Modelling the Generation of the Cochlear Microphonic

<p>The human ear is a remarkable sensory organ. A normal healthy human ear is able to process sounds covering a wide range of frequencies and intensities, while distinguishing between different components of complex sounds such as a musical chord. In the last four decades, knowledge about the cochlea and the mechanisms involved in its operation has greatly increased, but many details about these mechanisms remain unresolved and disputed. The cochlea has a vulnerable structure. Consequently, measuring and monitoring its mechanical and electrical activities even with contemporary devices is very difficult. Modelling can be used to fill gaps between those measurements that are feasible and actual cochlear function. Modelling techniques can also help to simplify complex cochlear operation to a tractable and comprehensible level while still reproducing certain behaviours of interest. Modelling therefore can play an essential role in developing a better understanding of the cochlea. The Cochlear Microphonic (CM) is an electrical signal generated inside the cochlea in response to sound. This electrical signal reflects mechanical activity in the cochlea and the excitation processes involved in its generation. However, the difficulty of obtaining this signal and the simplicity of other methods such as otoacoustic emissions have discouraged the use of the cochlear microphonic as a tool for studying cochlear functions. In this thesis, amodel of the cochlea is presented which integrates bothmechanical and electrical aspects, enabling the interaction between them to be investigated. The resulting model is then used to observe the effect of the cochlear amplifier on the CM. The results indicate that while the cochlear amplifier significantly amplifies the basilar membrane displacement, the effect on the CM is less significant. Both of these indications agree with previous physiological findings. A novel modelling approach is used to investigate the tuning discrepancy between basilar membrane and CMtuning curves. The results suggest that this discrepancy is primarily due to transversal phase cancellation in the outer hair cell rather than longitudinal phase cancellation along the basilar membrane. In addition, the results of the model suggest that spontaneous cochlear microphonic should exist in the cochlea. The existence of this spontaneous electrical signal has not yet been reported.</p>

Modelling the Generation of the Cochlear Microphonic

<p>The human ear is a remarkable sensory organ. A normal healthy human ear is able to process sounds covering a wide range of frequencies and intensities, while distinguishing between different components of complex sounds such as a musical chord. In the last four decades, knowledge about the cochlea and the mechanisms involved in its operation has greatly increased, but many details about these mechanisms remain unresolved and disputed. The cochlea has a vulnerable structure. Consequently, measuring and monitoring its mechanical and electrical activities even with contemporary devices is very difficult. Modelling can be used to fill gaps between those measurements that are feasible and actual cochlear function. Modelling techniques can also help to simplify complex cochlear operation to a tractable and comprehensible level while still reproducing certain behaviours of interest. Modelling therefore can play an essential role in developing a better understanding of the cochlea. The Cochlear Microphonic (CM) is an electrical signal generated inside the cochlea in response to sound. This electrical signal reflects mechanical activity in the cochlea and the excitation processes involved in its generation. However, the difficulty of obtaining this signal and the simplicity of other methods such as otoacoustic emissions have discouraged the use of the cochlear microphonic as a tool for studying cochlear functions. In this thesis, amodel of the cochlea is presented which integrates bothmechanical and electrical aspects, enabling the interaction between them to be investigated. The resulting model is then used to observe the effect of the cochlear amplifier on the CM. The results indicate that while the cochlear amplifier significantly amplifies the basilar membrane displacement, the effect on the CM is less significant. Both of these indications agree with previous physiological findings. A novel modelling approach is used to investigate the tuning discrepancy between basilar membrane and CMtuning curves. The results suggest that this discrepancy is primarily due to transversal phase cancellation in the outer hair cell rather than longitudinal phase cancellation along the basilar membrane. In addition, the results of the model suggest that spontaneous cochlear microphonic should exist in the cochlea. The existence of this spontaneous electrical signal has not yet been reported.</p>

Reduced BDNF Expression in Auditory Cortex Contributed to Neonatal Pain Induced Hearing Impairment and Dendritic Pruning Deficiency in Mice

Hearing loss in children is common especially in NICU with consequences of worse outcomes in speech, language, education, social functioning, cognitive abilities, and quality of life. Whether neonatal pain is link to increase risks for hearing loss remains to be explored. Here, we implemented Complete Freund's adjuvant (CFA) plantar injection and needle prick model to mimic neonatal pain in NICU during critical period of hearing development. Auditory brainstem response (ABR) test was used to determine the hearing threshold at 4w and 8w postnatal. Sufentanil and Oxycodone were used as analgesic to treat neonatal pain. Hair cell and ribbon synapse stanning were performed to detect cochlear function. Golgi-cox staining and BDNF immunofluorescence of auditory cortex were performed to determine dendritic spine pruning in auditory cortex. The dendritic pruning related protein CaMKII and Rac1/2 level were detected by western blot. We found that CFA induced neonatal pain and ABR threshold increased at 4w and 8w postnatal and the impairment were attenuated after analgesic administration. Neither the inner hair cell (IHC) nor the synapse of CFA mice was damaged in cochlear. CFA mice showed increased dendritic spine density at auditory cortex and reduced BDNF level. Furthermore, Rac1/2 and CaMKII might contributed to the disrupt dendritic spine pruning. Our study suggested that neonatal pain could induced hearing impairment in adulthood ascribed to the reduced BDNF level and AC dendritic spine pruning deficiency, optimal analgesic in early-life could beneficial for hearing development.

Nondeterministic nature of sensorineural outcomes following noise trauma

ABSTRACT Over 1.1 billion individuals are at risk for noise induced hearing loss yet there is no accepted therapy. A long history of research has demonstrated that excessive noise exposure will kill outer hair cells (OHCs). Such observations have fueled the notion that dead OHCs underlie hearing loss. Therefore, previous and current therapeutic approaches are based on preventing the loss of OHCs. However, the relationship between OHC loss and hearing loss is at best a modest correlation. This suggests that in addition to the death of OHCs, other mechanisms may regulate the type and degree of hearing loss. In the current study, we tested the hypothesis that permanent noise-induced-hearing loss is consequent to additional mechanisms beyond the noise dose and the death of OHCs. Hooded male rats were randomly divided into noise and control groups. Morphological and physiological assessments were conducted on both groups. The combined results suggest that beyond OHC loss, the surviving cochlear elements shape sensorineural outcomes, which can be nondeterministic. These findings provide the basis for individualized ototherapeutics that manipulate surviving cellular elements in order to bias cochlear function towards normal hearing even in the presence of dead OHCs.

The Hair Cell Analysis Toolbox: A machine learning-based whole cochlea analysis pipeline

Auditory hair cells, the whole length of the cochlea, are routinely visualized using light microscopy techniques. It is common, therefore, for one to collect more data than is practical to analyze manually. There are currently no widely accepted tools for unsupervised, unbiased, and comprehensive analysis of cells in an entire cochlea. This represents a stark gap between image-based data and other tests of cochlear function. To close this gap, we present a machine learning-based hair cell analysis toolbox, for the analysis of whole cochleae, imaged with confocal microscopy. The software presented here allows the automation of common image analysis tasks such as counting hair cells, determining their best frequency, as well as quantifying single cell immunofluorescence intensities along the entire cochlear coil. We hope these automated tools will remove a considerable barrier in cochlear image analysis, allowing for more informative and less selective data analysis practices.

A case series shows independent vestibular labyrinthine function after major surgical trauma to the human cochlea

Background The receptors for hearing and balance are housed together in the labyrinth of the inner ear and share the same fluids. Surgical damage to either receptor system was widely believed to cause certain permanent loss of the receptor function of the other. That principle, however, has been called into question because there have been anecdotal reports in individual patients of at least partial preservation of cochlear function after major surgical damage to the vestibular division and vice versa. Methods We performed specific objective vestibular function tests before and after surgical trauma (partial or subtotal cochlear removal) for treatment of intracochlear tumors in 27 consecutive patients in a tertiary referral center. Vestibular function was assessed by calorics (low-frequency response of the lateral semicircular canal), vestibulo-ocular reflex by video head impulse test (vHIT) of the three semicircular canals, cervical and ocular vestibular evoked myogenic potentials (cVEMP, saccule and oVEMP, utricle). Preoperative and postoperative distributions were compared with paired t-tests. Results Here we show that there was no significant difference between pre- and post-operative measures for all tests of the five vestibular organs, and that after major surgical cochlear trauma, the vestibular receptors continue to function independently. Conclusions These surprising observations have important implications for our understanding of the function and the surgery of the peripheral auditory and vestibular system in general and open up new possibilities for the development, construction and evaluation of neural interfaces for electrical or optical stimulation of the peripheral auditory and vestibular nervous system.

Norrie disease protein is essential for cochlear hair cell maturation

Mutations in the gene for Norrie disease protein (Ndp) cause syndromic deafness and blindness. We show here that cochlear function in an Ndp knockout mouse deteriorated with age: At P3-P4, hair cells (HCs) showed progressive loss of Pou4f3 and Gfi1, key transcription factors for HC maturation, and Myo7a, a specialized myosin required for normal function of HC stereocilia. Loss of expression of these genes correlated to increasing HC loss and profound hearing loss by 2 mo. We show that overexpression of the Ndp gene in neonatal supporting cells or, remarkably, up-regulation of canonical Wnt signaling in HCs rescued HCs and cochlear function. We conclude that Ndp secreted from supporting cells orchestrates a transcriptional network for the maintenance and survival of HCs and that increasing the level of β-catenin, the intracellular effector of Wnt signaling, is sufficient to replace the functional requirement for Ndp in the cochlea.

Reliability of Contralateral Suppression in Evoked Distortion Product Otoacoustic Emissions

Introduction Distortion product otoacoustic emissions (DPOAE) and their suppression may be considered useful in monitoring cochlear function and the efferent auditory pathway inhibitory effect. Nonetheless, the establishment of reliable parameters of response variations is of great importance. Objectives To verify the replicability of test and retest in the research of the inhibitory effect of the efferent pathway using contralateral suppressing stimulus during DPOAE recording for clinical applicability. Methods Cross-sectional study with 48 volunteers, aged 18 to 30 years, with normal audiometric thresholds. The procedures included were audiometric and immittance measures to overrule any conductive or sensorineural conditions and DPOAE recordings without and with contralateral suppression with a 60 dBHL white noise. Distortion product otoacoustic emissions amplitudes were analyzed and compared in both conditions with Wilcoxon test, and the Spearman correlation test was used to assess test-retest reliability. Results The comparative analysis showed differences between amplitudes in test and retest conditions only in 1,500 Hz for DPOAE measures with all other tested frequencies showing no differences, and no difference was observed in all recorded frequencies in the test and retest comparison for DPOAE suppression. The degree of correlation between test and retest of DPOAE amplitude was good at 6,000 Hz and strong (r > 0.880) at the other frequencies. For DPOAE with suppression, all frequencies presented strong correlation between test and retest: 1,500 Hz (r = 0.880), 2,000 Hz (r = 0.882), 3,000 Hz (r = 0.940), and 6,000 Hz (r = 0.957). Conclusions The study found good replicability in contralateral suppression of DPOAE with potential clinical applicability, and we recommend conducting the test from 2000Hz to higher frequencies for more reliable results.

A systematic review on the effect of low-dose radiation on hearing

Numerous studies have documented the adverse effects of high-dose radiation on hearing in patients. On the other hand, radiographers are exposed to a low dose of ionizing radiation, and the effect of a low dose of radiation on hearing is quite abstruse. Therefore, the present systematic review aimed to elucidate the effect of low-dose ionizing radiation on hearing. Two authors independently carried out a comprehensive data search in three electronic databases, including PUBMED/MEDLINE, CINAHL, and SCOPUS. Eligible articles were independently assessed for quality by two authors. Cochrane Risk of Bias tool was used assess quality of the included studies. Two articles met the low-dose radiation exposure criteria given by Atomic Energy Regulatory Board (AERB) and National Council on Radiation Protection (NCRP) guidelines. Both studies observed the behavioral symptoms, pure-tone hearing sensitivity at the standard, extended high frequencies, and the middle ear functioning in low-dose radiation-exposed individuals and compared with age and gender-matched controls. One study assessed the cochlear function using transient-evoked otoacoustic emissions (TEOAE). Both studies reported that behavioral symptoms of auditory dysfunction and hearing thresholds at extended high frequencies were higher in radiation-exposed individuals than in the controls. The current systematic review concludes that the low-dose ionizing radiation may affect the hearing adversely. Nevertheless, further studies with robust research design are required to explicate the cause and effect relationship between the occupational low-dose ionizing radiation exposure and hearing.