Auditory brainstem implants (ABIs) can restore useful hearing to patients with hearing loss who cannot benefit from cochlear implants. We provide an update on recent efforts to develop silicon-based, multisite, penetrating microelectrode arrays as a cochlear nucleus auditory prosthesis. We summarize technological advances with our devices in the feline model as steps toward validating the device for future clinical use.
Key wordscochlear nucleus implant – penetrating microelectrode array – silicon-based multisite device – microstimulation – amplitude modulation
19 Future Development: Penetrating Multisite Microelectrodes as Cochlear Nucleus Implant
19.1.1 Auditory Brainstem Prosthesis
While cochlear implants have become the most widely used neuroprostheses, patients without a functional auditory nerve or with a deformed or ossified cochlea cannot benefit from them. Studies have shown that electrode array implanted on the surface of the cochlear nucleus do convey auditory percepts that enable users to recognize important environmental sounds and aid with lipreading.3 In some instances good recognition of speech (“open-set” speech recognition) has been reported for patients whose deafness was not due to neurofibromatosis type 2 (NF2), the most common indication for an auditory brainstem implantation. 4 In this context, an array of microelectrodes that penetrates into the ventral cochlear nucleus (VCN) may be applicable to non-NF2 as well as to NF2 patients. The non-NF2 group may include a subset of cochlear implant users who do not receive significant benefit from their cochlear implants. 4 A growing number of cochlear implant users who are middle-aged or older adults may lose their hearing by presbycusis including cochlear synaptopathy. 6 In a small clinical trial, an array of iridium oxide microwire electrodes with a single electrode site at the tip was implanted into the VCN of 10 patients following resection of auditory nerve tumors, but the effort had limited success. 11
19.2 Multisite Arrays for Auditory Brainstem Prosthesis
Among the micromachining technology-based devices, the only silicon-based microelectrode array that has FDA approval is the Blackrock array (a version of the Utah intracortical array). 2 This device is approved for humans for less than 30 days and has only one microstimulating site on each shank that penetrates into the neural tissue. As a result, this device may not provide much additional benefit as an auditory prosthesis or implant. In contrast, it is possible that an array of penetrating multisite microelectrodes whose safety has been validated by adequate preclinical data may enable selective and localized access to the tonotopic gradients of the cochlear nucleus (CN), and thereby convey improved speech recognition to the users. Fig. 19.1 illustrates such an array of multisite penetrating electrodes intended for implantation into the feline VCN. Microelectrode arrays with multiple electrically independent stimulating sites on each penetrating shank have the potential for conveying electrical stimulation with high spatial selectivity while minimizing the number of penetrating shanks and attendant risks of tissue injury. Having multiple electrode sites per shank (“multisite”), the device allows access to the topography of the cochlear nucleus. In the past, the Michigan/NeuroNexus probes have been widely used in animal studies, 1 , 10 mainly for recording neuronal activity. However, this device has not been approved by the FDA for human use, and their materials and designs are not generally known to satisfy the brainstem prosthesis requirements.
19.3 Device Development and In-Vivo Preclinical Evaluation
We developed our multisite silicon probes for neural stimulating and recording and validated their function and longevity through long-term implantation in the feline brainstem (Fig. 19.2 , left). 5 The photolithography-based micromachining technology allows the individual microstimulating sites to be three-dimensionally arranged as a cluster of multiple penetrating shanks. These probes are fabricated by the deep reactive ion etching process followed by and mechanical sharpening of their tip, yielding a mechanically sturdy shank with a sharpened tip that reduces insertion force and tissue displacement during implantation into the brain. The microelectrode sites are electroplated or sputter-coated with iridium oxide. We have implanted these multisite silicon-substrate microelectrodes into the cochlear nucleus of adult cats for up to 314 days and we have monitored the tonotopic specificity of the stimulation by recording in the central nucleus of the contralateral inferior colliculus (IC). 7 , 9 To our knowledge this is one of the longest durations of recordings and stimulation achieved by silicon-based multisite arrays. Histopathology evaluation of neurons and astrocytes using immunohistochemical stains indicated minimal alterations of tissue architecture after chronic implantation.
19.4 A Combinational Approach: Surface and Penetrating Electrodes
An important question is how the performance of a central auditory prosthesis may be enhanced by combining macrostimulation applied on the surface of the nucleus with simultaneous microstimulation within the cochlear nucleus. The premise is that the surface electrodes would convey most of the range of loudness percepts while the intranuclear microelectrodes would sharpen and focus pitch percepts. To delineate potential differences between the two devices, stimulating electrodes were implanted chronically on the surface of the animal’s dorsal cochlear nucleus (DCN) and also within their VCN. 8 , 9 Recording microelectrodes were implanted into the central nucleus of the IC. The electrical stimuli were sinusoidally modulated stimulus pulse trains applied on the DCN and within the VCN. Fig. 19.2 shows contour plots of the time-depth distribution of the vector strength (VS) of the neuronal activity recorded in the cat’s IC in response to charge-balanced electrical stimulation delivered through a microelectrode in the cat’s contralateral posteroventral cochlear nucleus (PVCN) (Fig. 19.2a) and to stimuli applied via a macroelectrode on the cat’s DCN (Fig. 19.2b), and then to simultaneous stimulation at both sites (Fig. 19.2c). The plots’ ordinate is along the axis of the recording microelectrode in the IC and approximately along the tonotopic gradient of the IC. Fig. 19.2a,b illustrate the much smaller spread induced by the microstimulation in the PVCN and the large spread by the stimulation on the surface of the DCN, respectively. Fig. 19.2c shows how the response to simultaneous microstimulation in the PVCN and the macrostimulation on the surface of the DCN retained the small focus of the near-maximum response while only slightly reducing the spread of the response induced by the surface stimulation. This illustrates how the intranuclear microstimulation focuses the maxima of the neuronal activity into a small part of the IC’s tonotopic gradient while the surface stimulation retains the more broadly distributed activity.