Cochlea

Mutations in the GJB2 gene are a major cause of non‐syndromic recessive hearing loss in many countries. In a significant fraction of patients, only monoallelic GJB2 mutations known to be either recessive or of unclear pathogenicity are identified. This paper reports a novel GJB2 mutation, −3438C→T, found in the basal promoter of the gene, in trans with V84M, in a patient with profound hearing impairment. This novel mutation can abolish the basal promoter activity of GJB2. These results highlight the importance of extending the mutational screening to regions outside the coding region of GJB2.

Background:The Bluetooth wireless headset has been promoted as a ‘hands-free’ device with a low emission of electromagnetic radiation.Objective:To evaluate potential changes in hearing function as a consequence of using Bluetooth devices, by assessing changes in pure tone audiography and distortion production otoacoustic emissions.Design:Prospective study.Materials and methods:Thirty adult volunteers were exposed to a Bluetooth headset device (1) on ‘standby’ setting for 6 hours and (2) at full power for 10 minutes. Post-exposure hearing was evaluated using pure tone audiography and distortion production otoacoustic emission testing.Results:There were no statistically significant changes in hearing, as measured above, following either exposure type.Conclusion:Exposure to the electromagnetic field emitted by a Bluetooth headset, as described above, did not decrease hearing thresholds or alter distortion product otoacoustic emissions.

Processing of human temporal bones is a long, expensive process and the resulting celloidin sections are difficult to use for immunohistochemistry. We tested the ability of immunohistochemical assays to work in human temporal bones that were decalcified using a microwave oven. Tissue was trimmed to an approximate cube (1.5^2 cm/side) containing only the cochlea and immersed in fresh EDTA with paraformaldehyde every 6 h. This sized block required 190^400 h to decalcify. The decalcified tissue was embedded in paraffin and sectioned. Sections were immunoassayed with anti-cytochrome c oxidase, anti-neurofilament or anti-peripherin. All three antibodies labeled the appropriate structures. This procedure may stimulate advancement in the understanding of human inner ear pathology. ß

The vertebrate inner ear has been extensively studied as a model system of morphogenesis and differentiation. The interactions between epithelium and surrounding mesenchyme have not previously been studied directly, because an appropriate experimental system had not been established. Here we describe a mesenchyme-free culture system of E11.5 mouse otic vesicle which retains the ability for (1) formation of the cochlear loop, (2) emigration of ganglion cells from the epithelium and (3) invagination of semicircular canal epithelium. E10.5 otic vesicle was maintained using the same method, but morphogenesis was less successful. Culture of the E11.5 cochlear region alone resulted in regeneration of a structure with semicircular canal character from the cut end, indicating that region-specific cell fate within the otic vesicle is not irreversibly determined at this stage. Co-culturing otic vesicle with cochleovestibular ganglion (CVG) resulted in enhanced looping or ectopic diverticulum formation of the cochlear region, suggesting that the CVG provides a morphogenetic signal for cochlear looping. Cochlear looping was specifically blocked by inhibiting actin polymerization by cytochalasin D, while morphogenesis of the semicircular canal region remained intact. Hyaluronidase treatment inhibited semicircular canal morphogenesis, resulting in a cystic form of the otic vesicle. These data validate this culture system as a tool for elucidating the mechanism of morphogenesis of the otic vesicle.

Objective: To review current concepts of the mechanical processes of the human middle ear, and to apply them to practical issues in clinical otology and tympanoplasty surgery. Background: The wide range of conductive hearing losses associated with middle ear pathology and reconstruction cannot be adequately explained by simple models of middle ear function. Methods: Variables used to describe the system are sound pressure, volume velocity, and acoustic impedance. The relationship between specific middle ear structures and these variables is described such that inferences can be drawn regarding sound conduction in the normal, diseased, and reconstructed middle ear. Results and conclusions: Sound can be transmitted from the car canal to the cochlea via two mechanisms: the tympano-ossicular system (ossicular coupling) and direct acoustic stimulation of the oval and round windows (acoustic coupling). Acoustic coupling is negligibly small in normal ears, but can play a significant role in some diseased and reconstructed ears. In the normal ear, middle ear pressure gain (which is the result of ossicular coupling) is frequency-dependent and less than generally believed. The severity of conductive hearing loss due to middle-ear disease or after tympanoplasty surgery can be predicted by the degree to which ossicular coupling, acoustic coupling, and stapescochlear input impedance are altered. Hearing after type IV and V tympanoplasty is determined solely by acoustic coupling. The difference in magnitude between the oval- and round-window pressures is more important than the difference in phase in determining cochlear input. In tympanoplasty types I, II, and III, adequate middle-ear and round-window aeration is necessary and the tympanic membrane-ossicular configuration may be less crucial.

A dry skull added with damping material was used to investigate the vibratory pattern of bone conducted sound. Three orthogonal vibration responses of the cochleae were measured, by means of miniature accelerometers, in the frequency range 0.1-10 kHz. The exciter was attached to the temporal, parietal, and frontal bones, one at the time. In the transmission response to the ipsilateral cochlea, a profound low frequency antiresonance ͑attenuation͒ was found, verified psycho-acoustically, and shown to yield a distinct lateralization effect. It was also shown that, for the ipsilateral side, the direction of excitation coincides with that of maximum response. At the contralateral cochlea, no such dominating response direction was found for frequencies above the first skull resonance. An overall higher response level was achieved, for the total energy transmission in general and specifically for the direction of excitation, at the ipsilateral cochlea when the transducer was attached to the excitation point closest to the cochlea. The transranial attenuation was found to be frequency dependent, with values from Ϫ5 to 10 dB for the energy transmission and Ϫ30 to 40 dB for measurements in a single direction, with a tendency toward higher attenuation at the higher frequencies.

Objective: The aim of this study is to quantify changes in quality of life due to the use of BAHA. Patients and method: Twenty-eight patients were included. The instrument used to quantify the change in quality of life was the Glasgow Benefit Inventory and a questionnaire including 2 open questions, BAHA use, change in tinnitus, and postoperative pain. Results: The average total benefit score with the Glasgow Benefit Inventory was 38, and the general, social, and physical score were 54, 10, and 1, respectively. There was no significant association between preoperative hearing, aetiology or type of hearing loss, and quality of life. Tinnitus rate went from 37.5% to 20.8% following BAHA; this difference is significant. Conclusions: Our results show that the use of BAHA is associated with a great improvement in quality of life. Also, they show that its use has a positive effect upon tinnitus.

Recent advances in the developmental biology, genetics and cell biology of the inner ear are guiding research to novel therapeutic modalities -a market currently estimated to be at least US$10 billion. This article highlights prospects to manipulate the mammalian hearing organ with gene and stem cell delivery to the inner ear to protect, repair or regenerate the hair cells, supporting cells and associated nerves. IUBMB Life, 58: 525-530, 2006

Simultaneous electrical stimulation of neighboring electrodes in cochlear prosthesis systems generates channel interaction. However, intermediate channels, or virtual channels between the neighboring electrodes can be created through controlled channel interaction. This effect may be exploited for sending new information to the hearing nerves by stimulating in a suitable manner. The actual stimulation sites are therefore not limited to the number of electrodes. Clinical experiments, however, show that virtual channels are not always perceived. In this paper, electrical simulation with finite element analysis on a half turn human cochlea model is adopted to model the virtual channel effect, and the conditions for generating virtual channels are discussed. Five input current ratios (100/0, 70/30, 50/50, 30/70, 0/100) are applied to generate virtual channels. Three electrode arrays parameters are taken into consideration: distance between electrode contact and modiolus, spacing between adjacent electrode contacts and scale of electrode contact size. By observing the activating function contours, the virtual channel patterns and performances can be measured and examined. The results showed that a broad excitation pattern is necessary to produce the kind of electrode interaction that can form distinct virtual channels.

A 55-year-old woman had bilateral sensorineural hearing loss (SNHL), vertigo, uveitis, and aortitis associated with Cogan's syndrome (CS). She had a history of listeria meningitis and hypertrophic cranial pachymeningitis (HCP), both of which were considered to be related to SNHL progression. She developed bilateral profound deafness within 1 year, despite medical treatment with corticosteroids and methotrexate (MTX). She underwent cochlear implantation (CI) of the left ear. Although the left and right basal turns of the cochleae were ossified, all electrodes were successfully inserted, and subsequently the inferior segment of the basal turn was drilled out. The patient did not have any postoperative complications and showed good speech perception. #

A rapid, simple and sensitive liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay was developed for the determination of dexamethasone (Dex) and dexamethasone sodium phosphate (Dex SP) in plasma and human cochlear perilymph. After proteins were precipitated with a mixture of acetonitrile and methanol, Dex, Dex SP and flumethasone, the internal standard, were resolved on a C18 column using gradient elution of 5 mM ammonium acetate and methanol. The three compounds were detected using electrospray ionisation in the positive mode. Standard curves were linear over the concentration range 0.5-500 g/L (r > 0.99), bias was <±10%, intra-and inter-day coefficients of variation (imprecision) were <10%, and the limit of quantification was 0.5 g/L for both Dex and Dex SP. The assay has been used successfully in a clinical pharmacokinetics study of Dex and Dex SP in cochlear perilymph and plasma.

Objective: The fact that vibration of the skull causes a hearing sensation has been known since the 19th century. This mode of hearing was termed hearing by bone conduction. Although there has been more than a century of research on hearing by bone conduction, its physiology is not completely understood. Lately, new insights into the physiology of hearing by bone conduction have been reported. Knowledge of the physiology, clinical aspects, and limitations of bone conduction sound is important for clinicians dealing with hearing loss and is the purpose of this review. Data Sources: The data were compiled from the published literature in the areas of clinical bone conduction hearing, bone conduction hearing aids, basic research on bone conduction physiology, and recent research on bone conduction hearing from our laboratory. Conclusion: Five factors contributing to bone conduction hearing have been identified: 1) sound radiated into the external ear canal, 2) middle ear ossicle inertia, 3) inertia of the cochlear fluids, 4) compression of the cochlear walls, and 5) pressure transmission from the cerebrospinal fluid. Of these five, inertia of the cochlear fluid seems most important. Bone conduction sound is believed to reflect the true cochlear function; however, certain conditions such as middle ear diseases can affect bone conduction sensitivity, but less than for air conduction. The bone conduction route can also be used for hearing aids; since the bone conduction route is less efficient than the air conduction route, bone conduction hearing aids are primarily used for hearing losses where air conduction hearing aids are contraindicated.

Otoacoustic emission (OAE) data recorded for tone bursts presented separately and as a two-tone burst complex, that had been reported previously . Suppression of tone burst evoked otoacoustic emissions in relation to frequency separation. Hear. Res. 148, 95-106], were re-processed using the method of adaptive approximations by matching pursuit (MP). Two types of stimuli were applied to record tone burst OAEs (TBOAEs): (a) cosine-windowed tone bursts of 5-ms duration with center frequencies of 1, 1.5, 2 and 3 kHz, (b) complex stimuli consisting of a digital addition of the 1-kHz tone burst together with either the 1.5-, 2-or 3-kHz tone burst. The MP method allowed decomposition of signals into waveforms of defined frequency, latency, time span, and amplitude. This approach provided a high time-frequency (t-f) resolution and identified patterns of resonance modes that were characteristic for TBOAEs recorded in each individual ear. Individual responses to single-tone bursts were processed off-line to form 'sum of singles' responses. The results confirmed linear superposition behavior for a frequency separation of two-tone bursts of 2 kHz (the 1-kHz and 3-kHz condition). For the 1, 1.5-kHz condition, the MP results revealed the existence of closely positioned resonance modes associated with responses recorded individually with the stimuli differing in frequency by 500 Hz. Then, the differences between t-f distributions calculated for dual (two-tone bursts) and sum-of-singles conditions exhibited mutual suppression of resonance modes common to both stimuli. The degree of attenuation depended on the individual pattern of characteristic resonance modes, i.e., suppression occurred when two resonant modes excited by both stimuli overlapped. It was postulated that the suppression observed in case of dual stimuli with closely-spaced components is due to mutual attenuation of the overlapping resonance modes.

The role of the cochlea is to transduce complex sound waves into electrical neural activity in the auditory nerve. Hair cells of the organ of Corti are the sensory cells of hearing. The inner hair cells perform the transduction and initiate the depolarization of the spiral ganglion neurons. The outer hair cells are accessory sensory cells that enhance the sensitivity and selectivity of the cochlea. Neural feedback loops that bring efferent signals to the outer hair cells assist in sharpening and amplifying the signals. The stria vascularis generates the endocochlear potential and maintains the ionic composition of the endolymph, the fluid in which the apical surface of the hair cells is bathed. The mechanical characteristics of the basilar membrane and its related structures further enhance the frequency selectivity of the auditory transduction mechanism. The tectorial membrane is an extracellular matrix, which provides mass loading on top of the organ of Corti, facilitating deflection of the stereocilia. This review deals with the structure of the normal mature mammalian cochlea and includes recent data on the molecular organization of the main cell types within the cochlea.

Those suffering from a severe to profound sensorineural hearing loss can obtain substantial benefit from a cochlear implant prosthesis. An electrode array implanted in the inner ear stimulates auditory nerve fibers by direct injection of electrical current. A major limitation of today's technology is the imprecise control of intracochlear current flow, particularly the relatively wide spread of neural excitation. A better understanding of the intracochlear electrical fields is, therefore, required. This paper analyzes the structure of intracochlear potential measurements in relation to both the subject's anatomy and to the properties of the electrode array. An electrically equivalent network is proposed, composed of small lumped circuits for the interface impedance and for the cochlear tissues. The numerical methods required to estimate the model parameters from high-quality electrical potential recordings are developed. Finally, some models are presented for subjects wearing a Clarion CII device with a HiFocus electrode and discussed in terms of model reliability.

The extraordinary fine-tuning characteristic of normal mammalian hearing is attributed to physiological mechanisms collectively known as the cochlear amplifier ͑CA͒, which amplifies and sharpens the basilar membrane ͑BM͒ vibration response to incoming acoustic pressure oscillations. Electromechanical properties of outer hair cells ͑OHCs͒ are believed to be the critical component of the CA, but its ''circuitry'' as yet remains unknown. Here, the required frequency-space response characteristics of the CA are computationally determined when typical in vivo tuning data are introduced as input to a linear hydroelastic cochlear model whose cross-sectional dynamics are represented by two coupled vibrational degrees of freedom. It is assumed that the CA senses motion at the tectorial membrane ͑TM͒ reticular lamina ͑RL͒ and applies proportional, equal, and opposite forces to the BM and the RL. The results show the CA to be tonotopically tuned, meaning it conforms to a space-frequency similarity principle like other cochlear dynamical responses. This requires that the active mechanism use information distributed along the cochlear partition. The physiological mechanism responsible for such behavior remains unknown, but here the computed CA characteristics can be qualitatively reproduced by a circuit spanning the length of the cochlea. This does not preclude other mechanisms, but is intended to motivate closer experimental investigation of extracellular and intercellular ionic flow pathways. ͓S0001-4966͑99͒00109-5͔

The tetrapod auditory system transmits sound through the outer and middle ear to the organ of Corti or other sound pressure receivers of the inner ear where specialized hair cells translate vibrations of the basilar membrane into electrical potential changes that are conducted by the spiral ganglion neurons to the auditory nuclei. In other systems, notably the vertebrate limb, a detailed connection between the evolutionary variations in adaptive morphology and the underlying alterations in the genetic basis of development has been partially elucidated. In this review, we attempt to correlate evolutionary and partially characterized molecular data into a cohesive perspective of the evolution of the mammalian organ of Corti out of the tetrapod basilar papilla. We propose a stepwise, molecularly partially characterized transformation of the ancestral, vestibular developmental program of the vertebrate ear. This review provides a framework to decipher both discrete steps in development and the evolution of unique functional adaptations of the auditory system. The combined analysis of evolution and development establishes a powerful cross-correlation where conclusions derived from either approach become more meaningful in a larger context which is not possible through exclusively evolution or development centered perspectives.

In tissues cells show coordinated properties; for example in epithelia, cells are uniformly polarized along the apical-basal axis. However, in addition to apical-basal polarity, cells in most tissues also require positional information in the plane to generate polarized structures or to move or orient themselves in a directed fashion . This type of polarization of a field of cells is referred to as planar cell polarity (PCP).

Neural excitation profile widths at the neural level, for monopolar stimulation with Nucleus straight and contour arrays respectively, were simulated using a combined volume conduction-neural model. The electrically evoked compound action potential profile widths at the electrode array level were calculated with a simple approximation method employing stimulus attenuation inside the cochlear duct, and the results compared to profile width data from literature. The objective of the article is to develop a simple method to estimate stimulus attenuation values by calculating the values that best fit the modelled excitation profile widths to the measured evoked compound action potential profile widths. Results indicate that the modelled excitation profile widths decrease with increasing stimulus attenuation.

a b s t r a c t Spiral ganglion cell (SGC) degeneration following hair cell loss can be prevented by administration of exogenous neurotrophic factors. Many of these neurotrophic factors, in particular the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), have been described to be involved in the development of the rodent cochlea. While expression of most of the neurotrophins has decreased to below detectable levels during adulthood (only NT-3 remains highly expressed), their respective receptors remain present in SGCs. Indeed much less is known about the function of neurotrophins in the mature cochlea. Such knowledge is crucial in the search for tools to improve SGC survival following cochlear implantation. In this review, we will critically regard the current experimental findings of neurotrophic treatment of the SGCs in the perspective of fundamental cellular mechanisms underlying neurotrophin signaling. We conclude that, in order to fully apprehend the effects of neurotrophic treatment of degenerating SGCs and in order to consider clinical application of neurotrophins, future research should focus (a) on characterizing the expression pattern of neurotrophins in the cochlea after deafening, (b) on more detailed characterization of functional and morphological changes of SGCs associated with both deafening and neurotrophic treatment and (c) on the possible self-supporting state of SGCs after cessation of short-term neurotrophic treatment.

A processing scheme for speech signals is proposed that emulates synchrony capture in the auditory nerve. The role of stimulus-locked spike timing is important for representation of stimulus periodicity, low frequency spectrum, and spatial location. In synchrony capture, dominant single frequency components in each frequency region impress their time structures on temporal firing patterns of auditory nerve fibers with nearby characteristic frequencies (CFs). At low frequencies, for voiced sounds, synchrony capture divides the nerve into discrete CF territories associated with individual harmonics. An adaptive, synchrony capture filterbank (SCFB) consisting of a fixed array of traditional, passive linear (gammatone) filters cascaded with a bank of adaptively tunable, bandpass filter triplets is proposed. Differences in triplet output envelopes steer triplet center frequencies via voltage controlled oscillators (VCOs). The SCFB exhibits some cochlea-like responses, such as two-tone suppression and distortion products, and possesses many desirable properties for processing speech, music, and natural sounds. Strong signal components dominate relatively greater numbers of filter channels, thereby yielding robust encodings of relative component intensities. The VCOs precisely lock onto harmonics most important for formant tracking, pitch perception, and sound separation.

Outer (OHC) and inner (IHC) hair cells in the organ of Corti of the mammalian cochlea process sound. OHC and their efferent synapse are part of a feedback system assumed to control and modulate information carried by afferent neurons passing from IHC to the brain. Underlying mechanisms are not well understood. This paper discusses recent progress. In vivo and in vitro information is presented on structure, pharmacology, function and localization of the pre- and postsynaptic acetylcholine receptors (AChRs) at the efferent synapse. Recent data are given on a presynaptic M3 AChR subtype, probably an autoreceptor involved in transmitter release. Data from our lab on specific binding of [3H]3-quinuclidinyl benzilate ([3H]3-QNB) to non-enzymatically isolated guinea pig OHC reveal a KD several 100 x higher than that for any known muscarinic receptor subtype, including the above-mentioned presynaptic muscarinic AChR of the OHC efferent synapse. The extremely high concentrations of [3H]3-QNB needed for any binding at all to OHC thus rule out presynaptic membrane impurities as the cause of such binding, and also the presence of a typical mAChR subtype on OHC. The number of [3H]3-QNB binding sites (∼ 106/OHC) we found on OHC was of that we found for binding of nicotinic ligands to OHC, further making it questionable that an ACh-binding site on OHC binds [3H]3-QNB. Observations may instead point to the possibility of another binding site, e.g. an (allosteric) site involved with the as yet not understood ‘weak’ muscarinic properties of the OHC AChR. Further new data on the OHC AChR confirm reversible α-bungarotoxin, nicotine and d-tubocurarine binding. [3H]α-Bungarotoxin and [3H]-nicotine binding sites are estimated at ∼6 · 107 sites/OHC. Strychnine, a glycine receptor blocker suggested to interfere with cholinergic sites of the efferent OHC synapse, was found to bind to OHC (cold strychnine for unspecific binding). This binding, not seen in the presence of high [glycine], increased in the presence of depolarizing [K+], while ACh (100 μM) had no significant effect. Results suggest strychnine binding to the outside of OHC, but also to sites accessible only after cell depolarization, possibly to the hyperpolarizing Ca2+-dependent K+ channel. Recent molecular cloning of the OHC AChR indicates a novel α-subunit. An often observed ACh-activated Ca2+-influx close to zero into OHC leaves an unanswered question. OHC also carry P2-purinergic receptors (P2Rs), a more rapid ionotropic P2zR-like subtype and a quantitatively dominating slow metabotropic P2yR subtype coupled to a G protein-phospholipase C cascade and not desensitized. Both contribute to increased cytoplasmic [Ca2+], from respectively external and internal sources. Whether or not such receptors are part of efferent synaptic activity is unknown; their localization on the OHC plasma membrane is so far only indirect and synaptic vesicles of the efferent nerve endings have not yet been analyzed for their ATP content. Localization, function and interaction of [Ca2+] increases triggered by, respectively, ATP and ACh are currently studied in this laboratory.

Cochlear implants electrically stimulate residual spiral ganglion neurons (SGNs) to provide auditory cues for the severe-profoundly deaf. However, SGNs gradually degenerate following cochlear hair cell loss, leaving fewer neurons available for stimulation. Providing an exogenous supply of neurotrophins (NTs) has been shown to prevent SGN degeneration, and when combined with chronic intracochlear electrical stimulation (ES) following a short period of deafness (5 days), may also promote the formation of new neurons. The present study assessed the histopathological response of guinea pig cochleae treated with NTs (brain-derived neurotrophic factor and neurotrophin-3) with and without ES over a four week period, initiated two-weeks after deafening. Results were compared to both NT alone and artificial perilymph (AP) treated animals. AP/ES treated animals exhibited no evidence of SGN rescue compared with untreated deafened controls. In contrast, NT administration showed a significant SGN rescue effect in the lower and middle cochlear turns (two-way ANOVA, p < 0.05) compared with AP-treated control animals. ES in combination with NT did not enhance SGN survival compared with NT alone. SGN function was assessed by measuring electrically-evoked auditory brainstem response (EABR) thresholds. EABR thresholds following NT treatment were significantly lower than animals treated with AP (two-way ANOVA, p = 0.033). Finally, the potential for induced neurogenesis following the combined treatment was investigated using a marker of DNA synthesis. However, no evidence of neurogenesis was observed in the SGN population. The results indicate that chronic NT delivery to the cochlea may be beneficial to cochlear implant patients by increasing the number of viable SGNs and decreasing activation thresholds compared to chronic ES alone.

Brief tones of 1.0 and 8.0 kHz were used to evoke auditory brainstem responses (ABRs), and the differences between the wave-V latencies for those two frequencies were used as a proxy for cochlear length. The tone bursts (8 ms in duration including 2-ms rise/fall times, and 82 dB in level) were, or were not, accompanied by a continuous, moderately intense noise band, highpass filtered immediately above the tone. The proxy values for length were compared with various measures of otoacoustic emissions (OAEs) obtained from the same ears. All the correlations were low, suggesting that cochlear length, as measured by this proxy at least, is not strongly related to the various group and individual differences that exist in OAEs. Female latencies did not differ across the menstrual cycle, and the proxy length measure exhibited no sex difference (either for menses females vs. males or midluteal females vs. males) when the highpass noises were used. However, when the subjects were partitioned into Whites and Non-Whites, a substantial sex difference in cochlear length did emerge for the White group, although the correlations with OAEs remained low. Head size was not highly correlated with any of the ABR measures.

The design of contemporary multichannel cochlear implants is predicated on the presumption that they activate multiple independent sectors of the auditory nerve array. The independence of these channels, however, is limited by the spread of activation from each intracochlear electrode across the auditory nerve array. In this study, we evaluated factors that influence intracochlear spread of activation using two types of intracochlear electrodes: (1) a clinical-type device consisting of a linear series of ring contacts positioned along a silicon elastomer carrier, and (2) a pair of visually placed (VP) ball electrodes that could be positioned independently relative to particular intracochlear structures, e.g., the spiral ganglion. Activation spread was estimated by recording multineuronal evoked activity along the cochleotopic axis of the central nucleus of the inferior colliculus (ICC). This activity was recorded using silicon-based singleshank, 16-site recording probes, which were fixed within the ICC at a depth defined by responses to acoustic tones. After deafening, electric stimuli consisting of single biphasic electric pulses were presented with each electrode type in various stimulation configurations (monopolar, bipolar, tripolar) and/or various electrode orientations (radial, off-radial, longitudinal). The results indicate that monopolar (MP) stimulation with either electrode type produced widepread excitation across the ICC. Bipolar (BP) stimulation with banded pairs of electrodes oriented longitudinally produced activation that was somewhat less broad than MP stimulation, and tripolar (TP) stimulation produced activation that was more restricted than MP or BP stimulation. Bipolar stimulation with radially oriented pairs of VP ball electrodes produced the most restricted activation. The activity patterns evoked by radial VP balls were comparable to those produced by pure tones in normal-hearing animals. Variations in distance between radially oriented VP balls had little effect on activation spread, although increases in interelectrode spacing tended to reduce thresholds. Bipolar stimulation with longitudinally oriented VP electrodes produced broad activation that tended to broaden as the separation between electrodes increased.

Some published cochlear filterbanks are nonlinear but are fitted to animal basilar membrane ͑BM͒ responses. Others, like the gammatone, are based on human psychophysical data, but are linear. In this article, a human nonlinear filterbank is constructed by adapting a computational model of animal BM physiology to simulate human BM nonlinearity as measured by psychophysical pulsation-threshold experiments. The approach is based on a dual-resonance nonlinear type of filter whose basic structure was modeled using animal observations. In modeling the pulsation threshold data, the main assumption is that pulsation threshold occurs when the signal and the masker produce comparable excitation, that is the same filter output, at the place of the BM best tuned to the signal frequency. The filter is fitted at a discrete number of best frequencies ͑BFs͒ for which psychophysical data are available for a single listener and for an average response of six listeners. The filterbank is then created by linear regression of the resulting parameters to intermediate BFs.

The design of contemporary multichannel cochlear implants is predicated on the presumption that they activate multiple independent sectors of the auditory nerve array. The independence of these channels, however, is limited by the spread of activation from each intracochlear electrode across the auditory nerve array. In this study, we evaluated factors that influence intracochlear spread of activation using two types of intracochlear electrodes: (1) a clinical-type device consisting of a linear series of ring contacts positioned along a silicon elastomer carrier, and (2) a pair of visually placed (VP) ball electrodes that could be positioned independently relative to particular intracochlear structures, e.g., the spiral ganglion. Activation spread was estimated by recording multineuronal evoked activity along the cochleotopic axis of the central nucleus of the inferior colliculus (ICC). This activity was recorded using silicon-based singleshank, 16-site recording probes, which were fixed within the ICC at a depth defined by responses to acoustic tones. After deafening, electric stimuli consisting of single biphasic electric pulses were presented with each electrode type in various stimulation configurations (monopolar, bipolar, tripolar) and/or various electrode orientations (radial, off-radial, longitudinal). The results indicate that monopolar (MP) stimulation with either electrode type produced widepread excitation across the ICC. Bipolar (BP) stimulation with banded pairs of electrodes oriented longitudinally produced activation that was somewhat less broad than MP stimulation, and tripolar (TP) stimulation produced activation that was more restricted than MP or BP stimulation. Bipolar stimulation with radially oriented pairs of VP ball electrodes produced the most restricted activation. The activity patterns evoked by radial VP balls were comparable to those produced by pure tones in normal-hearing animals. Variations in distance between radially oriented VP balls had little effect on activation spread, although increases in interelectrode spacing tended to reduce thresholds. Bipolar stimulation with longitudinally oriented VP electrodes produced broad activation that tended to broaden as the separation between electrodes increased.

Slitrks are type I transmembrane proteins that share conserved leucine-rich repeat domains similar to those in the secreted axonal guidance molecule Slit. They also show similarities to Ntrk neurotrophin receptors in their carboxy-termini, sharing a conserved tyrosine residue. Among 6 Slitrk family genes in mammals, Slitrk6 has a unique expression pattern, with strong expression in the sensory epithelia of the inner ear. We generated Slitrk6-knockout mice and investigated the development of their auditory and vestibular sensory organs. Slitrk6-deficient mice showed pronounced reduction in the cochlear innervation. In the vestibule, the innervation to the posterior crista was often lost, reduced, or sometimes misguided. These defects were accompanied by the loss of neurons in the spiral and vestibular ganglia. Cochlear sensory epithelia from Slitrk6-knockout mice have reduced ability in promoting neurite outgrowth of spiral ganglion neurons. Indeed the Slitrk6deficient inner ear showed a mild but significant decrease in the expression of Bdnf and Ntf3, both of which are essential for the innervation and survival of sensory neurons. In addition, the expression of Ntrk receptors, including their phosphorylated forms was decreased in Slitrk6-knockout cochlea. These results suggest that Slitrk6 promotes innervation and survival of inner ear sensory neurons by regulating the expression of trophic and/or tropic factors including neurotrophins from sensory epithelia.

A major factor associated with recent improvements in the clinical performance of cochlear implant patients has been the development of speech-processing strategies based on high stimulation rates. While these processing strategies show clear clinical advantage, we know little of their long-term safety implications. The present study was designed to evaluate the physiological and histopathological effects of long-term intracochlear electrical stimulation using these high rates. Thirteen normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods of up to 2100 h using either two pairs of bipolar or three monopolar stimulating electrodes. Stimuli consisted of short duration (25-50 JlS/phase) charge-balanced biphasic current pulses presented at 1000 pulses per second (pps) per channel for monopolar stimulation, and 2000 pps/channel for bipolar stimulation. The electrodes were shorted between current pulses to minimize any residual direct current, and the pulse trains were presented using a 50% duty cycle (500 ms on; 500 ms off) in order to simulate speech. Both acoustic (ABR) and electrical (EABR) auditory brainstem responses were recorded periodically during the chronic stimulation program. All cochleas showed an increase in the click-evoked ABR threshold following implant surgery; however, recovery to near-normal levels occurred in approximately half of the stimulated cochleas 1 month post-operatively. The use of frequency-specific stimuli indicated that the most extensive hearing loss generally occurred in the high-frequency basal region of the cochlea (12 and 24 kHz) adjacent to the stimulating electrode. However, thresholds at lower frequencies (2, 4 and 8 kHz), appeared at near-normal levels despite long-term electrode implantation and electrical stimulation. Our longitudinal EABR results showed a statistically significant increase in threshold in nearly 40% of the chronically stimulated electrodes evaluated; however, the gradient of the EABR input/output (I/0) function (evoked potential response amplitude versus stimulus current) generally remained quite stable throughout the chronic stimulation period. Histopathological examination of the cochleas showed no statistically significant difference in ganglion cell densities between cochleas using monopolar and bipolar electrode configurations (P = 0.67), and no evidence of cochlear damage caused by high-rate electrical stimulation when compared with control cochleas. Indeed, there was no statistically significant relationship between spiral ganglion cell density and electrical stimulation (P = 0.459), or between the extent of loss of inner (IHC, P = 0.86) or outer (OHC, P = 0.30) hair cells and electrical stimulation. Spiral ganglion cell loss was, however, influenced by the degree of inflammation (P=O.Ol6) and electrode insertion trauma. These histopathological findings were consistent with the physiological data. Finally, electrode impedance, measured at completion of the chronic stimulation program, showed close correlation with the degree of tissue response adjacent to the electrode array. These results indicated that chronic intracochlear electrical stimulation, using carefully controlled charge-balanced biphasic current pulses at stimulus rates of up to 2000 pps/channel, does not appear to adversely affect residual auditory nerve elements or the cochlea in general. This study provides an important basis for the safe application of improved speech-processing strategies based on high-rate electrical stimulation.

The objective was to asses the feasibility of the endoscopic technique for cochlear implant (CI) positioning avoiding mastoidectomy and to discuss the benefits and drawbacks of the technique. The study design is a surgical procedure description and prospective case series report. From December 2011 to October 2012, six patients underwent endoscopic CI. All cases were selected based on CT and MRI studies. All surgical steps were analyzed; intra-and post-operative complications were noted. The length of time for each surgical procedure was recorded. The surgical procedure was described step by step focusing on the anatomy of the round window (RW) niche, analyzing the critical point during the dissection. The timing of the surgical procedures was 120 ± 21 (mean ± SD) min. In 1/6 patients, intra-operative injury of the chorda tympani occurred. In all cases, an endoscopic identification was performed and the anatomical details of the RW niche were noted. In 6/6 cases, a RW niche magnification was performed endoscopically. 5/6 cases showed a normal conformation of the RW. In 1/6 patients, obliteration of the RW niche was found. In 4/6 patients, an endoscopic cochleostomy through the RW was performed. In 1/6 patients, a difficult insertion of the array was observed. The current follow-up is 7.3 months (SD ± 3.7). No postoperative short-or long-term complications were noted in this series. Endoscopic CI is a safe and viable technique with a low rate of complications and with good outcomes.

Objectives: 1) To describe the hearing status of the at-risk infants in the National Institutes of Health-Identification of Neonatal Hearing Impairment study sample at 8 to 12 mo corrected age (chronologic age adjusted for prematurity). 2) To describe the visual reinforcement audiometry (VRA) protocol that was used to obtain monaural behavioral data for the sample.

Objectives/Hypothesis: Middle and external ear anomalies are well recognized in Down syndrome (DS, trisomy 21). Inner ear anomalies are much less frequently described. This study reviews inner ear morphology on imaging to determine the prevalence of cochlear and vestibular anomalies in children with DS. Study Design: The authors conducted a retrospective review of imaging features of (DS) inner ear structures. Methods: Fifty-nine sequential patients with DS with imaging of the inner ear were identified by a radiology report text search program. Quantitative biometric assessment of the inner ear was performed on patients with high-resolution computed tomography or magnetic resonance images of the petrous bone. Petrous imaging was performed for evaluation of inflammatory disease or hearing loss. Spinal imaging, which included petrous views, was performed in most cases to exclude C1 to 2 dislocation, a potential complication of DS. Measurements were compared with normative data. Results: Inner ear dysplasia is much more common in DS than previously reported. Inner ear structures are universally hypoplastic. Vestibular malformations are particularly common and a small bony island of the lateral semicircular canal (<3 mm in diameter) appears highly typical. Additional findings in some patients were persistent lateral semicircular anlage with fusion of the lateral semicircular canal and vestibule into a single cavity, vestibular aqueduct and endolymphatic sac fossa enlargement, cochlear nerve canal hypoplasia, and stenosis or duplication of the internal auditory canal. Stenosis of the external meatus, poor mastoid pneumatization, middle ear and mastoid opacification, and cholesteatoma were common, as expected. Key Words: Down syndrome, trisomy 21, inner ear dysplasia, temporal bone CT.

Hopf-type nonlinearities have been recently found to be the basic mechanism of the mammalian cochlear response. Physiology requires that these nonlinearities be coupled. By suitably implementing a biomorphic coupling scheme of cochlear nonlinearities, we obtain a simple cochlea model that faithfully reproduces measured basilar membrane response, validating the utility of the Hopf amplifier concept. Our results demonstrate that the correct coupling between nonlinearities is as important as the nonlinearities themselves.

Pneumolabyrinth due to late complications of stapes surgery is a rare entity. Symptoms may include various degrees of hearing loss, tinnitus and dizziness. We report the case of a 67-year-old patient who developed a unique pneumolabyrinth variant affecting the vestibule, cochlea and semicircular canals 28 years after stapedectomy. The patient presented with intractable paroxysmal positional vertigo of the lateral semicircular canal. The pneumolabyrinth was visualized by means of high resolution computed tomography. Exploratory tympanotomy findings were consistent with a perilymphatic fistula. One year after surgical treatment the subject was free of vertigo spells. Pathogenetic mechanisms are discussed. #

Objective: Otoacoustic emissions and the speech-evoked auditory brainstem response are objective indices of peripheral auditory physiology that are used clinically for assessing hearing function. While each measure has been extensively explored, their interdependence and the relationships between them remain relatively unexplored. Methods: Distortion product otoacoustic emissions (DPOAEs) and speech-evoked auditory brainstem responses (sABRs) were recorded from 28 normal-hearing adults. Through correlational analyses, DPOAE characteristics were compared to measures of sABR timing and frequency encoding. Data were organized into two DPOAE (Strength and Structure) and five brainstem (Onset, Spectrotemporal, Harmonics, Envelope Boundary, and Pitch) composite measures. Results: DPOAE Strength shows significant relationships with sABR Spectrotemporal and Harmonics measures. DPOAE Structure shows significant relationships with sABR Envelope Boundary. Neither DPOAE Strength nor Structure is related to sABR Pitch. Conclusions: The results of the present study show that certain aspects of the speech-evoked auditory brainstem responses are related to, or covary with, cochlear function as measured by distortion product otoacoustic emissions. Significance: These results form a foundation for future work in clinical populations. Analyzing cochlear and brainstem function in parallel in different clinical populations will provide a more sensitive clinical battery for identifying the locus of different disorders (e.g., language based learning impairments, hearing impairment).

Using conformal mapping, fluid motion inside the cochlear duct is derived from fluid motion in an infinite half plane. The cochlear duct is represented by a two-dimensional half-open box. Motion of the cochlear fluid creates a force acting on the cochlear partition, modeled by damped oscillators. The resulting equation is one-dimensional, more realistic, and can be handled more easily than existing ones derived by the method of images, making it useful for fast computations of physically plausible cochlear responses. Solving the equation of motion numerically, its ability to reproduce the essential features of cochlear partition motion is demonstrated. Because fluid coupling can be changed independently of any other physical parameter in this model, it allows the significance of hydrodynamic coupling of the cochlear partition to itself to be quantitatively studied. For the model parameters chosen, as hydrodynamic coupling is increased, the simple resonant frequency response becomes increasingly asymmetric. The stronger the hydrodynamic coupling is, the slower the velocity of the resulting traveling wave at the low frequency side is. The model's simplicity and straightforward mathematics make it useful for evaluating more complicated models and for education in hydrodynamics and biophysics of hearing.

Electronic mail: [email protected] (2004) investigated the effects of ITD ENV manipulation (the ITD FS was random and uncontrolled) in electric hearing by presenting acoustic stimuli via unsynchronized speech processors. They showed that JNDs differed between NH subjects (19 µs) and CI listeners (259 µs and 384 µs, best JNDs for CI listener S2 and S1, respectively) and depended on the type of stimulus (lowest for click trains, highest for speech or noise bursts).