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The effect of chronic intrascalar electrical stimulation on the spiral ganglion cell survival of the ototoxically deafened guinea pig was investigated. Immediately after ototoxic drug administration, unilateral sinusoidal (1 kHz) charge-balanced electrical stimulation on a 50% duty cycle was administered for 2 hours per day, 5 days per week, at intensities from 0 (control) to 400 μAmp via an implanted scala tympani electrode. The relationship of electrically evoked middle latency response (EMLR) to stimulation protocol and cell survival was studied. At 9 weeks post-drug treatment, the animals were killed and temporal bones were prepared for morphometric analysis of spiral ganglion cell density. The subjects showed essentially complete elimination of outer hair sensory cells, with minimal remaining inner hair cells confined to apical turns. Variable loss of spiral ganglion cell populations was observed, which related to electrical stimulation. In animals that received daily unilaterally electrical stimulation, statistically significant increases in survival of spiral ganglion cells were observed in the stimulated ear, compared to the nonstimulated ear—particularly in basal cochlear regions near the electrode. Spiral ganglion cell density was a function of stimulation current intensity level. Moreover, the slope of the amplitude input/output (I/O) function of the EMLR was found to be dependent on stimulating current level. The effect of stimulation on induced survival may be dependent on a number of mechanisms, including metabolic effects of direct activation of “deafferented” spiral ganglion cells. These data support the suggestion that implantation may provide optimal benefits when performed shortly after deafness.

The availability of thin-film multichannel electrodes provides new possibilities for implantation and direct stimulation of the modiolar portion of the auditory nerve. Electrodes in direct contact with the auditory nerve should be functional at lower thresholds and might require fewer remaining neurons for stimulation compared to electrodes in the scala tympani. This strategy would also provide close contact with neural elements subserving a greater frequency range. Implantation of the eighth nerve may also be advantageous in profoundly deaf subjects who lack an implantable scala tympani. In this study we evaluated the effect of surgical implantation and chronic placement of a silicon substrate implant in the modiolar portion of the auditory nerve of the guinea pig. Of six chronically implanted ears, five showed changes limited to the loss of spiral ganglion cells in the canal of Rosenthal, immediately adjacent to the Implant. The sixth ear showed more extensive cochlear alteration in a pattern suggestive of vascular injury. In separate acute experiments, implants were placed in the modiolar portion of the auditory nerve and electrophysiologic analysis was performed. Middle latency responses with good morphology were obtained at thresholds below those found with scala tympani implants. Input-output functions exhibited a plateau in response amplitude at stimulus levels below thresholds for seventh or vestibular portion of the eighth nerve. Further modifications of the modiolar portion of the auditory nerve electrode design will include development of an electrode interconnect that will allow chronic implantation with stimulation.

As part of a program to develop a central auditory system prosthesis, we have examined the reaction of tissue to different levels of stimulation from electrodes chronically implanted in the cochlear nucleus of the guinea pig. Tolerance and histologic reaction to 20 hours of periodic electrical stimulation of the cochlear nucleus were analyzed. Intraoperative and postoperative electrically evoked middle latency responses were monitored during stimulus trials. The threshold necessary to generate the middle latency responses was frequently below 50 µA. In the animals that received 50 and 100 µA of blphasic charge-balanced stimulation (corresponding to approximately 200 and 400 µC/cm2phase), adverse tissue reaction was minimal, and glial proliferation along the electrode tract never exceeded 25 µm in width. Stimulation intensities of 150 and 200 µA (approximately 600 and 800 µC/cm2phase) produced significant tissue response at the site of the electrode terminus, with necrosis, cell loss, and reactive cells present. Therefore neuronal damage was observed to occur at an intensity far greater than that required for eliciting an electrophysiologic response.

Prosthetic stimulation of the cochlear nucleus (CN) has been used for rehabilitation of profoundly deaf patients who are not suitable candidates for cochlear implants. The goal of this article was to assess the relative effectiveness of surface vs. penetrating stimulation of the CN. Electrophysiologic and autoradiographic measures were used to study central auditory system activation elicited by direct stimulation of the CN. Eighteen pigmented guinea pigs, divided into three groups, underwent acute implantation of bipolar electrodes in the CN. One group was not stimulated and acted as a control (n= 7). Electrodes were placed on the surface of the CN in one test group (n= 4) and within the CN in a second test group (n= 7). Thresholds for electrically evoked middle latency responses (EMLR) were determined and input/output (I/O) functions were obtained. The two test groups were then pulsed with [14C]-2-Deoxyglucose (2-DG) intramuscularly and stimulated for 1 hour with biphasic; charge-balanced pulses having a total duration of 400 µsec, a repetition rate of 100/sec, and an amplitude of 200 µA. After stimulation, animals were killed and brains were harvested and prepared for autoradiography using standard techniques. Threshold current for EMLRs in the surface-stimulated group had a mean of 67.5 ± 23.9 µA (range, 40 to 100 µA). Thresholds for in-depth stimulated group had a mean of 11.4 ± 3.5 µA (range, 10 to 20 µA). The saturation level of the I/O function for the surface-stimulated group had a mean of 287.5 ± 41.5 µA (range, 250 to 350 µA). The saturation level for the in-depth stimulated group had a mean of 192.9 ± 49.5 µA (range, 100 to 250 µA). The dynamic range for the surface electrodes had a mean of 13.1 ± 2.7 dB (range, 9.9 to 15.9 dB), whereas the dynamic range for the penetrating electrodes had a mean of 24.5 ± 2.6 dB (range, 20 to 28.0 dB). Autoradiographs generated by CNS tissue from stimulated animals demonstrated no significant difference in metabolic activity of the CN between surface and in-depth stimulated groups. However, there were highly significant differences in 2-DG uptake in the contralateral superior olivary complex, contralateral inferior colllculus, and ipsilateral and contralateral lateral lemniscus, with greater uptake in in-depth stimulated preparations. Electrophysiologic and autoradiographic data suggest that a penetrating CN prosthesis is capable of activating the auditory tract at a lower threshold, with a relatively wider dynamic range than a surface prosthesis. This probably reflects greater efficiency of neurostimulation by virtue of direct access to larger populations of second-order neurons and avoiding current injection through surface pial layers.

The effect of chronic intrascalar electrical stimulation on the spiral ganglion cell survival of the ototoxically deafened guinea pig was investigated. Immediately after ototoxic drug administration, unilateral sinusoidal (1 kHz) charge-balanced electrical stimulation on a 50% duty cycle was administered for 2 hours per day, 5 days per week, at intensities from 0 (control) to 400 µAmp via an implanted scala tympani electrode. The relationship of electrically evoked middle latency response (EMLR) to stimulation protocol and cell survival was studied. At 9 weeks post-drug treatment, the animals were killed and temporal bones were prepared for morphometric analysis of spiral ganglion cell density. The subjects showed essentially complete elimination of outer hair sensory cells, with minimal remaining inner hair cells confined to apical turns. Variable loss of spiral ganglion cell populations was observed, which related to electrical stimulation. In animals that received daily unilaterally electrical stimulation, statistically significant increases in survival of spiral ganglion cells were observed in the stimulated ear, compared to the nonstimulated ear—particularly in basal cochlear regions near the electrode. Spiral ganglion cell density was a function of stimulation current intensity level. Moreover, the slope of the amplitude input/output (I/O) function of the EMLR was found to be dependent on stimulating current level. The effect of stimulation on induced survival may be dependent on a number of mechanisms, including metabolic effects of direct activation of “deafferented” spiral ganglion cells. These data support the suggestion that implantation may provide optimal benefits when performed shortly after deafness.

Prosthetic stimulation of the cochlear nucleus (CN) has been used for rehabilitation of profoundly deaf patients who are not suitable candidates for cochlear implants. The goal of this article was to assess the relative effectiveness of surface vs. penetrating stimulation of the CN. Electrophysiologic and autoradiographic measures were used to study central auditory system activation elicited by direct stimulation of the CN. Eighteen pigmented guinea pigs, divided into three groups, underwent acute implantation of bipolar electrodes in the CN. One group was not stimulated and acted as a control (n= 7). Electrodes were placed on the surface of the CN in one test group (n= 4) and within the CN in a second test group (n= 7). Thresholds for electrically evoked middle latency responses (EMLR) were determined and input/output (I/O) functions were obtained. The two test groups were then pulsed with [14C]-2-Deoxyglucose (2-DG) intramuscularly and stimulated for 1 hour with biphasic; charge-balanced pulses having a total duration of 400 μsec, a repetition rate of 100/sec, and an amplitude of 200 μA. After stimulation, animals were killed and brains were harvested and prepared for autoradiography using standard techniques. Threshold current for EMLRs in the surface-stimulated group had a mean of 67.5 ± 23.9 μA (range, 40 to 100 μA). Thresholds for in-depth stimulated group had a mean of 11.4 ± 3.5 μA (range, 10 to 20 μA). The saturation level of the I/O function for the surface-stimulated group had a mean of 287.5 ± 41.5 μA (range, 250 to 350 μA). The saturation level for the in-depth stimulated group had a mean of 192.9 ± 49.5 μA (range, 100 to 250 μA). The dynamic range for the surface electrodes had a mean of 13.1 ± 2.7 dB (range, 9.9 to 15.9 dB), whereas the dynamic range for the penetrating electrodes had a mean of 24.5 ± 2.6 dB (range, 20 to 28.0 dB). Autoradiographs generated by CNS tissue from stimulated animals demonstrated no significant difference in metabolic activity of the CN between surface and in-depth stimulated groups. However, there were highly significant differences in 2-DG uptake in the contralateral superior olivary complex, contralateral inferior colllculus, and ipsilateral and contralateral lateral lemniscus, with greater uptake in in-depth stimulated preparations. Electrophysiologic and autoradiographic data suggest that a penetrating CN prosthesis is capable of activating the auditory tract at a lower threshold, with a relatively wider dynamic range than a surface prosthesis. This probably reflects greater efficiency of neurostimulation by virtue of direct access to larger populations of second-order neurons and avoiding current injection through surface pial layers.

As part of a program to develop a central auditory system prosthesis, we have examined the reaction of tissue to different levels of stimulation from electrodes chronically implanted in the cochlear nucleus of the guinea pig. Tolerance and histologic reaction to 20 hours of periodic electrical stimulation of the cochlear nucleus were analyzed. Intraoperative and postoperative electrically evoked middle latency responses were monitored during stimulus trials. The threshold necessary to generate the middle latency responses was frequently below 50 μA. In the animals that received 50 and 100 μA of blphasic charge-balanced stimulation (corresponding to approximately 200 and 400 μC/cm2phase), adverse tissue reaction was minimal, and glial proliferation along the electrode tract never exceeded 25 μm in width. Stimulation intensities of 150 and 200 μA (approximately 600 and 800 μC/cm2phase) produced significant tissue response at the site of the electrode terminus, with necrosis, cell loss, and reactive cells present. Therefore neuronal damage was observed to occur at an intensity far greater than that required for eliciting an electrophysiologic response.

The availability of thin-film multichannel electrodes provides new possibilities for implantation and direct stimulation of the modiolar portion of the auditory nerve. Electrodes in direct contact with the auditory nerve should be functional at lower thresholds and might require fewer remaining neurons for stimulation compared to electrodes in the scala tympani. This strategy would also provide close contact with neural elements subserving a greater frequency range. Implantation of the eighth nerve may also be advantageous in profoundly deaf subjects who lack an implantable scala tympani. In this study we evaluated the effect of surgical implantation and chronic placement of a silicon substrate implant in the modiolar portion of the auditory nerve of the guinea pig. Of six chronically implanted ears, five showed changes limited to the loss of spiral ganglion cells in the canal of Rosenthal, immediately adjacent to the Implant. The sixth ear showed more extensive cochlear alteration in a pattern suggestive of vascular injury. In separate acute experiments, implants were placed in the modiolar portion of the auditory nerve and electrophysiologic analysis was performed. Middle latency responses with good morphology were obtained at thresholds below those found with scala tympani implants. Input-output functions exhibited a plateau in response amplitude at stimulus levels below thresholds for seventh or vestibular portion of the eighth nerve. Further modifications of the modiolar portion of the auditory nerve electrode design will include development of an electrode interconnect that will allow chronic implantation with stimulation.