Evaluation of focused multipolar stimulation for cochlear implants in long-term deafened cats.

OBJECTIVE: Focused multipolar (FMP) stimulation has been shown to produce restricted neural activation using intracochlear stimulation in animals with a normal population of spiral ganglion neurons (SGNs). However, in a clinical setting, the widespread loss of SGNs and peripheral fibres following deafness is expected to influence the effectiveness of FMP. APPROACH: We compared the efficacy of FMP stimulation to both monopolar (MP) and tripolar (TP) stimulation in long-term deafened cat cochleae (n = 8). Unlike our previous study, these cochleae contained <10% of the normal SGN population adjacent to the electrode array. We also evaluated the effect of electrode position on stimulation modes by using either modiolar facing or lateral wall facing half-band electrodes. The spread of neural activity across the inferior colliculus, a major nucleus within the central auditory pathway, was used as a measure of spatial selectivity. MAIN RESULTS: In cochleae with significant SGN degeneration, we observed that FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation (p < 0.001). However, thresholds were significantly higher for FMP and TP stimulation compared to MP stimulation (p < 0.001). No difference between FMP and TP stimulation was found in any measures. The high threshold levels for FMP stimulation was significantly reduced without compromising spatial selectivity by varying the degree of current focusing (referred as 'partial-FMP' stimulation). Spatial selectivity of all stimulation modes was unaffected by the electrode position. Finally, spatial selectivity in long-term deafened cochleae was significantly less than that of cochleae with normal SGN population (George S S et al 2014 J. Neural Eng. 11 065003). SIGNIFICANCE: The present results indicate that the greater spatial selectivity of FMP and TP stimulation over MP stimulation is maintained in cochleae with significant neural degeneration and is not adversely affected by electrode position. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance.

Evaluation of focused multipolar stimulation for cochlear implants in acutely deafened cats.

OBJECTIVE: The conductive nature of the fluids and tissues of the cochlea can lead to broad activation of spiral ganglion neurons using contemporary cochlear implant stimulation configurations such as monopolar (MP) stimulation. The relatively poor spatial selectivity is thought to limit implant performance, particularly in noisy environments. Several current focusing techniques have been proposed to reduce the spread of activation with the aim towards achieving improved clinical performance. APPROACH: The present research evaluated the efficacy of focused multipolar (FMP) stimulation, a relatively new focusing technique in the cochlea, and compared its efficacy to both MP stimulation and tripolar (TP) stimulation. The spread of neural activity across the inferior colliculus (IC), measured by recording the spatial tuning curve, was used as a measure of spatial selectivity. Adult cats (n = 6) were acutely deafened and implanted with an intracochlear electrode array before multi-unit responses were recorded across the cochleotopic gradient of the contralateral IC. Recordings were made in response to acoustic and electrical stimulation using the MP, TP and FMP configurations. MAIN RESULTS: FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation. However, thresholds were significantly higher (p < 0.001) for FMP and TP stimulation compared to MP stimulation. There were no differences found in spatial selectivity and threshold between FMP and TP stimulation. SIGNIFICANCE: The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance. However, further research will be required to demonstrate the efficacy of these modes of stimulation after longer durations of deafness.

Effects of chronic cochlear electrical stimulation after an extended period of profound deafness on primary auditory cortex organization in cats.

Extended periods of deafness have profound effects on central auditory system function and organization. Neonatal deafening results in loss of the normal cochleotopic organization of the primary auditory cortex (AI), but environmentally-derived intracochlear electrical stimulation, via a cochlear implant, initiated shortly after deafening, can prevent this loss. We investigated whether such stimulation initiated after an extended period of deafness can restore cochleotopy. In two groups of neonatally-deafened cats, a multi-channel intracochlear electrode array was implanted at 8 weeks of age. One group received only minimal stimulation, associated with brief recordings at 4-6-week intervals, over the following 6 months to check the efficacy of the implant. In the other group, this 6-month period was followed by 6 months of near-continuous intracochlear electrical stimulation from a modified clinical cochlear implant system. We recorded multi-unit clusters in the auditory cortex and used two different methods to define the region of interest in the putative AI. There was no evidence of cochleotopy in any of the minimally stimulated animals, confirming our earlier finding. In three of six chronically stimulated cats there was clear evidence of AI cochleotopy, and in a fourth cat in which the majority of penetrations were in the anterior auditory field there was clear evidence of cochleotopy in that field. The finding that chronic intracochlear electrical stimulation after an extended period of deafness is able to restore cochleotopy in some (but not all) cases has implications for the performance of patients implanted after an extended period of deafness.

Development of a surgical approach for a wide-view suprachoroidal retinal prosthesis: evaluation of implantation trauma.

BACKGROUND: Our research goal is to develop a safe, reproducible surgical approach for implantation of a wide-field retinal stimulating array. The aim of this study was to evaluate the pathological response to acute implantation of a functional prototype electrode array in the suprachoroidal space. METHODS: The surgical techniques to implant a 72 platinum electrode array fabricated on 8 × 13 × 0.4 mm polyimide and silicone substrate were developed in a pilot study in anesthetized cats. For the main study, nine eyes were implanted in vivo and unoperated eyes were used as controls. Surgery consisted of a temporal approach with a full-thickness scleral incision 5 mm posterior to the limbus. A suprachoroidal "pocket" was created, the electrode array inserted to sit beneath the area centralis, and placement was confirmed visually. The eyes were collected subsequently for histopathology. RESULTS: The array was consistently inserted into the suprachoroidal space beneath the area centralis in nine eyes. There was a significant hemorrhage in two cases where implantation was complicated by choroidal congestion. Retinal folding occurred only when the array tip was within 2.6 mm of the optic disc (p < 0.01). There was choroidal incarceration at the incision in six eyes and scleral distortion at the array edges in five. No cases were found where the implant breached the retina, choroid, or sclera. CONCLUSIONS: A large stimulation array can be reliably inserted into the suprachoroidal space without trauma to the neuroretina. These findings suggest that this is an appropriate surgical approach for the placement of an electrode array for use in retinal stimulation.

Examining the auditory nerve fiber response to high rate cochlear implant stimulation: chronic sensorineural hearing loss and facilitation.

Neural prostheses, such as cochlear and retinal implants, induce perceptual responses by electrically stimulating sensory nerves. These devices restore sensory system function by using patterned electrical stimuli to evoke neural responses. An understanding of their function requires knowledge of the nerves responses to relevant electrical stimuli as well as the likely effects of pathology on nerve function. We describe how sensorineural hearing loss (SNHL) affects the response properties of single auditory nerve fibers (ANFs) to electrical stimuli relevant to cochlear implants. The response of 188 individual ANFs were recorded in response to trains of stimuli presented at 200, 1,000, 2,000, and 5,000 pulse/s in acutely and chronically deafened guinea pigs. The effects of stimulation rate and SNHL on ANF responses during the 0-2 ms period following stimulus onset were examined to minimize the influence of ANF adaptation. As stimulation rate increased to 5,000 pulse/s, threshold decreased, dynamic range increased and first spike latency decreased. Similar effects of stimulation rate were observed following chronic SNHL, although onset threshold and first spike latency were reduced and onset dynamic range increased compared with acutely deafened animals. Facilitation, defined as an increased nerve excitability caused by subthreshold stimulation, was observed in both acute and chronic SNHL groups, although the magnitude of its effect was diminished in the latter. These results indicate that facilitation, demonstrated here using stimuli similar to those used in cochlear implants, influences the ANF response to pulsatile electrical stimulation and may have important implications for cochlear implant signal processing strategies.

Bilateral cochlear implantation in the ferret: a novel animal model for behavioral studies.

Bilateral cochlear implantation has recently been introduced with the aim of improving both speech perception in background noise and sound localization. Although evidence suggests that binaural perception is possible with two cochlear implants, results in humans are variable. To explore potential contributing factors to these variable outcomes, we have developed a behavioral animal model of bilateral cochlear implantation in a novel species, the ferret. Although ferrets are ideally suited to psychophysical and physiological assessments of binaural hearing, cochlear implantation has not been previously described in this species. This paper describes the techniques of deafening with aminoglycoside administration, surgical implantation of an intracochlear array and chronic intracochlear electrical stimulation with monitoring for electrode integrity and efficacy of stimulation. Experiments have been presented elsewhere to show that the model can be used to study behavioral and electrophysiological measures of binaural hearing in chronically implanted animals. This paper demonstrates that cochlear implantation and chronic intracochlear electrical stimulation are both safe and effective in ferrets, opening up the possibility of using this model to study potential protective effects of bilateral cochlear implantation on the developing central auditory pathway. Since ferrets can be used to assess psychophysical and physiological aspects of hearing along with the structure of the auditory pathway in the same animals, we anticipate that this model will help develop novel neuroprosthetic therapies for use in humans.

Neurotrophic factors and neural prostheses: potential clinical applications based upon findings in the auditory system.

Spiral ganglion neurons (SGNs) are the target cells of the cochlear implant, a neural prosthesis designed to provide important auditory cues to severely or profoundly deaf patients. The ongoing degeneration of SGNs that occurs following a sensorineural hearing loss is, therefore, considered a limiting factor in cochlear implant efficacy. We review neurobiological techniques aimed at preventing SGN degeneration using exogenous delivery of neurotrophic factors. Application of these proteins prevents SGN degeneration and can enhance neurite outgrowth. Furthermore, chronic electrical stimulation of SGNs increases neurotrophic factor-induced survival and is correlated with functional benefits. The application of neurotrophic factors has the potential to enhance the benefits that patients can derive from cochlear implants; moreover, these techniques may be relevant for use with neural prostheses in other neurological conditions.

Does cochlear implantation and electrical stimulation affect residual hair cells and spiral ganglion neurons?

Increasing numbers of cochlear implant subjects have some level of residual hearing at the time of implantation. The present study examined whether (i) hair cells that have survived one pathological insult (aminoglycoside deafening), can survive and function following long-term cochlear implantation and electrical stimulation (ES); and (ii) chronic ES in these cochleae results in greater trophic support of spiral ganglion neurons (SGNs) compared with cochleae devoid of hair cells. Eight cats, with either partial (n=4) or severe (n=4) sensorineural hearing loss, were bilaterally implanted with scala tympani electrode arrays 2 months after deafening, and received unilateral ES using charge balanced biphasic current pulses for periods of up to 235 days. Frequency-specific compound action potentials and click-evoked auditory brainstem responses (ABRs) were recorded periodically to monitor the residual acoustic hearing. Electrically evoked ABRs (EABRs) were recorded to confirm the stimulus levels were 3-6 dB above the EABR threshold. On completion of the ES program the cochleae were examined histologically. Partially deafened animals showed no significant increase in acoustic thresholds over the implantation period. Moreover, chronic ES of an electrode array located in the base of the cochlea did not adversely affect hair cells in the middle or apical turns. There was evidence of a small but statistically significant rescue of SGNs in the middle and apical turns of stimulated cochleae in animals with partial hearing. Chronic ES did not, however, prevent a reduction in SGN density for the severely deaf cohort, although SGNs adjacent to the stimulating electrodes did exhibit a significant increase in soma area (p<0.01). In sum, chronic ES in partial hearing animals does not adversely affect functioning residual hair cells apical to the electrode array. Moreover, while there is an increase in the soma area of SGNs close to the stimulating electrodes in severely deaf cochleae, this trophic effect does not result in increased SGN survival.

Chronic depolarization enhances the trophic effects of brain-derived neurotrophic factor in rescuing auditory neurons following a sensorineural hearing loss.

The development and maintenance of spiral ganglion neurons (SGNs) appears to be supported by both neural activity and neurotrophins. Removal of this support leads to their gradual degeneration. Here, we examined whether the exogenous delivery of the neurotrophin brain-derived neurotrophic factor (BDNF) in concert with electrical stimulation (ES) provides a greater protective effect than delivery of BDNF alone in vivo. The left cochlea of profoundly deafened guinea pigs was implanted with an electrode array and drug-delivery system. BDNF or artificial perilymph (AP) was delivered continuously for 28 days. ES induced neural activity in two cohorts (BDNF/ES and AP/ES), and control animals received BDNF or AP without ES (BDNF/- and AP/-). The right cochleae of the animals served as deafened untreated controls. Electrically evoked auditory brainstem responses (EABRs) were recorded immediately following surgery and at completion of the drug-delivery period. AP/ES and AP/- cohorts showed an increase in EABR threshold over the implantation period, whereas both BDNF cohorts exhibited a reduction in threshold (P < 0.001, t-test). Changes in neural sensitivity were complemented by significant differences in both SGN survival and soma area. BDNF cohorts demonstrated a significant trophic or survival advantage and larger soma area compared with AP-treated and deafened control cochleae; this advantage was greatest in the base of the cochlea. ES significantly enhanced the survival effects of BDNF throughout the majority of the cochlea (P < 0.05, Bonferroni's t-test), although there was no evidence of trophic support provided by ES alone. Cotreatment of SGNs with BDNF and ES provides a substantial functional and trophic advantage; this treatment may have important implications for neural prostheses.