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Objective: To record crossed acoustic reflex thresholds (xART's) postoperatively from patients after surgical repair of unilateral congenital aural atresia (CAA). To seek explanations for when xARTs can and cannot be recorded. We hope to understand the implications for this central auditory reflex despite early afferent deprivation., Methods: Patients who underwent surgery to correct unilateral CAA at a tertiary academic medical were prospectively enrolled to evaluate for the presence of xART. Preoperative ARTs in the normal (non-atretic) ear, and postoperative ipsilateral ARTs (stimulus in the normal ear) and contralateral ARTs (stimulus in the newly reconstructed atretic ear; record in the normal ear) were measured at 500, 1000, and 2000 Hz., Results: Four of 11 patients with normal ipsilateral reflex thresholds preoperatively demonstrated crossed acoustic reflexes postoperatively (stimulus in reconstructed ear; record from normal ear). Four other patients demonstrated normal ipsilateral thresholds preoperatively but did not have crossed reflexes postoperatively. No reflexes (pre- or postoperatively) could be recorded in 3 patients. Crossed reflex threshold is significantly correlated with the postoperative audiometric threshold. There was no correlation between ipsilateral and contralateral reflex thresholds., Conclusion: Crossed acoustic reflexes can be recorded from some but not all postoperative atresia patients, and the thresholds for those reflexes correlate with the postoperative pure tone threshold. The presence of acoustic reflexes implies an intact CN VIII-to-opposite CN VII central reflex arc despite early unilateral sound deprivation.

The large external pinnae and extensive vocal repertoire of the African wild dog (Lycaon pictus) has led to the assumption that the auditory system of this unique canid may be specialized. Here, using cytoarchitecture, myeloarchitecture, and a range of immunohistochemical stains, we describe the systems-level anatomy of the auditory system of the African wild dog. We observed the cochlear nuclear complex, superior olivary nuclear complex, lateral lemniscus, inferior colliculus, medial geniculate body, and auditory cortex all being in their expected locations, and exhibiting the standard subdivisions of this system. While located in the ectosylvian gyri, the auditory cortex includes several areas, resembling the parcellation observed in cats and ferrets, although not all of the auditory areas known from these species could be identified in the African wild dog. These observations suggest that, broadly speaking, the systems-level anatomy of the auditory system, and by extension the processing of auditory information, within the brain of the African wild dog closely resembles that observed in other carnivores. Our findings indicate that it is likely that the extraction of the semantic content of the vocalizations of African wild dogs, and the behaviors generated, occurs beyond the classically defined auditory system, in limbic or association neocortical regions involved in cognitive functions. Thus, to obtain a deeper understanding of how auditory stimuli are processed, and how communication is achieved, in the African wild dog compared to other canids, cortical regions beyond the primary sensory areas will need to be examined in detail., (© 2020 Wiley Periodicals LLC.)

Most natural sounds, including speech, exhibit temporal amplitude fluctuations. This information is encoded as amplitude modulations (AM)-essential for auditory and speech perception. The neural representation of AM has been studied at various stages of the ascending auditory system from the auditory nerve to the cortex. In contrast, research on neural coding of AM in the efferent pathway has been extremely limited. The objective of this study was to investigate the encoding of AM signals in the medial olivocochlear system by measuring the modulation transfer functions of the efferent response in humans. A secondary goal was to replicate the controversial findings from the literature that efferent stimulation produces larger effects for the AM elicitor with 100 Hz modulation frequency in comparison with the unmodulated elicitor. The efferent response was quantified by measuring changes in stimulus-frequency otoacoustic emission magnitude due to various modulated and unmodulated elicitors. Unmodulated, broadband noise elicitors yielded either slightly larger or similar efferent responses relative to modulated elicitors depending on the modulation frequency. Efferent responses to the unmodulated and modulated elicitors with 100 Hz modulation frequency were not significantly different. The efferent system encoding of AM sounds-modulation transfer functions-can be modeled with a first-order Butterworth low-pass filter with different cutoff frequencies for ipsilateral and contralateral elicitors. The ipsilateral efferent pathway showed a greater sensitivity to AM information comparted to the contralateral pathway. Efferent modulation transfer functions suggest that the ability of the system to follow AM decreases with increasing modulation frequency and that efferents may not be fully operating on the envelope of the speech.

Despite remarkable advances made to ameliorate how cochlear implants process the acoustic environment, many improvements can still be made. One of most fundamental questions concerns a strategy to simulate an increase in sound intensity. Psychoacoustic studies indicated that acting on either the current, or the duration of the stimulating pulses leads to perception of changes in how loud the sound is. The present study compared the growth function of electrically evoked Compound Action Potentials (eCAP) of the 8th nerve using these two strategies to increase electrical charges (and potentially to increase the sound intensity). Both with chronically (experiment 1) or acutely (experiment 2) implanted guinea pigs, only a few differences were observed between the mean eCAP amplitude growth functions obtained with the two strategies. However, both in chronic and acute experiments, many animals showed larger increases of eCAP amplitude with current increase, whereas some animals showed larger of eCAP amplitude with duration increase, and other animals show no difference between either approaches. This indicates that the parameters allowing the largest increase in eCAP amplitude considerably differ between subjects. In addition, there was a significant correlation between the strength of neuronal firing rate in auditory cortex and the effect of these two strategies on the eCAP amplitude. This suggests that pre-selecting only one strategy for recruiting auditory nerve fibers in a given subject might not be appropriate for all human subjects., Competing Interests: Oticon Medical only provided some of the research material in the sole purpose of helping setting-up the experiment. The authors have no competing interests relating to employment, consultancy, patents, products in development or marketed products. PS provided help in the editing of the article based on his expertise in the research field to avoid errors and inaccuracies. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

The soft-tissue reconstruction and associated osteology of the North American therizinosaurian Nothronychus mckinleyi is updated. The cranial nerve topology is revised, bringing it more in line with coelurosaurs. The trunk of the trigeminal nerve is very short, with an incompletely intracranial trigeminal ganglion, an ophthalmic branch diverging anteriorly first, with later divergences of the maxillomandibular branches, following typical pathways. The facial nerve has been re-evaluated, resulting in a very typical configuration with an extracranial geniculate ganglion. The single foramen leading to the cochlea probably transmitted the vestibulocochlear nerve, along with some fibers of the facial. This configuration is reduced from the more standard three foramina (vestibular, cochlear, and facial) and may be apomorphic for therizinosaurs. Some alteration is proposed for the dorsiflexive musculature. The insertion point for m. transversospinalis capitis is partially changed to extend onto the parietal, along with a proposed functional difference in the moment arm. The expansion of the basicranial pneumatic system is limited to the paratympanic system, enhancing low frequency sound sensitivity. There is little expansion of the median pharyngeal and subcondylar sinuses. Ossification of the surrounding epithelium may provide some information on the embryology of the theropod skull. It may be associated with a reduced stress field, or the general similarity of the basicranium with anterior cervical vertebrae may reflect activation of a cervical vertebral (Hox) gene regulating ossification of the pneumatic sinuses. This might be a local, selectively neutral, fixed gene in the basicranium reflecting embryological regulation of cervical vertebrae development., Competing Interests: The authors have declared that no competing interests exist.

BACKGROUND MicroRNA 194 is involved in the differentiation of various types of cells, such as adipose derived stem cells, human embryonic stem cells, and bone marrow mesenchymal stem cells. Previously, we found that miR-194 was highly expressed in the inner ear sensory patch and neurons in mice embryos. However, the role of miR-194 in the development of the inner ear and its underlying mechanism have not been elucidated yet. MATERIAL AND METHODS The expression level of miR-194 has been altered by using antisense morpholino oligonucleotides (MO) and synthesized miRNAs in zebrafish. RESULTS We found that miR-194 was vastly expressed in the inner ear and central nervous system (CNS) in zebrafish. Loss of function of miR-194 could strongly affected the development of zebrafish embryos, including delayed embryonic development, edema of the pericardium, small head, axial deviation, delayed development of inner ear, closer location of two otoliths, delayed fusion of the semicircular canals, and abnormal otolith number in some cases. In addition, the behavior of zebrafish was also adversely affected with impaired balance and biased swimming route. Misexpression of miR-194 could strongly affected the development and differentiation of spiral ganglion neuron (SGN) in inner ear through Fgf4 in vitro. Similar results have also been observed that the overexpression and knockdown of miR-194 strongly disturbed the development and differentiation of the sensory patches and Statoacoustic ganglion (SAG) through Fgf4 in zebrafish in vivo. Our results indicated that miR-194 may regulate the development and differentiation of sensory patches and SAG through Fgf4. CONCLUSIONS Our data revealed a vital role of miR-194 in regulating the development and differentiation of the inner ear.

Question 1: Does intraoperative facial nerve monitoring during vestibular schwannoma surgery lead to better long-term facial nerve function?, Target Population: This recommendation applies to adult patients undergoing vestibular schwannoma surgery regardless of tumor characteristics., Recommendation: Level 3: It is recommended that intraoperative facial nerve monitoring be routinely utilized during vestibular schwannoma surgery to improve long-term facial nerve function., Question 2: Can intraoperative facial nerve monitoring be used to accurately predict favorable long-term facial nerve function after vestibular schwannoma surgery?, Target Population: This recommendation applies to adult patients undergoing vestibular schwannoma surgery., Recommendation: Level 3: Intraoperative facial nerve can be used to accurately predict favorable long-term facial nerve function after vestibular schwannoma surgery. Specifically, the presence of favorable testing reliably portends a good long-term facial nerve outcome. However, the absence of favorable testing in the setting of an anatomically intact facial nerve does not reliably predict poor long-term function and therefore cannot be used to direct decision-making regarding the need for early reinnervation procedures., Question 3: Does an anatomically intact facial nerve with poor electromyogram (EMG) electrical responses during intraoperative testing reliably predict poor long-term facial nerve function?, Target Population: This recommendation applies to adult patients undergoing vestibular schwannoma surgery., Recommendation: Level 3: Poor intraoperative EMG electrical response of the facial nerve should not be used as a reliable predictor of poor long-term facial nerve function., Question 4: Should intraoperative eighth cranial nerve monitoring be used during vestibular schwannoma surgery?, Target Population: This recommendation applies to adult patients undergoing vestibular schwannoma surgery with measurable preoperative hearing levels and tumors smaller than 1.5 cm., Recommendation: Level 3: Intraoperative eighth cranial nerve monitoring should be used during vestibular schwannoma surgery when hearing preservation is attempted., Question 5: Is direct monitoring of the eighth cranial nerve superior to the use of far-field auditory brain stem responses?, Target Population: This recommendation applies to adult patients undergoing vestibular schwannoma surgery with measurable preoperative hearing levels and tumors smaller than 1.5 cm., Recommendation: Level 3: There is insufficient evidence to make a definitive recommendation.  The full guideline can be found at: https://www.cns.org/guidelines/guidelines-manage-ment-patients-vestibular-schwannoma/chapter_4., (Copyright © 2017 by the Congress of Neurological Surgeons)

The response of the inner ear is modulated by the middle ear muscle (MEM) and olivocochlear (OC) efferent systems. Both systems can be activated reflexively by acoustic stimuli delivered to one or both ears. The acoustic middle ear muscle reflex (MEMR) controls the transmission of acoustic signals through the middle ear, while reflex activation of the medial component of the olivocochlear system (the MOCR) modulates cochlear mechanics. The relative prominence of the two efferent systems varies widely between species. Measuring the effect of either of these systems can be confounded by simultaneously activating the other. We describe a simple, sensitive online method that can identify the effects both systems have on otoacoustic emissions (OAEs) evoked by transient stimuli such as clicks or tone pips (TEOAEs). The method detects directly in the time domain the changes in the stimulus and/or emission pressures caused by contralateral noise. Measurements in human participants are consistent with other reports that the threshold for MOCR activation is consistently lower than for MEMR. The method appears to control for drift and subject-generated noise well enough to avoid the need for post hoc processing, making it promising for application in animal experiments (even if awake) and in the hearing clinic.

Descending neural pathways in the mammalian auditory system are known to modulate the function of the peripheral auditory system. These pathways include the medial olivocochlear (MOC) efferent innervation to outer hair cells (OHCs) and the acoustic reflex pathways mediating middle ear muscle (MEM) contractions. Based on measurements in humans (Marks and Siegel, companion paper), we applied a sensitive method to attempt to differentiate MEM and MOC reflexes using contralateral acoustic stimulation in mice under different levels of anesthesia. Separation of these effects is based on the knowledge that OHC-generated transient evoked otoacoustic emissions (TEOAE) are delayed relative to the stimulus, and that the MOC reflex affects the emission through its innervation of OHC. In contrast, the MEM-mediated changes in middle ear reflectance alter both the stimulus (with a short delay) and the emission. Using this approach, time averages to transient stimuli were evaluated to determine if thresholds for a contralateral effect on the delayed emission, indicating potential MOC activation, could be observed in the absence of a change in the stimulus pressure. This outcome was not observed in the majority of cases. There were also no statistically significant differences between MEM and putative MOC thresholds, and variability was high for both thresholds regardless of anesthesia level. Since the two reflex pathways could not be differentiated on the basis of activation thresholds, it was concluded that the MEM reflex dominates changes in TEOAEs induced by contralateral noise. This result complicates the identification of purely MOC-induced changes on OAEs in mice unless the MEM reflex is inactivated surgically or pharmacologically.

The active cochlear mechanism amplifies responses to low-intensity sounds, compresses the range of input sound intensities to a smaller output range, and increases cochlear frequency selectivity. The gain of the active mechanism can be modulated by the medial olivocochlear (MOC) efferent system, creating the possibility of top-down control at the earliest level of auditory processing. In humans, MOC function has mostly been measured by the suppression of otoacoustic emissions (OAEs), typically as a result of MOC activation by a contralateral elicitor sound. The exact relationship between OAE suppression and cochlear gain reduction, however, remains unclear. Here, we measured the effect of a contralateral MOC elicitor on perceptual estimates of cochlear gain and compression, obtained using the established temporal masking curve (TMC) method. The measurements were taken at a signal frequency of 2 kHz and compared with measurements of click-evoked OAE suppression. The elicitor was a broadband noise, set to a sound pressure level of 54 dB to avoid triggering the middle ear muscle reflex. Despite its low level, the elicitor had a significant effect on the TMCs, consistent with a reduction in cochlear gain. The amount of gain reduction was estimated as 4.4 dB on average, corresponding to around 18 % of the without-elicitor gain. As a result, the compression exponent increased from 0.18 to 0.27.

Gerbils possess a very specialized cochlea in which the low-frequency inner hair cells (IHCs) are contacted by auditory nerve fibers (ANFs) having a high spontaneous rate (SR), whereas high frequency IHCs are innervated by ANFs with a greater SR-based diversity. This specificity makes this animal a unique model to investigate, in the same cochlea, the functional role of different pools of ANFs. The distribution of the characteristic frequencies of fibers shows a clear bimodal shape (with a first mode around 1.5 kHz and a second around 12 kHz) and a notch in the histogram near 3.5 kHz. Whereas the mean thresholds did not significantly differ in the two frequency regions, the shape of the rate-intensity functions does vary significantly with the fiber characteristic frequency. Above 3.5 kHz, the sound-driven rate is greater and the slope of the rate-intensity function is steeper. Interestingly, high-SR fibers show a very good synchronized onset response in quiet (small first-spike latency jitter) but a weak response under noisy conditions. The low-SR fibers exhibit the opposite behavior, with poor onset synchronization in quiet but a robust response in noise. Finally, the greater vulnerability of low-SR fibers to various injuries including noise- and age-related hearing loss is discussed with regard to patients with poor speech intelligibility in noisy environments. Together, these results emphasize the need to perform relevant clinical tests to probe the distribution of ANFs in humans, and develop appropriate techniques of rehabilitation. This article is part of a Special Issue entitled ., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The mentalis muscle (MM) arises from the incisive fossa of the mandible, raises and protrudes the lower lip. Here, we aim to characterize responses obtained from MM by supraorbital and median electrical as well as auditory stimuli in a group of 16 healthy volunteers who did not have clinical palmomental reflex. Reflex activities were recorded from the MM and orbicularis oculi (O.oc) after supraorbital and median electrical as well as auditory stimuli. Response rates over MM were consistent after each stimulus, however, mean latencies of MM response were longer than O.oc responses by all stimulation modalities. Shapes and amplitudes of responses from O.oc and MM were similar. Based on our findings, we may say that MM motoneurons have connections with trigeminal, vestibulocochlear and lemniscal pathways similar to other facial muscles and electrophysiological recording of MM responses after electrical and auditory stimulation is possible in healthy subjects.

Improving the electrode-neuron interface to reduce current spread between individual electrodes has been identified as one of the main objectives in the search for future improvements in cochlear-implant performance. Here, we address this problem by presenting a novel stimulation strategy that takes account of the biophysical properties of the auditory neurons (spiral ganglion neurons, SGNs) stimulated in electrical hearing. This new strategy employs a ramped pulse shape, where the maximum amplitude is achieved through a linear slope in the injected current. We present the theoretical framework that supports this new strategy and that suggests it will improve the modulation of SGNs' activity by exploiting their sensitivity to the rising slope of current pulses. The theoretical consequence of this sensitivity to the slope is a reduction in the spread of excitation within the cochlea and, consequently, an increase in the neural dynamic range. To explore the impact of the novel stimulation method on neural activity, we performed in vitro recordings of SGNs in culture. We show that the stimulus efficacy required to evoke action potentials in SGNs falls as the stimulus slope decreases. This work lays the foundation for a novel, and more biomimetic, stimulation strategy with considerable potential for implementation in cochlear-implant technology., (© The Author(s) 2015.)

Purpose: Diffusion tensor tractography (DTT) is not adequately reliable for prediction of facial and vestibulocochlear (VII-VIII) nerve locations, especially relative to a vestibular schwannoma (VS). Furthermore, it is often not possible to visualize normal VII-VIII nerves by DTT (visualization rates were 12.5-63.6%). Therefore, DTT post-processing was optimized for normal VII-VIII nerve visualization with and without manual noise elimination., Methods: DTT examinations of ten patients were evaluated to assess the improvement in performance by modifying seed region of interest (ROI) and fractional anisotropy (FA) threshold. Seed ROI was placed at the porus of the internal auditory meatus, and FA threshold values were either fixed or variable for each patient. DTT visualization of cranial nerves VII-VIII was evaluated and the noise effect was measured., Results: Cranial nerves VII-VIII were visualized in 90% of patients without using manual noise elimination by modifying the seed ROI and FA threshold. The visualization rate with FA threshold of the upper limit in each patient (100%) was significantly higher than that with FA threshold of 0.1 (75%) (p = 0.02). The incidence rate of noise with FA threshold of the upper limit (10%) was not significantly different than the FA threshold of 0.1 (20%) (p = 0.66)., Conclusion: Seed ROI modification and FA thresholding can improve the visualization of cranial nerve VII-VIII locations in DTT. This technique is promising for its potential to determine the relationship of cranial nerves VII-VIII to VS.

Object: The middle cranial fossa (MCF) approach is a microsurgical technique described as a primary option in the treatment of small, intracanalicular schwannomas involving the eighth cranial nerve. Excellent rates of complete tumor resection, hearing preservation, preservation of facial nerve function, and low complication rates have been reproduced using this technique. However, the durability of hearing preservation attained using the various treatment options has not been adequately assessed. The purpose of this study was to evaluate the durability of long-term hearing preservation in patients with vestibular schwannoma (VS) treated via the MCF approach. The authors hypothesize that hearing preservation in these patients will prove to be durable years after treatment in a high percentage of cases., Methods: Retrospective medical chart review was performed in 103 consecutive patients undergoing resection of VS via a modified MCF approach between 1999 and 2008. Patients in whom surgical goals were gross-total resection and hearing preservation were included. Preoperative and postoperative hearing assessment was performed using standard audiometric testing, and classified according to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines as a primary outcome measure. Outcomes and neurological complications initially, and at 1, 3, and 5 years following operation were analyzed., Results: Initial hearing preservation rates were in keeping with the best previously published results. At initial postoperative audiometric follow-up, of the patients presenting with Class A hearing, 67% remained Class A, 17% were Class B, 1% were Class C, and 15% were Class D. Of patients presenting with Class B hearing, 24% were Class A, 53% remained Class B, 6% were Class C, and 18% were Class D. Of patients presenting with Class C hearing, 100% remained Class C. To assess the durability of hearing preservation in our patients, the authors evaluated hearing function at regular intervals after the initial postoperative audiometric follow-up. Audiometric data were available for 56 patients at 5-year follow-up. Of the 20 patients with Class A hearing at initial postoperative follow-up with 5-year follow-up, 13 (65%) remained Class A, 6 (30%) were Class B, and 1 (5%) was Class C. Of the 12 patients with Class B hearing at initial postoperative follow-up with 5-year follow-up, 4 (33%) were Class A, 4 (33%) remained Class B, and 4 (33%) were Class C. Of the 3 patients with Class C hearing at initial postoperative follow-up with 5-year follow-up, all 3 (100%) remained Class C., Conclusions: A majority of patients with preserved hearing following the MCF approach for treatment of VS experience durability of their preserved hearing at 5-year follow-up. The initial AAO-HNS classification was preserved in 13 (65%) of the 20 patients who had Class A hearing at 5 years, and in 8 (67%) of the 12 who had Class B hearing at 5 years. Overall, a decline in AAO-HNS classification was noted in 15% of patients with preserved Class A hearing, and in 33% of those with preserved Class B hearing. Facial nerve function was preserved in 91% of cases. Superior hearing preservation as well as good outcomes in facial nerve function and few serious complications can be accomplished using the MCF approach for resection of small VSs.

To assess when vestibulosympathetic projections become functional postnatally, and to establish a preparation in which vestibulosympathetic circuitry can be characterized more precisely, we used an optical approach to record VIIIth nerve-evoked synaptic inputs to thoracic sympathetic preganglionic neurons (SPNs) in newborn mice. Stimulation of the VIIIth nerve was performed in an isolated brainstem-spinal cord preparation after retrogradely labelling with the fluorescent calcium indicator Calcium Green 1-conjugated dextran amine, the SPNs and the somatic motoneurons (MNs) in the thoracic (T) segments T2, 4, 6, 8, 10 and 12. Synaptically mediated calcium responses could be visualized and recorded in individual SPNs and MNs, and analysed with respect to latency, temporal pattern, magnitude and synaptic pharmacology. VIIIth nerve stimulation evoked responses in all SPNs and MNs investigated. The SPN responses had onset latencies from 90 to 200 ms, compared with much shorter latencies in MNs, and were completely abolished by mephenesin, a drug that preferentially reduces polysynaptic over monosynaptic transmission. Bicuculline and picrotoxin, but not strychnine, increased the magnitudes of the SPN responses without changing the onset latencies, suggesting a convergence of concomitant excitatory and inhibitory synaptic inputs. Lesions strategically placed to test the involvement of direct vestibulospinal pathways versus indirect pathways within the brainstem showed that vestibulosympathetic inputs in the neonate are mediated predominantly, if not exclusively, by the latter. Thus, already at birth, synaptic connections in the vestibulosympathetic reflex are functional and require the involvement of the ventrolateral medulla as in adult mammals.

The motion of the vestibulo-cochlear nerve (VCN) was quantified at the level of the cerebello-pontine angle in 28 healthy volunteers enrolled in a prospective study performed on a 3T MRI scanner. A phase contrast MRI (PCMRI) sequence was used. The VCN was divided into a cisternal part and a meatic part, both of which were measured for motion in the cranio-caudal (CC) and antero-posterior (AP) directions. Motion was cardiac-cycle-dependent in these two directions. The meatic VCN motion was delayed compared to the cisternal VCN motion. In the CC direction, the mean amplitude of the cisternal VCN motion was twice larger than the mean amplitude of the meatic VCN motion (0.37+/-0.14 mm versus 0.17+/-0.08 mm). In the AP direction, the mean amplitude of the cisternal VCN was 0.19+/-0.08 mm versus 0.16+/-0.14 mm for the meatic VCN. We used an "oscillating string" to explain the VCN motion. Reproducibility tests have shown small variations in measurements of the CC motion. PCMRI can be used to assess the VCN motion at the level of the cerebello-pontine angle., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Neurosurgical procedures involving the skull base and structures within can pose a significant risk of damage to the brain stem and cranial nerves. This can have life-threatening consequences and/or result in devastating neurologic deficits. Over the past decade, intraoperative neurophysiology has significantly evolved and currently offers a great tool for live monitoring of the integrity of nervous structures. Thus, dysfunction can be identified early and prompt modification of the surgical management or operating conditions, leads to avoidance of permanent structural damage.Along these lines, the vestibulocochlear nerve (CN VIII) and, to a greater extent, the auditory pathways as they pass through the brain stem are especially at risk during cerebelopontine angle (CPA), posterior/middle fossa, or brain stem surgery. CN VIII can be damaged by several mechanisms, from vascular compromise to mechanical injury by stretch, compression, dissection, and heat injury. Additionally, cochlea itself can be significantly damaged during temporal bone drilling, by noise, mechanical destruction, or infarction, and because of rupture, occlusion, or vasospasm of the internal auditory artery.CN VIII monitoring can be successfully achieved by live recording of the function of one of its parts, the cochlear or auditory nerve (AN), using the brain stem auditory evoked potentials (BAEPs), electrocochleography (ECochG), and compound nerve action potentials (CNAPs) of the cochlear nerve.This is a review of these techniques, their principle, applications, methodology, interpretation of the evoked responses, and their change from baseline, within the context of surgical and anesthesia environments, and finally the appropriate management of these changes.

Introduction and Aim: Radiosurgery is among the treatment options for patients with vestibular schwannoma. We present the experience in our institution in the treatment of this disease with this technique., Patients and Methods: A retrospective study was made including 20 patients (11 women and 9 men; median age: 55.15 years-old) with vestibular schwannoma who received linear accelerator radiosurgery treatment since April 2005 until December 2008. Follow-up period was between 12 and 42 months, considering clinical examination of cranial nerves VII (House-Brackmann scale) and VIII (Gardner-Robertson scale) as well as radiological findings (considering tumor volume). For statistical analysis, the Fisher's exact test and logistic regression test were used., Results: Certain worsening of hearing function was present in 25% of the patients. Five patients had large tumors at the moment of the treatment (equal or larger than 3.5 cm3), from which four deteriorated from headache, unsteady gait, dizziness/vertigo, facial numbness and tinnitus, with statistical significance (p < 0.05). From the first year of treatment on, there was a tumor volume decrease tendency, with no tumor growth in the medium/long term follow-up, achieving a local control rate of 100%., Conclusions: Radiosurgery has become an alternative in the treatment of patients with vestibular schwannoma of appropriate size, with high safety level, using low radiation doses, low rate of complications and good tumor control rate in the medium term follow-up.

Proper control of movement and posture occurs partly via descending projections from the vestibular nuclei to spinal motor circuits. Days before birth in rodents, vestibulospinal neurons develop axonal projections that extend to the spinal cord. How functional these projections are just after birth is unknown. Our goal was to assess the overall functional organization of vestibulospinal inputs to spinal motoneurons in a brainstem-spinal cord preparation of the neonatal mouse (postnatal day (P) 0-5). Using calcium imaging, we recorded responses evoked by electrical stimulation of the VIIIth nerve, in many motoneurons simultaneously throughout the spinal cord (C2, C6, T7, L2 and L5 segments), in the medial and lateral motor columns. Selective lesions in the brainstem and/or spinal cord distinguished which tracts contributed to the responses: those in the cervical cord originated primarily from the medial vestibulospinal tracts but with a substantial contribution from the lateral vestibulospinal tract; those in the thoracolumbar cord originated exclusively from the lateral vestibulospinal tract. In the thoracolumbar but not the cervical cord, excitatory commissural connections mediated vestibular responses in contralateral motoneurons. Pharmacological blockade of GABA(A) receptors showed that responses involved a convergence of excitatory and inhibitory inputs which in combination produced temporal response patterns specific for different segmental levels. Our results show that by birth vestibulospinal projections in rodents have already established functional synapses and are organized to differentially regulate activity in neck and limb motoneurons in a tract- and segment-specific pattern similar to that in adult mammals. Thus, this particular set of descending projections develops several key features of connectivity appropriately at prenatal stages. We also present novel information about vestibulospinal inputs to axial motoneurons in mammals, providing a more comprehensive platform for future studies into the overall organization of vestibulospinal inputs and their role in regulating postural stability.

Background: Disorders of balance often pose a diagnostic conundrum for clinicians, and a multitude of investigations have emerged over the years. Vestibular evoked myogenic potential testing is a diagnostic tool which can be used to assess vestibular function. Over recent years, extensive study has begun to establish a broader clinical role for vestibular evoked myogenic potential testing., Objectives: To provide an overview of vestibular evoked myogenic potential testing, and to present the evidence for its clinical application. REVIEW TYPE: Structured literature search according to evidence-based medicine guidelines, performed between November 2008 and April 2009. No restrictions were applied to the dates searched., Conclusion: The benefits of vestibular evoked myogenic potential testing have already been established as regards the diagnosis and monitoring of several clinical conditions. Researchers continue to delve deeper into potential new clinical applications, with early results suggesting promising future developments.

Objective: To demonstrate anatomically a pathway for protein transport from the palate to the vestibular system., Method: The vestibulofacial anastomosis and associated ganglion cells were identified in a collection of 160 horizontally sectioned human temporal bones that had been stained with hematoxylin and eosin. Wheat germ agglutinin-horseradish peroxidase (HRP) was applied to the greater superficial petrosal nerve in 4 Sprague-Dawley rats. After 30 hours, the rats were killed by intracardiac perfusion, and the seventh and eighth nerves with adjacent brainstem removed. Frozen sections cut at 30 mum through this block were then reacted for HRP, counterstained with neutral red, and mounted on slides for examination in the light microscope., Results: Thirty-two of the 160 human temporal bones contained sections through the vestibulofacial anastomosis and its ganglion. In all cases, the ganglion was incorporated into the vestibular ganglion (VG) adjacent to the nervus intermedius. In all 4 experimental rats, HRP reaction product labeled a small number of ganglion cells in the VG adjacent to the nervus intermedius and facial nerve., Conclusion: These observations support the presence of a pathway from receptors in the palate to the VG.

Spontaneous activity and frequency threshold tuning curves were studied in thousands of auditory nerve fibers in chinchilla. The frequency distribution of spontaneous activity rates is strongly bimodal for auditory nerve fibers with characteristic frequency <3 kHz but only mildly bimodal for the entire sample. Spontaneous activity rates and thresholds at the characteristic frequency are inversely related. Auditory-nerve fibers with low spontaneous rate have tuning curves with lower tip-to-tail ratios and more sharply tuned tips than the tuning curves of fibers with high spontaneous rates. It is shown here that this dependence of tuning on spontaneous rates is consistent with a previously unnoticed nonmonotonic dependence on iso-velocity criterion of the frequency tuning of basilar membrane vibrations.

Primary auditory afferents are generally perceived as passive, timing-preserving lines of communication. Contrasting this view, identifiable auditory afferents to the goldfish Mauthner cell undergo potentiation of their mixed--electrical and chemical--synapses in response to high-frequency bursts of activity. This property likely represents a mechanism of input sensitization because they provide the Mauthner cell with essential information for the initiation of an escape response. Consistent with this synaptic specialization, we show here that these afferents exhibit an intrinsic ability to respond with bursts of 200-600 Hz and this property critically relies on the activation of a persistent sodium current, which is counterbalanced by the delayed activation of an A-type potassium current. Furthermore, the interaction between these conductances with the membrane passive properties supports the presence of electrical resonance, whose frequency preference is consistent with both the effective range of hearing in goldfish and the firing frequencies required for synaptic facilitation, an obligatory requisite for the induction of activity-dependent changes. Thus our data show that the presence of a persistent sodium current is functionally essential and allows these afferents to translate behaviorally relevant auditory signals into patterns of activity that match the requirements of their fast and highly modifiable synapses. The functional specializations of these neurons suggest that auditory afferents might be capable of more sophisticated contributions to auditory processing than has been generally recognized.

It is generally believed that the micromechanics of active cochlear transduction mature later than passive elements among altricial mammals. One consequence of this developmental order is the loss of transduction linearity, because an active, physiologically vulnerable process is superimposed on the passive elements of transduction. A triad of sensory advantage is gained as a consequence of acquiring active mechanics; sensitivity and frequency selectivity (frequency tuning) are enhanced and dynamic operating range increases. Evidence supporting this view is provided in this study by tracking the development of tuning curves in BALB/c mice. Active transduction, commonly known as cochlear amplification, enhances sensitivity in a narrow frequency band associated with the "tip" of the tuning curve. Passive aspects of transduction were assessed by considering the thresholds of responses elicited from the tuning curve "tail," a frequency region that lies below the active transduction zone. The magnitude of cochlear amplification was considered by computing tuning curve tip-to-tail ratios, a commonly used index of active transduction gain. Tuning curve tip thresholds, frequency selectivity and tip-to-tail ratios, all indices of the functional status of active biomechanics, matured between 2 and 7 days after tail thresholds achieved adultlike values. Additionally, two-tone suppression, another product of active cochlear transduction, was first observed in association with the earliest appearance of tuning curve tips and matured along an equivalent time course. These findings support a traditional view of development in which the maturation of passive transduction precedes the maturation of active mechanics in the most sensitive region of the mouse cochlea.

The dorsal nucleus of the lateral lemniscus (DNLL) receives afferent inputs from many brain stem nuclei and, in turn, is a major source of inhibitory inputs to the inferior colliculus (IC). The goal of this study was to characterize the monaural and binaural response properties of neurons in the DNLL of unanesthetized decerebrate cat. Monaural responses were classified according to the patterns of excitation and inhibition observed in contralateral and ipsilateral frequency response maps. Binaural classification was based on unit sensitivity to interaural level differences. The results show that units in the DNLL can be grouped into three distinct types. Type v units produce contralateral response maps that show a wide V-shaped excitatory area and no inhibition. These units receive ipsilateral excitation and exhibit binaural facilitation. The contralateral maps of type i units show a more restricted I-shaped region of excitation that is flanked by inhibition. Type o maps display an O-shaped island of excitation at low stimulus levels that is bounded by inhibition at higher levels. Both type i and type o units receive ipsilateral inhibition and exhibit binaural inhibition. Units that produce type v maps have a low best frequency (BF), whereas type i and type o units have high BFs. Type v and type i units give monotonic rate-level responses for both BF tones and broadband noise. Type o units are inhibited by tones at high levels, but are excited by high-level noise. These results show that the DNLL can exert strong, differential effects in the IC.

The experiments herein investigate whether the behavioral responses to transient and episodic vestibular disruption and permanent ablation are distinct in the absence of climbing fiber input. Subjects in group 1 received an IP injection of PBS followed by an IP injection of niacinamide. Seven days later these rats received the first of 3 serial transtympanic injections of TTX on the same side with 7 days between each injection. Following each TTX injection rats displayed unilateral vestibular symptoms that persisted beyond 48h. Spontaneous barrel rolling behavior was not observed. Group 2 subjects received an IP injection of 3-acetylpyridine (3-AP)+niacinamide followed by the same TTX regimen as group 1. Following each TTX injection vestibular symptoms (severe body twisting and persistent spontaneous barrel rolling) emerged rapidly (<15min) and resolved by 72h. Group 3 subjects received an IP injection of 3-AP+niacinamide and 7 days later a single unilateral transtympanic injection of sodium arsanilate. Rats in group 3 developed vestibular symptoms similar to those observed in group 2 although there was no resolution of these symptoms. The results indicate that TTX has a rapid rate of infiltration and blockade of the VIIIth nerve that persists for >48h and then completely resolves. The contrast in vestibular symptoms between groups 1 and 2 suggest that climbing fibers are recruited soon after onset of vestibular disruption and play a role in attenuating the severity of vestibular symptoms associated with transient/episodic vestibular disruption.

Recent biochemical and histochemical analyses explored different components of the extracellular matrix (ECM) in the nervous system, and either permissive or non-permissive roles in neuronal development and regeneration were suggested. The aim of this study was to detect the distribution pattern of a few of these molecules in the nervous system of intact frogs and during nerve regeneration. The hyaluronan (HA) and tenascin C reactions were negative in the peripheral nerves, but appeared in their entry zones. In the CNS, different populations of neurons were surrounded with HA and tenascin C-positive material, forming a perineuronal net (PN). The phosphacan reaction was weakly positive in the PNS, and a moderate intensity was detected in the entry zone and in the PN. Laminin and fibronectin immunoreactivity was strong in the PNS, but laminin could not be detected in the CNS. In animals with cut and regenerating vestibulocochlear nerve, the distribution of the ECM molecules in the CNS and PNS characteristically changed from that of the normal pattern. Our results showed a non-homogenous distribution of ECM components in the frog nervous system that could be associated with their different roles in physiological and pathological processes.

The availability of transgenic and mutant lines makes the mouse a valuable model for study of the inner ear, and a powerful window into cochlear function can be obtained by recordings from single auditory nerve (AN) fibers. This study provides the first systematic description of spontaneous and sound-evoked discharge properties of AN fibers in mouse, specifically in CBA/CaJ and C57BL/6 strains, both commonly used in auditory research. Response properties of 196 AN fibers from CBA/CaJ and 58 from C57BL/6 were analyzed, including spontaneous rates (SR), tuning curves, rate versus level functions, dynamic range, response adaptation, phase-locking, and the relation between SR and these response properties. The only significant interstrain difference was the elevation of high-frequency thresholds in C57BL/6. In general, mouse AN fibers showed similar responses to other mammals: sharpness of tuning increased with characteristic frequency, which ranged from 2.5 to 70 kHz; SRs ranged from 0 to 120 sp/s, and fibers with low SR (<1 sp/s) had higher thresholds, and wider dynamic ranges than fibers with high SR. Dynamic ranges for mouse high-SR fibers were smaller (<20 dB) than those seen in other mammals. Phase-locking was seen for tone frequencies <4 kHz. Maximum synchronization indices were lower than those in cat but similar to those found in guinea pig.

The nonlinear cochlear phenomenon of two-tone suppression is known to be very fast, but precisely how fast is unknown. We studied the timing of low-side suppression in the auditory nerve of the cat using multitone complexes as auditory stimuli. An evalution of the group delays of the responses to these complexes allowed us to measure the timing of the responses with sub-millisecond accuracy for a large number of fibers with characteristic frequencies (CFs) between 2 and 40 kHz. In particular, we measured the delays with which the same below-CF tone complexes affected the response either as an excitor (when presented alone) or as a suppressor (when combined with a CF probe). For CFs <10 kHz, we found that the delay of suppression was larger than the delay of excitation by several hundred microseconds. The difference between the delay of suppression and that of excitation decreased with increasing CF, becoming negligible for CFs >15 kHz. The results are analyzed in terms of traveling-wave delays and a purported cochlear gain control. The data suggest that suppression originates from a gain-control mechanism with an integration time in the order of two cycles of CF.

Distortion product otoacoustic emissions and auditory brainstem responses (ABRs) were measured in neonatal gerbils at three ages: at 15-16 days after birth (dab), near the onset of hearing when the endocochlear potential (EP) is known to be still immature; at 22 dab, when the EP first reaches mature levels; and at 30 dab. Comparing individual 15-16 dab animals to the 22 dab group, ABR threshold changes were typically larger than those for cubic distortion tone (CDT, 2f1-f2) emission thresholds which were, in turn, larger than those for the simple difference tone (DT, f2-f1). In contrast, from 22 to 30 dab there were no important changes in CDT or DT emission thresholds. Observed threshold-change relationships were very similar to those found in differential diagnosis investigations, where the EP was experimentally decreased using a chronic furosemide application. Therefore, most of the change in cochlear function over the two week period studied could be attributed to the maturation of EP during the first week. Model calculations further show that relative changes in CDT and DT emission thresholds are compatible with a movement of the operating point of the cochlear amplifier toward its symmetrical "central" point as the EP reaches mature levels.

For seasonally breeding vertebrates, reproductive cycling is often coupled with changes in vocalizations that function in courtship and territoriality. Less is known about changes in auditory sensitivity to those vocalizations. Here, we show that nonreproductive female midshipman fish treated with either testosterone or 17beta-estradiol exhibit an increase in the degree of temporal encoding of the frequency content of male vocalizations by the inner ear that mimics the reproductive female's auditory phenotype. This sensory plasticity provides an adaptable mechanism that enhances coupling between sender and receiver in vocal communication.

The mechanisms that regulate the acquisition of distinctive neuronal traits in the developing nervous system are poorly defined. It is shown here that the mammalian runt-related gene Runx1 is expressed in selected populations of postmitotic neurons of the embryonic central and peripheral nervous systems. These include cholinergic branchial and visceral motor neurons in the hindbrain, restricted populations of somatic motor neurons of the median and lateral motor columns in the spinal cord, as well as nociceptive and mechanoreceptor neurons in trigeminal and vestibulocochlear ganglia. In mouse embryos lacking Runx1 activity, hindbrain branchiovisceral motor neuron precursors of the cholinergic lineage are correctly specified but then fail to progress to a more differentiated state and undergo increased cell death, resulting in a neuronal loss in the mantle layer. In contrast, the development of cholinergic somatic motor neurons is unaffected. Runx1 inactivation also leads to a loss of selected sensory neurons in trigeminal and vestibulocochlear ganglia. These findings uncover previously unrecognized roles for Runx1 in the regulation of mammalian neuronal subtype development.

Characterization of synaptic transmission between the inner ear sensory cells and primary neuron dendrites has been hampered by the limited access to the postsynaptic terminals. Because direct physiological recording of postsynaptic currents are difficult to achieve, no information regarding the synaptic and dendritic events are available. This is due to the small size of the postsynaptic afferent nerve endings that do not allow a clear identification, and thus compromise direct electrophysiological recordings of the buttons. To study the physiology of afferent nerve endings, we have developed a two-photon imaging technique in cochlear and vestibular slice preparations from neonatal rats and turtles. This technique is based on a retrograde labeling of afferent nerve endings with high-affinity calcium-sensitive dyes. Dye filling was achieved by 6 h application of the dextran-amine conjugate of calcium green-1. Calcium changes were measured in afferent nerve endings in line scan and time lap mode. To address recording in a near-physiological situation, iontophoretic application of K+ was performed in the area of the stereocilia whereas glutamate was applied at the basal pole of sensory hair cells. Both types of application cause a reversible and sustained increase of Ca2+ in the button of afferent nerve fibers. Typical recordings are presented and potential interests for pharmacological studies of inner ear sensory cell synapses are discussed., (Copyright 2004 Elsevier B.V.)

Voltage-dependent changes in electrical coupling are often attributed to a direct effect on the properties of gap junction channels. Identifiable auditory afferents terminate as mixed (electrical and chemical) synapses on the distal portion of the lateral dendrite of the goldfish Mauthner cells, a pair of large reticulospinal neurons involved in the organization of sensory-evoked escape responses. At these afferents, the amplitude of the coupling potential produced by the retrograde spread of signals from the postsynaptic Mauthner cell is dramatically enhanced by depolarization of the presynaptic terminal. We demonstrate here that this voltage-dependent enhancement of electrical coupling does not represent a property of the junctions themselves but the activation of a subthreshold sodium current present at presynaptic terminals that acts to amplify the synaptic response. We also provide evidence that this amplification operates under physiological conditions, enhancing synaptic communication from the Mauthner cells to the auditory afferents where electrical and geometrical properties of the coupled cells are unfavorable for retrograde transmission. Retrograde electrical communication at these afferents may play an important functional role by promoting cooperativity between afferents and enhancing transmitter release. Thus, the efficacy of an electrical synapse can be dynamically modulated in a voltage-dependent manner by properties of the nonjunctional membrane. Finally, asymmetric amplification of electrical coupling by intrinsic membrane properties, as at the synapses between auditory afferents and the Mauthner cell, may ensure efficient communication between neuronal processes of dissimilar size and shape, promoting neuronal synchronization.

Velocity storage (VS), a brainstem function, extends the low-frequency response of the vestibular system. To better understand VS mechanisms and characteristics in humans, we analyzed retrospectively functional measures of gait, electrophysiological measures of vestibular function, and imaging studies in an attempt to determine clinical, electrophysiological, and anatomical correlates of abnormalities in VS. Two cohorts of patients referred to our Risk of Falls Assessment Clinic participated in this investigation. Group 1 (control) patients demonstrated normal caloric and rotary chair tests. Group 2 patients with impaired velocity storage (experimentals) differed clinically from Group 1 only by demonstrating abnormal multifrequency vestibulocular reflex phase measures on rotational testing. Results showed that Group 2 patients had greater impairments in postural stability and gait than Group 1 patients. Additionally, 80% of patients in Group 2 and none in Group 1 showed pontine hyperintense lesions on MRI.

The spectro-temporal receptive field [Hear. Res 5 (1981) 147; IEEE Trans BME 15 (1993) 177] provides an explicit image of the spectral and temporal aspects of the responsiveness of a primary auditory afferent axon. It exhibits the net effects of the competition between excitatory and inhibitory (or suppressive) phenomena. In this paper, we introduce a method for derivation of the spectro-temporal receptive field directly from a second-order Wiener kernel (produced by second-order reverse correlation between spike responses and broad-band white-noise stimulus); and we expand the concept of the spectro-temporal receptive field by applying the new method not only to the second-order kernel itself, but also to its excitatory and inhibitory subkernels. This produces separate spectro-temporal images of the excitatory and inhibitory phenomena putatively underlying the competition. Applied, in simulations, to models with known underlying excitatory and suppressive tuning and timing properties, the method successfully extracted a faithful image of those properties for excitation and one for inhibition. Applied to three auditory axons from the frog, it produced images consistent with previously published physiology.

Objective: One of the clinical characteristics of benign paroxysmal positional vertigo (BPPV) is that the more quickly the head position changes, the more severe the vertigo. This suggests that the velocity of the head change is critical in determining the occurrence and severity of vertigo. The aim of this study was to examine factors determining the symptoms of BPPV using models of canalolithiasis and cupulolithiasis., Material and Methods: Canalolithiasis and cupulolithiasis models were prepared using the bullfrog posterior semicircular canal (PSC). The ampullary nerve discharges were compared between quick and slow positional changes to examine factors determining the symptoms of BPPV., Results: In the canalolithiasis model, the acceleration of the otoconia was greater for the quick positional change. This resulted in a greater discharge with a longer duration. With the slow positional change, the discharges were smaller and shorter. In the cupulolithiasis model, the discharges were sustained and their magnitude did not differ between the quick and slow positional changes. The canalolithiasis model influenced the magnitude of discharge of the PSC depending on the speed of the positional change., Conclusion: Canalolithiasis is the more likely mechanism of BPPV, which is characterized by various degrees of vertigo upon kinetic positional change.

The number and arising sites of the rootlet comprising the intermediate nerve root were investigated in 100 sides of human brains. The arising sites of the rootlets were the pons halfway between the facial and vestibulocochlear nerves (31.9%), the arising portion of the vestibulocochlear nerve on the pons (28.8%) and the stem of the vestibulocochlear nerve (15.9%). The number of roots varied from one to five, with the most common being one root (58%). The number of rootlets per root also varied from one to five. Most of the roots had one rootlet (63%), while 2% of the roots had five rootlets. The variation of the arising sites of the intermediate nerve rootlets and its clinical significance were also discussed.

Functional organization of the brain stem vestibulocochlear nuclei during embryogenesis was investigated using a multiple-site optical recording technique with a fast voltage-sensitive dye. Brain stem slices with the cochlear and/or vestibular nerves attached were dissected from 6- to 8-day-old (E6-E8) chick embryos. Electrical responses evoked by cochlear or vestibular nerve stimulation were optically recorded simultaneously from many loci of the preparations. In E7 and E8 preparations, we identified two components of the optical response with cochlear or vestibular nerve stimulation; one was a fast spike-like signal related to the action potential, and the other was a slow signal related to the glutamate-mediated excitatory postsynaptic potential. The location of the cochlear nerve response area was mainly located on the dorsolateral region, while that of the vestibular nerve was deviated ventromedially. At E6, cochlear nerve stimulation evoked only the fast spike-like signals in normal Ringer solution. However, when we removed Mg2+ from the extracellular solution, significant slow signals were elicited in the E6 preparation. The present results demonstrated that in the chick vestibulocochlear nuclei, functional synapses are already generated by the E7 embryonic stage and that postsynaptic activity related to N-methyl-d-aspartate receptors emerges latently, at least in the cochlear nerve-related nucleus, at the E6 embryonic stage. This chronological sequence of the emergence of postsynaptic function is different from that reported previously (E10-E11), suggesting that the developmental origin of sensory information transfer in the auditory pathway is much earlier than has been anticipated.

The sodium channel blocker, tetrodotoxin (TTX), is an effective tool for blockade of action potentials in neurons. Unilateral transtympanic administration of 3 mM TTX produced behavioral symptoms paralleling those previously reported following unilateral vestibular ablation. Behavioral symptoms were evident as early as 15 min post-TTX. Fos immunocytochemistry revealed an initial bilateral distribution of Fos in the inferior olive (IO) followed by an almost exclusively unilateral distribution of Fos. By 1 h, Fos was predominantly localized in subdivisions of the IO contralateral to TTX treatment. Fos labeling in the IO was most pronounced at 2- and 6-h survival times and was localized in the contralateral IOA, IOB, IOC, IOBe, and IOK subdivisions and bilaterally in the IOM and IODM. Other regions of the brainstem including the vestibular nuclei, prepositus hypoglossi, dorsal paragigantocellular reticular nucleus, nucleus of the tractus solitarius and locus coeruleus also exhibited altered patterns of Fos labeling following TTX. The finding that Fos activity in the IO is initially bilateral and then rapidly becomes unilateral has not been reported for the traditional vestibular ablation models and may be unique to the TTX model. In addition, since altered Fos activity is readily detected in the IO at time-points prior to detectable changes in Fos in the central vestibular complex it is possible that the IO is particularly sensitive to events precipitated by unilateral vestibular disturbance.

Female midshipman fish (Porichthys notatus) use the auditory sense to detect and locate vocalizing males during the breeding season. Detection of conspecific vocal signals is essential to their reproductive success and can evoke strong phonotactic responses in gravid females but not in spent females that have released all of their eggs. Here, we test the hypothesis that seasonal variation in reproductive state affects the neurophysiological response properties of the peripheral auditory system in female midshipman fish. Iso-intensity responses of eighth nerve afferents from the sacculus, the main auditory end organ of the inner ear, to individual tones were measured for spike rate and vector strength (VS) of synchronization. Most auditory saccular units in reproductive, summer females showed robust temporal encoding up to 340 Hz, whereas nonreproductive winter females showed comparable encoding only up to 100 Hz. The dramatic upward shift in temporal encoding among summer fish was paralleled by increases in best frequency (BF), maximum evoked spike rate at BF, VS values at BF, and the percentage of units that showed significant VS to iso-intensity tones >140 Hz. Reproductive summer females were best suited to encode the higher harmonic components of male advertisement calls. This first demonstration of a natural cyclicity in peripheral auditory frequency sensitivity among vertebrates may represent, in this case, an adaptive plasticity of the female midshipman's auditory system to enhance the acquisition of auditory information needed for mate identification and localization during the breeding season.

This article reviews studies of the organization and development of the vestibulo-ocular reflex arc in the chicken embryo. It summarizes some of the principal features that characterize the development of this circuit, including the gradual clustering of motoneurons in the oculomotor nucleus into functionally identifiable motoneuron pools, the patterning of vestibular projection neurons into coherent clusters with specific axonal trajectories and terminations onto the oculomotor motoneuron pools, the reverse order of synapse formation during development (motoneuron to muscle, then vestibular projection neuron to motoneuron), and the selectivity of initial synaptic termination at both the ultimate and penultimate relays within the reflex arc. Reference to studies in other vertebrate species is made to provide a comparative context, and potential mechanisms are discussed that may contribute to the underlying synaptic specificity in this circuit.

While particle motion is thought to directly stimulate the inner ear of most fish species, it is difficult to measure and might not be predictable from pressure measurements in a small tank. It is therefore important to replicate experiments conducted relative to pressure measurements using stimuli of known particle motion, to ensure that unmeasured components of the stimulus field do not produce misleading frequency response profiles. The frequency sensitivity of the inner ear of the plainfin midshipman fish, Porichthys notatus, in response to isopressure stimuli has been described. This study now examines the frequency and directional response properties of midshipman saccular afferents in response to whole-body displacements simulating acoustic particle motion. Best frequencies were distributed bimodally, with peaks at 50 Hz and 100 Hz. Most units had cosinusoidally shaped directional response profiles in the horizontal and vertical planes, though some units showed slight deviations from this pattern. A few units (probably saccular efferents) had omnidirectional directional response profiles and did not phase lock to the stimulus waveform. These results are consistent with responses of the midshipman saccular nerve to isopressure stimuli, and strengthen the hypothesis that the frequency sensitivity of the midshipman ear matches the frequency content of behaviorally relevant vocalizations.

In an earlier study, biphasic and monphasic electrical stimulation of the auditory nerve was performed in cats with a cochlear implant. Single-unit recordings demonstrated that spikes resulting from monophasic and biphasic stimuli have different thresholds and latencies. Monophasic thresholds are lower and latencies are shorter under cathodic stimulation. Results from stochastic simulations of a biophysical model of electrical stimulation are similar. A simple analysis of a linear, "integrate to threshold" membrane model accounts for the threshold and latency differences observed experimentally and computationally. Since biphasic stimuli are used extensively in functional electrical stimulation, this analysis greatly simplifies the biophysical interpretation of responses to clinically relevant stimuli by relating them to the responses obtained with monophasic stimuli.

Synaptic plasticity was studied in the lateral vestibular nuclei (LVN) of the guinea pig in vivo. High frequency stimulation (HFS) of increasing or decreasing frequencies was applied to the ipsilateral vestibular nerve. Vestibular field potentials (VFPs) and extracellular single unit activity evoked in the LVN by electrical stimulation of the ipsilateral vestibular nerve, were analyzed before and after the application of different protocols of HFS. Results show that the monosynaptic component of the VFPs undergo long-term potentiation (LTP) with stimulation of 100 Hz applied for 20 s lower frequencies, applied for shorter periods, induce only a transient post-tetanic potentiation. This potentiation, although long lasting, is not permanent since it is susceptible of a reversal or cancellation by opposite patterns of HFS that determine a depression or depotentiation of the previously acquired potentiation. The results demonstrate that the plasticity phenomena that take place at the level of the LVN neurons are not steady but undergo continuous adjustment of their sign and gain depending on the variable flow of vestibular information that reach the nuclei from the labyrinthine receptors.