Intracochlear Scala Media Pressure Measurement: Implications for Models of Cochlear Mechanics.

Models of the active cochlea build upon the underlying passive mechanics. Passive cochlear mechanics is based on physical and geometrical properties of the cochlea and the fluid-tissue interaction between the cochlear partition and the surrounding fluid. Although the fluid-tissue interaction between the basilar membrane and the fluid in scala tympani (ST) has been explored in both active and passive cochleae, there was no experimental data on the fluid-tissue interaction on the scala media (SM) side of the partition. To this aim, we measured sound-evoked intracochlear pressure in SM close to the partition using micropressure sensors. All the SM pressure data are from passive cochleae, likely because the SM cochleostomy led to loss of endocochlear potential. Thus, these experiments are studies of passive cochlear mechanics. SM pressure close to the tissue showed a pattern of peaks and notches, which could be explained as an interaction between fast and slow (i.e., traveling wave) pressure modes. In several animals SM and ST pressure were measured in the same cochlea. Similar to previous studies, ST-pressure was dominated by a slow, traveling wave mode at stimulus frequencies in the vicinity of the best frequency of the measurement location, and by a fast mode above best frequency. Antisymmetric pressure between SM and ST supported the classic single-partition cochlear models, or a dual-partition model with tight coupling between partitions. From the SM and ST pressure we calculated slow and fast modes, and from active ST pressure we extrapolated the passive findings to the active case. The passive slow mode estimated from SM and ST data was low-pass in nature, as predicted by cochlear models.

Fabrication and evaluation of an improved polymer-based cochlear electrode array for atraumatic insertion.

An atraumatic cochlear electrode array has become indispensable to high-performance cochlear implants such as electric acoustic stimulation (EAS), wherein the preservation of residual hearing is significant. For an atraumatic implantation, we propose and demonstrate a new improved design of a cochlear electrode array based on liquid crystal polymer (LCP), which can be fabricated by precise batch processes and a thermal lamination process, in contrast to conventional wire-based cochlear electrode arrays. Using a thin-film process of LCP-film-mounted silicon wafer and thermal press lamination, we devise a multi-layered structure with variable layers of LCP films to achieve a sufficient degree of basal rigidity and a flexible tip. A peripheral blind via and self-aligned silicone elastomer molding process can reduce the width of the array. Measuring the insertion and extraction forces in a human scala tympani model, we investigate five human temporal bone insertion trials and record electrically evoked auditory brainstem responses (EABR) acutely in a guinea pig model. The diameters of the finalized electrode arrays are 0.3 mm (tip) and 0.75 mm (base). The insertion force with a displacement of 8 mm from a round window and the maximum extraction force are 2.4 mN and 34.0 mN, respectively. The electrode arrays can be inserted from 360° to 630° without trauma at the basal turn. The EABR data confirm the efficacy of the array. A new design of LCP-based cochlear electrode array for atraumatic implantation is fabricated. Verification indicates that foretells the development of an atraumatic cochlear electrode array and clinical implant.

Acoustic stimulation of the human round window by laser-induced nonlinear optoacoustics.

The feasibility of low frequency pure tone generation in the inner ear by laser-induced nonlinear optoacoustic effect at the round window was demonstrated in three human cadaveric temporal bones (TB) using an integral pulse density modulation (IPDM). Nanosecond laser pulses with a wavelength in the near-infrared (NIR) region were delivered to the round window niche by an optical fiber with two spherical lenses glued to the end and a viscous gel at the site of the laser focus. Using IPDM, acoustic tones with frequencies between 20 Hz and 1 kHz were generated in the inner ear. The sound pressures in scala tympani and vestibuli were recorded and the intracochlear pressure difference (ICPD) was used to calculate the equivalent sound pressure level (eq. dB SPL) as an equivalent for perceived loudness. The results demonstrate that the optoacoustic effect produced sound pressure levels ranging from 140 eq. dB SPL at low frequencies ≤ 200 Hz to 90 eq. dB SPL at 1 kHz. Therefore, the produced sound pressure level is potentially sufficient for patients requiring acoustic low frequency stimulation. Hence, the presented method offers a potentially viable solution in the future to provide the acoustic stimulus component in combined electro-acoustic stimulation with a cochlear implant.

Auditory nerve fiber excitability for alternative electrode placement in the obstructed human cochlea: electrode insertion in scala vestibuli versus scala tympani.

Objective. The cochlear implant (CI) belongs to the most successful neuro-prostheses. Traditionally, the stimulating electrode arrays are inserted into the scala tympani (ST), the lower cochlear cavity, which enables simple surgical access. However, often deep insertion is blocked, e.g. by ossification, and the auditory nerve fibers (ANFs) of lower frequency regions cannot be stimulated causing severe restrictions in speech understanding. As an alternative, the CI can be inserted into the scala vestibuli (SV), the other upper cochlear cavity.Approach. In this computational study, the excitability of 25 ANFs are compared for stimulation with ST and SV implants. We employed a 3-dimensional realistic human cochlear model with lateral wall electrodes based on aµ-CT dataset and manually traced fibers. A finite element approach in combination with a compartment model of a spiral ganglion cell was used to simulate monophasic stimulation with anodic (ANO) and cathodic (CAT) pulses of 50µs.Main results. ANO thresholds are lower in ST (mean/std =µ/σ= 189/55µA) stimulation compared to SV (µ/σ= 323/119µA) stimulation. Contrary, CAT thresholds are higher for the ST array (µ/σ= 165/42µA) compared to the SV array (µ/σ= 122/46µA). The threshold amplitude depends on the specific fiber-electrode spatial relationship, such as lateral distance from the cochlear axis, the angle between electrode and target ANF, and the curvature of the peripheral process. For CAT stimulation the SV electrodes show a higher selectivity leading to less cross-stimulation of additional fibers from different cochlear areas.Significance. We present a first simulation study with a human cochlear model that investigates an additional CI placement into the SV and its impact on the excitation behavior. Results predict comparable outcomes to ST electrodes which confirms that SV implantation might be an alternative for patients with a highly obstructed ST.

The impact of round window reinforcement on middle and inner ear mechanics with air and bone conduction stimulation.

The round window (RW) membrane plays an important role in normal inner ear mechanics. Occlusion or reinforcement of the RW has been described in the context of congenital anomalies or after cochlear implantation and is applied as a surgical treatment for hyperacusis. Multiple lumped and finite element models predict a low-frequency hearing loss with air conduction of up to 20 dB after RW reinforcement and limited to no effect on hearing with bone conduction stimulation. Experimental verification of these results, however, remains limited. Here, we present an experimental study measuring the impact of RW reinforcement on the middle and inner ear mechanics with air and bone conduction stimulation. In a within-specimen repeated measures design with human cadaveric specimens (n = 6), we compared the intracochlear pressures in scala vestibuli (PSV) and scala tympani (PST) before and after RW reinforcement with soft tissue, cartilage, and bone cement. The differential pressure (PDIFF) across the basilar membrane - known to be closely related to the hearing sensation - was calculated as the complex difference between PSV and PST. With air conduction stimulation, both PSV and PSTincreased on average up to 22 dB at frequencies below 1500 Hz with larger effect sizes for PST compared to PSV. The PDIFF, in contrast, decreased up to 11 dB at frequencies between 700 and 800 Hz after reinforcement with bone cement. With bone conduction, the average within-specimen effects were less than 5 dB for either PSV, PST, or PDIFF. The inter-specimen variability with bone conduction, however, was considerably larger than with air conduction. This experimental study shows that RW reinforcement impacts air conduction stimulation at low frequencies. Bone conduction stimulation seems to be largely unaffected. From a clinical point of view, these results support the hypothesis that delayed loss of air conduction hearing after cochlear implantation could be partially explained by the impact of RW reinforcement.

The mechanism underlying maintenance of the endocochlear potential by the K+ transport system in fibrocytes of the inner ear.

The endocochlear potential (EP) of +80 mV in the scala media, which is indispensable for audition, is controlled by K+ transport across the lateral cochlear wall. This wall includes two epithelial barriers, the syncytium and the marginal cells. The former contains multiple cell types, such as fibrocytes, which are exposed to perilymph on their basolateral surfaces. The apical surfaces of the marginal cells face endolymph. Between the two barriers lies the intrastrial space (IS), an extracellular space with a low K+ concentration ([K+]) and a potential similar to the EP. This intrastrial potential (ISP) dominates the EP and represents the sum of the diffusion potential elicited by a large K+ gradient across the apical surface of the syncytium and the syncytium's potential, which is slightly positive relative to perilymph. Although a K+ transport system in fibrocytes seems to contribute to the EP, the mechanism remains uncertain. We examined the electrochemical properties of the lateral wall of guinea pigs with electrodes sensitive to potential and K+ while perfusing into the perilymph of the scala tympani blockers of Na+,K+-ATPase, the K+ pump thought to be essential to the system. Inhibiting Na+,K+-ATPase barely affected [K+] in the IS but greatly decreased [K+] within the syncytium, reducing the K+ gradient across its apical surface. The treatment hyperpolarized the syncytium only moderately. Consequently, both the ISP and the EP declined. Fibrocytes evidently use the Na+,K+-ATPase to achieve local K+ transport, maintaining the syncytium's high [K+] that is crucial for the K+ diffusion underlying the positive ISP.

Inner-ear sound pressures near the base of the cochlea in chinchilla: further investigation.

The middle-ear pressure gain GMEP, the ratio of sound pressure in the cochlear vestibule PV to sound pressure at the tympanic membrane PTM, is a descriptor of middle-ear sound transfer and the cochlear input for a given stimulus in the ear canal. GMEP and the cochlear partition differential pressure near the cochlear base ΔPCP, which determines the stimulus for cochlear partition motion and has been linked to hearing ability, were computed from simultaneous measurements of PV, PTM, and the sound pressure in scala tympani near the round window PST in chinchilla. GMEP magnitude was approximately 30 dB between 0.1 and 10 kHz and decreased sharply above 20 kHz, which is not consistent with an ideal transformer or a lossless transmission line. The GMEP phase was consistent with a roughly 50-µs delay between PV and PTM. GMEP was little affected by the inner-ear modifications necessary to measure PST. GMEP is a good predictor of ΔPCP at low and moderate frequencies where PV >> PST but overestimates ΔPCP above a few kilohertz where PV ≈ PST. The ratio of PST to PV provides insight into the distribution of sound pressure within the cochlear scalae.

Cochlear implant insertion forces in microdissected human cochlea to evaluate a prototype array.

Cochlear implant array insertion forces are potentially related to cochlear trauma. We compared these forces between a standard (Digisonic SP; Neurelec, Vallauris, France) and an array prototype (Neurelec) with a smaller diameter. The arrays were inserted by a mechatronic tool in 23 dissected human cochlea specimens exposing the basilar membrane. The array progression under the basilar membrane was filmed together with dynamic force measurements. Insertion force profiles and depth of insertion were compared. The recordings showed lower insertion forces beyond 270° of insertion and deeper insertions with the thin prototype array. This will potentially allow larger cochlear coverage with less trauma.

Functional roles of high-affinity glutamate transporters in cochlear afferent synaptic transmission in the mouse.

In the cochlea, afferent transmission between inner hair cells and auditory neurons is mediated by glutamate receptors. Glutamate transporters located near the synapse and in spiral ganglion neurons are thought to maintain low synaptic levels of glutamate. We analyzed three glutamate transporter blockers for their ability to alter the effects of glutamate, exogenously applied to the synapse via perfusion of the scala tympani of the mouse, and compared that action to their ability to alter the effects of intense acoustic stimulation. Threo-beta-benzyloxyaspartate (TBOA) is a broad-spectrum glutamate transporter antagonist, affecting all three transporters [glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT1), and excitatory amino acid carrier 1 (EAAC1)]. l-serine-O-sulfate (SOS) blocks both GLAST and EAAC1 without effect on GLT1. Dihydrokainate (DHK) is selective for GLT1. Infusion of glutamate (10 microM for 220 min), TBOA (200 microM for 220 min), or SOS (100 microM for 180 min) alone did not alter auditory neural thresholds. When infused together with glutamate, TBOA and SOS produced significant neural threshold shifts, leaving otoacoustic emissions intact. In addition, both TBOA and SOS exacerbated noise-induced hearing loss by producing larger neural threshold shifts and delaying recovery. DHK did not alter glutamate- or noise-induced hearing loss. The evidence points to a major role for GLAST, both in protecting the synapse from exposure to excess extracellular glutamate and in attenuating hearing loss due to acoustic overstimulation.

Bone-conduction hyperacusis induced by superior canal dehiscence in human: the underlying mechanism.

Our ability to hear through bone conduction (BC) has long been recognized, but the underlying mechanism is poorly understood. Why certain perturbations affect BC hearing is also unclear. An example is BC hyperacusis (hypersensitive BC hearing)-an unnerving symptom experienced by patients with superior canal dehiscence (SCD). We measured BC-evoked sound pressures in scala vestibuli (PSV) and scala tympani (PST) at the basal cochlea in cadaveric human ears, and estimated hearing by the cochlear input drive (PDIFF = PSV - PST) before and after creating an SCD. Consistent with clinical audiograms, SCD increased BC-driven PDIFF below 1 kHz. However, SCD affected the individual scalae pressures in unexpected ways: SCD increased PSV below 1 kHz, but had little effect on PST. These new findings are inconsistent with the inner-ear compression mechanism that some have used to explain BC hyperacusis. We developed a computational BC model based on the inner-ear fluid-inertia mechanism, and the simulated effects of SCD were similar to the experimental findings. This experimental-modeling study suggests that (1) inner-ear fluid inertia is an important mechanism for BC hearing, and (2) SCD facilitates the flow of sound volume velocity through the cochlear partition at low frequencies, resulting in BC hyperacusis.

Stem cell transplantation for auditory nerve replacement.

The successful function of cochlear prostheses depends on activation of auditory nerve. The survival of auditory nerve neurons, however, can vary widely in candidates for cochlear implants and influence implant efficacy. Stem cells offer the potential for improving the function of cochlear prostheses and increasing the candidate pool by replacing lost auditory nerve. The first phase of studies for stem cell replacement of auditory nerve has examined the in vitro survival and differentiation as well as in vivo differentiation and survival of exogenous embryonic and tissue stem cells placed into scala tympani and/or modiolus. These studies are reviewed and new results on in vivo placement of B-5 mouse embryonic stem cells into scala tympani of the guinea pig cochleae with differentiation into a glutamatergic neuronal phenotype are presented. Research on the integration and connections of stem cell derived neurons in the cochlea is described. Finally, an alternative approach is considered, based on the use of endogenous progenitors rather than exogenous stem cells, with a review of promising findings that have identified stem cell-like progenitors in cochlear and vestibular tissues to provide the potential for auditory nerve replacement.

Changes in cochlear responses in guinea pig with changes in perilymphatic K+. Part I: summating potentials, compound action potentials and DPOAEs.

We have measured the effects of changing perilymphatic K+ by perfusing scala tympani in guinea pigs with salt solutions high or low in K+, while monitoring the distortion product otoacoustic emissions (DPOAEs) in the ear canal (a measure of mechanical vibration of the organ of Corti), the summating potential (SP) evoked by high-frequency tone-bursts (taken to be a measure of pre-synaptic electrical activity of the inner hair cells) and the compound action potential (CAP) of the auditory nerve (taken to be a measure of post-synaptic neural activity). We have attempted to investigate the osmotic effects of our perfusates by comparison with simple hyperosmotic sucrose perfusates and iso-osmotic versions of perfusates, and for the effects of changes in other ions (e.g. Na+ and Cl-) by keeping these constant in some perfusates while elevating K+. We have found that changing the K+ concentration over the range 0-30mM elevated the SP and CAP thresholds almost equally in normal animals, and not at all in animals devoid of outer hair cells (OHCs), showing that OHCs are sensitive to the perfusates we have used, but the inner hair cells (IHCs) and the type I afferent dendrites are not, presumably because IHCs are shielded from perilymph by supporting cells, and the membranes of the afferent dendrite membranes exposed directly to our perfusates are dominated by Cl(-) permeability, rather than by K+ permeability. This view is supported by experiments in which the perilymphatic Cl(-) concentration was reduced, producing a large elevation in CAP threshold, but a much smaller elevation of SP threshold, suggesting disruption of action potential initiation. The view that threshold elevations with changes in perilymphatic K+ are due almost solely to a disruption of OHC function and a consequent change in the mechanical sensitivity of the organ of Corti was supported by measurements of amplitude of the 2f1-f2 distortion product otoacoustic emission. During elevations in K+, DPOAEs followed a similar time-course to that for SP and CAP, although the changes were less for DPOAEs. The lack of a 1:1 relationship between DPOAEs and SP and CAP is probably because the iso-input DPOAE measure used is a more complex indicator of mechanical sensitivity than the iso-output measure used by others. Taken together, these results suggest that changes in K+ in pathological conditions probably produce a hearing loss by disrupting OHCs rather than IHCs or neurones, and that OHC disruption in our experiments was due to a mixture of osmotic, K+ and possibly Cl(-) effects.

[Impedance of cochlear implant electrode array in scalae tympani].

OBJECTIVE: To study the relationship between the impedance of paired cochlear implant electrodes and their position in scalae tympani as well as the relationship between the impedance and the current frequency. METHODS: REZ-1 electrodes were implanted in 6 fresh human adult temporal bone specimens. Alternating electrical source was used. A 1 Kohm resistance was in series with the paired electrodes. The voltages of the resistance and the sum voltages of both the paired electrodes and the resistance were recorded. Thus, the impedances of paired electrodes could be calculated. The impedances of neighboring paired electrodes and paired electrodes separated by one electrode were calculated. The frequencies of signals were 2 Hz, 10 Hz, 100 Hz, 1 KHz, and 10 KHz respectively. RESULTS: The impedances of neighboring electrodes increased, as the electrodes were closer to the apical turn of the cochlea (liner regression, F = 198.97, P < 0.001). The impedances of paired electrodes separated by one electrode increased, as the electrodes were closer to the apical turn of the cochlea (liner regression, F = 126.35, P < 0.001). The impedance decreased when the frequency increased. CONCLUSIONS: The impedances of neighboring electrodes increase, as the electrodes are closer to the apical turn of the cochlea. The impedances of neighboring paired electrodes increase, as they are closer to the apical turn in the scalae tympani. The impedances of paired electrodes that are separated by one electrode increase, as they are closer to the apical turn in the scalae tympani. The impedance decreases when the frequency increases.

Auditory prosthesis with a penetrating nerve array.

Contemporary auditory prostheses ("cochlear implants") employ arrays of stimulating electrodes implanted in the scala tympani of the cochlea. Such arrays have been implanted in some 100,000 profoundly or severely deaf people worldwide and arguably are the most successful of present-day neural prostheses. Nevertheless, most implant users show poor understanding of speech in noisy backgrounds, poor pitch recognition, and poor spatial hearing, even when using bilateral implants. Many of these limitations can be attributed to the remote location of stimulating electrodes relative to excitable cochlear neural elements. That is, a scala tympani electrode array lies within a bony compartment filled with electrically conductive fluid. Moreover, scala tympani arrays typically do not extend to the apical turn of the cochlea in which low frequencies are represented. In the present study, we have tested in an animal model an alternative to the conventional cochlear implant: a multielectrode array implanted directly into the auditory nerve. We monitored the specificity of stimulation of the auditory pathway by recording extracellular unit activity at 32 sites along the tonotopic axis of the inferior colliculus. The results demonstrate the activation of specific auditory nerve populations throughout essentially the entire frequency range that is represented by characteristic frequencies in the inferior colliculus. Compared to conventional scala tympani stimulation, thresholds for neural excitation are as much as 50-fold lower and interference between electrodes stimulated simultaneously is markedly reduced. The results suggest that if an intraneural stimulating array were incorporated into an auditory prosthesis system for humans, it could offer substantial improvement in hearing replacement compared to contemporary cochlear implants.

Sendai virus vector-mediated transgene expression in the cochlea in vivo.

We injected a recombinant Sendai virus (SeV) vector into the guinea pig cochlea using two different approaches--the scala media and scala tympani--and investigated which cell types took up the vector. The hearing threshold shift and distribution of transfected cells in animals using the scala media approach were different compared to those using the scala tympani approach. SeV can transfect very different types of cells, including stria vascularis, spiral ganglion neurons, and sensory epithelia of the organ of Corti, and fibrocytes of the scala tympani. Because SeV vectors can potentially deliver stimuli to the cochlea to induce hair cell regeneration, it may be a powerful tool for repairing the organ of Corti.

Otosclerosis: selection of ear for cochlear implantation.

OBJECTIVES: 1. To examine whether speech perception after implantation is correlated with the total duration of deafness, the duration of deafness in the implanted ear, or age at implantation. 2. To examine whether the rate of facial nerve stimulation postoperatively is correlated with the type of electrode used. STUDY DESIGN: Retrospective case note review. SETTING: Tertiary referral center. PATIENTS: Fifty-nine adults with profound postlingual sensorineural hearing loss due to otosclerosis. INTERVENTION: Cochlear implantation with the Nucleus device using either a straight (n = 35) or Contour (n = 29) electrode array. MAIN OUTCOME MEASURES: Speech perception scores for patients at 3, 6 and 12 months postimplantation were correlated against duration of deafness in the implanted ear, duration of total deafness, and age at implantation. Data on facial nerve stimulation rates postoperatively were collected. RESULTS: Implantation in the shortest deafened ear conferred an initial advantage for speech perception 3 months after surgery; however, this effect was lost by 6 months. There were no significant correlations between the duration of bilateral deafness and hearing outcomes. Age at implantation was negatively correlated with outcome at 3 months, but not at 6 and 12 months. Fourteen of 35 patients with straight electrodes and 0 of 24 patients with Contour electrodes experienced facial nerve stimulation during mapping sessions (p < 0.005, chi). CONCLUSION: Patients with otosclerosis are not disadvantaged in the long term by implantation in the longest deafened ear. Increasing age at implantation did not predict poorer outcomes. A perimodiolar design of electrode should be used in otosclerotic patients when possible to reduce the risk of facial nerve stimulation.

Stapes displacement and intracochlear pressure in response to very high level, low frequency sounds.

The stapes is held in the oval window by the stapedial annular ligament (SAL), which restricts total peak-to-peak displacement of the stapes. Previous studies have suggested that for moderate (<130 dB SPL) sound levels intracochlear pressure (PIC), measured at the base of the cochlea far from the basilar membrane, increases directly proportionally with stapes displacement (DStap), thus a current model of impulse noise exposure (the Auditory Hazard Assessment Algorithm for Humans, or AHAAH) predicts that peak PIC will vary linearly with DStap up to some saturation point. However, no direct tests of DStap, or of the relationship with PIC during such motion, have been performed during acoustic stimulation of the human ear. In order to examine the relationship between DStap and PIC to very high level sounds, measurements of DStap and PIC were made in cadaveric human temporal bones. Specimens were prepared by mastoidectomy and extended facial recess to expose the ossicular chain. Measurements of PIC were made in scala vestibuli (PSV) and scala tympani (PST), along with the SPL in the external auditory canal (PEAC), concurrently with laser Doppler vibrometry (LDV) measurements of stapes velocity (VStap). Stimuli were moderate (∼100 dB SPL) to very high level (up to ∼170 dB SPL), low frequency tones (20-2560 Hz). Both DStap and PSV increased proportionally with sound pressure level in the ear canal up to approximately ∼150 dB SPL, above which both DStap and PSV showed a distinct deviation from proportionality with PEAC. Both DStap and PSV approached saturation: DStap at a value exceeding 150 µm, which is substantially higher than has been reported for small mammals, while PSV showed substantial frequency dependence in the saturation point. The relationship between PSV and DStap remained constant, and cochlear input impedance did not vary across the levels tested, consistent with prior measurements at lower sound levels. These results suggest that PSV sound pressure holds constant relationship with DStap, described by the cochlear input impedance, at these, but perhaps not higher, stimulation levels. Additionally, these results indicate that the AHAAH model, which was developed using results from small animals, underestimates the sound pressure levels in the cochlea in response to high level sound stimulation, and must be revised.

Spiral ganglion cell site of excitation I: comparison of scala tympani and intrameatal electrode responses.

To determine the site of excitation on the spiral ganglion cell in response to electrical stimulation similar to that from a cochlear implant, single-fiber responses to electrical stimuli delivered by an electrode positioned in the scala tympani were compared to responses from stimuli delivered by an electrode placed in the internal auditory meatus. The response to intrameatal stimulation provided a control set of data with a known excitation site, the central axon of the spiral ganglion cell. For both intrameatal and scala tympani stimuli, the responses to single-pulse, summation, and refractory stimulus protocols were recorded. The data demonstrated that summation pulses, as opposed to single pulses, are likely to give the most insightful measures for determination of the site of excitation. Single-fiber summation data for both scala tympani and intrameatally stimulated fibers were analyzed with a clustering algorithm. Combining cluster analysis and additional numerical modeling data, it was hypothesized that the scala tympani responses corresponded to central excitation, peripheral excitation adjacent to the cell body, and peripheral excitation at a site distant from the cell body. Fibers stimulated by an intrameatal electrode demonstrated the greatest range of jitter measurements indicating that greater fiber independence may be achieved with intrameatal stimulation.

The consequences of neural degeneration regarding optimal cochlear implant position in scala tympani: a model approach.

Cochlear implant research endeavors to optimize the spatial selectivity, threshold and dynamic range with the objective of improving the speech perception performance of the implant user. One of the ways to achieve some of these goals is by electrode design. New cochlear implant electrode designs strive to bring the electrode contacts into close proximity to the nerve fibers in the modiolus: this is done by placing the contacts on the medial side of the array and positioning the implant against the medial wall of scala tympani. The question remains whether this is the optimal position for a cochlea with intact neural fibers and, if so, whether it is also true for a cochlea with degenerated neural fibers. In this study a computational model of the implanted human cochlea is used to investigate the optimal position of the array with respect to threshold, dynamic range and spatial selectivity for a cochlea with intact nerve fibers and for degenerated nerve fibers. In addition, the model is used to evaluate the predictive value of eCAP measurements for obtaining peri-operative information on the neural status. The model predicts improved threshold, dynamic range and spatial selectivity for the peri-modiolar position at the basal end of the cochlea, with minimal influence of neural degeneration. At the apical end of the array (1.5 cochlear turns), the dynamic range and the spatial selectivity are limited due to the occurrence of cross-turn stimulation, with the exception of the condition without neural degeneration and with the electrode array along the lateral wall of scala tympani. The eCAP simulations indicate that a large P(0) peak occurs before the N(1)P(1) complex when the fibers are not degenerated. The absence of this peak might be used as an indicator for neural degeneration.

Electrode array-eluted dexamethasone protects against electrode insertion trauma induced hearing and hair cell losses, damage to neural elements, increases in impedance and fibrosis: A dose response study.

We evaluated the effects of dexamethasone base (DXMb) containing electrode arrays in a guinea pig model of cochlear implantation to determine if eluted DXMb could protect the cochlea against electrode insertion trauma (EIT)-induced: 1) loss of hair cells; 2) disruption of neural elements; 3) increases in hearing thresholds; 4) increased electrical impedance and 5) fibrosis. A guinea pig model of EIT-induced hearing and hair cell losses was used to test silicone electrode arrays that contained either 10%, 1%, 0.1%, or 0% levels of micronized DXMb. These four types of electrode arrays were implanted into the scala tympani via basal turn cochleostomies and left in place for 3 months. Hearing thresholds were determined by ABR and CAP recordings in response to a series of defined pure tone stimuli (i.e. 16-0.5 kHz). Changes in impedance were measured between the implant electrode and a reference electrode. Hair cell counts and neural element integrity were determined by confocal microscopy analyses of stained organ of Corti whole mounts obtained from 90 day post-implantation animals. Fibrosis was measured in Masson trichrome stained cross-sections through the organ of Corti. The results showed that either 10% or 1.0% DXMb eluting electrode arrays protected; hearing thresholds, hair cells, and neural elements against EIT-induced losses and damage. Electrode arrays with 0.1% DXMb only partial protected against EIT-induced hearing loss and damage to the cochlea. Protection of hearing thresholds and organ of Corti sensory elements by electrode-eluted DXMb was still apparent at 3 months post-EIT. All three concentrations of DXMb in the electrode arrays prevented EIT-induced increases in impedance. EIT-initiated fibrosis was significantly reduced within the implanted cochlea of the two DXMb concentrations tested. In conclusion, DXMb eluting electrodes protected the cochlea against long term increases in hearing thresholds, loss of hair cells, damage to neural elements and increases in impedance and fibrosis that result from EIT-initiated damage. The protection achieved by DXMb-eluting electrodes was dose dependent. Establishing a significant level of trauma induced elevation in hearing thresholds was important for the determination of the otoprotective effects of array-eluted DXMb.