Effects of Kainic Acid-Induced Auditory Nerve Damage on Envelope-Following Responses in the Budgerigar (Melopsittacus undulatus).

Sensorineural hearing loss is a prevalent problem that adversely impacts quality of life by compromising interpersonal communication. While hair cell damage is readily detectable with the clinical audiogram, this traditional diagnostic tool appears inadequate to detect lost afferent connections between inner hair cells and auditory nerve (AN) fibers, known as cochlear synaptopathy. The envelope-following response (EFR) is a scalp-recorded response to amplitude modulation, a critical acoustic feature of speech. Because EFRs can have greater amplitude than wave I of the auditory brainstem response (ABR; i.e., the AN-generated component) in humans, the EFR may provide a more sensitive way to detect cochlear synaptopathy. We explored the effects of kainate- (kainic acid) induced excitotoxic AN injury on EFRs and ABRs in the budgerigar (Melopsittacus undulatus), a parakeet species used in studies of complex sound discrimination. Kainate reduced ABR wave I by 65-75 % across animals while leaving otoacoustic emissions unaffected or mildly enhanced, consistent with substantial and selective AN synaptic loss. Compared to wave I loss, EFRs showed similar or greater percent reduction following kainate for amplitude-modulation frequencies from 380 to 940 Hz and slightly less reduction from 80 to 120 Hz. In contrast, forebrain-generated middle latency responses showed no consistent change post-kainate, potentially due to elevated "central gain" in the time period following AN damage. EFR reduction in all modulation frequency ranges was highly correlated with wave I reduction, though within-animal effect sizes were greater for higher modulation frequencies. These results suggest that even low-frequency EFRs generated primarily by central auditory nuclei might provide a useful noninvasive tool for detecting synaptic injury clinically.

Noninvasive Measures of Distorted Tonotopic Speech Coding Following Noise-Induced Hearing Loss.

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.

Normal Tone-In-Noise Sensitivity in Trained Budgerigars despite Substantial Auditory-Nerve Injury: No Evidence of Hidden Hearing Loss.

Loss of auditory-nerve (AN) afferent cochlear innervation is a prevalent human condition that does not affect audiometric thresholds and therefore remains largely undetectable with standard clinical tests. AN loss is widely expected to cause hearing difficulties in noise, known as "hidden hearing loss," but support for this hypothesis is controversial. Here, we used operant conditioning procedures to examine the perceptual impact of AN loss on behavioral tone-in-noise (TIN) sensitivity in the budgerigar (Melopsittacus undulatus; of either sex), an avian animal model with complex hearing abilities similar to humans. Bilateral kainic acid (KA) infusions depressed compound AN responses by 40-70% without impacting otoacoustic emissions or behavioral tone sensitivity in quiet. Surprisingly, animals with AN damage showed normal thresholds for tone detection in noise (0.1 ± 1.0 dB compared to control animals; mean difference ± SE), even under a challenging roving-level condition with random stimulus variation across trials. Furthermore, decision-variable correlations (DVCs) showed no difference for AN-damaged animals in their use of energy and envelope cues to perform the task. These results show that AN damage has less impact on TIN detection than generally expected, even under a difficult roving-level condition known to impact TIN detection in individuals with sensorineural hearing loss (SNHL). Perceptual deficits could emerge for different perceptual tasks or with greater AN loss but are potentially minor compared with those caused by SNHL.SIGNIFICANCE STATEMENT Loss of auditory-nerve (AN) cochlear innervation is a common problem in humans that does not affect audiometric thresholds on a clinical hearing test. AN loss is widely expected to cause hearing problems in noise, known as "hidden hearing loss," but existing studies are controversial. Here, using an avian animal model with complex hearing abilities similar to humans, we examined for the first time the impact of an experimentally induced AN lesion on behavioral tone sensitivity in noise. Surprisingly, AN-lesioned animals showed no difference in hearing performance in noise or detection strategy compared with controls. These results show that perceptual deficits from AN damage are smaller than generally expected, and potentially minor compared with those caused by sensorineural hearing loss (SNHL).

Effects of selective auditory-nerve damage on the behavioral audiogram and temporal integration in the budgerigar.

Auditory-nerve fibers are lost steadily with age and as a possible consequence of noise-induced glutamate excitotoxicity. Auditory-nerve loss in the absence of other cochlear pathologies is thought to be undetectable with a pure-tone audiogram while degrading real-world speech perception (hidden hearing loss). Perceptual deficits remain unclear, however, due in part to the limited behavioral capacity of existing rodent models to discriminate complex sounds. The budgerigar is an avian vocal learner with human-like behavioral sensitivity to many simple and complex sounds and the capacity to mimic speech. Previous studies in this species show that intracochlear kainic-acid infusion reduces wave 1 of the auditory brainstem response by 40-70%, consistent with substantial excitotoxic auditory-nerve damage. The present study used operant-conditioning procedures in trained budgerigars to quantify kainic-acid effects on tone detection across frequency (0.25-8 kHz; the audiogram) and as a function of duration (20-160 ms; temporal integration). Tone thresholds in control animals were lowest from 1 to 4 kHz and decreased with increasing duration as in previous studies of the budgerigar. Behavioral results in kainic-acid-exposed animals were as sensitive as in controls, suggesting preservation of the audiogram and temporal integration despite auditory-nerve loss associated with up to 70% wave 1 reduction. Distortion-product otoacoustic emissions were also preserved in kainic-acid exposed animals, consistent with normal hair-cell function. These results highlight considerable perceptual resistance of tone-detection performance with selective auditory-nerve loss. Future behavioral studies in budgerigars with auditory-nerve damage can use complex speech-like stimuli to help clarify aspects of auditory perception impacted by this common cochlear pathology.

Sensory overamplification in layer 5 auditory corticofugal projection neurons following cochlear nerve synaptic damage.

Layer 5 (L5) cortical projection neurons innervate far-ranging brain areas to coordinate integrative sensory processing and adaptive behaviors. Here, we characterize a plasticity in L5 auditory cortex (ACtx) neurons that innervate the inferior colliculus (IC), thalamus, lateral amygdala and striatum. We track daily changes in sound processing using chronic widefield calcium imaging of L5 axon terminals on the dorsal cap of the IC in awake, adult mice. Sound level growth functions at the level of the auditory nerve and corticocollicular axon terminals are both strongly depressed hours after noise-induced damage of cochlear afferent synapses. Corticocollicular response gain rebounded above baseline levels by the following day and remained elevated for several weeks despite a persistent reduction in auditory nerve input. Sustained potentiation of excitatory ACtx projection neurons that innervate multiple limbic and subcortical auditory centers may underlie hyperexcitability and aberrant functional coupling of distributed brain networks in tinnitus and hyperacusis.

Effect of granulocyte colony-stimulating factor on the cochlear nuclei after creation of a partial nerve lesion: an experimental study in rats.

OBJECTIVE The risk of injury of the cochlear nerve during angle (CPA) surgery is high. Granulocyte colony-stimulating factor (G-CSF) has been found in various experimental models of peripheral and CNS injury to have a neuroprotective effect by inhibiting apoptosis and inflammation. However, to the authors' knowledge, the influence of G-CSF on cochlear nerve regeneration has not been reported. This study investigated the neuroprotective effect of G-CSF after a partial cochlear nerve lesion in rats. METHODS A lesion of the right cochlear nerve in adult male Sprague-Dawley rats was created using a water-jet dissector with a pressure of 8 bar. In the first group (G-CSF-post), G-CSF was administrated on Days 1, 3, and 5 after the surgery. The second group (G-CSF-pre/post) was treated with G-CSF 1 day before and 1, 3, and 5 days after applying the nerve injury. The control group received sodium chloride after nerve injury at the various time points. Brainstem auditory evoked potentials (BAEPs) were measured directly before and after nerve injury and on Days 1 and 7 to evaluate the acoustic function of the cochlear nerve. The animals were sacrificed 1 week after the operation, and their brains were fixed in formalin. Nissl staining of the cochlear nuclei was performed, and histological sections were analyzed with a light microscope and an image-processing program. The numbers of neurons in the cochlear nuclei were assessed. RESULTS The values for Waves 2 and 4 of the BAEPs decreased abruptly in all 3 groups in the direct postoperative measurement. Although the amplitude in the control group did not recover, it increased in both treatment groups. According to 2-way ANOVA, groups treated with G-CSF had a significant increase in BAEP Wave II amplitudes on the right side (p = 0.0401) after the applied cochlear nerve injury. With respect to Wave IV, a trend toward better recovery in the G-CSF groups was found, but this difference did not reach statistical significance. In the histological analysis, higher numbers of neurons were found in the G-CSF groups. In the statistical analysis, the difference in the numbers of neurons between the control and G-CSF-post groups reached significance (p = 0.0086). The difference in the numbers of neurons between the control and G-CSF-pre/post groups and between the G-CSF-post and G-CSF-pre/post groups did not reach statistical significance. CONCLUSIONS The use of G-CSF improved the function of the eighth cranial nerve and protected cochlear nucleus cells from destruction after a controlled partial injury of the nerve. These findings might be relevant for surgery that involves CPA tumors. The use of G-CSF in patients with a lesion in the CPA might improve postoperative outcomes.

Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage.

Higher stages of central auditory processing compensate for a loss of cochlear nerve synapses by increasing the gain on remaining afferent inputs, thereby restoring firing rate codes for rudimentary sound features. The benefits of this compensatory plasticity are limited, as the recovery of precise temporal coding is comparatively modest. We reasoned that persistent temporal coding deficits could be ameliorated through modulation of voltage-gated potassium (Kv) channels that regulate temporal firing patterns. Here, we characterize AUT00063, a pharmacological compound that modulates Kv3.1, a high-threshold channel expressed in fast-spiking neurons throughout the central auditory pathway. Patch clamp recordings from auditory brainstem neurons and in silico modeling revealed that application of AUT00063 reduced action potential timing variability and improved temporal coding precision. Systemic injections of AUT00063 in vivo improved auditory synchronization and supported more accurate decoding of temporal sound features in the inferior colliculus and auditory cortex in adult mice with a near-complete loss of auditory nerve afferent synapses in the contralateral ear. These findings suggest modulating Kv3.1 in central neurons could be a promising therapeutic approach to mitigate temporal processing deficits that commonly accompany aging, tinnitus, ototoxic drug exposure or noise damage.

Malformaciones del octavo par en niños / Malformation of the eighth cranial nerve in children

Introducción y objetivos: La prevalencia de la hipoacusia neurosensorial (HNS) congénita es aproximadamente de 1,5-6 de cada 1.000 nacimientos. La disfunción del nervio auditivo (neuropatía auditiva) puede estar presente hasta en el 1-10% de los casos de HNS en niños, siendo menos frecuentes aquellas pérdidas debidas a una aplasia o hipoplasia del nervio auditivo. Los objetivos del estudio son describir la clínica, umbrales auditivos y etiología en una muestra de niños con HNS y aplasia o hipoplasia del octavo par. Metodología: Presentamos 34 niños (edad media 20 meses) con malformación del nervio auditivo e HNS profunda de una muestra de 385 niños implantados en los últimos 10 años. Estudiamos las características demográficas, clínicas y malformaciones asociadas (clasificaciones de Casselman y Sennaroglu). Los datos fueron procesados usando un análisis estadístico descriptivo bivariante (p<0,05). Resultados: Un 58,8% fueron bilaterales (IIa/IIa y I/I fueron los más frecuentes). De los unilaterales el IIb fue el más frecuente. La sensibilidad del cribado auditivo fue de un 77,4%. Encontramos diferencias estadísticamente significativas entre el grado de hipoacusia y los distintos tipos de aplasia (clasificación de Casselman). La sensibilidad de la TC fue del 46,3% y la especificidad del 85,7%. La RNM fue la prueba de imagen más sensible. Conclusiones: Un 10% de los niños en estudio para un implante coclear tienen una aplasia o hipoplasia del nervio auditivo. El grado de pérdida auditiva está directamente relacionado con los distintos tipos de aplasia (clasificación de Casselman). Aunque la TC y la RNM son complementarias, la RNM es el test de elección para la detección de malformaciones del nervio auditivo (AU)

Introduction and objectives: Prevalence of congenital sensorineural hearing loss (SNHL) is approximately 1.5-6 in every 1,000 newborns. Dysfunction of the auditory nerve (auditory neuropathy) may be involved in up to 1%-10% of cases; hearing losses because of vestibulocochlear nerve (VCN) aplasia are less frequent. The objectives of this study were to describe clinical manifestations, hearing thresholds and aetiology of children with SNHL and VCN aplasia. Methodology: We present 34 children (mean age 20 months) with auditory nerve malformation and profound HL taken from a sample of 385 children implanted in a 10-year period. We studied demographic characteristics, hearing, genetics, risk factors and associated malformations (Casselman's and Sennaroglu's classifications). Data were processed using a bivariate descriptive statistical analysis (P<.05). Results: Of all the cases, 58.8% were bilateral (IIa/IIa and I/I were the most common). Of the unilateral cases, IIb was the most frequent. Auditory screening showed a sensitivity of 77.4%. A relationship among bilateral cases and systemic pathology was observed. We found a statistically significant difference when comparing hearing loss impairment and patients with different types of aplasia as defined by Casselman's classification. Computed tomography (CT) scan yielded a sensitivity of 46.3% and a specificity of 85.7%. However, magnetic resonance imaging (MRI) was the most sensitive imaging test. Conclusions: Ten percent of the children in a cochlear implant study had aplasia or hypoplasia of the auditory nerve. The degree of auditory loss was directly related to the different types of aplasia (Casselman's classification) Although CT scan and MRI are complementary, the MRI is the test of choice for detecting auditory nerve malformation (AU)

Contributions of Mouse and Human Hematopoietic Cells to Remodeling of the Adult Auditory Nerve After Neuron Loss.

The peripheral auditory nerve (AN) carries sound information from sensory hair cells to the brain. The present study investigated the contribution of mouse and human hematopoietic stem cells (HSCs) to cellular diversity in the AN following the destruction of neuron cell bodies, also known as spiral ganglion neurons (SGNs). Exposure of the adult mouse cochlea to ouabain selectively killed type I SGNs and disrupted the blood-labyrinth barrier. This procedure also resulted in the upregulation of genes associated with hematopoietic cell homing and differentiation, and provided an environment conducive to the tissue engraftment of circulating stem/progenitor cells into the AN. Experiments were performed using both a mouse-mouse bone marrow transplantation model and a severely immune-incompetent mouse model transplanted with human CD34+ cord blood cells. Quantitative immunohistochemical analysis of recipient mice demonstrated that ouabain injury promoted an increase in the number of both HSC-derived macrophages and HSC-derived nonmacrophages in the AN. Although rare, a few HSC-derived cells in the injured AN exhibited glial-like qualities. These results suggest that human hematopoietic cells participate in remodeling of the AN after neuron cell body loss and that hematopoietic cells can be an important resource for promoting AN repair/regeneration in the adult inner ear.

The immediate effects of acoustic trauma on excitation and inhibition in the inferior colliculus: A Wiener-kernel analysis.

Noise-induced tinnitus and hyperacusis are thought to correspond to a disrupted balance between excitation and inhibition in the central auditory system. Excitation and inhibition are often studied using pure tones; however, these responses do not reveal inhibition within the excitatory pass band. Therefore, we used a Wiener-kernel analysis, complemented with singular value decomposition (SVD), to investigate the immediate effects of acoustic trauma on excitation and inhibition in the inferior colliculus (IC). Neural responses were recorded from the IC of three anesthetized albino guinea pigs before and immediately after a one-hour bilateral exposure to an 11-kHz tone of 124 dB SPL. Neural activity was recorded during the presentation of a 1-h continuous 70 dB SPL Gaussian-noise stimulus. Spike trains were subjected to Wiener-kernel analysis in which the second-order kernel was decomposed into excitatory and inhibitory components using SVD. Hearing thresholds between 3 and 22 kHz were elevated (13-47 dB) immediately after acoustic trauma. The presence and frequency tuning of excitation and inhibition in units with a low characteristic frequency (CF; < 3 kHz) was not affected, inhibition disappeared whereas excitation was not affected in mid-CF units (3 < CF < 11 kHz), and both excitation and inhibition disappeared in high-CF units (CF > 11 kHz). This specific differentiation could not be identified by tone-evoked receptive-field analysis, in which inhibitory responses disappeared in all units, along with excitatory responses in high-CF units. This study is the first to apply Wiener-kernel analysis, complemented with SVD, to study the effects of acoustic trauma on spike trains derived from the IC. With this analysis, a reduction of inhibition and preservation of good response thresholds was shown in mid-CF units immediately after acoustic trauma. These neurons may mediate noise-induced tinnitus and/or hyperacusis. Moreover, an immediate profound high-frequency hearing loss was reflected by reduced evoked firing rates and loss of both excitation and inhibition in high-CF units.

Neural stem/progenitor cell properties of glial cells in the adult mouse auditory nerve.

The auditory nerve is the primary conveyor of hearing information from sensory hair cells to the brain. It has been believed that loss of the auditory nerve is irreversible in the adult mammalian ear, resulting in sensorineural hearing loss. We examined the regenerative potential of the auditory nerve in a mouse model of auditory neuropathy. Following neuronal degeneration, quiescent glial cells converted to an activated state showing a decrease in nuclear chromatin condensation, altered histone deacetylase expression and up-regulation of numerous genes associated with neurogenesis or development. Neurosphere formation assays showed that adult auditory nerves contain neural stem/progenitor cells (NSPs) that were within a Sox2-positive glial population. Production of neurospheres from auditory nerve cells was stimulated by acute neuronal injury and hypoxic conditioning. These results demonstrate that a subset of glial cells in the adult auditory nerve exhibit several characteristics of NSPs and are therefore potential targets for promoting auditory nerve regeneration.

Facial and Cochlear Nerve Complications following Microsurgical Resection of Vestibular Schwannomas in a Series of 221 Cases.

BACKGROUND: Despite improvements in microsurgical technique and the use of intraoperative electrophysiological monitoring, the potential for facial and cochlear nerve injury remains a possibility in the resection of vestibular schwannomas (VS). We reviewed a series of 221 cases of VS resected via a retrosigmoid approach at our institution from October 2008 to April 2014 and determined the incidence of postoperative facial and cochlear deficits. MATERIAL AND METHODS: A total of 221 patients - 105 (47.5%) male and 116 (52.5%) female - with a mean age of 46.1 years (range 29-73 years), with VS ≥3 cm (n=183, 82.8%) and <3 cm (n=38, 17.2%) underwent surgical resection via a retrosigmoid approach and were evaluated for postoperative facial and cochlear nerve deficits. RESULTS: Near-total resection (>95% removal) was achieved in 199 cases (90%) and subtotal resection (>90% removal) in 22 cases (10%). At 6 month follow-up, House-Brackmann grades I-III were observed in 183 cases (82.8%), grade IV in 16 cases (7.2%), and grade V in 22 cases (10%). Of the 10 patients that had preoperative functional hearing, 3 (33%) retained hearing postoperatively. Cerebrospinal fluid leakage occurred in 6 patients (2.7%), lower cranial nerve palsies in 9 patients (4.1%), and intracranial hematomas 3 cases (1.4%). CONCLUSIONS: The observed incidence of persistent postoperative nerve deficits is very low. Meticulous microsurgical dissection of and around the facial and cochlear nerves with the aid of intraoperative electrophysiological nerve monitoring in the retrosigmoid approach allows for near-total resection of medium and large VS with the possibility of preservation of facial and cochlear nerve function.

Effect of cochlear nerve electrocautery on the adult cochlear nucleus.

HYPOTHESIS: Electrocauterization and subsequent transection of the cochlear nerve induce greater injury to the cochlear nucleus than sharp transection alone. BACKGROUND: Some studies show that neurofibromatosis Type 2 (NF2) patients fit with auditory brainstem implants (ABIs) fail to achieve speech perception abilities similar to ABI recipients without NF2. Reasons for these differences remain speculative. One hypothesis posits poorer performance to surgically induced trauma to the cochlear nucleus from electrocautery. Sustained electrosurgical depolarization of the cochlear nerve may cause excitotoxic-induced postsynaptic nuclear injury. Equally plausible is that cautery in the vicinity of the cochlear nucleus induces necrosis. METHODS: The cochlear nerve was transected in anesthetized adult gerbils sharply with or without bipolar electrocautery at varying intensities. Gerbils were perfused at 1, 3, 5, and 7 days postoperatively; their brainstem and cochleas were embedded in paraffin and sectioned at 10 µm. Alternate sections were stained with flourescent markers for neuronal injury or Nissl substance. In additional experiments, anterograde tracers were applied directly to a sectioned eighth nerve to verify that fluorescent-labeled profiles seen were terminating auditory nerve fibers. RESULTS: Cochlear nerve injury was observed from 72 hours postoperatively and was identical across cases regardless of surgical technique. Postsynaptic cochlear nucleus injury was not seen after distal transection of the nerve. By contrast, proximal transection was associated with trauma to the cochlear nucleus. CONCLUSION: Distal application of bipolar electrocautery seems safe for the cochlear nucleus. Application near the root entry zone must be used cautiously because this may compromise nuclear viability needed to support ABI stimulation.

Auditory brainstem implant: electrophysiologic responses and subject perception.

OBJECTIVES: The primary aim of this study was to compare the perceptual sensation produced by bipolar electrical stimulation of auditory brainstem implant (ABI) electrodes with the morphology of electrically evoked responses elicited by the same bipolar stimulus in the same unanesthetized, postsurgical state. Secondary aims were to (1) examine the relationships between sensations elicited by the bipolar stimulation used for evoked potential recording and the sensations elicited by the monopolar pulse-train stimulation used by the implant processor, and (2) examine the relationships between evoked potential morphology (elicited by bipolar stimulation) to the sensations elicited by monopolar stimulation. DESIGN: Electrically evoked early-latency and middle-latency responses to bipolar, biphasic low-rate pulses were recorded postoperatively in four adults with ABIs. Before recording, the perceptual sensations elicited by these bipolar stimuli were obtained and categorized as (1) auditory sensations only, (2) mixed sensations (both auditory and nonauditory), (3) side effect (nonauditory sensations), or (4) no sensation. In addition, the sensations elicited by monopolar higher-rate pulse-train stimuli similar to that used in processor programming were measured for all electrodes in the ABI array and classified using the same categories. Comparisons were made between evoked response morphology, bipolar stimulation sensation, and monopolar stimulation sensation. RESULTS: Sensations were classified for 33 bipolar pairs as follows: 21 pairs were auditory, 6 were mixed, 5 were side effect, and 1 was no sensation. When these sensations were compared with the electrically evoked response morphology for these signals, P3 of the electrically evoked auditory brainstem response (eABR) and the presence of a middle-latency positive wave, usually between 15 and 25 msec (electrical early middle-latency response [eMLR]), were only present when the perceptual sensation had an auditory component (either auditory or mixed pairs). The presence of other waves in the early-latency response such as N1 or P2 or a positive wave after 4 msec did not distinguish between only auditory or only nonauditory sensations. For monopolar stimulation, 42 were classified as auditory, 16 were mixed, and 26 were classified as side effect or no sensation. When bipolar sensations were compared with monopolar sensations for the 21 bipolar pairs categorized as auditory, 7 pairs had monopolar sensations of auditory for both electrodes, 9 pairs had only one electrode with a monopolar sensation of auditory, with the remainder having neither electrode as auditory. Of 6 bipolar pairs categorized as mixed, 3 had monopolar auditory sensations for one of the electrodes. When monopolar stimulation was compared with evoked potential morphology elicited by bipolar stimulation, P3 and the eMLR were more likely to be present when one or both of the electrodes in the bipolar pair elicited an auditory or mixed sensation with monopolar stimulation and were less likely to occur when neither of the electrodes had an auditory monopolar sensation. Again, other eABR waves did not distinguish between auditory and nonauditory sensations. CONCLUSIONS: ABI electrodes that are associated with auditory sensations elicited by bipolar stimulation are more likely to elicit evoked responses with a P3 wave or a middle-latency wave. P3 of the eABR and M15-25 of the eMLR are less likely to be present if neither electrode of the bipolar pair evoked an auditory sensation with monopolar stimulation.

Both central and peripheral auditory systems are involved in salicylate-induced tinnitus in rats: a behavioral study.

OBJECTIVE: This study was designed to establish a low dose salicylate-induced tinnitus rat model and to investigate whether central or peripheral auditory system is involved in tinnitus. METHODS: Lick suppression ratio (R), lick count and lick latency of conditioned rats in salicylate group (120 mg/kg, intraperitoneally) and saline group were first compared. Bilateral auditory nerves were ablated in unconditioned rats and lick count and lick latency were compared before and after ablation. The ablation was then performed in conditioned rats and lick count and lick latency were compared between salicylate group and saline group and between ablated and unablated salicylate groups. RESULTS: Both the R value and the lick count in salicylate group were significantly higher than those in saline group and lick latency in salicylate group was significantly shorter than that in saline group. No significant changes were observed in lick count and lick latency before and after ablation. After ablation, lick count and lick latency in salicylate group were significantly higher and shorter respectively than those in saline group, but they were significantly lower and longer respectively than those in unablated salicylate group. CONCLUSION: A low dose of salicylate (120 mg/kg) can induce tinnitus in rats and both central and peripheral auditory systems participate in the generation of salicylate-induced tinnitus.

Challenges for stem cells to functionally repair the damaged auditory nerve.

INTRODUCTION: In the auditory system, a specialized subset of sensory neurons are responsible for correctly relaying precise pitch and temporal cues to the brain. In individuals with severe-to-profound sensorineural hearing impairment these sensory auditory neurons can be directly stimulated by a cochlear implant, which restores sound input to the brainstem after the loss of hair cells. This neural prosthesis therefore depends on a residual population of functional neurons in order to function effectively. AREAS COVERED: In severe cases of sensorineural hearing loss where the numbers of auditory neurons are significantly depleted, the benefits derived from a cochlear implant may be minimal. One way in which to restore function to the auditory nerve is to replace these lost neurons using differentiated stem cells, thus re-establishing the neural circuit required for cochlear implant function. Such a therapy relies on producing an appropriate population of electrophysiologically functional neurons from stem cells, and on these cells integrating and reconnecting in an appropriate manner in the deaf cochlea. EXPERT OPINION: Here we review progress in the field to date, including some of the key functional features that stem cell-derived neurons would need to possess and how these might be enhanced using electrical stimulation from a cochlear implant.

[Direct recording from cochlear nerve via a ball-electrode in transtemporal acoustic neuroma surgery]. / Direkte Ableitung vom Nervus cochlearis bei transtemporaler Resektion von Vestibularisschwannomen.

BACKGROUND: Intraoperative monitoring (IOM) of the cochlear nerve function during acoustic neuroma surgery is employed to assist in preserving hearing. So far, Auditory Brain-stem Response (ABR) is considered to be an optimal method for intraoperative monitoring in transtemporal approach. The aim of this study was to perform direct recording of the cochlear nerve action potential after resection of the tumor by using a ball-electrode and to evaluate the use of this method in predicting the postoperative hearing. The obtained data were compared to the simultaneous ABR results and to the postoperative hearing. MATERIAL AND METHODS: In 2009, 38 patients have undergone acoustic Neuroma Surgery at the ENT University hospital, Wuerzburg. In 33 patients an intraoperative ABR as well as a direct measurement from the cochlear nerve using a ball electrode were performed. In 5 patients the postoperative hearing was predicted using the direct measurement at the cochlear nerve only. RESULTS: The direct recording from the cochlear nerve gave very robust responses. Even in cases where ABR recording was not possible, the identification of clear cochlear nerve action potential could still be reached. Using the direct recordings from the cochlear nerve to predict the post operative hearing turned out to have a sensitivity of 100% and a specificity of 70%. CONCLUSIONS: These results show that intraoperative monitoring with direct recording from the cochlear nerve via a ball-electrode in transtemporal approaches offers a valuable method to predict the postoperative hearing. Further investigation will be made to provide additional information.

Role of stromal cell-derived factor-1 expression in the injured mouse auditory nerve.

OBJECTIVE: The degeneration of hair cells and spiral ganglion neurons (SGNs) is an important pathologic process in the development of sensorineural hearing loss. In a murine model, predictable and reproducible damage to SGNs occurs through the application of ouabain to the round window. Recent evidence has shown that the chemokine stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant of hematopoietic stem cells (HSCs) and provides trophic support to injured tissues during development and maturation. The hypothesis for the current study is that expression of SDF-1 plays an important role in protecting SGNs and preventing further degeneration in the setting of cochlear injury. STUDY DESIGN: Prospective, controlled. SETTING: Academic research laboratory. SUBJECT AND METHODS: Auditory brainstem response (ABR) and the expression of SDF-1 mRNA and protein were examined 1, 3, 7, 14, and 30 days after application of ouabain in 35 adult mice. RESULTS: Following ouabain application, real-time reverse-transcription polymerase chain reaction for SDF demonstrates increased mRNA expression following ouabain injury in nontransplanted mice. A significant increase in SDF protein expression was also observed using immunolabeling techniques and Western blot analysis. CONCLUSIONS: SDF-1 expression is increased in the auditory nerve following cochlear injury. Further knowledge about the cochlear microenvironment, including SDF-1, is critical to maximizing HSC engraftment in the injured cochlea and providing a therapeutic option for sensorineural hearing loss.