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Although the cochlear implant has been widely acknowledged as the most successful neural prosthesis, only a fraction of hearing-impaired people who can potentially benefit from a cochlear implant have actually received one due to its limited awareness, accessibility, and affordability. To help overcome these limitations, a 26-electrode cochlear implant has been developed to receive China's Food and Drug Administration (CFDA) approval in 2011 and Conformité Européenne (CE) Marking in 2012. The present article describes design philosophy, system specification, and technical verification of the Nurotron device, which includes advanced digital signal processing and 4 current sources with multiple amplitude resolutions that not only are compatible with perceptual capability but also allow interleaved or simultaneous stimulation. The article also presents 3-year longitudinal evaluation data from 60 human subjects who have received the Nurotron device. The objective measures show that electrode impedance decreased within the first month of device use, but was stable until a slight increase at the end of two years. The subjective loudness measures show that electric stimulation threshold was stable while the maximal comfort level increased over the 3 years. Mandarin sentence recognition increased from the pre-surgical 0%-correct score to a plateau of about 80% correct with 6-month use of the device. Both indirect and direct comparisons indicate indistinguishable performance differences between the Nurotron system and other commercially available devices. The present 26-electrode cochlear implant has already helped to lower the price of cochlear implantation in China and will likely contribute to increased cochlear implant access and success in the rest of the world.This article is part of a Special Issue entitled .

The level of hearing rehabilitation enjoyed by cochlear implant (CI) recipients has increased dramatically since the introduction of these devices. This improvement is the result of continual development of these systems and the inclusion of subjects with less severe auditory pathology. Developments include advanced signal processing, higher stimulation rates, greater numbers of channels, and more efficient electrode arrays that are less likely to produce insertion damage. New directions in the application of CIs, particularly in combined acoustic and electrical stimulation, and increasing performance expectations will place greater demands on future electrode arrays. Specifically, the next generation of arrays must be reliably inserted without damage, must maintain residual acoustic function, and may need to be inserted more deeply. In this study, we measured the mechanical properties of eight clinical and prototype human CI electrode arrays and evaluated insertion trauma and insertion depth in 79 implanted cadaver temporal bones. We found that the size and shape of the array directly affect the incidence of observed trauma. Further, arrays with greater stiffness in the plane perpendicular to the plane of the cochlear spiral are less likely to cause severe trauma than arrays with similar vertical and horizontal stiffness. [ABSTRACT FROM AUTHOR]

Outcomes with contemporary cochlear implants (CI) depend partly upon the survival and condition of the cochlear spiral ganglion (SG) neurons. Previous studies indicate that CI stimulation can ameliorate SG neural degeneration after deafness, and brain-derived neurotrophic factor (BDNF) delivered by an osmotic pump can further improve neural survival. However, direct infusion of BDNF elicits undesirable side effects, and osmotic pumps are impractical for clinical application. In this study, we explored the potential for two adeno-associated viral vectors (AAV) to elicit targeted neurotrophic factor expression in the cochlea and promote improved SG and radial nerve fiber survival. Juvenile cats were deafened prior to hearing onset by systemic aminoglycoside injections. Auditory brainstem responses showed profound hearing loss by 16-18 days postnatal. At ~ 4 weeks of age, AAV2-GFP (green fluorescent protein), AAV5-GFP, AAV2-hBDNF, or AAV5-hGDNF (glial-derived neurotrophic factor) was injected through the round window unilaterally. For GFP immunofluorescence, animals were studied ~ 4 weeks post-injection to assess cell types transfected and their distributions. AAV2-GFP immunofluorescence demonstrated strong expression of the GFP reporter gene in residual inner (IHCs), outer hair cells (OHCs), inner pillar cells, and in some SG neurons throughout the cochlea. AAV5-GFP elicited robust transduction of IHCs and some SG neurons, but few OHCs and supporting cells. After AAV-neurotrophic factor injections, animals were studied ~ 3 months post-injection to evaluate neural survival. AAV5-hGDNF elicited a modest neurotrophic effect, with 6 % higher SG density, but had no trophic effect on radial nerve fiber survival, and undesirable ectopic fiber sprouting occurred. AAV2-hBDNF elicited a similar 6 % increase in SG survival, but also resulted in greatly improved radial nerve fiber survival, with no ectopic fiber sprouting. A further study assessed whether AAV2-hBDNF neurotrophic effects would persist over longer post-injection periods. Animals examined 6 months after virus injection showed substantial neurotrophic effects, with 14 % higher SG density and greatly improved radial nerve fiber survival. Our results suggest that AAV-neurotrophin gene therapy can elicit expression of physiological concentrations of neurotrophins in the cochlea, supporting improved SG neuronal and radial nerve fiber survival while avoiding undesirable side effects. These studies also demonstrate the potential for application of cochlear gene therapy in a large mammalian cochlea comparable to the human cochlea and in an animal model of congenital/early acquired deafness.

Objective: To describe histologic and radiographic findings associated with insertion of a new lateral wall electrode in human temporal bones, as well as quantify the ease of insertion as characterized by multiple cochlear implant surgeons., Setting: Multi-institutional cadaveric study., Methods: The Slim J electrode was inserted in cadaveric temporal bones via a standard mastoidectomy and facial recess approach. Insertion was performed by five cochlear implant surgeons with no previous experience with the Slim J electrode array. Electrode array insertion was performed via a round window, an extended round window, or a cochleostomy approach. Intracochlear trauma, and angular insertion depth was assessed histologically and radiologically, respectively, after placement of the Slim J electrode array., Results: Scala tympani insertion was accomplished in all 40 specimens. Thirty-eight specimens (95%) showed minimal trauma (Esrhaghi grade 0 or 1). One patient had rupture of basilar membrane (grade 2 trauma) at 380 degrees. One patient had grade 4 trauma with scalar translocation beginning at 210 degrees. The mean angular insertion depth was 416.4 degrees (range: 338.7-509.2 degrees, SD 44 degrees). Surgical handling was described as easy in 38 cases (95%)., Conclusion: In a human cadaveric model the lateral wall Slim J electrode produced minimal intracochlear trauma that was positioned completely within the scala tympani in 97.5% of cases.

Although the cochlear implant has been widely acknowledged as the most successful neural prosthesis, only a fraction of hearing-impaired people who can potentially benefit from a cochlear implant have actually received one due to its limited awareness, accessibility, and affordability. To help overcome these limitations, a 26-electrode cochlear implant has been developed to receive China's Food and Drug Administration (CFDA) approval in 2011 and Conformité Européenne (CE) Marking in 2012. The present article describes design philosophy, system specification, and technical verification of the Nurotron device, which includes advanced digital signal processing and 4 current sources with multiple amplitude resolutions that not only are compatible with perceptual capability but also allow interleaved or simultaneous stimulation. The article also presents 3-year longitudinal evaluation data from 60 human subjects who have received the Nurotron device. The objective measures show that electrode impedance decreased within the first month of device use, but was stable until a slight increase at the end of two years. The subjective loudness measures show that electric stimulation threshold was stable while the maximal comfort level increased over the 3 years. Mandarin sentence recognition increased from the pre-surgical 0%-correct score to a plateau of about 80% correct with 6-month use of the device. Both indirect and direct comparisons indicate indistinguishable performance differences between the Nurotron system and other commercially available devices. The present 26-electrode cochlear implant has already helped to lower the price of cochlear implantation in China and will likely contribute to increased cochlear implant access and success in the rest of the world. This article is part of a Special Issue entitled ., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Both neurotrophic support and neural activity are required for normal postnatal development and survival of cochlear spiral ganglion (SG) neurons. Previous studies in neonatally deafened cats demonstrated that electrical stimulation (ES) from a cochlear implant can promote improved SG survival but does not completely prevent progressive neural degeneration. Neurotrophic agents combined with an implant may further improve neural survival. Short-term studies in rodents have shown that brain-derived neurotrophic factor (BDNF) promotes SG survival after deafness and may be additive to trophic effects of stimulation. Our recent study in neonatally deafened cats provided the first evidence of BDNF neurotrophic effects in the developing auditory system over a prolonged duration Leake et al. (J Comp Neurol 519:1526-1545, 2011). Ten weeks of intracochlear BDNF infusion starting at 4 weeks of age elicited significant improvement in SG survival and larger soma size compared to contralateral. In the present study, the same deafening and BDNF infusion procedures were combined with several months of ES from an implant. After combined BDNF + ES, a highly significant increase in SG numerical density (>50 % improvement re: contralateral) was observed, which was significantly greater than the neurotrophic effect seen with ES-only over comparable durations. Combined BDNF + ES also resulted in a higher density of myelinated radial nerve fibers within the osseous spiral lamina. However, substantial ectopic and disorganized sprouting of these fibers into the scala tympani also occurred, which may be deleterious to implant function. EABR thresholds improved (re: initial thresholds at time of implantation) on the chronically stimulated channels of the implant. Terminal electrophysiological studies recording in the inferior colliculus (IC) revealed that the basic cochleotopic organization was intact in the midbrain in all studied groups. In deafened controls or after ES-only, lower IC thresholds were correlated with more selective activation widths as expected, but no such correlation was seen after BDNF + ES due to much greater variability in both measures.

The effectiveness of multichannel cochlear implants depends on the activation of perceptually distinct regions of the auditory nerve. Increased information transfer is possible as the number of channels and dynamic range are increased and electrical and neural interaction among channels is reduced. Human and animal studies have demonstrated that specific design features of the intracochlear electrode directly affect these performance factors. These features include the geometry, size, and orientation of the stimulating sites, proximity of the device to spiral ganglion neurons, shape and position of the insulating carrier, and the stimulation mode (monopolar, bipolar, etc.). Animal studies to directly measure the effects of changes in electrode design are currently constrained by the lack of available electrodes that model contemporary clinical devices. This report presents methods to design and fabricate species-specific customizable electrode arrays. We have successfully implanted these arrays in guinea pigs and cats for periods of up to 14 months and have conducted acute electrophysiological experiments in these animals. Modifications enabling long-term intracochlear drug infusion are also described. Studies using these scale model arrays will improve our understanding of how these devices function in human subjects and how we can best optimize future cochlear implants.

A simplified cochlear implant (CI) system would be appropriate for widespread use in developing countries. Here, we describe a CI that we have designed to realize such a concept. The system implements 8 channels of processing and stimulation using the continuous interleaved sampling (CIS) strategy. A generic digital signal processing (DSP) chip is used for the processing, and the filtering functions are performed with a fast Fourier transform (FFT) of a microphone or other input. Data derived from the processing are transmitted through an inductive link using pulse width modulation (PWM) encoding and amplitude shift keying (ASK) modulation. The same link is used in the reverse direction for backward telemetry of electrode and system information. A custom receiver-stimulator chip has been developed that demodulates incoming data using pulse counting and produces charge balanced biphasic pulses at 1000 pulses/s/electrode. This chip is encased in a titanium package that is hermetically sealed using a simple but effective method. A low cost metal-silicon hybrid mold has been developed for fabricating an intracochlear electrode array with 16 ball-shaped stimulating contacts.

Previous studies have shown that electrical stimulation of the cochlea by a cochlear implant promotes increased survival of spiral ganglion (SG) neurons in animals deafened early in life (Leake et al. [1999] J Comp Neurol 412:543-562). However, electrical stimulation only partially prevents SG degeneration after deafening and other neurotrophic agents that may be used along with an implant are of great interest. GM1 ganglioside is a glycosphingolipid that has been reported to be beneficial in treating stroke, spinal cord injuries, and Alzheimer's disease. GM1 activates trkB signaling and potentiates neurotrophins, and exogenous administration of GM1 has been shown to reduce SG degeneration after hearing loss. In the present study, animals were deafened as neonates and received daily injections of GM1, beginning either at birth or after animals were deafened and continuing until the time of cochlear implantation. GM1-treated and deafened control groups were examined at 7-8 weeks of age; additional GM1 and no-GM1 deafened control groups received a cochlear implant at 7-8 weeks of age and at least 6 months of unilateral electrical stimulation. Electrical stimulation elicited a significant trophic effect in both the GM1 group and the no-GM1 group as compared to the contralateral, nonstimulated ears. The results also demonstrated a modest initial improvement in SG density with GM1 treatment, which was maintained by and additive with the trophic effect of subsequent electrical stimulation. However, in the deafened ears contralateral to the implant SG soma size was severely reduced several months after withdrawal of GM1 in the absence of electrical activation., ((c) 2007 Wiley-Liss, Inc.)

In an animal model of prelingual deafness, we examined the anatomical and physiological effects of prolonged deafness and chronic electrical stimulation on temporal resolution in the adult central auditory system. Maximum following frequencies (Fmax) and first spike latencies of single neurons responding to electrical pulse trains were evaluated in the inferior colliculus of two groups of neonatally deafened cats after prolonged periods of deafness (>2.5 yr): the first group was implanted with an intracochlear electrode and studied acutely (long-deafened unstimulated, LDU); the second group (LDS) received a chronic implant and several weeks of electrical stimulation (pulse rates > or =300 pps). Acutely deafened and implanted adult cats served as controls. Spiral ganglion cell density in all long-deafened animals was markedly reduced (mean <5.8% of normal). Both long-term deafness and chronic electrical stimulation altered temporal resolution of neurons in the central nucleus (ICC) but not in the external nucleus. Specifically, LDU animals exhibited significantly poorer temporal resolution of ICC neurons (lower Fmax, longer response latencies) as compared with control animals. In contrast, chronic stimulation in LDS animals led to a significant increase in temporal resolution. Changes in temporal resolution after long-term deafness and chronic stimulation occurred broadly across the entire ICC and were not correlated with its tonotopic gradient. These results indicate that chronic electrical stimulation can reverse the degradation in temporal resolution in the auditory midbrain after long-term deafness and suggest the importance of factors other than peripheral pathology on plastic changes in the temporal processing capabilities of the central auditory system.

In recent years, several new designs of cochlear implant electrodes have been introduced clinically with the goal of optimizing perimodiolar placement of stimulation sites. Previous studies suggest that perimodiolar electrodes may increase both the efficiency and performance of a cochlear implant. This is the second of two studies designed to examine the positioning of electrodes and the occurrence of insertion-related injury with these newer designs and to directly compare two perimodiolar electrodes to their predecessors. In our previous report we compared the Nucleus banded electrode with the Nucleus Contour perimodiolar electrode. In the present study, using the same protocol, we examine the Spiral Clarion electrode and its successor, the HiFocus II electrode with attached positioner. Eight Spiral Clarion arrays and 20 HiFocus II electrodes with positioners were inserted into human cadaver temporal bones. Following insertion, the specimens were embedded in acrylic resin, cut in quarters with a diamond saw and polished. Insertion depth, proximity to the modiolus and trauma were evaluated in X-ray images and light microscopy. The newer electrode was consistently positioned closer to the modiolus than the previous device whereas the angular depth of insertion measured for the two electrodes was similar. The incidence of trauma was minimal when either electrode was inserted to a depth of less than 400 degrees . However, severe trauma was observed in every case in which the HiFocus II with positioner was inserted beyond 400 degrees and in some cases in which the Spiral Clarion was inserted beyond 400 degrees . To evaluate the possible role of electrode size in the trauma observed we modeled both devices relative to the dimensions of the scala tympani. We found that the fully inserted HiFocus II electrode with positioner was larger than the scala tympani in approximately 70% of temporal bones measured. The results suggest that both the Clarion spiral and HiFocus II with positioner can be inserted with minimal trauma, but in many cases not to the maximum depth allowed by the design.

In recent years, new designs of cochlear implant electrodes have been introduced in an attempt to improve efficiency and performance by locating stimulation sites closer to spiral ganglion neurons and deeper into the scala tympani. The goal of this study was to document insertion depth, intracochlear position and insertion trauma with the Nucleus Contour electrode and to compare results to those observed with the earlier generation Nucleus banded electrode. For this comparison eight Nuclears banded electrodes and 18 Contour electrodes were implanted in cadaver temporal bones using a realistic surgical exposure. Two experienced cochlear implant surgeons and two otology fellows with specialized training in cochlear implant surgery were selected for the study to represent a range of surgical experience similar to that of surgeons currently performing the procedure throughout the world. Following insertion of the electrodes, specimens were imaged using plain film X-ray, embedded in acrylic resin, cut in radial sections with the electrodes in place, and each cut surface was polished. Insertion depth was measured in digitized X-ray images, and trauma was assessed in each cross-section. The Contour electrode inserted more deeply (mean depth=17.9 mm or 417 degrees ) than the banded electrode (mean depth=15.3 mm or 285 degrees ). The incidence and severity of trauma varied substantially among the temporal bones studied. However, the nature and frequency of injuries observed with the two devices were very similar. The Contour electrode was clearly positioned closer to the modiolus than the banded model, and also appeared easier to use. Based on this difference in position and data from previous studies we conclude that the Contour electrode may provide lower thresholds and improved channel selectivity, but the incidence of trauma remains a problem with the newer design. The relative influences of electrode positioning and neural degeneration that may result from trauma are as yet unclear.

Previous studies have shown that chronic electrical stimulation through a cochlear implant causes significant alterations in the central auditory system of neonatally deafened cats. The goal of this study was to investigate the effects of chronic stimulation in the mature auditory system. Normal hearing adult animals were deafened by ototoxic drugs and received daily electrical stimulation over periods of 4-6 months. In terminal physiology experiments, response thresholds to pulsatile and sinusoidal signals were recorded within the inferior colliculus (IC). Using previously established methods, spatial tuning curves (STCs; threshold vs. IC depth functions) were constructed, and their widths measured to infer spatial selectivity. The IC spatial representations were similar for pulsatile and sinusoidal stimulation when phase duration was taken into consideration. However, sinusoidal signals consistently elicited much lower thresholds than pulsatile signals, a difference not solely attributable to differences in charge/phase. The average STC width was significantly broader in the adult deafened/stimulated animals than in controls (adult deafened/unstimulated cats), suggesting that electrical stimulation can induce spatial expansion of the IC representation of the chronically stimulated cochlear sector. Further, results in these adult animals were not significantly different from results in neonatally deafened, early stimulated animals, suggesting that a similar degree of plasticity was induced within the auditory midbrains of mature animals.

This report examines the effects of intracochlear electrode configuration and mode of stimulation (bipolar or monopolar) on neural threshold and spatial selectivity in the inferior colliculus (IC) of the cat. Single and multiunit IC recordings were made in three groups of animals; acutely deafened adults (controls), neonatally deafened animals studied at 6 to 18 months of age and neonatally deafened cats studied at 2.5 to 6.5 years. Response thresholds were plotted versus IC depth to measure the spatial distribution of responses. The response selectivity for each stimulating configuration was defined as the width of the resulting spatial tuning curve (STC) measured at 6 dB above threshold. Spiral ganglion cell (SG) survival was examined histologically in all neonatally deafened animals and correlated with physiological results. Animals studied at less than 1.5 years had SG densities of 23.5%-64.4% of normal (mean=42.7%) while animals studied at greater than 2.5 years had densities of 5.1%-18.3% of normal (mean=9.9%). Electrophysiological results include the following. (1) Monopolar thresholds were 7-8 dB lower than bipolar thresholds in the same animals. (2) Varying the configuration of bipolar contacts (measured as radial, offset radial and longitudinal pairs) did not systematically affect IC threshold in either controls or short-term neonatally deafened animals. In contrast, the long-term neonatally deafened animals showed a difference in threshold with each configuration. (3) The spatial distributions (Q(6 dB)) of responses to bipolar stimulation were approximately 40% more restricted than those for monopolar stimulation. (4) The spatial selectivity of neonatally deafened animals studied at ages up to 1.5 years was equal to that of control animals with normal auditory experience. However, selectivity was degraded in the older animals. (5) Selectivity was decreased in some animals with the longitudinal bipolar configuration and multiple response peaks were seen in several cases using this stimulus configuration.

The goal of this research is to examine the functional consequences of patterned electrical stimulation delivered by a cochlear implant in the deafened developing auditory system. In previous electrophysiological experiments conducted in the inferior colliculus (IC), we have demonstrated that the precise cochleotopic organization of the central nucleus (ICC) develops normally in neonatally deafened unstimulated cats and is unaltered despite the lack of normal auditory input during development. However, these studies also showed that chronic electrical stimulation delivered at a single intracochlear location by one bipolar channel of a cochlear implant induces significant expansion of the central representation of the stimulated cochlear sector and degrades the cochleotopic organization of the IC. This report presents additional data from a new experimental series of neonatally deafened cats that received chronic stimulation on two adjacent bipolar intracochlear channels of a cochlear implant. Results suggest that competing inputs elicited by electrical stimulation delivered by two adjacent channels can maintain the selective representations of each activated cochlear sector within the central auditory system and prevent the expansion seen after single-channel stimulation. Alternating stimulation of two channels and use of highly controlled electrical signals may be particularly effective in maintaining or even sharpening selectivity of central representations of stimulated cochlear sectors. In contrast, simultaneous stimulation using two channels of a model analog cochlear implant processor in one experimental animal failed to maintain channel selectivity and resulted in marked expansion and fusion of the central representations of the stimulated channels. This potentially important preliminary result suggests that under some conditions the central auditory system may be unable to discriminate simultaneous, overlapping inputs from adjacent cochlear implant channels as distinct.

Current cochlear prostheses use amplitude-modulated pulse trains to encode acoustic signals. In this study we examined the responses of inferior colliculus (IC) neurons to sinusoidal amplitude-modulated pulses and compared the maximum unmodulated pulse rate (Fmax) to which they responded with the maximum modulation frequency (maxFm) that they followed. Consistent with previous results, responses to unmodulated pulses were all low-pass functions of pulse rate. Mean Fmax to unmodulated pulses was 104 pulses per second (pps) and modal Fmax was 60 pps. Above Fmax IC neurons ceased responding except for an onset burst at the beginning of the stimulus. However, IC neurons responded to much higher pulse rates when these pulses were amplitude modulated; 74% were relatively insensitive to carrier rate and responded to all modulated carriers including those exceeding 600 pps. In contrast, the responses of these neurons (70%) were low-pass functions of modulation frequency, and the remaining (30%) had band-pass functions with a maxFm of 42 and 34 Hz, respectively. Thus temporal resolution of IC neurons for modulated frequencies is significantly lower than that for unmodulated pulses. These two measures of temporal resolution (Fmax and maxFm) were uncorrelated (r(2) = 0.101). Several parameters influenced the amplitude and temporal structure of modulation responses including modulation depth, overall intensity and modulation-to-carrier rate ratio. We observed distortions in unit responses to amplitude-modulated signals when this ratio was 1/4 to 1/6. Since most current cochlear implant speech processors permit ratios that are significantly greater than this, severe distortion and signal degradation may occur frequently in these devices.

As cochlear implants have become increasingly successful in the rehabilitation of adults with profound hearing impairment, the number of pediatric implant subjects has increased. We have developed an animal model of congenital deafness and investigated the effect of electrical stimulus frequency on the temporal resolution of central neurons in the developing auditory system of deaf cats. Maximum following frequencies (Fmax) and response latencies of isolated single neurons to intracochlear electrical pulse trains (charge balanced, constant current biphasic pulses) were recorded in the contralateral inferior colliculus (IC) of two groups of neonatally deafened, barbiturate-anesthetized cats: animals chronically stimulated with low-frequency signals (< or = 80 Hz) and animals receiving chronic high-frequency stimulation (> or = 300 pps). The results were compared with data from unstimulated, acutely deafened and implanted adult cats with previously normal hearing (controls). Characteristic differences were seen between the temporal response properties of neurons in the external nucleus (ICX; approximately 16% of the recordings) and neurons in the central nucleus (ICC; approximately 81% of all recordings) of the IC: 1) in all three experimental groups, neurons in the ICX had significantly lower Fmax and longer response latencies than those in the ICC. 2) Chronic electrical stimulation in neonatally deafened cats altered the temporal resolution of neurons exclusively in the ICC but not in the ICX. The magnitude of this effect was dependent on the frequency of the chronic stimulation. Specifically, low-frequency signals (30 pps, 80 pps) maintained the temporal resolution of ICC neurons, whereas higher-frequency stimuli significantly improved temporal resolution of ICC neurons (i.e., higher Fmax and shorter response latencies) compared with neurons in control cats. Furthermore, Fmax and latencies to electrical stimuli were not correlated with the tonotopic gradient of the ICC, and changes in temporal resolution following chronic electrical stimulation occurred uniformly throughout the entire ICC. In all three experimental groups, increasing Fmax was correlated with shorter response latencies. The results indicate that the temporal features of the chronically applied electrical signals critically influence temporal processing of neurons in the cochleotopically organized ICC. We suggest that such plastic changes in temporal processing of central auditory neurons may contribute to the intersubject variability and gradual improvements in speech recognition performance observed in clinical studies of deaf children using cochlear implants.

An injection-molded internal supporting rib has been produced to control the flexibility of silicone rubber encapsulated electrodes designed to electrically stimulate the auditory nerve in human subjects with severe to profound hearing loss. The rib molding dies, and molds for silicone rubber encapsulation of the electrode, were designed and machined using AutoCad and MasterCam software packages in a PC environment. After molding, the prototype plastic ribs were iteratively modified based on observations of the performance of the rib/silicone composite insert in a clear plastic model of the human scala tympani cavity. The rib-based electrodes were reliably inserted farther into these models, required less insertion force and were positioned closer to the target auditory neural elements than currently available cochlear implant electrodes. With further design improvements the injection-molded rib may also function to accurately support metal stimulating contacts and wire leads during assembly to significantly increase the manufacturing efficiency of these devices. This method to reliably control the mechanical properties of miniature implantable devices with multiple electrical leads may be valuable in other areas of biomedical device design.

A dimensionally accurate clear model of the human scala tympani has been produced to evaluate the insertion and position of clinically applied intracochlear electrodes for electrical stimulation. Replicates of the human scala tympani were made from low melting point metal alloy (LMA) and from polymethylmeth-acrylate (PMMA) resin. The LMA metal casts were embedded in blocks of epoxy and in clear silicone rubber. After removal of the metal alloy, a cavity was produced that accurately models the human scala tympani. Investment casting molds were made from the PMMA scala tympani casts to enable production of multiple LMA casts from which identical models were fabricated. Total dimensional distortion of the LMA casting process was less than 1% in length and 2% in diameter. The models have been successfully integrated into the design process for the iterative development of advanced intracochlear electrode arrays at UCSF. These fabrication techniques are applicable to a wide range of biomedical design problems that require modelling of visually obscured cavities.

This investigation examined the consequences of neonatal deafness and chronic electrical stimulation of the cochlea in the developing auditory system. Cats were bilaterally deafened by daily ototoxic drug administration for two weeks after birth. Electrical stimulation was initiated at 6-9 weeks of age and continued for up to 6 months, using monopolar round window electrodes that synchronously excited auditory neurons throughout the cochlea. Morphometric evaluation of the density of spiral ganglion cell somata within Rosenthal's canal demonstrated that chronic stimulation induced an increase of about 6% in neuronal survival. Although this difference was statistically significant, extracochlear stimulation in these cats was less effective in preventing neural degeneration than lower intensity, more restricted intracochlear stimulation that was shown in a previous study to induce an average increase of about 13% in neuronal survival. Electrophysiological recording experiments conducted in the inferior colliculus in these animals indicated that monopolar extracochlear stimulation can induce profound alterations in the spatial (frequency) selectivity of the auditory midbrain. On average, results were similar to those previously reported for bipolar intracochlear stimulation, showing about a two-fold expansion of the central representation of chronically stimulated electrodes. However, results with extracochlear stimulation showed much greater variability among individual animals. The results presented suggest that it is problematic to effect consistent 'whole' nerve stimulation using monopolar round window electrodes. Moreover, this mode of stimulation can induce profound functional alterations in the central nervous system and is substantially less effective in forestalling the degeneration of auditory neurons than intracochlear stimulation. Both these results contraindicate the implantation of such electrodes in young children for the purpose of maintaining the integrity of the auditory system for later application of a multichannel cochlear implant.

The effects of chronic intracochlear electrical stimulation on the cochlear nucleus (CN) were studied in eight cats that were neonatally deafened by daily intramuscular injections of neomycin. Profound hearing loss was confirmed in each animal by auditory brainstem response (ABR) and frequency following response (500 Hz) testing. Five of the kittens were implanted unilaterally with a scala tympani electrode array at ages 8-16 weeks. These kittens were stimulated daily for four hours at 2 dB above the evoked ABR threshold, over a period of three months, and subsequently euthanized for histological analysis at 26-32 weeks of age. The three remaining deaf kittens were maintained without stimulation over prolonged periods in order to study the long-term consequences of neonatal deafening, and were euthanized at 66-133 weeks of age. This study compares the CN of these deafened experimental animals and the CN of normal adult cats. Three experimental parameters were examined: CN volume, cross-sectional area of spherical cells in the rostral anteroventral cochlear nucleus (AVCN), and spherical cell density in this same region. The CN in animals that received electrical stimulation showed significant bilateral degenerative changes in all three measured parameters. Total nuclear volume was reduced by 35-36%, spherical cell size was reduced by 20-26%, and spherical cell density decreased by 36-42%, as compared to the normal cat CN. Comparisons were also made in the stimulated animals between CN ipsilateral to the stimulated cochlea and the contralateral, unstimulated CN.(ABSTRACT TRUNCATED AT 250 WORDS)

An earlier study conducted in this laboratory suggested that chronic intracochelear electrical stimulation at moderate current levels can at least partially delay or prevent the retrograde degeneration of primary auditory (spiral ganglion) neurons that otherwise is progressive after neonatal deafness induced by ototoxic drug administration. Increased survival of spiral ganglion neurons was observed within the basal cochlear region near the stimulating biopolar electrode pairs, while in more apical regions there was no significant difference between the stimulated and control cochleas. The mechanisms underlying this maintenance of spiral ganglion neurons induced by chronic electrical stimulation are uncertain, especially since increased neuronal survival was observed over broader sectors of the ganglion than would be expected to be directly activated by the bipolar electrodes and moderate stimulation intensity (6 dB above electrically evoked auditory brainstem response threshold) used. In this report, data are presented from a second series of neonatally deafened and chronically stimulated cats. The parameters for chronic electrical stimulation were manipulated in two simple ways. First, the intensity of the electrical stimulus was reduced from the earlier study, while the duration of chronic stimualtion periods was increased; and secondly, two different intracochlear positions of stimulating electrodes were employed in different experimental groups. Results indicate that elecrical stimulation of the cochlea at an extremely low intensity (2 dB above electrically evoked auditory brainstem response threshold) is sufficient to at least partially prevent or delay ganglion cell degeneration in the deafened cochlea. In addition, data suggest a differential distribution of the maintained or conserved ganglion cells, such that when the stimulating electrode pair was positioned near the base of the cochlea increased ganglion survival in a more basal cochlear sector, while stimulation at a more apical site resulted in increased neuronal survival extending to more apical regions.

The major focus of this study was to define the effects of chronic intracochlear electrical stimulation (ICES) on single unit responses in the inferior colliculus from three experimental groups: 1) normal adults 2) neonatally-deafened/unstimulated adults; and 3) neonatally-deafened/chronically stimulated adults. The major findings include: 1) IC neurons in normal adults showed a diversity of perstimulus responses to ICES which were qualitatively similar to those evoked by acoustic stimuli. They responded with: an onset burst, a sustained discharge, a decrease in their spontaneous activity, or a strong post-stimulus response. The excitatory responses showed either a monotonic or a nonmonotonic increase in activity with increasing stimulus intensity. Response latencies ranged from 5 to over 40 ms. 2) Responses to ICES in normal and deafened/unstimulated animals were virtually indistinguishable from one another. 3) In contrast, responses to ICES in neonatally deafened stimulated animals were different from normal and from deafened, unstimulated animals. Their perstimulus response latencies were significantly shorter, their late response latencies were significantly longer, and the frequency of occurrence of inhibitory and late responses were significantly higher. From these results we conclude that the responses to intracochlear electrical stimulation are directly comparable to those observed following normal acoustic stimulation; that development of cochleotopic organization of the inferior colliculus is not affected by the almost complete lack of normal acoustic input experienced by neonatally deafened animals; and that the basic response properties of IC units are likewise unaffected by neonatal deafening. Moreover, the results suggest that, although the limited regime of electrical stimulation employed in these studies produced no major qualitative distortions in the perstimulus response patterns of IC neurons, it did result in some quantitative changes in those responses.

Ten newborn kittens were deafened by systemic administration of neomycin sulfate. Profound hearing losses were documented by ABR and FFR (500 Hz) testing. At 9-17 weeks of age, the young deafened cats were unilaterally implanted with a multichannel scala tympani electrode. Six of the animals were chronically stimulated at 6 dB above electrically evoked ABR thresholds for 1 h/day for periods of 1 month or 3 months. Stimuli were charge-balanced biphasic pulses (200 microseconds/phase, 30 pps.) The remaining 4 cats underwent identical deafening and implantation schedules but were not stimulated. Results indicate that administration of neomycin in neonatal cats induced degeneration of hair cells and spiral ganglion cell loss that was bilaterally symmetrical between the two cochleas of each individual animal, although there was variation between animals in the severity of the ototoxic drug effect. In animals receiving passive (unstimulated) implants, morphometric analysis of spiral ganglion cell density showed no significant difference in ganglion cell survival between the implanted cochleas and the contralateral control ears. In contrast, animals that were chronically stimulated for 3 months showed significantly better neuronal survival in implanted and stimulated cochleas as compared to contralateral deafened control ears. The induced conservation of spiral ganglion neurons was observed consistently within the basal cochlear region near the stimulating electrodes. In more apical regions there was no significant difference between the stimulated and control cochleas. The mechanisms underlying this selective conservation of spiral ganglion neurons induced by chronic intracochlear electrical stimulation are uncertain. Since no comparable chronic stimulation studies have been conducted in adults, it is not known whether similar conservation effects could be induced in mature animals.

Intracochlear electrical stimulation via cochlear prostheses has been employed as a means of providing some hearing to deaf children. Since chronically restricted stimuli are known to have profound effects on central nervous system development, it is important to examine the effects of chronic intracochlear electrical stimulation in a neonatally deafened animal model. In this study neonatally deafened cats were implanted with a scala tympani electrode consisting of two pairs of electrodes. Chronic electrical stimulation was delivered using one electrode pair and consisted of charge-balanced biphasic pulses (200 microseconds/phase, 30 pps) at 2 dB above the electrically evoked auditory brain stem response (EABR) threshold for 4 h/day or at 6 dB 1 h/day, 5 days/week, for up to 3 months. The second electrode pair was unstimulated and served as an internal control. Following chronic stimulation, acute mapping experiments were performed in the central nucleus of the inferior colliculus (ICC) using single unit and multi-unit recording techniques and activating each electrode pair separately. In addition to these chronically stimulated animals, 2 other groups of experimental animals were studied: A normal group consisting of prior normal adult cats that were acutely implanted; and an unstimulated control group consisting of neonatally deafened adult cats that were either acutely implanted or implanted at 8-10 weeks of age but not chronically stimulated. Among the major findings of this study are: Electrical stimulation of the intracochlear bipolar electrode consistently produces activation of a reproducibly limited sector of the ICC. The location of this activated sector was found to be consistent with the known cochleotopic organization of the ICC and the intracochlear location of the stimulating electrodes. No major differences in the spatial representation of activated electrodes were found between prior normal cats and neonatally deafened unstimulated cats. The locations, shapes and widths of these spatial representations were virtually indistinguishable indicating that ICC cochleotopic organizations were equivalent in these two experimental groups. In contrast, the ICC representation of chronically stimulated electrode pairs were found to be significantly different. The average area activated by chronically stimulated electrode pairs at 6 dB above minimum threshold was approximately twice that of unstimulated deafened animals and prior normal animals; and it was larger, but not significantly so, than the average of the unstimulated electrode pair in the same experimental group.(ABSTRACT TRUNCATED AT 400 WORDS)

Using the four channel cochlear implant system with a vocoder-based processor developed at UCSF over an extensive period of research, clinical trials of the UCSF/Storz device were initiated in February 1985, under the sponsorship of Storz Instrument Company. To date, 13 patients have been implanted with this device, nine of whom have been fitted with their external processor and transmitter and have received at least their initial postoperative evaluation. Patient results have been extremely promising, with eight of the nine patients obtaining some open-set auditory only speech understanding. Most patients have demonstrated improvement over time and all patients have attained an enhancement in lipreading ability with the use of the UCSF/Storz device.

In summary, these results with chronic implantation of three types of scala tympani electrode indicate the critical importance of two factors in reducing the risk of additional damage to cochlear structure by implantation surgery: (1) The shape and mechanical characteristics of the array must be precisely controlled such that insertion can be performed with an acceptably low incidence of trauma; and (2) the specific electrode materials and fabrication procedures must be demonstrated to be highly biocompatible in in vivo animal control studies. It appears that the neuronal elements of a prior normal cochlea (in the cat) can withstand chronic implantation of scala tympani electrodes (for at least 1 year) if these two prerequisites are met. The effects of chronic electrical stimulation with these arrays at current levels appropriate for the operation of such devices in patients is not known at present.

Sixteen patients have been implanted with the UCSF/Storz multichannel implant, 11 of whom have been fitted with their external speech processors and transmitters and administered postoperative audiological evaluations. Both the surgical procedures used and the hearing results for these patients are presented. The potential medical/surgical complications of implant surgery and the future direction of research and development within the UCSF/Storz implant program are discussed.

Using a four-channel implant system with a vocoder-based processor developed at UCSF over an extensive period of research, clinical trials of the UCSF/Storz device were initiated in February 1985 under the sponsorship of Storz Instrument Company. To date, 13 patients have been implanted with the UCSF/Storz device, 10 of whom have been fitted with their external processor and transmitter and have received at least their initial postoperative evaluations. Of these 10 patients, nine are able to use all four channels of their implant system. The device fitting/adjusting process for these patients has been remarkably easy, requiring only approximately 30 to 60 minutes. Patient results have been extremely good, with eight of the 10 patients obtaining some open-set auditory only speech understanding. Without extensive rehabilitation and training, most patients have demonstrated an improvement in speech reception over time. Lip-reading and tracking results indicate that all patients have attained an enhancement of lip-reading ability with the use of the device, suggesting that improved general communication skills have been provided for each UCSF/Storz patient.