Graeme Clark Collection

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    Cochlear pathology following chronic electrical stimulation of the auditory nerve. I: Normal hearing kittens
    Ni, Daofeng ; Shepherd, Robert K. ; Seldon, Lee ; Xu, Shi-Ang ; Clark, Graeme M. ; Millard, Rodney E. ( 1992)
    The present study examines the histopathological effects of long-term intracochlear electrical stimulation in young normal hearing animals. Eight-week old kittens were implanted with scala tympani electrode arrays and stimulated for periods of up to 1500 h using charge balanced biphasic current pulses at charge densities in the range 21-52 µC cm^-2 geom. per phase. Both click and electrically evoked auditory brainstem responses were periodically recorded to monitor the status of the hair cell and spiral ganglion cell populations. In addition, the impedance of the stimulating electrodes was measured daily to monitor their electrical characteristics during chronic implantation. Histopathological examination of the cochleas showed no evidence of stimulus induced damage to cochlear structures when compared with implanted, unstimulated control cochleas. Indeed, there was no statistically significant difference in the ganglion cell density adjacent to the stimulating electrodes when compared with a similar population in implanted control cochleas. In addition, hair cell loss, which was restricted to regions adjacent to the electrode array, was not influenced by the degree of electrical stimulation. These histopathological findings were consistent with the evoked potential recordings. Finally, electrode impedance data correlated well with the degree of tissue growth observed within the scala tympani. The present findings indicate that the young mammalian cochlea is no more susceptible to cochlear pathology following chronic implantation and electrical stimulation than is the adult.
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    A physiological investigation of chronic electrical stimulation with scala tympani electrodes in kittens
    Ni, Daofeng ; Shepherd, Robert K. ; Clark, Graeme M. ( 1992)
    A physiological investigation of cochlear electrical stimulation was undertaken in six two-month-old kittens. The scala tympani electrodes were implanted and electrically stimulated using biphasic balanced electrical pulses' for periods of 1000-1500h in four ears. Four ears received implants for same period but without electrical stimulation. The other two ears served as normal control. The results indicated: 1) Chronic electrical stimulation of the cochlea within electrochemically safe limits did not influence the hearing of kittens and the normal delivery of impulses evoked by acoustic and electrical signals on the auditory brainstem pathway. 2) The wave shapes of EABRs were similar to those of ABRs. The aptitudes of EABRs showed a significant increase following chronic electrical stimulation, resulting in a leftward shift in the input/ output function. The absolute latencies and interwave latencies of waves II-III , III -IV and II -IV were significantly shorter than those of ABRs. These results imply that there was no adverse effect of chronic electrical stimulation on the maturing auditory systems of kittens using these electrical parameters and the mechanism of electrical hearing should be further studied.
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    Experimental study on extracochlear electric stimulation [Abstract]
    Ni, Daofeng ; Shepherd, Robert K. ; Clark, Graeme M. ( 1992)
    The efficiency and feasibility of chronic extracochlear implantation and electric stimulation were studied in two adult cats and four 2-month kittens. The first electrode was placed on the round window by fixing the leadwire on the bridge of aditus between the middle ear and bulla cavity; the second electrode was placed on the surface of the tympanic promontory; the third was inserted into the temporal muscle out of the bulla and the forth fixed in transverse sinus with dental cement. ABRs and EABRs were recorded pre-and postoperatively and during electric stimulation.
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    Cochleotopic selectivity of a multichannel scala tympani electrode array using the 2-deoxyglucose technique
    Brown, M. ; Shepherd, R. K. ; Webster, W. R. ; Martin, R. L. ; Clark, Graeme M. ( 1992)
    The 2-deoxyglucose (2-DG) technique was used to study the cochleotopic selectivity of a multichannel scala tympani electrode array in four cats with another acting as an unstimulated control. Each animal was unilaterally deafened and a multichannel electrode array inserted 6 mm into the scala tympani. Thresholds to electrical stimulation were determined by recording electrically evoked auditory brainstem responses (EABRs). Each animal was injected with 2-DG, and electrically stimulated using bipolar electrodes located either distal or proximal to the round window. The contralateral- ear was stimulated with acoustic tone pips at frequencies that matched the electrode place. Stimulation of both distal and proximal bipolar electrodes at 3X EABR threshold, evoked localized 2-DG labelling in both ipsilateral cochlear nucleus (CN) and the contralateral inferior colliculus (IC), which was very similar in orientation and breadth to labelling evoked by the contralateral tone pips. The cochleotopic position of labelling to proximal stimulation was located in the 24-26 kHz region of each structure, whereas the distal labelling was located around 12 kHz. Distal stimulation at 10 X EABR threshold produced very broad 2-DG labelling in IC centered around the 12 kHz place. The present 2-DG results clearly illustrate cochleotopic selectivity using multichannel bipolar scala tympani electrodes. The extent of this selectivity is dependent on electrical stimulus levels. The 2-DG technique has great potential in evaluating the efficacy of new electrode array designs.
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    Evaluation of expandable leadwires for paediatric cochlear implants
    Xu, Shi-Ang. ; Shepherd, Robert K. ; Clark, Graeme M. ; Tong, Yit C. ; Williams, John F. ( 1993)
    The development of cochlear implants for use in very young children (1-2 years old) will require techniques designed to accommodate temporal bone growth. Previous anatomic studies have shown that the leadwire of a cochlear implant must be capable of expanding up to 20 mm between the round window and the implanted receiver-stimulator in response to skull growth. In the present study morphologic and biomechanical evaluation of five expandable leadwire designs was conducted following their implantation in young cats. Two helical shaped leadwire designs frequently exhibited extensive fibrous tissue adhesions and broke during long-term implantation. In contrast, thin, flexible Silastic envelopes were effective in minimizing tissue adhesions. Residual V- and Z-shaped leadwires, placed in these envelopes, showed little evidence of fibrous tissue adhesions following implantation periods of up to 2 years. Moreover, these leadwires readily expanded both during the growth of the animal and when biomechanical expansion studies performed at the completion of the implant period. These expandable leadwire designs appear to be appropriate candidates for use in pediatric cochlear implants.
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    Profound hearing loss in the cat following the single co-administration of kanamycin and ethacrynic acid
    Xu, Shi-Ang ; Shepherd, Robert K. ; Chen, Yin ; Clark, Graeme M. ( 1993)
    Co-administration of kanamycin (KA) with the loop diuretic ethacrynic acid (EA) has previously been shown to produce a rapid and profound hearing loss in guinea pigs. In the present study we describe a modified technique for developing a profound hearing loss in cats. By monitoring the animal's hearing status during the intravenous infusion of EA the technique minimizes the effects of individual variability to the drug regime. Seven cats received a subcutaneous injection of KA (300 mg/kg) followed by intravenous infusion of EA (1 mg/min). Click-evoked auditory brainstem responses (ABRs) were recorded to monitor the animal's hearing during the infusion. When the ABR thresholds rose rapidly to levels in excess of 90 dB SPL the infusion of EA was stopped. This occurred at EA doses of 10-25 mg/kg, indicating considerable individual variability to the deafening procedure. However, there was a strong negative correlation (r = - 0.93) between the EA dose and body weight which accounted for much of this variability. Subsequent ABR monitoring showed that this profound hearing loss was both bilateral and permanent. Significantly, blood urea and creatinine levels, monitored for periods of up to three days after the procedure, remained within the normal range. Furthermore, there was no clinical evidence of renal dysfunction as indicated by weight loss or oliguria. Cochlear histopathology, examined after a two months to three year survival period, showed an absence of all inner and outer hair cells in the majority of cochleas. The extent of loss of spiral ganglion cells was dependent on their distance from the round window and the period of survival following the deafening procedure. Clearly, the degeneration of spiral ganglion cells continued for several years following the initial insult. Finally, we observed no evidence of renal histopathology. In conclusion, the co-administration of KA and EA produces a profound hearing loss in cats without evidence of renal impairment. Monitoring the animal's hearing status during the procedure ensures that the dose of EA can be optimised for individual animals. Moreover, it may be possible to adapt this procedure to produce animal models with controlled high frequency hearing losses.
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    Paediatric cochlear implantation: radiologic observations of skull growth
    XU, JIN ; Shepherd, Robert K. ; Xu, Shi-Ang ; Seldon, H. Lee ; Clark, Graeme M. ( 1993)
    We investigated the effects of long-term implantation of auditory prostheses on skull growth in young animals. Four monkeys were implanted with dummy cochlear implants at 6 months of age. To simulate implantation in children, the bed for the receiver-stimulator or interconnecting plug was drilled across a calvarial suture down to the underlying dura. Plain skull oentgenograms were periodically taken to monitor head growth for up to 3 years after implantation. These longitudinal measurements revealed no significant asymmetric skull growth. Postmortem measurements using computed tomographic scans confirmed these results and showed no significant difference in the intracranial volumes between the implanted and control sides of each animal or between experimental and nonimplanted control monkeys. These results suggest that long-term cochlear implantation in very young children will not cause any significant deformity of the skull.
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    Electrical stimulation of the auditory nerve: the effect of electrode position on neural excitation
    Shepherd, R. K. ; Hatsushika, S. ; Clark, Graeme M. ( 1993)
    Histological studies have shown that the Melbourne/Cochlear electrode array lies along the outer wall of the scala tympani and is therefore some distance from the residual VIIIth nerve elements. In order to investigate the influence of electrode position on neural excitation we systematically varied the position of the electrode array within the cat scala tympani while recording electrically evoked auditory brainstem responses (EABRs). Using both normal hearing and long-term deafened animals, we observed significant reductions in EABR thresholds as the electrode array was moved from the outer wall towards the modiolus. Further threshold reductions were observed when the array was placed underneath the osseous spiral lamina (OSL) close to the peripheral dendrites. These changes were independent of the bipolar inter-electrode separation, and were observed over a wide range of cochlear pathologies varying from normal to a moderate spiral ganglion cell loss. Interestingly, the one animal exhibiting extensive neural loss showed no correlation between EABR threshold and electrode position. There was also a general decrease in the gradient of the EABR input-output function as the electrode array was moved closer to the neural elements. This was, however, only statistically significant when the electrode was positioned adjacent to the peripheral dendrites. Significant reductions in EABR threshold were also observed as the inter-electrode spacing of the bipolar electrodes was increased. The gradient of the EABR input-output function also increased with increasing inter-electrode spacing, although again, this was only significant when the electrode array was positioned close to the neural elements. The present results indicate that the optimum placement of a Melbourne/Cochlear electrode array is adjacent to the peripheral dendrites. However, such a site would be difficult to achieve in practice while minimizing insertion trauma. An array lying adjacent to the modiolus would be a safe alternative while ensuring a significant reduction in threshold compared with the existing site (outer wall). This placement should result in more localized neural excitation patterns, an increase in the number of bipolar electrodes available, together with an increase in their dynamic range. These changes may lead to further improvements in speech perception among cochlear implant patients.
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    Tinnitus management in the profoundly and totally deaf
    Shepherd, R. K. ( 1993)
    Tinnitus is a common symptom of many cochlear or auditory system pathologies. Since tinnitus is frequently associated with a sensorineural hearing loss, it is not surprising that a large proportion of profoundly and totally deaf patients describe tinnitus as a symptom. The clinical management of severe tinnitus in these patients is discussed with particular emphasis on the use of electrical stimulation. While cochlear implants appear to provide a measure of relief when being used, significant improvements in the management of severe tinnitus will only occur when we have a greater understanding of the underlying pathophysiology, diagnostic procedures that can accurately establish the site of tinnitus generation, and more objective clinical trial procedures that include the use of controls.
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    Effect of chronic electrical stimulation on cochlear nucleus neuron size in normal hearing kittens
    Ni, Daofeng ; Seldon, H. Lee. ; Shepherd, Robert K. ; Clark, Graeme M. ( 1993)
    Very young cochlear-implant candidates may have undetected islands of residual hearing. Would the maturation of these functioning auditory neurons be affected by chronic cochlear stimulation? This was tested by examining neuron sizes in the cochlear nuclei of young, normal hearing kittens with and without chronic cochlear stimulation. Six animals received bilateral intra-or extracochlear implants and were electrically stimulated unilaterally for periods of 1,000-1,500 hours. After sacrifice, cross-sectional areas of approximately 11,000 neuron somata in the cochlear nuclei were measured with an image-analysis system. There were statistically significant differences between stimulated and unstimulated nuclei, especially the posteroventral cochlear nucleus (PYCN), in individual cats, but the directions of the differences were inconsistent. Overall, there was no significant effect of electrical stimulation on soma size. These results indicate that chronic electrical stimulation of the auditory nerve has no positive or negative trophic effects on otherwise innervated, maturing cochlear nucleus neurons.