Search

The electrically evoked compound action potential (eCAP) is a direct measure of the responsiveness of the auditory nerve to electrical stimulation from a cochlear implant (CI). CIs offer a unique opportunity to study the auditory nerve’s electrophysiological behavior in individual human subjects over time. In order to understand exactly how the eCAP relates to the condition of the auditory nerve, it is crucial to compare changes in the eCAP over time in a controlled model of deafness-induced auditory nerve degeneration. In the present study, 10 normal-hearing young adult guinea pigs were implanted and deafened 4 weeks later, so that the effect of deafening could be monitored within-subject over time. Following implantation, but before deafening, most examined eCAP characteristics significantly changed, suggesting increasing excitation efficacy (e.g., higher maximum amplitude, lower threshold, shorter latency). Conversely, inter-phase gap (IPG) effects on these measures – within-subject difference measures that have been shown to correlate well with auditory nerve survival – did not vary for most eCAP characteristics. After deafening, we observed an initial increase in excitability (steeper slope of the eCAP amplitude growth function (AGF), lower threshold, shorter latency and peak width) which typically returned to normal-hearing levels within a week, after which a slower process, probably reflecting spiral ganglion cell loss, took place over the remaining 6 weeks (e.g., decrease in maximum amplitude, AGF slope, peak area, and IPG effect for AGF slope; increase in IPG effect for latency). Our results suggest that gradual changes in peak width and latency reflect the rate of neural degeneration, while peak area, maximum amplitude, and AGF slope reflect neural population size, which may be valuable for clinical diagnostics.

Auditory function declines with age, as evidenced by communication difficulties in challenging listening environments for older adults. Declining auditory function may arise, in part, from an age-related loss and/or inactivity of low-spontaneous-rate (SR) auditory nerve (AN) fibers, a subgroup of neurons important for suprathreshold processing. Compared to high-SR fibers, low-SR fibers take longer to recover from prior stimulation. Taking advantage of this difference, the forward-masked recovery function paradigm estimates the relative proportions of low- and high-SR fibers in the AN by quantifying the time needed for AN responses to recover from prior stimulation (ΔT(recovery)). Due to the slower recovery of low-SR fibers, ANs that need more time to fully recover (longer ΔT(recovery)) are estimated to have a larger proportion of low-SR fibers than ANs that need less time (shorter ΔT(recovery)). To test the hypothesis that low-SR fiber activity is reduced in older humans, the current study assessed recovery functions in 32 older and 16 younger adults using the compound action potential. Results show that ΔT(recovery) is shorter for older adults than for younger adults, consistent with a theorized age-related loss and/or inactivity of low-SR fibers. ΔT(recovery) did not differ between individuals with and without a prior history of noise exposure as assessed by self-report. This study is the first to successfully assess forward-masked recovery functions in both younger and older adults and provides important insights into the structural and functional changes occurring in the AN with increasing age.

ZusammenfassungAusgewertet wurden 86 Patienten mit einem retrosigmoidal mikrochirurgisch resezierten Vestibularisschwannom im Tumorstadium Koos II–IV. Es zeigte sich, dass im Bereich des inneren Gehörgangs in über 2/3 der Fälle der Nervus cochlearis dem elektroneurographisch leicht zu identifizierenden Nervus facialis in immer wiederkehrenden ähnlichen Verlaufsmustern folgte. Ausgehend vom Fundus erleichterte dies die frühzeitige Identifizierung und damit den Kontinuitätserhalt des Nervus cochlearis im Verlauf des inneren Gehörgangs. Dies war vor allem dann von Bedeutung, wenn ein sicherer Funktionserhalt aufgrund der Tumorgröße oder -formation trotz intraoperativer Ableitung somatosensorischer Potenziale nicht sicher gewährleistet werden konnte, aber die Möglichkeit einer späteren Hörrehabilitation mit einem Cochleaimplantat bestehen bleiben sollte. Präoperative Magnetresonanztomographie(MRT)-Sequenzen ergaben zwar in einigen Fällen einen Hinweis auf die möglichen Nervenverläufe, die intraoperative Darstellung im inneren Gehörgang war der MRT aber überlegen.

The human inner ear contains minute three-dimensional neurosensory structures that are deeply embedded within the skull base, rendering them relatively inaccessible to regenerative therapies for hearing loss. Here we provide a detailed characterisation of the functional architecture of the space that hosts the cell bodies of the auditory nerve to make them safely accessible for the first time for therapeutic intervention. We used synchrotron phase-contrast imaging which offers the required microscopic soft-tissue contrast definition while simultaneously displaying precise bony anatomic detail. Using volume-rendering software we constructed highly accurate 3-dimensional representations of the inner ear. The cell bodies are arranged in a bony helical canal that spirals from the base of the cochlea to its apex; the canal volume is 1.6 μL but with a diffusion potential of 15 μL. Modelling data from 10 temporal bones enabled definition of a safe trajectory for therapeutic access while preserving the cochlea’s internal architecture. We validated the approach through surgical simulation, anatomical dissection and micro-radiographic analysis. These findings will facilitate future clinical trials of novel therapeutic interventions to restore hearing.

Determining the etiology of severe-to-profound sensorineural hearing loss (SP-SNHL) in pediatric subjects is particularly important in aiding the decision for auditory rehabilitation. We aimed to update the etiologic spectrum of pediatric SP-SNHL by combining internal auditory canal (IAC)-MRI with comprehensive and state-of-the-art genetic testings. From May 2013 to September 2020, 119 cochlear implantees under the age of 15 years with SP-SNHL were all prospectively recruited. They were subjected to genetic tests, including exome sequencing, and IAC-MRI for etiologic diagnosis. Strict interpretation of results were made based on ACMG/AMP guidelines and by an experienced neuroradiologist. The etiology was determined in of 65.5% (78/119) of our cohort. If only one of the two tests was done, the etiologic diagnostic rate would be reduced by at least 21.8%. Notably, cochlear nerve deficiency (n = 20) detected by IAC-MRI topped the etiology list of our cohort, followed by DFNB4 (n = 18), DFNB1 (n = 10), DFNB9 (n = 10) and periventricular leukomalacia associated with congenital CMV infection (n = 8). Simultaneous application of state-of-the-art genetic tests and IAC-MRI is essential for etiologic diagnosis, and if lesions of the auditory nerve or central nerve system are carefully examined on an MRI, we can identify the cause of deafness in more than 65% of pediatric SP-SNHL cases.

Cochlear nerve deficiency is one of the known causes of congenital sensorineural hearing loss. Management of hearing loss in children with cochlear nerve deficiency poses a multidimensional challenge. The absent or hypoplastic cochlear nerve may prevent electrical stimulation from reaching the brainstem and the auditory cortex. A deficient cochlear nerve can be associated with other inner ear malformations, which may diminish the success of cochlear implantation in those children. Promising results in adults after auditory brainstem implantation led to the expansion of candidacy to include the pediatric populations who were contraindicated for CIs. To review the outcomes of cochlear implantation versus that of auditory brainstem implantation in children with various conditions of the auditory nerve. This retrospective chart review study comprised two pediatric groups. The first group consisted of seven ABI recipients with cochlear nerve aplasia and the second group consisted of another seven children with cochlear nerve deficiencies who underwent CI surgery. The participants’ auditory skills and speech outcomes were assessed using different tests selected from the Evaluation of Auditory Responses to Speech (EARS) test battery. There were some individual variations in outcomes depending on the status of the auditory nerve. The mean CAP score of the ABI group was 2.87, while the mean SIR score was 0.62. On the other hand, the mean CAP score of the CI group was 1.29, while the mean SIR score was 0.42. Our results are in good agreement with the reported auditory perception and speech and language development outcomes of pediatric auditory brainstem implantation. We added to the growing body of literature on the importance of verifying and identifying the status of the cochlear nerve in the decision-making process of the surgical management of those pediatric groups.

Vestibular schwannomas (VS) are benign tumors that originate from the nerve sheath of one of the two vestibular nerves. VS can have a severe impact on everyday life of the patient and may lead to symptoms such as vertigo, hearing loss (e.g., as sudden deafness), deafness, and tinnitus. Treatment concepts include observational waiting with regular imaging control (“wait and scan”), radiotherapy, or surgical resection. Depending on the size of the tumor and status of functional hearing, the surgical approach may be retrosigmoidal, transtemporal, retrolabyrinthine, or translabyrinthine. The translabyrinthine approach always results in complete deafness due to opening of the bony labyrinth. If the nerve structure of the cochlear nerve is preserved, hearing rehabilitation with a cochlear implant (CI) may be successful. In this article the surgical technique for microsurgical resection of VS using a translabyrinthine approach with simultaneous cochlear implantation under intraoperative monitoring of the cochlear nerve by electrical stimulation is presented.

In cochlear implants, loudness has been shown to grow more slowly with increasing pulse phase duration (PPD) than with pulse amplitude (PA), possibly due to “leaky” charge integration. This leakiness has been recently quantified in terms of “charge integration efficiency,” defined as the log difference between the PPD dynamic range and PA dynamic range (both expressed in charge units), relative to a common threshold anchor. Such leakiness may differ across electrodes and/or test ears, and may reflect underlying neural health. In this study, we examined the across-site variation of charge integration in recipients of Cochlear© devices. PPD and PA dynamic ranges were measured relative to two threshold anchors with either a 25- or 50-microsecond PPD. Strength-duration functions, previously shown to relate to survival of spiral ganglion cells and peripheral processes, were compared to charge integration efficiency on selected electrodes. Results showed no significant or systematic relationship between the across-site variation in charge integration efficiency and electrode position or threshold levels. Charge integration efficiency was poorer with the 50-μs threshold anchor, suggesting that greater leakiness was associated with larger PPD dynamic ranges. Poorer and more variable charge integration efficiency across electrodes was associated with longer duration of any hearing loss, consistent with the idea that poor integration is related to neural degeneration. More variable integration efficiency was also associated with poorer speech recognition performance across test ears. The slopes of the strength-duration functions at maximum acceptable loudness were significantly correlated with charge integration efficiency. However, the strength-duration slopes were not predictive of duration of any hearing loss or speech recognition performance in our participants. As such, charge integration efficiency may be a better candidate to measure leakiness in neural populations across the electrode array, as well as the general health of the auditory nerve in human cochlear implant recipients.

Management of small vestibular schwannomas (VSs) remains controversial. When surgery is chosen, the preservation of facial and cochlear nerve function is a priority. In this report, we introduce and evaluate a technique to anatomically preserve the vestibular nerves to minimize manipulation and preserve the function of the facial and cochlear nerves. The vestibular nerve preservation technique was prospectively applied to resect small VS tumors in patients with serviceable preoperative hearing (American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) class A or B). Clinical and radiological data were recorded and analyzed. Ten patients met the inclusion criteria. The mean (SD) age was 40.4 (12.5) years. Follow-up ranged from 6 weeks to 2 years. The maximum tumor diameter parallel to the internal auditory canal ranged from 10 to 20 mm (mean, 14.9 (3.1) mm). There were three Koos grade 3 and seven Koos grade 2 tumors. Gross total resection was achieved in all cases. Both the facial and cochlear nerves were anatomically preserved in all cases. Postoperatively, 7 patients (70%) remained in the AAO-HNS class A or B hearing category. None of the patients had new vestibular symptoms, and all had House–Brackmann grade 1 facial function. Nervus intermedius dysfunction was observed in 1 patient preoperatively, which worsened postoperatively. Two patients had new nervus intermedius symptoms postoperatively. Improvement of facial nerve and hearing outcomes is feasible through the intentional preservation of the vestibular nerves in the resection of small VSs. Longer follow-up is required to rule out tumor recurrence.

Animal models of noise-induced hearing loss (NIHL) show a dramatic mismatch between cochlear characteristic frequency (CF, based on place of innervation) and the dominant response frequency in single auditory-nerve-fiber responses to broadband sounds (i.e., distorted tonotopy, DT). This noise trauma effect is associated with decreased frequency-tuning-curve (FTC) tip-to-tail ratio, which results from decreased tip sensitivity and enhanced tail sensitivity. Notably, DT is more severe for noise trauma than for metabolic (e.g., age-related) losses of comparable degree, suggesting that individual differences in DT may contribute to speech intelligibility differences in patients with similar audiograms. Although DT has implications for many neural-coding theories for real-world sounds, it has primarily been explored in single-neuron studies that are not viable with humans. Thus, there are no noninvasive measures to detect DT. Here, frequency following responses (FFRs) to a conversational speech sentence were recorded in anesthetized male chinchillas with either normal hearing or NIHL. Tonotopic sources of FFR envelope and temporal fine structure (TFS) were evaluated in normal-hearing chinchillas. Results suggest that FFR envelope primarily reflects activity from high-frequency neurons, whereas FFR-TFS receives broad tonotopic contributions. Representation of low- and high-frequency speech power in FFRs was also assessed. FFRs in hearing-impaired animals were dominated by low-frequency stimulus power, consistent with oversensitivity of high-frequency neurons to low-frequency power. These results suggest that DT can be diagnosed noninvasively. A normalized DT metric computed from speech FFRs provides a potential diagnostic tool to test for DT in humans. A sensitive noninvasive DT metric could be used to evaluate perceptual consequences of DT and to optimize hearing-aid amplification strategies to improve tonotopic coding for hearing-impaired listeners.

This review highlights our current understanding of the impact of unilateral hearing loss and single-sided deafness in children, offering insight into diagnosis and management. Children with unilateral hearing loss develop an aural preference toward their better hearing ear, leading to difficulties with spatial navigation, balance, speech/language skills, and quality of life when compared with typical hearing peers. Cochlear nerve aplasia and cytomegalovirus are among the most common etiologies for unilateral hearing loss, which has important implications for treatment. Hearing rehabilitation relies upon early correction of hearing loss with an appropriate auditory prosthesis. In children with single-sided deafness, cochlear implants are the only intervention that potentially offers restoration of bilateral hearing, and studies continue to refine candidacy protocols. Unilateral hearing loss has important consequences for children. Recent studies emphasize the importance of early diagnosis and investigate ways to appropriately restore bilateral hearing in these children.

Single-sided deafness (SSD) is a condition where an individual has non-functional hearing in one ear and receives no clinical benefit from amplification in that ear, with the contralateral ear possessing normal audiometric function. Cochlear implant presents a good choice in rehabilitation of SSD. The presence of a deficient cochlear nerve (CN) has been linked to poor performance with cochlear implants. CN can be measured by imaging techniques. The objective of this study was to compare CN diameter in patients who had a history of single-sided deafness because of sudden hearing loss. Retrospective study where radiologist was blind designed. 53 SSD patients who had a history of sudden hearing loss and MRI at least 5 years after the sudden hearing loss were included in this retrospective study. High-resolution 3-D constructive interference in steady state (CISS)-sequence magnetic resonance (MRI) images was review by the neurotology-experienced blind radiologist. Vertical, horizontal and area measurements of cochlear nerve between the deaf and the normal ear were made. There was no statistically significant difference between the normal ear and deaf ear of the subjects in terms of cochlear nerve vertical diameter, horizontal diameter and area. (respectively, p = 0.250; p = 0.183; p = 0.874) The numbers of remaining cochlear neurons and spiral ganglion cells in the implanted deaf ears are critical and evidence was not found for spiral ganglion cell loss in the sudden hearing loss deaf ear with SSD in MRI. In the light of all these findings, implantation would be a good choice for rehabilitation in postlingual SSD regardless of auditory deprivation duration.

Hearing or/and balance impairments may be caused by disorders of the labyrinthine artery (LA) and their branches. Most findings regarding the LA anatomy have been acquired through investigation of the cerebellopontine angle (CPA) in animal or adult human specimens. Eighty-eight CPAs and LAs of human fetuses were investigated using angio-techniques and microdissections. We found 15 intricate forms of distribution of LA. The LA usually originated from the extra-meatus loop in the anterior inferior cerebellar artery (AICA). The distribution of its terminal branches was 53.42% uni-arterial, 44.31% bi-arterial, and 2.27% tri-arterial systems. In the uni-arterial system, the LA described an anterior superior path to the cochlear nerve (CN) and originated its terminal branches in the gap between CN and the inferior part of the vestibular nerve. In the bi-arterial system, the anterior LA was located anterior and superior to the CN while the posterior LA appeared posterosuperior to the superior part of the vestibular nerve. In the tri-arterial system, the terminal branches originated directly from the AICA loop. Our results provide anatomical support to explain how compressions in the LA branches inside the internal acoustic meatus, as evoked by Schwannomas in the VII and VIII nerves, can lead to hearing and balance loss. The zone of the posterior vestibular nerve appeared to be a "safe area" for invasive procedures in these specimens.

The reticulotegmental nucleus (RtTg) has long been recognized as a crucial component of brainstem reticular formation (RF). However, the function of RtTg and its related circuits remain elusive. Here, we report a role of the RtTg in startle reflex, a highly conserved innate defensive behaviour. Optogenetic activation of RtTg neurons evokes robust startle responses in mice. The glutamatergic neurons in the RtTg are significantly activated during acoustic startle reflexes (ASR). Chemogenetic inhibition of the RtTg glutamatergic neurons decreases the ASR amplitudes. Viral tracing reveals an ASR neural circuit that the cochlear nucleus carrying auditory information sends direct excitatory innervations to the RtTg glutamatergic neurons, which in turn project to spinal motor neurons. Together, our findings describe a functional role of RtTg and its related neural circuit in startle reflexes, and demonstrate how the RF connects auditory system with motor functions., The function of brainstem reticulotegmental nucleus (RtTg) and its related circuits are not fully understood. Here, the authors report a cochlear nucleus-RtTg-spinal motor neuron circuit that specifically mediates acoustic startle reflexes.

Background A previously performed phase III trial on 112 subjects investigating prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery showed no clear beneficial effects on preservation of facial and cochlear nerve functions, though it should be considered that protection of facial nerve function was the primary outcome. However, the risk for postoperative hearing loss was halved in the nimodipine group compared to the control group (OR 0.49; 95% CI 0.18–1.30; p = 0.15). Accordingly, this phase III extension trial investigates the efficacy and safety of prophylactic nimodipine for hearing preservation in VS surgery. Methods This is a randomized, multi-center, two-armed, open-label phase III trial with blinded expert review and two-stage with interim analysis. Three hundred thirty-six adults with the indication for microsurgical removal of VS (Koos I–IV) and serviceable preoperative hearing (Gardner-Robertson scale (GR) 1–3) are assigned to either the therapy (intravenous nimodipine 1–2 mg/h from the day before surgery until the fifth postoperative day and standard of care) or the control group (surgery only and standard of care). The primary endpoint of the trial is postoperative cochlear nerve function measured before discharge according to GR 1–3 versus GR 4–5 (binary). Hearing function will be determined by pre- and postoperative audiometry with speech discrimination, which will be evaluated by a blinded expert reviewer. Furthermore, patient-reported outcomes using standardized questionnaires will be analyzed. Discussion Prophylactic parenteral nimodipine treatment may have a positive effect on hearing preservation in VS surgery and would improve patient’s quality of life. Further secondary analyses are planned. Except for dose-depending hypotension, nimodipine is known as a safe drug. In the future, prophylactic nimodipine treatment may be recommended as a routine medication in VS surgery. VS can be considered as an ideal model for clinical evaluation of neuroprotection, since hearing outcome can be classified by well-recognized criteria. The beneficial effect of nimodipine may be transferable to other surgical procedures with nerves at risk and may have impact on basic research. Trial registration EudraCT 2019-002317-19, DRKS00019107. 8th May 2020.

Auditory brainstem implant (ABI) is used to provide auditory sensations in patients with neurofibromatosis type 2 who lost their hearing due to a surgical removal of the tumor. ABI surgery, implant activation and follow-up sessions present unique challenges including the exact placement of the electrode pad in the lateral recess of the IVth ventricle, identification of electrodes that trigger non-auditory sensation and their deactivation which lowers the number of electrodes responsible for hearing, changes of T- and C-levels across follow-up sessions. We present a complete procedure using an example case starting from the surgical part with the detailed description of intraoperative eABR measurement as a guidance for pad placement to the ABI activation and first fitting sessions with auditory sensation assessment. Since the first ABI electrode pad position presented non-satisfactory intraoperative eABR results it was decided to move the pad slightly which resulted in better eABR (more electrodes with auditory responses). The discussed patient demonstrated great auditory and speech perception results after the first ABI fitting (which included three sessions over 2 consecutive days). Repositioning of the ABI electrode pad during the surgery was carried out taking into account the intraoperative eABR results and this led to an overall positive outcome for the patient. The placement of ABI electrode pad is crucial for later auditory results. This study provides detailed insight in this very specialized procedure that is not performed in every clinic and adds to the knowledge of intraoperative navigation using eABR measurements during ABI surgery.

Incomplete partition type III (IP III) is defined by a missing lamina cribrosa between the cochlea and the internal auditory canal (IAC). Cochlear implantation (CI) may result in an insertion of the electrode array into the IAC. The aim of this study is to evaluate CI surgery protocols, long-term audiological outcome, mapping and electrophysiological data after CI in IP III patients. Nine IP III patients were implanted with perimodiolar electrode arrays between 1999 and 2014; eight of them were included in this study. We evaluated mapping data, stapedius reflexes, electrode impedances and ECAP thresholds. We matched them with 3 CI patients each with normal cochlear morphology regarding sex, age, side, implant type and surgical date. Speech discrimination was evaluated with the Oldenburger sentence test for adults, Gottingen audiometric speech test for children and the Freiburger monosyllabic word test. 3 years after CI IP III patients showed a significant increase in pulse width, calculated electric load and electrode impedances in basal electrodes. Intraoperative electrically-evoked stapedius reflexes could be measured in all patients. Speech recognition scores were lower than average scores for matched patients, but without statistical significance. The significant increase of pulse width, electric load and electrode impedances of basal electrodes over time seem to be characteristic for IP III patients probably occurring due to fibrosis and neurodegeneration of the cochlear nerve. The long term audiological results are stable. Intraoperative imaging and stapedius reflexes are highly recommended to control the right position of the electrode array.

Reliable confirmation of the presence or absence of endolymphatic hydrops is essential to avoid confusing vestibular migraine with Meniere's disease. MRI inner ear imaging is a promising new method to confirm hydrops, avoiding both unnecessary invasive or destructive inner ear treatments, but it is not universally available. Tone burst electrocochleography is an older simple, quick, safe, and sensitive test that is potentially available, with existing (or minorly upgraded) equipment at most tertiary medical centers. In Meniere's disease hydrops remains after intratympanic treatments. A case is presented of a 45 year-old man with a long history of recurrent vertigo attacks who, due to an erroneous diagnosis of Meniere's disease, was given five intratympanic treatments with no effect. He was subsequently found by tone burst electrocochleography to have no hydrops and was differentially diagnosed with probable vestibular migraine. Response to treatment confirms this diagnosis. This patient's electrocochleographic findings are compared with two other patients with definite Meniere's disease, one of whom had demonstrable hydrops despite intratympanic gentamycin treatments.

We investigated if loop characteristics correlate with audio-vestibular symptoms or hemifacial spasm in patients with a vascular loop in the root entry zone (VII and VIII) and in the internal auditory canal. A retrospective, multicenter study analyzed 2622 consecutive magnetic resonance imaging (MRI) scans of the cerebellopontine angle of patients with asymmetric audio-vestibular symptom or hemifacial spasm; patients’ symptoms were confirmed by clinical tests. MRIs displaying vascular loops visible in the axial view were analyzed using multiplanar reconstruction. We evaluated (1) depth of penetration of the loop into the internal auditory canal (IAC); (2) largest diameter of the vessel; (3) nerve(s) involved in the vascular impingement, position of the loop relative to such nerve(s) and number of contacts between vessel and nerve(s); (4) length of such contact. The loop metrics described above were correlated with the patients’ audio-vestibular symptoms and hemifacial spasm. Three hundred ninety-nine patients displayed a loop visible in the MRI axial view and out of them only 118 displayed a direct contact between loop and nerve. The cochlear nerve was involved in a contact in 57.7%. Loops in direct nerve contact had a calibre > 0.85 mm, were located in the middle portion of the IAC, and correlated with vertigo (p = 0.002), tinnitus (p = 0.003), and hemifacial spasm (p

This article presents the modeling of spike trains in auditory nerve fiber (ANF) models with a one-memory self-exciting point process (SEPP) of the von Mises type. The ANF models were acoustically stimulated by a synaptic current of inner hair cells, or electrically stimulated by sinusoidally amplitude-modulated pulsatile waveforms. It has been shown that the parameters of one-memory SEPP of the von Mises type could be estimated by numerically maximizing the likelihood function from sample realizations of the spike trains in response to acoustic or electric stimulus. Furthermore, it was found that period histograms of the one-memory SEPP generated artificially on the basis of the estimated von Mises parameters agreed well with those of acoustic or electric stimulus, by performing the uniform-scores test. It implies that the waveforms of pulsatile electric stimuli should be selected such that the spike trains can be represented by one-memory SEPP of the von Mises type with appropriate parameters, efficiently carrying information to the cochlear implant user's brain, like that in acoustic stimulation of the healthy ear. The findings presented in this paper may play an important role in determining optimal parameters of pulsatile electric stimuli by using one-memory SEPP of the von Mises type, and further in the design of better cochlear prostheses.

Various studies on medial olivocochlear (MOC) efferents have implicated it in multiple roles in the auditory system (e.g., dynamic range adaptation, masking reduction, and selective attention). This study presents a systematic simulation of inferior colliculus (IC) responses with and without electrical stimulation of the MOC. Phenomenological models of the responses of auditory nerve (AN) fibers and IC neurons were used to this end. The simulated responses were highly consistent with physiological data (replicated 3 of the 4 known rate-level responses all MOC effects-shifts, high stimulus level reduction and enhancement). Complex MOC efferent effects which were previously thought to require integration from different characteristic frequency (CF) neurons were simulated using the same frequency inhibition excitation circuitry. MOC-induced enhancing effects were found only in neurons with a CF range from 750 Hz to 2 kHz. This limited effect is indicative of the role of MOC activation on the AN responses at the stimulus offset.

The use of neonatal hearing screening has enabled the identification of congenital unilateral sensorineural hearing loss (USNHL) immediately after birth, and today there are several intervention options available to minimize potential adverse effects of this disease, including cochlear implantation. This study aims to analyze the characteristics of the inner ear of a homogeneous group of congenital non-syndromic USNHL to highlight the features of the inner ear, which can help in clinical, surgical, and rehabilitative decision-making. A retrospective chart review was carried out at a tertiary referral center. Systematic diagnostic work-up and rigorous inclusion–exclusion criteria were applied to 126 children with unilateral hearing impairment, leading to a selection of 39 strictly congenital and non-syndromic USNHL cases, undergoing computed tomography (CT) and magnetic resonance (MR) imaging studies. The frequency and type of malformations of the inner ear in USNHL and unaffected contralateral ears were assessed, with an in-depth analysis of the deficiency of the cochlear nerve (CND), the internal auditory canal (IAC) and the cochlear aperture (CA). Inner ear anomalies were found in 18 out of 39 (46%) of the USNHL patients. In 1 subject, the anomalies were bilateral, and the CND resulted in the predominant identified defect (78% of our abnormal case series), frequently associated with CA stenosis. Only 3 out of 14 children with CND presented stenosis of the IAC. CND and CA stenosis (and to a much lesser extent IAC stenosis) are a frequent association within congenital and non-syndromic USNHL that could represent a distinct pathological entity affecting otherwise healthy infants. In the context of a diagnostic work-up, the evaluation with CT and MRI measurements should take place in a shared decision-making setting with thorough counseling. Both imaging techniques have proven useful in differentiating the cases that will most likely benefit from the cochlear implant, from those with potentially poor implant performance.

Background Cochlear implants (CIs) have become important for the treatment of severe-to-profound sensorineural hearing loss (SNHL). Meanwhile, electrically evoked compound action potentials (ECAPs) and electrically evoked auditory brainstem responses (EABRs), which can be examined and evaluated with minimal patient cooperation, have become more reliable for tone measurement and speech recognition postoperatively. However, few studies have compared the electrophysiological characteristics of the auditory nerve using ECAPs and EABRs under different functional states of the auditory nerve (FSANs). We used guinea pig models in which six electrodes were implanted unilaterally with continuous electrical stimulation (ES) for 4 h. The amplitude growth functions (AGFs) of the alternating polarity ECAP (AP-ECAP) and forward-masking subtraction ECAP (FM-ECAP), as well as the EABR waves under “normal” and “abnormal” FSANs, were obtained. Results Both the AP-ECAP and FM-ECAP thresholds were significantly higher than those measured by EABR under both “normal” FSAN and “abnormal” FSANs (p p p Conclusions Both of the ECAP thresholds were higher than the EABR thresholds. The AP-ECAP was more sensitive than the FM-ECAP under the “abnormal” FSAN.

The purpose of this study was to evaluate the structural integrity of the auditory neural pathway in patients with unilateral sensorineural hearing loss using quantitative diffusion-tensor tractography. Diffusion-tensor tractography imaging was performed using a 3T magnetic resonance imaging system to evaluate structural alterations in the auditory neural pathway of patients with unilateral sensorineural hearing loss. The two diffusion-tensor tractography parameters, fractional anisotropy and the apparent diffusion coefficient were compared between the ipsilateral side and the contralateral side in patients and controls. Additionally, correlations between the parameter values and the hearing loss level in patients were evaluated. A total of 24 sensorineural hearing loss patients (14 males; age range, 17–65 years; average age, 45.3 years) and 24 age and sex-matched control subjects were enrolled. Fractional anisotropy values on the ipsilateral and contralateral sides were significantly lower in patients than in the control group (p = 0.004 and 0.001, respectively). The differences in the apparent diffusion coefficient values for the ipsilateral and contralateral sides between the two groups were not significant (p = 0.279 and 0.248, respectively). There was an inverse relationship between fractional anisotropy and the severity of hearing impairment on the ipsilateral and contralateral sides (r = −0.519, p = 0.005 and r = −0.454, p = 0.015, respectively). No significant correlation was found between the apparent diffusion coefficient and hearing loss level on the ipsilateral and contralateral sides (r = 0.172, p = 0.380 and r = 0.131, p = 0.508, respectively). Quantitative diffusion-tensor tractography can be used to detect microstructural alterations in the auditory neural pathway in sensorineural hearing loss patients with normal results in standard imaging studies.

To investigate the outcomes of cochlear implantation in patients with neurofibromatosis type 2 (NF2), and to discuss the current management strategy for NF2 patients. The medical records of NF2 patients who received cochlear implants (CI) at our center between 2012 and 2016 were retrospectively reviewed. Pre-operative hearing status, tumor status, treatment of tumors, and auditory outcomes post-implantation were evaluated. Twelve patients were included in the study. Five were implanted with the tumor in situ; two of them received radiotherapy pre-implantation, and three were implanted without any previous treatment. Four patients were implanted simultaneously with tumor removal. Three patients were implanted as second-stage after failed hearing preservation surgery. The mean pure tone audiometry with the implant was 44 dB (range 25–80 dB) and the mean sentence recognition score (SRS) in a quiet environment without lip reading was 63% (range 0–97%). A poorer objective auditory outcome was identified in one patient who showed no response to electrical promontory stimulation (EPS), but the sound perception was still helpful. In total, 11 of 12 (91%) patients were daily users, and the other patient used the implant as a “sleeper” device due to its interference with contralateral hearing provided by a hearing aid. CI is an effective option in auditory rehabilitation and should be considered primarily for NF2 patients with intact cochlear nerve. EPS might be a predictor for cochlear implant performance. Good contralateral hearing may present a barrier to daily use.

To report neuroradiologic findings, surgical strategies and clinical and audiological results in a series of children with CHARGE syndrome (CS) who had been evaluated for cochlear implantation (CI). Retrospective case series. Tertiary referral university hospital. Eight profoundly deafened children with CS were included. Routine audiometric measurements, speech perception categories and speech intelligibility ratings were performed pre- and post-operatively. Neuroradiological and intraoperative findings, surgical planning, and post-operative complications were analyzed. Six children were profoundly deaf from birth and 2 had progressive hearing loss to profound levels. Cochlear nerve deficiency (CND) was noted in 5 out of the 6 patients with congenital sensorineural hearing loss (SNHL). Seven children underwent CI. Surgery was performed using standard transmastoid facial recess approach in 3 ears, subtotal petrosectomy in 3, and transmastoid single-slit labyrinthotomy in one. Temporary facial palsy occurred in one patient. In the group of patients with congenital SNHL, 2 children benefitted from CI and developed spoken language; the remaining 3 children obtained improved access to environmental sounds and used signs and gestures as their main mode of communication. The two patients with progressive SNHL had preoperative verbal language and continued to use verbal language after CI. The constant presence of temporal bone anomalies in children with CS requires surgical expertise in performing non-standard approaches for safe and effective CI. Patients with progressive SNHL and normal cochlear nerves had satisfactory results with CI. Limited benefits have been observed in presence of CND.

Permanent loss of auditory nerve (AN) fibers occurs with increasing age and sound overexposure, sometimes without hair cell damage or associated audiometric threshold elevation. Rodent studies suggest effects of AN damage on central processing and behavior, but these species have limited capacity to discriminate low-frequency speech-like sounds. Here, we introduce a new animal model of AN damage in an avian communication specialist, the budgerigar (Melopsittacus undulatus). The budgerigar is a vocal learner and speech mimic with sensitive low-frequency hearing and human-like behavioral sensitivity to many complex signals including speech components. Excitotoxic AN damage was induced through bilateral cochlear infusions of kainic acid (KA). Acute KA effects on cochlear function were assessed using AN compound action potentials (CAPs) and hair cell cochlear microphonics (CMs). Long-term KA effects were assessed using auditory brainstem response (ABR) measurements for up to 31 weeks post-KA exposure. KA infusion immediately abolished AN CAPs while having mild impact on the CM. ABR wave I, the far-field AN response, showed a pronounced 40-75 % amplitude reduction at moderate-to-high sound levels that persisted for the duration of the study. In contrast, wave I latency and the amplitude of wave V were nearly unaffected by KA, and waves II-IV were less reduced than wave I. ABR thresholds, calculated based on complete response waveforms, showed no impairment following KA. These results demonstrate that KA exposure in the budgerigar causes irreversible AN damage, most likely through excitotoxic injury to afferent fibers or synapses as in other species, while sparing ABR thresholds. Normal wave V amplitude, assumed to originate centrally, may persist through compensatory mechanisms that restore central response amplitude by downregulating inhibition. Future studies in this new animal model of AN damage can explore effects of this neural lesion, in isolation from hair cell trauma and threshold elevation, on central processing and perception of complex sounds.

Objectives: Evaluating the value of MRI for assessing congenital anomalies of the inner ear in children with congenital sensorineural hearing loss (SNHL) before cochlear implantation. Patients and methods: This study included 56 children, suffering from severe to profound bilateral congenital SNHL. All included patients were potential candidates for cochlear implants. All patients were evaluated by MRI of the temporal bone. Results: This study detected abnormalities in 27 (24.11%) ears out of 112 ears. We detected dilated vestibular aqueduct in 12/27 (44.44%) of abnormal ears, incomplete partition type-II in 8/27 (29.63%) of abnormal ears, cochlear hypoplasia in 8/27 (29.63%) of abnormal ears, semicircular canals hypoplasia in 2/27 (7.41%) of abnormal ears, Michel deformity in 2/27 (7.41%) of abnormal ears, common cavity deformity in 2/27 (7.41%) of abnormal ears and cochlear aplasia in 1/27 (3.7%) of abnormal ears. Conclusion: MRI is a valuable tool in the evaluation of inner ear abnormalities in children with congenital SNHL. It allows for the detection of aplasia of the cochlea or the cochlear nerve which represent absolute contraindications to a cochlear implant surgery. Keywords: Congenital sensorineural hearing loss, Inner ear malformations, Cochlear implants, MRI of the temporal bone

Ototoxicity diagnosis and management has historically been approached using a variety of methods. However, in recent years a consensus on useful and practical approaches has been developed through clinical guidelines of the American Speech Language Hearing Association, the American Academy of Audiology, and multiple clinical trials published in peer-reviewed literature. Some of the guidelines and approaches are used to detect and monitor ototoxicity, while others are used to grade adverse events. Some of the audiologic measures are primary, while others are adjunct measures and may be tailored to the specific needs of the patient or clinical trial. For some types of monitoring, such as drug-induced tinnitus or dizziness, validated paper survey instruments can be both sensitive and easy for fragile patients. This review addresses the characteristics of some of the most common clinical ototoxins and the most common methods for detecting and monitoring ototoxicity in clinical practice and clinical trials.

The study presents the application of a purely conductance-based stochastic nerve fibre model to human auditory nerve fibres within finite element volume conduction models of a semi-generic head and user-specific cochleae. The stochastic, threshold and temporal characteristics of the human model are compared and successfully validated against physiological feline results with the application of a mono-polar, bi-phasic, cathodic first stimulus. Stochastic characteristics validated include: (i) the log(Relative Spread) versus log(fibre diameter) distribution for the discharge probability versus stimulus intensity plots and (ii) the required exponential membrane noise versus transmembrane voltage distribution. Intra-user, and to a lesser degree inter-user, comparisons are made with respect to threshold and dynamic range at short and long pulse widths for full versus degenerate single fibres as well as for populations of degenerate fibres of a single user having distributed and aligned somas with varying and equal diameters. Temporal characteristics validated through application of different stimulus pulse rates and different stimulus intensities include: (i) discharge rate, latency and latency standard deviation versus stimulus intensity, (ii) period histograms and (iii) interspike interval histograms. Although the stochastic population model does not reduce the modelled single deterministic fibre threshold, the simulated stochastic and temporal characteristics show that it could be used in future studies to model user-specific temporally encoded information, which influences the speech perception of CI users.

Children with unilateral deafness may experience challenges with language development, educational progress, and social interaction. Rehabilitation with a cochlear implant (CI) may minimize these impacts. This review examines the characteristics of children with unilateral deafness presenting for candidacy assessment. Forty-nine children with unilateral deafness were assessed. Many (15/49) did not meet candidacy criteria due to cochlear nerve aplasia/hypoplasia (12/49), while 17/49 elected not to pursue CI. The most common etiologies in those 17/49 (35%) who met candidacy and consented to CI were congenital cytomegalovirus (cCMV) (41%) and trauma (26%). Many children with unilateral deafness who present for assessment do not go on to receive an implant due to anatomic contraindications or their desire for non-intervention. This review highlights the high prevalence of cCMV amongst children with unilateral deafness presenting for CI where the potential for progression to bilateral hearing loss may influence decision for implantation.

Although aminoglycoside antibiotics such as kanamycin are widely used clinically to treat life threatening bacterial infections, ototoxicity remains a significant dose-limiting side effect. The prevailing view is that the hair cells are the primary ototoxic target of aminoglycosides and that spiral ganglion neurons begin to degenerate weeks or months after the hair cells have died due to lack of neurotrophic support. To test the early developmental aspects of this issue, we compared kanamycin-induced hair cell and spiral ganglion pathology in rat postnatal day 3 cochlear organotypic cultures with adult whole cochlear explants. In both adult and postnatal day 3 cultures, hair cell damage began at the base of the cochleae and progressed towards the apex in a dose dependent manner. In postnatal day 3 cultures, spiral ganglion neurons were rapidly destroyed by kanamycin prior to hair cell loss. In contrast, adult spiral ganglion neurons were resistant to kanamycin damage even at the highest concentration, consistent with in vivo models of delayed SGN degeneration. In postnatal day 3 cultures, kanamycin preferentially damaged type I spiral ganglion neurons whereas type II neurons were resistant. Spiral ganglion degeneration of postnatal day 3 neurons was associated with upregulation of the superoxide radical and caspase-3 mediated cell death. These results show for the first time that kanamycin is toxic to postnatal day 3 spiral ganglion neurons, but not adult neurons.

Loss of neural structures (such as hair cells or neurones within the spiral ganglion) has been proposed to be involved in Meniere’s disease (MD) (Spoendlin et al. Acta oto-laryngologica Supplementum 499:1–21, 1; Merchant et al. Eur Arch Oto-Rhino-Laryngol Off J Eur Feder Oto-Rhino-Laryngol Soc (EUFOS) Affil German Soc Oto-Rhino-Laryngol Head Neck Surg 252(2):63–75, 2; Tsuji et al. Ann Otol Rhinol Laryngol Suppl 81:26–31, 3; Kariya, Otol Neurotol Off Publ Am Otol Soc Am Neurotol Soc Eur Acad Otol Neurotol 28(8):1063–1068, 4; Megerian Laryngoscope 115(9):1525–1535, 5) but this has yet to be confirmed. Therefore, the aim of this study was to investigate morphometric changes of VIIth and VIIIth cranial nerve in MD. MD is characterized by episodic vertigo, tinnitus, fluctuating hearing loss, and aural fullness. The exact pathophysiological mechanisms involved such as viral infections, autoimmune processes, genetic predisposition, cellular apoptosis, and oxidative stress are still not clear. Using a T2-weighted 3D-GE “constructive interference in steady state” (CISS) 3T magnetic resonance imaging (MRI) sequence, we evaluated the properties of the VIIth and VIIIth cranial nerves as they passed from the cerebellopontine angle to the inner ear modiolus. 21 patients with MD were examined along with 39 normal controls. Bidirectional nerve diameters and cross-sectional areas (CSA) were measured in a transverse plane. The comparison of study and control group showed statistically significant (P

Made available in DSpace on 2018-12-11T17:11:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-11-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Ministerio de Ciencia e Innovación Ministerio de Economía y Competitividad The noradrenergic locus coeruleus (LC) plays an important role in the promotion and maintenance of arousal and alertness. Our group recently described coerulean projections to cochlear root neurons (CRNs), the first relay of the primary acoustic startle reflex (ASR) circuit. However, the role of the LC in the ASR and its modulation, prepulse inhibition (PPI), is not clear. In this study, we damaged LC neurons and fibers using a highly selective neurotoxin, DSP-4, and then assessed ASR and PPI in male and female rats. Our results showed that ASR amplitude was higher in males at 14 days after DSP-4 injection when compared to pre-administration values and those in the male control group. Such modifications in ASR amplitude did not occur in DSP-4-injected females, which exhibited ASR amplitude within the range of control values. PPI differences between males and females seen in controls were not observed in DSP-4-injected rats for any interstimulus interval tested. DSP-4 injection did not affect ASR and PPI latencies in either the male or the female groups, showing values that were consistent with the sex-related variability observed in control rats. Furthermore, we studied the noradrenergic receptor system in the cochlear nerve root using gene expression analysis. When compared to controls, DSP-4-injected males showed higher levels of expression in all adrenoceptor subtypes; however, DSP-4-injected females showed varied effects depending on the receptor type, with either up-, downregulations, or maintenance of expression levels. Lastly, we determined noradrenaline levels in CRNs and other LC-targeted areas using HPLC assays, and these results correlated with behavioral and adrenoceptor expression changes post DSP-4 injection. Our study supports the participation of LC in ASR and PPI, and contributes toward a better understanding of sex-related differences observed in somatosensory gating paradigms. Institute for Neuroscience of Castilla y León (INCYL) University of Salamanca Institute of Biomedical Research of Salamanca (IBSAL) University of Salamanca Department of Cell Biology and Pathology University of Salamanca Department of Physiology and Pharmacology University of Salamanca Department of Anatomy Institute of Biosciences of Botucatu Univ. Estadual Paulista (UNESP), Distrito de Rubião Jr., S/N, PO.Box 510 Department of Anatomy Institute of Biosciences of Botucatu Univ. Estadual Paulista (UNESP), Distrito de Rubião Jr., S/N, PO.Box 510 FAPESP: 2008/02771-6 Ministerio de Ciencia e Innovación: BFU2010-17754 Ministerio de Economía y Competitividad: SAF2016-78898-C2-2R

Noninvasive transcranial electric stimulation is increasingly being used as an advantageous therapy alternative that may activate deep tissues while avoiding drug side-effects. However, not only is there limited evidence for activation of deep tissues by transcranial electric stimulation, its evoked human sensation is understudied and often dismissed as a placebo or secondary effect. By systematically characterizing the human sensation evoked by transcranial alternating-current stimulation, we observed not only stimulus frequency and electrode position dependencies specific for auditory and visual sensation but also a broader presence of somatic sensation ranging from touch and vibration to pain and pressure. We found generally monotonic input-output functions at suprathreshold levels, and often multiple types of sensation occurring simultaneously in response to the same electric stimulation. We further used a recording circuit embedded in a cochlear implant to directly and objectively measure the amount of transcranial electric stimulation reaching the auditory nerve, a deep intercranial target located in the densest bone of the skull. We found an optimal configuration using an ear canal electrode and low-frequency (

The outcome of cochlear implantation (CI) in patients with cochlear nerve deficiency (CND) is variable, resulting in a wide range of speech perception performance, from degrees of environmental sound perception to conversation without lip-reading. Twenty-five cochlear implantees with CND were enrolled retrospectively to determine the factors correlated with CI outcome in patients with CND and to develop a predictive model for CI outcome. CI outcome was evaluated using the Categories of Auditory Performance (CAP) score at 2 years after CI. Patients with negative auditory brainstem response (ABR) showed a significantly lower CAP score than those with positive ABR (2.5 ± 1.7, 4.8 ± 0.7; p = 0.001). The area ratio of vestibulocochlear nerve (VCN) to facial nerve (FN) at the cerebellopontine angle on magnetic resonance images was positively correlated with CI outcome (p $${\bf{deduced}}:{\bf{CAP}}\,{\bf{score}}{\boldsymbol{=}}{\bf{0.7}}{\boldsymbol{+}}{\bf{1.9}}{\boldsymbol{\ast }}{\boldsymbol{(}}{\bf{ABR}}{\boldsymbol{)}}{\boldsymbol{+}}{\bf{1.2}}{\boldsymbol{\ast }}(\frac{{\boldsymbol{V}}{\boldsymbol{C}}{\boldsymbol{N}}}{{\boldsymbol{F}}{\boldsymbol{N}}})$$ deduced : CAP score = 0.7 + 1.9 ∗ ( ABR ) + 1.2 ∗ ( V C N F N ) . We found that preoperative ABR and area ratio of VCN to FN at the cerebellopontine angle could predict CI outcome in patients with CND. Preoperative counselling based on our predictive model might be helpful to determine treatment modality for auditory rehabilitation and which ear to implant.

Background Cochlear implants (CI) have been established as the therapy of choice for functional deafness. The number of CI-rehabilitated patients is continuously growing. The resulting data can provide important information for physicians, health insurance companies, and scientists. Assessment and structuring of data becomes more feasible with the application of modern database systems. Materials and methods In collaboration with Innoforce Est., Liechtenstein, the authors developed a database module for the specific needs of CI patients. Data of 100 patients were included and evaluated. The main features of the module and an example data analysis are presented. Results Analysis of data from these 100 patients reveals 50 men and 50 women aged between 1 and 87 years, with a maximum value in the 51-60-years age group. More than 50% of the patients were also severely hearing impaired in the contralateral ear and fitted the CI indication criteria. Functional deafness in the ear subsequently fitted with CI in most of the patients had arisen more than 20 years previously. Preoperative diagnostic electrical stimulation of the cochlear nerve was positive in 67 patients. All 100 patients perceived auditory sensations with the CI. Conclusion The presented patient cohort is representative of patients at the Department of Otorhinolaryngology, University of Heidelberg Medical Center, Germany, and the demographic distribution is in accordance with the literature. The state of the contralateral ear, often also fitting the CI indication, is not surprising, as cochlear implantation is a comparatively new procedure. Preoperative electrical stimulation turned out not to be significant by itself. The hearing results and overview of complications were easy to calculate in comparison to a pure data storage system such as i.s.h.med.

Tinnitus is the perception of a sound that has no external source. Sound stimuli can suppress spontaneous firing in auditory neurons long after stimulus offset. It is unknown how changes in sound stimulus parameters affect this forward suppression. Using in vivo extracellular recording in awake mice, we found that about 40 % of spontaneously active inferior colliculus (IC) neurons exhibited forward suppression of spontaneous activity after sound offset. The duration of this suppression increased with sound duration and lasted about 40 s following a 30-s stimulus offset. Pure tones presented at the neuron's characteristic frequency (CF) were more effective in triggering suppression compared to non-CF or wideband noise stimuli. In contrast, non-CF stimuli often induced forward facilitation. About one third of IC neurons exhibited shorter suppression durations with each subsequent sound presentation. These characteristics of forward suppression are similar to the psychoacoustic properties of residual inhibition of tinnitus: a phenomenon of brief (about 30 s) suppression of tinnitus observed in tinnitus patients after sound presentations. Because elevated spontaneous firing in central auditory neurons has been linked to tinnitus, forward suppression of this firing with sound might be an underlying mechanism of residual inhibition.

Vowels make a strong contribution to speech perception under natural conditions. Vowels are encoded in the auditory nerve primarily through neural synchrony to temporal fine structure and to envelope fluctuations rather than through average discharge rate. Neural synchrony is thought to contribute less to vowel coding in central auditory nuclei, consistent with more limited synchronization to fine structure and the emergence of average-rate coding of envelope fluctuations. However, this hypothesis is largely unexplored, especially in background noise. The present study examined coding mechanisms at the level of the midbrain that support behavioral sensitivity to simple vowel-like sounds using neurophysiological recordings and matched behavioral experiments in the budgerigar. Stimuli were harmonic tone complexes with energy concentrated at one spectral peak, or formant frequency, presented in quiet and in noise. Behavioral thresholds for formant-frequency discrimination decreased with increasing amplitude of stimulus envelope fluctuations, increased in noise, and were similar between budgerigars and humans. Multiunit recordings in awake birds showed that the midbrain encodes vowel-like sounds both through response synchrony to envelope structure and through average rate. Whereas neural discrimination thresholds based on either coding scheme were sufficient to support behavioral thresholds in quiet, only synchrony-based neural thresholds could account for behavioral thresholds in background noise. These results reveal an incomplete transformation to average-rate coding of vowel-like sounds in the midbrain. Model simulations suggest that this transformation emerges due to modulation tuning, which is shared between birds and mammals. Furthermore, the results underscore the behavioral relevance of envelope synchrony in the midbrain for detection of small differences in vowel formant frequency under real-world listening conditions.

This study presents the development of an alternative noise current term and novel voltage-dependent current noise algorithm for conductance-based stochastic auditory nerve fibre (ANF) models. ANFs are known to have significant variance in threshold stimulus which affects temporal characteristics such as latency. This variance is primarily caused by the stochastic behaviour or microscopic fluctuations of the node of Ranvier's voltage-dependent sodium channels of which the intensity is a function of membrane voltage. Though easy to implement and low in computational cost, existing current noise models have two deficiencies: it is independent of membrane voltage, and it is unable to inherently determine the noise intensity required to produce in vivo measured discharge probability functions. The proposed algorithm overcomes these deficiencies while maintaining its low computational cost and ease of implementation compared to other conductance and Markovian-based stochastic models. The algorithm is applied to a Hodgkin---Huxley-based compartmental cat ANF model and validated via comparison of the threshold probability and latency distributions to measured cat ANF data. Simulation results show the algorithm's adherence to in vivo stochastic fibre characteristics such as an exponential relationship between the membrane noise and transmembrane voltage, a negative linear relationship between the log of the relative spread of the discharge probability and the log of the fibre diameter and a decrease in latency with an increase in stimulus intensity.

Neural spike trains are commonly characterized as a Poisson point process. However, the Poisson assumption is a poor model for spiking in auditory nerve fibres because it is known that interspike intervals display positive correlation over long time scales and negative correlation over shorter time scales. We have therefore developed a biophysical model based on the well-known Meddis model of the peripheral auditory system, to produce simulated auditory nerve fibre spiking statistics that more closely match the firing correlations observed in empirical data. We achieve this by introducing biophysically realistic ion channel noise to an inner hair cell membrane potential model that includes fractal fast potassium channels and deterministic slow potassium channels. We succeed in producing simulated spike train statistics that match empirically observed firing correlations. Our model thus replicates macro-scale stochastic spiking statistics in the auditory nerve fibres due to modeling stochasticity at the micro-scale of potassium channels. Refereed/Peer-reviewed

Within the context of treatment with cochlear implants (CIs), different electrical and electrophysiological diagnostic procedures are applied both intra- and postoperatively. These assess electrical measures from the CI and electrophysiological measures from CI patients, respectively. The electrophysiological diagnostic procedures comprise measurement of electrically evoked compound action potentials of the auditory nerve, the registration of electrically evoked auditory brainstem potentials and the assessment of electrically evoked auditory cortical potentials. These potentials reflect auditory nerve excitation and stimulus processing in different parts of the ascending auditory pathway for intracochlear electrical stimulation via a CI. For current CIs, assessment of electrode position and examination of the implant's coupling to the auditory nerve are important domains of application for electrophysiological diagnostic procedures. Another substantial application area is the examination of stimulus processing in the auditory pathway. However, the main field of application of these procedures is supporting the fitting of CI speech processors in infants and toddlers on the basis of electrophysiological thresholds.

Cavernous angiomas originating in the internal auditory canal are very rare. In the available literature, only 65 cases of cavernomas in this location have been previously reported. We describe the case of a 22-year-old woman surgically treated for a cavernous hemangioma in the left internal auditory canal, mimicking on preoperative magnetic resonance imaging MRI an acoustic neuroma. Neurological symptoms were hypoacusia and dizziness. The cavernous angioma encased the seventh and, partially, the eighth cranial nerve complex. A "nearly total" removal was performed, leaving a thin residual of malformation adherent to the facial nerve. Postoperative period was uneventful; hearing was unchanged, but the patient had a moderate inferior left facial palsy (House-Brackmann grade II) slightly improved during the following weeks. On the basis of the observation of this uncommon case, we propose a revision of the literature and discuss clinical features, differential diagnosis, and treatment.

Previous psychophysical and modelling studies suggest that cathodic stimulation by a cochlear implant (CI) may preferentially activate the peripheral processes of the auditory nerve, whereas anodic stimulation may preferentially activate the central axons. Because neural degeneration typically starts with loss of the peripheral processes, lower thresholds for cathodic than for anodic stimulation may indicate good local neural survival. We measured thresholds for 99-pulse-per-second trains of triphasic (TP) pulses where the central high-amplitude phase was either anodic (TP-A) or cathodic (TP-C). Thresholds were obtained in monopolar mode from four or five electrodes and a total of eight ears from subjects implanted with the Advanced Bionics CI. When between–subject differences were removed, there was a modest but significant correlation between the polarity effect (TP-C threshold minus TP-A threshold) and the average of TP-C and TP-A thresholds, consistent with the hypothesis that a large polarity effect corresponds to good neural survival. When data were averaged across electrodes for each subject, relatively low thresholds for TP-C correlated with a high “upper limit” (the pulse rate up to which pitch continues to increase) from a previous study [Cosentino S, Carlyon RP, Deeks JM, Parkinson W, Bierer JA (2016) Rate discrimination, gap detection and ranking of temporal pitch in cochlear implant users. J Assoc Otolaryngol 17:371– 382]. Overall the results provide modest indirect support for the hypothesis that the polarity effect provides an estimate of local neural survival.

Cochlear implantation, a surgical method to bypass cochlear hair cells and directly stimulate the spiral ganglion, is the standard treatment for severe-to-profound hearing loss. Changes in cochlear implant electrode array design and surgical approach now allow for preservation of acoustic hearing in the implanted ear. Electrocochleography (ECochG) was performed in eight hearing preservation subjects to assess hair cell and neural function and elucidate underlying genetic hearing loss. Three subjects had pathogenic variants in TMPRSS3 and five had pathogenic variants in genes known to affect the cochlear sensory partition. The mechanism by which variants in TMPRSS3 cause genetic hearing loss is unknown. We used a 500-Hz tone burst to record ECochG responses from an intracochlear electrode. Responses consist of a cochlear microphonic (hair cell) and an auditory nerve neurophonic. Cochlear microphonics did not differ between groups. Auditory nerve neurophonics were smaller, on average, in subjects with TMPRSS3 deafness. Results of this proof-of-concept study provide evidence that pathogenic variants in TMPRSS3 may impact function of the spiral ganglion. While ECochG as a clinical and research tool has been around for decades, this study illustrates a new application of ECochG in the study of genetic hearing and deafness in vivo.

In the originally published version of this Article, refs. 54 to 63 were incorrectly cited in the first sentence of the fifth paragraph of the Discussion section. This has now been corrected in both the PDF and HTML versions of the Article.

Morphological abnormalities of the internal acoustic canal (IAC), albeit rare, are sometimes associated with hearing loss in children. We present an illustration of the spectrum of IAC abnormalities together with a brief review of the embryology and anatomy of the IAC and the techniques used when imaging the petrous temporal bone. This review focuses on morphological abnormalities of the IAC together with their clinical implications and impact on clinical management.

More than 100 genes have been associated with deafness. However, SMAD4 is rarely considered a contributor to deafness in humans, except for its well-defined role in cell differentiation and regeneration. Here, we report that a SMAD4 defect in mice can cause auditory neuropathy, which was defined as a mysterious hearing and speech perception disorder in human for which the genetic background remains unclear. Our study showed that a SMAD4 defect induces failed formation of cochlear ribbon synapse during the earlier stage of auditory development in mice. Further investigation found that there are nearly normal morphology of outer hair cells (OHCs) and post-synapse spiral ganglion nerves (SGNs) in SMAD4 conditional knockout mice (cKO); however, a preserved distortion product of otoacoustic emission (DPOAE) and cochlear microphonic (CM) still can be evoked in cKO mice. Moreover, a partial restoration of hearing detected by electric auditory brainstem response (eABR) has been obtained in the cKO mice using electrode stimuli toward auditory nerves. Additionally, the ribbon synapses in retina are not affected by this SMAD4 defect. Thus, our findings suggest that this SMAD4 defect causes auditory neuropathy via specialized disruption of cochlear ribbon synapses.

Trimethyltin (TMT), which has a variety of applications in industry and agricultural is a neurotoxin that is known to affect the auditory system as well as central nervous system (CNS) of humans and experimental animals. However, the mechanisms underlying TMT-induced auditory dysfunction are poorly understood. To gain insights into the neurotoxic effect of TMT on the peripheral auditory system, we treated cochlear organotypic cultures with concentrations of TMT ranging from 5 to 100 μM for 24 h. Interestingly, TMT preferentially damaged auditory nerve fibers and spiral ganglion neurons in a dose-dependent manner, but had no noticeable effects on the sensory hair cells at the doses employed. TMT-induced damage to auditory neurons was associated with significant soma shrinkage, nuclear condensation and activation of caspase-3, biomarkers indicative of apoptotic cell death. Our findings show that TMT is exclusively neurotoxicity in rat cochlear organotypic culture and that TMT-induced auditory neuron death occurs through a caspase-mediated apoptotic pathway.