Nonhuman primate vestibuloocular reflex responses to prosthetic vestibular stimulation are robust to pulse timing errors caused by temporal discretization.

Electrical stimulation of vestibular afferent neurons to partially restore semicircular canal sensation of head rotation and the stabilizing reflexes that sensation supports has potential to effectively treat individuals disabled by bilateral vestibular hypofunction. Ideally, a vestibular implant system using this approach would be integrated with a cochlear implant, which would provide clinicians with a means to simultaneously treat loss of both vestibular and auditory sensation. Despite obvious similarities, merging these technologies poses several challenges, including stimulus pulse timing errors that arise when a system must implement a pulse frequency modulation-encoding scheme (as is used in vestibular implants to mimic normal vestibular nerve encoding of head movement) within fixed-rate continuous interleaved sampling (CIS) strategies used in cochlear implants. Pulse timing errors caused by temporal discretization inherent to CIS create stair step discontinuities of the vestibular implant's smooth mapping of head velocity to stimulus pulse frequency. In this study, we assayed electrically evoked vestibuloocular reflex responses in two rhesus macaques using both a smooth pulse frequency modulation map and a discretized map corrupted by temporal errors typical of those arising in a combined cochlear-vestibular implant. Responses were measured using three-dimensional scleral coil oculography for prosthetic electrical stimuli representing sinusoidal head velocity waveforms that varied over 50-400°/s and 0.1-5 Hz. Pulse timing errors produced negligible effects on responses across all canals in both animals, indicating that temporal discretization inherent to implementing a pulse frequency modulation-coding scheme within a cochlear implant's CIS fixed pulse timing framework need not sacrifice performance of the combined system's vestibular implant portion. NEW & NOTEWORTHY Merging a vestibular implant system with existing cochlear implant technology can provide clinicians with a means to restore both vestibular and auditory sensation. Pulse timing errors inherent to integration of pulse frequency modulation vestibular stimulation with fixed-rate, continuous interleaved sampling cochlear implant stimulation would discretize the smooth head velocity encoding of a combined device. In this study, we show these pulse timing errors produce negligible effects on electrically evoked vestibulo-ocular reflex responses in two rhesus macaques.

A Virtual Inner Ear Model Selects Ramped Pulse Shapes for Vestibular Afferent Stimulation.

Bilateral vestibular deficiency (BVD) results in chronic dizziness, blurry vision when moving the head, and postural instability. Vestibular prostheses (VPs) show promise as a treatment, but the VP-restored vestibulo-ocular reflex (VOR) gain in human trials falls short of expectations. We hypothesize that the slope of the rising ramp in stimulation pulses plays an important role in the recruitment of vestibular afferent units. To test this hypothesis, we utilized customized programming to generate ramped pulses with different slopes, testing their efficacy in inducing electrically evoked compound action potentials (eCAPs) and current spread via bench tests and simulations in a virtual inner model created in this study. The results confirmed that the slope of the ramping pulses influenced the recruitment of vestibular afferent units. Subsequently, an optimized stimulation pulse train was identified using model simulations, exhibiting improved modulation of vestibular afferent activity. This optimized slope not only reduced the excitation spread within the semicircular canals (SCCs) but also expanded the neural dynamic range. While the model simulations exhibited promising results, in vitro and in vivo experiments are warranted to validate the findings of this study in future investigations.

Finite Element Modeling of Residual Hearing after Cochlear Implant Surgery in Chinchillas.

Cochlear implant (CI) surgery is one of the most utilized treatments for severe hearing loss. However, the effects of a successful scala tympani insertion on the mechanics of hearing are not yet fully understood. This paper presents a finite element (FE) model of the chinchilla inner ear for studying the interrelationship between the mechanical function and the insertion angle of a CI electrode. This FE model includes a three-chambered cochlea and full vestibular system, accomplished using µ-MRI and µ-CT scanning technologies. This model's first application found minimal loss of residual hearing due to insertion angle after CI surgery, and this indicates that it is a reliable and helpful tool for future applications in CI design, surgical planning, and stimuli setup.

A comprehensive finite element model for studying Cochlear-Vestibular interaction.

We present a 3-D finite element (FE) model of the chinchilla's inner ear consisting of the entire cochlea structure and the vestibular system. The reaction of the basilar membrane to the head rotation and the reaction of ampulla to the stapes movement were investigated. These results demonstrate the existence of hearing-vestibular system interaction. They provide an explanation to the clinical finding on the coexistence between hearing loss and equilibration dysfunction. It is a preliminary, yet critical step toward the development of a comprehensive FE model of an entire ear for mechano-acoustic analysis.

Cross-axis adaptation improves 3D vestibulo-ocular reflex alignment during chronic stimulation via a head-mounted multichannel vestibular prosthesis.

By sensing three-dimensional (3D) head rotation and electrically stimulating the three ampullary branches of a vestibular nerve to encode head angular velocity, a multichannel vestibular prosthesis (MVP) can restore vestibular sensation to individuals disabled by loss of vestibular hair cell function. However, current spread to afferent fibers innervating non-targeted canals and otolith end organs can distort the vestibular nerve activation pattern, causing misalignment between the perceived and actual axis of head rotation. We hypothesized that over time, central neural mechanisms can adapt to correct this misalignment. To test this, we rendered five chinchillas vestibular deficient via bilateral gentamicin treatment and unilaterally implanted them with a head-mounted MVP. Comparison of 3D angular vestibulo-ocular reflex (aVOR) responses during 2 Hz, 50°/s peak horizontal sinusoidal head rotations in darkness on the first, third, and seventh days of continual MVP use revealed that eye responses about the intended axis remained stable (at about 70% of the normal gain) while misalignment improved significantly by the end of 1 week of prosthetic stimulation. A comparable time course of improvement was also observed for head rotations about the other two semicircular canal axes and at every stimulus frequency examined (0.2-5 Hz). In addition, the extent of disconjugacy between the two eyes progressively improved during the same time window. These results indicate that the central nervous system rapidly adapts to multichannel prosthetic vestibular stimulation to markedly improve 3D aVOR alignment within the first week after activation. Similar adaptive improvements are likely to occur in other species, including humans.

Dual-laser measurement of human stapes footplate motion under blast exposure.

Hearing damage is one of the most frequently observed injuries in Service members and Veterans even though hearing protection devices (HPDs, e.g. earplugs) have been implemented to prevent blast-induced hearing loss. However, the formation and prevention mechanism of the blast-induced hearing damage remains unclear due to the difficulty for conducting biomechanical measurements in ears during blast exposure. Recently, an approach reported by Jiang et al. (2019) used two laser Doppler vibrometers (LDVs) to measure the motion of the tympanic membrane (TM) in human temporal bones during blast exposure. Using the dual laser setup, we further developed the technology to detect the movement of the stapes footplate (SFP) in ears with and without HPDs while under blast exposure. Eight fresh human cadaveric temporal bones (TBs) were involved in this study. The TB was mounted in a "head block" after performing a facial recess surgery to access the SFP, and a pressure sensor was inserted near the TM in the ear canal to measure the pressure reaching the TM (P1). The TB was exposed to a blast overpressure measuring around 7 psi or 48 kPa at the entrance of the ear canal (P0). Two LDVs were used to measure the vibrations of the SFP and TB (as a reference). The exact motion of the SFP was determined by subtracting the TB motion from the SFP data. Results included a measured peak-to-peak SFP displacement of 68.7 ± 31.6 µm (mean ± SD) from all eight TBs without HPDs. In five of the TBs, the insertion of a foam earplug reduced the SFP displacement from 48.3 ± 6.3 µm to 21.8 ± 10.4 µm. The time-frequency analysis of the SFP velocity signals indicated that most of the energy spectrum was concentrated at frequencies below 4 kHz within the first 2 ms after blast and the energy was reduced after the insertion of HPDs. This study describes a new methodology to quantitatively characterize the response of the middle ear and the energy entering the cochlea during blast exposure. The experimental data are critical for determining the injury of the peripheral auditory system and elucidating the damage formation and prevention mechanism in an ear exposed to blast.

Investigating the Geometry and Mechanical Properties of Human Round Window Membranes Using Micro-Fringe Projection.

HYPOTHESIS: The geometry and the mechanical property of the round window membrane (RWM) have a fundamental impact on the function of cochlea. BACKGROUND: Understanding the mechanical behavior of RWM is important for cochlear surgery and design for the cochlear implant. Although the anatomy of RWM has been widely studied and described in the literature, argument remains regarding the true shape of RWM. The mechanical properties of RWM are also scarcely reported due to the difficulty of the measurement of the small size RWM. METHODS: In this paper, micro-fringe projection was used to reconstruct the 3-dimensional geometries of 14 RWMs. Mechanical properties of the RWMs were subsequently measured using finite element (FE) model and an inverse method. The three-dimensional surface topographies and the curvatures of the two major directions reconstructed from the micro-fringe projection both demonstrated wide variations among samples. RESULTS: The diameters of the RWMs vary from 1.65 to 2.2 mm and the curvatures vary from -0.97 to 3.76 mm-1. The nonlinear elasticity parameters in the Ogden model for each sample was measured and the average effective Young's modulus is approximately 1.98 MPa. CONCLUSION: The geometries and mechanical properties of the human RWM measured in the work could potentially be applied to surgery design and on modeling analysis for the cochlea.

A novel 3D video oculography system for measuring cross-axis vestibulo-ocular reflex.

We present a video oculography (VOG) system with 6-degree-of-freedom (6-DOF) mobility for real-time measurements of the binocular 3D eye position of a small animal. A hybrid hexapod that allowed for multi-axis complex motions with the resolution of the microscopic level was used to control the motion of the animal. The instantaneous eyeball movement of the animal was determined based on two approaches: (1) tracking of marker arrays affixed to the cornea; and (2) tracking the pupil outline. The tracking of the eyeball movement and the motion control of the hexapod were implemented with the LabVIEW virtual instruments. Compared with our previous measurements using a servo-motor-based single-axis VOG system, positional error reduced from more than 4% to less than 0.7%. Validation showed that the tracking errors in three rotational axes are less than 2% for the magnitude and less than 5° for the direction angle. The present VOG system is an effective tool for cross-axis 3D vestibulo-ocular reflex study on small animals.

Change in cochlear response in an animal model of otitis media with effusion.

Our previous studies confirm that middle ear mobility is reduced in the presence of otitis media with effusion (OME). Variations in middle ear function may result in changes in cochlear response in OME ears. With the long-term goal of evaluating cochlear function in OME ears, the aim of this study was to measure the displacement of the basilar membrane (BM) in guinea pig ears with OME. Vibrations of the BM at the apex and basal turn were measured in an in vitro preparation extracted 3 and 14 days after injection of lipopolysaccharide in the middle ear of guinea pigs. The results show that the displacement sensitivity of the BM at the apex and the basal turn to sound pressure in the ear canal was reduced up to 25 dB at their characteristic frequencies, respectively. Cochlear gain with respect to umbo movement was also changed in ears with OME in both groups. This study provides data for analysis of the change of BM vibration in a guinea pig OME model.

Mechanical Properties of Baboon Tympanic Membrane from Young to Adult.

Mechanical properties of the tympanic membrane (TM) play an important role in sound transmission through the middle ear. While numerous studies have investigated the mechanical properties of the adult human TM, the effects of age on the TM's properties remain unclear because of the limited published data on the TM of young children. To address this deprivation, we used baboons in this study as an animal model for investigating the effect of age on the mechanical properties of the TM. Temporal bones were harvested from baboons (Papio anubis) of four different age groups: less than 1 year, 1-3 years, 3-5 years, and older than 5 years of age or adult. The TM specimens were harvested from baboon temporal bones and cut into rectangle strips along the inferior-superior direction, mainly capturing the influence of the circumferential direction fibers on the TM's mechanical properties. The elasticity, ultimate tensile strength, and relaxation behavior of the baboon TM were measured in each of the four age groups with a mechanical analyzer. The average effective Young's modulus of adult baboon TM was approximately 3.1 MPa, about two times higher than that of a human TM. The Young's moduli of the TM samples demonstrated a 26 % decrease from newborn to adult (from 4.2 to 3.1 MPa). The average ultimate tensile strength of the TMs for all the age groups was ~ 2.5 MPa. There was no significant change in the ultimate tensile strength and relaxation behavior among age groups. The preliminary results reported in this study provide a first step towards understanding the effect of age on the TM mechanical properties from young to adult.

Finite element modeling of sound transmission with perforations of tympanic membrane.

A three-dimensional finite element (FE) model of human ear with structures of the external ear canal, middle ear, and cochlea has been developed recently. In this paper, the FE model was used to predict the effect of tympanic membrane (TM) perforations on sound transmission through the middle ear. Two perforations were made in the posterior-inferior quadrant and inferior site of the TM in the model with areas of 1.33 and 0.82 mm(2), respectively. These perforations were also created in human temporal bones with the same size and location. The vibrations of the TM (umbo) and stapes footplate were calculated from the model and measured from the temporal bones using laser Doppler vibrometers. The sound pressure in the middle ear cavity was derived from the model and measured from the bones. The results demonstrate that the TM perforations can be simulated in the FE model with geometrical visualization. The FE model provides reasonable predictions on effects of perforation size and location on middle ear transfer function. The middle ear structure-function relationship can be revealed with multi-field coupled FE analysis.

Virtual Rhesus Labyrinth Model Predicts Responses to Electrical Stimulation Delivered by a Vestibular Prosthesis.

To better understand the spread of prosthetic current in the inner ear and to facilitate design of electrode arrays and stimulation protocols for a vestibular implant system intended to restore sensation after loss of vestibular hair cell function, we created a model of the primate labyrinth. Because the geometry of the implanted ear is complex, accurately modeling effects of prosthetic stimuli on vestibular afferent activity required a detailed representation of labyrinthine anatomy. Model geometry was therefore generated from three-dimensional (3D) reconstructions of a normal rhesus temporal bone imaged using micro-MRI and micro-CT. For systematically varied combinations of active and return electrode location, the extracellular potential field during a biphasic current pulse was computed using finite element methods. Potential field values served as inputs to stochastic, nonlinear dynamic models for each of 2415 vestibular afferent axons, each with unique origin on the neuroepithelium and spiking dynamics based on a modified Smith and Goldberg model. We tested the model by comparing predicted and actual 3D vestibulo-ocular reflex (VOR) responses for eye rotation elicited by prosthetic stimuli. The model was individualized for each implanted animal by placing model electrodes in the standard labyrinth geometry based on CT localization of actual implanted electrodes. Eye rotation 3D axes were predicted from relative proportions of model axons excited within each of the three ampullary nerves, and predictions were compared to archival eye movement response data measured in three alert rhesus monkeys using 3D scleral coil oculography. Multiple empirically observed features emerged as properties of the model, including effects of changing active and return electrode position. The model predicts improved prosthesis performance when the reference electrode is in the labyrinth's common crus (CC) rather than outside the temporal bone, especially if the reference electrode is inserted nearly to the junction of the CC with the vestibule. Extension of the model to human anatomy should facilitate optimal design of electrode arrays for clinical application.

Change of middle ear transfer function in otitis media with effusion model of guinea pigs.

Otitis media with effusion (OME) is an inflammatory disease of the middle ear that causes most cases of conductive hearing loss observed in the pediatric population. With the long term goal of evaluating middle ear function with OME, the aim of the current study was to create an animal model of OME in which middle ear transfer functions could be measured. In guinea pigs, OME was created by injecting lipopolysaccharide (LPS) into the middle ear. Evidence of OME was assessed by otoscopy, tympanometry, histology, and by measuring the volume of fluid in the middle ear. Vibrations of the umbo and round window membrane were measured with a laser Doppler vibrometer at frequency range of 200-40 kHz in three groups of 3, 7, and 14 days after injection of LPS. Changes in displacement of the umbo and round window membrane in response to 80 dB SPL sound in the ear canal were measured across the frequency range. Displacement of both the umbo and round window membrane was reduced at all time points following LPS injections. Further, the change of the displacement transmission ratio (DTR) from the tympanic membrane to the round window occurred mainly in chronic (e.g. 14 days post-LPS injection) OME ears. This study provides useful data for analyzing the change of middle ear transfer function in OME ears.

Combined effect of fluid and pressure on middle ear function.

In our previous studies, the effects of effusion and pressure on sound transmission were investigated separately. The aim of this study is to investigate the combined effect of fluid and pressure on middle ear function. An otitis media with effusion model was created by injecting saline solution and air pressure simultaneously into the middle ear of human temporal bones. Tympanic membrane displacement in response to 90 dB SPL sound input was measured by a laser vibrometer and the compliance of the middle ear was measured by a tympanometer. The movement of the tympanic membrane at the umbo was reduced up to 17 dB by the combination of fluid and pressure in the middle ear over the auditory frequency range. The fluid and pressure effects on the umbo movement in the fluid-pressure combination are not additive. The combined effect of fluid and pressure on the umbo movement is different compared with that of only fluid or pressure change in the middle ear. Negative pressure in fluid-pressure combination had more effect on middle ear function than positive pressure. Tympanometry can detect the middle ear pressure of the fluid-pressure combination. This study provides quantitative information for analysis of the combined effect of fluid and pressure on tympanic membrane movement.

Fixation and detachment of superior and anterior malleolar ligaments in human middle ear: experiment and modeling.

The aim of this study is to investigate the function of the superior malleolar ligament (SML) and the anterior malleolar ligament (AML) in human middle ear for sound transmission through simulations of fixation and detachment of these ligaments in human temporal bones and a finite element (FE) ear model. Two laser vibrometers were used to measure the vibrations of the tympanic membrane (TM) and stapes footplate. A 3-D FE ear model was used to predict the transfer function of the middle ear with ligament fixation and detachment. The results demonstrate that fixations and detachments of the SML and AML had different effects on TM and stapes footplate movements. Fixation of the SML resulted in a reduction of displacement of the TM (umbo) and the footplate at low frequencies (f<1000 Hz), but also caused a shift of displacement peak to higher frequencies. Fixation of both SML and AML caused a reduction of 15 dB at umbo or stapes at low frequencies. Detachment of the SML had almost no effect on TM and footplate mobility, but AML detachment had a minor effect on TM and footplate movement. The FE model was able to predict the effects of SML and AML fixation and detachment.

Tympanometry and laser Doppler interferometry measurements on otitis media with effusion model in human temporal bones.

HYPOTHESIS: The aim of this study is to investigate the effect of middle ear fluid and pressure on tympanic membrane mobility by using laser Doppler interferometry and to compare these results with tympanometry. BACKGROUND: Tympanometry has been commonly used for evaluation of otitis media with effusion, a middle ear disease with fluid in the cavity. However, this test lacks specific interpretations of middle ear disorders based on tympanometric data. Laser interferometry, as an advanced research tool to measure middle ear function, may provide knowledge of how tympanic membrane mobility is affected by middle ear fluid and pressure. METHODS: An otitis media with effusion model was created in seven human temporal bones for conducting experiments with tympanometry and laser interferometry. Middle ear pressure varied from -20 to +20 cm water, and the amount of fluid in the middle ear was gradually increased to fill the cavity. RESULTS: The displacement of the tympanic membrane measured by laser interferometry at selected frequencies decreased significantly corresponding to the middle ear air pressure changes. Tympanometry detected middle ear pressure by the change of tympanometric peak location, but the tympanogram shape was not affected by the middle ear pressure. The middle ear fluid was detected by tympanometry with as little as 0.3 mL, and laser interferometry was able to measure the displacement change of the tympanic membrane with 0.2 or 0.3 mL fluid at different frequencies. CONCLUSION: Laser interferometry can detect the effect of middle ear pressure and fluid on tympanic membrane movement as well as tympanometry does.

Rhesus Cochlear and Vestibular Functions Are Preserved After Inner Ear Injection of Saline Volume Sufficient for Gene Therapy Delivery.

Sensorineural losses of hearing and vestibular sensation due to hair cell dysfunction are among the most common disabilities. Recent preclinical research demonstrates that treatment of the inner ear with a variety of compounds, including gene therapy agents, may elicit regeneration and/or repair of hair cells in animals exposed to ototoxic medications or other insults to the inner ear. Delivery of gene therapy may also offer a means for treatment of hereditary hearing loss. However, injection of a fluid volume sufficient to deliver an adequate dose of a pharmacologic agent could, in theory, cause inner ear trauma that compromises functional outcome. The primary goal of the present study was to assess that risk in rhesus monkeys, which closely approximates humans with regard to middle and inner ear anatomy. Secondary goals were to identify the best delivery route into the primate ear from among two common surgical approaches (i.e., via an oval window stapedotomy and via the round window) and to determine the relative volumes of rhesus, rodent, and human labyrinths for extrapolation of results to other species. We measured hearing and vestibular functions before and 2, 4, and 8 weeks after unilateral injection of phosphate-buffered saline vehicle (PBSV) into the perilymphatic space of normal rhesus monkeys at volumes sufficient to deliver an atoh1 gene therapy vector. To isolate effects of injection, PBSV without vector was used. Assays included behavioral observation, auditory brainstem responses, distortion product otoacoustic emissions, and scleral coil measurement of vestibulo-ocular reflexes during whole-body rotation in darkness. Three groups (N = 3 each) were studied. Group A received a 10 µL transmastoid/trans-stapes injection via a laser stapedotomy. Group B received a 10 µL transmastoid/trans-round window injection. Group C received a 30 µL transmastoid/trans-round window injection. We also measured inner ear fluid space volume via 3D reconstruction of computed tomography (CT) images of adult C57BL6 mouse, rat, rhesus macaque, and human temporal bones (N = 3 each). Injection was well tolerated by all animals, with eight of nine exhibiting no signs of disequilibrium and one animal exhibiting transient disequilibrium that resolved spontaneously by 24 h after surgery. Physiologic results at the final, 8-week post-injection measurement showed that injection was well tolerated. Compared to its pretreatment values, no treated ear's ABR threshold had worsened by more than 5 dB at any stimulus frequency; distortion product otoacoustic emissions remained detectable above the noise floor for every treated ear (mean, SD and maximum deviation from baseline: -1.3, 9.0, and -18 dB, respectively); and no animal exhibited a reduction of more than 3 % in vestibulo-ocular reflex gain during high-acceleration, whole-body, passive yaw rotations in darkness toward the treated side. All control ears and all operated ears with definite histologic evidence of injection through the intended site showed similar findings, with intact hair cells in all five inner ear sensory epithelia and intact auditory/vestibular neurons. The relative volumes of mouse, rat, rhesus, and human inner ears as measured by CT were (mean ± SD) 2.5 ± 0.1, 5.5 ± 0.4, 59.4 ± 4.7 and 191.1 ± 4.7 µL. These results indicate that injection of PBSV at volumes sufficient for gene therapy delivery can be accomplished without destruction of inner ear structures required for hearing and vestibular sensation.

A CMOS Neural Interface for a Multichannel Vestibular Prosthesis.

We present a high-voltage CMOS neural-interface chip for a multichannel vestibular prosthesis (MVP) that measures head motion and modulates vestibular nerve activity to restore vision- and posture-stabilizing reflexes. This application specific integrated circuit neural interface (ASIC-NI) chip was designed to work with a commercially available microcontroller, which controls the ASIC-NI via a fast parallel interface to deliver biphasic stimulation pulses with 9-bit programmable current amplitude via 16 stimulation channels. The chip was fabricated in the ONSemi C5 0.5 micron, high-voltage CMOS process and can accommodate compliance voltages up to 12 V, stimulating vestibular nerve branches using biphasic current pulses up to 1.45±0.06 mA with durations as short as 10 µs/phase. The ASIC-NI includes a dedicated digital-to-analog converter for each channel, enabling it to perform complex multipolar stimulation. The ASIC-NI replaces discrete components that cover nearly half of the 2nd generation MVP (MVP2) printed circuit board, reducing the MVP system size by 48% and power consumption by 17%. Physiological tests of the ASIC-based MVP system (MVP2A) in a rhesus monkey produced reflexive eye movement responses to prosthetic stimulation similar to those observed when using the MVP2. Sinusoidal modulation of stimulus pulse rate from 68-130 pulses per second at frequencies from 0.1 to 5 Hz elicited appropriately-directed slow phase eye velocities ranging in amplitude from 1.9-16.7 °/s for the MVP2 and 2.0-14.2 °/s for the MVP2A. The eye velocities evoked by MVP2 and MVP2A showed no significant difference ( t-test, p=0.34), suggesting that the MVP2A achieves performance at least as good as the larger MVP2.

Histopathologic Changes of the Inner ear in Rhesus Monkeys After Intratympanic Gentamicin Injection and Vestibular Prosthesis Electrode Array Implantation.

Bilateral vestibular deficiency (BVD) due to gentamicin ototoxicity can significantly impact quality of life and result in large socioeconomic burdens. Restoring sensation of head rotation using an implantable multichannel vestibular prosthesis (MVP) is a promising treatment approach that has been tested in animals and humans. However, uncertainty remains regarding the histopathologic effects of gentamicin ototoxicity alone or in combination with electrode implantation. Understanding these histological changes is important because selective MVP-driven stimulation of semicircular canals (SCCs) depends on persistence of primary afferent innervation in each SCC crista despite both the primary cause of BVD (e.g., ototoxic injury) and surgical trauma associated with MVP implantation. Retraction of primary afferents out of the cristae and back toward Scarpa's ganglion would render spatially selective stimulation difficult to achieve and could limit utility of an MVP that relies on electrodes implanted in the lumen of each ampulla. We investigated histopathologic changes of the inner ear associated with intratympanic gentamicin (ITG) injection and/or MVP electrode array implantation in 11 temporal bones from six rhesus macaque monkeys. Hematoxylin and eosin-stained 10-µm temporal bone sections were examined under light microscopy for four treatment groups: normal (three ears), ITG-only (two ears), MVP-only (two ears), and ITG + MVP (four ears). We estimated vestibular hair cell (HC) surface densities for each sensory neuroepithelium and compared findings across end organs and treatment groups. In ITG-only, MVP-only, and ITG + MVP ears, we observed decreased but persistent ampullary nerve fibers of SCC cristae despite ITG treatment and/or MVP electrode implantation. ITG-only and ITG + MVP ears exhibited neuroepithelial thinning and loss of type I HCs in the cristae but little effect on the maculae. MVP-only and ITG + MVP ears exhibited no signs of trauma to the cochlea or otolith end organs except in a single case of saccular injury due to over-insertion of the posterior SCC electrode. While implanted electrodes reached to within 50-760 µm of the target cristae and were usually ensheathed in a thin fibrotic capsule, dense fibrotic reaction and osteoneogenesis were each observed in only one of six electrode tracts examined. Consistent with physiologic studies that have demonstrated directionally appropriate vestibulo-ocular reflex responses to MVP electrical stimulation years after implantation in these animals, histologic findings in the present study indicate that although intralabyrinthine MVP implantation causes some inner ear trauma, it can be accomplished without destroying the distal afferent fibers an MVP is designed to excite.

Skin grafting facilitates the maintenance of head recording chambers for neurophysiological recording.

Maintaining a clean, quiescent tissue surface that is free of granulation and infection in the floor of a head-mounted chamber used for intracranial single-unit recording studies typically requires frequent cleaning. Considering the favourable outcomes of ontological surgical techniques that have long been used to create a dry, skin-lined mastoid cavity in patients with chronic otitis media, skin should be an ideal biological dressing to cover otherwise exposed dura mater in recording chambers. In chambers that required frequent cleaning, we harvested a thin layer of skin without hair follicles from the medial surface of the upper arms of two Rhesus monkeys and grafted the skin on the exposed dura surface. Each case resulted in a clean, dry, insensate, self-healing, easily maintained tissue surface that remained healthy despite the reduced frequency of chamber maintenance. We recommend this technique to reduce the potential for infection, to prevent cerebral spinal fluid leakage or bleeding in experiment and to minimise animal anxiety that might otherwise result from frequent chamber cleanings.