Cochlear implants (CIs) enable hearing via direct electrical stimulation of the spiral ganglion neurons (SGN). Outcomes with a CI depend, in part, on the number and excitability of the SGNs. In an animal model, we introduced the Failure Index (FI) as an electrically-evoked compound action potential (eCAP)-derived marker of cochlear health. The FI informs about the presence, site, and size of SGN lesions. Here, we translated the FI to clinical recordings from human MED-EL CI users. In this retrospective study, we included patient data recorded between 2016 and 2024 from 199 ears with postlingual hearing loss and 79 ears with prelingual hearing loss. The averaged FI values over all contacts of the array were stable within the analysis period (3 rd month to 1 st year postoperatively). The FI increased with age and was elevated in etiologies associated with higher SGN loss. Using 3D reconstruction from cone-beam computed tomography scans, we confirmed that the FI was independent of electrode-to-modiolus distance (0.1–2.5 mm). The FI showed individual patterns along the array, with maxima usually found at basal contacts, corresponding to reduced neural health at high-frequency cochlear regions. In a selected group of postlingual-deaf ears, we found higher correlation coefficients between speech-perception scores and the FI compared to other eCAP-derived markers (i.e., threshold, slope, and amplitude). These results were in line with the hypothesis that the FI may serve as a clinical tool to identify implanted ears with reduced neural health and to identify contacts stimulating areas of reduced SGN survival and integrity.

INTRODUCTION:Cochlear implants (CIs) enhance hearing by stimulating spiral ganglion neurons (SGNs) but are less effective in individuals with compromised SGN functionality. Advances in regenerative medicine suggest that local delivery of medical drugs or cell therapy could regenerate the auditory nerve. This study evaluates a minimally invasive technique for precise delivery of cell-sized beads, simulating cell therapy, into the cochlear modiolus of human temporal bones. METHODS:Ten fresh-frozen human temporal bone specimens were used. Five bones served to establish the injection trajectory using a tungsten rod probe, and the remaining five for injecting microbeads into the modiolus. The surgical procedure involved accessing the middle ear via the external ear canal, performing a cochleostomy at the first cochlear turn, and drilling into the modiolus. Beads were injected into the modiolus using a Hamilton syringe connected to an injection pump, followed by micro-computed tomography imaging and histological assessment. RESULTS:Accurate placement of the tungsten rod probe within the modiolus was achieved in four out of five bones. Microbead injections indicated 89 to 97% retention within the modiolus, with minimal leakage. The technique showed consistent trajectory with low variability. CONCLUSION:The study demonstrates the feasibility of a minimally invasive, precise injection method for delivering and retaining cell-sized beads into the cochlear modiolus. This technique enables future local delivery of medical drugs or cell therapy drugs aimed at hearing restoration, benefiting both current CI users and CI candidates. Further research is necessary to evaluate precision, reproducibility, and long-term outcomes of the procedure.

While cochlear implants (CIs) historically use cathodic-leading pulses for stimulation, studies in humans found that anodic-leading pulses are perceived louder than cathodic-leading ones. Modeling studies proposed that cathodic pulses excite the spiral ganglion neurons (SGNs) more peripherally than anodic pulses. Thus, the anodic-benefit in human CI listeners is thought to reflect degenerated peripheral processes. We used an animal model to test the contributions of peripheral dendrites and central axons of SGNs to polarity-effectiveness in CI stimulation. We mechanically lesioned the SGN (∼400 µm diameter; n = 18 cochleae) and introduced a 9-day degeneration time (n = 13 cochleae) to mimic human SGN degeneration. These lesions were compared to 20 control ears. We stimulated via a guinea-pig adjusted CI with symmetric, biphasic pulses (monopolar mode) of alternating leading-phase polarity (50µs/phase). Electrically-evoked compound action potential recordings to anodic- and cathodic-leading pulses were separated in the analysis to calculate the polarity effect. We confirmed the cathodic-benefit for cochleae with healthy SGN (lower threshold, larger amplitudes, dynamic ranges, and steeper slopes). Longer latencies (50-70µs) to cathodic than anodic monophasic and biphasic pulses confirmed the proposed peripheral (cathodic) and central (anodic) spike-initiation sites. The cathodic benefit persisted after acute lesioning, which prolonged latencies for anodic- but not for cathodic-leading pulses - consistent with remaining structures being excited by both polarities. After chronic degeneration, the threshold showed polarity-specific changes, leading to an anodic-benefit. The observed decline in cathodic-effectiveness with reduced neural health confirmed theoretical considerations for human CI users with stimulus-polarity and degeneration-type dependent changes in spike-initiation site.

Cochlear implants (CIs) enable hearing with the deafened ear, via direct, electrical stimulation of the spiral ganglion neurons (SGN). Thus, the outcome depends on the number and excitability of the SGNs. We recently established the electrically-evoked compound action potential (eCAP)-derived Failure Index (FI) as cochlear-health marker in the animal model. The FI informs about the presence, site, and size of a SGN lesion. Here, we translated the FI to clinical recordings of MED-EL CI users. For the retrospective study, we selected patient data from the database of the German Hearing Center Hannover recorded 2017 to 2024. We included 199 post-lingually and 79 pre-lingually deafened ears. Averaged FIs over all contacts of a CI were stable within the analysis period (3 rd month to 1 st year postoperatively). The FI increased with age and was elevated for etiologies associated with higher SGN loss. Utilizing 3D information from cone beam-computed tomography scans, we confirmed that the FI was independent of distance (0.1-2.5 mm) to the modiolus. The FI showed individual patterns along the array with maxima usually at basal contacts, corresponding to elevated SGN loss at high frequencies. In a selected group of post-lingually deaf ears, we confirmed the correlation of the FI with speech perception in quiet and in noise (n=28, r 2 =0.12-0.55). Thus, we propose the FI as promising clinical tool to identify CI-implanted ears with reduced neural health and contacts close to areas of SGN loss. Thereby, it can serve to guide speech-processor fitting to optimize CI outcomes.

Spiral ganglion neuron (SGN) degeneration is a candidate factor for reduced hearing outcomes in cochlear implant (CI) users. However, there is no procedure available to identify CI contacts close to focal SGN degeneration in human patients. In an animal model, we assessed the impact of focal SGN degeneration on electrical responsiveness and derived an electrophysiological marker for the presence, location, and size of such lesions. We introduced cochlear microlesions in 13 guinea pigs (six female) and recorded electrically evoked compound action potentials (eCAP) after 8-12 d. These were compared with recordings from controls (N = 8) and acutely lesioned cochleae (N = 12). We stimulated via 6-contact CIs in monopolar configuration with symmetric, biphasic pulses of alternating polarity. We histologically assessed the lesion and its relative position to the CI contacts. The lesions (230-850 µm) significantly elevated thresholds and reduced amplitudes. The effect was found at stimulation distances of 3.5 mm from the lesion. A novel eCAP marker, Failure Index (FI: maximal input/output ratio), was significantly elevated in the presence of degenerated SGN. It indicates the failure to efficiently transduce the stimulation current into neural activation (N1P1 amplitude). The FI showed classification accuracies of 80% and identified contacts closest to the lesion in ∼80% of cases within ±700 µm (∼electrode spacing) from the lesion site and was correlated with the lesion size. Thus, the FI is a clinically relevant, noninvasive marker that is suitable for clinical datasets without a priori knowledge on lesions, when combined with the statistical method of median splitting.

Congenital single-sided deafness (SSD) leads to an aural preference syndrome that is characterized by overrepresentation of the hearing ear in the auditory system. Cochlear implantation (CI) of the deaf ear is an effective treatment for SSD. However, the newly introduced auditory input in congenital SSD often does not reach expectations in late-implanted CI recipients with respect to binaural hearing and speech perception. In a previous study, a reduction of the interaural time difference (ITD) sensitivity has been shown in unilaterally congenitally deaf cats (uCDCs). In the present study, we focused on the interaural level difference (ILD) processing in the primary auditory cortex. The uCDC group was compared with hearing cats (HCs) and bilaterally congenitally deaf cats (CDCs). The ILD representation was reorganized, replacing the preference for the contralateral ear with a preference for the hearing ear, regardless of the cortical hemisphere. In accordance with the previous study, uCDCs were less sensitive to interaural time differences than HCs, resulting in unmodulated ITD responses, thus lacking directional information. Such incongruent ITDs and ILDs cannot be integrated for binaural sound source localization. In normal hearing, the predominant effect of each ear is excitation of the auditory cortex in the contralateral cortical hemisphere and inhibition in the ipsilateral hemisphere. In SSD, however, auditory pathways reorganized such that the hearing ear produced greater excitation in both cortical hemispheres and the deaf ear produced weaker excitation and preserved inhibition in both cortical hemispheres.

Objectives: Cochlear implantation criteria include subjects with residual low-frequency hearing. To minimize implantation trauma and to avoid unwanted interactions of electric- and acoustic stimuli, it is often recommended to stop cochlear implantation before the cochlear implant (CI) reaches the cochlear partition with residual hearing, as determined by an audiogram. For this purpose, the implant can be used to record acoustically evoked signals during implantation, including cochlear compound action potentials (CAP), cochlear microphonics (CMs), and summating potentials (SPs). The former two have previously been used to monitor residual hearing in clinical settings. Design: In the present study we investigated the use of intracochlear, bipolar SP recordings to determine the exact cochlear position of the contacts of implanted CIs in guinea pig cochleae (n = 13). Polarity reversals of SPs were used as a functional marker of intracochlear position. Micro computed tomography (µCT) imaging and a modified Greenwood function were used to determine the cochleotopic positions of the contacts in the cochlea. These anatomical reconstructions were used to validate the SP-based position estimates. Results: The precision of the SP-based position estimation was on average within ± 0.37 octaves and was not impaired by moderate hearing loss caused by noise exposure after implantation. It is important to note that acute hearing impairment did not reduce the precision of the method. The cochleotopic position of CI accounted for ~70% of the variability of SP polarity reversals. Outliers in the dataset were associated with lateral CI positions. Last, we propose a simplified method to avoid implantation in functioning parts of the cochlea by approaching a predefined frequency region using bipolar SP recordings through a CI. Conclusions: Bipolar SP recordings provide reliable information on electrode position in the cochlea. The position estimate remains reliable after moderate hearing loss. The technique presented here could be applied during CI surgery to monitor the CI approach to a predefined frequency region.

Introduction Electrical stimulation of the auditory nerve in cochlear implants (CI) is known to result in facial-nerve stimulation (FNS) in a subset of CI users. These FNS are alleviate in the clinics via reprogramming of processor settings, or even CI revision surgery.

Noise-induced hearing loss (NIHL) is one of the leading causes of sensorineural hearing loss with global importance. The current treatment of choice for patients with hearing problems is a hearing aid or a cochlear implant. However, there is currently no treatment to restore physiological hearing. The development of preventive drugs is currently the focus of hearing research. In order to test the efficacy of a drug, the active ingredient has to be applied at reliable concentrations over a period of time. Osmotic minipumps can provide local drug delivery into the perilymph. Combined with a cochlear implant or a tube, the implantation of the pumps may lead to increased hearing thresholds. Such surgery-related threshold shifts complicate the examination of other factors, such as noise. The aim of the present study was to develop an animal model for the examination of substances that potentially prevent NIHL. For this purpose, six male guinea pigs were unilaterally implanted with a silicon catheter with a hook-shaped microcannula at its tip, attached to an artificial perilymph containing osmotic minipump. One week after surgery, the animals were exposed to four hours of a musical piece, presented at 120 dB SPL, to induce a threshold shift. The implantation of the hook-delivery device caused a moderate threshold shift that allows to detect an additional noise-induced temporary threshold shift. This method enables to investigate drug effects delivered prior to the noise insult in order to establish a preventive strategy against noise-induced temporary threshold shifts. The established drug delivery approach allows the release of drugs into the inner ear in a known concentration and for a known duration. This provides a scientific tool for basic research on drug effects in normal hearing animals.

One severe side effect of the use of cochlear implants (CI) is coincidental facial nerve stimulation (FNS). Clinical methods to alleviate FNS range from the reprogramming of processor settings to revision surgery. We systematically assessed different changes in CI stimulation modes that have been discussed in the literature as "rescue factors" from FNS: electrode configuration (broad to focused), pulse shape (symmetric biphasic to pseudo-monophasic), and pulse polarity (cathodic to anodic). An FNS was assessed, based on electrophysiological thresholds, in 204 electrically evoked compound action potential (eCAP) input/output functions recorded from 33 ears of 26 guinea pigs. The stimulation level difference between auditory nerve eCAP threshold and FNS threshold was expressed as the eCAP-to-FNS offset. Coincidental FNS occurred in all animals and in 45% of all recordings. A change from monopolar to focused (bipolar, tripolar) configurations minimized FNS. The Euclidean distance between the CI contacts and the facial nerve explained no more than 33% of the variance in FNS thresholds. For both the FNS threshold and the eCAP-to-FNS offset, the change from cathodic to anodic pulse polarity significantly reduced FNS and permitted a gain of 14-71% of the dynamic range of the eCAP response. This "anodic rescue effect" was stronger for pseudo-monophasic pulses as compared to the symmetric biphasic pulse shape. These results provide possible mechanisms underlying recent clinical interventions to alleviate FNS. The "anodic-rescue effect" may offer a non-invasive therapeutic option for FNS in human CI users that should be tested clinically, preferably in combination with current-focusing methods.

Introduction: Electrocochleography has recently emerged as a diagnostic tool in cochlear implant surgery, purposing hearing preservation and optimal electrode positioning. Objective: In this experimental study, extra-cochlear potentials were obtained during cochlear implant surgery in guinea pigs. The aim was to determine electrophysiological changes indicating cochlear trauma after cochleostomy and after electrode implantation in different insertion depths. Methods: Normal-hearing guinea pigs (n = 14) were implanted uni- or bilaterally with a multichannel electrode. The extra-cochlear cochlear nerve action potentials were obtained in response to acoustic stimuli at specific frequencies before and after cochleostomy, and after introduction of the electrode bundle. After the electrophysiological experiments, the guinea pigs were euthanized and microtomography was performed, in order to determine the position of the electrode and to calculate of the depth of insertion. Based on the changes of amplitude and thresholds in relation to the stimulus frequency, the electrophysiological data and the position obtained by the microtomography reconstruction were compared. Results: Cochleostomy promoted a small electrophysiological impact, while electrode insertion caused changes in the amplitude of extra-cochlear electrophysiological potentials over a wide range of frequencies, especially in the deepest insertions. There was, however, preservation of the electrical response to low frequency stimuli in most cases, indicating a limited auditory impact in the intraoperative evaluation. The mean insertion depth of the apical electrodes was 5339.56 mu m (+/- 306.45 - 6 inserted contacts) and 4447.75 mu m (+/- 290.23 - 5 inserted contacts). Conclusions: The main electrophysiological changes observed during surgical procedures occurred during implantation of the electrode, especially the deepest insertions, whereas the cochleostomy disturbed the potentials to a lesser extent. While hearing loss was often observed apical to the cochlear implant, it was possible to preserve low frequencies after insertion.

The facial nerve stimulation (FNS) is an adverse site effect in cochlear implant (CI) stimulation. Approaches to avoid FNS are silencing the affected CI contacts and shifting to triphasic pulses. However, when switching the pulse shape, also the polarity of the dominant phase (i.e. 1st in biphasic and 2nd in triphasic) is changed. We assessed influences of stimulation polarity on FNS thresholds in an animal model.

Current developments of electrodes for neural recordings address the need of biomedical research and applications for high spatial acuity in electrophysiological recordings. One approach is the usage of novel materials to overcome electrochemical constraints of state-of-the-art metal contacts. Promising materials are carbon nanotubes (CNTs), as they are well suited for neural interfacing. The CNTs increase the effective contact surface area to decrease high impedances while keeping minimal contact diameters. However, to prevent toxic dissolving of CNTs, an appropriate surface coating is required. In this study, we tested flexible surface electrocorticographic (ECoG) electrodes, coated with a CNT-silicone rubber composite. First, we describe the outcome of surface etching, which exposes the contact nanostructure while anchoring the CNTs. Subsequently, the ECoG electrodes were used for acute in vivo recordings of auditory evoked potentials from the guinea pig auditory cortex. Both the impedances and the signal-to-noise ratios of coated contacts were similar to uncoated gold contacts. This novel approach for a safe application of CNTs, embedded in a surface etched silicone rubber, showed promising results but did not lead to improvements during acute recordings.

Hearing misfortune that happens progressively as you age (presbycusis) is normal. Practically a large portion of individuals in the US more seasoned than age 65 have some level of hearing misfortune. Hearing misfortune is characterized as one of three sorts are Conductive (includes external or center ear), Sensor neural (includes internal ear), Blended (mix of the two), Maturing and ongoing openness to noisy commotions both add to hearing misfortune. Different variables, like over the top earwax, can briefly decrease how well your ears lead sounds. You can't invert most kinds of hearing misfortune. Nonetheless, you and your PCP or a conference expert can find ways to further develop what you hear.

Cochlear implants (CIs) are the treatment of choice for profoundly hearing impaired people. It has been proposed that speech perception in CI users is influenced by the neural health (deafferentation, demyelination and degeneration) of the cochlea, which may be heterogeneous along an individual cochlea. Several options have been put forward to account for these local differences in neural health when fitting the speech processor settings, however with mixed results. The interpretation of the results is hampered by the fact that reliable markers of locally restricted changes in spiral ganglion neuron (SGN) health are lacking.The aim of the study was (i) to establish mechanical micro-lesions in the guinea pig as a model of heterogeneous SGN deafferentation and degeneration and (ii) to assess potential electrophysiological markers that can also be used in human subjects. First, we defined the extent of micro-lesions in normal hearing animals using acoustically-evoked compound action potentials (aCAPs); second, we measured electrically-evoked CAPs (eCAPs) before and after focal lesioning in neomycin-deafened and implanted animals. Therefore, we inserted guinea pig adjusted 6-contact CIs through a cochleostomy in the scala tympani. The eCAP was recorded from a ball electrode at the round window niche in response to monopolar or bipolar, 50 µs/phase biphasic pulses of alternating anodic- and cathodic-leading polarity. To exclude the large electrical artifact from the analysis, we focused on the late eCAP component. We systematically isolated the eCAP parameter that showed local pre- versus post-lesion changes and lesion-target specificity.Histological evaluation of the cleared cochleae revealed focal damage of an average size of 0.0036 mm3 with an apical-basal span of maximal 440 µm. We found that the threshold of the late N2P2 eCAP component was significantly elevated after lesioning when stimulating at basal (near the lesion), but not apical (distant to the lesion) CI contacts. To circumvent the potentially conflicting influence of the apical-basal gradient in eCAP thresholds, we used the polarity effect (PE=cathodic-anodic) as a relative measure. During monopolar stimulation, but not bipolar stimulation, the PE was sensitive to the lesion target and showed significantly better cathodic than anodic thresholds after soma lesions.We conclude that the difference in N2P2 thresholds in response to cathodic versus anodic-leading monopolar stimulation corresponds to the presence of SGN soma damage, and may therefore be a marker for SGN loss. We consider this electrophysiological estimate of local neural health a potentially relevant tool for human applications because of the temporal separation from the stimulation artifact and possible implementation into common eCAP measurements.

Conventional loudness coding with CIs by pulse current amplitude has a disadvantage: Increasing the stimulation current increases the spread of excitation in the auditory nerve, resulting in stronger channel interactions at high stimulation levels. These limit the number of effective information channels that a CI user can perceive. Stimulus intensity information (loudness) can alternatively be transmitted via pulse phase duration. We hypothesized that loudness coding by phase duration avoids the increase in the spread of the electric field and thus leads to less channel interactions at high stimulation levels. To avoid polarity effects, we combined this coding with pseudomonophasic stimuli. To test whether this affects the spread of excitation, 16 acutely deafened guinea pigs were implanted with CIs and neural activity from the inferior colliculus was recorded while stimulating with either biphasic, amplitude-coded pulses, or pseudomonophasic, duration- or amplitude-coded pulses. Pseudomonophasic stimuli combined with phase duration loudness coding reduced the lowest response thresholds and the spread of excitation. We investigated the channel interactions at suprathreshold levels by computing the phase-locking to a pulse train in the presence of an interacting pulse train on a different electrode on the CI. Pseudomonophasic pulses coupled with phase duration loudness coding reduced the interference by 4-5% compared to biphasic pulses, depending on the place of stimulation. This effect of pseudomonophasic stimuli was achieved with amplitude coding only in the basal cochlea, indicating a distance- or volume dependent effect. Our results show that pseudomonophasic, phase-duration-coded stimuli slightly reduce channel interactions, suggesting a potential benefit for speech understanding in humans.

Intraoperative control of insertion depth is crucial during cochlear implantation (CI) in the presence of residual hearing. We determined the intracochlear position of CI with regard to cochleotopy using bipolar electrocochleograms (ECochG) recorded over a CI in guinea pigs.

Bei der restgehörerhaltenden Versorgung mit Cochlea-Implantaten (CI) ist die Intraoperative Kontrolle der Insertionstiefe von großer Bedeutung. Anhand der Analyse des über CI bipolar abgeleiteten Elektrocochleograms (ECochG) haben wir im Tierexperiment die intracochleäre Position des CI relativ zur Cochleotopie bestimmt.

Intracochlear optical stimulation has been suggested as an alternative approach to hearing prosthetics in recent years. This study investigated the properties of a near infrared laser (NIR) induced optoacoustic effect. Pressure recordings were performed at the external meatus of anaesthetized guinea pigs during intracochlear NIR stimulation. The sound pressure and power spectra were determined. The results were compared to multi unit responses in the inferior colliculus (IC). Additionally, the responses to NIR stimulation were compared to IC responses induced by intracochlear electric stimulation at the same cochlear position to investigate a potentially confounding contribution of direct neural NIR stimulation. The power spectra of the sound recorded at the external meatus (n = 7) had most power at frequencies below 10 kHz and showed little variation for different stimulation sites. The mean spike rates of IC units responding to intracochlear NIR stimulation (n = 222) of 17 animals were significantly correlated with the power of the externally recorded signal at frequencies corresponding to the best frequencies of the IC units. The response strength as well as the sound pressure at the external meatus depended on the pulse peak power of the optical stimulus. The sound pressure recorded at the external meatus reached levels above 70 dB SPL peak equivalent. In hearing animals a cochlear activation apical to the location of the fiber was found. The absence of any NIR responses after pharmacologically deafening and the comparison to electric stimulation at the NIR stimulation site revealed no indication of a confounding direct neural NIR stimulation. Intracochlear optoacoustic stimulation might become useful in combined electro-acoustic stimulation devices in the future.

In neuroscience, single-shank penetrating multi-electrode arrays are standard for sequentially sampling several cortical sites with high spatial and temporal resolution, with the disadvantage of neuronal damage. Non-penetrating surface grids used in electrocorticography (ECoG) permit simultaneous recording of multiple cortical sites, with limited spatial resolution, due to distance to neuronal tissue, large contact size and high impedances. Here we compared new thin-film parylene C ECoG grids, covering the guinea pig primary auditory cortex, with simultaneous recordings from penetrating electrode array (PEAs), inserted through openings in the grid material. ECoG grid local field potentials (LFP) showed higher response thresholds and amplitudes compared to PEAs. They enabled, however, fast and reliable tonotopic mapping of the auditory cortex (place-frequency slope: 0.7 mm/octave), with tuning widths similar to PEAs. The ECoG signal correlated best with supragranular layers, exponentially decreasing with cortical depth. The grids also enabled recording of multi-unit activity (MUA), yielding several advantages over LFP recordings, including sharper frequency tunings. ECoG first spike latency showed highest similarity to superficial PEA contacts and MUA traces maximally correlated with PEA recordings from the granular layer. These results confirm high quality of the ECoG grid recordings and the possibility to collect LFP and MUA simultaneously.