A fully implantable stimulator for use in small laboratory animals.

This paper describes a low cost, fully implantable, single channel stimulator that can be manufactured in a research laboratory. The stimulator generates charge-balanced biphasic current pulses which are delivered to a bipolar electrode array for chronic stimulation of neural tissue in free-running laboratory animals such as rats and mice. The system is magnetically coupled and contains no batteries or external leadwires. The subject is placed in a chamber surrounded by three orthogonal coils of wire which are driven to generate a magnetic field. Currents are induced in wire coils in the implanted stimulator then regulated to produce biphasic current pulses with fixed amplitude of up to 500 microA. Phase duration is adjustable from 25 to 250 micros per phase. Charge balance is maintained by capacitive coupling and shorting of the electrodes between pulses. Stimulus rate can be continuously varied, and the temporal precision of the stimulus means that the stimulator can be used in behavioural experiments or for generating electrically evoked potentials. We describe the application of this stimulator for chronic electrical stimulation of the auditory nerve (i.e. a cochlear implant); however it will have application in other areas of neuroscience requiring controlled safe electrical stimulation of neural tissue over extended periods. Circuit diagrams and manufacturing details are provided as supplementary data.

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.

Brain-derived neurotrophic factor modulates auditory function in the hearing cochlea.

Neurotrophins prevent spiral ganglion neuron (SGN) degeneration in animal models of ototoxin-induced deafness and may be used in the future to improve the hearing of cochlear implant patients. It is increasingly common for patients with residual hearing to undergo cochlear implantation. However, the effect of neurotrophin treatment on acoustic hearing is not known. In this study, brain-derived neurotrophic factor (BDNF) was applied to the round window membrane of adult guinea pigs for 4 weeks using a cannula attached to a mini-osmotic pump. SGN survival was first assessed in ototoxically deafened guinea pigs to establish that the delivery method was effective. Increased survival of SGNs was observed in the basal and middle cochlear turns of deafened guinea pigs treated with BDNF, confirming that delivery to the cochlea was successful. The effects of BDNF treatment in animals with normal hearing were then assessed using distortion product otoacoustic emissions (DPOAEs), pure tone, and click-evoked auditory brainstem responses (ABRs). DPOAE assessment indicated a mild deficit of 5 dB SPL in treated and control groups at 1 and 4 weeks after cannula placement. In contrast, ABR evaluation showed that BDNF lowered thresholds at specific frequencies (8 and 16 kHz) after 1 and 4 weeks posttreatment when compared to the control cohort receiving Ringer's solution. Longer treatment for 4 weeks not only widened the range of frequencies ameliorated from 2 to 32 kHz but also lowered the threshold by at least 28 dB SPL at frequencies ≥16 kHz. BDNF treatment for 4 weeks also increased the amplitude of the ABR response when compared to either the control cohort or prior to treatment. We show that BDNF applied to the round window reduces auditory thresholds and could potentially be used clinically to protect residual hearing following cochlear implantation.

An automated system for rapid evaluation of high-density electrode arrays in neural prostheses.

The success of high-density electrode arrays for use in neural prostheses depends on efficient impedance monitoring and fault detection. Conventional methods of impedance testing and fault detection are time consuming and not always suited for in vivo assessment of high-density electrode arrays. Additionally, the ability to evaluate impedances and faults such as open and short circuits, both in vitro and in vivo, are important to ensure safe and effective stimulation. In this work we describe an automated system for the rapid evaluation of high-density electrode arrays. The system uses a current pulse similar to that used to stimulate neural tissue and measures the voltage across the electrode in order to calculate the impedance. The switching of the system was validated by emulating a high-density electrode array using light-emitting diodes and a resistor-capacitor network. The system was tested in vitro and in vivo using a range of commercially available and in-house developed electrode arrays. The system accurately identified faults in an 84-electrode array in less than 20 s and reliably measured impedances up to 110 kΩ using a 200 µA, 250 µs per phase current pulse. This system has direct application for screening high-density electrode arrays in both clinical and experimental settings.