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R K Shepherd

Publications and source records attributed to R K Shepherd.

At least 19 recordsLinked to original sources
PubMed2006

Auditory hair cell explant co-cultures promote the differentiation of stem cells into bipolar neurons.

Auditory neurons, the target neurons of the cochlear implant, degenerate following a sensorineural hearing loss. The goal of this research is to direct the differentiation of embryonic stem cells (SCs) into bipolar auditory neurons that can be used to replace degenerating neurons in the deafened mammalian cochlea. Successful replacement of auditory neurons is likely to result in improved clinical outcomes for cochlear implant recipients. We examined two post-natal auditory co-culture models with and without neurotrophic support, for their potential to direct the differentiation of mouse embryonic SCs into characteristic, bipolar, auditory neurons. The differentiation of SCs into neuron-like cells was facilitated by co-culture with auditory neurons or hair cell explants, isolated from post-natal day five rats. The most successful combination was the co-culture of hair cell explants with whole embryoid bodies, which resulted in significantly greater numbers of neurofilament-positive, neuron-like cells. While further characterization of these differentiated cells will be essential before transplantation studies commence, these data illustrate the effectiveness of post-natal hair cell explant co-culture, at providing valuable molecular cues for directed differentiation of SCs towards an auditory neuron lineage.

Animals↗
PubMed2006

Measurement of ATP production in mitochondrial disorders.

Mitochondrial diseases are a heterogeneous group of disorders caused by mutations in both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Mitochondrial disease leads to impaired respiratory chain function and reduced ATP production. The aim of this study was to compare disturbances in mitochondrial function by measuring ATP synthesis in fibroblasts derived from patients with nDNA and mtDNA defects. Skin fibroblasts derived from 22 patients with either nDNA-related disorders (n = 8) or mtDNA-related disorders (n = 14) were analysed. ATP synthesis was markedly decreased in fibroblasts derived from patients with nDNA-related disorders but only variably so in patients with mtDNA mutations. In fibroblasts with the MELAS 3243A > G mutation, ATP synthesis correlated with mutant load. We believe that the observed differences in ATP production between cell lines derived from patients with nDNA-related disorders and mtDNA-related disorders may help in the assessment of patients with undiagnosed mitochondrial disease. The clinical comparisons observed in patients with nDNA- and mtDNA-related disorders may be explained by differences in the disturbance of ATP synthesis measured in the two conditions.

Adenosine Triphosphate↗
PubMed2002

Functional and morphological response of the stria vascularis following a sensorineural hearing loss.

Cochlear endolymph is maintained at a potential of (+)80 mV by an active transport mechanism involving the stria vascularis (SV). This so-called endocochlear potential (EP) is integral to hair cell transduction. We compared the EP with changes in SV area and Na(+),K(+)-ATPase expression following a sensorineural hearing loss. Guinea pigs were deafened using kanamycin and a loop diuretic, and the EP was measured at two, 14, 56, 112 or 224 days following deafening. Auditory brainstem responses were used to confirm that each animal had a severe-profound hearing loss. There was a significant reduction in EP following two days of deafness (normal, 73.5 mV S.E.M.=2.4; deaf, 42.1 mV, S.E.M.=2.8; P<0.0001, t-test). In animals deafened for 14 days the EP had partially recovered (65.2 mV, S.E.M.=5.08), while animals deafened for longer periods exhibited a complete recovery (56 days 80.5 mV, S.E.M.=5.36; 112 days 75.7 mV, S.E.M.=2.71; 224 days 81.0 mV; S.E.M.=6.0). Despite this recovery, there was a systematic reduction in SV area with duration of deafness over the first 112 days of deafness. Significant reductions were localised to the basal turn in animals deafened for two days, but had extended to all turns in animals deafened for 112 days. While there was a significant reduction in strial area, the optical density of Na(+),K(+)-ATPase within the remaining SV was normal. Since the treated animals exhibited essentially a complete elimination of all hair cells, the total K(+) leakage current from the scala media would be expected to be significantly reduced. The large reduction in the extent of the SV after deafening suggests that a reduced strial volume is capable of maintaining a normal EP under conditions of reduced K(+) leakage current.

Animals↗
PubMed2001

Perinuclear mRNA localisation by vimentin 3'-untranslated region requires a 100 nucleotide sequence and intermediate filaments.

The role of the vimentin 3'-untranslated region (3'-UTR) in mRNA localisation was studied in cells transfected with a reporter sequence linked to subregions of the 3'-UTR. In situ hybridisation showed that nucleotides 37-137, including a previously identified protein-binding domain, were sufficient to localise transcripts to perinuclear cytoplasm. Transfection of two SW13 cell lines that do and do not express vimentin showed that perinuclear localisation due to either the vimentin or c-myc 3'-UTR requires intermediate filaments. The data suggest that both a specific protein-binding region of the vimentin 3'-UTR and intermediate filaments themselves are required to determine the site of vimentin synthesis.

3' Untranslated Regions↗
PubMed2001

Distortion product otoacoustic emission and auditory brainstem responses in the echidna (Tachyglossus aculeatus).

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

Acoustic Stimulation↗
PubMed2001

Electrical stimulation of the auditory nerve: single neuron strength-duration functions in deafened animals.

Destruction of cochlear hair cells initiates degenerative changes within auditory nerve fibres (ANFs), including loss of peripheral processes and demyelination of the cell body. These changes are likely to affect the biophysical processes involved in action potential generation to an electrical stimulus. We measured the strength-duration relationship in acutely deafened (100% ANF survival) versus long-term deafened cochleae (approximately 15% ANF survival) by recording from single neurons in the central nucleus of the inferior colliculus (ICC). Input/output functions were constructed for 22 ICC neurons in response to stimulation of the auditory nerve using biphasic current pulses of 20-1000 micros/phase. Strength-duration curves were derived and found to be of the same general form for both acute and long-term deafened cochleae. While there was an increase in rheobase for neurons from long-term versus acute deafened cochleae, this increase was not statistically significant (p=0.097). In contrast, chronaxie--which is related to the membrane time constant--was significantly shorter in the long-term deafened cochleae (p = 0.004). This presumably reflects a shift in the site of action potential initiation to the larger diameter, heavily myelinated central axon as a result of the pathology. These changes in the site of action potential generation have implications for the delivery of charge to ANFs via cochlear implants.

Animals↗
PubMed2001

Stimulus induced pH changes in cochlear implants: an in vitro and in vivo study.

Large pH changes have been shown to be potentially harmful to tissue. The present study was designed to examine stimulus induced changes in pH for a variety of stimulus parameters both in vitro and in vivo, in order to ensure that stimulation strategies for neural prostheses result in minimal pH change. Stimulation using charge balanced biphasic pulses at intensities both within and well above maximum clinical levels for cochlear implants (0.025-0.68 microC per phase), were delivered to platinum electrodes in vitro [saline, phosphate buffered saline (PBS), or saline with human serum albumin (HSA)], and in vivo (scala tympani). Stimulus rates were typically varied from 62.5 to 1000 pulses per second (pps), although rates of up to 14,500 pps were used in some experiments. The pH level was recorded using a pH indicator (Phenol red) or pH microelectrodes. While electrical stimulation at intensities and rates used clinically showed no evidence of a pH shift, intensities significantly above these levels induced pH changes both in vitro and in vivo. The extent of pH change was related to stimulus rate and intensity. In addition, pH change was closely associated with the residual direct current (dc) level. As expected, stimulation with capacitive coupling induced little dc and a minimal pH shift. Moreover, no pH shift was observed using alternating leading phase pulse trains at intensities up to 0.68 microC per phase and 1000 pps. Saline with HSA or buffered solutions dramatically reduced the extent of pH shift observed following stimulation in unbuffered inorganic saline. Reduced pH shift was also observed following in vivo stimulation. These findings provide an insight into mechanisms of safe change injection in neural prostheses.

Animals↗
PubMed2000

Effects of intracochlear factors on spiral ganglion cells and auditory brain stem response after long-term electrical stimulation in deafened kittens.

Using an animal model, we have studied the response of the auditory brain stem to cochlear implantation and the effect of intracochlear factors on this response. Neonatally, pharmacologically deafened cats (100 to more than 180 days old) were implanted with a 4-electrode array in both cochleas. Then, the left cochlea of each cat was electrically stimulated for total periods of up to 1000 hours. After a terminal (14)C-2-deoxyglucose (2DG) experiment, the fraction of the right inferior colliculus with a significant accumulation of 2DG label was calculated. Using 3-dimensional computer-aided reconstruction, we examined the cochleas of these animals for spiral ganglion cell (SGC) survival and intracochlear factors such as electrode positions, degeneration of the organ of Corti, and the degree of fibrosis of the scala tympani. The distribution of each parameter was calculated along the organ of Corti from the basal end. There was a positive correlation between SGC survival and the level of fibrosis in the scala tympani, and a negative correlation between SGC survival and the degree of organ of Corti degeneration. Finally, there was a negative correlation between the 2DG-labeled inferior colliculus volume fraction and the degree of fibrosis, particularly in the 1-mm region nearest the pair of electrodes, and presumably in the basal turn.

Animals↗
PubMed2000

Comparison of electrode position in the human cochlea using various perimodiolar electrode arrays.

OBJECTIVE: This study was conducted to evaluate the insertion properties and intracochlear trajectories of three perimodiolar electrode array designs and to compare these designs with the standard Cochlear/Melbourne array. BACKGROUND: Advantages to be expected of a perimodiolar electrode array include both a reduction in stimulus thresholds and an increase in dynamic range, resulting in a more localized stimulation pattern of the spiral ganglion cells, reduced power consumption, and, therefore, longer speech processor battery life. METHODS: The test arrays were implanted into human temporal bones. Image analysis was performed on a radiograph taken after the insertion. The cochleas were then histologically processed with the electrode array in situ, and the resulting sections were subsequently assessed for position of the electrode array as well as insertion-related intracochlear damage. RESULTS: All perimodiolar electrode arrays were inserted deeper and showed trajectories that were generally closer to the modiolus compared with the standard electrode array. However, although the precurved array designs did not show significant insertion trauma, the method of insertion needed improvement. After insertion of the straight electrode array with positioner, signs of severe insertion trauma in the majority of implanted cochleas were found. CONCLUSIONS: Although it was possible to position the electrode arrays close to the modiolus, none of the three perimodiolar designs investigated fulfilled satisfactorily all three criteria of being easy, safe, and atraumatic to implant.

Cochlear Implantation↗
PubMed2000

Reduction in excitability of the auditory nerve following electrical stimulation at high stimulus rates: V. Effects of electrode surface area.

High rate intracochlear electrical stimulation at high intensities can induce significant reductions in the excitability of the auditory nerve as measured by a decrement in the amplitude of the electrically evoked auditory brainstem response (EABR). Such changes are primarily associated with stimulus induced neuronal activity, although direct current (DC) can also contribute. We examined the extent of stimulus induced change in auditory nerve excitability using large surface area platinum electrodes ('high-Q' electrodes). These electrodes have a surface area approximately 70 times greater than standard Pt electrodes of the same geometric area, resulting in lower DC and charge density (charge/electrode surface area) for a common stimulus. Guinea pigs were bilaterally implanted with either high-Q or standard Pt electrodes, and unilaterally stimulated for 2 h using stimulus intensities of 12 dB or 20-30 dB above EABR threshold (0.34 microC/phase) at stimulus rates of 200, 400, or 1000 pulses per second (pps). EABRs were recorded before and following the acute stimulation. While there were significant reductions in EABR amplitudes and elevated EABR thresholds following stimulation at 12 dB above threshold using 400 and 1000 pps delivered to standard Pt electrodes, there were fewer or no significant changes in the post-stimulus EABR amplitude and threshold using high-Q electrodes under equivalent stimulus conditions. At a higher stimulus intensity (20-30 dB above EABR threshold), no reduction in EABR amplitude was observed at 200 pps for both stimulating electrodes. However, EABRs were reduced significantly at 400 and 1000 pps. There was significantly greater EABR recovery following stimulation using high-Q electrodes compared with standard Pt electrodes at 400 (P<0.05) and 1000 pps (P<0.05). These data indicate that large surface area electrodes can significantly reduce stimulus induced changes in auditory nerve excitability, and may therefore have important clinical application.

Animals↗
PubMed2000

Neonatal sensorineural hearing loss affects neurone size in cat auditory midbrain.

We examined the effect of a neonatal sensorineural hearing loss on the soma area of neurones in the central nucleus of the inferior colliculus (ICC) in adult cats to evaluate the role of auditory experience on neuronal atrophy within the auditory midbrain. Three groups of animals were used: bilaterally deafened, unilaterally deafened and normal hearing controls. Soma area measurements were made from the laminated central and medial divisions of the ICC of eight deafened and two normal hearing cats. A small but significant reduction in soma area was evident for bilaterally deafened animals compared with normal hearing controls (P<0.05, Dunnett's test). In contrast, there was no significant difference in mean soma area between normal hearing and unilaterally deafened animals (P0.05) irrespective of whether the ICC examined was ipsi- or contralateral to the deafened ear. These results demonstrate that the reduction in soma area of auditory brainstem neurones reported following a sensorineural hearing loss is also evident at the level of the auditory midbrain.

Acoustic Stimulation↗
PubMed2000

Electrical stimulation of the auditory nerve. III. Response initiation sites and temporal fine structure.

Latency, temporal dispersion and input-output characteristics of auditory nerve fiber responses to electrical pulse trains in normal and chronically deafened cat ears were classified and tentatively associated with sites where activity is initiated. Spikes occurred in one or more of four discrete time ranges whose endpoints overlapped partially. A responses had latencies <0.44 ms, exhibited asymptotic temporal dispersion of 8-12 micros and possessed an average dynamic range of 1.2 dB for 200 pulses/s (pps) pulse trains. They likely originated from central processes of spiral ganglion cells. B(1) and B(2) responses (0.45-0.9 ms, 25-40 micros, 1.9 dB) likely stemmed from activity at myelinated and unmyelinated peripheral processes, respectively. C100 micros) likely originated from direct stimulation of inner hair cells, and D8 dB) arose from propagating traveling waves possibly caused by electrically induced motion of outer hair cells. C and D responses were recorded only in acoustically responsive ears. Mean latencies of spikes in all time ranges usually decreased with intensity, and activity at two or even three discrete latencies was often observed in the same spike train. Latency shifts from one discrete time range to another often occurred as intensity increased. Some shifts could be attributed to responses to the opposite-polarity phase of the biphasic pulse. In these cases, temporal dispersion and dynamic range were approximately equal for activity at each latency. A second type of latency shift was also often observed, in which responses at each latency exhibited dissimilar temporal dispersion and dynamic range. This behavior was attributed to a centralward shift in the spike initiation site and it occurred for monophasic as well as biphasic signals. Several fibers exhibited dual latency activity with a 40-90 micros time difference between response peaks. This may have stemmed from spike initiation at nodes on either side of the cell body. Increasing the stimulus pulse rate to 800-1000 pps produced small increases in temporal dispersion and proportionate increases in asymptotic discharge rate and dynamic range, but thresholds did not improve and slopes of rate-intensity functions (in spikes/s/dB) did not change. Responses to high-rate stimuli also exhibited discrete latency increases when discharge rates exceeded 300-400 spikes/s. Spike by spike latencies in these cases depended strongly on the discharge history. Implications for high-rate speech processing strategies are discussed.

Animals↗
PubMed2000

Technical note: Constrained optimization of breed composition in composite populations to balance net merit and risk.

We developed a method to derive optimum composite genotypes when the proportion of a specific breed (or combination of breeds) in the composite is constrained to a desired level. The method allows development of composites that balance net merit according to available parameters and reflects the production system and(or) risk preference, particularly when traits in the breeding objective do not represent all traits important for production. The method can also be used to evaluate the cost of constraining breed use. For example, when the true optimal composite is difficult to obtain in the time frame available to the producer, the predicted merit of the composite with breed proportion restricted to those that are obtainable in practice can be compared with the predicted merit of the true optimum composite. In a case study the method is used to optimize a tropical composite using Brahman, Charolais, and Belmont Red breeds. The proportion of Charolais is to be constrained to 50%. Using growth parameters from a tropical crossbreeding experiment, the unconstrained optimum composite was 32.5% Brahman, 11.1% Belmont Red, and 56.3% Charolais. When the proportion of Charolais in the composite was constrained to 50%, optimum proportions of Brahman and Belmont Red were 33.9% and 16.1% respectively. In the case study net merit (annualized profit per cow exposed, $), as defined by the growth parameters, was .2% less than that of the unconstrained optimum composite.

Animal Husbandry↗
PubMed2000

Activation of adenosine A2 alpha receptors inhibits mast cell degranulation and mast cell-dependent vasoconstriction.

OBJECTIVE: Adenosine and inosine accumulate in tissue during periods of ischemia and both molecules have been shown to degranulate mast cells in the hamster cheek pouch via activation of an A3 receptor. An A2-mediated inhibitory action of adenosine on mast cell degranulation has also been reported (16), and the objective of this research was to investigate the role of adenosine A2 receptors in modulating inosine-induced mast cell degranulation and subsequent vasoconstriction of microvessels. METHODS: Cheek pouches of the Golden hamster were prepared for in vivo microscopy. Adenosine, inosine, and other agents were applied either globally in the superfusion solution or to selected regions of the tissue by pipette. RESULTS: Micropipette application of 10(-4) M inosine to periarteriolar mast cells caused a vasoconstriction and an associated mast cell degranulation in 71% of the arterioles tested. The average diameter reduction was 29 +/- 5%. To establish a modulatory role for the A2 receptor, low doses of adenosine (100 nM and 10 nM) were applied globally via the superfusion prior to inosine stimulation. This adenosine pretreatment resulted in a decrease in the incidence of the inosine-induced vasoconstriction (17% and 31%), as well as smaller constrictions (0.5 +/- 1% and 7 +/- 3%). Mast cell degranulation was also reduced by pretreatment with adenosine, as evidenced by a decreased number of mast cells exhibiting ruthenium red dye uptake. The inhibitory effect of adenosine could be eliminated by pretreatment with the nonselective A1/A2 antagonist 8-(p-sulfophenyl) theophylline, which restored the inosine-induced responses to control values. To demonstrate that the effect was A2 alpha-mediated, vessels were pretreated with the selective A2 alpha agonist 2-[4-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680). Following this treatment, constriction in response to microapplication of inosine (10(-4) M) occurred in only 11% of the vessels tested; the average constriction was reduced to 2 +/- 2% and no mast cell degranulation was observed. CONCLUSIONS: We conclude that mast cell degranulation can be inhibited via activation of an adenosine A2 alpha receptor; which activation occurs at a lower concentration of adenosine than stimulatory A3 receptor activation. This finding may have implications for the pathology of ischemia.

Adenosine↗
PubMed1999

Sensorineural hearing loss during development: morphological and physiological response of the cochlea and auditory brainstem.

We have investigated the effects of sensorineural hearing loss on the cochlea and central auditory system of profoundly deafened cats. Seventeen adult cats were used: four had normal hearing; 12 were deafened neonatally for periods of < 2.5 years (five bilaterally, seven unilaterally); and one animal had a long-term (approximately 8 years) profound bilateral hearing loss. Bipolar scala tympani stimulating electrodes were bilaterally implanted in each animal, and electrically evoked auditory brainstem responses (EABRs) were recorded in an acute study to evaluate the basic physiologic response properties of the deafened auditory pathway. The cochleae and cochlear nuclei (CN) of each animal were examined with light microscopy. Spiral ganglion cell density in neonatally deafened cochleae was 17% of normal, and only 1.5% of normal in the long-term deaf animal. There was a 46% reduction in total CN volume in neonatally deafened animals compared to normal, and a 60% reduction in the long-term deaf animal. Neural density in the anteroventral CN of bilaterally deafened animals was 37% higher than normal; 44% higher in the long-term deaf animal. Significantly, however, we saw no evidence of a loss of neurones within the anteroventral CN in any deafened animal. There was a significant increase in EABR threshold and wave IV latency in the deafened animals, and a significant decrease in response amplitude and input/output function gradient. Again, these changes were more extensive in the long-term deaf animal. These data show that a sensorineural hearing loss can evoke significant morphological and physiological changes within the cochlea and auditory brainstem, and these changes become greater with duration of deafness. It remains to be seen whether these changes can be reversed following the introduction of afferent activity via chronic electrical stimulation of the auditory nerve.

Action Potentials↗
PubMed1999

Electrical stimulation of the auditory nerve: II. Effect of stimulus waveshape on single fibre response properties.

To investigate the generation of action potentials by electrical stimulation we studied the response of auditory nerve fibres (ANFs) to a variety of stimulus waveforms. Current pulses were presented to longitudinal bipolar scala tympani electrodes implanted in normal and deafened cochleae. Capacitively coupled monophasic current pulses evoked single ANF responses that were more sensitive to one phase (the 'excitatory' phase) than the other. Anodic pulses produced a significantly shorter mean latency compared with cathodic pulses, indicating that their site for spike initiation is located more centrally along the ANF. The fine temporal structure of ANF responses to biphasic pulses appeared similar to that evoked by monophasic pulses. An excitatory monophasic pulse evoked a significantly lower threshold than a biphasic current pulse having the same polarity and duration leading phase, i.e. the addition of a second phase leads to an increase in threshold. Increasing the temporal separation of the two phases of a biphasic pulse resulted in a moderate reduction in threshold which approached that of an excitatory monophasic pulse for interphase gaps > 100 micros. Greater threshold reductions were observed with narrower current pulses. There was a systematic reduction in threshold with increasing pulse width for biphasic current pulses, reflecting the general charge-dependent properties of ANFs for narrow pulse widths. Chopped biphasic current pulses, which uniformly delivered multiple packets of charge (2 x 30 micros, 3 x 20 micros or 6 x 10 micros) with the same polarity over a 120 micros period, followed by a similar series in the reverse polarity, demonstrated the ability of the neural membrane to integrate sub-threshold packets of charge to achieve depolarisation. Moreover, thresholds for these current pulses were approximately 1.5 dB lower than 60 micros/phase biphasic current pulses with no interphase gap. Finally, stimulation using charge-balanced triphasic and asymmetric current pulses produced systematic changes in threshold and latency consistent with the charge-dependent properties of ANFs. These findings provide insight into the mechanisms underlying the generation of action potentials using electrical stimuli. Moreover, a number of these novel stimuli may have potential clinical application.

Animals↗
PubMed1999

Reduction in excitability of the auditory nerve following electrical stimulation at high stimulus rates. IV. Effects of stimulus intensity.

High rate intracochlear electrical stimulation using stimulus intensities well above clinical limits can induce a significant reduction in the excitability of the auditory nerve as measured by a reduction in the amplitude of the electrically evoked auditory brainstem response (EABR). The purpose of the present study was to assess the effect of stimulus intensity on these stimulus induced changes by comparing the effects of acute stimulation using stimulus intensities within normal clinical levels (6 dB and 12 dB above EABR threshold) and significantly above normal clinical levels (> 20 dB above EABR threshold; 0.34 microC/phase). Stimulus rates of 200, 400, or 1000 pulses/s (pps) were delivered to bipolar scala tympani electrodes. EABRs were recorded before and periodically following 2 h of continuous stimulation. No reduction in EABR amplitude was observed following stimulation at 6 dB above EABR threshold for the three stimulus rates examined. However, EABRs were reduced when stimulated at 12 dB above EABR threshold at 400 pps, and significantly reduced when stimulated at a rate of 1000 pps. Immediate post-stimulus response amplitudes of wave III were 63% and 35% of the pre-stimulus amplitude at 400 and 1000 pps respectively. More significant reductions in EABR amplitude were observed following stimulation at levels more than 20 dB above EABR threshold for both 400 and 1000 pps stimuli. Our findings indicate that stimulus induced changes in EABR amplitude are related to both stimulus rate and stimulus intensity. Moreover, stimulation using intensities within the normal clinical range show little evidence of prolonged reductions in auditory nerve excitability at stimulus rates of up to 1000 pps.

Animals↗