Electrical Stimulation publications

Background: Otitis media (OM) is an inflammatory disease of the middle ear characterized by mucosal remodeling, effusion, and conductive hearing loss. Although antibiotics and surgical procedures remain standard treatments, their efficacy is often limited by recurrence, antibiotic resistance, and chronic progression. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulatory technique that activates the cholinergic anti-inflammatory pathway through α7 nicotinic acetylcholine receptor (α7nAChR) signaling. This study aimed to evaluate the anti-inflammatory effects of taVNS in a lipopolysaccharide (LPS)-induced mouse model of acute otitis media (AOM) and to assess whether these effects may involve α7nAChR-dependent mechanisms. Methods: AOM was induced by transtympanic injection of LPS in BALB/c mice, followed by taVNS applied to the auricular concha using biphasic square pulses (0.3 mA, 20 Hz, 200 μs). Methyllycaconitine, a selective α7nAChR antagonist, was administered to assess receptor involvement. Auditory function, tympanic membrane morphology, and mucosal changes were assessed through auditory brainstem response testing, otoscopic imaging, and histological analysis. Cytokine levels in middle ear effusion and serum were quantified by ELISA, while inflammatory gene and protein expression were analyzed using qPCR and Western blotting. Statistical analyses were performed using one-way ANOVA or Kruskal-Wallis tests with post hoc comparisons. Results: taVNS significantly improved hearing thresholds and reduced mucosal thickening and goblet cell hyperplasia in AOM mice. It markedly decreased tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in middle ear effusion, and mechanistically, this anti-inflammatory effect was associated with suppression of NF-κB activation without altering TLR4 or MYD88 expression. These effects were abolished by methyllycaconitine pretreatment. taVNS also reduced spleen enlargement and systemic cytokine concentrations, indicating modulation of both local and systemic inflammation. Conclusions: taVNS was associated with attenuation of LPS-induced acute otitis media and reduced NF-κB activation and downstream cytokine expression in a manner consistent with the involvement of α7nAChR-related signaling. By attenuating excessive inflammatory responses, taVNS was associated with improved auditory function and reduced middle ear injury, suggesting its potential as a non-invasive therapeutic strategy for LPS-induced acute otitis media.

Objective: The purpose of this paper is to present a chronic, preclinical, pilot study of a multi-electrode auditory nerve implant. To date, the most successful auditory neuroprosthesis is the cochlear implant, but these devices have known limitations. Intraneural stimulation of the auditory nerve is a promising alternative, but preclinical investigations of multi-electrode devices have been limited to acute or semi-chronic studies. Methods: Six cats were chronically implanted in the right auditory nerve with a 15-channel Utah Slant ArrayTM. The array's position in the internal auditory canal was confirmed using computed tomography. Electrode impedance and evoked responses were recorded regularly during the indwelling period to evaluate performance. Results: Two of the six implants met endpoint criteria at 6 months, with stable electrode impedances and robust evoked responses on at least 50% of their channels. Another two implants exhibited stable electrode impedances, but activation thresholds increased over three months. Two implants failed within the first two weeks due to device migration caused by connector-related issues. Conclusion: This study reports the first successful chronic deployment of an multi-electrode auditory nerve implant in a preclinical model. Two implanted cats exhibited stable chronic performance, marked by a consistent set of electrodes capable of eliciting evoked responses. The failure modes of the remaining four cats are discussed and recommendations are made to stabilize implant placement. The study lays a solid foundation for future chronic safety and efficacy investigations as part of an effort to translate this new neuroprosthetic technology into the clinic.

In adults with acquired hearing loss, cortical reorganization and cross‐modal plasticity critically influence the timing and outcomes of cochlear implantation. This study examined the effects of 2 weeks of bilateral auditory deprivation—induced by intense broadband noise—on the structure and gene expression in the primary auditory (A1) and visual (V1) cortices of adult rats. The results revealed that the total neuronal counts in both the A1 and V1 remained unchanged compared to controls. Morphological analysis showed no significant change in mature dendritic spine density in either region, but immature spine density was significantly reduced in the V1 cortex. Ultrastructural examination demonstrated notable synaptic alterations in the A1 cortex, including significant reductions in postsynaptic density (PSD) length, thickness, area, and synaptic vesicle number—changes that were not observed in the V1 cortex. Transcriptomic profiling indicated a region‐specific response, with 197 differentially expressed genes (DEGs) in the A1 cortex, compared to a broader alteration of 545 DEGs in the V1 cortex, which were significantly involved in neuronal signaling and synaptic transmission. These findings demonstrate that auditory deprivation induces distinct molecular and synaptic remodeling in the A1 and V1 cortices, identifying neuronal plasticity and synaptic regulation as central mechanisms for cross‐modal reorganization in the adult brain.

Objectives: Following deafness, a cochlear implant (CI) can be used for the restoration of hearing. CI effectiveness relies on the condition of the auditory nerve, which typically degenerates after deafness. The nerve’s condition can be assessed with the electrically evoked compound action potential (eCAP), the whole-nerve response to an electric pulse. Changes in the eCAP following an increase in the inter-phase gap (IPG) of a biphasic pulse have been reported to be informative of neural survival. This IPG effect can be explained by the temporal separation of the hyperpolarizing phase from the depolarizing phase. We hypothesize that increasing the phase duration (PD) has a similar effect. Design: We investigated the PD effect in normal hearing and in ototoxically deafened guinea pigs (total N = 40) with various conditions of the auditory nerve by recording eCAPs to biphasic current pulses with alternating polarity and with varying PD and IPG. The eCAP data were obtained from both chronically and acutely implanted guinea pigs by using CI stimulation paradigms with a fixed charge and varying PD (30, 50, or 100 µs) and IPG (2.1 or 30 µs). We evaluated six eCAP measures: five derived from the amplitude growth function and the N 1 latency. We examined the relationships of PD and IPG effects with the survival of the spiral ganglion cells. Results: The PD effects were stronger for latency than IPG effects, but weaker for the other five evaluated eCAP measures. The PD effect did not correlate as well with neural survival as the IPG effect. The IPG effect decreased with increasing PD, and accordingly, the stronger correlations between the IPG effect and neural survival were found for a short PD. Notably, the latency increase with increasing PD was greater than 1, which indicates the second phase of the pulse significantly contributes to the eCAP. This second-phase contribution was larger for lower neural survival. Conclusions: The PD effect of latency has predictive power in assessing neural survival. When using other eCAP measures than latency, the best approach to assess neural survival is using the IPG effect with a short PD (around 30 µs).

For patients with severe and profound hearing loss, cochlear implant (CI), a common and effective modality for restoring hearing, directly stimulates spiral ganglion neurons (SGNs) to generate electrical activity and form auditory perception. However, the postoperative outcome of CI is significantly influenced by the number of surviving SGNs, ​​which is a key focus of preoperative evaluation​​. Existing audiologic function and radiographic tests cannot directly demonstrate the integrity of inner ear primary neurons. In this study, ​​we developed and validated​​ a radionuclide‐labeled anti‐vesicular glutamate transporter 1 (anti‐VGLUT1) antibody‐drug and achieved animal‐level in vivo imaging of cochlear SGNs using nuclear imaging. By screening the public single‐cell sequencing database, it is found that VGLUT1 can serve as a representative cell membrane marker for SGN in the cochlea. The potential of anti‐VGLUT1 conjugated to the long half‐life 177 Lu as a molecular probe to detect the relative number of SGNs in SGN‐injured mouse and pig models is explored. The study provides a novel method for assessing cochlear nerve integrity in vivo by visualizing target antigen expression levels through nuclear imaging. This approach is promising to help CI candidates with preoperative inner ear SGN integrity assessment, contributing to clinical decision‐making.

Presbycusis or age-related hearing loss (ARHL) affects millions of people worldwide, increasing their risk of cognitive decline and poor quality of life. However, ARHL remains an irreversible condition due to our inability to induce inner-ear hair cell regeneration. Nevertheless, multisession epidural stimulation of the auditory cortex (AC) at the onset of ARHL prevents hearing threshold elevation in naturally aging Wistar rats. Accordingly, we hypothesized that anodal direct current (DC) stimulation of the AC may also compensate for age-related maladaptive, activity-dependent changes. Here, we examined immunocytochemical markers in the AC, including early genes (c-fos and Arc), AMPA receptors (GluR2/3), parvalbumin (PV), and GAD67, along with auditory-evoked potentials (CAEPs) recorded in both auditory and visual (VC) cortices. When comparing 6 and 18.13-month-old rats without AC simulation, we observed loss of c-fos and Arc-positive neurons and decreased GluR2/3 expression, confirming altered AC neuronal network plasticity and activation. In addition, we noted changes in PV and decreased GAD67 immunoreactivity suggesting disrupted inhibition and significantly increased wave amplitudes in CAEPs, altered AC latencies, and decreased VC responses. By contrast, electrically stimulated rats showed no significant variations in early gene markers, GluR2/3, PV, or GAD67 with age, and the amplitudes and latencies of CAEPs recorded in their AC and VC resembled those of young rat. These findings indicate that anodal DC stimulation at the onset of ARHL delays AC aging by minimizing the loss of inhibition and preventing increases in cortical excitability in Wistar rats.

Tinnitus, a widespread condition affecting numerous individuals worldwide, remains a significant challenge due to limited effective therapeutic interventions. Intriguingly, patients using cochlear implants (CIs) have reported significant relief from tinnitus symptoms, although the underlying mechanisms remain unclear and intracochlear implantation risks cochlear damage and hearing loss. This study demonstrates that targeted intracochlear electrical stimulation (ES) in guinea pigs with noise‐induced hearing loss reversed tinnitus‐related maladaptive plasticity in the cochlear nucleus (CN), characterized by reduced auditory innervation, increased somatosensory innervation, and diminished inhibitory neural networks. Additionally, a customized extracochlear ES delivered by a newly designed extracochlear electrode array to guinea pigs with salicylate‐induced tinnitus also reversed the aforementioned maladaptive plasticity and alleviated tinnitus without causing additional cochlear damage or hearing loss. These findings suggest that CI‐delivered ES may alleviate tinnitus by reversing maladaptive CN plasticity. Additionally, the extracochlear ES strategy offers a promising tinnitus treatment with minimal risk to hearing.

Spiral ganglion neurons (SGNs) transmit auditory information from cochlear hair cells to the brain. SGNs are thus not only important for normal hearing, but also for effective functioning of cochlear implants, which stimulate SGNs when hair cells are missing. SGNs slowly degenerate following aminoglycoside-induced hair cell loss, a process thought to involve an immune response. However, the specific immune response pathways involved remain unknown. We used RNAseq to gain a deeper understanding immune-related and other transcriptomic changes that occur in the rat spiral ganglion after kanamycin-induced deafening. Among the immune and inflammatory genes that were selectively upregulated in deafened spiral ganglia, the complement cascade genes were prominent. We then assessed SGN survival, as well as immune cell numbers and activation, in the spiral ganglia of rats with a CRISPR-Cas9-mediated knockout of complement component 3 (C3). Similar to previous findings in our lab and other deafened rodent models, we observed an increase in macrophage number and increased expression of CD68, a marker of phagocytic activity and cell activation, in macrophages in the deafened ganglia. Moreover, we found an increase in MHCII expression on spiral ganglion macrophages and an increase in lymphocyte number in the deafened ganglia, suggestive of an adaptive immune response. However, C3 knockout did not affect SGN survival or increase in macrophage number/activation, implying that complement activation does not play a role in SGN death after deafening. Together, these data suggest that both innate and adaptive immune responses are activated in the deafened spiral ganglion, with the adaptive response directly contributing to cochlear neurodegeneration.

Hearing loss can lead to long-lasting effects on the central nervous system, and current therapies, such as auditory training and rehabilitation, show mixed success in improving perception and speech comprehension. Vagus nerve stimulation (VNS) is an adjunctive therapy that can be paired with rehabilitation to facilitate behavioral recovery after neural injury. However, VNS for auditory recovery has not been tested after severe hearing loss or significant damage to peripheral receptors. This study investigated the utility of pairing VNS with passive or active auditory rehabilitation in a rat model of noise-induced hearing loss. Although auditory rehabilitation helped rats improve their frequency discrimination, learn novel speech discrimination tasks, and achieve speech-in-noise performance similar to normal hearing controls, VNS did not enhance recovery of speech sound perception. These results highlight the limitations of VNS as an adjunctive therapy for hearing loss rehabilitation and suggest that optimal benefits from neuromodulation may require restored peripheral signaling.

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.

Cochlear Implants (CI) are an effective neuroprosthesis for humans with profound hearing loss, enabling deaf adults to have phone calls without lipreading and babies to have successful language development. However, CIs have significant limitations in complex hearing situations, motivating the need for further research, including studies in animal models. Here, we demonstrate the usefulness of wide field Ca++ imaging in assessing different CI stimulation strategies. One major challenge in electrophysiology in CI animals lies in excluding the CI electric artifacts from the recording, since they are orders of magnitude larger than the amplitude of action potentials. Also, electrophysiology can rarely sample large areas of neuropil at high spatial resolution. To circumvent these problems, we have set up an imaging system allowing us to monitor neural activity in the auditory cortex (AC) of CI supplied rats using the Ca++ sensitive dye OGB. Here we describe an initial experiment with this setup, in which we recorded cortical responses to 4 different stimulation patterns which were delivered across 3 CI channels to the contralateral ear. We then investigated two parameters that have been shown to affect intelligibility in CI users: pulse rate and relative pulse timing across CI channels. While pulse rate had only a very modest effect on the discriminability of the neural responses, the stimulation mode had a major effect, with simultaneous pulse timing, perhaps surprisingly, allowing much better pattern discrimination than interleaved sampling. The result suggests that allowing collisions of pulses on neighboring channels may not always be detrimental, at least if partial overlaps of pulses, in which anodic and cathodic pulse phases might cancel, are avoided.

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.

Introduction Obesity affects millions of Americans. The vagal nerves convey the degree of stomach fullness to the brain via afferent visceral fibers. Studies have found that vagal nerve stimulation (VNS) promotes reduced food intake, causes weight loss, and reduces cravings and appetite. Methods Here, we evaluate the efficacy of a novel stimulus waveform applied bilaterally to the subdiaphragmatic vagal nerve stimulation (sVNS) for almost 13 weeks. A stimulating cuff electrode was implanted in obesity-prone Sprague Dawley rats maintained on a high-fat diet. Body weight, food consumption, and daily movement were tracked over time and compared against three control groups: sham rats on a high-fat diet that were implanted with non-operational cuffs, rats on a high-fat diet that were not implanted, and rats on a standard diet that were not implanted. Results Results showed that rats on a high-fat diet that received sVNS attained a similar weight to rats on a standard diet due primarily to a reduction in daily caloric intake. Rats on a high-fat diet that received sVNS had significantly less body fat than other high-fat controls. Rats receiving sVNS also began moving a similar amount to rats on the standard diet. Conclusion Results from this study suggest that bilateral subdiaphragmatic vagal nerve stimulation can alter the rate of growth of rats maintained on a high-fat diet through a reduction in daily caloric intake, returning their body weight to that which is similar to rats on a standard diet over approximately 13 weeks. Graphical Abstract

Sensorineural hearing loss is very difficult to treat. Currently, one of the techniques used for hearing rehabilitation is a cochlear implant that can transform sound into electrical signals instead of inner ear hair cells. However, the prognosis remains very poor if sufficient auditory nerve cells are not secured. In this study, the effect of mouse embryonic stem cells (mESC) and photobiomodulation (PBM) combined treatment on auditory function and auditory nerve cells in a secondary neuropathy animal model was investigated. To confirm the engraftment of stem cells in vitro, cochlear explants were treated with kanamycin (KM) to mimic nerve damage and then cocultured with GFP-mESC. GFP-mESCs were observed to have attached and integrated into the explanted samples. An animal model for secondary neurodegeneration was achieved by KM treatment and was treated by a combination therapy of GFP-mESC and NIR-PBM at 8 weeks of KM treatment. Hearing recovery by functional testing using auditory brain stem response (ABR) and eABR was measured as well as morphological changes and epifluorescence analysis were conducted after 2 weeks of combination therapy. KM treatment elevated the hearing threshold at 70–80 dB and even after the combination treatment with GFP-mESC and PBM was applied, the auditory function was not restored. In addition, the stem cells transplanted into cochlea has exponentially increased due to PBM treatment although did not produce any malignancy. This study confirmed that the combined treatment with mESC and PBM could not improve hearing or increase the response of the auditory nerve. Nevertheless, it is noteworthy in this study that the cells are distributed in most cochlear tissues and the proliferation of stem cells was very active in animals irradiated with PBM compared to other groups wherein the stem cells had disappeared immediately after transplantation or existed for only a short period of time.

Objectives This study investigated the effect of synchronized activation of automatic gain control (AGC) on sound-localization and speech-recognition performance in cochlear implant users who use a contralateral hearing aid (bimodal listeners). Bimodal listeners often have poor spatial-hearing abilities, which could be partly due to perturbed interaural spatial acoustic cues from the two devices, as these act independently and provide incongruent or mismatched information. Synchronized AGC activation may remove this perturbation and improve spatial hearing. Design Ten bimodal listeners were fitted with a bimodal prototype allowing real-time communication between hearing aid and CI. They were tested for their horizontal localization ability of brief (150 ms) noise bursts presented in the frontal hemisphere. To test for frequency- and level-specific effects, sounds were band-passed (broadband 0.25-6 kHz, high-pass 1.5-6 kHz, and low-pass 0.25-0.85 kHz) and presented at levels of 50 and 80 dBA (i.e., below and above AGC activation threshold). Speech-in-noise recognition was assessed for short sentences presented at 75 dBA with a noise-adaptive algorithm. Sentences were presented from the front, with the noise presented either from the front or at a horizontal angle of ±70 deg. The sound-localization and speech-recognition tests were performed both with independently acting and synchronized AGC settings. Results Localization bias (mean error [95% confidence interval lower, upper range]) varied with sound type: -46 [-53, -38], -31 [-37, -23] and -2 [-16, 10] deg for high-pass, broadband and low-pass sounds, respectively. AGC synchronization did not systematically affect bias (paired difference in mean error with independent and synchronized AGCs: 6 [-3, 20] deg). However, AGC synchronization did reduce sound-localization error variability for 80-dB broadband sounds by 15 [6, 26] deg from an error standard deviation of 67 [63, 77] to 52 [45, 59] deg for independent and synchronized AGCs, respectively (no systematic difference was found for 50-dB and the high-pass and low-pass sounds). Speech-in-noise thresholds differed for noise presented from the front (0.3 [-1.3, 1.1] dB), implanted side (0.6 [-1.3, 2.3] dB), and non-implanted side (-2.4 [-4.6, 0.1] dB), but synchronization did not have an effect in these conditions. However, spatial release from masking thresholds did improve with synchronization when the noise was presented at the hearing-aid side: -2.7 [-4.5, -0.6] dB. Conclusions AGC synchronization improved the localization of broadband sounds presented above the AGC activation threshold in bimodal listeners. This is in line with the hypothesis that bimodal interaural level differences can be preserved for loud broadband sounds through AGC synchronization. Synchronization did not compromise the listener’s speech perception abilities, despite the reduction of the level of speech when AGC kicks in. Moreover, spatial release from masking was enhanced, suggesting that improved spatial hearing benefits speech recognition in noise

This protocol was used to collect data now published in the Journal of Neural Engineering, Spatially selective stimulation of the pig vagus nerve to modulate target effect versus side effect using the multi-contact ImThera stimulating device. https://doi.org/10.1088/1741-2552/acb3fd Dataset has been published to pennsieve.io and can be found at: https://doi.org/10.26275/efbj-8evl

Sensory cortical areas are robustly modulated by higher-order cortices. Our previous study shows that the anterior cingulate cortex (ACC) can immediately and transiently enhance responses in the mouse auditory cortex (ACx). Here, we further examined whether strong activation of ACC neurons can induce long-term effects in mice of both sexes. To our surprise, only stimulation of cell bodies in the ACC, but not ACC-to-ACx terminal activation, induced long-term enhancement of auditory responses in the ACx. Anatomical examination showed that the ACC indirectly projects to the ACx via the rhinal cortex (RCx). High-frequency stimulation of ACC-projecting terminals to the RCx or RCx-projecting terminals to the ACx induced a similar effect as the cell body activation of ACC neurons, whereas silencing the RCx blocked this long-term enhancement. High-frequency stimulation of ACC projections to the RCx also induced long-term augmentation of sound-evoked flight behavior in male mice. These results show that the ACC promotes the long-term enhancement of auditory responses in the ACx through an indirect pathway via the RCx. SIGNIFICANCE STATEMENT In this study, we demonstrate that the anterior part of the anterior cingulate cortex (ACC) evokes long-term enhancement of auditory responses in the auditory cortex (ACx) when it is strongly activated. Importantly, instead of a direct projection, we show that the ACC implements this effect via an indirect pathway through the lateral rhinal cortex using a series of physiological, optogenetic, anatomic, and behavioral experiments. Along with a short-term effect, this long-term enhancement induced by an indirect ACC-to-ACx projection could increase the odds of survival when animals are faced with threats after a significant event.

Fear and anxiety are brain states that evolved to mediate defensive responses to threats. The defense reaction includes multiple interacting behavioral, autonomic and endocrine adjustments, but their integrative nature is poorly understood. In particular, although threat has been associated with various cardiac changes, there is no clear consensus regarding the relevance of these changes for the integrated defense reaction. Here we identify rapid microstates that are associated with specific behaviors and heart rate dynamics, which are affected by long-lasting macrostates and reflect context-dependent threat levels. In addition, we demonstrate that one of the most commonly used defensive behavioral responses—freezing as measured by immobility—is part of an integrated cardio-behavioral microstate mediated by Chx10 + neurons in the periaqueductal gray. Our framework for systematic integration of cardiac and behavioral readouts presents the basis for a better understanding of complex neural defensive states and their associated systemic functions.

Introduction Electrocochleography (ECochG) is increasingly used in cochlear implant (CI) surgery, in order to monitor the effect of insertion of the electrode array aiming to preserve residual hearing. However, obtained results are often difficult to interpret. Here we aim to relate changes in ECochG responses to acute trauma induced by different stages of cochlear implantation by performing ECochG at multiple time points during the procedure in normal-hearing guinea pigs. Materials and methods Eleven normal-hearing guinea pigs received a gold-ball electrode that was fixed in the round-window niche. ECochG recordings were performed during the four steps of cochlear implantation using the gold-ball electrode: (1) Bullostomy to expose the round window, (2) hand-drilling of 0.5–0.6 mm cochleostomy in the basal turn near the round window, (3) insertion of a short flexible electrode array, and (4) withdrawal of electrode array. Acoustical stimuli were tones varying in frequency (0.25–16 kHz) and sound level. The ECochG signal was primarily analyzed in terms of threshold, amplitude, and latency of the compound action potential (CAP). Midmodiolar sections of the implanted cochleas were analyzed in terms of trauma to hair cells, modiolar wall, osseous spiral lamina (OSL) and lateral wall. Results Animals were assigned to cochlear trauma categories: minimal ( n = 3), moderate ( n = 5), or severe ( n = 3). After cochleostomy and array insertion, CAP threshold shifts increased with trauma severity. At each stage a threshold shift at high frequencies (4–16 kHz) was accompanied with a threshold shift at low frequencies (0.25–2 kHz) that was 10–20 dB smaller. Withdrawal of the array led to a further worsening of responses, which probably indicates that insertion and removal trauma affected the responses rather than the mere presence of the array. In two instances, CAP threshold shifts were considerably larger than threshold shifts of cochlear microphonics, which could be explained by neural damage due to OSL fracture. A change in amplitudes at high sound levels was strongly correlated with threshold shifts, which is relevant for clinical ECochG performed at one sound level. Conclusion Basal trauma caused by cochleostomy and/or array insertion should be minimized in order to preserve the low-frequency residual hearing of CI recipients.

This protocol was used to collect data now published in the Journal of Neural Engineering, Spatially selective stimulation of the pig vagus nerve to modulate target effect versus side effect using the multi-contact ImThera stimulating device. https://doi.org/10.1088/1741-2552/acb3fd Dataset has been published to pennsieve.io and can be found at: https://doi.org/10.26275/efbj-8evl