Distortion Product Otoacoustic Emission and Auditory Brainstem Responses in the Echidna (Tachyglossus aculeatus)

The auditory function of four wild-caught echidnas was measured using distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs). Emission audiograms were constructed by finding the stimulus levels required to produce a criterion emission amplitude at a given stimulus frequency. For an emission amplitude of -10 dB SPL, the median "best threshold" was 28 dB SPL, and this minimum threshold occurred between 4 and 8 kHz for all animals. The relative effective range of auditory function was defined by the frequencies at which the audiogram was 30 dB above its best threshold. For the emission audiograms, the median lower-frequency limit was 2.3 kHz, the upper limit was 18.4 kHz, and the effective range was 2.7 octaves. The audiogram as measured by ABR was also found to be strongly "U" shaped with similar low- and high-frequency limits, i.e., from 1.6 to 13.9 kHz, with an effective range of 3.1 octaves. These results suggest that the echidna has a behavioral hearing sensitivity comparable to that of typical therian mammals (e.g., rabbits and gerbils) but with a significantly narrower frequency range. DPOAE responses were also measured in selected animals as a function of the variation of all four stimulus parameters (frequencies and intensities of both stimulus tones). Overall, the measured emission responses establish that the echidna does have a cochlear amplifier, and that it could be the same type as in therian mammals. The amplification mechanism in the echidna, currently unidentified, clearly operates to frequencies above 20 kHz, higher than the hearing function observed in any birds or reptiles but lower than for typical therian mammals. This raises the possibility that at least some aspects of the mammalian cochlear amplifier developed early in evolution, before the divergence of the monotremes (echidna and platypus) from the mainstream therian mammals (marsupials and placentals). In this respect, the presence or absence of outer hair cell electromotility in monotremes would have important consequences for understanding the function and evolution of the vertebrate inner ear.     

The surgical technique for implantation of the temporal bone stimulator (Audiant ABC)

Microsurgical techniques and modern hearing aids are very limited in providing hearing improvement to patients with a vast number of middle ear and external ear canal conditions. A new electromagnetic temporal bone stimulator (TBS), capable of direct stimulation of the cochlea, has been developed. Nothing is placed in the external ear canal. The internal portion of the device is placed in the mastoid portion of the temporal bone, thus completely bypassing the external canal, the ossicles, and the middle ear. This provides stimulation to the inner ear regardless of the condition of the external canal and the middle ear. Unilateral hearing losses may also be benefited by transfer of energy to the opposite ear. Selection of patients, the surgical technique, and the instrumental armamentarium are discussed. The pitfalls and expected results are described.     

The Conductive Hearing Loss Due to an Experimentally Induced Middle Ear Effusion Alters the Interaural Level and Time Difference Cues to Sound Location

Otitis media with effusion (OME) is a pathologic condition of the middle ear that leads to a mild to moderate conductive hearing loss as a result of fluid in the middle ear. Recurring OME in children during the first few years of life has been shown to be associated with poor detection and recognition of sounds in noisy environments, hypothesized to result due to altered sound localization cues. To explore this hypothesis, we simulated a middle ear effusion by filling the middle ear space of chinchillas with different viscosities and volumes of silicone oil to simulate varying degrees of OME. While the effects of middle ear effusions on the interaural level difference (ILD) cue to location are known, little is known about whether and how middle ear effusions affect interaural time differences (ITDs). Cochlear microphonic amplitudes and phases were measured in response to sounds delivered from several locations in azimuth before and after filling the middle ear with fluid. Significant attenuations (20–40 dB) of sound were observed when the middle ear was filled with at least 1.0 ml of fluid with a viscosity of 3.5 Poise (P) or greater. As expected, ILDs were altered by ~30 dB. Additionally, ITDs were shifted by ~600 μs for low frequency stimuli (<4 kHz) due to a delay in the transmission of sound to the inner ear. The data show that in an experimental model of OME, ILDs and ITDs are shifted in the spatial direction of the ear without the experimental effusion.     

Hearing and Age-Related Changes in the Gray Mouse Lemur

In order to examine auditory thresholds and hearing sensitivity during aging in the gray mouse lemur (Microcebus murinus), suggested to represent a model for early primate evolution and Alzheimer research, we applied brainstem-evoked response audiometry (BERA), traditionally used for screening hearing sensitivity in human babies. To assess the effect of age, we determined auditory thresholds in two age groups of adult mouse lemurs (young adults, 1–5 years; old adults, ≥7 years) using clicks and tone pips. Auditory thresholds indicated frequency sensitivity from 800 Hz to almost 50 kHz, covering the species tonal communication range with fundamentals from about 8 to 40 kHz. The frequency of best hearing at 7.9 kHz was slightly lower than that and coincided with the dominant frequencies of communication signals of a predator. Aging shifted auditory thresholds in the range between 2 and 50.4 kHz significantly by 12–27 dB. This mild presbyacusis, expressed in a drop of amplitudes of BERA signals, but not discernible in latencies of responses, suggests a metabolic age-related decrease potentially combined with an accompanying degeneration of the cochlear nerve. Our findings on hearing range of this species support the hypothesis that predation was a driving factor for the evolution of hearing in small ancestral primates. Likewise, results provide the empirical basis for future approaches trying to differentiate peripheral from central factors when studying Alzheimer’s disease-like pathologies in the aging brain.     

Representation of acoustic signals in the human cochlea in presence of a cochlear implant electrode

BACKGROUND: In subjects with remaining low frequency hearing, combined electric-acoustic stimulation (EAS) of the auditory system is a new therapeutic perspective. Intracochlear introduction of a cochlear implant electrode, however, may alter the biomechanical properties of the inner ear and thus affect perception of acoustic stimuli. STUDY DESIGN: Based on histological observations of morphologic changes after cochlear implantation in cadaveric and post mortem studies the effects of basilar membrane (BM) stiffening in the ascending basal and middle turns of the cochlea due to close contact of the BM with the electrode were simulated in a 3D-computational finite element model of the inner ear. To verify our simulated results, pre- and postoperative pure-tone audiograms of 13 subjects with substantial residual hearing, who underwent cochlear implantation, were evaluated. RESULTS: In the scenario of partial BM-fixation, acoustic energy of middle (2 kHz) and high (6 kHz) frequency was focused basally and apically to the fixed section, increasing BM displacement amplitudes up to 6 dB at a stimulation level of 94 dB (SPL). Lower frequencies were not affected by fixation in the basal and middle turn of the cochlea. In implanted subjects, a small but significant decrease of thresholds was observed at 1.5 kHz, a place in tonotopy adjacent to the tip region of the implanted electrode. CONCLUSION: Our model suggests that stiffening of the basilar membrane adjacent to an implanted electrode into the basal and middle cochlear turn did not affect BM movement in the low frequency area. Focussing of acoustic energy may increase perception in regions adjacent to the fixed section. Observations in implanted subjects were concordant with our model predictions. High frequencies, however, should not be amplified in patients using EAS to avoid disturbances in discrimination due to tonotopically incorrect frequency representation.     

An Electric Frequency-to-place Map for a Cochlear Implant Patient with Hearing in the Nonimplanted Ear

The aim of this study was to relate the pitch of high-rate electrical stimulation delivered to individual cochlear implant electrodes to electrode insertion depth and insertion angle. The patient (CH1) was able to provide pitch matches between electric and acoustic stimulation because he had auditory thresholds in his nonimplanted ear ranging between 30 and 60 dB HL over the range, 250 Hz to 8 kHz. Electrode depth and insertion angle were measured from high-resolution computed tomography (CT) scans of the patient’s temporal bones. The scans were used to create a 3D image volume reconstruction of the cochlea, which allowed visualization of electrode position within the scala. The method of limits was used to establish pitch matches between acoustic pure tones and electric stimulation (a 1,652-pps, unmodulated, pulse train). The pitch matching data demonstrated that, for insertion angles of greater than 450 degrees or greater than approximately 20 mm insertion depth, pitch saturated at approximately 420 Hz. From 20 to 15 mm insertion depth pitch estimates were about one-half octave lower than the Greenwood function. From 13 to 3 mm insertion depth the pitch estimates were approximately one octave lower than the Greenwood function. The pitch match for an electrode only 3.4 mm into the cochlea was 3,447 Hz. These data are consistent with other reports, e.g., Boëx et al. (2006), of a frequency-to-place map for the electrically stimulated cochlea in which perceived pitches for stimulation on individual electrodes are significantly lower than those predicted by the Greenwood function for stimulation at the level of the hair cell.     

Nonlinear Vibration Response Measured at Umbo and Stapes in the Rabbit Middle ear

Using laser vibrometry and a stimulation and signal analysis method based on multisines, we have measured the response and the nonlinearities in the vibration of the rabbit middle ear at the level of the umbo and the stapes. With our method, we were able to detect and quantify nonlinearities starting at sound pressure levels of 93-dB SPL. The current results show that no significant additional nonlinearity is generated as the vibration signal is passed through the middle ear chain. Nonlinearities are most prominent in the lower frequencies (125 Hz to 1 kHz), where their level is about 40 dB below the vibration response. The level of nonlinearities rises with a factor of nearly 2 as a function of sound pressure level, indicating that they may become important at very high sound pressure levels such as those used in high-power hearing aids.     

Protective effect of brain-derived neurotrophic factor against the ototoxicity of Pseudomonas aeruginosa exotoxin A

OBJECTIVE: The protective effect of brain-derived neurotrophic factor (BDNF) against the ototoxicity resulting from exposure of Pseudomonas aeruginosa exotoxin A (PaExoA) to the middle ear was analyzed. The combined effect of BDNF and N(G)-nitro-L-arginine methyl ester (L-NAME) was also investigated. MATERIAL AND METHODS: Six groups of albino rats were instilled through the tympanic membrane into the round window niche with the following solutions: saline; PaExoA; BDNF; L-NAME; PaExoA + BDNF; and PaExoA + BDNF + L-NAME. Frequency-specific (2-31.5 kHz) auditory brainstem responses were used to obtain the hearing thresholds before and 2, 5 and 15 days after instillation. RESULTS: PaExoA penetrated from the middle ear into the cochlea, causing initially mixed hearing loss, followed by persistent sensorineural hearing loss. This impairment was blocked by BDNF at 6, 8 and 10 kHz on Day 2 and at 8 kHz on Day 5. L-NAME given in combination with BDNF did not show any additional protective effect. There were no significant differences in the thickness of the round window membrane between control ears and those in each instillation group. CONCLUSION: Our results suggest that BDNF may protect against cochlear damage caused by PaExoA in the middle turns of the ear.     

Comparative Auditory Neuroscience: Understanding the Evolution and Function of Ears

Comparative auditory studies make it possible both to understand the origins of modern ears and the factors underlying the similarities and differences in their performance. After all lineages of land vertebrates had independently evolved tympanic middle ears in the early Mesozoic era, the subsequent tens of millions of years led to the hearing organ of lizards, birds, and mammals becoming larger and their upper frequency limits higher. In extant species, lizard papillae remained relatively small (<2 mm), but avian papillae attained a maximum length of 11 mm, with the highest frequencies in both groups near 12 kHz. Hearing-organ sizes in modern mammals vary more than tenfold, up to >70 mm (made possible by coiling), as do their upper frequency limits (from 12 to >200 kHz). The auditory organs of the three amniote groups differ characteristically in their cellular structure, but their hearing sensitivity and frequency selectivity within their respective hearing ranges hardly differ. In the immediate primate ancestors of humans, the cochlea became larger and lowered its upper frequency limit. Modern humans show an unusual trend in frequency selectivity as a function of frequency. It is conceivable that the frequency selectivity patterns in humans were influenced in their evolution by the development of speech.     

A temporal bone preparation for the study of cochlear micromechanics at the cellular level

An in vitro preparation of the guinea pig temporal bone was developed for studying the micromechanical behaviour of the cochlea. The preparation consists of the cochlea opened at the apex, allowing observation of cellular structures within the cochlear partition with an optical sectioning microscope and measurements of cellular vibration with laser interferometry. The middle ear ossicles and the tympanic membrane are left intact as well as the bony part of the external auditory canal, which is used for delivering a sound stimulus to the cochlea.     

Mondini dysplasia without functional impairment in the framework of a CHARGE association

A male child with fully developed CHARGE association was referred to our hospital several times because of choanal atresia and suspected hearing loss in his first two years of life. As far as they are a main symptom malformations of the ear appear frequently in CHARGE association. This report describes that an obvious anatomic dysplasia of the inner ear can have normal function, which is shown by objective measurement. METHODS AND RESULTS: Computed tomography of the petrous bone showed bilateral Mondini malformation of the cochlea combined with bulky deformation of middle ear ossicles. By the age of one year brainstem evoked response audiometry (BERA) was performed. The result demonstrated a hearing loss of 60 dB on the right ear, but no measurable hearing loss on the left ear. CONCLUSION: This case report proves that a Mondini-type malformation of the cochlea does not need to be combined with hearing loss.     

Stapes Vibration in the Chinchilla Middle Ear: Relation to Behavioral and Auditory-Nerve Thresholds

The vibratory responses to tones of the stapes and incus were measured in the middle ears of deeply anesthetized chinchillas using a wide-band acoustic-stimulus system and a laser velocimeter coupled to a microscope. With the laser beam at an angle of about 40 ° relative to the axis of stapes piston-like motion, the sensitivity-vs.-frequency curves of vibrations at the head of the stapes and the incus lenticular process were very similar to each other but larger, in the range 15–30 kHz, than the vibrations of the incus just peripheral to the pedicle. With the laser beam aligned with the axis of piston-like stapes motion, vibrations of the incus just peripheral to its pedicle were very similar to the vibrations of the lenticular process or the stapes head measured at the 40 ° angle. Thus, the pedicle prevents transmission to the stapes of components of incus vibration not aligned with the axis of stapes piston-like motion. The mean magnitude curve of stapes velocities is fairly flat over a wide frequency range, with a mean value of about 0.19 mm^.(s Pa⁻¹), has a high-frequency cutoff of 25 kHz (measured at −3 dB re the mean value), and decreases with a slope of about −60 dB/octave at higher frequencies. According to our measurements, the chinchilla middle ear transmits acoustic signals into the cochlea at frequencies exceeding both the bandwidth of responses of auditory-nerve fibers and the upper cutoff of hearing. The phase lags of stapes velocity relative to ear-canal pressure increase approximately linearly, with slopes equivalent to pure delays of about 57–76 μs.     

Inner ear structure and electrophysiological audiograms of the subterranean mole rat, Spalax ehrenbergi

Subterranean mole rats of the Spalax ehrenbergi superspecies in Israel have a distinctly developed vocal repertoire, presumably compensating together with olfaction for their complete blindness, thus providing an efficient communication system underground. Here we describe the unique organization of the cochlea of Spalax among mammals. The cochlea is subdivided into different subsystems where in the apical subsystem the fluid space and the organ of Corti differ remarkably from that in the basal subsystem, a feature as yet unknown in other mammals. The audiograms based on cochlear microphonics and on evoked potential recordings from the midbrain and brainstem, reveal a hearing range from 0.1 kHz-10 kHz with a best sensitivity between 0.5 and 1 kHz.     

Tinnitus aurium: Fact… or fancy.

We have used the 14C 2-deoxyglucose (2DG) technique to examine changes in metabolic activity in the auditory pathway of 29 guinea pigs after removal of the cochlea, removal of the middle ear ossicles, and after treatment with sodium salicylate. Three experiments were performed. In the first experiment we examined the levels of neuronal activity at 1–2 hours to 42 days after unilateral and bilateral cochlear ablations. In this series of experiments, we observed a spontaneous increase in activity which appeared at 3–14 days in brain stem regions having major connections to the ablated cochlea. In the second series, we performed unilateral and bilateral removal of the middle ear ossicles. These manipulations, in contrast to cochlear removal, caused little or no spontaneous increase on the side connected to the lesion when examined at either 1 day or 21 days. This observation suggested that the increased activity seen several days after cochlear removal was due to the process of deafferentation per se and not to the deafness which was caused by both cochlear and ossicle removals. These findings are consistent with the possibility that the spontaneous increase in metabolic activity seen after cochlear removal may be a reflection of the subjective sensation of tinnitus experienced by human beings after cochlear damage or VIIIth nerve section. In the third experimental series, we administered sodium salicylate orally to animals. All animals had unilateral ossicle removal. This experiment was designed to determine whether high levels of a salicylate, known to produce tinnitus in human beings, could elicit increased activity in those animals which would normally have experienced a conductive hearing loss and, therefore, absent neuronal activity. In the animals examined to date after salicylate administration, an increase in 2DG uptake was observed. These preliminary data are consistent with the findings seen after cochlear ablation and further suggest that increased neuronal activity may reflect a tinnituslike phenomenon in the experimental animal. We believe the findings from these three sets of experiments form the basis for development of an experimental animal model which can be used to study a profound otologic symptom about which there is yet no pathophysiological information. As such, these data represent a very important first step in developing a reasonable and successful therapeutic regimen for afflicted human beings.     

High frequency distortion product otoacoustic emissions in children with and without middle ear dysfunction

OBJECTIVE: Distortion product otoacoustic emissions (DPOAEs) (9-16kHz) are a useful measure of the function of the cochlea, which may be damaged by ototoxic drugs during anticancer chemotherapy. As children undergoing chemotherapy may also have middle ear problems, it is necessary to know if middle ear problems would have a confounding effect on the ability of DPOAEs to assess cochlear function in the extend high frequency region (9-16kHz). The present study aimed to investigate the effect of middle ear dysfunction on DPOAEs in the extended high frequency region in young children. METHODS: The sample was comprised of 100 ears of 50 school-aged children (21 boys and 29 girls) with a mean age of 6.3 years (S.D.=0.5; range 5.3-7.3). Otoscopy, pure tone hearing screening, tympanometry, acoustic reflexes and DPOAEs for both the conventional and extended high frequencies were administered to each child under typical school screening conditions. Participants were classified into one of three groups based on immittance (tympanometry and acoustic reflex) results. They included a "pass immittance" group, a "fail immittance" group and an "undetermined" group (with a pass in either tympanometry or acoustic reflexes, but not both). DPOAE amplitudes and signal-to-noise ratios (SNRs) were measured and compared across the three groups of participants. RESULTS: The fail immittance group showed significantly smaller DPOAE amplitudes and SNRs when compared to the other two groups at frequencies ranging from 1 to 9.5kHz and at 13kHz, but not at 10, 11, 12 and 14kHz. There was no significant difference in DPOAE results between the pass immittance and undetermined groups. CONCLUSIONS: Despite the adverse effects of middle ear dysfunction, its effect on DPOAEs in the extended high frequency region was not as severe as that in the lower frequency region. Hence, assessment of cochlear function in children with a middle ear lesion in the extended high frequencies using DPOAEs should be made with caution.     

Middle ear and cochlear disorders result in different DPOAE growth behaviour: implications for the differentiation of sound conductive and cochlear hearing loss

Input/output functions of distortion product otoacoustic emissions (DPOAE I/O-functions) give an insight into the compressive, non-linear sound processing of the cochlea. With an inner ear dysfunction a steeper I/O-function is observed. Due to the linear sound processing of the middle ear, one can assume that the DPOAE growth behaviour remains unaltered with a sound conduction dysfunction. If that is true, a differentiation between middle and inner ear dysfunction will be possible by using the slope of DPOAE I/O-functions as a means for assessing cochlear compression. In order to test that hypothesis, DPOAE I/O-functions were recorded in a wide primary tone level range at up to 8 f2 frequencies between 2.0 and 8.0 kHz (15 dB SPL < L2< 60 dB SPL; L1=0.46 L2 + 41 dB SPL; f2/f1=1.2) in guinea pigs in which middle (saline solution in the bulla) and inner ear (exposure to loud broadband noise) disorders were induced. Middle ear dysfunction resulted in a reduction of the DPOAE amplitude independent of the primary tone level. Consequently, DPOAE growth behaviour was not affected. In contrast to that, during cochlear impairment, steepened DPOAE I/O-functions were observed reflecting loss of compression of the cochlear amplifier. Accordingly, DPOAE I/O-functions allow a differentiation between middle and inner ear dysfunction. Further studies will have to show the usability of this method for clinical diagnostics, e.g. for detecting sound conduction disturbances in newborn hearing screening due to amniotic fluid or Eustachian tube dysfunctions during the early postnatal period.     

Acoustic overstimulation alters the morphology of the tectorial membrane

After a permanent threshold shift was induced by exposing guinea pigs to a 1 kHz pure tone at 105 dB(A) for 72 h, light microscopic observations of freshly dissected and stained tectorial membranes showed an increased waviness and clumping of the fibers of the middle zone. Hensen's stripe was not seen as a continuous dense structure running through the middle zone but was at times discontinuous and curved. As measured from cross-sections of the cochlea, the thickness of the tectorial membrane was decreased after acoustic overstimulation. The stereocilia of the inner and outer hair cells lie directly under the middle zone. Visual detection levels of threshold of tectorial membrane movement was determined by stimulating the marginal zone of the tectorial membrane of isolated cochlear coils by an oscillating water jet. After acoustic overstimulation the tectorial membrane became more compliant. The tectorial membrane abnormalities were restricted to the regions of the cochlea that demonstrated a 40–50 dB hearing loss.     

A surgical approach appropriate for targeted cochlear gene therapy in the mouse

Therapeutic manipulations of the mammalian cochlea, including cochlear gene transfer, have been predominantly studied using the guinea pig as the experimental model. With the significant developments in mouse genomics and the availability of mutant strains of mice with well-characterized hearing loss, the mouse justifiably will be the preferred animal model for therapeutic manipulations. However, the potential advantages of the mouse model have not been fully realized due to the surgical difficulty of accessing its small cochlea. This study describes a ventral approach, instead of the routinely used postauricular approach in other rodents, for accessing the mouse middle and inner ear, and its application in cochlear gene transfer. This ventral approach enabled rapid and direct delivery of liposome-transgene complex to the mouse inner ear while avoiding blood loss, facial nerve morbidity, and mortality. Transgene expression at 3 days was detected in Reissner's membrane, spiral limbus, spiral ligament, and spiral ganglion cells, in a pattern similar to that previously described in the guinea pig. The successful access and delivery of material to the mouse cochlea and the replication of gene expression seen in the guinea pig demonstrated in this study should promote the use of the mouse in future studies investigating targeted cochlear therapy.     

The organ of Corti in the bat Hipposideros bicolor

The bat Hipposideros bicolor (Hipposideridae, Microchiroptera) is the mammalian species with the highest upper limit of hearing in which the structure of the organ of Corti has been studied. H. bicolor emits pure tone echo-locating signals of 153 kHz, compensates for Doppler shifts in the echo and hears ultrasonic frequencies up to 200 kHz (Neuweiler et al., 1984). The organ of Corti was investigated qualitatively and quantitatively using the technique of semi-thin sectioning. Some complementary ultra-thin sections were also examined. Length, width and cross-sectional area of the basilar membrane, the tectorial membrane, the hair cells with their stereocilia and the organ of Corti were measured at equi-distant positions on the basilar membrane. The organ of Corti of H. bicolor is composed of elements similar to those found in the cochleae of other eutherian mammals studied. However, in H. bicolor some of these elements show species-specific differences when compared to auditorily unspecialized mammals. The most basal region of the cochlea is characterized by miniaturization and re-inforcement of macro- and micro-mechanically important elements. This is interpreted as an adaptation for hearing extremely high frequencies. Specialized structures as well as local maxima of 'normal' elements in the basal and middle cochlear region are associated with evaluation of the echos of emitted pure tones. Besides the basal specializations. Hipposideros also shows specializations in the apical, low frequency, region which can be correlated with passive acoustic orientation.