation of methods for prediction of clinical output levels of active middle ear implants from measurements in human cadaveric ears.

Today, the standard method to predict output levels of active middle ear implants (AMEIs) before clinical data are available is stapes vibration measurement in human cadaveric ears, according to ASTM standard F2504-05. Although this procedure is well established, the validity of the predicted output levels has never been demonstrated clinically. Furthermore, this procedure requires a mobile and visually accessible stapes and an AMEI stimulating the ossicular chain. Thus, an alternative method is needed to quantify the output level of AMEIs in all other stimulation modes, e.g. reverse stimulation of the round window. Intracochlear pressure difference (ICPD) is a good candidate for such a method as it correlates with evoked potentials in animals and it is measurable in cadaveric ears. To validate this method we correlated AMEI output levels calculated from ICPD and from stapes vibration in cadaveric ears with outputs levels determined from clinical data. Output levels calculated from ICPD were similar to output levels calculated from stapes vibration and almost identical to clinical data. Our results demonstrate that both ICPD and stapes vibration can be used as a measure to predict AMEI clinical output levels in cadaveric ears and that ICPD as reference provided even more accurate results.

Resistance of Gerbil Auditory Function to Reversible Decrease in Cochlear Blood Flow.

The objective was to design in gerbils a model of reversible decrease in cochlear blood flow (CBF) and analyze its influence on cochlear function. In Mongolian gerbils injected with ferromagnetic microbeads, a magnet placed near the porus acusticus allowed CBF to be manipulated. The cochlear microphonic potential (CM) from the basal cochlea was monitored by a round-window electrode. In 13 of the 20 successfully injected gerbils, stable CBF reduction was obtained for 11.5 min on average. The CM was affected only when CBF fell to less than 60% of its baseline, yet remained >40% of its initial level in about 2/3 of such cases. After CBF restoration, CM recovery was fast and usually complete. Reduced CM came with a 35- to 45-dB threshold elevation of neural responses determined by compound action potentials. This method allowing reversible changes of CBF confirms the robustness of cochlear function to decreased CBF. It can be used to study whether a hypovascularized cochlea is abnormally sensitive to stress.

A connexin30 mutation rescues hearing and reveals roles for gap junctions in cochlear amplification and micromechanics.

Accelerated age-related hearing loss disrupts high-frequency hearing in inbred CD-1 mice. The p.Ala88Val (A88V) mutation in the gene coding for the gap-junction protein connexin30 (Cx30) protects the cochlear basal turn of adult CD-1Cx30A88V/A88V mice from degeneration and rescues hearing. Here we report that the passive compliance of the cochlear partition and active frequency tuning of the basilar membrane are enhanced in the cochleae of CD-1Cx30A88V/A88V compared to CBA/J mice with sensitive high-frequency hearing, suggesting that gap junctions contribute to passive cochlear mechanics and energy distribution in the active cochlea. Surprisingly, the endocochlear potential that drives mechanoelectrical transduction currents in outer hair cells and hence cochlear amplification is greatly reduced in CD-1Cx30A88V/A88V mice. Yet, the saturating amplitudes of cochlear microphonic potentials in CD-1Cx30A88V/A88V and CBA/J mice are comparable. Although not conclusive, these results are compatible with the proposal that transmembrane potentials, determined mainly by extracellular potentials, drive somatic electromotility of outer hair cells.

Frequency-dependent fine structure in the frequency-following response: The byproduct of multiple generators.

The frequency-following response (FFR) is an auditory-evoked response recorded at the scalp that captures the spectrotemporal properties of tonal stimuli. Previous investigations report that the amplitude of the FFR fluctuates as a function of stimulus frequency, a phenomenon thought to reflect multiple neural generators phase-locking to the stimulus with different response latencies. When phase-locked responses are offset by different latencies, constructive and destructive phase interferences emerge in the volume-conducted signals, culminating in an attenuation or amplification of the scalp-recorded response in a frequency-specific manner. Borrowing from the literature on the audiogram and otoacoustic emissions (OAEs), we refer to this frequency-specific waxing and waning of the FFR amplitude as fine structure. While prior work on the human FFR was limited by small sets of stimulus frequencies, here, we provide the first systematic investigation of FFR fine structure using a broad stimulus set (90 + frequencies) that spanned the limits of human pitch perception. Consistent with predictions, the magnitude of the FFR response varied systematically as a function of stimulus frequency between 16.35 and 880 Hz. In our dataset, FFR high points (local maxima) emerged at ∼44, 87, 208, and 415 Hz with FFR valleys (local minima) emerging ∼62, 110, 311, and 448 Hz. To investigate whether these amplitude fluctuations are the result of multiple neural generators with distinct latencies, we created a theoretical model of the FFR that included six putative generators. Based on the extant literature on the sources of the FFR, our model adopted latencies characteristic of the cochlear microphonic (0 ms), cochlear nucleus (∼1.25 ms), superior olive (∼3.7 ms), and inferior colliculus (∼5 ms). In addition, we included two longer latency putative generators (∼13 ms, and ∼25 ms) reflective of the characteristic latencies of primary and non-primary auditory cortical structures. Our model revealed that the FFR fine structure observed between 16.35 and 880 Hz can be explained by the phase-interaction patterns created by six generators with relative latencies spaced between 0 and 25 ms. In addition, our model provides confirmatory evidence that both subcortical and cortical structures are activated by low-frequency (<100 Hz) tones, with the cortex being less sensitive to frequencies > 100 Hz. Collectively, these findings highlight (1) that the FFR is a composite response; (2) that the FFR at any given frequency can reflect activity from multiple generators; (3) that the fine-structure pattern between 16.35 and 880 Hz is the collective outcome of short- and long-latency generators; (4) that FFR fine structure is epiphenomenal in that it reflects how volume-conducted electrical potentials originating from different sources with different latencies interact at scalp locations, not how these different sources actually interact in the brain; and (5) that as a byproduct of these phase-interaction patterns low-amplitude responses will emerge at some frequencies, even when the underlying generators are fully functioning. We believe these findings call for a re-examination of how FFR amplitude is interpreted in both clinical and experimental contexts.

Study of cochlear microphonic potentials in auditory neuropathy / Estudo do microfonismo coclear na neuropatia auditiva

Abstract Introduction: Auditory Neuropathy/Dyssynchrony is a disorder characterized by the presence of Otoacoustic Emissions and Cochlear Microphonic Potentials, an absence or severe alteration of Brainstem Evoked Auditory Potential, auditory thresholds incompatible with speech thresholds and altered acoustic reflexes. The study of the Cochlear Microphonic Potential appears to be the most important tool for an accurate diagnosis of this pathology. Objective: Determine the characteristics of the Cochlear Microphonic in Auditory Neuropathy/Dyssynchrony using an integrative review. Methods: Bibliographic survey of Pubmed and Bireme platforms and MedLine, LILACS and SciELO data banks, with standardized searches up to July 2014, using keywords. Criteria were established for the selection and assessment of the scientific studies surveyed, considering the following aspects: author, year/place, degree of recommendation/level of scientific evidence, objective, sample, age range, mean age, tests, results and conclusion. Results: Of the 1959 articles found, 1914 were excluded for the title, 20 for the abstract, 9 for the text of the article, 2 for being repeated and 14 were selected for the study. Conclusion: The presence of the Cochlear Microphonic is a determining finding in the differential diagnosis of Auditory Neuropathy/Dyssynchrony. The protocol for the determination of Cochlear Microphonic must include the use of insert earphones, reverse polarity and blocking the stimulus tube to eliminate electrical artifact interference. The amplitude of the Cochlear Microphonic in Auditory Neuropathy/Dyssynchrony shows no significant difference from that of normal individuals. The duration of the Cochlear Microphonic is longer in individuals with Auditory Neuropathy/Dyssynchrony.

Resumo Introdução: A Neuropatia/Dessincronia Auditiva é uma doença caracterizada pela presença das Emissões Otoacústicas e do Microfonismo Coclear, com ausência ou grave alteração do Potencial Evocado Auditivo de Tronco Encefálico, limiares auditivos incompatíveis com limiares vocais e reflexos acústicos alterados. O estudo do Microfonismo Coclear parece ser a ferramenta mais importante para um diagnóstico preciso desta patologia. Objetivo: Verificar por meio de uma revisão integrativa as características do Microfonismo Coclear na Neuropatia/Dessincronia Auditiva. Método: Levantamento bibliográfico nas plataformas Pubmed e Bireme e nas bases de dados MedLine, LILACS e SciELO, com buscas padronizadas até julho de 2014, utilizando-se palavraschave. Para a seleção e avaliação dos estudos científicos levantados, foram estabelecidos critérios, contemplando os aspectos: autor, ano/local, grau de recomendação/nível de evidência científica, objetivo, amostra, faixa etária, média de idade em anos, testes, resultados e conclusão. Resultados: Dos 1959 artigos encontrados, 1914 foram excluídos pelo título, 20 pelo resumo, nove pela leitura do artigo, dois eram repetidos e 14 foram selecionados para o estudo. Conclusão: A presença do Microfonismo Coclear é um achado determinante no diagnóstico diferencial da Neuropatia/Dessincronia auditiva. O protocolo de registro do Microfonismo Coclear deve contar com o uso de fones de inserção, a inversão da polaridade e o bloqueio do tubo do estímulo para impedir a interferência de artefato elétrico. A amplitude do Microfonismo Coclear na Neuropatia/Dessincronia auditiva não apresenta diferença significante entre a amplitude do Microfonismo Coclear em ouvintes normais. A duração do Microfonismo Coclear é maior em indivíduos com Neuropatia/Dessincronia auditiva.