Development of a feline model for preclinical research of a new translabyrinthine auditory nerve implant

Abstract

Cochlear implants are among the most successful neural prosthetic devices to date but exhibit poor frequency selectivity and the inability to consistently activate apical (low frequency) spiral ganglion neurons. These issues can limit hearing performance in many cochlear implant patients, especially for understanding speech in noisy environments and in perceiving or appreciating more complex inputs such as music and multiple talkers. For cochlear implants, electrical current must pass through the bony wall of the cochlea, leading to widespread activation of auditory nerve fibers. Cochlear implants also cannot be implanted in some individuals with an obstruction or severe malformations of the cochlea. Alternatively, intraneural stimulation delivered via an auditory nerve implant could provide direct contact with neural fibers and thus reduce unwanted current spread. More confined current during stimulation can increase selectivity of frequency fiber activation. Furthermore, devices such as the Utah Slanted Electrode Array can provide access to the full cross section of the auditory nerve, including low frequency fibers that are difficult to reach using a cochlear implant. However, further scientific and preclinical research of these Utah Slanted Electrode Array devices is limited by the lack of a chronic large animal model for the auditory nerve implant, especially one that leverages an appropriate surgical approach relevant for human translation. This paper presents a newly developed transbullar translabyrinthine surgical approach for implanting the auditory nerve implant into the cat auditory nerve. In our first of a series of studies, we demonstrate a surgical approach in non-recovery experiments that enables implantation of the auditory nerve implant into the auditory nerve, without damaging the device and enabling effective activation of the auditory nerve fibers, as measured by electrode impedances and electrically evoked auditory brainstem responses. These positive results motivate performing future chronic cat studies to assess the long-term stability and function of these auditory nerve implant devices, as well as development of novel stimulation strategies that can be translated to human patients.

Keywords: Utah electrode array; auditory nerve implant; auditory prostheses; cat; feline; nerve stimulation; preclinical model; translabyrinthine approach.

Figure 1

Photographs of (A) the external lateral view of the feline skull and (B) the interior posteroinferior view of the tympanic bulla after bullotomy. Key anatomical markers are labeled. The area of the tympanic bulla that will be removed during an ANI procedure is traced with a black dotted line in the lower photograph. In both panels, rostral is to the right.

Figure 2

(A) Micrograph of the 3×5 ANI USEA of the second design. Going along a column, shaft lengths progress from 0.5 to 0.9 mm. The platinum fin at the end of the device facilitates surgical handling during implantation procedures. A 1,000 μm scale bar is shown at the bottom left. Electrodes 3 and 13 and the back side of the array are indicated for orientation purposes. (B) is a schematic representation of the ANI USEA from the back side of the array (i.e., bondpad side) with numbered electrodes.

Figure 3

Micrographs from the left bulla region of a feline cadaver exploring the transbullar translabyrinthine approach. The white arrows denote the exposed round window niche (A), the exposed cochlea (B), the exposure of the modular region (C), and the exposure of the auditory nerve (boxed) within the modiolar region (D). Anatomical directions for posterior [P], anterior [A], dorsal [D], and ventral [V] are indicated. Scale bars for (A–C) are estimated using feline cadaveric skulls' round window niche diameter. (D) is at higher magnification.

Figure 4

Operative microscopy views of the translabyrinthine ANI procedure. (A) Surgical landmarks used to identify the auditory nerve, including the tegmen and basal turn of the cochlea are identified. Millimeter paper is placed in the field for scale. The auditory nerve target is depicted with a dotted line border. (B) 3 × 5 ANI USEA implanted into the auditory nerve. IAC, internal auditory canal. The inset box shows a close-up view of the implanted ANI USEA.

Figure 5

A violin plot comparing in-vitro (saline) and in-vivo (implant) electrode impedances of three of the devices used for electrophysiology in the study. The median (black dashed) and interquartile range (black dotted) of electrode impedance increased following implant but remained within expected values for electrodes within the tissue. The numbers above each set indicate the number of electrodes below 500 kΩ. Electrodes that presented an impedance value above 500 kΩ were removed from the plot. The shift in in-vitro and in-vivo impedance was statistically significant for arrays 1 and 3 (^**p < 0.01, ^***p < 0.001).

Figure 6

Plot of eABRs (voltage versus post-stimulus latency) collected as a function of stimulation currents from 10 to 100 μA. Response measurements from the cathodic-first and anodic-first begin with the expected large stimulus artifact between 0 and 0.5 ms. The consistent polarity and structure of the eABR peaks across cathodic leading and anodic leading (reversed polarity) stimulation indicate that these responses are not stimulation artifacts. The average of the (A) cathodic-first and (B) anodic-first responses results in artifact cancellation, allowing the (C) common eABR signals to be quantified. eABR peaks II, III, IV, and V are labeled in (C). The vertical dashed line denotes stimulation time (t = 0).

Figure 7

eABR responses for stimulation currents from 10 to 100 μA as a function of electrode site on the array. Electrode positions are denoted by the colored square in the lower left corner near each plot. Thresholds, amplitudes, latencies, and waveform characteristics varied as a function of both stimulation level and electrode site location. The locations of the long and the short shanks are denoted in the array diagram on the bottom right, as well as references to key auditory transduction pathway landmarks. Scale bars are identical for all plots. The vertical dashed line denotes stimulation time (t = 0).